bluuebunny/crossref_metadata_2025 huggingface dataset:
Idea Management
Authors: Baumgartner Jeffrey
Published: December 2010

Although suggestion schemes have been around for hundreds of years, idea management is still relatively new. Idea management is a structured business process for capturing focused business ideas from employees of a company, or any other group, and evaluating those ideas to identify the most promising ones. The approach is typically based around established creative problem solving (CPS) methodology, which allows managers to focus suggestions on actual business needs. The idea management process is typically facilitated by an enterprise software application with a front end for the submission of ideas and a back end where those ideas are evaluated by experts. This system is normally web based and all actions are performed via a web browser. However, software alone is not sufficient for a successful idea management initiative. An innovation manager or team needs to promote the system to colleagues, provide incentives for participation, and oversee the review and implementation of ideas. Likewise, top management buy‐in ensures better results. The purpose of any idea management initiative should be the profitable implementation of ideas generated by the system.
Open Innovation
Authors: West Joel
Published: December 2010

Inspired by studies of twentieth century vertically integrated corporate giants, the traditional model of industrial innovation assumed an internal pipeline of product innovation from R&D to manufacturing. However, the open innovation paradigm developed by Chesbrough extends this model, identifying existing and new practices in which innovation commercialization crosses firm boundaries. Open innovation considers two primary commercialization modes: the inbound in which firms use external sources of innovation, and the outbound in which firms find other ways to profit from internal innovation. Although most research has focused on for‐profit dyadic exchanges between corporate actors, the paradigm subsumes a broader scope of pecuniary and nonpecuniary motivations at the individual, organizational, community, network, industry, or national level of analysis.
Brainstorming
Authors: Goldenberg Jacob , Mazursky David
Published: December 2010

Brainstorming is the most widely used and recognized procedure in firms to find new concepts or solutions. However, extensive research in the last three decades casts doubts about the efficiency and effectiveness of this approach. Apparently, the group dynamics, instead of increasing the fluency and originality of individuals, may block them. This results in fewer ideas and in less originality compared to that in a nominal group (the same number of people, but working separately). Brainstorming is not without any value. Its effects on extensive knowledge transfer and sharing, and its influence on organization atmosphere, have been reported. The current research focuses on variations that may help individuals overcome brainstorming obstacles, and make this process more successful (for example, electronic brainstorming).
Concept Testing
Authors: Kahn Kenneth B.
Published: December 2010

Concept testing represents those activities undertaken during the concept evaluation phase of the new‐product development process. The purpose of concept testing is to assess and incorporate customer opinion into evaluating the feasibility of a concept early on, prior to committing substantial funds for commercialization of the concept. There are four general types of concept testing: the narrative concept test, the pictorial concept test, the prototype concept test, and the virtual concept test.
Core Competencies
Authors: Sarin Shikhar
Published: December 2010

Core competencies are collective learnings in an organization that result from a unique coordination of diverse production skills and/or the integration of multiple streams of technologies. They provide firms with a long‐term competitive advantage by allowing them to develop unanticipated products faster and cheaper than their competitors. Core competencies provide firms with access to a wide variety of markets, make significant contributions to the perceived customer benefits of the end products, and are difficult to imitate by the competition. Core competencies manifest themselves as core products, which are subassemblies and components that contribute to the value of a variety of end products. Battle for global leadership will take place on three planes: core competencies, core products, and end products. To compete effectively in the future, organizations will need to think of themselves as a portfolio of core competencies and core products, rather than as a collection of discrete businesses.
Competitive Advantage
Authors: Sarin Shikhar
Published: December 2010

Competitive advantage is the relative advantage one business has over another that is sustainable and translates into a benefit that is important to target customers. There are two basic types of competitive advantages: cost leadership and differentiation. When combined with the scope of a firm's activities, they give rise to three generic business strategies: (i) cost leadership – where the firm seeks to become the low‐cost producer in an industry; (ii) differentiation – where the firm seeks to position itself uniquely along one or two dimensions that the customer values; and (iii) focus – where a firm tries to optimize its strategy by selecting a segment or a group of segments in the industry, and seeks to achieve competitive advantage in the target segment(s). Suggestions for sustaining these competitive advantages are explored.
Locale of Innovation
Authors: Sivakumar K.
Published: December 2010

In this article, the focus is on local and transnational innovations. With the increasing globalization of firms, markets, and the factors influencing development and consumption of goods and services, the words “local” and “transnational” can be considered to be ideas on a continuum rather than as discrete categories. Therefore, discussion of one cannot be exclusive of the other. As a result, local and transnational innovation are discussed in tandem.
Product Positioning
Authors: Reibstein David
Published: December 2010

Product positioning should directly follow from the value proposition of the firm and be directed to the selected target market. It is the perceived level of the product offering to the customers vis‐a‐vis competition and the critical dimension that customers use to assess alternative choices. Positioning is the process marketers use to create an image or perception of their offering.
Open Source
Authors: Franke Nikolaus
Published: December 2010

“Open‐source” software means that the source code can be accessed by any user and is distributed under a specific copyright license that ensures that anyone who wishes can use, modify, and improve the product, and redistribute it in modified or unmodified versions to others. In many cases, open‐source software is very innovative and successful, and its importance is still growing. Its economic and organizational principles may therefore be especially important to managers, as those principles can be adapted for the benefit of private companies for software and other products as well.
Technology
S
‐Curve
Authors: Sood Ashish
Published: December 2010

This article encompasses the technology S‐curve that describes the phenomenon of technological evolution and suggests that technologies evolve through an initial period of slow growth, followed by one of fast growth culminating in a plateau. The field does not enjoy a single, strong, and unified theory of technological evolution. However, an emerging, and probably the most compelling explanation, revolves around the dynamics of firms and researchers as the technology evolves through the three major stages of the S‐curve of technological evolution: introduction, growth, and maturity. Recent empirical findings suggest there is sparse support for the theory. In contrast to the dominant view in the literature, the path of technological evolution does not resemble an S‐curve. On the contrary, the path of technological evolution follow a series of irregular step functions better approximated with multiple S‐curves than with a single S‐curve.
Prototype
Authors: Blackburn Richard
Published: December 2010

Prototyping gives new‐product/service development teams an opportunity to examine successive approximations to a new product/service before committing to more costly steps of the development process. Prototypes can (i) help teams learn; (ii) facilitate team communication; (iii) assist in information exchange; and (iv) function as team milestones. Teams working in prototyping cultures (as opposed to specification cultures) tend to develop more radical innovations.
Product Specifications
Authors: Veryzer Robert W.
Published: December 2010

This article treats
product specifications
as the final step in the sequence of steps from determining product
requirements
to the development of
objectives
that provide guidance for detailed descriptions of how a product is to be made. Although the process for determining product specifications may vary depending on the type of product being designed (for example, consumer durables vs. electronics products vs. computer software), the product requirements – objectives – specifications sequence is explained in terms of translation into precise targets or product specifications, which detail in precise, measurable ways how a product is to be made. Product specifications – which may range over various dimensions of a product: physical elements and materials, structure or architecture, control or operating systems, and so on – consist of metrics or measures relevant to a particular product dimension, and indicate the desired level (or value) that is to be achieved for each measure. Several considerations for developing product specifications are also presented.
Process Innovation
Authors: Robben Henry
Published: December 2010

Process innovations change the ways in which a supplier creates products or services. They are incremental when they improve production costs or product quality. They are radical when there is a significant alteration in the production process. Typically, process innovations are most important in the growth phase of the product life cycle.

There are several approaches to trigger off process innovation. This article identifies and describes the following triggers: gap analysis, quality circles and process improvement teams, total quality management, quality function deployment, ISO 9000, The EFQM excellence model, and six sigma.

A procedure to arrive at process innovation may involve the following steps: process mapping, analysis of the
ist
‐situation, benchmarking – best practices – next practices, determination of the
soll
‐situation, and implementation.
Product Diversification
Authors: Sood Ashish
Published: December 2010

This article encompasses product diversification, a tool that helps firms formulate their product and market growth strategy. Diversification is the most risky of the four growth strategies since it requires a firm to acquire new skills, new techniques, and new facilities. There are three types of product diversification: vertical, horizontal, and lateral diversification. Firms may employ these three types of diversification on the basis of market growth conditions.
Research & Development
Authors: Prabhu Jaideep C. , Chandy Rajesh K.
Published: December 2010

This article discusses the following questions concerning Research & Development (R&D): (i) What is R&D? (ii) Who does R&D (governments versus firms)? and (iii) Where is R&D done (the developed West and Japan vs. emerging markets)? This article ends with a discussion on R&D in relation to innovation more broadly as well as on its importance to firms, governments, and policy makers worldwide.
Global Consumerism and Consumption
Authors: Belk Russell
Published: December 2010

It is a commonplace observation that contemporary consumption has globalized on an unprecedented scale, and, along with it, the rampant desire to participate in the global indulgence labeledconsumerismorconsumer culture. Theories about the global spread of consumerism have gone through a number of phases and have included concepts like cultural imperialism, globalization, nationalism, and hybridity. This short article attempts to sort out these debates as well as consider the consequences of such global consumption, especially for rapidly expanding consumer cultures like China.
International Marketing Channels
Authors: Bello Daniel C.
Published: December 2010

International marketing channels consist of interdependent organizations participating in business activities necessary to make a product or service available for use in markets around the world. The structure or design of global channels can vary widely, comprising various organizational participants (foreign distributors, agents, subsidiaries, etc.) engaged in a diverse set of functional activities (selling to foreign customers, warehousing inventory, etc.). The determinants of channel design include key drivers associated with manufacturers, international middlemen, and foreign end users. A complex interplay among these key players and the characteristics of channel activities yields the particular contractual, ownership, and other institutional arrangements that govern cross‐border channel systems. Further, channel designs are subject to important feasibility constraints emanating from the regulative, normative, and cultural‐cognitive elements of the institutional environment of the home and host countries. International marketing channels are one of the most complex and dynamic aspects of global marketing, and require careful analysis to achieve the most productive balance among the many determinants of channel design.
Global Marketing Strategy: Perspectives and Approaches
Authors: Douglas Susan P. , Craig C. Samuel
Published: December 2010

Global marketing strategy involves formulating marketing strategy across a range of countries. A number of different approaches have been taken in studying global marketing strategy, including the transaction cost perspective, standardization/adaptation, configuration/coordination perspective, global integration perspective, and the evolutionary perspective. Typically, each focuses on different decisions or aspects of global marketing strategy and corresponds in many respects to differences in the experience of the firm in international markets. Depending on the degree of experience in international markets, the firm must deal with issues related to beginning operations in global markets, refining and developing global marketing strategy, or consolidating/integrating global strategy. In beginning global market operations, the firm needs to decide which international markets to enter and how they should be entered, as well as the timing and sequencing of international market entry. As the firm expands within international markets, attention shifts to deciding how far to tailor various elements of the marketing mix to local market characteristics. Attention is then required to coordinate and integrate marketing strategy across countries and regions. The design of global marketing strategy is thus a continually evolving and adaptive process requiring an ability to respond to new demand and competitive factors as well as changing global environmental conditions and pressures.
Market Entry and Expansion
Authors: Brouthers Keith D.
Published: December 2010

When firms expand abroad one task they need to do is to determine the best way to structure their new foreign operation. Research focusing on this choice of market entry mode has grown rapidly over the past two decades but still much more work is needed. Primarily, past research has focused on country‐ and firm‐specific attributes and has used rational decision‐making models. Marketing scholars can add to our knowledge by exploring the impact of marketing strategy on market entry decisions. In this article, we briefly review the existing research and then offer suggestions on adding marketing insights that can impact foreign subsidiary choice and performance.
Family Conglomerates
Authors: Kim Daekwan , Cavusgil S. Tamer
Published: December 2010

Family conglomerates are a common business phenomenon across emerging markets, offering some partnership opportunities as well as potential threats to multinational firms interested in doing business in those emerging markets. They often grow with their economy while enjoying the strong brand recognition and government protection among other advantages. Some eventually become formidable multinational firms. Their future most likely depends on to what extent they are able to exercise their unified control as a family of owners and to transform themselves to become more efficient, justifying their presence against some concerns raised by domestic and international communities.
Countertrade
Authors: Palia Aspy P.
Published: December 2010

Countertrade involves the linked trade obligations of two or more enterprises in two or more countries as stipulated in their import and export commitments. Exporters are often required to accept commodities/services in payment for the goods they sell overseas. If they accept these terms and conclude a countertrade agreement, they acquire a large inventory of countertraded commodities. Otherwise, they forego additional sales, market share, and entry into growing markets. Trading houses, multinational corporations (MNCs), and other countertrade specialists help dispose the surplus countertraded commodities. They specialize by services rendered, by product category, and by geographic region served. The countertrade literature refers to a variety of transactions, which include barter, buybacks, clearing agreements, compensation, counterpurchase, evidence accounts, offsets, parallel trading, and switching. This article covers five basic forms of countertrade: counterpurchase, compensation, offsets, barter, and switch, recognized by the US International Trade Commission. International marketing managers need to be familiar with the patterns of countertrade practiced and the variety of trade, trade finance, consulting, international banking, marketing research, information, and other services provided by countertrade service organizations for specific products in specific markets. This knowledge will enable them to identify and take advantage of emerging opportunities in overseas markets.
International Trade Intermediaries
Authors: Ellis Paul D.
Published: December 2010

International trade intermediaries (ITIs) are specialist intermediaries involved in the management of international trade. This service either involves an agency‐brokerage or a merchant‐reselling role. ITIs are ubiquitous in global markets and are one of the most enduring organizational entities in the history of international business. Acting as agents, ITIs exist because manufacturers sometimes lack the ability or the incentive to engage in exporting directly. However, manufacturers may hesitate to contract with independent intermediaries because of the threat of opportunism. The circumstances under which manufacturers would prefer ITIs to in‐house exporting can be predicted using transaction cost analysis, which describes the matching of exchange characteristics with particular exchange modes or governance structures. Acting as merchant resellers, ITIs create new markets for goods and services by developing exchanges between buyers and sellers located in different nations. In developing these links, the ITI may also transfer marketing skills to others in the channel. Although ITIs improve the efficiency of exchange and entrepreneurially create markets where none existed previously, their survival within cross‐border channels of distribution is inherently impermanent. The information asymmetries that give ITIs their “edge” in a market tend to diminish over time, undermining their position in the channel.
International Negotiations
Authors: Money Bruce
Published: December 2010

Basic to negotiation are issues such as anchoring (who makes the first offer) and making concessions. Various models have been forwarded, including the framework of bargainer characteristics and situational factors affecting the process, which in turn, affects the outcome. Regarding international negotiations, various issues complicate this or any model, in dealing with, for example, language differences, perception of time, and simply what people in other countries consider to be good negotiation. National culture as a situational factor, dramatically affects the process. The article highlights two of the most prominent frameworks, Hofstede's five dimensions (subject to the well‐placed and ongoing debate about applying group‐based measures to individual levels of behavior, the so‐called “ecological fallacy”) and the Halls' construct of context, or the amount of “code” implicit in a particular national culture. Finally, other issues (such as societal and governmental factors) which may impact international negotiation are explored.
Consumer Affinity Construct
Authors: Diamantopoulos Adamantios , Oberecker Eva M.
Published: December 2010

Sentiments toward foreign countries have potential power in explaining consumption behavior and are therefore, of importance to marketers. While
negative
sentiments toward foreign countries in general (e.g., due to ethnocentric tendencies), as well as toward a specific foreign country (e.g., due to feelings of animosity) have received considerable attention in the literature, research efforts on
positive
sentiments toward foreign countries, their sources, and their consequences on consumption behavior, such as intentions to consume products or brands, are still limited. The consumer affinity construct addresses the behavioral consequences of
favorable
, affectively based sentiments toward a
specific
foreign country. Specifically, research reveals that consumers indeed have affinities for certain countries. These affinities are based on so‐called affinity drivers, which capture direct and/or indirect experiences with the affinity country. Overall, the consumer affinity segment shows a heightened willingness to buy products from the affinity country and thus represents a potentially interesting segment for international marketing activities.
Consumer World‐Mindedness
Authors: Douglas Susan P. , Nijssen Edwin J.
Published: December 2010

As geographic distances shrink with advances in communications technology, the Internet, the spread of global media, and increased international travel, consumers become aware of and exposed to products, customs, and life‐styles in other cultures and countries. They may also develop international social networks communicating with other people across the world. As a result, rather than having ethnocentric attitudes, more consumers are becoming open to and interested in consumer products, services, and ideas from other cultures and parts of the world. This has tended to result in greater availability of and preference for foreign products and brands in retail stores, including grocery stores and supermarkets.
Global Product
R
&
D
Authors: Özsomer Aysegul
Published: December 2010

Global Product R&D refers to a firm's attempt to concentrate and coordinate its product‐related R&D activities in a few countries. R&D activities are undertaken with a focus on multiple customer groups from multiple types of markets (e.g., advanced and emerging). Concentration enables a firm to benefit from the location advantages associated with different countries and coordination exploits cross‐country synergies. A primary driver of global product R&D networks is differentiation and division of labor. Different centers work on different product projects or on different activities for the same project leading to increased specialization.
Product Ethnicity
Authors: Usunier Jean‐Claude
Published: December 2010

In a globalizing world, products are increasingly stateless. Many products can be manufactured with a world‐class technology, branded globally, and sold worldwide. However, consumers still make associations between products and countries, on the basis of objective information, language‐based cues such as brand names, as well as commonly held stereotypes. Such associations reflect product ethnicity, which is based on country–product associations made by consumers with either product or country as initial stimulus, resulting in a combined two‐way measurement.
Smuggling
Authors: Gillespie Kate
Published: December 2010

Smuggling encompasses the import or export of goods in violation of domestic or international law. Most smuggling, however, involves the illegal import of goods that face import quotas, significant tariffs, or other high taxes. Trade liberalization has decreased smuggling but has failed to eradicate it completely. Instead, the smuggling of common consumer products has come increasingly under the auspices of transnational organized crime and has become intertwined with international counterfeiting and money laundering. Although smuggling presents several threats to global brands, multinational firms have been known to participate in smuggling in the attempt to increase sales and profits.
Offshoring and Marketing
Authors: Bharadwaj Neeraj
Published: December 2010

Although offshoring has become ubiquitous in business practice, it has attracted only minimal academic attention. This article briefly describes current marketing research that has examined the impact of offshoring on customer appraisals and also current operations research that has assessed its ability to affect cost savings. It also identifies some more interesting opportunities in offshoring and marketing that await learning, including integrating thinking from marketing
and operations research to better understand when cutting costs by engaging in offshoring may come at the expense of weakening customer relationships.
Further molecular and clinical delineation of the Wisconsin syndrome phenotype associated with interstitial 3q24q25 deletions
Authors: Willemsen Marjolein H. , de Leeuw Nicole , Mercer Catherine , Eisenhauer Helen , Morris Joanne , Collinson Morag N. , Barber John C.K. , Lam Stephen T.S. , Lo Ivan F.M. , Rensen Hanneke , Ferwerda Annemarie , Hamel Ben C.J. , Kleefstra Tjitske
Published: December 2010

Deletions of the distal 3q22.3 region encompassing the gene forkhead transcription factor FOXL2 (FOXL2) usually result in intellectual disability (ID) and the highly recognizable blepharophimosis–ptosis–epicanthus inversus syndrome (BPES). We encountered three patients with molecularly defined interstitial deletions distal to the FOXL2 gene. They present with remarkably similar manifestations comprising variable ID, a coarse facial appearance, including prominent nose and eyebrows, hypogonadism and skin pigmentation abnormalities, and they share an approximately 8.8 Mb overlapping 3q24q25 deletion. Interestingly, one of the present patients was described previously in a clinical report with emphasis on her clinical similarity to the Wisconsin syndrome, suggesting that Wisconsin syndrome might be caused by a (micro) deletion within the 3q24q25 region. © 2010 Wiley‐Liss, Inc.
Association of the CD226 Ser307 variant with systemic sclerosis: Evidence of a contribution of costimulation pathways in systemic sclerosis pathogenesis
Authors: Dieudé P. , Guedj M. , Truchetet M. E. , Wipff J. , Revillod L. , Riemekasten G. , Matucci‐Cerinic M. , Melchers I. , Hachulla E. , Airo P. , Diot E. , Hunzelmann N. , Mouthon L. , Cabane J. , Cracowski J. L. , Riccieri V. , Distler J. , Amoura Z. , Valentini G. , Camaraschi P. , Tarner I. , Frances C. , Carpentier P. , Brembilla N. C. , Meyer O. , Kahan A. , Chizzolini C. , Boileau C. , Allanore Y.
Published: December 2010

Objective

The nonsynonymous polymorphism rs763361 of the CD226 gene, which encodes DNAX accessory molecule 1, which is involved in T cell costimulation pathways, has recently been identified as a genetic risk factor for autoimmunity. The purpose of this study was to test for association of the CD226 rs763361 polymorphism with systemic sclerosis (SSc) in European Caucasian populations.

Methods

CD226 rs763361 was genotyped in 3,632 individuals, consisting of a discovery sample (991 SSc patients and 1,008 controls) and a replication sample (999 SSc patients and 634 controls). All study subjects were of European Caucasian origin. Expression of CD226 was assessed on peripheral blood mononuclear cells obtained from 21 healthy donors genotyped for CD226 rs763361.

Results

The CD226 rs763361 T allele was found to be associated with SSc in both the discovery and the replication samples, showing the following results in the combined populations: odds ratio (OR) 1.22 (95% confidence interval [95% CI] 1.10–1.34), P = 5.69 × 10–5. The CD226 T allele was also associated with various SSc subsets, highlighting a potential contribution to disease severity. The most remarkable associations of the CD226 TT risk genotype were observed with the diffuse cutaneous SSc subtype, the anti–topoisomerase I antibody–positive, and SSc‐related fibrosing alveolitis subsets: OR 1.86 (95% CI 1.42–2.43), P = 5.15 × 10–6, OR 1.82 (95% CI 1.38–2.40), P = 2.16 × 10–5, and OR 1.61 (95% CI 1.25–2.08), P = 2.73 × 10–4, respectively. CD226 expression was not significantly influenced by CD226 rs763361 genotypes whatever the T cell subtype investigated.

Conclusion

Our results establish CD226 as a new SSc genetic susceptibility factor underlying the contribution of costimulation pathways in the pathogenesis of SSc. Further work is nevertheless needed to define the causal variant at the CD226 locus as well as the functional consequences.
Impact of bevacizumab on functional recovery and histology of the liver after resection of colorectal metastases
Authors: Wicherts D A , de Haas R J , Sebagh M , Saenz Corrales E , Gorden D L , Lévi F , Paule B , Azoulay D , Castaing D , Adam R
Published: December 2010

Background

The impact of bevacizumab on functional recovery and histology of the liver was evaluated in patients undergoing hepatic resection for colorectal liver metastases (CLM) following bevacizumab treatment.

Methods

Consecutive patients who had resection of CLM between July 2005 and July 2009 following preoperative chemotherapy were identified retrospectively from a prospectively collected database. Patients who had received bevacizumab before the last chemotherapy line were excluded. Postoperative liver function and histology were compared between patients with and without bevacizumab treatment. Recorded parameters included serum prothrombin time, total bilirubin concentration, and levels of aspartate and alanine aminotransferase and γ-glutamyltransferase.

Results

Of 208 patients identified, 67 had received last-line bevacizumab, 44 were excluded and 97 had not received bevacizumab. Most patients in the bevacizumab group (66 per cent) received a single line of chemotherapy. Bevacizumab was most often combined with 5-flurouracil/leucovorin and irinotecan (68 per cent). The median number of bevacizumab cycles was 8·6 (range 1–34). Bevacizumab administration was stopped a median of 8 (range 3–19) weeks before surgery. There were no deaths. Postoperative morbidity occurred in 43 and 36 per cent of patients in the bevacizumab and no-bevacizumab groups respectively (P = 0·353). The mean(s.d.) degree of tumour necrosis was significantly higher in the bevacizumab group (55(27) versus 32(29) per cent; P = 0·001). Complete pathological response rates were comparable (3 versus 8 per cent; P = 0·307). Postoperative changes in functional parameters and objective signs of hepatic toxicity were similar in both groups.

Conclusion

Preoperative administration of bevacizumab does not seem to affect functional recovery of the liver after resection of CLM. Tumour necrosis is increased following bevacizumab treatment.
Synthesis and DNA‐Binding Affinities of Protoberberine‐Based Multivalent Agents
Authors: Cui Jie‐Shun , Xu Fang , Pang Ji‐Yan , Chen Wen‐Hua , Jiang Zhi‐Hong
Published: December 2010

Three novel berberine derivatives bearing two, three, and four primary amino groups at C(9), respectively, were synthesized and characterized on the basis of 1H‐ and 13C‐NMR, MS, and HR‐MS data. Their non‐covalent binding with calf thymus (CT) DNA was investigated by means of spectrophotometric titration and ethidium bromide (EB) displacement experiments. The results indicated that these multivalent berberine derivatives exhibited up to 130‐fold enhanced binding affinities relative to berberine, and thus, may be exploitable as potent DNA‐binding agents.
Two New Resveratrol Tetramers Isolated from Cayratia japonica (Thunb.) Gagn. with Strong Inhibitory Activity on Fatty Acid Synthase and Antioxidant Activity
Authors: Bao Li , Ma Xiaofeng , Song Xiaohong , Wang Manyuan , Liu Hongwei
Published: December 2010

Two new resveratrol tetramers, cajyphenol A (1) and cajyphenol B (2), together with two known resveratrol dimers, quadrangularin A (3) and pallidol (4), and resveratrol (5) were isolated from the stems of Cayratia japonica (Thunb.) Gagn. Their structures were established by means of NMR (1H,1H‐COSY, 1H,13C‐HSQC, HMBC, and NOESY) and ESI‐MS analyses. Compounds 1–5 showed fast‐binding inhibitory activities on fatty acid synthase with the IC50 values of 1.63±0.02, 1.49±0.03, 7.50±0.01, 11.1±0.01, and 10.2±0.01 μM, respectively. Compounds 1–5 also exhibited antioxidant activities in the ORAC assay.
Chemical Constituents of Papulaspora immersa, an Endophyte from Smallanthus sonchifolius (Asteraceae), and Their Cytotoxic Activity
Authors: Borges Coutinho Gallo Margareth , Coêlho Cavalcanti Bruno , Washington Araújo Barros Francisco , Odorico de Moraes Manoel , Veras Costa‐Lotufo Letícia , Pessoa Cláudia , Kenupp Bastos Jairo , Tallarico Pupo Mônica
Published: December 2010

Papulaspora immersa H. H. Hotson was isolated from roots and leaves of Smallanthus sonchifolius (Poepp. and Endl.) H. Rob. (Asteraceae), traditionally known as Yacon. The fungus was cultured in rice, and, from the AcOEt fraction, 14 compounds were isolated. Among them, (22E,24R)‐8,14‐epoxyergosta‐4,22‐diene‐3,6‐dione (4), 2,3‐epoxy‐1,2,3,4‐tetrahydronaphthalene‐c‐1,c‐4,8‐triol (10), and the chromone papulasporin (13) were new secondary metabolites. The spectral data of the known natural products were compared with the literature data, and their structures were established as the (24R)‐stigmast‐4‐en‐3‐one (1), 24‐methylenecycloartan‐3β‐ol (2), (22E,24R)‐ergosta‐4,6,8(14),22‐tetraen‐3‐one (3), (−)‐(3R,4R)‐4‐hydroxymellein (5), (−)‐(3R)‐5‐hydroxymellein (6), 6,8‐dihydroxy‐3‐methylisocoumarin (7), (−)‐(4S)‐4,8‐dihydroxy‐α‐tetralone (8), naphthalene‐1,8‐diol (9), 6,7,8‐trihydroxy‐3‐methylisocoumarin (11), 7‐hydroxy‐2,5‐dimethylchromone (12), and tyrosol (14). Compound 4 showed the highest cytotoxic activity against the human tumor cell lines MDA‐MB435 (melanoma), HCT‐8 (colon), SF295 (glioblastoma), and HL‐60 (promyelocytic leukemia), with IC50 values of 3.3, 14.7, 5.0 and 1.6 μM, respectively. Strong synergistic effects were also observed with compound 5 and some of the isolated steroidal compounds.
Asymmetric Synthesis and Biological Activity of nor‐α‐Tocopherol, a New Vitamin E Analogue
Authors: Chapelat Julien , Hengartner Urs , Chougnet Antoinette , Liu Kegang , Huebbe Patricia , Rimbach Gerald , Woggon Wolf‐D.
Published: December 2010

The vitamin E analogues (2R,4′R,8′R)‐nor‐α‐tocopherol (94 % de) and (2RS,4′R,8′R)‐nor‐α‐tocopherol have been synthesized from (all R)‐hexahydrofarnesol and phytol, respectively. According to in vitro experiments with murine macrophages nor‐α‐tocopherol is an anti‐inflammatory compound more potent than α‐tocopherol.
Energetic Salts of the Binary 5‐Cyanotetrazolate Anion ([C2N5]−) with Nitrogen‐Rich Cations
Authors: Crawford Margaret‐Jane , Klapötke Thomas M. , Martin Franz A. , Miró Sabaté Carles , Rusan Magdalena
Published: December 2010

The reaction of cyanogen (NCCN) with MN3 (M=Na, K) in liquid SO2 leads to the formation of the 5‐cyanotetrazolate anion as the monohemihydrate sodium (1⋅1.5 H2O) and potassium (2) salts, respectively. Both 1⋅1.5 H2O and 2 were used as starting materials for the synthesis of a new family of nitrogen‐rich salts containing the 5‐cyanotetrazolate anion and nitrogen‐rich cations, namely ammonium (3), hydrazinium (4), semicarbazidium (5), guanidinium (6), aminoguanidinium (7), diaminoguanidinium (8), and triaminoguanidinium (9). Compounds 1–9 were synthesised in good yields and characterised by using analytical and spectroscopic methods. In addition, the crystal structures of 1⋅1.5 H2O, 2, 3, 5, 6, and 9⋅H2O were determined by using low‐temperature single‐crystal X‐ray diffraction. An insight into the hydrogen bonding in the solid state is described in terms of graph‐set analysis. Differential scanning calorimetry and sensitivity tests were used to assess the thermal stability and sensitivity against impact and friction of the materials, respectively. For the assessment of the energetic character of the nitrogen‐rich salts 3–9, quantum chemical methods were used to determine the constant volume energies of combustion, and these values were used to calculate the detonation velocity and pressure of the salts using the EXPLO5 computer code. Additionally, the performances of formulations of the new compounds with ammonium nitrate and ammonium dinitramide were also predicted. Lastly, the ICT code was used to determine the gases and heats of explosion released upon decomposition of the 5‐cyanotetrazolate salts.
Amyloid Formation from an α‐Helix Peptide Bundle Is Seeded by 310‐Helix Aggregates
Authors: Singh Yogendra , Sharpe Philip C. , Hoang Huy N. , Lucke Andrew J. , McDowall Alasdair W. , Bottomley Stephen P. , Fairlie David P.
Published: December 2010

Transformation of proteins and peptides to fibrillar aggregates rich in β sheets underlies many diseases, but mechanistic details of these structural transitions are poorly understood. To simulate aggregation, four equivalents of a water‐soluble, α‐helical (65 %) amphipathic peptide (AEQLLQEAEQLLQEL) were assembled in parallel on an oxazole‐containing macrocyclic scaffold. The resulting 4α‐helix bundle is monomeric and even more α helical (85 %), but it is also unstable at pH 4 and undergoes concentration‐dependent conversion to β‐sheet aggregates and amyloid fibrils. Fibrils twist and grow with time, remaining flexible like rope (>1 μm long, 5–50 nm wide) with multiple strings (2 nm), before ageing to matted fibers. At pH 7 the fibrils revert back to soluble monomeric 4α‐helix bundles. During α→β folding we were able to detect soluble 310 helices in solution by using 2D‐NMR, CD and FTIR spectroscopy. This intermediate satisfies the need for peptide elongation, from the compressed α helix to the fully extended β strand/sheet, and is driven here by 310‐helix aggregation triggered in this case by template‐promoted helical bundling and by hydrogen‐bonding glutamic acid side chains. A mechanism involving α⇌α4⇌(310)4⇌(310)n⇌(β)n⇋m(β)n equilibria is plausible for this peptide and also for peptides lacking hydrogen‐bonding side chains, with unfavourable equilibria slowing the α→β conversion.
Synthesis and Evaluation of Indatraline‐Based Inhibitors for Trypanothione Reductase
Authors: Walton Jeffrey G. A. , Jones Deuan C. , Kiuru Paula , Durie Alastair J. , Westwood Nicholas J. , Fairlamb Alan H.
Published: December 2010

The search for novel compounds of relevance to the treatment of diseases caused by trypanosomatid protozoan parasites continues. Screening of a large library of known bioactive compounds has led to several drug‐like starting points for further optimisation. In this study, novel analogues of the monoamine uptake inhibitor indatraline were prepared and assessed both as inhibitors of trypanothione reductase (TryR) and against the parasiteTrypanosoma brucei. Although it proved difficult to significantly increase the potency of the original compound as an inhibitor of TryR, some insight into the preferred substituent on the amine group and in the two aromatic rings of the parent indatraline was deduced. In addition, detailed mode of action studies indicated that two of the inhibitors exhibit a mixed mode of inhibition.
Varenicline does not alter brain stimulation reward thresholds and reverses nicotine‐facilitated thresholds in rats
Authors: Vann R.E. , Tobey K.M. , Lobe S.L. , Kipps B. , Kwilasz A.J. , Aceto M.D. , Harris L.S.
Published: December 2010

The partial α4β2 nicotinic acetylcholine receptor (nAChR) agonist, varenicline, shares some but not all preclinical effects of nicotine. This unique profile may be crucial to its effectiveness as a therapeutic aid for smoking cessation. The present study evaluated the ability of varenicline to alter brain stimulation reward (BSR) and to alter nicotine facilitation of BSR in a rate‐independent intracranial self‐stimulation discrete trial procedure. Male Sprague‐Dawley rats were stereotaxically implanted with electrodes and trained to respond for direct electrical stimulation aimed at the medial forebrain bundle. Once stable thresholds were established, nicotine, varenicline, and mecamylamine were tested alone to determine their effects on BSR. Subsequently, challenge tests for nicotine facilitation of BSR with nonthreshold altering doses of varenicline and mecamylamine were conducted. This study demonstrated that nicotine dose‐ dependently facilitated BSR, whereas varenicline did not. Similarly to mecamylamine, varenicline reversed nicotine facilitation of BSR, suggesting that nAChRs mediate the effects of nicotine on BSR. Thus, specifically targeting α4β2 nAChRs inhibits the ability of nicotine to facilitate BSR. The efficacy of varenicline as a treatment for smoking cessation may be related to its unique ability to reduce the rewarding effects of nicotine while not producing rewarding effects alone, a critical consideration in effective drug replacement therapies. Drug Dev Res 72: 310–314, 2011. © 2010 Wiley‐Liss, Inc.
Expression of doublecortin reveals articular chondrocyte lineage in mouse embryonic limbs
Authors: Zhang Qiuyang , Cigan Alexander D. , Marrero Luis , Lopreore Courtney , Liu Sen , Ge Dongxia , Savoie Felix H. , You Zongbing
Published: December 2010

The doublecortin (Dcx) gene encodes a microtubule‐binding protein that was originally found in immature neurons. In this study, we used two mouse strains that express reporter genes (LacZ and enhanced green fluorescence protein, respectively) driven by the endogenous Dcx promoter. We found that Dcx was expressed in the mesenchymal cells in the mouse embryonic limb buds. A population of the mesenchymal cells continued Dcx expression after they differentiated into joint interzone cells and then articular chondrocytes. In contrast, the endochondral chondrocytes lost Dcx expression when the mesenchymal cells differentiated into endochondral chondrocytes. These data support a concept that the articular and endochondral chondrocytes originate from the same mesenchymal cells that express Dcx. In contrast to the notion that articular chondrocytes are derived from de‐differentiated endochondral chondrocytes, our findings demonstrate that the lineages of articular and endochondral chondrocytes bifurcate at the stage of endochondral chondrogenesis. genesis 49:75–82, 2011. © 2010 Wiley‐Liss, Inc.
Transpiration, evapotranspiration and energy fluxes in a temperate wetland dominated by Phalaris arundinacea under hot summer conditions
Authors: Rejšková Alžběta , Čížková Hana , Brom Jakub , Pokorný Jan
Published: December 2010

Transpiration, evapotranspiration and evaporative fraction (EF) were measured in a temperate zone wetland dominated by Phalaris arundinacea L. under extremely high temperature and intense irradiation conditions. The infrared (IR) camera recorded no temperature extremes within the stand, indicating that the stand was capable of regulating the overheating by transpiration. The transpiration rate of individual leaves (measured by the gas‐exchange method) was positively correlated with the water vapour pressure deficit of the air (R2 = 0·56, df = 1, 60, p < 0·001) reaching values of up to 7·8 mmol m−2 s−1 of leaf area. Evapotranspiration of the stand reached values of 5·3 and 5·9 mm day−1 on the 27 and 28 July 2005, respectively. The EF showed that more than one half of the available energy was consumed in the evapotranspiration processes. In the afternoon, the influence of hot air advection was obvious. A strong cooling effect of the wetland was shown. The results support the idea that wetlands sufficiently supplied with water are important in the energy and water budget of drained cultural landscapes. Copyright © 2010 John Wiley & Sons, Ltd.
Voltammetric Determination of Selected Nitro Compounds at a Polished Silver Solid Amalgam Composite Electrode
Authors: Vyskočil Vlastimil , Navrátil Tomáš , Daňhel Aleš , Dědík Jan , Krejčová Zuzana , Škvorová Lucie , Tvrdíková Jana , Barek Jiří
Published: December 2010

Voltammetric behavior of selected biologically active organic nitro compounds, namely 2‐nitrofluorene, picric acid (2,4,6‐trinitrophenol) and metronidazole, has been investigated using direct current voltammetry (DCV) and differential pulse voltammetry (DPV) at a polished silver solid amalgam composite electrode (p‐AgSA‐CE). The optimum conditions have been found for their determination in a 1 : 1 mixture of methanol and aqueous Britton–Robinson buffer of pH 5.0 for 2‐nitrofluorene and in the aqueous Britton–Robinson buffer solutions of pH 2.0 and 4.0 for picric acid and metronidazole, respectively, with the limits of quantification (LQs) 4, 0.1 and 2 µmol L−1 (DCV at p‐AgSA‐CE) and 3, 1 and 4 µmol L−1 (DPV at p‐AgSA‐CE) for 2‐nitrofluorene, picric acid and metronidazole, respectively. An attempt to increase the sensitivity using adsorptive stripping voltammetry was not successful for all three test substances. For comparison, the UV‐vis spectrophotometric determinations of studied compounds have also been carried out in methanol for 2‐nitrofluorene (LQ≈1 µmol L−1) and in deionized water for picric acid (LQ≈3 µmol L−1) and metronidazole (LQ≈2 µmol L−1). Practical applicability of the newly developed voltammetric methods was verified on direct determination of the studied compounds in drinking and river waters with LQs around 10−6 mol L−1 for all the studied compounds.
A Label‐Free Amperometric Immunosensor Based on Redox‐Active Ferrocene‐Branched Chitosan/Multiwalled Carbon Nanotubes Conductive Composite and Gold Nanoparticles
Authors: Liang Ru‐Ping , Fan Li‐Xia , Huang Dong‐Ming , Qiu Jian‐Ding
Published: December 2010

A novel immunosensor has been developed by self‐assembling Au NPs onto a ferrocene‐branched chitosan/multiwalled carbon nanotubes (CS‐Fc/MWCNTs) modified electrode for the sensitive determination of hepatitis B surface antigen (HBsAg). The formation of CS‐Fc effectively avoids the leakage of Fc and retains its electrochemical activity. Incorporation of MWCNTs and Au NPs into CS‐Fc further increases the electrochemical active Fc in the CS films and provides interactive sites for the immobilization of HBsAb. The morphologies and electrochemistry of the formed biofilm were investigated by using scanning electron microscopy and electrochemical techniques. The immunosensor exhibits a specific response to HBsAg in the range of 1.0–420 ng mL−1. Excellent analytical performance, fabrication reproducibility and operational stability of the proposed immunosensor indicated its promising application in clinical diagnostics.