bluuebunny/crossref_metadata_2025 huggingface dataset:
A strategy to study tyrosinase transgenes in mouse melanocytes
Authors: Lavado Alfonso , Matheu Ander , Serrano Manuel , Montoliu Lluís
Published: April 2005

Background

A number of transgenic mice carrying different deletions in the Locus Control Region (LCR) of the mouse tyrosinase (Tyr) gene have been developed and analysed in our laboratory. We require melanocytes from these mice, to further study, at the cellular level, the effect of these deletions on the expression of the Tyr transgene, without potential interference with or from the endogenous Tyr alleles. It has been previously reported that it is possible to obtain and immortalise melanocyte cell cultures from postnatal mouse skin.

Results

Here, we describe the efforts towards obtaining melanocyte cultures from our Tyr transgenic mice. We have bred our Tyr transgenic mice into Tyr
c-32DSD
mutant background, lacking the endogenous Tyr locus. In these conditions, we failed to obtain immortalised melanocytes. We decided to include the inactivation of the Ink4a-Arf locus to promote melanocyte immortalisation. For this purpose, we report the segregation of the Ink4a-Arf null allele from the brown (Tyrp1
b
) mutation in mice. Finally, we found that Ink4a-Arf+/- and Ink4a-Arf-/- melanocytes had undistinguishable tyrosine hydroxylase activities, although the latter showed reduced cellular pigmentation content.

Conclusion

The simultaneous presence of precise genomic deletions that include the tyrosinase locus, such as the Tyr
c-32DSD
allele, the Tyr transgene itself and the inactivated Ink4a-Arf locus in Tyrp1
B
genetic background appear as the crucial combination to perform forthcoming experiments. We cannot exclude that Ink4a-Arf mutations could affect the melanin biosynthetic pathway. Therefore, subsequent experiments with melanocytes will have to be performed in a normalized genetic background regarding the Ink4a-Arf locus.
Hepatocyte growth factor (HGF) in fecal samples: rapid detection by surface plasmon resonance
Authors: Nayeri Fariba , Aili Daniel , Nayeri Tayeb , Xu Junyang , Almer Sven , Lundström Ingemar , Åkerlind Britt , Liedberg Bo
Published: April 2005

Background

The development of biosensors, based on surface plasmon resonance (SPR) technology, enables monitoring of a variety of biospecific interactions without the need for chemical-, biological- or radiological-labelled reagents.

Method

We utilised SPR to detect hepatocyte growth factor (HGF) in reconstituted faecal samples and studied samples from patients with infectious gastroenteritis (n = 20) and normal controls (n = 10). Mouse anti-human HGF monoclonal antibodies and recombinant human HGF receptor (c-Met)/Fc chimera were immobilised in flow cells of a CM5 biosensor chip.

Results

We found that infectious gastroenteritis produced a higher signal response compared to controls, due to binding of HGF to monoclonal anti-HGF antibody as well as binding of HGF to c-Met receptor (p < 0.01). The SPR signal response correlated with results from ELISA (r = 72%, p > 0.001). The signal response decreased significantly (p < 0.05) when samples were diluted with dextran, because of reduction in both specific as well as unspecific binding of HGF to dextran. The decrease in the specific response might imply that the dextran- binding site for HGF overlaps with the antibody binding epitope, or that dextran binding induces a conformational change of the HGF molecule. Bands corresponding to HGF were found by gel electrophoresis of purified faeces in an affinity chromatography column immobilised by HGF ligands.

Conclusion

Determination of HGF by SPR might be beneficial in diagnosis of acute situations that present with symptoms of gastroenteritis and may, possibly, guide appropriate medical treatments. This is to our knowledge the first report on the use of SPR for detection of HGF in faeces samples.
Myeloid antigens in childhood lymphoblastic leukemia:clinical data point to regulation of CD66c distinct from other myeloid antigens
Authors: Kalina Tomas , Vaskova Martina , Mejstrikova Ester , Madzo Jozef , Trka Jan , Stary Jan , Hrusak Ondrej
Published: April 2005

Background

Aberrant expression of myeloid antigens (MyAgs) on acute lymphoblastic leukemia (ALL) cells is a well-documented phenomenon, although its regulating mechanisms are unclear. MyAgs in ALL are interpreted e.g. as hallmarks of early differentiation stage and/or lineage indecisiveness. Granulocytic marker CD66c – Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is aberrantly expressed on ALL with strong correlation to genotype (negative in TEL/AML1 and MLL/AF4, positive in BCR/ABL and hyperdiploid cases).

Methods

In a cohort of 365 consecutively diagnosed Czech B-precursor ALL patients, we analyze distribution of MyAg+ cases and mutual relationship among CD13, CD15, CD33, CD65 and CD66c. The most frequent MyAg (CD66c) is studied further regarding its stability from diagnosis to relapse, prognostic significance and regulation of surface expression. For the latter, flow cytometry, Western blot and quantitative RT-PCR on sorted cells is used.

Results

We show CD66c is expressed in 43% patients, which is more frequent than other MyAgs studied. In addition, CD66c expression negatively correlates with CD13 (p < 0.0001), CD33 (p = 0.002) and/or CD65 (p = 0.029). Our data show that different myeloid antigens often differ in biological importance, which may be obscured by combining them into "MyAg positive ALL". We show that unlike other MyAgs, CD66c expression is not shifted from the onset of ALL to relapse (n = 39, time to relapse 0.3–5.3 years). Although opposite has previously been suggested, we show that CEACAM6 transcription is invariably followed by surface expression (by quantitative RT-PCR on sorted cells) and that malignant cells containing CD66c in cytoplasm without surface expression are not found by flow cytometry nor by Western blot in vivo. We report no prognostic significance of CD66c, globally or separately in genotype subsets of B-precursor ALL, nor an association with known risk factors (n = 254).

Conclusion

In contrast to general notion we show that different MyAgs in lymphoblastic leukemia represent different biological circumstances. We chose the most frequent and tightly genotype-associated MyAg CD66c to show its stabile expression in patients from diagnosis to relapse, which differs from what is known on the other MyAgs. Surface expression of CD66c is regulated at the gene transcription level, in contrast to previous reports.
Subjective face recognition difficulties, aberrant sensibility, sleeping disturbances and aberrant eating habits in families with Asperger syndrome
Authors: Nieminen-von Wendt Taina , Paavonen Juulia E , Ylisaukko-Oja Tero , Sarenius Susan , Källman Tiia , Järvelä Irma , von Wendt Lennart
Published: April 2005

Background

The present study was undertaken in order to determine whether a set of clinical features, which are not included in the DSM-IV or ICD-10 for Asperger Syndrome (AS), are associated with AS in particular or whether they are merely a familial trait that is not related to the diagnosis.

Methods

Ten large families, a total of 138 persons, of whom 58 individuals fulfilled the diagnostic criteria for AS and another 56 did not to fulfill these criteria, were studied using a structured interview focusing on the possible presence of face recognition difficulties, aberrant sensibility and eating habits and sleeping disturbances.

Results

The prevalence for face recognition difficulties was 46.6% in individuals with AS compared with 10.7% in the control group. The corresponding figures for subjectively reported presence of aberrant sensibilities were 91.4% and 46.6%, for sleeping disturbances 48.3% and 23.2% and for aberrant eating habits 60.3% and 14.3%, respectively.

Conclusion

An aberrant processing of sensory information appears to be a common feature in AS. The impact of these and other clinical features that are not incorporated in the ICD-10 and DSM-IV on our understanding of AS may hitherto have been underestimated. These associated clinical traits may well be reflected by the behavioural characteristics of these individuals.
Assessing spatio-temporal variability of risk surfaces using residential history data in a case control study of breast cancer
Authors: Han Daikwon , Rogerson Peter A , Bonner Matthew R , Nie Jing , Vena John E , Muti Paola , Trevisan Maurizio , Freudenheim Jo L
Published: April 2005

Background

Most analyses of spatial clustering of disease have been based on either residence at the time of diagnosis or current residence. An underlying assumption in these analyses is that residence can be used as a proxy for environmental exposure. However, exposures earlier in life and not just those in the most recent period may be of significance. In breast cancer, there is accumulating evidence that early life exposures may contribute to risk. We explored spatio-temporal patterns of risk surfaces using data on lifetime residential history in a case control study of breast cancer, and identified elevated areas of risk and areas potentially having more exposure opportunities, defined as risk surfaces in this study. This approach may be more relevant in understanding the environmental etiology of breast cancer, since lifetime cumulative exposures or exposures at critical times may be more strongly associated with risk for breast cancer than exposures from the recent period.

Results

A GIS-based exploratory spatial analysis was applied, and spatio-temporal variability of those risk surfaces was evaluated using the standardized difference in density surfaces between cases and controls. The significance of the resulting risk surfaces was tested and reported asp-values. These surfaces were compared for premenopausal and postmenopausal women, and were obtained for each decade, from the 1940s to 1990s. We found strong evidence of clustering of lifetime residence for premenopausal women (for cases relative to controls), and a less strong suggestion of such clustering for postmenopausal women, and identified a substantial degree of temporal variability of the risk surfaces.

Conclusion

We were able to pinpoint geographic areas with higher risk through exploratory spatial analyses, and to assess temporal variability of the risk surfaces, thus providing a working hypothesis on breast cancer and environmental exposures. Geographic areas with higher case densities need further epidemiologic investigation for potential relationships between lifetime environmental exposures and breast cancer risk. Examination of lifetime residential history provided additional information on geographic areas associated with higher risk; limiting exploration of chronic disease clustering to current residence may neglect important relationships between location and disease.
Breakdown of accommodation in nerve: a possible role for persistent sodium current
Authors: Hennings Kristian , Arendt-Nielsen Lars , Andersen Ole K
Published: April 2005

Background

Accommodation and breakdown of accommodation are important elements of information processing in nerve fibers, as they determine how nerve fibers react to natural slowly changing stimuli or electrical stimulation. The aim of the present study was to elucidate the biophysical mechanism of breakdown of accommodation, which at present is unknown.

Results

A model of a space-clamped motor nerve fiber was developed. It was found that this new model could reproduce breakdown of accommodation when it included a low-threshold, rapidly activating, persistent sodium current. However, the phenomenon was not reproduced when the persistent sodium current did not have fast activation kinetics or a low activation threshold.

Conclusion

The present modeling study suggests that persistent, low-threshold, rapidly activating sodium currents have a key role in breakdown of accommodation, and that breakdown of accommodation can be used as a tool for studying persistent sodium current under normal and pathological conditions.
Monitoring processed, mature Human Immunodeficiency Virus type 1 particles immediately following treatment with a protease inhibitor-containing treatment regimen
Authors: Baird Heather A , Marozsan Andre J , Lederman Michael M , Landay Alan , Mildvan Donna , Kuritzkes Daniel R , Kessler Harold A , Arts Eric J
Published: April 2005

Protease inhibitors (PIs) block HIV-1 maturation into an infectious virus particle by inhibiting the protease processing of gag and gag-pol precursor proteins. We have used a simple anti-HIV-1 p24 Western blot to monitor the processing of p55gag precursor into the mature p24 capsid immediately following the first dosage of a PI-containing treatment regimen. Evidence of PI activity was observed in plasma virus as early as 72 hours post treatment-initiation and was predictive of plasma viral RNA decrease at 4 weeks.
COUP-TFIIis essential for radial and anteroposterior patterning of the stomach
Authors: Takamoto Norio , You Li-Ru , Moses Kelvin , Chiang Chin , Zimmer Warren E. , Schwartz Robert J. , DeMayo Francesco J. , Tsai Ming-Jer , Tsai Sophia Y.
Published: April 2005

COUP-TFII, an orphan member of the steroid receptor superfamily,has been implicated in mesenchymal-epithelial interaction during organogenesis. The generation of a lacZ knock-in allele in the COUP-TFII locus in mice allows us to use X-gal staining to follow the expression of COUP-TFII in the developing stomach. We found COUP-TFII is expressed in the mesenchyme and the epithelium of the developing stomach. Conditional ablation of floxed COUP-TFII by Nkx3-2Cre recombinase in the gastric mesenchyme results in dysmorphogenesis of the developing stomach manifested by major patterning defects in posteriorization and radial patterning. The epithelial outgrowth,the expansion of the circular smooth muscle layer and enteric neurons as well as the posteriorization of the stomach resemble phenotypes exhibited by inhibition of hedgehog signaling pathways. Using organ cultures and cyclopamine treatment, we showed downregulation of COUP-TFII level in the stomach, suggesting COUP-TFII as a target of hedgehog signaling in the stomach. Our results are consistent with a functional link between hedgehog proteins and COUP-TFII, factors that are vital for epithelial-mesenchymal interactions.
Selective Golgi export of Kir2.1 controls the stoichiometry of functional Kir2.x channel heteromers
Authors: Hofherr Alexis , Fakler Bernd , Klöcker Nikolaj
Published: April 2005

Surface expression of ion channels and receptors often depends on intrinsic sequence motifs that control their intracellular transport along the secretory pathway. Although members of the Kir2.x subfamily share two such motifs – a diacidic ER export motif and a positively charged Golgi export motif – they strongly differ in their surface expression. Whereas Kir2.1 shows prominent plasma membrane localization, Kir2.4 channels accumulate within the Golgi complex. By constructing chimeras between Kir2.1 and Kir2.4 subunits, a stretch of 20 amino acids was identified in the Kir2.1 C-terminus that is both necessary and sufficient to promote anterograde transport of Kir channel subunits at the level of trafficking from the Golgi to the plasma membrane. The core element of the identified sequence bears a tyrosine-dependent YXXΦ consensus motif for adaptin binding, with the flanking residues determining its functional efficiency. As the signal is dominant in promoting surface transport of Kir2.1/Kir2.4 channel heteromers and is recognized by both the epithelial and neuronal intracellular sorting machinery, the preferential Golgi export of Kir2.1 will control the stoichiometry of Kir2.x heteromers expressed on the cell surface.
The goal‐dependent automaticity of drinking habits
Authors: Sheeran Paschal , Aarts Henk , Custers Ruud , Rivis Amanda , Webb Thomas L. , Cooke Richard
Published: April 2005

In recent treatments of habitual social behaviour, habits are conceptualized as a form of goal‐directed automatic behaviour that are mentally represented as goal‐action links. Three experiments tested this conceptualization in the context of students' drinking (alcohol consumption) habits. Participants were randomly assigned to conditions where either a goal related to drinking behaviour (socializing) was activated, or an unrelated goal was activated. In addition, participants' drinking habits were measured. The dependent variable in Experiments 1 and 2 was readiness to drink, operationalized by speed of responding to the action concept ‘drinking’ in a verb verification task. Experiment 3 used the uptake of a voucher to measure drinking behaviour. Findings supported the view that when habits are established, simply activating a goal related to the focal behaviour automatically elicits that behaviour. These findings are consistent with a goal‐dependent conception of habit. Possibilities for interventions designed to attenuate undesirable habitual behaviours are considered.
Peer influences on body dissatisfaction and dieting awareness in young girls
Authors: Dohnt Hayley K. , Tiggemann Marika
Published: April 2005

Aim. This study aimed to explore the role of peer influences in the development of body dissatisfaction and dieting awareness in young girls.

Method. A sample of 81 girls (aged 5–8 years) were recruited from the first 3 years of formal schooling. Girls were individually interviewed. Body dissatisfaction was assessed by means of figure rating preferences, and dieting awareness by responses to a brief scenario. A number of sources of peer influence were also assessed.

Results. Year 2 girls were found to display significantly greater body dissatisfaction than younger girls. All girls, irrespective of age, preferred a similar thin ideal figure. Year level constituted the only significant predictor of dieting awareness, with older girls demonstrating a greater understanding of dieting than younger girls. Importantly, girls' perception of their peers' body dissatisfaction emerged as the strongest predictor of their own level of body dissatisfaction.

Conclusions. Body dissatisfaction in girls first emerges during the junior primary school years, between ages 5 and 7 years, and appears to be a function of shared peer norms for thinness.
Moral/non‐moral domain shift in young adolescents in relation to delinquent behaviour
Authors: Leenders Ineke , Brugman Daniel
Published: April 2005

Because moral transgressions are considered more serious than non‐moral (i.e. conventional or personal) transgressions, it is less threatening to self‐esteem to interpret one's own delinquent act as a non‐moral transgression rather than a moral transgression. This ‘domain shift’ could be a way of reducing cognitive dissonance. It was expected that adolescents who report a certain category of delinquent behaviour would evaluate hypothetical transgressions in the same category as more non‐moral than would adolescents who did not report that category of delinquent behaviour. A group of 278 students from the first (M(age)=13.1), second (M(age)=14.3) and third (M(age)=15.2) grade of intermediate secondary schools in the Netherlands participated in the research. The results showed a domain shift from the moral towards non‐moral domains in the evaluation of hypothetical situations about delinquent behaviour reported by the adolescent. At the same time, this domain shift did not occur in situations concerning delinquent behaviour not reported by the adolescent, even when delinquent behaviour occurred in the adolescent's peer group. This finding is consistent with the hypothesis that the domain shift takes place as a consequence of cognitive dissonance. The results also showed that the attitude towards delinquent behaviour and the prevalence of delinquent behaviour in the peer group both predicted a unique part of the variance in reported delinquent behaviour (RDB; 28% and 10%, respectively). The level of moral reasoning (measured by the Sociomoral Reflection Measure–Short Form [SRM‐SF]) did not appear to be a significant predictor of RDB.
Theory of mind and mental state discourse during book reading and story‐telling tasks
Authors: Symons Douglas K. , Peterson Candida C. , Slaughter Virginia , Roche Jackie , Doyle Emily
Published: April 2005

This article presents three studies conducted in Canada and Australia that relate theory of mind (ToM) development to mental state discourse. In Study 1, mental state discourse was examined while parents and their 5–7‐year‐old children jointly read a storybook which had a surprise ending about the identity of the main character. Comments specific to the mental states of the story characters and discourse after the book had ended were positively related to children's ToM, and this was due to parent elaborations. Studies 2 and 3 examined children's mental state discourse during story‐telling tasks, and in both, mental state discourse of children during narrative was concurrently related to ToM performance. While research has shown that mental state discourse of parents is related to children's ToM acquisition, the current research indicates that children's spontaneous use of mental state language examined outside of the interactional context is also a strong correlate.
Essay Review
Authors: Wertsch James V.
Published: April 2005

Making human beings human: Bioecological perspectives on human development: Edited by U. Bronfenbrenner Thousand Oaks, CA: Sage Publications. 2004. Pp. 336. Paperback, $34.95. ISBN 0761927123. Hardback, $74.95. ISBN 0761927115
How language does (and does not) relate to theory of mind: A longitudinal study of syntax, semantics, working memory and false belief
Authors: Slade Lance , Ruffman Ted
Published: April 2005

Forty‐four children (mean 3.8 years) were given three false belief, a working memory, and four language tasks (each designed to tap a different aspect of syntax or semantics), and were tested again 6 months later. Once the range of scores in the language and false belief tasks were equated, there was a bidirectional relation between language and theory of mind. There was no evidence for syntax playing a unique role in the contribution of language to theory of mind. No one measure of syntax or semantics was more likely than any other to predict later false belief. Nor was false belief related more to one aspect of later language (syntax vs. semantics) than another. Our data, taken with other findings, are consistent with the idea that both syntax and semantics contribute to false belief understanding. Working memory did not mediate the relation between language and theory of mind, nor did it facilitate later false belief.
The Boundaries of Loss Aversion
Authors: Novemsky Nathan , Kahneman Daniel
Published: April 2005

In this article, the authors propose some psychological principles to describe the boundaries of loss aversion. A key idea is that exchange goods that are given up “as intended” do not exhibit loss aversion. For example, the authors propose that money given up in purchases is not generally subject to loss aversion. The results of several experiments provide preliminary support for the hypotheses. The authors find that, consistent with prospect theory, loss aversion provides a complete account of risk aversion for risks with equal probability to win or lose. The authors propose boundaries for this result and suggest further tests of the model.
Three Cheers—Psychological, Theoretical, Empirical—for Loss Aversion
Authors: Camerer Colin
Published: April 2005

This note emphasizes the special role of prospect theory in drawing psychophysical considerations into theories of decision making with respect to risk. An example of such a consideration is the dependence of outcome value on a reference point and the increased sensitivity of loss relative to gain (i.e., loss aversion). Loss aversion can explain the St. Petersburg paradox without requiring concave utility, it has the correct psychological foundation, it is theoretically useful, and it is a parsimonious principle that can explain many puzzles. A few open questions are whether loss aversion is a stable feature of preference, whether it is an expression of fear, and what are its properties.
When Do Losses Loom Larger than Gains?
Authors: Ariely Dan , Huber Joel , Wertenbroch Klaus
Published: April 2005

In defining limits to loss aversion, Novemsky and Kahneman (2005) offer important new data and a needed summary of appropriate ways to think about loss aversion. In this comment to Novemsky and Kahneman's article, the authors consider the new empirical results that involve probabilistic buying and selling, suggesting caution in generalizing the results to nonprobabilistic commerce. The authors expand Novemsky and Kahneman's summary by exploring two critical constructs that help define the boundaries of loss aversion: emotional attachment and cognitive perspective. Emotional attachment alters loss aversion by moderating the degree to which parting with an item involves a loss, whereas shifts in cognitive perspective explain why items typically viewed as a loss are given more or less weight. The goal is to use these constructs to characterize more specifically contexts in which losses loom larger than gains and to suggest specific ways that research into loss aversion could evolve.
How Do Intentions Affect Loss Aversion?
Authors: Novemsky Nathan , Kahneman Daniel
Published: April 2005

Previously (see Novemsky and Kahneman 2005 ), the authors proposed that intentions to exchange versus to consume a good moderate loss aversion for that good. In this rejoinder, the authors follow up on this idea, discussing several mechanisms that Ariely, Huber, and Wertenbroch (2005) propose by which intentions can moderate loss aversion. The authors consider both emotional attachment to the good and cognitive focus during evaluation as potential mediators of the effects of intentions on loss aversion.
New Empirical Generalizations on the Determinants of Price Elasticity
Authors: Bijmolt Tammo H.A. , Van Heerde Harald J. , Pieters Rik G.M.
Published: April 2005

The importance of pricing decisions for firms has fueled an extensive stream of research on price elasticities. In an influential meta-analytical study, Tellis (1988) summarized price elasticity research findings until 1986. However, empirical generalizations on price elasticity require modifications because of (1) changes in market characteristics (i.e., characteristics of brands, product categories, and economic conditions) and (2) changes in the research methodology used to assess price elasticities. Therefore, the authors present a meta-analysis of price elasticity with new empirical generalizations on its determinants. Across a set of 1851 price elasticities based on 81 studies, the average price elasticity is −2.62. A salient finding is that over the past four decades, sales elasticities have significantly increased in magnitude, whereas share and choice elasticities have remained fairly constant. The authors find that accommodating price endogeneity has a strong (magnitude-increasing) impact on price elasticities. A striking null result is that accounting for heterogeneity does not affect elasticities significantly. The authors also present an analysis that explains the difference between their findings and Tellis's findings, and they indicate which new price elasticity studies are most desirable.
The Influence of Consumer Distractions on the Effectiveness of Food-Sampling Programs
Authors: Nowlis Stephen M. , Shiv Baba
Published: April 2005

Sampling programs are a significant element of the promotions mix, particularly in the food category. In this research, the authors find that the degree to which consumers are distracted while sampling a product can influence the effectiveness of such programs. In particular, the authors find that distraction actually increases subsequent choice of the sampled food, a finding that is contrary to what industry experts predict. The authors propose a dual-process model of somatosensory experiences to account for the findings. In line with the model, the findings suggest that the ultimate pleasure that a consumer derives from the taste of a food sample depends on two components, an informational component and an affective component. Furthermore, the findings suggest that distraction affects the subsequent choice of the sampled item by increasing (decreasing) the impact of the affective component (informational component) on subsequent choice.
Recovering Stockkeeping-Unit-Level Preferences and Response Sensitivities from Market Share Models Estimated on Item Aggregates
Authors: Bell David R. , Bonfrer André , Chintagunta Pradeep K.
Published: April 2005

The authors propose a new approach to obtaining stockkeeping-unit (SKU)-level preferences and response sensitivities. The authors distinguish an attribute-level model, in which the unit of analysis is the market share for an alternative created by aggregation (e.g., Colgate toothpaste), from a truly disaggregate SKU-level model, and they establish an analytical relationship between parameters that they obtain from the two models. The authors show that SKU-level parameters can be recovered by calculation from estimated attribute-level parameters, circumventing the need for direct estimation of the more complex SKU-level model. They calibrate the store data market share model using 98 weeks of data for ten brands and 168 SKUs of toothpaste. Rather than estimate 168 preference parameters (when there is an “outside” alternative in addition to the 168 “inside” ones), it is only necessary to estimate ten brand-preference parameters from which the 168 parameters can be computed, as long as share and marketing-mix data are available at the SKU level. Covariate effects, such as marketing-mix response parameters, can be recovered in a similar fashion. Holdout tests demonstrate superior predictive performance, and the authors discuss implications for the derivation of elasticities for new SKU introductions.
Brand Counterextensions: The Impact of Brand Extension Success versus Failure
Authors: Kumar Piyush
Published: April 2005

In this article, the author investigates the impact of a brand extension's success versus failure on customer evaluation of brand counter-extensions. A counterextension is a brand extension that is launched into Category A by Brand 2 that belongs to Category B in a reciprocal direction to a launch of a previous extension into Category B by Brand 1 that belongs to Category A. The results from five studies show that customers evaluate a counterextension more favorably when the preceding extension is a success rather than a failure. Furthermore, the evaluation of the counterextension is superior if it is launched by a major brand, especially if the previous successful extension was also launched by a major brand. Finally, a successful extension indirectly dilutes a brand and results in a greater loss in choice share to a counterextension than does a failed extension. The key findings generalize to a sequence of extensions across more than one intercategory boundary.
Modeling Preferences for Common Attributes in Multicategory Brand Choice
Authors: Singh Vishal P. , Hansen Karsten T. , Gupta Sachin
Published: April 2005

The authors propose a multicategory brand choice model based on the conceptualization that the intrinsic utility for a brand is a function of underlying attributes, some of which are common across categories. The premise is that household preferences for attributes that are common across categories are likely to be correlated. The model that the authors develop projects the unobserved preferences for attributes to a lower dimensional space of unobserved factors. The factors are interpretable as household “traits” that transcend categories, and they can be used to predict preferences for attributes in new categories. The authors apply the proposed model to household panel data for three closely related snack categories and for two less-related food categories. The authors find strong correlations in preferences for product attributes such as brand names and low fat or fat free. This study demonstrates that these high correlations in product attribute preferences across categories are useful in targeting activities in existing and new categories.
Heterogeneous Conjoint Choice Designs
Authors: Sándor Zsolt , Wedel Michel
Published: April 2005

Previous conjoint choice design construction procedures have produced a single homogeneous design that is administered to all study participants. In contrast, this article proposes to construct a limited set of different designs. The principle of heterogeneous designs is applicable to a variety of types of models. This article illustrates this principle for Bayesian designs, taking into account prior uncertainty about the parameter values, and for mixed logit designs that accommodate respondent heterogeneity. The authors develop and investigate a computational procedure that enables quick and easy implementation. Although the number of different designs in the optimal set is small, the authors use a Monte Carlo study to demonstrate that their heterogeneous design achieves substantial gains in efficiency compared with homogeneous designs.
Do Strategic Conclusions Depend on how Price is Defined in Models of Distribution Channels?
Authors: Tyagi Rajeev K.
Published: April 2005

Models of distribution channels have defined retailer and manufacturer pricing decision variables in different ways, such as absolute retail price or absolute retail margin and absolute manufacturer price or absolute manufacturer margin. This article examines whether this choice of definition affects the equilibrium outcomes from such models. It shows that the equilibrium outcomes do not change with these definitions if manufacturers are modeled as Stackelberg pricing leaders to their retailer. However, if manufacturers are modeled as Bertrand-Nash competitors to their retailer or as Stackelberg pricing followers to their retailer, the equilibrium outcomes change depending on how the retailer's pricing decision variables are defined. Moreover, if in these two cases manufacturers and retailer are allowed to define their own pricing decision variables, then (1) manufacturers are indifferent about choosing among absolute prices, absolute margins, and percentage margins, but (2) the retailer chooses percentage margins. These results have implications for both theoretical and empirical models of price competition in distribution channels.
Cross-Selling Sequentially Ordered Products: An Application to Consumer Banking Services
Authors: Li Shibo , Sun Baohong , Wilcox Ronald T.
Published: April 2005

Customers have predictable life cycles. As a result of these life cycles, firms that sell multiple products or services frequently observe that, in general, certain items are purchased before others. This predictable phenomenon provides opportunities for firms to cross-sell additional products and services to existing customers. This article presents a structural multivariate probit model to investigate how customer demand for multiple products evolves over time and its implications for the sequential acquisition patterns of naturally ordered products. The authors investigate customer purchase patterns for products that are marketed by a large midwestern bank. Among the substantive findings are that women and older customers are more sensitive to their overall satisfaction with the bank than are men and younger customers when determining whether to purchase additional financial services, and households whose head has a greater level of education or is male move more quickly along the financial maturity continuum than do households whose head has less education or is female.
AMPA Receptor Binding Cleft Mutations That Alter Affinity, Efficacy, and Recovery from Desensitization
Authors: Robert Antoine , Armstrong Neali , Gouaux J. Eric , Howe James R.
Published: April 2005

Glutamate binds to AMPA receptors within a deep cleft between two globular protein domains (domains 1 and 2). Once glutamate binds, the cleft closes, and agonist-bound structures of the isolated ligand binding core suggest that closure of the binding cleft is sufficiently complete that it essentially prevents ligand dissociation. There is also considerable evidence supporting the view that cleft closure is the initial conformational change that triggers receptor activation and desensitization, and it has been clearly demonstrated that there is a correlation between the degree of cleft closure and agonist efficacy. It is unknown, however, whether the stability of binding cleft closure also influences receptor-channel properties. The crystallographic structures indicate that closed-cleft conformations are stabilized by the formation of hydrogen bonds that involve amino acid side chains of residues in domains 1 and 2. We show here that mutations that disrupt one such cross-cleft hydrogen bond (in the AMPA receptor subunit GluR2) decrease both agonist affinity and efficacy. The same mutations also hasten recovery from desensitization. We conclude that the stability of binding cleft closure has a significant impact on AMPA receptor function and is a major determinant of the apparent affinity of agonists. The results suggest that the stability of cleft closure has been tuned so that glutamate dissociates as rapidly as possible yet remains a full agonist.
Role of Amygdalo-Nigral Circuitry in Conditioning of a Visual Stimulus Paired with Food
Authors: Lee Hongjoo J. , Groshek Frank , Petrovich Gorica D. , Cantalini Joseph P. , Gallagher Michela , Holland Peter C.
Published: April 2005

The amygdala central nucleus (CeA) plays an important part in associative learning. Although most research has focused on functions of its descending projections to brainstem areas involved in autonomic and somatomotor responses, the ascending projections of CeA also play critical roles in learning. For example, a CeA-nigrostriatal pathway is important for acquiring orienting responses (ORs) to conditioned stimuli (CSs) that signal food delivery. In this study, the function of this CeA-nigrostriatal pathway in appetitive conditioning of rats was considered in more detail.

In experiment 1, we combined anatomical tracing and methods for detecting neuronal activation to examine whether CeA neurons that project to the substantia nigra pars compacta (SNc) are activated by a visual CS for food. After injection of the retrograde tracer Fluoro-Gold (FG) into SNc, the rats received pairings of a visual CS with food. After a test with the CS alone, the brains were prepared to assess FG labeling and CS-induced Fos expression in CeA with immunohistochemical procedures. Colocalization of Fos and FG in CeA neurons was visualized with confocal-fluorescence microscopy. The CS induced Fos expression in CeA, and a majority of these Fos-positive neurons were also FG positive, indicating activation of the CeA-SNc pathway by the CS. In experiment 2, lesions that disconnected CeA and SNc prevented the acquisition of conditioned ORs but did not affect the acquisition of conditioned food-related responses or the display of unconditioned ORs. These experiments demonstrate a role for amygdalo-nigral circuitry in learned modulation of attention to signals for biologically significant events.
Optical Current Source Density Analysis in Hippocampal Organotypic Culture Shows That Spreading Depression Occurs with Uniquely Reversing Currents
Authors: Kunkler Phillip E. , Hulse Raymond E. , Schmitt Michael W. , Nicholson Charles , Kraig Richard P.
Published: April 2005

Spreading depression (SD) involves current flow through principal neurons, but the pattern of current flow over the expanse of susceptible tissues or individual principal neurons remains undefined. Accordingly, tissue and single cell maps made from digital imaging of voltage-sensitive dye changes in hippocampal organotypic cultures undergoing SD were processed via optical current source density analysis to reveal the currents associated with pyramidal neurons. Two distinctive current flow patterns were seen. The first was a trilaminar pattern (420 μm2) that developed with the onset of SD in CA3 pyramidal neurons, in which SD most often began. This initial pattern comprised a somatic current sink with current sources to either side in the dendrites that lasted for seconds extending into the first aspect of the classical “inverted saddle” interstitial direct current waveform of SD. Next, the somatic sink backpropagated at a speed of millimeters per minute into the proximal dendrites, resulting in a reversal of the initial current flow pattern to its second orientation, namely dendritic sinks associated with a somatic source. The latter persisted for the remainder of SD in CA3 and was the only pattern seen in CA1, in which SD was rarely initiated. This backpropagating SD current flow resembles that of activity-dependent synaptic activation. Retrograde and associative signaling via principal neuron current flow is a key means to affect tissue function, including synaptic activation and, by extension, perhaps SD. Such current-related postsynaptic signaling might not only help explain SD but also neuroprotection and migraine, two phenomena increasingly recognized as being related to SD.
Hearing Loss Raises Excitability in the Auditory Cortex
Authors: Kotak Vibhakar C. , Fujisawa Sho , Lee Fanyee Anja , Karthikeyan Omkar , Aoki Chiye , Sanes Dan H.
Published: April 2005

Developmental hearing impairments compromise sound discrimination, speech acquisition, and cognitive function; however, the adjustments of functional properties in the primary auditory cortex (A1) remain unknown. We induced sensorineural hearing loss (SNHL) in developing gerbils and then reared the animals for several days. The intrinsic membrane and synaptic properties of layer 2/3 pyramidal neurons were subsequently examined in a thalamocortical brain slice preparation with whole-cell recordings and electron microscopic immunocytochemistry. SNHL neurons displayed a depolarized resting membrane potential, an increased input resistance, and a higher incidence of sustained firing. They also exhibited significantly larger thalamocortically and intracortically evoked excitatory synaptic responses, including a greater susceptibility to the NMDA receptor antagonist AP-5 and the NR2B subunit antagonist ifenprodil. This correlated with an increase in NR2B labeling of asymmetric synapses, as visualized ultrastructurally. Furthermore, decreased frequency and increased amplitude of miniature EPSCs (mEPSCs) in SNHL neurons suggest that a decline in presynaptic release properties is compensated by an increased excitatory response. To verify that the increased thalamocortical excitation was elicited by putative monosynaptic connections, minimum amplitude ventral medial geniculate nucleus-evoked EPSCs were recorded. These minimum-evoked responses were of larger amplitude, and the NMDAergic currents were also larger and longer in SNHL neurons. These findings were supported by significantly longer AP-5-sensitive durations and larger amplitudes of mEPSCs. Last, the amplitudes of intracortically evoked monosynaptic and polysynaptic GABAergic inhibitory synaptic responses were significantly smaller in SNHL neurons. These alterations in cellular properties after deafness reflect an attempt by A1 to sustain an operative level of cortical excitability that may involve homeostatic mechanisms.
A Strict Correlation between Dendritic and Somatic Plateau Depolarizations in the Rat Prefrontal Cortex Pyramidal Neurons
Authors: Milojkovic Bogdan A. , Radojicic Mihailo S. , Antic Srdjan D.
Published: April 2005

One of the fundamental problems in neurobiology is to understand the cellular mechanism for sustained neuronal activity (neuronal UP states). Prefrontal pyramidal neurons readily switch to a long-lasting depolarized state after suprathreshold stimulation of basal dendrites. Analysis of the dendritic input-output function revealed that basal dendrites operate in a somewhat binary regimen (DOWN or UP) in regard to the amplitude of the glutamate-evoked electrical signal. Although the amplitude of the dendritic potential quickly becomes saturated (dendritic UP state), basal dendrites preserve their ability to code additional increase in glutamatergic input. Namely, after the saturation of the plateau amplitude, an additional increase in excitatory input is interpreted as an increase in plateau duration. Experiments performed in tetrodotoxin indicate that the maintenance of a stable depolarized state does not require inhibitory inputs to “balance” the excitation. In the absence of action potential-dependent (network-driven) GABAergic transmission, pyramidal neurons respond to brief (5 ms) glutamate pulses with stable long-lasting (∼500 ms) depolarizations. Voltage-sensitive dye recordings revealed that this somatic plateau depolarization is precisely time-locked with the regenerative dendritic plateau potential. The somatic plateau rises a few milliseconds after the onset of the dendritic transient and collapses with the breakdown of the dendritic plateau depolarization. In ourin vitromodel, the stable long-lasting somatic depolarization (UP state like) is a direct consequence of the local processing of a strong excitatory glutamatergic input arriving on the basal dendrite. The slow component of the somatic depolarization accurately mirrors the glutamate-evoked dendritic plateau potential (dendritic UP state).
On the existence of Levi Foliations
Authors: OSTWALD RENATA N.
Published: April 2005

Let L   be a real 3 dimensional analytic variety. For each regular point p  L there exists a unique complex line l p on the space tangent to L at p. When the field of complex line p  l p is completely integrable, we say that L is Levi variety. More generally; let L  M be a real subvariety in an holomorphic complex variety M. If there exists a real 2 dimensional integrable distribution on L which is invariant by the holomorphic structure J induced by M, we say that L is a Levi variety. We shall prove: Theorem. Let  be a Levi foliation and let  be the induced holomorphic foliation. Then,  admits a Liouvillian first integral. In other words, if  is a 3 dimensional analytic foliation such that the induced complex distribution defines an holomorphic foliation ; that is, if  is a Levi foliation; then  admits a Liouvillian first integral--a function which can be constructed by the composition of rational functions, exponentiation, integration, and algebraic functions (Singer 1992). For example, if f is an holomorphic function and if theta is real a 1-form on ; then the pull-back of theta by f defines a Levi foliation  : f*theta = 0 which is tangent to the holomorphic foliation  : df = 0. This problem was proposed by D. Cerveau in a meeting (see Fernandez 1997).
Computer simulations for biological aging and sexual reproduction
Authors: STAUFFER DIETRICH , OLIVEIRA PAULO M.C. DE , OLIVEIRA SUZANA MOSS DE , PENNA THADEU J.P. , MARTINS JORGE S. SÁ
Published: April 2005

The sexual version of the Penna model of biological aging, simulated since 1996, is compared here with alternative forms of reproduction as well as with models not involving aging. In particular we want to check how sexual forms of life could have evolved and won over earlier asexual forms hundreds of million years ago. This computer model is based on the mutation-accumulation theory of aging, using bits-strings to represent the genome. Its population dynamics is studied by Monte Carlo methods.