bluuebunny/crossref_metadata_2025 huggingface dataset:
Competitive Entry and Pricing Responses to Product Innovation
Authors: Bayus Barry , Chintagunta Pradeep
Published: February 2006

In this paper, we study competitive response to a product innovation. We consider the dynamic interaction between a Defender (a firm with a first generation product) and an Attacker (a firm with a second generation product). The second generation product entry decision of the Defender, as well as the pricing decisions of both firms, are analyzed. Analytical results are derived by developing a 3-period pricing game, and studying closed-loop policies for a Nash equilibrium. These results allow us to identify strategies in which the Attacker can prevent (or delay) a competitive response by the Defender. Some empirical support for our analytical results is also provided by pricing data and information on the timing of successive product generation introductions in the semiconductor and personal computer industries.
The Economic Viability of Frequency Reward Programs in a Strategic Competitive Environment
Authors: Kopalle Praveen K , Neslin Scott A
Published: February 2006

We examine the conditions that enhance the economic viability of frequency reward programs in a strategic competitive environment. We focus particularly on conditions related to consumer behavior, namely the extent to which consumers value the future benefits offered by the reward, the expandability of the category, and consumers preferences for competing brands. Consumers maximize utility over a long-term time horizon, taking into account the value of the reward. Two firms maximize profits over a long-term time horizon. They first decide between implementing a frequency reward program or a traditional pricing policy (a constant price), and then decide on the specific prices. We numerically solve for the sub-game perfect equilibrium for this two-stage game. We find that a brand is more likely to find reward programs to be viable strategies if consumers value future benefits, if reward programs can expand the market, and if the brand has a higher preference. The market expandability finding is particularly interesting. If the sales increases generated by reward programs represent category growth, the power of frequency reward programs makes them an effective vehicle for generating profits. However, if gains come mainly from competitors, the power of frequency reward programs precipitates a strong competitive response that erodes profits in a classic prisoners dilemma. We use the airline industry to explore our market expandability finding. We find evidence that the major airlines introduced reward programs to counter-act a stronger outside category (new entrants), and in doing so, they expanded their market.
Assessing Heterogeneity in Discrete Choice Models Using a Dirichlet Process Prior
Authors: Kim Jin Gyo , Menzefricke Ulrich , Feinberg Fred M.
Published: February 2006

The finite normal mixture model has emerged as a dominant methodology for assessing heterogeneity in choice models. Although it extends the classic mixture models by allowing within component variablility, it requires that a relatively large number of models be separately estimated and fairly difficult test procedures to determine the correct number of mixing components. We present a very general formulation, based on Dirichlet Process Piror, which yields the number and composition of mixing components a posteriori, obviating the need for post hoc test procedures and is capable of approximating any target heterogeneity distribution. Adapting Stephens (2000) algorithm allows the determination of substantively different clusters, as well as a way to sidestep problems arising from label-switching and overlapping mixtures. These methods are illustrated both on simulated data and A.C. Nielsen scanner panel data for liquid detergents. We find that the large number of mixing components required to adequately represent the heterogeneity distribution can be reduced in practice to a far smaller number of segments of managerial relevance.
Durable Good, Extended Warranty and Channel Coordination
Authors: Desai Preyas S , Padmanabhan Paddy
Published: February 2006

The marketing literature on product warranty and extended warranty has largely focused on their role as segmentation instruments in risk-averse consumer markets. Preserving this insurance rationale, we highlight the role of extended warranty in channel coordination.We derive explicit demand functions for the durable good and extended warranty from a traditional model of consumer utility. This derivation explicitly captures the complementary goods flavor of extended warranty. We then investigate the impact of different distributional arrangements commonly observed in the marketplace for market outcomes and manufacturer profitability. We show that two key forces drive the results-the complementary goods effect and the double marginalization effect. Different channel arrangements for marketing of extended warranty cause these effects occur at different levels within a distribution channel and these are shown to have significant implications for the optimal warranty policy.
The Relationship between Market Share and Information in a High-Tech Industry
Authors: Theoharakis Vasilis , Vakratsas Demetrios , Wong Veronica
Published: February 2006

The role of information in high-technology markets is critical (Dutta, Narasimhan and Rajiv 1999; Farrell and Saloner 1986; Weiss and Heide 1993). In these markets, the volatility and volume of information present managers and researchers with the considerable challenge of monitoring such information and examining how potential customers may respond to it. This article examines the effects of the type and volume of information on the market share of different technological standards in the Local Area Networks (LAN) industry. We identify three different types of information: technological, availability and adoption. Our empirical application suggests that all three types of information have significant effects on the market share of a technological standard, but their direction and magnitude differ. More specifically, technology-related information is negatively related to market share as it demonstrates that the underlying technology is immature and still evolving. Both availability and adoption-related information have a positive effect on market share, but the former is larger than the latter. We conclude that high-tech firms should emphasize the dissemination of information, especially availability-related, as part of their promotional strategy for a new technology. Otherwise, they may risk missing an opportunity to achieve a higher share and establish their market presence.
Product Entry Timing in Dual Distribution Channels: The Case of the Movie Industry
Authors: Prasad Ashutosh , Bronnenberg Bart , Mahajan Vijay
Published: February 2006

In many durable goods industries, firms continuously offer new products to customers and market them in different versions through different channel of distribution. This paper examines the issue of when to introduce the product into the different channels. The determinants of entry time include the discounting of future profits, the foresight of the firm, customers' expectations, and the possibility of cannibalization. Of special interest is the effect of customers' expectations about the timing of sequential entries. Specifically, it is shown here that profits decline if firms ignore the role of customer expectations. We discuss how our results can be used to get insights into the workings of the US motion picture industry, which is characterized by sequential introduction of movies first into theaters followed by home video. Finally, a closed form solution for an optimal sequential timing policy is provided.
Buyer Shopping Costs and Retail Pricing: An Indirect Empirical Test
Authors: Lee Sang-Yong T. , Png Ivan P.L.
Published: February 2006

Suppose that consumers incur fixed shopping costs and choose stores according to advertised discounts. Then, the extent to which a store will discount advertised items should increase with the profit from other regularly-priced items. Bookstores customarily advertise discounts on bestsellers. Among conventional bookstores, we found that the bestseller discount systematically increased with the store area, selection of titles, and presence of other product categories. One standard deviation increase in store area was associated with a 3.7 (± 1.8) higher bestseller percentage discount. Among online stores, we found that the bestseller discount systematically increased with the selection of titles and number of product categories. One standard deviation increase in selection was associated with a 9.5 (± 2.2) higher bestseller percentage discount. These results indirectly confirm that booksellers discount bestsellers to attract consumers, and that consumers bear significant fixed shopping costs.
A New Approach for Capturing and Potraying the Competitive Structure of a Market: An Application To The Bush-Kerry-Nader Presidential Contest
Authors: Batsell Richard R.
Published: February 2006

This short note introduces a new methodology for capturing and portraying the competitive structure of a market. Using the current Presidential contest as the context, the methodology first describes a simple and efficient data collection approach that generates the data necessary for applying Tverskys Elimination-By-Aspects Model (1972a, 1972b) at the market level. Then, relying on recently published mathematical results (Batsell, Polking, Cramer, and Miller, 2003) the method shows the complete decomposition of the competitive structure of a market based on the elimination model. Also introduced is a new way to graphically portray the competitive structure of a market in the form of a choice-based perceptual map, which has several desirable properties.
An Empirical Real-Time Test for Takeoff with Applications to Cellular Telephony
Authors: Wiorkowski John J , Gylys Victoria A
Published: February 2006

No methodology exists to aid the manager in empirically identifying a takeoff event in a real-time. This paper addresses this problem by developing generally applicable, simple and empirical tests for the determination of the takeoff point of a growth curve. The tests are applied to the adoption of wireless cellular telephony across 40 countries. The tests are shown to provide useful insight into the temporal development and dissemination of this technology.
Development and Psychometric Evaluation of the Eldercare Cultural Self-Efficacy Scale
Authors: Shellman Juliette
Published: February 2006

The purpose of this study was to describe the development and psychometric evaluation of the Eldercare Cultural Self-Efficacy Scale (ECSES). Bandura's Theory of Self-Efficacy provided the theoretical framework. The sample consisted of students (N=248) from seven schools of nursing in a northeast state. The psychometric evaluation included: item analysis, principal factor analysis (PFA) with orthogonal rotation, and internal consistency reliability using Cronbach's alpha. Descriptive statistics were used to determine levels of eldercare cultural self-efficacy among the sample. The PFA revealed a four factor structure (Assessing for Lifestyle and Social Patterns, Determining Cultural Health Practices, Determining Cultural Beliefs, and Dealing with Grief and the Losses Associated with Aging) that accounted for 61% of explained variance. The subscales alpha coefficients ranged from .82 to .95. Findings demonstrate the 28 item scale to be a reliable and valid instrument for use in nursing education to examine students' confidence in caring for ethnically diverse elders.
Action Methods in the Classroom: Creative Strategies for Nursing Education
Authors: McLaughlin Dorcas E. , Freed Patricia E. , Tadych Rita A.
Published: February 2006

Nursing education recognizes the need for a framework of experiential learning that supports the development of professional roles. Action methods, originated by Jacob L. Moreno (1953), can be readily adapted to any nursing classroom to create the conditions under which students learn and practice professional nursing roles. While nurse faculty can learn to use action methods, they may not fully comprehend their theoretical underpinnings or may believe they are only used in therapy. This article explores Morenos ideas related to psychodrama and sociodrama applied in classroom settings, and presents many examples and tips for classroom teachers who wish to incorporate action methods into their classes.
Valuing Ecosystem Services
Authors: Barbier Edward B , Heal Geoffrey M
Published: February 2006

Edward Barbier and Geoffrey Heal explain an emerging field aimed at valuing ecosystems, whose purpose is to help policy makers decide things like how best to get New York clean water or the role that expanded wetlands might play in limiting storm damage in New Orleans.
Influence of Flour Type on Mechanical Properties of Calcium-Induced Egg Albumen-Flour Composite Gel
Authors: Hongsprabhas Parichat , Dit-udom-po Srivikorn
Published: February 2006

The mechanical properties of composite network of hen egg albumen (EA) and flours; i.e., rice flour (RF) and/or cassava starch (CS) formed at 80 degree C using a salt-induced two-step gelation process were investigated. This structure-forming process induced gelation of pre-heated EA suspension in the presence of calcium ion and subsequent gelatinization of starch during the second heating regime. Increasing calcium lactate concentration up to 50 mM increased the aggregation of EA suspension and the Youngs modulus of EA gel. Above 50 mM, both aggregation of EA suspension and Youngs modulus of EA gel decreased. Addition of flour fillers to the EA suspension increased Youngs modulus, stress at fracture, initial stress at 20% deformation and residual stress after 20% deformation for 5 min. Raising the calcium lactate concentration influenced the mechanical characteristics of only EA-RF and EA-RF-CS but had no effect on those of EA-CS gel. The composite gels containing RF were more rigid than the ones containing CS. The EA-CS composite gel relaxed faster and to a much greater extent than the EA-RF gel. This was likely due to the high capacity of CS to absorb water, which weakened the strength of the granule after the composite structure was heated during the structure-forming process. Overall, results suggest that different flour fillers create composite gels with different mechanical properties due to the different pasting characteristics of flour constituents.
Finding nuggets in documents: A machine learning approach
Authors: Brook Wu Yi‐fang , Li Quanzhi , Bot Razvan Stefan , Chen Xin
Published: February 2006

Document keyphrases provide a concise summary of a document's content, offering semantic metadata summarizing a document. They can be used in many applications related to knowledge management and text mining, such as automatic text summarization, development of search engines, document clustering, document classification, thesaurus construction, and browsing interfaces. Because only a small portion of documents have keyphrases assigned by authors, and it is time‐consuming and costly to manually assign keyphrases to documents, it is necessary to develop an algorithm to automatically generate keyphrases for documents. This paper describes a Keyphrase Identification Program (KIP), which extracts document keyphrases by using prior positive samples of human identified phrases to assign weights to the candidate keyphrases. The logic of our algorithm is: The more keywords a candidate keyphrase contains and the more significant these keywords are, the more likely this candidate phrase is a keyphrase. KIP's learning function can enrich the glossary database by automatically adding new identified keyphrases to the database. KIP's personalization feature will let the user build a glossary database specifically suitable for the area of his/her interest. The evaluation results show that KIP's performance is better than the systems we compared to and that the learning function is effective.
A “stereo” document representation for textual information retrieval
Authors: Chen Liang , Zeng Jia , Tokuda Naoyuki
Published: February 2006

A new document representation model is presented in this paper. This model is based on the idea of representing a document by two or more pictures of the document taken from different perspectives. It is shown that by applying the stereo representation model, enhanced textual retrieval performance is achieved because the new model improves the capability of capturing individual features of the document. Experiments have been conducted on two standard corpora, TIME and ADI, using the standard term vector method and the latent semantic indexing (LSI) method based upon both the stereo representation model and the traditional representation model. Statistical t‐tests on the experimental results have convincingly illustrated that these methods achieve significant improvements in retrieval performances with the stereo representation model over those with the traditional representation model.
Unprecedented chemiluminescence behaviour during peroxyoxalate chemiluminescence of oxalates with fluorescent or electron‐donating aryloxy groups
Authors: Koike Ryu , Kato Yuji , Motoyoshiya Jiro , Nishii Yoshinori , Aoyama Hiromu
Published: February 2006

A series of diaryl and bis(4‐styrylphenyl) oxalates with electron‐donating substituents or fluorescent moieties were subjected to the peroxyoxalate chemiluminescence (PO‐CL) reaction, some of which were found to behave in a unprecedented manner. The reaction of bis(p‐methyoxyphenyl) oxalate, as a representative example, emits light due not only to the emission from the externally added excited fluorophore, but also from the presumable excimer of p‐methoxyphenol. Also, during the reaction of the bis(4‐styrylphenyl) oxalates, the emission based on the fluorescence as well as the excimer of the eliminating group were observed. These experimental results suggest that such emitting species would be formed by an intra‐ and intermolecular electronic interaction with a high‐energy intermediate, such as a dioxetanone. Copyright © 2006 John Wiley & Sons, Ltd.
Novel reporter gene in a fluorescent‐based whole cell sensing system
Authors: Feliciano Jessika , Liu Yue , Daunert Sylvia
Published: February 2006

A common problem encountered when using fluorescence detection in real samples analysis is that the matrix may contain compounds that autofluoresce or that can be excited at the wavelengths of commonly employed fluorescent reporter molecules. This causes an increase in background fluorescence, which in turn tends to compromise the detection limits of the system. To address this issue, we investigated the use of a reporter enzyme that produces fluorescent compounds, which can be excited at wavelengths that are not commonly encountered in compounds present in real samples. For that, a whole cell‐based sensing system for arsenite that employs cobA as the reporter gene was developed. The system utilizes genetically engineered bacteria that incorporate the specificity of the ars operon with the sensitivity of the cobA gene. The cobA gene codes for uroporphyrinogen III methyltransferase that converts the substrate uroporphyrinogen (urogen) III into two fluorescent compounds sirohydrochlorin and trimethylpyrrocorphin. Urogen III is ubiquitous within the cell, however, because the cells use it for vitamin B12 and siroheme biosynthesis, this sensing system is limited by substrate availability. By supplementing the media with ALA, a precursor of urogen III, a more stable and reproducible response was obtained. We observed three excitation maxima at 357, 378, and 498 nm, with a single emission maximum at 605 nm. Excitation at 498 nm was selected because it results in less background interference as most endogenous substances are not active at this wavelength. Advantages and limitations of using the cobA gene in whole‐cell sensing applications are presented. © 2006 Wiley Periodicals, Inc.
Visible laser and UV‐A radiation impact on a PNP degrading Moraxella strain and its rpoS mutant
Authors: Nandakumar Kanavillil , Keeler Werden , Schraft Heidi , Leung Kam T.
Published: February 2006

The role of stationary phase sigma factor gene (rpoS) in the stress response of Moraxella strain when exposed to radiation was determined by comparing the stress responses of the wild‐type (WT) and its rpoS knockout (KO) mutant. The rpoS was turned on by starving the WT cultures for 24 h in minimal salt medium. Under non‐starved condition, both WT and KO planktonic Moraxella cells showed an increase in mortality with the increase in duration of irradiation. In the planktonic non‐starved Moraxella, for the power intensity tested, UV radiation caused a substantially higher mortality rate than did by the visible laser light (the mortality rate observed for 15‐min laser radiation was 53.4 ± 10.5 and 48.7 ± 8.9 for WT and KO, respectively, and 97.6 ± 0 and 98.5 ± 0 for 25 s of UV irradiation in WT and KO, respectively). However, the mortality rate decreased significantly in the starved WT when exposed to these two radiations. In comparison, rpoS protected the WT against the visible laser light more effectively than it did for the UV radiation. The WT and KO strains of Moraxella formed distinctly different types of biofilms on stainless steel coupons. The KO strain formed a denser biofilm than did the WT. Visible laser light removed biofilms from the surfaces more effectively than did the UV. This was true when comparing the mortality of bacteria in the biofilms as well. The inability of UV radiation to penetrate biofilms due to greater rates of surface absorption is considered to be the major reason for the weaker removal of biofilms in comparison to that of the visible laser light. This result suggests that high power visible laser light might be an effective tool for the removal of biofilms. © 2006 Wiley Periodicals, Inc.
Scaled‐up production of mammalian neural precursor cell aggregates in computer‐controlled suspension bioreactors
Authors: Gilbertson Jane A. , Sen Arindom , Behie Leo A. , Kallos Michael S.
Published: February 2006

The clinical use of neural precursor cells (NPCs) for the treatment of neurological diseases, such as Parkinson's disease and Huntington's disease, requires overcoming the scarcity of these cells through controlled expansion. The main objective of the present study was to develop a large‐scale computer‐controlled bioprocess for the expansion of mammalian NPCs in suspension culture by scaling up existing reactor protocols. In order to support the oxygen demands of the maximum cell densities achieved, the volumetric mass transfer coefficient was kept above 1.10/h while scaling‐up from small‐scale 125 mL vessels to large‐scale 500 mL bioreactors. In addition, the maximum shear stress at the impeller tip was maintained between 0.30 and 0.75 Pa to reduce damage to the cells. The resulting large‐scale bioprocess achieved maximum viable cell densities of 1.2 × 106 cells/mL and a batch multiplication ratio of 9.1. Moreover, the process successfully maintained the NPC characteristics observed in small‐scale studies. © 2006 Wiley Periodicals, Inc.
Population-based study of risk factors for postoperative death after anterior resection of the rectum
Authors: Matthiessen P , Hallböök O , Rutegård J , Sjödahl R
Published: February 2006

Background

The aim of this population-based study was to analyse risk factors for death within 30 days after anterior resection of the rectum.

Methods

Between 1987 and 1995 a total of 6833 patients underwent elective anterior resection of the rectum in Sweden. One hundred and forty of these patients died within 30 days or during the initial hospital stay. These patients were compared with a randomly chosen cohort of 423 patients who underwent the same operation during the same interval, and were alive after 30 days and discharged from hospital. The association between death and 12 putative risk factors was studied.

Results

The mortality rate after elective anterior resection was 2·1 per cent (140 of 6833). The incidence of clinical anastomotic leakage was 42·1 per cent (59 of 140) among those who died and 10·9 per cent (46 of 423) in the cohort group. Multivariate regression analysis identified clinical leakage, increased age, male sex, Dukes' ‘D’ stage and intraoperative adverse events as independent risk factors for death within 30 days.

Conclusion

Clinical anastomotic leakage was a major cause of postoperative death after anterior resection.
Whose job is poverty? the problems of therapeutic intervention with children who are sexually violent
Authors: Allan Julaine
Published: February 2006

Children who commit sexually violent acts have been identified in increasing numbers since the 1980s. Professionals who practise therapeutic intervention with this group have struggled to find explanations for their client's deviant behaviour. Current explanations for, and discourses on, the occurrence of sexual violence minimize the effect of poverty in the therapeutic arena. The most difficult and worrisome child clients for participants of this research are the poor ones, yet the practice of counselling is unable to address structural disadvantage. This leads to a poverty culture explanation for sexual violence and child abuse which recognizes poverty yet pathologizes the individual. The identification of a new problem—children's sexual violence—the individualized case‐based approach to intervention and current social policy minimize the continuing and persistent problem of poverty. Copyright © 2006 John Wiley & Sons, Ltd.
Expanding indications for the treatment of pulmonary artery stenosis in children by using cutting balloon angioplasty
Authors: Butera Gianfranco , Antonio La Torre Marco , Massimo Chessa , Mario Carminati
Published: February 2006

Objectives: To evaluate the role of cutting balloon angioplasty in children with pulmonary artery stenosis. Background: Pulmonary artery stenoses can be either congenital or secondary to postoperative scar formation. Isolated multiple small‐vessel pulmonary artery stenoses are very rare. No surgical procedures for their treatment are currently available. Methods: We report on four patients in whom standard and high‐pressure balloon angioplasty had failed. Three of the four (2.5‐, 3‐, and 3.5‐years‐old; two girls) had isolated multiple peripheral pulmonary artery stenosis. The fourth patient was an 11‐month‐old girl (8 kg) with tetralogy of Fallot and hypoplastic pulmonary artery branches treated with the implantation of two stents in the pulmonary arteries. During the follow‐up this patient developed severe intrastent restenosis and showed severely hypoplasic distal left pulmonary artery. Results: We treated 11 vessels. The mean vessel diameter increased by 81% (P < 0.0001) and RV/LV pressure ratio decreased from 1.15 to 0.75 (P = 0.05). Patient treated for intrastent restenosis underwent successful complete tetralogy of Fallot repair. None of the patients suffered procedure‐related complications. At a median follow‐up of 18 months, results were stable and no late complications had occurred. Conclusions: Cutting balloon angioplasty is a promising technique for the treatment of highly challenging pathologies such as small vessel pulmonary artery stenoses and intrastent restenosis. © 2006 Wiley‐Liss, Inc.
Reaction time as a predictor of imaginative suggestibility and hypnotizability
Authors: Braffman Wayne , Kirsch Irving
Published: February 2006

The purpose of this exploratory investigation was to examine the relationship between reaction time, hypnotizability and imaginative suggestibility. The study participants were 119 undergraduate students who were assessed for non‐hypnotic and hypnotic suggestibility, performed simple and go/no‐go reaction time tasks and completed response expectancy, motivation, absorption and fantasy‐proneness scales. Faster simple response times were associated with greater hypnotic suggestibility, hypnotizability, response expectancies, absorption, fantasy‐proneness and non‐hypnotic motivation. Go/no‐go response time was not significantly correlated with any of these measures. With the other controlled, each reaction time measure was uniquely associated with hypnotic expectancy, hypnotic suggestibility, and hypnotizability, but in opposite directions. Copyright © 2001 British Society of Experimental and Clinical Hypnosis
A theory of hypnosis based on principles of conditioning and inhibition
Authors: Barrios Alfred A.
Published: February 2006

A theory of hypnosis based mainly on principles of conditioning and inhibition is proposed, covering the hypnotic induction process, hypnotic phenomena and post‐hypnotic phenomena. The overall explanation presented is delineated in a set of three initial postulates and seven subsequent hypotheses. Hypnotic induction is defined as the giving of a series of suggestions so that a positive response to a previous suggestion conditions the subject to respond more strongly to the next suggestion. This induction process is placed in a conditioning paradigm, with the condition stimulus (CS), unconditioned stimulus (UCS), conditioned response (CR) and unconditioned response (UCR), trials and reinforcement clearly delineated. Summarized in brief, hypnotic induction is explained as the conditioning of an inhibitory set, a set which increases responsiveness to suggestion by inhibiting stimuli and thoughts which would contradict the suggested response. The various hypnotic and post‐hypnotic phenomena are explained in terms of this set. Post‐hypnotic behaviour changes are further explained as produced through a process of higher‐order conditioning; hypnosis facilitates such conditioning thanks to the inhibitory set which suppresses any interfering stimuli. The theory may be broad enough to cover not only hypnosis but also related areas such as persuasion, the placebo effect and faith. Copyright © 2001 British Society of Experimental and Clinical Hypnosis
Old Molecules for New Receptors: Trp(Nps) Dipeptide Derivatives as Vanilloid TRPV1 Channel Blockers
Authors: Bonache M. Angeles , García‐Martínez Carolina , García de Diego Laura , Carreño Cristina , Pérez de Vega M. Jesús , García‐López M. Teresa , Ferrer‐Montiel Antonio , González‐Muñiz Rosario
Published: February 2006

The transient receptor potential vanilloid member 1 (TRPV1), an integrator of multiple pain‐producing stimuli, is regarded nowadays as an important biological target for the discovery of novel analgesics. Here, we describe the first experimental evidence for the behavior of an old family of analgesic dipeptides, namely Xaa‐Trp(Nps) and Trp(Nps)‐Xaa (Xaa=Lys, Arg) derivatives, as potent TRPV1 channel blockers. We also report the synthesis and biological investigation of a series of new conformationally restricted Trp(Nps)‐dipeptide derivatives with improved TRPV1/NMDA selectivity. Compound15 b, which incorporates an N‐terminal 2S‐azetidine‐derived Arg residue, was the most selective compound in this series. Collectively, a new family of TRPV1 channel blockers emerged from our results, although further modifications are required to fine‐tune the potency/selectivity/toxicity balance.
A PEG‐Based Biocompatible Block Catiomer with High Buffering Capacity for the Construction of Polyplex Micelles Showing Efficient Gene Transfer toward Primary Cells
Authors: Kanayama Naoki , Fukushima Shigeto , Nishiyama Nobuhiro , Itaka Keiji , Jang Woo‐Dong , Miyata Kanjiro , Yamasaki Yuichi , Chung Ung‐il , Kataoka Kazunori
Published: February 2006

Nonviral gene vectors from synthetic catiomers (polyplexes) are a promising alternative to viral vectors. In particular, many recent efforts have been devoted to the construction of biocompatible polyplexes for in vivo nonviral gene therapy. A promising approach in this regard is the use of poly(ethylene glycol) (PEG)‐based block catiomers, which form a nanoscaled core–shell polyplex with biocompatible PEG palisades. In this study, a series of PEG‐based block catiomers with different amine functionalities were newly prepared by a simple and affordable synthetic procedure based on an aminolysis reaction, and their utility as gene carriers was investigated. This study revealed that the block catiomers carrying the ethylenediamine unit at the side chain are capable of efficient and less toxic transfection even toward primary cells, highlighting critical structural factors of the cationic units in the construction of polyplex‐type gene vectors. Moreover, the availability of the polyplex micelle for transfection with primary osteoblasts will facilitate its use for bone regeneration in vivo mediated by nonviral gene transfection.
Quantitative analysis of promoter hypermethylation in multiple genes in osteosarcoma
Authors: Hou Peng , Ji Meiju , Yang Bin , Chen Zaozao , Qiu Junjun , Shi Xin , Lu Zuhong
Published: February 2006

BACKGROUND

Osteosarcoma is the most common solid malignant diseases of childhood, occurring in approximately 6 children per million annually; however, to the authors' knowledge to date, the cause of osteosarcoma has remained mostly unknown. Genetic alterations of genes that are specific for osteosarcoma have not been identified. Genetic alternations in the status of DNA methylation, known as epigenetic alterations, are the most common molecular alterations in human neoplasia. Aberrant methylation in the promoter region of tumor‐related genes is associated closely with epigenetically mediated gene silencing, which is a common feature in human tumors.

METHODS

The authors analyzed CpG islands of 5 different gene loci for aberrant methylation profiles in 30 pairs of osteosarcoma and corresponding normal tissues by using the quantitative methylation‐specific polymerase chain reaction method. The objectives of this study were to characterize the methylation changes in osteosarcoma more extensively and to identify epigenetic biomarkers that may be useful in the diagnosis and prevention of osteosarcoma.

RESULTS

For the Ras effector homologue (RASSF1A), tissue inhibitor of metalloproteinase 3 (TIMP3), O‐6‐methylguanine DNA methyltransferase (MGMT), and death‐associated protein kinase 1 (DAPK1) genes, significant differences were observed in the degree of hypermethylation between tumors and normal tissues (P < 0.01 and P < 0.001, respectively). Measurement of the cumulative multiple promoter hypermethylation revealed striking differences between tumor specimens and normal tissues (t = 7.31; P < .001). There also was a significant difference in the levels of DNA methylation between the metastatic and nonmetastatic high‐grade osteosarcomas (t = 4.57; P < .01). In addition, the methylation levels were associated closely with gender (t = 6.44; P < .001).

CONCLUSIONS

The results indicated that tumor tissues from patients with osteosarcoma had a significantly higher incidence of hypermethylation for several genes compared with corresponding normal tissues. The epigenetic changes observed in this study may have prognostic importance for patients with osteosarcoma. Cancer 2006. © 2006 American Cancer Society.
Nonsteroidal antiinflammatory drugs, cyclooxygenase polymorphisms, and the risk of developing breast carcinoma among women with benign breast disease
Authors: Gallicchio Lisa , McSorley Meghan A. , Newschaffer Craig J. , Thuita Lucy W. , Huang Han‐Yao , Hoffman Sandra C. , Helzlsouer Kathy J.
Published: February 2006

BACKGROUND

Biopsy‐proven benign breast disease (BBD) is a risk factor for developing breast carcinoma; however, to the authors' knowledge, little is known regarding factors related to progression to carcinoma. A cohort study was conducted to examine the role of cyclooxygenase (COX) polymorphisms and nonsteroidal anti‐inflammatory drugs (NSAIDs) in the progression of BBD to breast carcinoma.

METHODS

Among participants in an ongoing cohort study, 1467 women underwent a breast biopsy for BBD. Of these women, 91 subsequently developed breast carcinoma. Medication data were collected in 1989 and in 1996. COX genotypes were determined using DNA extracted from blood specimens collected in 1989.

RESULTS

A decrease in breast carcinoma risk was observed among women who reported using aspirin in 1989 (odds ratio [OR] of .46; 95% confidence interval [95% CI], .22–.98) and in 1996 (OR of .47, 95% CI, .18–1.21). Furthermore, a higher frequency, dose, and longer duration of aspirin use were associated with a decrease in the odds of developing breast carcinoma. Overall, no association was observed between COX genotypes and the subsequent development of breast carcinoma. However, among women not using NSAIDs, one COX‐2 polymorphism (rs2143416) was found to be significantly associated with the development of breast carcinoma.

CONCLUSIONS

Findings from the current study suggest that inflammation through COX‐2 pathways may play a role in the progression of BBD to breast carcinoma and that aspirin may help to lower the risk of progression to breast carcinoma among women with BBD. Cancer 2006. © 2006 American Cancer Society.
Incidence and clinical relevance of abnormal complete blood counts in long‐term survivors of childhood cancer
Authors: Long Zsofia B. , Oeffinger Kevin C. , Brooks Sandra L. , Fischbach Lori , Harris T. Robert , Eshelman Debra A. , Tomlinson Gail E. , Buchanan George R.
Published: February 2006

BACKGROUND

The purpose of the study was to determine the incidence and clinical significance of abnormal complete blood counts (CBCs) obtained during follow‐up of childhood cancer survivors.

METHODS

A retrospective cohort study was conducted on 193 survivors, diagnosed between 1970–1986, who were followed in our center's After Cancer Experience Program and are participants in the Childhood Cancer Survivor Study. Of these patients, 49% were female and 25% were racial/ethnic minorities. The primary outcome was determination of the cumulative percentage of patients having an abnormal CBC by 2 or 3 standard deviations (SDs). Four components of the CBC were examined and employed to define an abnormal CBC: low white blood cell count (WBC), high mean corpuscular volume (MCV), low platelet count, and low hemoglobin concentration. Association of treatment exposures to abnormal values was assessed with a multilevel logistic model.

RESULTS

There were 1297 patient visits during 1401 person‐years of follow‐up. The mean number of visits per survivor was 6.7 (SD 4.2). The cumulative percentage of subjects with at least one abnormal CBC was 70%. The cumulative percent of subjects with a value abnormal by 2 SD was WBC = 23%, MCV = 37%, platelets = 9%, hemoglobin = 49%. For values abnormal by 3 SD, the frequencies were WBC = 3%, MCV = 20%, platelets = 1%, hemoglobin = 27%. None of the patients developed myelodysplastic syndrome or a secondary leukemia during the follow‐up period. Exposure to epipodophyllotoxins was associated with an increased risk of having abnormally high MCV values.

CONCLUSIONS

Mildly abnormal CBC values are common in survivors of childhood cancer. Abnormal values are often of questionable significance but seem to persist over time. Epipodophyllotoxin therapy was found to be associated with increased frequency of high MCV levels. Cancer 2006. © 2006 American Cancer Society.
Comparison of two alternative methods for CD4+ T‐cell determination (Coulter manual CD4 count and CyFlow) against standard dual platform flow cytometry in Uganda
Authors: Karcher Heiko , Böhning Dankmar , Downing Robert , Mashate Silver , Harms Gundel
Published: February 2006

Background

In this study we evaluated alternative CD4+ T‐cell counting methods in clients of a PMTCT Programme in rural Uganda.

Methods

The Coulter Manual CD4 Count method for CD4+ T‐cell enumeration (Cyto‐Spheres) and an automated method (volumetric, single‐platform flow cytometry; CyFlow) were compared with a standard, dual‐platform flow cytometry protocol (DPFC, FACScan).

Results

Correlation and precision of agreement were higher for the CyFlow method (r = 0.929 and η = 0.08) when compared to DPFC than for the Cyto‐Spheres method (r = 0.725 and η = 0.3). Multiple linear regression analysis showed that CD4+ cell counts by the CyFlow method were a stronger predictor for results of DPFC than those of the Cyto‐Spheres method (r2 = 0.864 and r2 = 0.552, respectively). When compared to DPFC the CyFlow method generated higher CD4+ cell counts than the Cyto‐Spheres method, as expressed by a higher median and mean difference (+70 and +90 cells for CyFlow, +28 and −1.4 cells for Cyto‐Spheres).

Conclusion

Both, the manual Cyto‐Spheres method and the CyFlow method can be used for the enumeration of CD4+ cells in resource‐limited settings. Under supervised conditions, the CyFlow method produced results more consistent with the reference method than the Cyto‐Spheres method. © 2006 International Society for Analytical Cytology
The First Centrohexaindane Bearing Twelve Functional Groups at Its Outer Molecular Periphery and Related Lower Veratrole‐Derived Centropolyindanes
Authors: Harig Marco , Kuck Dietmar
Published: February 2006

The first Td‐symmetrical derivative of centrohexaindane bearing twelve functional groups has been synthesized. Six pairs of methoxy groups, each of which belong to six veratrole units fused to the topologically nonplanar (K5) core, point outwards from the molecular center into the six directions of the Cartesian space. The synthesis of this first dodeca‐substituted centrohexaindane was achieved along the “propellane route” established previously for the parent centrohexaindane, but the electron‐rich character of some of the intermediates was found to require considerably modified methodology. Two hexamethoxy‐substituted centrotriindanes, representing lower congeners of the title compound and bearing three veratrole units, were also synthesized. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)
In vivo mutagenesis in the lungs of gpt‐delta transgenic mice treated intratracheally with 1,6‐dinitropyrene
Authors: Hashimoto Akiko H. , Amanuma Kimiko , Hiyoshi Kyoko , Takano Hirohisa , Masumura Ken‐ichi , Nohmi Takehiko , Aoki Yasunobu
Published: February 2006

1,6‐Dinitropyrene (1,6‐DNP) is a ubiquitous airborne pollutant found in diesel exhaust. In this study, mutagenesis was examined in the lungs of gpt‐delta transgenic mice after intratracheal instillation of 0–0.1 mg 1,6‐DNP. In addition, the 1,6‐DNP‐induced gpt mutation spectrum was compared with that of control mice. A single intratracheal injection of 0–0.05 mg 1,6‐DNP resulted in significant dose‐dependent increases in mutant frequency; the induced mutant frequency declined at the 0.1 mg dose. The average lung mutant frequencies at doses of 0.025, 0.05, and 0.1 mg 1,6‐DNP were 2.9‐, 4.1‐, and 1.9‐times higher than for control mice ((0.50 ± 0.16) × 10−5). The major mutations induced by 1,6‐DNP included G:C→A:T transitions, G:C→T:A transversions, and 1‐base deletions. Among the G:C→A:T transitions isolated from 1,6‐DNP‐treated mice, five (at nucleotide positions 64, 110, 115, 116, and 418) were observed in four or more animals. These positions therefore are potential hotspots for 1,6‐DNP mutation. The predominant frameshift mutations following 1,6‐DNP treatment included single base pair deletions at G:C (9/13 = 69%). The results of this study indicate that 1,6‐DNP is mutagenic for the lungs of mice. Environ. Mol. Mutagen., 2006. © 2006 Wiley‐Liss, Inc.
Assessment of occupational exposure to welding fumes by inductively coupled plasma‐mass spectroscopy and by the alkaline Comet assay
Authors: Botta Céline , Iarmarcovai Gwenaëlle , Chaspoul Florence , Sari‐Minodier Irène , Pompili Jocelyne , Orsière Thierry , Bergé‐Lefranc Jean‐Louis , Botta Alain , Gallice Philippe , De Méo Michel
Published: February 2006

Welding fumes are classified as possibly carcinogenic to humans (Group 2B) by the International Agency for Research on Cancer. In the current study, blood and urine concentrations of aluminum (Al), cadmium (Cd), cobalt (Co), chromium (Cr), manganese (Mn), nickel (Ni), lead (Pb), and zinc (Zn) were monitored by inductively coupled plasma‐mass spectrometry (ICP‐MS) in 30 welders and in 22 controls. In addition, DNA damage was examined in the lymphocytes of these subjects by the alkaline Comet assay. Two biological samples were taken from the welders at the beginning (BW) and at the end (EW) of a work week. In controls, collection of samples was limited to BW. Blood concentrations of Cd, Co, Cr, Ni, and Pb were higher in the welders than in the control group while higher concentrations of Al, Cd, Co, Cr, Ni, and Pb were detected in welder urines. There was no significant difference in the metal concentrations for the BW and EW welder samples. Increased levels of DNA damage were found in lymphocytes from welders as compared to the controls, and 20/30 welders had higher levels of DNA lesions in the EW than in the BW samples. Age had a significant effect on DNA damage in the control group. Spearman's rank correlation analysis indicated that there were positive correlations between blood concentrations of Al, Co, Ni, and Pb and the levels of DNA damage. A negative correlation was found between DNA damage and Mn in blood, while there was a positive correlation between urinary Mn concentration and DNA damage. These data indicate that occupational exposure to welding fumes increases DNA damage in lymphocytes. Environ. Mol. Mutagen., 2006. © 2006 Wiley‐Liss, Inc.
Performance analysis of an integrated tangential microfilter‐fermenter
Authors: Naja Ghinwa , Volesky Bohumil , Schnell Andre
Published: February 2006

A specially designed bioreactor including an axial microfilter for cell retention was evaluated for continuous‐flow operation with selected liquid media as controls and in aerobic cultivations of Saccharomyces yeasts. In the initial tests, performance characteristics such as filtration rates and cell accumulation were assessed as a function of filter rotational speed, operating pressure, cultivation time and microfilter type (i.e. membrane or porous metal). The bioreactor did not perform satisfactorily when viscous extracellular polymer was present in the liquid. In the continuous‐flow culture enabling cell retention, Saccharomyces cerevisiae yeast cell concentrations were enhanced by as much as 16‐fold over ordinary batch growth. Concomitant filtration rates were stable over operating times of up to 130 h and hence were independent of the cell concentration. The maximum steady‐state flux was enhanced at rotational speeds up to 400‐700 rpm ranging from 22 to 42 L m−2 h−1. Higher rotation rates offered no further improvements. The maximum stabilized flux was independent of operating pressure. Pressure increases caused momentary flux improvements, which rapidly declined and eventually restabilized. Copyright © 2006 Society of Chemical Industry
Biotransformation of isoflavones by Aspergillus niger as biocatalyst
Authors: Miyazawa Mitsuo , Takahashi Koji , Araki Hideo
Published: February 2006

Biotransformation of the isoflavones, 6,7,4′‐trimethoxyisoflavone (1) and 5,7,4′‐trimethoxyisoflavone (2) by Aspergillus niger was investigated. Compound 1 was transformed to 4′‐hydroxy‐6,7‐dimethoxyisoflavone (3) and 2 to 4′‐hydroxy‐5,7‐dimethoxyisoflavone (4). This suggested that 1 and 2 were demethylated at the C‐4′ position with regioselectivity by Aspergillus niger. Copyright © 2006 Society of Chemical Industry