bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiogenesis impairment in Id-deficient mice cooperates with an Hsp90 inhibitor to completely suppress HER2/neu-dependent breast tumors
Authors: de Candia Paola , Solit David B. , Giri Dilip , Brogi Edi , Siegel Peter M. , Olshen Adam B. , Muller William J. , Rosen Neal , Benezra Robert
Published: October 2003

Id proteins bind basic helix–loop–helix transcription factors and function as dominant negative inhibitors of gene expression. Id1 and Id3 are required for the recruitment of bone marrow-derived endothelial cell precursors and tumors transplanted into Id-deficient mice demonstrate impaired angiogenesis. Mouse mammary tumor virus–
neu
mice were bred with
Id1
–/–
Id3
+/–
mice to ascertain the role of Id1 and Id3 in mammary tumorigenesis in a more physiologically relevant model. In mammary tumors from these mice, Id1 and Id3 expression was restricted to the vascular endothelium. Id1 and Id3 deficiency did not prevent or delay tumor formation but did alter tumor phenotype. The tumors that developed in the Id-deficient mice were larger and cystic with a viable rim of tumor cells surrounding a nonviable core of cellular debris. The Hsp90 chaperone protein is required for cellular survival under condition of environmental stress and for the stability of the
neu
oncogene. 17-Allylamino-17-demethoxygeldanamycin, an Hsp90 inhibitor, was used to treat these mice. Whereas 17-allylamino-17-demethoxygeldanamycin only modestly delayed the growth of established mammary tumors in WT mice for Id, tumor suppression was dramatically more effective in an Id1- or Id3-deficient background. These data suggest that tumorigenesis can occur in a background of defective angiogenesis but that tumors developing in such an environment may be especially sensitive to inhibitors of
neu
and stress-activated survival pathways. Thus angiogenesis inhibitors in combination with inhibitors of Hsp90 function should be evaluated for the treatment of advanced breast cancer.
Positive selection on protein-length in the evolution of a primate sperm ion channel
Authors: Podlaha Ondrej , Zhang Jianzhi
Published: October 2003

Positive Darwinian selection on advantageous point substitutions has been demonstrated in many genes. We here provide empirical evidence, for the first time, that positive selection can also act on insertion/deletion (indel) substitutions in the evolution of a protein. CATSPER1 is a voltage-gated calcium channel found exclusively in the plasma membrane of the mammalian sperm tail and it is essential for sperm motility. We determined the DNA sequences of the first exon of the CATSPER1 gene from 15 primates, which encodes the intracellular N terminus region of ≈400 aa. These sequences exhibit an excessively high frequency of indels. However, all indels have lengths that are multiples of 3 nt (
3n
indels) and do not disrupt the ORF. The number of indel substitutions per site per year in CATSPER1 is five to eight times the corresponding rates calculated from two large-scale primate genomic comparisons, which represent the neutral rate of indel substitutions. Moreover, CATSPER1 indels are considerably longer than neutral indels. These observations strongly suggest that positive selection has been promoting the fixation of indel mutations in CATSPER1 exon 1. It has been shown in certain ion channels that the length of the N terminus region affects the rate of channel inactivation. This finding suggests that the selection detected may be related to the regulation of the CATSPER1 channel, which can affect sperm motility, an important determinant in sperm competition.
How fast is protein hydrophobic collapse?
Authors: Sadqi Mourad , Lapidus Lisa J. , Muñoz Victor
Published: October 2003

One of the most recurring questions in protein folding refers to the interplay between formation of secondary structure and hydrophobic collapse. In contrast with secondary structure, it is hard to isolate hydrophobic collapse from other folding events. We have directly measured the dynamics of protein hydrophobic collapse in the absence of competing processes. Collapse was triggered with laser-induced temperature jumps in the acid-denatured form of a simple protein and monitored by fluorescence resonance energy transfer between probes placed at the protein ends. The relaxation time for hydrophobic collapse is only ≈60 ns at 305 K, even faster than secondary structure formation. At higher temperatures, as the protein becomes increasingly compact by a stronger hydrophobic force, we observe a slowdown of the dynamics of collapse. This dynamic hydrophobic effect is a high-temperature analogue of the dynamic glass transition predicted by theory. Our results indicate that in physiological conditions many proteins will initiate folding by collapsing to an unstructured globule. Local motions will presumably drive the following search for native structure in the collapsed globule.
Single-cell analysis of covalently closed circular DNA copy numbers in a hepadnavirus-infected liver
Authors: Zhang Yong-Yuan , Zhang Bai-Hua , Theele Daniel , Litwin Samuel , Toll Eugene , Summers Jesse
Published: October 2003

Hepatitis B virus (hepadnavirus) infections are maintained by the presence of a small and regulated number of episomal viral genomes [covalently closed circular DNA (cccDNA)] in the nuclei of infected cells. Although a number of studies have measured the mean copy number of cccDNA molecules in hepadnaviral-infected cells, the distribution of individual copy numbers have not been reported. Using a PCR-based assay, we examined the number of cccDNA molecules of the duck hepatitis B virus in single nuclei isolated from the liver of a chronically infected duck over the course of 131 days of infection. Nuclei were isolated from frozen serial biopsies and individually deposited into PCR microplates by flow sorting. Each nucleus was assayed by nested PCR for cccDNA and for cellular IFN-α genes as an internal control. We found that 90% of the nuclei assayed contained between 1 and 17 cccDNA molecules, with the remaining 10% containing more (90% confidence), and that differences in the mean number of copies and distribution of copy numbers occurred within the same animal at different times postinfection. Overall, the data suggest (
i
) that the number of cccDNA molecules per cell may fluctuate over time, and (
ii
) that, according to these fluctuations, a substantial fraction of cells may contain only one or a few copies. We infer from the results that infected hepatocytes express virus at different levels and that during cell division it is possible to segregate cells containing no cccDNA.
Microtubule destabilization and nuclear entry are sequential steps leading to toxicity in Huntington's disease
Authors: Trushina Eugenia , Heldebrant Michael P. , Perez-Terzic Carmen M. , Bortolon Ryan , Kovtun Irina V. , Badger John D. , Terzic Andre , Estévez Alvaro , Windebank Anthony J. , Dyer Roy B. , Yao Janet , McMurray Cynthia T.
Published: October 2003

There has been a longstanding debate regarding the role of proteolysis in Huntington's disease. The toxic peptide theory posits that N-terminal cleavage fragments of mutant Huntington's disease protein [mutant huntingtin (mhtt)] enter the nucleus to cause transcriptional dysfunction. However, recent data suggest a second model in which proteolysis of full-length mhtt is inhibited. Importantly, the two competing theories differ with respect to subcellular distribution of mhtt at initiation of toxicity: nuclear if cleaved and cytoplasmic in the absence of cleavage. Using quantitative single-cell analysis and time-lapse imaging, we show here that transcriptional dysfunction is “downstream” of cytoplasmic dysfunction. Primary and reversible toxic events involve destabilization of microtubules mediated by full-length mhtt before cleavage. Restoration of microtubule structure by taxol inhibits nuclear entry and increases cell survival.
Dopamine-dependent neurodegeneration in rats induced by viral vector-mediated overexpression of the parkin target protein, CDCrel-1
Authors: Dong Zhizhong , Ferger Boris , Paterna Jean-Charles , Vogel Denise , Furler Sven , Osinde Maribel , Feldon Joram , Büeler Hansruedi
Published: October 2003

Mutations in the
parkin
gene are linked to autosomal-recessive juvenile parkinsonism (AR-JP). Parkin functions as a ubiquitin protein ligase in the degradation of several proteins, including the neuron-specific septin CDCrel-1. AR-JP-associated parkin mutations inhibit ubiquitination and degradation of CDCrel-1 and other parkin target proteins. Here we show that recombinant adeno-associated virus-mediated CDCrel-1 gene transfer to the substantia nigra of rats results in a rapid onset (6-10 days) of nigral and striatal CDCrel-1 expression that is followed by a progressive loss of nigral dopaminergic neurons and a decline of the striatal dopamine levels. In contrast, neurons of the globus pallidus are spared from CDCrel-1 toxicity. Furthermore, CDCrel-1 inhibits the release of dopamine from stably-transfected PC12 cells, and pharmacological inhibition of tyrosine hydroxylase and dopamine synthesis in rats prevents CDCrel-1-induced nigral neurodegeneration. These results show that CDCrel-1 overexpression exerts dopamine-dependent neurotoxicity and suggest that inhibition of dopamine secretion by CDCrel-1 may contribute to the development of AR-JP.
The L box regulon: Lysine sensing by leader RNAs of bacterial lysine biosynthesis genes
Authors: Grundy Frank J. , Lehman Susan C. , Henkin Tina M.
Published: October 2003

Expression of amino acid biosynthesis genes in bacteria is often repressed when abundant supplies of the cognate amino acid are available. Repression of the
Bacillus subtilis lysC
gene by lysine was previously shown to occur at the level of premature termination of transcription. In this study we show that lysine directly promotes transcription termination during
in vitro
transcription with
B. subtilis
RNA polymerase and causes a structural shift in the
lysC
leader RNA. We find that
B. subtilis lysC
is a member of a large family of bacterial lysine biosynthesis genes that contain similar leader RNA elements. By analogy with related regulatory systems, we designate this leader RNA pattern the “L box.” Genes in the L box family from Gram-negative bacteria appear to be regulated at the level of translation initiation rather than transcription termination. Mutations of
B. subtilis lysC
that disrupt conserved leader features result in loss of lysine repression
in vivo
and loss of lysine-dependent transcription termination
in vitro
. The identification of the L box pattern also provides an explanation for previously described mutations in both
B. subtilis
and
Escherichia coli lysC
that result in
lysC
overexpression and resistance to the lysine analog aminoethylcysteine. The L box regulatory system represents an example of gene regulation using an RNA element that directly senses the intracellular concentration of a small molecule.
The HLA-DQ2 gene dose effect in celiac disease is directly related to the magnitude and breadth of gluten-specific T cell responses
Authors: Vader Willemijn , Stepniak Dariusz , Kooy Yvonne , Mearin Luisa , Thompson Allan , van Rood Jon J. , Spaenij Liesbeth , Koning Frits
Published: October 2003

In patients with celiac disease, inflammatory T cell responses to HLA-DQ2-bound gluten peptides are thought to cause disease. Two types of HLA-DQ2 molecules exist, termed HLA-DQ2.5 and HLA-DQ2.2. Whereas HLA-DQ2.5 predisposes to celiac disease, HLA-DQ2.2 does not. We now provide evidence that the disease-associated HLA-DQ2.5 molecule presents a large repertoire of gluten peptides, whereas the non-disease-associated HLA-DQ2.2 molecule can present only a subset of these. Moreover, gluten presentation by HLA-DQ2 homozygous antigen-presenting cells was superior to presentation by HLA-DQ2/non-DQ2 heterozygous antigen-presenting cells in terms of T cell proliferation and cytokine secretion. Gluten presentation by HLA-DQ2.5/2.2 heterozygous antigen-presenting cells induced intermediate T cell stimulation. These results correlated with peptide binding to the antigen-presenting cells. Finally, we demonstrate that HLA-DQ trans dimers formed in HLA-DQ2.5/2.2 heterozygous individuals have properties identical with HLA-DQ2.5 dimers. Our findings explain the strongly increased risk of disease development for HLA-DQ2.5 homozygous and HLA-DQ2.2/2.5 heterozygous individuals, and they are indicative of a quantitative model for disease development, where HLA-DQ expression and the available number of T cell-stimulatory gluten peptides are critical limiting factors. This model may have important implications for disease prevention.
The Adaptor Protein AP-3 Is Required for CD1d-Mediated Antigen Presentation of Glycosphingolipids and Development of Vα14i NKT Cells
Authors: Elewaut Dirk , Lawton Anna P. , Nagarajan Niranjana A. , Maverakis Emanual , Khurana Archana , Höning Stefan , Benedict Chris A. , Sercarz Eli , Bakke Oddmund , Kronenberg Mitchell , Prigozy Theodore I.
Published: October 2003

Relatively little is known about the pathway leading to the presentation of glycolipids by CD1 molecules. Here we show that the adaptor protein complex 3 (AP-3) is required for the efficient presentation of glycolipid antigens that require internalization and processing. AP-3 interacts with mouse CD1d, and cells from mice deficient for AP-3 have increased cell surface levels of CD1d and decreased expression in late endosomes. Spleen cells from AP-3–deficient mice have a reduced ability to present glycolipids to natural killer T (NKT) cells. Furthermore, AP-3–deficient mice have a significantly reduced NKT cell population, although this is not caused by self-tolerance that might result from increased CD1d surface levels. These data suggest that the generation of the endogenous ligand that selects NKT cells may also be AP-3 dependent. However, the function of MHC class II–reactive CD4+ T lymphocytes is not altered by AP-3 deficiency. Consistent with this divergence from the class II pathway, NKT cell development and antigen presentation by CD1d are not reduced by invariant chain deficiency. These data demonstrate that the AP-3 requirement is a particular attribute of the CD1d pathway in mice and that, although MHC class II molecules and CD1d are both found in late endosomes or lysosomes, different pathways mediate their intracellular trafficking.
The Role of Loop 5 in Acetylcholine Receptor Channel Gating
Authors: Chakrapani Sudha , Bailey Timothy D. , Auerbach Anthony
Published: October 2003

Nicotinic acetylcholine receptor channel (AChR) gating is an organized sequence of molecular motions that couples a change in the affinity for ligands at the two transmitter binding sites with a change in the ionic conductance of the pore. Loop 5 (L5) is a nine-residue segment (mouse α-subunit 92–100) that links the β4 and β5 strands of the extracellular domain and that (in the α-subunit) contains binding segment A. Based on the structure of the acetylcholine binding protein, we speculate that in AChRs L5 projects from the transmitter binding site toward the membrane along a subunit interface. We used single-channel kinetics to quantify the effects of mutations to αD97 and other L5 residues with respect to agonist binding (to both open and closed AChRs), channel gating (for both unliganded and fully-liganded AChRs), and desensitization. Most αD97 mutations increase gating (up to 168-fold) but have little or no effect on ligand binding or desensitization. Rate-equilibrium free energy relationship analysis indicates that αD97 moves early in the gating reaction, in synchrony with the movement of the transmitter binding site (Φ = 0.93, which implies an open-like character at the transition state). αD97 mutations in the two α-subunits have unequal energetic consequences for gating, but their contributions are independent. We conclude that the key, underlying functional consequence of αD97 perturbations is to increase the unliganded gating equilibrium constant. L5 emerges as an important and early link in the AChR gating reaction which, in the absence of agonist, serves to increase the relative stability of the closed conformation of the protein.
Rigidity properties of ℤ^{𝕕}-actions on tori and solenoids
Authors: Einsiedler Manfred , Lindenstrauss Elon
Published: October 2003

We show that Haar measure is a unique measure on a torus or more generally a solenoid

X
X

invariant under a not virtually cyclic totally irreducible

Z

d

\mathbb Z^d

-action by automorphisms of

X
X

such that at least one element of the action acts with positive entropy. We also give a corresponding theorem in the non-irreducible case. These results have applications regarding measurable factors and joinings of these algebraic

Z

d

\mathbb Z^d

-actions.
Truth
Authors: Austin J. L. , Urmson J. O. , Warnock G. J.
Published: October 2003

Deals with the question of whether there is a use of ‘is true’ that is the primary or generic name for that which at bottom we are always saying ‘is true’. Austin discusses the views that truth is primarily a property of beliefs and of true statements. He goes on to argue that the word ‘true’ denotes the validity of an intended (or expected) correspondence between a representation and what it represents, and dismantles confusions about the meaning of the words that underlie such a view, such as ‘fact that’ and ‘corresponds’.
Ifs and Cans
Authors: Austin J. L. , Urmson J. O. , Warnock G. J.
Published: October 2003

Criticises G. E. Moore’s highly influential proposal that ascriptions of agent ability implying freedom of choice or action, what the agent could do, are analyzable as conditional statements regarding what the agent would do under certain circumstances. Austin objects against Moore that some uses of ‘if’ are non-conditional and goes on to examine the uses of these non-conditional cases. Moore’s proposal also lies at the heart of some compatibilist theories of free will and determinism. Austin argues determinism to be a pseudo-problem, so long as it remains a notion that is not itself clear cut.
Project storyboards: catalysts for collaborative improvement
Authors: Fraser Sarah W.
Published: October 2003

This action‐orientated evaluation uses case studies from project facilitators involved in three different collaborative improvement programmes in the UK; medicines management services, cancer processes and services for older adults. The objective of this evaluation was to compare and contrast their perspectives of the benefits and limitations of storyboards, with the aim of feeding back to organisers of large‐scale improvement programmes and users of the collaborative methodology, how the impact of the storyboard process can be positive and constructive. Storyboards are an effective technique for improvement project teams to describe their project, demonstrate progress and share information with other improvement teams working on similar topics, as part of a collaborative improvement process. Additional benefits include using the design and production of storyboards as an opportunity to develop team relationships and to provide those team members who desire it, with a chance to use their creative abilities in a positive way.
Efficient retailer assortment: a consumer choice evaluation perspective
Authors: Amine Abdelmajid , Cadenat Sandrine
Published: October 2003

This research shows that to reach their prime goal of building an efficient assortment, retailers need, beside increasing the outlet’s cost‐efficiency, to evaluate shoppers’ assortment perceptions so that what the store actually offers can be tailored to meet customers’ needs and expectations. Our findings reveal that consumers’ perceptions of the assortment range stems from the combination of few indicators, mainly the number of stock‐keeping units proposed and the availability of the favorite brands. Also demonstrates that consumers evaluation of the overall store assortment draws on the perceived choice within the product categories where they are highly sensitive to the assortment range.
Management attitudes and perceptions of older employees in hospitality management
Authors: Magd Hesham
Published: October 2003

This paper presents the results of a study to identify the perceived benefits, disadvantages and future employment of older workers in Scottish small and medium‐sized hospitality firms. Towards this goal, a sample consisting of 21 managing directors in Scotland was obtained. Results indicated that hospitality managers in Scotland perceived older workers as offering positive attributes, which can be used in the Scottish hospitality industry. From the participants’ viewpoint, the strengths of older workers were perceived as: to have fewer accidents, generate a positive image, ability to learn as much as younger workers, self‐motivated, disciplined, respect for authority, happier/satisfied on the job, dependable, ability to produce quality work, good communication skills and have credibility with customers, co‐operate more on the job, loyal to the organisation, willing to train, lower absentee rate, and they make better employees. On the other hand, high costs associated with the employment of older workers, inflexible and reluctant to change, keep up with the speed required, and hard to adopt new technology tended to be their weaknesses. The majority of the sample surveyed indicated that they would employ older workers in greater percentages in the near future.
Learning as an activity of interdependent people
Authors: Stacey Ralph
Published: October 2003

This paper argues that to talk about organisations learning is to reify and anthropomorphise organisations. Instead of thinking of an organisation as if it were a thing or a person it is closer to experience to think of an organisation as the patterning of peoples' interactions with each other. This paper explores the assumptions that are being made when we talk about organisations or groups that learn, or about individuals learning in groups or organisations. It suggests an alternative to thinking in these ways, namely, that learning is an activity of interdependent people. If one takes the view an organisation is the organising activities of interdependent people, it leads to a particular perspective on learning. Much of the communicative and power relating activities of interdependent people take the form of continually iterated patterns of repetition in which meaning and power figurations have the quality of stability which we call identity. But because of the nonlinear iterative nature of human interaction there is always the potential for small differences to be amplified into transformative shifts in identity. Learning is then understood as the emerging shifts in the patterning of human communicative interaction and power relating. Learning is the activity of interdependent people and can only be understood in terms of self‐organising communicative interaction and power relating in which identities are potentially transformed. Individuals cannot learn in isolation and organisations can never learn.
A complex adaptive perspective on learning within innovation projects
Authors: Harkema Saskia
Published: October 2003

Innovation is the lifeblood of companies, while simultaneously being one of the most difficult and elusive processes to manage. Failure rates are high – varying between six out of ten to nine out of ten – while the need to innovate is high. Departing from a real‐life case of a company, Sara Lee/Douwe Egberts, that has set learning within and from innovation projects high on the agenda, the main ideas about learning and innovation will be unfolded in the course of this article. It will be argued that most learning theories rest on a sender‐receiver model of knowledge transmission and this affects how people learn within innovation projects. A complex adaptive approach offers an alternative perspective from which one can evaluate and analyze learning and innovation processes. The most important characteristics of complex adaptive systems are non‐linearity, dynamic behavior, emergence and self‐organization. The implications of these phenomena for learning in innovation projects will be explained. The article finalizes with the preliminary findings of a multi‐agent simulation model, which explores what the underlying forces are beneath learning in innovation projects.
What Distinguishes the Top Performing New Products in Financial Services
Authors: Cooper Robert G. , Easingwood Christopher J. , Edgett Scott , Kleinschmidt Elko J. , Storey Chris
Published: October 2003

Despite previous comparisons of success and unsuccessful new products, an Important question remains unaddressed: What separates very successful new service products from the ordinary? Robert Cooper, Christopher Easingwood, Scott Edgett, Elko Kleinschmidt, and Chris Storey obtained data on 173 new financial services and identified three performance dimensions: financial performance, relationship enhancement, and market development. Of eleven potential success determinants, nine were found to be drivers of performance. Management implications included the need for a market‐driven, customer‐focused new product process, greater emphasis on planning and executing the launch, the role of product design, and project prioritization factors.
Strategies for Linking Vertical Cooperative R&D to Commercialization in Korea
Authors: Lee Chulwon , Bae Zong‐Tae , Lee Jinjoo
Published: October 2003

Since 1982, the government of Korea has actively promoted vertical cooperative R&D programs between government‐sponsored research institutes (GRIs) and private firms. A number affirms participated in the programs because cooperative R&D could lower the risk and could contribute to rapid commercialization of many technologies. In this article, Chulwon Lee, Zong‐Tae Bae, and Jinjoo Lee examine the effectiveness of participant firms' strategies for commercial utilization of cooperative R&D results, from the viewpoint of technology sourcing at the project level. The data have been obtained from 162 cases of vertical cooperative R&D projects from a diverse group of industries in Korea. Three different commercialization strategies are empirically derived through cluster analysis of the relative usage rates of cooperative R&D and of other supplementary technology acquisition methods. They find that the effectiveness of these strategy clusters varies significantly according to the types of innovation, that is, project‐business relatedness. If the project belongs to an existing business area, in‐house development augmented cooperative R&D strategy is the most effective. On the other hand, licensing‐in supplemented cooperative R&D strategy is the most successful, if the project belongs to a new business area. Findings suggest that firms participating in cooperative R&D projects should try to utilize other supplementary technology acquisition methods in order to achieve commercial utilization of cooperative R&D results.
Determinants of New Product Performance: A Review and Meta‐Analysis
Authors: Montoya‐Weiss Mitzi M. , Calantone Roger
Published: October 2003

Previous empirical research on new product performance has provided considerable evidence that a wide variety of antecedent factors can influence the outcomes of new product development activity. Mitzi Montoya‐Weiss and Roger Calantone conducted a comprehensive review of this literature and observed a wide variety of study designs and methodological approaches. They developed quantitative comparisons of the results, which, although cumbersome, provide a look at the persistent exploratory nature of this research. They report a wide variation in results that are surprisingly nonconvergent. Recommendations for broadening the range of factors considered and other approaches for accelerating the forward movement of the discipline are provided.
Product Replacement: Strategies for Simultaneous Product Deletion and Launch
Authors: Saunders John , Jobber David
Published: October 2003

John Saunders and David Jobber report results of their study of strategies for the simultaneous deletion and introduction of new products. Companies' long‐term survival depends upon their replacement of existing products with new ones. Managers have to accomplish the task successfully. This article explores product replacement and examines the difference between successful and unsuccessful replacements. Qualitative research helps formulate a conceptual model of product replacement strategies and to set hypotheses. A quantitative study of American and British firms helps to test the hypotheses.
Significant Issues for the Future of Product Innovation
Authors: Voss C. A.
Published: October 2003

In recognition of JPIM's eleventh year of publication, the editor‐in‐chief solicited a series of thoughtful contributions from members of the editorial board. Members were asked to reflect upon changes and opportunities that they see influencing our profession during the coming decade. In this issue, Chris Voss examines our growing recognition of the interdependence of a variety of business processes: product innovation, product development, process innovation, technology acquisition, industrial design, total quality management, and quality function deployment. He supports the need to establish tighter linkages among these important elements of a successful new products program, which he labels “total innovation management.” Like earlier contributions, this short essay is designed to introduce new perspectives. It is not essential that you agree with the recommendations, but we hope that you are stimulated as you reflect on the included issues.
An Approach for Determining Optimal Product Sampling for the Diffusion of a New Product
Authors: Jain Dipak , Mahajan Vijay , Muller Eitan
Published: October 2003

Free samples are an effective means for introducing and promoting a new product. However, product sampling is also expensive. As a result, careful consideration must be given to the question of how many samples should be distributed. To encourage product adoption in any target market, a company needs to determine the “right” amount of sampling. In other words, a firm needs to determine the optimal number of samples that must be available for trial by the innovators, early adopters, and other key consumers who influence the adoption rate of the new product. With too few samples, the product might not reach enough of these key consumers to generate the word‐of‐mouth recommendations necessary for market success. On the other hand, offering too many free samples is a waste of a company's resources.

Dipak Jain, Vijay Mahajan, and Eitan Muller propose a framework for determining the optimal levels of product sampling. In addition to identifying the upper bounds for the sampling levels of both durable and nondurable products, their model identifies the optimal size of product sampling based on such parameters as the coefficients of innovation and imitation, market potential, discount rate, and gross margin.

Several observations are made regarding the relationships between the optimal sampling level and the various parameters used in the model. For example, a high sampling level is not appropriate for a product with a high coefficient of innovation. On the other hand, if a product has a high coefficient of imitation, the sampling level should be high because a significant number of trials are necessary for word of mouth to be effective. High sampling levels are also indicated by a high discount rate or gross margin.

For durable goods, the optimal level of neutral sampling (i.e., sampling that does not specifically target innovators and early adopters) rarely exceeds 5%, and the maximum level is 7%. The optimal target sampling level is always higher than the corresponding neutral case, but, in most cases, only marginally so. For the parameter ranges chosen in this article, the maximum level for target sampling is approximately 9%. However, it is important to note that the theoretical upper bounds are no more than benchmarks for the maximum possible level of sampling. In practical situations, the optimal level may be considerably lower than these upper bounds. In such cases, the actual values will depend on the values for the various parameters used in the model.
Measuring New Product Success: The Difference that Time Perspective Makes
Authors: Hultink Erik Jan , Robben Henry S. J.
Published: October 2003

Management is often criticized for overemphasizing short‐term profits at the expense of long‐term growth. On the other hand, although numerous studies have explored the factors underlying new product success and failure, such studies rarely distinguish between short‐ and long‐term success. In fact, little research has been conducted to explore the relationship between a company's time perspective and its choice of criteria for measuring new product success. For that matter, little consensus exists as to just what we mean by the term success.

Expanding on work done by a PDMA task force on measurement of new product success and failure, Erik Jan Hultink and Henry S.J. Robben identify 16 core measures of new product success. In a survey of large Dutch companies, they explore managers' perceptions of new product success, hypothesizing that the importance attached to each of the 16 core measures depends on the company's time perspective. For example, they propose that criteria such as development cost and speed‐to‐market are more important in the short term, and return‐on‐investiment (ROI) is more important in the long term.

The study also examines the type of market served, the innovation strategy, and the perceived innovativeness of the company's products. It is hypothesized that these factors will influence the importance the company attaches to the core measures of new product success. For example, it is expected that speed‐to‐market is probably more important for technological innovators than for fast imitators or cost minimizers.

The findings support the hypothesis that the firm's time perspective influences the perceived importance of the core measures of success. For the short term, the respondents emphasize product‐level measures such as speed‐to‐market and whether the product was launched on time. In the long term, the focus is on customer acceptance and financial performance, including attaining goals for profitability, margins, and ROI. Four factors are perceived as being equally important for short‐term and long‐term success: customer satisfaction, customer acceptance, meeting quality guidelines, and product performance level. Customer satisfaction was found to be the most important measure, regardless of a company's time perspective.

Contrary to expectations, the perceived importance of the 16 core measures does not differ on the basis of the type of market, the innovation strategy, or the product's perceived innovativeness. In addition, the firm's functional orientation—technology push or market pull—does not affect the importance attached to the core measures of new product success.
How Canon and Sony Drive Product Innovation Through Networking and Application‐Focused R&D
Authors: Harryson Sigvald J.
Published: October 2003

To ensure the ongoing vitality of a company's product offerings, R&D professionals must play a daunting array of roles. The already rapid, yet still accelerating, pace of technological change may lead some companies to devote more resources to intensive internal research efforts. However, the shift toward global competition demands a more market‐oriented focus from R&D; clear understanding of current and potential markets must drive R&D efforts. And efficient, cost‐effective manufacturing of new products requires an R&D organization that understands and interacts effectively with the production department. How does a company create an environment in which its R&D organization comprises market‐savvy, production‐friendly experts in diverse technologies?

With case studies of R&D efforts at Canon and Sony, Sigvald Harryson identifies and illustrates the key mechanisms that these companies use to foster product innovation. His examples show how Canon and Sony use a combination of external and internal networking mechanisms to identify and acquire key technologies and related skills, gain market knowledge, improve the results of internal R&D efforts, and ensure the successful transfer of these results to efficient production processes.

He identifies four key mechanisms underlying successful product innovation at Canon and Sony: strategic training and job rotation for engineers, application‐driven R&D, direct transfer of development teams from R&D to production, and extensive networking with external centers of excellence and key suppliers. At Canon, the initial training program for all researchers and engineers begins with three months of work on a production line. Sony's new researchers and development engineers spend one month in production. Both companies also give their new R&D professionals three months of training in sales and marketing.

The emphasis on market‐driven research at both companies means that researchers have identified some commercial application for almost every initial research proposal that gains approval. Neither company treats research as a long‐term assignment; almost all engineers at both companies eventually move from the labs to production. And rather than viewing this job rotation strategy as a drain on the technological expertise in their labs, both companies rely on strong external networks with key suppliers and university‐based researchers as important sources for acquiring new technologies and the competencies needed to support them.
Risky Business or Competitive Power? Supplier Involvement in Japanese Product Design
Authors: Wasti S. Nazli , Liker Jeffrey K.
Published: October 2003

Notwithstanding the alleged risks of outsourcing design work, leading manufacturers in the Japanese automotive industry collaborate closely with their key suppliers. Despite widespread recognition of the effectiveness of these close‐knit supplier networks, however, little research exists on the factors that affect the purchase of design work from suppliers.

S. Nazli Wasti and Jeffrey K. Liker fill this gap by exploring the factors that affect Japanese automotive firms' purchase of design work from their component suppliers. Using data from a survey of 122 Japanese automotive component suppliers, their study addresses two key questions. First, what factors lead Japanese buyers to involve some suppliers heavily in design while giving others relatively little control over design decisions? And second, does the Japanese practice of involving suppliers in design offer performance benefits? The study focuses on first‐tier suppliers of parts, assemblies, and complete subsystems (e.g., audio, fuel and emissions, heating and air conditioning). The study does not include suppliers of raw materials and chemicals, assembly and processing equipment, indirect materials, tooling and dies, computers and software, or engineering and business consulting services.

The study breaks down the broad concept of supplier involvement in design work into three measurable elements: the extent to which the supplier influences decision‐making during the early stages of product development; the amount of control the buyer retains over the design; and the frequency of design‐related communication between the buyer and the supplier. Factors that have a positive effect on the level of supplier involvement among the companies studied include technological uncertainty of the component and the supplier's in‐house technical capabilities. For companies in the study, the level of competition in the supplier market has a negative effect on the degree of supplier involvement in design.

The responses indicate that supplier involvement offers performance benefits for both the supplier and the buyer. For the supplier firms studied, increased involvement in the design process permits greater focus on design for manufacturability (DFM). And of course, supplier‐generated design improvements clearly benefit the buyers, allowing these firms to capitalize on the experience and the insight that their suppliers have regarding the parts that they supply.
Perspective: Changing Product Development Strategy—A Managerial Challenge
Authors: Karlsson Christer , Åhlstrom Pär
Published: October 2003

By changing its product development strategies to match more closely the wants and needs of the marketplace, a firm can transform product development into a formidable competitive weapon. Just as formidible, however, is the effort that this transformation requires. Established organizational structures and corporate politics present significant barriers to acheiving fundamental changes in product development strategy.

Christer Karlsson and Pär Åhlstrom present a case study of one firm's efforts to build capabilities for creating new products quickly and efficiently. Rather than focus on the content of the firm's product development strategies, however, they emphasize the process this electromechanical manufacturing firm used for changing its product development strategy. Drawing on their experiences as clinical researchers in this effort, they describe key lessons learned during the change process, and they offer suggestions for managing the process of changing product development strategy.

They highlight five key lessons learned during the strategy development process. First, rather than viewing product development as a line function, a firm should view product development as a key executive area with responsibility for the company's competitive position. Second, market issues are the responsibility, not only of marketing, but also of product development and production. Third, to avoid corporate myopia, management control systems must consider not only time and money, but also acheivement of goals. Fourth, strategic planning flows more smoothly if the participants start by mapping the firm's past and present position before attempting to define the desired position. Finally, formulation of a product development strategy is the responsibility of a multifunctional team of executives.

Managers should keep a few rules in mind when devising a process for formulating a product development strategy. First, adopt a learning strategy throughout the change process. Formulation of a product development strategy involves many abstract concepts, and a successful strategy requires cross‐functional consensus. Second, combine tangible, direct activities with long‐term strategic aims. Third, avoid the pitfall of best practice. The form that the product development organization takes depends, to a great extent, on the type of development work. Finally, before discussing future strategies, the strategy formulation process should focus on analyzing the current situation.
Critical Development Activities for Really New versus Incremental Products
Authors: Song X. Michael , Montoya‐Weiss Mitzi M.
Published: October 2003

Does the development of really new products require a different approach from that of incremental new products? Current research and management practice seem to suggest that any successful new product development (NPD) process comprises a set of key activities, regardless of a product's innovativeness. It seems almost foolhardy to suggest that NPD could proceed without proficiency in all of the following tasks: strategic planning, idea development and screening, business and market opportunity analysis, technical development, product testing, and product commercialization.

Suggesting that the difference may be in the details, X. Michael Song and Mitzi Montoya‐Weiss present the results of a study that examines the development of 163 really new products and 169 incremental new products. The study's objective is to compare the NPD processes and performance outcomes of really new and incremental products. In other words, the study examines the interplay between a product's innovativeness, the NPD process, and the product's performance in the marketplace.

For the firms in the study, four sets of NPD activities—strategic planning, market analysis, technical development, and product commercialization—are key determinants of new product success for both really new products and incremental products. However, strategic planning and business and market opportunity analysis activities play contrasting roles for the two types of products. Working to improve proficiency in business and market opportunity analysis may be counterproductive for really new products, but it can increase the profitability of incremental products. Conversely, improving the proficiency of strategic planning activities has a positive effect on the profitability of the really new products, but it has a negative effect for the incremental products. Overall, the really new products in the study surpass the incremental products in meeting profit objectives.

Comparing current practice to best practice, the firms in the study have room for improvement. For both really new and incremental products, the firms in the study do not place sufficient emphasis on product commercialization activities. The participants also need to reassess the relative emphasis they place on strategic planning activities. The projects involving really new products do not place sufficient emphasis on strategic planning, while the incremental projects exhibit a relatively high level of proficiency in this area—exactly the opposite of the order that this study recommends.
Market Learning and Radical Innovation: A Cross Case Comparison of Eight Radical Innovation Projects
Authors: O'Connor Gina Colarelli
Published: October 2003

Does customer input play the same key role in every successful new‐product development (NPD) project? For incremental NPD projects, market information keeps the project team focused on customer wants and needs. Well‐documented methods exist for obtaining and using market information throughout the stages of an incremental NPD project. However, the role of market learning seems less apparent if the NPD project involves a really new product—that is, a radical innovation that creates a line of business that is new not only for the firm but also for the marketplace. In all likelihood, customers will not be able to describe their requirements for a product that opens up entirely new markets and applications.

To provide insight into the role that market learning plays in NPD projects involving really new products, Gina Colarelli O'Connor describes findings from case studies of eight radical innovation projects. Participants in the study come from member companies of the Industrial Research Institute, a consortium of large company R&D managers. With a focus on exploring how market learning for radical innovations differs from that of incremental NPD projects, the case studies examine the following issues: the nature and the timing of market‐related inquiry; market learning methods and processes; and the scope of responsibility for market learning, and confidence in the results.

Observations from the case studies suggest that the market‐related questions that are asked during a radical innovation project differ by stage of development, and they differ from the questions that project teams typically ask during an incremental NPD effort. For example, assessments of market potential, size, and growth were not at issue during the early stages of the projects in this study. Such issues came into play after the innovations were proven to work under controlled conditions and attention turned to finding applications for the technology.

For several projects in the study, internal data and informal networks of people throughout relevant business units provide the means for learning about the hurdles the innovation faces and about markets that are unfamiliar to the development group. The projects in this study employ various techniques for reducing market uncertainty, including offering the product to the most familiar market and using a strategic ally who is familiar with the market to act as an intermediary between the project team and the marketplace.