bluuebunny/crossref_metadata_2025 huggingface dataset:
Speed‐to‐Market and New Product Performance Trade‐offs
Authors: Bayus Barry L.
Published: October 2003

When pressed to accelerate a development effort, more than a few managers have responded in terms such as “Good, fast, cheap … Pick any two.” Time‐to‐market decisions clearly play an important role in determining the ultimate success or failure of a new product. Just as clearly, however, speed to market is not the sole determinant of success. The seemingly offhanded “Pick any two” response points to the tradeoffs that product development managers must make in their decisions about development time and costs.

Barry Bayus discusses the relationship between product development time and costs, and he fomulates a mathematical model that simultaneously considers the decisions regarding time‐to‐market and product performance levels. He applies the model to two competitive scenarios, and he identifies the optimal entry timing and product performance decisions for various market, demand, and cost conditions.

In the first scenario, a firm must decide whether to accelerate development efforts to catch a competitor that has just introduced a new product. Analysis of the tradeoffs among the various parameters in the model suggests that fast development of low‐performance products is optimal under the following conditions: a relatively short window of market opportunity, a weak competitor, and relatively high development costs. For example, if the competitor is weak, high performance levels are not necessary and the firm can safely reduce time‐to‐market. Under the same scenario (that is, accelerating development to catch a competitor), the analysis suggests that fast development of products with high performance levels is optimal under conditions of relatively high sales and relatively flat development costs.

In the second scenario, the firm must decide whether to speed development efforts to beat the competition to market. Analysis of the various tradeoffs for this scenario suggests that first‐to‐market status for a product with a high performnace level is optimal under the following conditions: a relatively long window of market opportunity, relatively high sales, and relatively flat development costs. With a long product lifecycle, stable margins, and high sales, the firm can generate sufficient revenue to offset the increased cost incurred in speeding a high‐performance product to market. Beating a competitor to market with a low‐performance product is never optimal for the cases considered here.
Are Really New Product Development Projects Harder to Shut Down?
Authors: Schmidt Jeffrey B. , Calantone Roger J.
Published: October 2003

Just as a good houseguest knows when it's time to say good‐bye, effective managers must recognize when it's time to terminate a new product development (NPD) project. As a product progresses toward commercialization, a manager's reluctance to terminate a failing project becomes increasingly expensive. Despite this growing expense, however, many managers are reluctant to shut down failing NPD projects.

Jeffrey Schmidt and Roger Calantone hypothesize that this reluctance may be even more pronounced for innovative new products than for incremental NPD efforts. They suggest that perhaps the excitement that really new products engender within a company makes managers more reluctant to shut down the NPD project, even in the face of clear‐cut evidence that the project is not a winner. To test these assumptions, they conducted a decision‐making experiment in which managers were asked to make go/no‐go decisions at each stage in a hypothetical NPD project. One project involved an innovative new product; the other project involved an incremental development—that is, a line extension that offered only marginal size and cost reductions compared to current models.

At the outset of the experiment, participants were given market share and profit objectives for assessing the new product's performance. At each stage in the hypothetical NPD project, the participants then received updated performance data. The performance data provided to participants was identical for the two hypothetical projects, and fell increasingly farther below the performance objectives as the project progressed.

The results of the experiment support the hypothesized relationship between product innovativeness and managers' reluctance to terminate a failing NPD project. Given identical, poor, performance forecasts, the managers who participated in this experiment were more optimistic about the likelihood of success, were more committed to the project, and were more likely to opt for continuing the project when it involved the more innovative product. In fact, the participants were more likely to allow the highly innovative NPD project to proceed all the way through commercialization, notwithstanding the progressively ominous performance feedback.
Discontinuous Innovation and the New Product Development Process
Authors: Veryzer Robert W.
Published: October 2003

Although many new‐products professionals may harbor hopes of developing “the next big thing” in their respective industries, most product development efforts focus on incremental innovations. Accordingly, most research on the new‐product development (NPD) process focuses on the development of evolutionary products. For new‐products professionals seeking insights into the means for achieving breakthrough innovations, a fundamental question remains unanswered: Does the NPD process for discontinuous products differ from the process for incremental, or continuous, products?

To provide a better understanding of managerial practices associated with discontinuous innovation, Robert Veryzer presents findings from an in‐depth study of eight discontinuous product development projects. The study explores the key factors that affect the discontinuous NPD process, as well as the methods that the firms in this study use for assessing the radically new products they have in development. From the findings in this study, he develops a descriptive model of the discontinuous product development process, and he offers insights into the requirements for effective management of discontinuous innovation projects.

Although half the firms in the study use a formal process for evaluating radically innovative products, the participants in the study generally do not employ a formal, highly structured process for managing discontinuous NPD efforts. However, these firms do follow a consistent, logical process in the development of radical innovations, and their process differs significantly from incremental NPD processes.

The processes used by the firms in this study are more exploratory and less customer driven than the typical, incremental NPD process. The impetus for all the projects in this study comes from the convergence of developing technologies, various contextual or environmental factors (for example, government regulations), and a product champion or visionary. Starting from these drivers, the discontinuous NPD process focuses on formulating a product application for the emerging technologies. In all cases, these firms developed prototypes at an earlier stage than the typical, incremental NPD process. To aid in the formulation of a new product application from emerging technologies, prototype construction in these discontinuous NPD projects precedes opportunity analysis, assessment of market attractiveness, market research, and financial analysis.
Enhancing New Product Development Performance: An Organizational Learning Perspective
Authors: Adams Marjorie E. , Day George S. , Dougherty Deborah
Published: October 2003

Several years ago, an editorial in a software industry journal asked readers, “Why aren't they using all those marvelous methods?” The focus of the editorial was on software engineering methods, but the question also applies to the broader realm of new product development (NPD). Proven tools exist for gathering, disseminating, and using market information. But despite widespread recognition of the important role that market knowledge plays in NPD, most firms fail to employ these tools in a consistent manner.

Marjorie E. Adams, George S. Day, and Deborah Dougherty contend that the tools for successful NPD cannot be implemented successfully until we understand the barriers that hinder an organization's capabilities for learning about markets. To foster that understanding, they describe the results of a study that explores the organizational barriers to learning about markets for new products. The study examines 40 NPD efforts in 15 large firms, and it has the following goals: identifying the processes through which organizational barriers impede market learning, developing specific ideas for how NPD professionals can cope more effectively with these barriers, and offering suggestions for improving market tools and techniques to help overcome these barriers.

The study identifies three organizational learning barriers: avoiding ambiguity, compartmentalized thinking, and inertia. For the participants in this study, these barriers persistently act in specific ways to inhibit market learning. In acquiring market information, people typically focus on less ambiguous, more easily understood technologies and business truisms. Dissemination of market information is hindered because people focus on their own goals, which are often defined within their department's role instead of the overall goals of the project. Inertia acts as a barrier to the effective use of market information. That is, people tend to proceed as they always have, maintaining the status quo rather than adjusting actions to capitalize on market learning.

By encouraging broad functional participation in the acquisition and interpretation of data, NPD organizations can reduce the perceived ambiguity of market information. However, cross‐functional approaches are only one step in overcoming organizational barriers. Managers must enable teams to develop rich, vivid market data, help people extend established routines into new practices, and promote trust. Specific market research tools and methods that promote market learning are also suggested.
A Longitudinal Examination of How Champions Influence Others to Support Their Projects
Authors: Markham Stephen K.
Published: October 2003

The image of the project champion fighting corporate inertia, rallying support, and leading a project to success makes for a great story, but that story may not reveal the true nature of the champion's role. All those oft‐told tales about champions fail to provide hard evidence of the techniques that champions use, the activities they perform, and the effects that champions have on project success.

Stephen K. Markham addresses this knowledge gap in a study that examines how champions influence other people and what effects champions have on projects and the people those projects involve. The study uses responses from 53 champions of innovation projects in four large firms as well as team members from those projects. Rather than look at the champions' work on project tasks, the study focuses on the influence champions have on other people to support their projects.

The results of the study only partially support the idea that champions affect projects by influencing people. In the four firms studied, champions use cooperative rather than confrontative tactics to influence other people. However, the champions' choice of influence tactics does not affect the level of compliance or the willingness to participate in the project that those people demonstrate. On the other hand, the champions appear to have a strong influence on their target's behavior if the champions enjoy positive personal relationships with those people.

In general, the tactics used by the champions do not seem to play an important role in the projects studied. From the perspective of the team members, the results of this study do not support the notion that champions make a positive contribution to project performance. However, the champions in this study consistently hold a more positive view of the project than those of the team members.
Environmental Uncertainty, Organizational Integration, and New Product Development Effectiveness: A Test of Contingency Theory
Authors: Souder William E. , Sherman J. Daniel , Davies‐Cooper Rachel
Published: October 2003

R&D/marketing integration clearly improves new‐product development (NPD) effectiveness. However, achieving this integration increases the costs of NPD efforts. If technical and market uncertainty moderate the effects of integration on NPD effectiveness, perhaps a firm can achieve NPD success in a more cost‐effective manner by seeking the appropriate level of integration, based on the perceived level of uncertainty.

In a study of 101 NPD projects at high‐tech firms in the U.S. and the U.K., William E. Souder, J. Daniel Sherman, and Rachel Davies‐Cooper explore the interplay between technical and market uncertainty, integration, and NPD effectiveness. Their study examines two types of integration: R&D/marketing integration and direct R&D/customer integration. The study measures NPD effectiveness in terms of such indicators as NPD cycle time, prototype development proficiency, design change frequency (a negative performance indicator), and product launch proficiency. The responses from both the U.S. and the U.K. firms provide balanced samples of high and low uncertainty projects, as well as successful and unsuccessful projects.

The results of this study support previous research regarding the positive effects of both R&D/marketing integration and direct R&D/customer integration on NPD effectiveness. However, only one measure of NPD effectiveness—R&D comercialization effectiveness—was affected by both R&D/marketing integration and direct R&D/customer integration. This result suggests that the two types of integration are distinct from one another and that managers need to emphasize different types of integration, depending on which aspects of NPD effectiveness their firms need to improve.

The results also suggest that technical and market uncertainty influence some aspects of NPD effectiveness. For example, the perceived level of technical uncertainty was found to influence prototype development proficiency and to moderate design change frequency. In other words, these results support the idea that a high level of technical uncertainty warrants paying extra attention to increasing prototype development proficiency in the interest of reducing design change frequency. However, the results also reinforce the idea that NPD activities generally involve high levels of technical and market uncertainty, which means that the high cost of integration may be a requirement for NPD success.
Competitive Advantage Through Product Performance Innovation in a Competitive Market
Authors: Friar John H.
Published: October 2003

Superior product performance does not necessarily ensure commercial success. In many industries, companies seek competitive advantage primarily through product innovation. Competition in such markets is based on claims of technological superiority. However, unless a company can clearly establish the superiority of its products in its customers' minds, a differentiation strategy based on relative product performance is likely to be ineffective. This is particularly true in markets characterized by numerous product introductions from many competitors.

Product innovation success declines as the intensity of market competition increases. This may be caused by customers' inability to differentiate products on the basis of functional performance. John H. Friar tests this hypothesis by examining an industry, medical diagnostic ultrasound equipment, that is characterized by frequent product introductions from numerous companies.

Technical experts from the competing manufacturers believe there are differences in the image quality of their equipment and strongly agree on the factors that distinguish better performance. In most cases, however, customers could not distinguish product performance. Ironically, in a market where everyone is competing by improving product performance, product performance innovation alone may not be enough to create meaningful differentiation.

To succeed in such an environment, companies must compete on two levels. Continued emphasis on product innovation is necessary to keep pace with the competition. However, because product innovation alone is not sufficient to provide market differentiation, companies must shift their competitive thrust to other dimensions.
A Theory of Vacant Urban Land
Authors: Schenk Robert E.
Published: October 2003

The purpose of this paper is to examine the prevalence and causes of vacant urban land. The paper is organized in four parts. The first part summarizes the available information on the extent of vacant urban land. The second section attempts to explain the existence of vacant land by using concepts often applied to labor unemployment. In part three that vacant land which the labor concepts do not explain is attacked with another tool from the economic tool box, the “optimal‐harvest‐time” solution, but this solution is found to have limited applicability. The paper concludes with a brief discussion of how the framework developed in parts two and three might be used.

Central in this paper is the attempt to analyze vacant land with theories developed for unemployed labor. This procedure stems from the belief that, whenever possible, new phenomena should be attacked with old theories. Such a methodology conserves effort, for if the old and new phenomena are indeed similar, new theories may not only be unnecessary but undesirable–product differentiation has a cost. Moreover, an old theory can bring out similarities that may not be obvious at first glance, and may suggest areas that deserve more attention.
A Simulation Approach to the Appraisal of Income Producing Real Estate
Authors: Wofford Larry E.
Published: October 2003

The income approach to appraising real property has been criticized in at least three general areas: the use of point estimates for input variables and market value, the failure to use an after‐tax valuation model, and the ability of a single valuation model to capture the market for a given property. The objectives of this study are the development of an analytical framework and computer model to overcome these criticisms. The computer model is developed using Monte Carlo simulation and allows the appraiser to consider uncertainty, after‐tax cash flows and numerous valuation models. The ability of appraisers to generate the necessary inputs and the interpretation of the output from the model are demonstrated using a case study.
Residential Mortgage Markets and the Cost of Mortgage Funds
Authors: Hendershott Patric H. , Villani Kevin E.
Published: October 2003

Early federal housing finance policy appears to have been largely directed at making mortgages more marketable. The creation of FHA, FNMA and FHLMC were designed to homogenize the mortgage instrument and to develop a secondary market for it. Apparently because of a lack of demand for marketability by investors, extensive trading of mortgages has not developed. Nonetheless, the fantastic growth in mortgage pools (as well as the unanticipated growth in FNMA holdings) has increased competition in the supplying of some intermediation functions (mortgage bankers have greatly expanded originations and servicing), has improved interregional flows of mortgage funds, and has given mortgage borrowers a greater access to capital markets generally. The principal result has been a decline in the mortgage rate relative to other market rates, although the inflation‐triggered explosion in the demand for mortgage funds in recent years appears to be offsetting the impact of the growth in federal credit broadly defined.
Real Estate Investment Analysis: New Developments in Traditional Leverage Concepts
Authors: Bible Douglas S. , Celec Stephen E.
Published: October 2003

The advantages of utilizing leverage in real estate investments has received much attention in the past, but little guidance has been offered that shows the investor the most opportune leverage position for a given investment alternative. Traditional leverage concepts are explored in this article, prior to developing a financial indifference point model and a continuous‐function degree of financial leverage (DFL) formula. The indifference point and DFL as shown here are relatively simple to calculate and provide additional insights into risk, return and leverage concepts for real estate investments.
Regional Market Variations: The Northeast Versus The South
Authors: Sternlieb George , Hughes James W.
Published: October 2003

The notion of the “rise of the Sunbelt” and the “decline of the Northeast” has raised the spectre of relentless economic disintegration of the northeastern states and the lure of boundless affluence across the southern and southwestern rim. What is myth and what is reality in these emerging perceptions? This paper reviews the trends of the past fifteen years, and speculates on the possibility of unsettled economic weather in the Sunbelt and valid investment potentials in the Northeast. Alternative future scenarios are suggested in the light of the marked acceleration of the thrusts of change of the last five years.
Housing Policy in a Nongrowth Era: Problems of the Northeast United States
Authors: Kristof Frank S.
Published: October 2003

The ambivalent results of the federal government's large‐scale subsidization of low‐ and moderate‐rent housing production in the early 1970s have produced new preoccupations about the directions federal housing programs should take in the light of sharply divergent growth trends among Regions that have become apparent in 1977. As economic and demographic growth in the South and West Regions poses classic problems of adaption to growth, the Northeast and North Central Regions are faced with either nongrowth or decreases in population and employment. This paper discusses adaptions designed to conserve and improve existing housing resources in areas that require only minimal new residential construction. These adaptions include new levels of state‐federal housing coordination to make more intense use of private financing in conjunction with the federal Section 8, Coinsurance, and Section 233(f) programs.
The Affordability of New Homes
Authors: Weicher John C.
Published: October 2003

There has been much recent public discussion about the rising price of new homes, and concern that an increasing number of families are priced out of the new home market. This paper argues that new homes are no more expensive, relative to income, than they have historically been, although the large volume of subsidized new home production during the early 1970s has tended to distort the recent trends. The main problem for new home buyers is the increase in mortgage interest rates generated by inflation in the past decade. However, current homeowners have also benefited from inflation and may be better able to afford a new house as a result. This paper also presents data on recent new home buyers, showing that a large number of families are buying new homes supposedly beyond their means, and that the typical buyer has a much lower income than has been thought feasible by many housing market analysts.
How Well Do Section 8 FMRs (Fair Market Rent) Match the Cost of Rental Housing? Data from Thirty‐Nine Large Cities
Authors: Follain James R.
Published: October 2003

The FMR (Fair Market Rent) idea was built into the Section 8 lower income rental assistance program to provide a means to reflect variations in the rental cost of comparable housing in different market areas and also rental cost differences within a market area due to size variations in housing units. Does the FMR schedule for the Section 8 Existing Housing Program parallel the actual differences in the rents of comparable housing among metropolitan areas? We find the 1975 schedule fulfills some of the criteria for an efficient and equitable Section 8 Existing Housing Program but not all.
Extension and Application of the Mills‐Muth Urban Residential Land Use Simulation Model: Milwaukee, 1977–2020
Authors: Altmann James L. , DeSalvo Joseph S.
Published: October 2003

The Mills‐Muth urban residential land use simulation model is extended to include two residential income classes and a proportion of residential to urban land that varies with distance from the CBD. Land area, population, households, population density and residential property value are simulated for the central city, its suburbs and the Milwaukee urban area for the years 1977, 1980, 1985, 1990 and 2020, for two scenarios that differ primarily with respect to income growth rates and automobile commuting costs. The main finding is the powerful positive effect of even relatively small real income growth on suburbanization.
The Growth of Residential Capital Since World War II
Authors: Grebler Leo
Published: October 2003

The growth rate of residential capital in constant dollars shows a downward trend. Its decline since the early postwar years conforms broadly to the growth retardation found in an earlier study for the 1890–1950 period. The article analyzes the forces associated with the slowing rate of real capital increase in 1945–77 and concludes that they differed substantially from those operative in the earlier era. The growth patterns of residential and of fixed business capital since World War II have been quite dissimilar and generally in disfavor of the residential sector.
The Mortgage Acquisition Process: A Comparison of VRM and FRM Borrowers*
Authors: Albaum Gerald , Kaufman George G.
Published: October 2003

In recent years a number of alternative types of residential mortgage plans (i.e., alternative to the fixed‐rate level‐payment mortgage) have been proposed, and some of these have been available in various parts of the country. The most often proposed innovation has been the variable rate mortgage (VRM). The most widespread use of the VRM has been in the State of California, starting in early 1975. This paper discusses some of the results of a survey of over 1,700 homeowners in California that examined consumer reaction to the VRM. Specifically, this paper looks at the impact of the VRM on the mortgage acquisition process and the features of mortgages demanded by consumers. The data seem to indicate that the process of acquiring a mortgage has not been affected significantly by the availability of the VRM. However, the existence of alternative mortgage plans means that consumer choice can be broadened to include type of mortgage as well as lending institution.
Aid, conflict and migration: the Canada‐Sri Lanka connection
Authors: Hyndman Jennifer
Published: October 2003

This paper aims to disentangle patterns of aid, trade, conflict and migration between Canada and Sri Lanka, illustrating the surprisingly significant traffic between the two countries and exploring the significance and quality of these connections. International aid to Sri Lanka is closely related to the opening of markets to multinational investment beginning in 1977. This economic liberalisation overlaps with periods of conflict in Sri Lanka and of macroeconomic growth. The prosperity it has generated, however, has not benefited all social classes and ethnic groups. Accordingly, conflict in Sri Lanka has been characterised by uprisings led by unemployed youth, peaceful and violent protests of discrimination against Sri Lankan Tamils and militarised government reprisals to both. A long period of macroeconomic growth ended in the final quarter of 2001, after the bombing of commercial airliners at Sri Lanka's international airport. Geopolitical and geoeconomic conditions in Sri Lanka changed dramatically. In this context, Canada's International Development Agency (CIDA) and other aid agencies aspire to ‘correct for conflict’ and promote a democratic and peaceful Sri Lanka through peace‐building and other aid measures. Militarised conflict over at least the past 20 years has generated massive human displacement both within and beyond the country's borders, spawning international migrants in search of asylum. In 1999, Sri Lanka was the leading source country of refugee claimants to Canada. Canada hosts the single largest Sri Lankan diaspora of any country. By examining the nexus of economic liberalisation and aid, I analyse its relation to conflict in Sri Lanka and migration to Canada.
Constructing contemporary artistic identities in Toronto neighbourhoods
Authors: Bain Alison L.
Published: October 2003

This paper examines the role of the neighbourhood in the construction of artistic identities. Drawing upon in‐depth, semistructured interviews with Canadian visual artists from Toronto, I identify some of the common features of downtown Toronto neighbourhoods where artists congregate. I demonstrate that artists are drawn to neighbourhoods that have not been gentrified and do not directly reflect current dominant values in society. I focus, in particular, on the importance of marginal niches of improvisational space within the urban fabric. Marginal spaces, often neglected and overlooked, weakly classified and in a state of becoming, I argue, are essential to the development and sustenance of an artistic identity.
Null Mutation of gp91phox Reduces Muscle Membrane Lysis During Muscle Inflammation in Mice
Authors: Nguyen Hal X. , Tidball James G.
Published: October 2003

Muscle inflammation is a common feature in muscle injury and disease. Recently, investigators have speculated that inflammatory cells may increase or decrease muscle damage following modified muscle use, although there are few experimental observations to confirm either possibility. In the present study, a null mutation of gp91phox in neutrophils prevented superoxide production in cytotoxicity assays in which muscle cells were targets, and prevented most neutrophil‐mediated cytolysis of muscle cells in comparison to wild‐type neutrophils in vitro. We further tested whether deficiency in superoxide production caused a decrease in muscle membrane damage in vivo during modified muscle use. Gp91phox null mutant mice and wild‐type mice were subjected to 10 days of muscle hindlimb unloading followed by reloading through return to normal locomotion, which induced muscle membrane lesions and muscle inflammation. Membrane lesions were quantified by measuring the presence of extracellular marker dye in reloaded soleus muscle fibres. There was a 90 % reduction in the number of fibres showing extensive membrane injury in gp91phox null mice compared to controls. Mutation of gp91phox did not change the concentration of neutrophils or macrophages in the reloaded muscle. Furthermore, muscle fibre growth during the reloading period was unaffected by the reduction in membrane injury. Together, these findings show that neutrophils can induce muscle membrane lysis through superoxide‐mediated events, and indicate that superoxide‐mediated membrane damage in vivo is not required for myeloid cell chemotaxis or muscle growth during muscle reloading.
Acute Stress Modulates the Histamine Content of Mast Cells in the Gastrointestinal Tract Through Interleukin‐1 and Corticotropin‐Releasing Factor Release in Rats
Authors: Eutamene Helene , Theodorou Vassilia , Fioramonti Jean , Bueno Lionel
Published: October 2003

Stress results in activation of the hypothalamic pituitary adrenal axis and affects illnesses such as neuroinflammatory syndrome. In vivo acute stress (restraint stress) induces gastrointestinal function disturbances through colonic mast cell activation. This study investigated the effect of acute stress in histamine content of colonic mast cells, and the central role of interleukin‐1 (IL‐1) and corticotropin‐releasing factor (CRF) in this effect. After a restraint stress session colonic segments were isolated and submitted to three protocols: (i) determination of histamine levels by radioimmunoassay (RIA) after incubation with 48/80 compound, (ii) evaluation by histology of mucosal mast cell (MMC) number and (iii) determination of histamine immunoreactivity of MMC. These procedures were conducted (1) in sham or stressed rats, (2) in stressed rats previously treated with intracerebroventricular (i.c.v.) IL‐1ra or α‐helical CRF9‐41, (3) in naive rats pretreated with i.c.v. rhIL‐1β or CRF and (4) in rats treated with central IL‐1β and CRF plus α‐helical CRF and IL‐1ra, respectively (cross‐antagonism reaction). Acute stress increases histamine content in colonic mast cells, without degranulation. i.c.v. pretreatment with IL‐1ra or α‐helical CRF9‐41 blocked stress‐induced mast cell histamine content increase. Both i.c.v. rhIL‐1β and CRF injections reproduced the stress‐linked changes. i.c.v. treatment with CRF antagonist blocked i.c.v. rhIL‐1β‐induced mast cell histamine content increase, whereas central IL‐1ra did not affect stress events induced by i.c.v. CRF administration. These results suggest that in rats acute stress increases colonic mast cell histamine content. This effect is mediated by the release in cascade in the brain first of IL‐1 and secondly of CRF.
Activation of M1 Muscarinic Receptors Triggers Transmitter Release from Rat Sympathetic Neurons Through an Inhibition of M‐Type K+ Channels
Authors: Lechner Stefan G. , Mayer Martina , Boehm Stefan
Published: October 2003

Acetylcholine has long been known to excite sympathetic neurons via M1 muscarinic receptors through an inhibition of M‐currents. Nevertheless, it remained controversial whether activation of muscarinic receptors is also sufficient to trigger noradrenaline release from sympathetic neurons. In primary cultures of rat superior cervical ganglia, the muscarinic agonist oxotremorine M inhibited M‐currents with half‐maximal effects at 1 μm and induced the release of previously incorporated [3H]noradrenaline with half‐maximal effects at 10 μm. This latter action was not affected by the nicotinic antagonist mecamylamine which, however, abolished currents through nicotinic receptors elicited by high oxotremorine M concentrations. Ablation of the signalling cascades linked to inhibitory G proteins by pertussis toxin potentiated the release stimulating effect of oxotremorine M, and the half‐maximal concentration required to stimulate noradrenaline release was decreased to 3 μm. Pirenzepine antagonized the inhibition of M‐currents and the induction of release by oxotremorine M with identical apparent affinity, and both effects were abolished by the muscarinic toxin 7. These results indicate that one muscarinic receptor subtype, namely M1, mediates these two effects. Retigabine, which enhances M‐currents, abolished the release induced by oxotremorine M, but left electrically induced release unaltered. Moreover, retigabine shifted the voltage‐dependent activation of M‐currents by about 20 mV to more negative potentials and caused 20 mV hyperpolarisations of the membrane potential. In the absence of retigabine, oxotremorine M depolarised the neurons and elicited action potential discharges in 8 of 23 neurons; in its presence, oxotremorine M still caused equal depolarisations, but always failed to trigger action potentials. Action potential waveforms caused by current injection were not affected by retigabine. These results indicate that the inhibition of M‐currents is the basis for the stimulation of transmitter release from sympathetic neurons via M1 muscarinic receptors.
The Modulation by 5‐HT of Glutamatergic Inputs from the Raphe Pallidus to Rat Hypoglossal Motoneurones, in vitro
Authors: Bouryi Vitali A. , Lewis David I.
Published: October 2003

Decreases in the activity of 5‐HT‐containing caudal raphe neurones during sleep are thought to be partially responsible for the resultant disfacilitation of hypoglossal motoneurones. Whilst 5‐HT has a direct excitatory action on hypoglossal motoneurones as a result of activation of 5‐HT2 receptors, microinjection of 5‐HT2 antagonists into the hypoglossal nucleus reduces motor activity to a much lesser extent compared to the suppression observed during sleep suggesting other transmitters co‐localised in caudal raphe neurones may also be involved. The aim of the present study was therefore to characterise raphe pallidus inputs to hypoglossal motoneurones. Whole cell recordings were made from hypoglossal motoneurones in vitro. 5‐HT evoked a direct membrane depolarisation (8.45 ± 3.8 mV, P < 0.001) and increase in cell input resistance (53 ± 40 %, P < 0.001) which was blocked by the 5‐HT2 antagonist, ritanserin (2.40 ± 2.7 vs. 7.04 ± 4.6 mV). Stimulation within the raphe pallidus evoked a monosynaptic EPSC that was significantly reduced by the AMPA/kainateantagonist, NBQX (22.8 ± 16 % of control, P < 0.001). In contrast, the 5‐HT2 antagonist, ritanserin, had no effect on the amplitude of these EPSCs (106 ± 31 % of control, P= n.s.). 5‐HT reduced these EPSCs to 50.0 ± 13 % of control (P < 0.001), as did the 5‐HT1A agonist, 8‐OH‐DPAT (52.5 ± 17 %, P < 0.001) and the 5‐HT1B agonist, CP 93129 (40.6 ± 29 %, P < 0.01). 8‐OH‐DPAT and CP 93129 increased the paired pulse ratio (1.38 ± 0.27 to 1.91 ± 0.54, P < 0.05 & 1.27 ± 0.08 to 1.44 ± 0.13, P < 0.01 respectively) but had no effect on the postsynaptic glutamate response (99 ± 4.4 % and 100 ± 2.5 %, P= n.s.). They also increased the frequency (P < 0.001), but not the amplitude, of miniature glutamatergic EPSCs in hypoglossal motoneurones. These data demonstrate that raphe pallidus inputs to hypoglossal motoneurones are predominantly glutamatergic in nature, with 5‐HT decreasing the release of glutamate from these projections as a result of activation of 5‐HT1A and/or5‐HT1B receptors located on presynaptic terminals.
Small Conductance Ca2+‐Activated K+ Channels Formed by the Expression of Rat SK1 and SK2 Genes in HEK 293 Cells
Authors: Benton David C. H. , Monaghan Alan S. , Hosseini Ramine , Bahia Parmvir K. , Haylett Dennis G. , Moss Guy W. J.
Published: October 2003

The rat SK1 gene (rSK1) does not form functional Ca2+‐activated potassium channels when expressed alone in mammalian cell lines. Using a selective antibody to the rSK1 subunit and a yellow fluorescent protein (YFP) tag we have discovered that rSK1 expression produces protein that remains largely at intracellular locations. We tested the idea that rSK1 may need an expression partner, rSK2, in order to form functional channels. When rSK1 was co‐expressed with rSK2 in HEK 293 cells it increased the current magnitude by 77 ± 34 % (as compared with cells expressing rSK2 alone). Co‐expression of rSK1 with rSK2 also changed the channel pharmacology. The sensitivity of SK current to block by apamin was reduced ~16‐fold from an IC50 of 94 pm (for SK2 alone) to 1.4 nm (for SK2 and SK1 together). The sensitivity to block by UCL 1848 (a potent small molecule blocker of SK channels) was similarly reduced, ~26‐fold, from an IC50 of 110 pm to 2.9 nm. These data clearly demonstrate that rSK1 and rSK2 subunits interact. The most likely explanation for this is that the subunits are able to form heteromeric assemblies.
Oceanic Forcing of Sahel Rainfall on Interannual to Interdecadal Time Scales
Authors: Giannini A. , Saravanan R. , Chang P.
Published: October 2003

We present evidence, based on an ensemble of integrations with NSIPP1 (version 1 of the atmospheric general circulation model developed at NASA's Goddard Space Flight Center in the framework of the Seasonal-to-Interannual Prediction Project) forced only by the observed record of sea surface temperature from 1930 to 2000, to suggest that variability of rainfall in the Sahel results from the response of the African summer monsoon to oceanic forcing, amplified by land-atmosphere interaction. The recent drying trend in the semiarid Sahel is attributed to warmer-than-average low-latitude waters around Africa, which, by favoring the establishment of deep convection over the ocean, weaken the continental convergence associated with the monsoon and engender widespread drought from Senegal to Ethiopia.
Technology Tools, A Web-Based Learning Environment for the Science and Mathematics Classroom
Authors: Meisner Gerald W. , Hoffman Harol
Published: October 2003

TechTools™ is a professional development program for science and mathematics teachers for purposes of promoting a constructivist pedagogy with modern technologies: probeware, image processing, multimedia, e-mail, and the WWW. We report preliminary results on (1) changes in teachers' use of technology tools, classroom pedagogy and attitude, and (2) systemic ingredients which are catalytic and inhibitors to the technology reformation necessary in the educational system.
Phase Diagram of a Two-Dimensional Dilute Binary Alloy
Authors: Khalil G. K. , Yaldram K. , Sadiq A.
Published: October 2003

Phase diagrams of two-dimensional binary alloy with vacancies (ABV) is studied with pairwise interaction εAA, εBB, and εAB between the nearest neighbors. Attention is focussed on the case where the vacancies are annealed and εBA = ε, εAA= εBB=0. For vacancy concentrations cv<0.2, the critical temperature decreases linearly with cv. The vacancies remain randomly distributed within the A and B phase separated regions. For cv>0.2 the critical temperature no longer shows this linear trend and falls to zero very sharply at cv=0.39. This critical vacancy concentration is slightly lower than the one expected for quenched vacancies, where the percolation threshold of atomic species is 0.59 (cv=0.41). The mobility of vacancies and the nature of atomic interactions makes it energetically favorable for the vacancies to occupy the boundary layers between A and B phase separated regions, thus making the process of phase separation difficult. This lowers the critical temperature below that of the case where the vacancies are quenched. Salient features of the phase diagram are discussed by comparison with previously studied similar systems with different interaction energies.
Numerical Solutions of the Von Karman Equations for a Thin Plate
Authors: Patrício da Silva Pedro , Krauth Werner
Published: October 2003

In this paper, we present an algorithm for the solution of the von Karman equations of elasticity theory and related problems. Our method of successive reconditioning is able to avoid convergence problems at any ratio of the nonlinear stretching and the pure bending energies. We illustrate the power of the method by numerical calculations of pinched or compressed plates subject to fixed boundaries.
Simulation of a Two-Dimensional Dipolar System on a APE100/Quadrics Simd Architecture
Authors: Bruno Alessandro , Pisacane Fabrizio , Rosato Vittorio
Published: October 2003

The temperature behavior of a system of dipoles with long-range interactions has been simulated via a two-dimensional lattice Monte Carlo on a massively SIMD platform (Quadrics/APE100). Thermodynamic quantities have been evaluated in order to locate and to characterize the phase transition in absence of applied field. Emphasis is given to the code implementation on the SIMD architecture and to the relevant features which have been used to improve code capabilities and performances.
Simulating the Immune Response on a Distributed Parallel Computer
Authors: Castiglione F. , Bernaschi M. , Succi S.
Published: October 2003

The application of ideas and methods of statistical mechanics to problems of biological relevance is one of the most promising frontiers of theoretical and computational mathematical physics.1,2 Among others, the computer simulation of the immune system dynamics stands out as one of the prominent candidates for this type of investigations.

In the recent years immunological research has been drawing increasing benefits from the resort to advanced mathematical modeling on modern computers.3,4

Among others, Cellular Automata (CA), i.e., fully discrete dynamical systems evolving according to boolean laws, appear to be extremely well suited to computer simulation of biological systems.5

A prominent example of immunological CA is represented by the Celada–Seiden automaton, that has proven capable of providing several new insights into the dynamics of the immune system response.

To date, the Celada–Seiden automaton was not in a position to exploit the impressive advances of computer technology, and notably parallel processing, simply because no parallel version of this automaton had been developed yet.

In this paper we fill this gap and describe a parallel version of the Celada–Seiden cellular automaton aimed at simulating the dynamic response of the immune system.

Details on the parallel implementation as well as performance data on the IBM SP2 parallel platform are presented and commented on.
Visualization of Series Analysis for Critical Behavior with Logarithms
Authors: Adler Joan , Chang Iksoo
Published: October 2003

The exact series method is a useful approach for studying critical behavior in the presence of logarithmic corrections to power-law divergences. We describe a visual implementation and several applications of one algorithm for evaluating critical exponents and critical points from series expansions for quantities that exhibit logarithmic forms.
AMADEUS Project and Microscopic Simulation of Boiling Two-Phase Flow by the Lattice-Boltzmann Method
Authors: Kato Yasuyoshi , Kono Koji , Seta Takeshi , Martínez Daniel , Chen Shiyi
Published: October 2003

A two-dimensional lattice-Boltzmann model with a hexagonal lattice is developed to simulate a boiling two-phase flow microscopically. Liquid-gas phase transition and bubble dynamics, including bubble formation, growth and deformation, are modeled by using an interparticle potential based on the van der Waals equation of state. Thermohydrodynamics is incorporated into the model by adding extra velocities to define temperature. The lattice-Boltzmann model is solved by a finite difference scheme so that numerical stability can be ensured at large discontinuity across the liquid-gas phase boundary and the narrow phase interface thickness can be attained. It is shown from numerical simulations that the model has the ability to reproduce phase transition, bubble dynamics and thermohydrodynamics while assuring numerical instability and narrow phase interface.
Computer Simulation of Non-Newtonian Fluid Rheology
Authors: Schlijper A. G. , Manke C. W. , Madden W. G. , Kong Y.
Published: October 2003

Dissipative Particle Dynamics (DPD) is a new simulation technique that focuses on intermediate time and length scales. With this technique it is possible to simulate the essential aspects of the rheological behavior of polymeric liquids quite efficiently. Model studies show that DPD reveals the expected shear thinning and normal stress effects. We also show that the effects of thermodynamic solvent quality on the configurations and rheological behavior of dissolved polymers can be studied with the DPD model.
Simulations of Polymer Interpenetration in 2D Melts
Authors: Ostrovsky B. , Smith M. A. , Bar-Yam Y.
Published: October 2003

Polymers in high density 2D melts are believed to segregate into compact disks. This is in contrast to the entanglement and interpenetration characteristic of 3D melts. We investigate this problem using the two-space algorithm, which is both a Cellular Automaton and a Monte Carlo algorithm for polymer structure and dynamics. Our simulations of high density melts in 2D show that contrary to expectations polymers do not completely segregate at high density — there is significant interpenetration. We show that the characteristic size of a polymer in the high density limit is intermediate between the size of a compact disk and a random walk. We then introduce a "shape factor" that measures the ratio of the polymer circumference squared to the area. The shape factor increases with increasing melt density, clearly indicating the observed interpenetration.
Simulation of Griffeath Majority Rule on Large Square Lattice
Authors: Stauffer D.
Published: October 2003

Even for 693760 * 693760 square lattices, we found fast convergence into fixed points when each spin ± 1 was flipped if and only if more than half of its four neighbors point into the opposite direction. A percolation threshold was found near an initial concentration of 0.5007 and may belong to the universality class of random percolation.