bluuebunny/crossref_metadata_2025 huggingface dataset:
Marketing Strategy
Authors: Varadarajan Rajan
Published: December 2010

A cursory examination of marketing literature suggests that the term
marketing strategy
is used in a wide variety of contexts. At one extreme, marketing strategy is broadly conceptualized as a multidimensional construct encompassing a broad array of integrated and internally consistent set of coordinated behaviors by an organization in the marketplace; that is, behaviors directed at consumers, customers, competitors, and/or other key constituencies in the marketplace. At the other extreme, narrow conceptualizations of marketing strategy essentially focus on specific aspects or subsets of the broader array of behaviors that essentially constitute an organization's marketing strategy. In multibusiness firms, the marketing strategies of individual businesses in the firm's portfolio are influenced by as well as influence the firm's corporate strategy. This article provides an overview of the scope of marketing strategy and presents a definition of marketing strategy. It also highlights the relevance of a number of other articles in this volume of the encyclopedia in the broader context of marketing strategy content and formulation process, and marketing strategy drivers and outcomes.
Causal Research
Authors: Oppewal Harmen
Published: December 2010

Causal knowledge is one of the most useful types of knowledge. Causal research aims to investigate causal relationships and therefore always involves one or more independent variables (or hypothesized causes) and their relationships with one or multiple dependent variables. Causal relationships can be tested using statistical and econometric methods. However, in many cases conclusions about causality are stronger if they can be based on
designed
experiments. Experiments typically include one or more experimental conditions and a control condition. Random assignment of units to these conditions allows the application of statistical theory to infer the probability of effects being caused by other factors than the designed, manipulated factor. Designing an experiment involves making a series of decisions about, among others, the unit of observation, the setting in which the experiment is to be conducted, the creation of experimental stimuli and observation instruments, the number of conditions to create and how many test units to include, and how to assign units to the conditions. Design types vary based on whether they are quasi‐experimental or true experiments, how many independent factors they include, whether they include all possible conditions or only a subset of conditions, and whether they expose units to single or multiple treatments.
Marketing Research Proposal
Authors: Bhalla Gaurav
Published: December 2010

One of the defining characteristics of contemporary management practice is information‐based decision making. However, business/marketing executives do not always have a complete or an accurate understanding of markets and their elements, such as customers, competitors, and consumption occasions. Marketing research (MR) is widely used to provide relevant and timely information to client companies and their decision makers. The MR departments of client companies issue request for proposals (RFP)s and review MR proposals from competing service providers to identify and select the best company for the assignment. The quality of the MR proposal plays a significant role in determining which company wins the business. Key drivers of the quality of an MR proposal are a deep understanding of the client's business issue, how well that understanding is parlayed into designing a research study, the conceptual framework guiding data collection, and the analytical tools used to extract information and insights from the data collected. The article presents a framework for proposal development and discusses how its various elements should be discussed to ensure that what is communicated to the client is rigorous, systematic, and complete.
Conjoint Analysis
Authors: Rao Vithala R.
Published: December 2010

This article chapter provides an up‐to‐date review of methods that have come to be calledconjoint analysis. These methods enable marketing researchers to determine trade‐offs among attributes of a new product based on responses of stated preferences and stated choices. These trade‐offs can assist in product design, pricing, market segmentation, and similar marketing decisions. There are essentially four types of conjoint analysis; these are traditional conjoint analysis that uses stated preferences, choice‐based conjoint analysis (CBCA) that uses stated choices, self‐explicated conjoint analysis that uses direct elicitation of attribute importances and ratings on attribute levels, and adaptive conjoint analysis (ACA) which involves a staged and adaptive data collection. Over several thousand conjoint studies were conducted since the introduction of this method in the early 1970s. The chapterarticle also covers significant advances in estimation methods and design of stimuli (profiles and choice sets) over these years. Essentially, this methodology is alive and thriving well.
Hypothesis Testing Related to Differences Parametric Tests
Authors: Schmidt Marcus J.
Published: December 2010

This article covers parametric tests of one and two samples. First, the implications of making decisions under uncertainty are discussed. Next, the concepts of hypothesis testing, probability values, and confidence intervals are introduced, and the steps of the hypothesis testing procedure are explicated. The consequences of making false decisions (type I and type II errors) are clarified and the difference between a one‐ and a two‐tailed test is made clear. The following tests are covered: large sample test (i) of the mean and (ii) of the population proportion, and small sample test of (iii) mean and (iv) proportion. First, we show how to conduct the tests based on one sample where the empirical dataset is compared to a hypothesized value. Thereafter, we repeat the same four test conditions but now the focus is on the difference between two empirical samples. In separate sections, we describe how to carry out a matched sample test, a test for equality of two population variances, and a test of difference between means when variances are not equal.
Latent Class and Finite Mixture Models
Authors: Dillon William R.
Published: December 2010

Latent class analysis and, more generally, finite mixture models have seen increased use in marketing since the early 1980s. The popularity of latent class and finite mixture models can, in large measure, be traced to the important role individual differences (i.e., heterogeneity) play in understanding marketing and consumer behavior phenomenon. At the most basic level, latent class and finite mixture models have allowed marketing researchers to account for individual heterogeneity when estimating model parameters. Our objectives in this article are twofold: First, we provide an overview of latent class and finite mixture models, which considers basic model forms, estimation, and special cases. Second, we provide a brief discussion of the various model forms and application settings that have relied on latent class and finite mixture models to account for individual‐level heterogeneity and, in so doing, provide both a historical perspective and a treatment of some recent developments.
Common Methods Bias
Authors: Kamakura Wagner A.
Published: December 2010

Common methods bias is a well‐documented phenomenon observed in research based on self‐reported measures. The fact that multiple constructs are measured using common methods (e.g., multiple‐item scales presented within the same survey) leads to spurious effects due to the measurement instruments rather than to the constructs being measured. For example, the fact that subjects are asked to report their own perceptions or impressions on two or more constructs in the same survey is likely to produce spurious correlations among the items measuring these constructs owing to response styles, social desirability, priming effects which are independent from the true correlations among the constructs being measured. The most common approach for assessing and controlling for common methods bias is to conduct a multitrait–multimethod study, which requires that the same subjects are measured on multiple constructs using multiple methods or instruments.
Random Coefficients Modeling
Authors: Arora Neeraj
Published: December 2010

In marketing, it is important to recognize interpersonal differences in model parameters such as brand preference and price sensitivity. In recent years, random coefficient modeling has significantly simplified our ability to characterize heterogeneity. A particularly useful aspect of random coefficient models is that each provides individual‐level inference. To model unobserved heterogeneity, one can assume that individual response coefficients (β

i

) come from an underlying distribution. In the finite mixture approach, this distribution is discrete. If the true underlying distribution of preference is continuous, a simple approach to characterize heterogeneity may be to use a multivariate normal distribution. Because of its simplicity and conceptual appeal, the multivariate normal distribution of heterogeneity has experienced considerable popularity in marketing. An even more flexible approach may be to use a normal component mixture model that is capable of representing a wide variety of distributions of heterogeneity. To carry out estimation, finite mixture models use maximum likelihood methods. For continuous distributions of heterogeneity, Markov chain Monte Carlo (MCMC) estimation methods are commonly used. A particular advantage of MCMC methods is that they offer significant flexibility in specifying the functional form of the heterogeneity distribution.
Customer Satisfaction
Authors: Oliver Richard L.
Published: December 2010

The concept of customer satisfaction is reviewed from a theory‐based applied perspective based on a large body of work in the academic community that has only recently found its way into nonacademic surveys. Although other conceptualizations have been suggested, the expectancy disconfirmation with performance model is used here as a guiding framework wherein satisfaction is viewed as an end‐state with distinct antecedents. Each of the focal determinants, namely expectations, performance, and subjective disconfirmation, is defined, explained from a conceptual perspective, and suggested as to how they might be used in satisfaction studies. Additionally, a number of issues facing satisfaction researchers are explored and resolved throughout the discussion.
The Stage‐Gate Idea to Launch System
Authors: Cooper Robert G.
Published: December 2010

Because new‐product projects underperform at an alarming rate, many companies have sought solutions in the form of a professional idea‐to‐launch process or methodology, such as Stage‐Gate
®
. A Stage‐Gate
®
system consists of a series of stages, typically five; each stage prescribes the key tasks and best practices for the project team to execute. Stages are preceded by gates, which are the quality check and Go/Kill or investment decision points in the process. Stage‐Gate
®
systems build in known best practices in the field of new‐product development, and hence improve project success rates and performance.
Product Platforms
Authors: Meyer Marc H. , de Weck Olivier , Marion Tucker
Published: December 2010

This article presents definitions for market segments and market applications, product portfolios, and product and process platforms. It also provides methods for planning product architecture and product platforms within that architecture.
GE
/
Mc
Kinsey
Matrix
Authors: Sood Ashish
Published: December 2010

This article encompasses the GE/McKinsey matrix, which is a nine‐cell portfolio matrix tool developed by McKinsey & Company for GE's large portfolio of strategic business units (SBU). The GE/McKinsey matrix was designed as an extension of the Boston Consulting group's BCG growth‐share matrix. The two factors used in the analysis are the attractiveness of the relevant industry and the SBU's competitive strength within that industry. The nine cells in the matrix can be grouped into three major segments. Managers can formulate appropriate strategies to strengthen their positions through the portfolio analysis.
Takeoff
Authors: Van den Bulte Christophe
Published: December 2010

Takeoff is the first marked increase in sales of a new product. This corresponds to the transition between the introduction and growth stages of the product life cycle, and to the kink in the hockey‐stick pattern of new product or market sales. Takeoff is important to managers and investors as it greatly affects the timing of cash inflows and of necessary investments in manufacturing, logistics, marketing communications, and customer support. Having some consensus within the company about when the product is likely to take off also prevents management from prematurely “pulling the plug” on a slow‐selling new product. Research indicates that, on average, new‐product categories experience takeoff 5–15 years after launch. Recent research indicates that the entry of new firms rather than price declines is the main trigger of takeoff. There is no strong evidence that economic conditions or national culture greatly affect the time to takeoff.
Strategic Export Marketing – Achieving Success in a Harsh Environment
Authors: Katsikeas Constantine S. , Leonidou Leonidas C.
Published: December 2010

Sound export strategies are critical in achieving success in today's harsh business environment. This article highlights the process of formulating such strategies. As a starting point, the firm has first to gain appropriate resources and capabilities that are conducive to exporting. It is also important to identify opportunities and threats from an analysis of both the foreign task environment and the macroenvironment. Following this assessment of the internal and external situation, the next step is to select the most attractive foreign countries to enter, as well as target the most promising customer groups within each market. Clear, measurable, and achievable objectives have then to be set for the whole export operation, and then these are to be broken down for each country and customer group selected. To achieve the objectives set, a strategy has to be proposed for each of the elements of the marketing mix (i.e., product, price, distribution, logistics, and promotion). To effectively and efficiently execute the export marketing strategy, it is crucial to have a proper export department staffed with adequate personnel, and managed by capable people. Finally, it is essential to set up a mechanism for controlling the implementation of the marketing strategy and to prepare contingency plans.
Digital Medium and Global Marketing
Authors: Shankar Venkatesh
Published: December 2010

The digital revolution is transforming the business landscape and profoundly influencing marketing in an increasingly global environment. The digital medium and global Internet marketing strategy have direct and moderating effects on the impact of marketing mix decisions on firm performance globally. With regard to global product development, the Internet significantly influences the effectiveness and speed of new product development and its impact on firm performance. The Internet has an important role in the effects of both company‐ and user‐generated communication efforts on firm performance. On the global pricing dimension, the Web allows more pricing transparency, while allowing firms to differentiate across countries. With regard to global distribution, the Web may serve as either a substitute or a complementary channel in different global markets and firms can improve performance in global markets by coordinating the Internet with other channels. In the future, rising Internet penetration and the surging growth of mobile media may change global marketing further. More research is needed to better understand the relationships among the Internet, mobile Internet, marketing mix decisions, and firm performance in the global context.
Global Account Management: The Rationale and Motivation
Authors: Harvey Michael , Moeller Miriam
Published: December 2010

As organizations are entering an increasingly complex global context, rapidly expanding operations overseas demand appropriate responses from multinational/global suppliers. Global account management (GAM) is a mechanism through which organizations are able to provide greater consistency and coordination to their customers, addressing the needs of a single customer in multiple environmental contexts. GAM structures allow the multinational corporation (MNC)/global organization to increase its information‐processing capacity as well as its bargaining power with regard to the global customer. Strategically, suppliers have the opportunity to become more global organizations. Both the motivation and responsibilities of GAM teams are explored, including a discussion on the promotion of social capital through trust building. We conclude by acknowledging that GAM allows organizations to cater to their customers efficiently and effectively, thereby gaining viability within the global arena. It is expected, however, that, in the future, newer forms of organizational structure will replace the present GAM configuration.
Forces Affecting Global Integration and Global Marketing
Authors: Gillespie Kate
Published: December 2010

Global integration is the state in which one national market (including a firm's home market) is significantly affected by other national markets. Because of global integration, international marketers cannot continue to successfully employ multiple single‐market strategies but instead must adopt global strategies that address multiple, if not all, national markets at the same time. Examples of such global strategies include global rollouts of new products, centralized production of standardized products, and global‐theme advertising. In the last quarter of the twentieth century, several forces, some interrelated, resulted in greater global integration. These forces have been categorized in different ways but generally fall into five categories: technological, buyer behavior, competitive, cost, and regulatory. Each industry is affected differently by the forces of global integration, but virtually all industries are affected in some way by these forces.
Services Globalization
Authors: Chan Haksin
Published: December 2010

The last two decades have witnessed phenomenal growth in the service sectors, domestic and international. Global expansion poses major challenges for service operations, since they involve prominent human elements. The adage “think globally, act locally” is especially applicable to services marketers. In global expansion, services such as lodging and healthcare that are “inseparable” (i.e., that cannot be performed away from the customer) require more local adaptation and incur greater risk than “separable” services such as repair and delivery. With technological advances, however, the inseparability problem may be circumvented to some extent. Another issue is the culture‐specific responses to the inevitable service failures. When the nature of failure is “economic” (e.g., a delayed flight), collectivists are more tolerant than individualists. But the pattern is reversed when the failure is “social” (e.g., an unfriendly flight attendant). Culture is clearly an important consideration for the control of service quality and the design of service‐recovery programs. Furthermore, protectionism is a major concern in times of economic downturn. The high visibility of many global service operations also makes them easy targets in social and political crises. On a positive note, global services research is at the “takeoff stage” of its life cycle. The trend of “servicization” should prompt refinement of global marketing theories. Research opportunities also abound in global service contexts – for pinpointing culture‐specific service quality dimensions, (dis)satisfaction responses, and recovery strategies.
Emerging Markets
Authors: Styles Chris , Voola Ranjit
Published: December 2010

While many definitions of
emerging markets
exist, all tend to have three characteristics in common: (i) rapid economic growth; (ii) proactive adoption of market‐based frameworks; and (iii) being in a transition phase between developing‐ and developed‐country status. The so‐called BRIC countries (Brazil, Russia, India, and China) have been highlighted as exemplars of emerging markets. It is projected that by 2050 the BRIC economies have the potential to overtake the current richest countries in terms of economic wealth. Markets within the emerging category have been further classified on the basis of national income and progress on market infrastructure development. For example, the
FTSE
index divides emerging markets into advanced emerging, emerging markets, and frontier markets. The key challenges facing emerging markets include governance, political risk, rapid urbanization, a shortage of highly skilled labor, poor infrastructure, and more recently, the global economic slowdown that began in 2008.
Marketing Aspects of Psychic Distance
Authors: Evans Jody
Published: December 2010

The term
psychic distance
was first introduced in 1956. It is the work done at the Uppsala University during the 1970s, however, that is credited with developing and popularizing the construct.
Psychic distance
is defined as
the distance between the home market and a foreign market, resulting from the perception of both cultural and business differences
. Such differences include culture, language, religion, education, legislation, politics, economic conditions, market structure, and business practices. While there is general agreement regarding the constituent elements of psychic distance, the primary source of current debate relates to the manner in which psychic distance is operationalized. In terms of outcomes, psychic distance has been linked to foreign market selection, entry mode, the standardization/adaptation of marketing strategies, and firm performance.
Marketing Aspects of Cultural Distance
Authors: Sousa Carlos M. P.
Published: December 2010

Cultural distance is a widely used construct in international marketing, where it has been identified as a key variable in explaining the behavior of firms in a vast array of areas including entry‐mode choice, foreign‐market selection, level of control, international‐marketing strategies, and performance. Existing studies, however, have provided mixed empirical results regarding the importance of cultural distance in the literature. Various reasons have been proposed to explain these inconclusive results. The argument that preferences and tastes of consumers in different countries are converging to a global norm appears to be plausible considering the emergence of the Internet, greater ease of information flow, and more frequent/easier international travel. Nonetheless, these inconsistent findings could also be attributed to the difficulty that exists in the conceptualization and operationalization of the cultural‐distance concept. Researchers are encouraged to provide a clear definition of cultural distance in their studies and be aware that the operationalization must be consistent with the conceptualization of the construct. Finally, the overreliance on Kogut and Singh's formula or an adapted version as a measure of cultural distance has led to an increasing call in the literature to develop new measures of cultural distance.
Export Assistance Programs
Authors: Gencturk Esra F.
Published: December 2010

This article encompasses Export Assistance Programs as the provision of both indirect and direct government support to encourage and assist exporting activites of individual firms and/or specific domestic industries. Almost all governments have an incentive to support national exports in order to improve the international competitiveness of domestic firms and hence the country's balance of trade. Yet, these assistance programs take different forms in different countries depending on a country's trade policy and its views toward government intervention in the business sector. These programs are regulated by World Trade Organization (WTO) and may be subject to threat of retaliation or dumping investigations if they violate (WTO) regulations. In terms of different types of export assistance programs considered, the direct export support services are grouped into (i) financial acitivities, (ii) information services, and (iii) export facilitating activities. Each of these services are then described briefly.
International Relationship Marketing
Authors: Pels Jaqueline
Published: December 2010

Relationship marketing suggests a different way of understanding the environment and, as a result, diverse ways of interacting with it. Both the academic as well as the managerial world have much to gain in studying and understanding these types of exchanges. By studying scholarly debates and the papers that have been published on this topic, it could be argued that there seems to be an academic shift toward relationship marketing. The question that is being addressed in this article is “Is this shift occurring at a managerial level and, more specifically, is it an international trend?” The researchers on contemporary marketing practice (CMP) perceived tension between theory and practice and designed a study with the objective to “profile marketing practice in a contemporary environment, and to examine the relevance of relational marketing in different organizational, economic, and cultural contexts.” A strong conceptual classification scheme was developed and studies undertaken in multiple countries in Europe, North America, South America, Asia, and Africa. The empirical studies do not support a shift toward relationship marketing. We need to be very cautious before proclaiming the universality of this view. In this postmodern world where diversity is the rule we, the academics, would serve the business community better if we start by acknowledging the diversity in marketing modes!
International Business‐to‐Business Marketing
Authors: Matthyssens Paul
Published: December 2010

Business‐to‐business (B2B) marketing has gone international. This article identifies the drivers of this development: delocalization of customers, growth in international trade, global purchasing by customers, the emergence of networks, and electronic commerce. The consequence is that business marketers internationalize faster and with diverse entry modes. They also face growing complexity in their marketing, leading to dilemmas regarding aggregation (grouping countries), arbitration (exploiting differences), and adaptation.
Microactuators: Control of the Properties of Micrometer Sized Actuators from Liquid Crystalline Elastomers Prepared in a Microfluidic Setup (Adv. Funct. Mater. 24/2010)
Authors: Ohm Christian , Fleischmann Eva‐Kristina , Kraus Isabelle , Serra Christophe , Zentel Rudolf
Published: December 2010

In this article new results on the preparation of monodisperse particles from a liquid crystalline elastomer in a microfluidic setup are presnted. For this, droplets from a liquid crystalline monomer are prepared in a microfluidic device and polymerized while they are flowing inside a microtube. The parti­cles obtained by this method possess an internal orientation, which gives them actuating properties. When they are heated into the isotropic phase of the liquid crystalline material they show a reversible change in shape whereby they change their length in one direction by almost 100%. It is shown how the variation of experimental parameters during their synthesis impacts the properties of these micro‐actuators. Influence over their primal shape, the strength of their shape changing properties, their size, and their mechanical properties is demontrated. From the systematic variation of experimental parameters a deep understanding of the complex processes taking place in a flowing droplet of a liquid crystalline material is obtainted. Additionally NMR analysis and swelling experiments on these actuating materials are provided.
Asymmetric Synthesis of 2‐Substituted Dihydrobenzofurans and 3‐Hydroxydihydrobenzopyrans through the Enantioselective Epoxidation of O‐Silyl‐Protected ortho‐Allylphenols
Authors: Jiang Hang , Sugiyama Takaya , Hamajima Akinari , Hamada Yasumasa
Published: December 2010

The Shi‐type epoxidation of O‐tert‐butyldiphenylsilyl (TBDPS) protected o‐allylphenols serves as an efficient strategy to construct the dihydrobenzofurans and dihydrobenzopyrans in up to 97% ee. This methodology led to the enantioselective synthesis of (+)‐marmesin, (−)‐(3′R)‐decursinol, and (+)‐lomatin.
The Direct Conversion of Heat to Electricity Using Multiferroic Alloys
Authors: Srivastava Vijay , Song Yintao , Bhatti Kanwal , James R. D.
Published: December 2010

We demonstrate a new method for the direct conversion of heat to electricity using the recently discovered multiferroic alloy, Ni45Co5Mn40Sn101. This alloy undergoes a low hysteresis, reversible martensitic phase transformation from a nonmagnetic martensite phase to a strongly ferromagnetic austenite phase upon heating. When biased by a suitably placed permanent magnet, heating through the phase transformation causes a sudden increase of the magnetic moment to a large value. As a consequence of Faraday’s law of induction, this drives a current in a surrounding circuit. Theory predicts that under optimal conditions the performance compares favorably with the best thermoelectrics. Because of the low hysteresis of the alloy, a promising area of application of this concept appears to be energy conversion at small ΔT, suggesting a possible route to the conversion of the vast amounts of energy stored on earth at small temperature difference. We postulate other new methods for the direct conversion of heat to electricity suggested by the underlying theory.
An extension of Khalatnikov's theory of Kapitsa thermal resistance
Authors: Budaev B.V. , Bogy D.B.
Published: December 2010

This paper develops a novel approach to Kapitsa thermal resistance which extends Khalatnikov's acoustic mismatch theory by inclusion of a previously excluded broad class of acoustic waves that violate the Sommerfeld radiation condition, which is essential for the theory of sound but is not relevant for the analysis of heat transport. This extension not only preserves the main ideas of Khalatnikov's theory but we show it also provides reasonable estimates of the Kapitsa resistance.
Network analysis of associations between serum interferon‐α activity, autoantibodies, and clinical features in systemic lupus erythematosus
Authors: Weckerle Corinna E. , Franek Beverly S. , Kelly Jennifer A. , Kumabe Marissa , Mikolaitis Rachel A. , Green Stephanie L. , Utset Tammy O. , Jolly Meenakshi , James Judith A. , Harley John B. , Niewold Timothy B.
Published: December 2010

Objective

Interferon‐α (IFNα) is a primary pathogenic factor in systemic lupus erythematosus (SLE), and high IFNα levels may be associated with particular clinical manifestations. The prevalence of individual clinical and serologic features differs significantly by ancestry. This study was undertaken to detect associations between clinical and serologic disease manifestations and serum IFNα activity in a large diverse SLE cohort, using multivariate and network analyses.

Methods

We studied 1,089 SLE patients (387 African American, 186 Hispanic American, and 516 European American patients). The presence or absence of individual American College of Rheumatology (ACR) clinical criteria for SLE, autoantibodies, and serum IFNα activity data were analyzed in univariate and multivariate models. Iterative multivariate logistic regression was performed in each ancestral background group separately to establish the network of associations between variables that were independently significant following Bonferroni correction.

Results

In all ancestral backgrounds, high IFNα activity was associated with anti‐Ro and anti–double‐stranded DNA antibodies (P = 4.6 × 10−18 and P = 2.9 × 10−16, respectively). Younger age, non‐European ancestry, and anti‐RNP were also independently associated with increased serum IFNα activity (P ≤ 6.7 × 10−4). We found 14 unique associations between variables in network analysis, and only 7 of these associations were shared among >1 ancestral background. Associations between clinical criteria were different for different ancestral backgrounds, while autoantibody–IFNα relationships were similar across backgrounds. IFNα activity and autoantibodies were not associated with ACR clinical features in multivariate models.

Conclusion

Our findings indicate that serum IFNα activity is strongly and consistently associated with autoantibodies, and not independently associated with clinical features in SLE. IFNα may be more relevant to humoral tolerance and initial pathogenesis than later clinical disease manifestations.
Macrophage migration inhibitory factor regulates neutrophil chemotactic responses in inflammatory arthritis in mice
Authors: Santos Leilani L. , Fan Huapeng , Hall Pam , Ngo Devi , Mackay Charles R. , Fingerle‐Rowson Gunter , Bucala Richard , Hickey Michael J. , Morand Eric F.
Published: December 2010

Objective

Macrophage migration inhibitory factor (MIF) facilitates multiple aspects of inflammatory arthritis, the pathogenesis of which has been significantly linked to the activity of neutrophils. The effects of MIF on neutrophil recruitment are unknown. This study was undertaken to investigate the contribution of MIF to the regulation of neutrophil chemotactic responses.

Methods

K/BxN serum‐transfer arthritis was induced in wild‐type (WT), MIF−/−, and monocyte chemotactic protein 1 (MCP‐1; CCL2)–deficient mice as well as in WT mice treated with monoclonal antibodies to cytokine‐induced neutrophil chemoattractant (anti‐KC). Leukocyte trafficking in vivo was examined using intravital microscopy, and neutrophil function in vitro was examined using migration chambers and assessment of MAP kinase activation.

Results

K/BxN serum‐transfer arthritis was markedly attenuated in MIF−/− mice, with reductions in the clinical and histologic severity of arthritis and the synovial expression of KC and interleukin‐1. Arthritis was also reduced by anti‐KC antibody treatment, but not in MCP‐1–deficient mice. In vivo, neutrophil recruitment responses to KC were reduced in MIF−/− mice. Similarly, MIF−/− mouse neutrophils exhibited reduced chemotactic responses to KC in vitro, despite displaying unaltered chemokine receptor expression. Reduced chemotactic responses of MIF−/− mouse neutrophils were associated with reduced phosphorylation of p38 and ERK MAP kinases.

Conclusion

These findings suggest that MIF promotes neutrophil trafficking in inflammatory arthritis via facilitation of chemokine‐induced migratory responses and MAP kinase activation. Therapeutic MIF inhibition could limit synovial neutrophil recruitment.
Chiral Iridium Spiro Aminophosphine Complexes: Asymmetric Hydrogenation of Simple Ketones, Structure, and Plausible Mechanism
Authors: Xie Jian‐Bo , Xie Jian‐Hua , Liu Xiao‐Yan , Zhang Qian‐Qian , Zhou Qi‐Lin
Published: December 2010

The iridium complexes of chiral spiro aminophophine ligands, especially the ligand with 3,5‐di‐tert‐butylphenyl groups on the P atom (1c) were demonstrated to be highly efficient catalysts for the asymmetric hydrogenation of alkyl aryl ketones. In the presence of KOtBu as a base and under mild reaction conditions, a series of chiral alcohols were synthesized in up to 97 % ee with high turnover number (TON up to 10 000) and high turnover frequency (TOF up to 3.7×104 h−1). Investigation on the structures of the iridium complexes of ligands (R)‐1a and 1c by X‐ray analyses disclosed that the 3,5‐di‐tert‐butyl groups on the P‐phenyl rings of the ligand are the key factor for achieving high activity and enantioselectivity of the catalyst. Study of the catalysts generated from the Ir‐(R)‐1c complex and H2 by means of ESI‐MS and NMR spectroscopy indicated that the early formed iridium dihydride complex with one (R)‐1c ligand was the active species, which was slowly transformed into an inactive iridium dihydride complex with two (R)‐1c ligands. A plausible mechanism for the reaction was also suggested to explain the observations of the hydrogenation reactions.
Long-term global quality of life in patients treated for colorectal liver metastases
Authors: Wiering B , Oyen W J G , Adang E M M , van der Sijp J R M , Roumen R M , de Jong K P , Ruers T J M , Krabbe P F M
Published: December 2010

Background

Surgical treatment of colorectal liver metastases has become increasingly aggressive. The influence of this more active surgical approach on patients' health-related quality of life (HRQoL) has hardly been evaluated. This study investigated the impact of surgical and systemic treatment on HRQoL in patients undergoing hepatic resection for colorectal metastases.

Methods

A total of 145 patients with colorectal liver metastases were entered prospectively into the study. Based on HRQoL values derived from the EuroQol—5D, health summary measures were calculated to express the overall impact on four distinct clinical states. The HRQoL instrument was used at baseline, 3 and 6 weeks after surgery, and every 3 months thereafter for up to 3 years.

Results

Patients showed a clear deterioration in HRQoL in the first weeks after surgery, followed by a recovery to baseline levels at 3 months after potentially curative surgery. In contrast, a sustained decline was noted when initial surgery for colorectal liver metastases was considered futile and palliative chemotherapy was started immediately. Three years after initial surgery, there were distinct differences in HRQoL between patients with or without recurrence. The latter group still had HRQoL scores at baseline levels, whereas patients with tumour recurrence showed a significant deterioration in HRQoL. Remarkably, there was no decline in HRQoL in patients with recurrent disease who could be treated by secondary surgical intervention.

Conclusion

Superior overall HRQoL in the first 3 years after initial successful surgical intervention merits an aggressive surgical approach and intensive follow-up to detect recurrence early.
Screening 64 cultivars Catharanthus roseus for the production of vindoline, catharanthine, and serpentine
Authors: Chung Ill‐Min , Kim Eun‐Hye , Li Mai , Peebles Christie A. M. , Jung Woo‐Suk , Song Hog‐Keun , Ahn Joung‐Kuk , San Ka‐Yiu
Published: December 2010

The leaves of Catharanthus roseus (L.) G. Don. are a valuable source of the terpenoid indole alkaloid (TIA) anticancer drugs, vinblastine and vincristine. In particular, the precursor molecules vindoline and catharanthine are harvested from leaves and used for the semisynthetic production of vinblastine and vincristine. Because of this application, catharanthine and vindoline can be used to screen for high‐yielding TIA cultivars. In this study, we compared the TIA concentrations in the leaves of 64 different cultivars of C. roseus in the soil experiments. The highest concentration of serpentine was found in Cooler Rose Hot (461 ± 46 μg/g DW). Concentrations of vindoline (2082 ± 113 μg/g DW) and catharanthine (2903 ± 384 μg/g DW) were highest in Pacifica Peach. To eliminate the abiotic and biotic effects of the soils on the plant growth, sterile agar experiments were performed to investigate the TIA concentrations and mRNA transcript levels of selected TIA pathway genes. Six cultivars were investigated (two each of the high level, mid level, and low level producers of TIAs). © 2011 American Institute of Chemical Engineers Biotechnol. Prog., 2011
Chemical Variations of the Essential Oils in Flower Heads of Chrysanthemum indicum L. from China
Authors: Zhang Cong , Qin Min‐Jian , Shu Pan , Hong Jun‐Li , Lü Lin , He Dan‐Xia
Published: December 2010

The volatile compositions of hydrodistilled essential oils in the flower heads of Chrysanthemum indicum L. from eight populations in China were analyzed by GC/MS. A total of 169 compounds representing 88.79–99.53% of the oils were identified, and some remarkable differences were found in the constituent percentages of the eight populations. The predominant components of the essential oils were 1,8‐cineole (0.62–7.34%), (+)‐(1R,4R)‐camphor (0.17–27.56%), caryophyllene oxide (0.54–5.8%), β‐phellandrene (0.72–1.87%), (−)‐(1S,2R,4S)‐borneol acetate (0.33–8.46%), 2‐methyl‐6‐(p‐tolyl)hept‐2‐ene (0.3–8.6%), 4,6,6‐trimethylbicyclo[3.1.1]hept‐3‐en‐2‐yl acetate (0.17–26.48%), and hexadecanoic acid (0.72–15.97%). The chemotaxonomic value of the essential‐oil compositions was discussed according to the results of cluster analysis (CA) and principal‐component analysis (PCA). The eight populations were divided into five groups as different chemotypes (Groups A–E), and the scores together with the loadings revealed clearly different chemical properties of each population. In conclusion, GC/MS in combination with chemometric techniques provided a flexible and reliable method for characterizing the essential oils of different populations of C. indicum L.
Structure–Activity Relationships of Precursors and Analogs of Natural 3‐Enoyl‐tetramic Acids
Authors: Barnickel Bertram , Bayliffe Frances , Diestel Randi , Kempf Karl , Laschat Sabine , Pachali Steffen , Sasse Florenz , Schlenk Andrea , Schobert Rainer
Published: December 2010

Fragments and synthetic precursors prepared en route to the macrocyclic 3‐acyltetramic acids (=3‐acyl‐1,5‐dihydro‐4‐hydroxy‐2H‐pyrrol‐2‐ones) aburatubolactam and macrocidin A, as well as other analogs with variance in the ring heteroatom (N, O, S), and the residues at N(1), C(3), and C(5) were tested for cytotoxic and antimicrobial effects. Anticancer activity against various tumor cell lines in vitro did not necessarily require an intact pyrrolidin‐2,4‐dione ring. An acyclic β‐hydroxy‐octatrienoyl amide precursor to aburatubolactam also exhibited distinct activity with an IC50 (120 h) value of <2.5 μM. The length of 3‐oligoenoyl residues had little influence on the anticancer activity, but 3‐alka‐oligoenoyl tetramic acids were far more efficacious than their 3‐(4‐methoxycinnamoyl) congeners. N‐H‐3‐acyltetramic acids were generally more active than their N‐Me or N‐Boc analogs, unless further polar groups necessitated an increased lipophilicity for sufficient uptake. Tetronic and thiotetronic acids were far less antiproliferative in cancer cells when compared with identically substituted tetramic acids.
Noncovalent Binding of Some New Lipophilic Gadolinium  DTPA Complexes to Human Serum Albumin. A Structure–Affinity Relationship
Authors: Laurent Sophie , Vander Elst Luce , Henrotte Virginie , Muller Robert N.
Published: December 2010

Four Gadolinium⋅DTPA complexes bearing long lipophilic alkyl chains were synthesized: two bis[amide] and two 4‐substituted derivatives. In two of them (one bis[amide] and one 4‐substituted), the alkyl chain ends with a carboxylate function. Their relaxometric properties in H2O show the self aggregation of Gd⋅DTPA‐BdodecylAmide, the better stability of the 4‐substituted derivatives vs. Zn transmetallation, and the very good stability of Gd⋅(4‐(carboxyundecylisothiourea‐Bz)DTPA). Amongst the four compounds, only Gd⋅(4‐(carboxyundecylisothiourea‐Bz)DTPA) shows a strong interaction with human serum albumin (HSA) as demonstrated by proton relaxometry and ESI mass spectrometry. These data highlight the importance of the negative charge on the alkyl chain in the context of the interaction of Gd⋅(4‐substituted DTPA) derivatives with HSA.
Reaction Site Diversity in the Reactions of Titanium Hydrazides with Organic Nitriles, Isonitriles and Isocyanates: TiNα Cycloaddition, TiNα Insertion and NαNβ Bond Cleavage
Authors: Schofield A. Daniel , Nova Ainara , Selby Jonathan D. , Schwarz Andrew D. , Clot Eric , Mountford Philip
Published: December 2010

We report a range of new transformations of the diamide–amine supported TiNNPh2 functional group with a variety of unsaturated substrates, along with DFT studies of the key mechanisms. Reaction of [Ti(N2Npy)(NNPh2)(py)] (4, N2Npy=(2‐NC5H4)CMe(CH2NSiMe3)2; py=pyridine) with MeCN gave the dimeric species [Ti2(N2Npy)2{μ‐NC(Me)(NNPh2)}2] through a [2+2] cycloaddition process. Reaction of 4 or [Ti(N2NMe)(NNPh2)(py)] (5, N2NMe=MeN(CH2CH2NSiMe3)2) with fluorinated benzonitriles gave the terminal hydrazonamide complexes [Ti(N2NR){NC(Ar)NNPh2}(py)] (R=py or Me; Ar=2,6‐C6H3F2 or C6F5). DFT studies showed that this proceeds through an overall [2+2] cycloaddition–reverse cycloaddition, resulting in net insertion of ArCN into the TiNα bonds of the respective hydrazides. Reaction of 4 with a mixture of MeCN and PhCCMe gave the metallacycle [Ti(N2Npy){NC(Me)C(Ph)C(Me)NNPh2}] by sequential coupling of TiNNPh2 with PhCCMe and then MeCN. A related product, [Ti(N2Npy){NC(Me)C(ArF)C(H)NNPh2}], was formed by insertion of MeCN into the TiC bond of the isolated azatitanacyclobutene [Ti(N2Npy){N(NPh2)C(H)C(ArF)}] (ArF=3‐C6H4F). Reaction of 4 with two equivalents of B(Ar)3 (Ar=C6F5) formed the zwitterionic borate [Ti(N2Npy){η2‐N(NPh2)B(Ar)3}] by electrophilic attack at Nα. Compounds 4 and 5 reacted with tBuNC and/or XylNC (Xyl=2,6‐C6H3Me2) to give the NαNβ bond cleavage products, [Ti(N2NR)(NCNR′)(NPh2)] (R=py or Me; R′=tBu or Xyl), containing metallated carbodiimide ligands. DFT studies of these reactions found an initial addition of RNC across TiNα followed by Nβ coordination, and finally complete Nα transfer from the NNPh2 to the RNC fragment. Reaction of 5 with Ar′NCE (E=O, S, Se; Ar′=2,6‐C6H3iPr2) gave the [2+2] cycloaddition products [Ti(N2NMe){N(NPh2)C(NAr′)O}(py)] and [Ti(N2NMe){N(NPh2)C(NAr′)E}] (E=S or Se), which did not undergo further transformation of the TiNNPh2 moiety.
A Combined Ligand‐ and Structure‐Based Virtual Screening Protocol Identifies Submicromolar PPARγ Partial Agonists
Authors: Vidović Dušica , Busby Scott A. , Griffin Patrick R. , Schürer Stephan C.
Published: December 2010

Peroxisome proliferator‐activated receptor γ (PPARγ) is involved in expression of genes that control glucose and lipid metabolism. PPARγ is the molecular target of the thiazolidinedione (TZD) class of antidiabetic drugs. However, despite their clinical use these drugs are associated with numerous adverse effects, which are related to their full activation of PPARγ transcriptional responses. PPARγ partial agonists are the focus of development efforts towards second‐generation PPARγ modulators with favorable pharmacology, potent insulin sensitization without the severe full agonists’ adverse effects. In order to identify novel PPARγ partial agonist lead compounds, we developed a virtual screening protocol based on three‐dimensional ligand‐shape similarity and docking. Prioritization gave 235 compounds for experimental screening from the National Institutes of Health (NIH) Molecular Libraries Small Molecule Repository (MLSMR)—a chemical library containing 340 000 compounds. Seven novel potent partial agonists were confirmed in cell‐based transactivation and competitive binding assays. Our results illustrate a well‐designed virtual screening campaign successfully identifying novel lead compounds as potential entry points for the development of antidiabetic drugs.
Indirect Anodic Stripping Voltammetric Determination of Tl(I) and Tl(III) in the Baltic Seawater Samples Enriched in Thallium Species
Authors: Krasnodębska‐Ostręga Beata , Pałdyna Joanna , Wawrzyńska Marta , Stryjewska Ewa
Published: December 2010

The sensitive method DPASV with HMDE in the presence of DTPA and acetic buffer was used for determination of Tl(I) and Tl(III) in spiked seawater sample. The proposed method was based on the appropriate chemical conservation of Tl speciation. To determine the total amount of Tl, an addition of ascorbic acid to sub‐sample was necessary, but to determine Tl(I) to the second sub‐sample addition of DTPA was needed. Various factors influencing the stability of Tl(III) and electrochemical parameters were investigated. The quantification limit of 1.8 ng mL−1 Tl(I) was found for 8 min preconcentration. The procedure was validated using recovery study and HPLC ICP MS determinations.