bluuebunny/crossref_metadata_2025 huggingface dataset:
Self-Assembly of Amphoteric Azopyridine Carboxylic Acids II: Aspect Ratio Control of Anisotropic Self-Assembled Fibers By Tuning the π–π Stacking Interaction
Authors: Aoki Ken’ichi , Nakagawa Masaru , Seki Takahiro , Ichimura Kunihiro
Published: November 2002

Two ways to control the macroscopic morphology of fibrous organizates of amphoteric azopyridine carboxylic acids by tuning the strength of π–π stacking among the component molecules are presented. The self-organization of the azopyridine carboxylic acids (1–5) from aqueous solutions is governed not only by carboxyl/pyridyl hydrogen bondings, but also by dipole–dipole and π–π stacking interactions. The level of the latter could be tuned by the substituent structure at the phenyl ring. As a result, whereas leaflet crystals were formed from non-substituted derivative 1, 3 with a propyl substituent gave fibrous assemblages, and needle-like assemblages were obtained from 2, 4, and 5 with methyl, s-butyl, and ethoxy substituents, respectively. The propyl-substitution is likely to enhance an anisotropic growth rate of the intermolecular hydrogen bonds due to efficient suppression of π–π stacking among aromatic cores, leading to the appearance of microfibers with the highest aspect ratio. The second way to control the organization morphology is based on “supramolecular copolymerization”, which is attained by mixing 1 and 3 to modulate the strength of the π–π stacking. The aspect ratio of fibrous materials was significantly influenced by the mixing ratio.
Effect of Anionic 4.5-Generation Polyamidoamine Dendrimer on the Formation of Calcium Carbonate Polymorphs
Authors: Naka Kensuke , Kobayashi Akihiro , Chujo Yoshiki
Published: November 2002

The precipitation of CaCO3 in the absence or the presence of the G4.5 PAMAM dendrimer was carried out by a “carbonate diffusion method”. Formation of crystalline CaCO3 at different feed ratios of the G4.5 dendrimer to calcium ions was studied with the concentration of calcium ions kept at 0.1 M. Although calcite was predominantly formed at the concentration of the G4.5 PAMAM dendrimer corresponding to 2.65 mM of –COONa, the crystal phase of the obtained CaCO3 at the higher concentration of the G4.5 PAMAM dendrimer at 5.3 mM consisted entirely of vaterite. As the concentration of –COONa increased from 5.3 to 10.6 mM, the particle sizes of the spherical vaterites were reduced from 8.7 ± 1.0 to 5.2 ± 3.0 μm determined by SEM observation. The crystal phase of the obtained CaCO3 in the absence of any additives was a mixture of calcite and vaterite. Although vaterite was predominantly formed by the G4.5 dendrimer, relatively high amounts of calcite were observed in the case of the G3.5 and G1.5 dendrimers. These results suggest that the G4.5 dendrimer more effectively induces vaterite formation compared with the earlier generation of the dendrimers.
Interactions between Spinacia oleracea and Bradysia impatiens: A role for phytoecdysteroids
Authors: Schmelz Eric A. , Grebenok Robert J. , Ohnmeiss Thomas E. , Bowers William S.
Published: November 2002

Plant produced insect molting hormones, termed phytoecdysteroids (PEs), are thought to function as plant defenses against insects by acting as either feeding deterrents or through developmental disruption. In spinach (Spinacia oleracea), 20‐hydroxyecdysone (20E) concentrations in the roots rapidly increase following root damage, root herbivory, or methyl jasmonate (MJ) applications. In this inducible system, we investigated the plant defense hypothesis by examining interactions of roots, 20E concentrations, and larvae of the dark‐winged fungus gnat (Bradysia impatiens). Root herbivory by B. impatiens larvae resulted in a 4.0‐ to 6.6‐fold increase in root 20E concentrations. In paired‐choice tests, increases in dietary 20E stimulated B. impatiens feeding deterrency. B. impatiens larvae preferred control diets, low in 20E, to those constructed from induced roots and those amended with 20E (25 to 50 μg/g wet mass). When confined to 20E‐treated diets, concentrations as low as 5 μg/g (wet mass) resulted in significantly reduced B. impatiens survivorship compared to controls. The induction of root 20E levels with MJ resulted in a 2.1‐fold increase in 20E levels and a 50% reduction in B. impatiens larval establishment. In a paired‐choice arena, untreated control roots were damaged significantly more by B. impatiens larvae than MJ‐induced roots that contained 3‐fold greater 20E levels. Based on dietary preference tests, the 20E concentrations present in the MJ‐induced roots (28 μg/g wet mass) were sufficient to explain this reduction in herbivory. Interactions between spinach roots and B. impatiens larvae demonstrate that PEs can act as inducible defenses and provide protection against insect herbivory. Arch. Insect Biochem. Physiol. 51:204–221, 2002. Published 2002 Wiley‐Liss, Inc.
Induced responses in clover to an herbaceous mite
Authors: Ridsdill‐Smith James , Ghisalberti Emilio , Jiang Yong
Published: November 2002

Halotydeus destructor feeding on subterranean clover cotyledons can cause severe damage. The mites live on the soil surface and move up onto plants to feed. Foraging behaviour consists of palpating, probing, and feeding with frequent transitions between them. Sustained feeding is made up of a series of short (1–2 min) feeds separated by periods of palpating. The mites tend to feed in aggregations, and are attracted to cotyledons damaged by other mites feeding or by mechanical damage. Mites can distinguish between resistant and susceptible cotyledons within 30 min and resistance is antixenotic due to deterrence. Study of the mechanisms shows this to be induced plant resistance. Several green leaf volatiles are involved in the plant/mite interaction. After feeding commences, 2‐E‐hexenal is released that at low concentrations is attractive to mites, perhaps causing the feeding aggregations. The wound‐induced C8 compound, 1‐octen‐3‐one, plays a significant role in the deterrence of cotyledons of resistant subterranean clover varieties to H. destructor. Damaged cotyledons of resistant varieties produce more 1‐octen‐3‐one that those of susceptible varieties. Screening for resistance has identified varieties from Italy showing resistance. H. destructor does not occur in Europe. Production of damage‐induced volatiles by the resistant plants may have resulted from invasion by herbivores or pathogens, but not from coevolution with these mites. The responses of H. destructor are probably an adaptation to these general plant defensive compounds. Arch. Insect Biochem. Physiol. 51:170–181, 2002. © 2002 Wiley‐Liss, Inc.
Gene expression profiling of Arabidopsis thaliana in compatible plant‐aphid interactions
Authors: Moran Patrick J. , Cheng Youfa , Cassell Jeffery L. , Thompson Gary A.
Published: November 2002

Phloem feeding involves unique biological interactions between the herbivore and its host plant. The economic importance of aphids, whiteflies, and other phloem‐feeding insects as pests has prompted research to isolate sources of resistance to piercing‐sucking insects in crops. However, little information exists about the molecular nature of plant sensitivity to phloem feeding. Recent discoveries involving elicitation by plant pathogens and chewing insects and limited studies on phloem feeders suggest that aphids are capable of inducing responses in plants broadly similar to those associated with pathogen infection and wounding. Our past work showed that compatible aphid feeding on leaves of Arabidopsis thaliana induces localized changes in levels of transcripts of genes that are also associated with infection, mechanical damage, chewing herbivory, or resource allocation shifts. We used microarray and macroarray gene expression analyses of infested plants to better define the response profile of A. thaliana to M. persicae feeding. The results suggest that genes involved in oxidative stress, calcium‐dependent signaling, pathogenesis‐related responses, and signaling are key components of this profile in plants infested for 72 or 96 h. The use of plant resistance to aphids in crops will benefit from a better understanding of induced responses. The establishment of links between insect elicitation, plant signaling associated with phloem feeding, and proximal resistance mechanisms is critical to further research progress in this area. Arch. Insect Biochem. Physiol. 51:182–203, 2002. Published 2002 Wiley‐Liss, Inc.
Potential for the use of elicitors of plant resistance in arthropod management programs
Authors: Stout Michael J. , Zehnder Geoffrey W. , Baur Matthew E.
Published: November 2002

Plants protect themselves from arthropod herbivores both directly, by expressing biochemical and morphological traits that interfere with herbivore development or behavior, and indirectly, by facilitating the action of natural enemies of herbivores. These direct and indirect resistance mechanisms are not always expressed at maximal levels by plants, but rather can be induced to higher levels by a variety of stimuli, most notably prior herbivory. The recent discovery of chemical elicitors of induced responses has led to interest in manipulating the inducible responses of plants for crop protection. Applications of elicitors of induced responses made at appropriate times during the growing season of a crop have the potential of activating both direct and indirect mechanisms of plant resistance and thereby simultaneously augmenting host‐plant resistance and biological control. This strategy may serve as an important component of a multifaceted, ecologically‐based pest management program and is unlikely to precipitate the rapid evolution of countermeasures by target pests. However, this strategy will not be appropriate in all crops or against all arthropod pests. The conditions under which the use of an elicitor is likely to be successful are discussed, and examples of the successful use of elicitors are reviewed. Arch. Insect Biochem. Physiol. 51:222–235, 2002. © 2002 Wiley‐Liss, Inc.
What is in a family? Adolescent perceptions
Authors: Anyan Stacey E. , Pryor Jan
Published: November 2002

The ways in which adolescents conceptualise families is not well understood. In this study perceptions of families by 232 adolescents were examined using vignettes describing groupings of people (e.g. married couple with children, two women and a child). Eighty per cent or more endorsed married and cohabiting families, lone‐parent households, and extended family members as families. Few differences were found according to their own family structure. Asian (Chinese) adolescents were less likely overall to endorse groupings as families. Love and affection were given as primary criteria for being a family. Overall, young people endorsed a diversity of family forms. Copyright © 2002 John Wiley & Sons, Ltd.
Language, discourse and empowerment: changing approaches to children and young people who have sexually abused others
Authors: Myers Steve
Published: November 2002

The sexual abuse of children by other children and young people has gained an increasing profile during the previous decade. It has been increasingly recognised that there has been a significant change in the way that this issue has been responded to, both in philosophy and practice, as research has developed and also as the value base of initial constructions of this behaviour has been questioned. This article describes the development of a project to work with children and young people who have sexually abused from its inception in 1995 to the present, outlining the original assumptions and working practices and the reasoning behind changes. The growth of the project illustrates the changing nature of constructions of this behaviour, along with the introduction of new theoretical approaches to respond to this change. In particular, the changes can be seen to reflect a move away from a ‘modernist’ position and this is discussed. Copyright © 2002 John Wiley & Sons, Ltd.
The sexual abuse of children by strangers: its extent, nature and victims' characteristics
Authors: Gallagher Bernard , Bradford Michael , Pease Ken
Published: November 2002

This paper reports a school‐based questionnaire survey conducted among 2420 children aged nine to 16 years. It examines the extent of stranger abuse, its nature and the characteristics of victims. The research contains complex messages in terms of the ‘seriousness’ of stranger abuse and identifies a number of challenges to understanding this phenomenon. It highlights the need for much more sophistication in debates over, and policy and practice responses to, stranger abuse. Copyright © 2002 John Wiley & Sons, Ltd.
Elimination of the effect of an ambient reflection in the measurement of S parameter between two log‐periodic dipole array antennas
Authors: Fujii Katsumi , Ye Nan , Iwasaki Takashi
Published: November 2002

The transmission S parameter S21 of transmitting and receiving antennas can be used for site evaluation different from the normalized site attenuation. For instance, the effect of reflection from ambient objects can be removed by the Fourier transform and time domain gating process so that the transmission S parameter without ambient influence can be predicted. In this paper, a log‐periodic dipole antenna is used as a transmission and reception antenna that is a type of broadband antenna. It is shown for this antenna that the time domain gating becomes possible and the effect of reflection can be removed if the complex antenna factor indicating the antenna characteristic is taken into account. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 86(3): 35–43, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.10042
On carrier pulse transmission systems with the modified cosine roll‐off characteristics
Authors: Ishida Noriaki
Published: November 2002

In this paper, we verify the implementation of the Modified Cosine Roll‐off (MCR) spectrum for carrier pulse transmission systems that use the newly proposed MCR spectrum, and present various calculations. Specifically, we discuss the relationship between the filter placement and the interchannel interference, the relationship between the number of stages and the bandwidth of the receive filter that produces a zero crossing at the adjacent time slot, and the interchannel interference of channels having different speeds. The result shows that the MCR spectrum has the same degree of intersymbol interference as the cosine roll‐off spectrum and can decrease the channel spacing for cellular phones. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 86(3): 17–25, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.10047
Subband signal processing adaptive array with a data transmission scheme inserting a cyclic prefix
Authors: Karasawa Yoshio , Shinozawa Masahiro
Published: November 2002

The advantages of subband signal processing adaptive array (SBAA) are the ability to perform parallel signal processing in each subband division and the substantial reduction in the total computational load. However, the price is not preventing a drop in performance, for example, the incorporation of delayed waves, and a countermeasure must be found. Therefore, in this paper, we propose introducing a scheme that inserts a guard interval (cyclic prefix), which is commonly adopted in Orthogonal Frequency Division Multiplexing (OFDM), into ordinary data transmission, and extracts the best possible performance of SBAA. We also evaluate the performance by a computer simulation. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 86(3): 1–8, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.10055
Performance of adaptive array antenna at PHS base station
Authors: Yoshinaga Hisashi , Taromaru Makoto , Akaiwa Yoshihiko
Published: November 2002

Assuming the PHS channel, the transmission characteristics of a system in which adaptive arrays are installed only at the base stations are studied. In order to handle co‐channel interference and fading at the same time, the effect of the adaptive array is studied when the antenna element spacing is increased. A computer simulation shows that the bit error rate is improved because a sufficient space diversity effect is obtained and the interference suppression characteristics are not degraded. Improvement of the characteristics is achieved when the weights determined in the uplink are used in the downlink. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 86(3): 92–101, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.1158
Social identity, relative group status and intergroup attitudes: when favourable outcomes change intergroup relations…for the worse
Authors: Guimond Serge , Dif Stéphane , Aupy Annabelle
Published: November 2002

This study examines in a natural setting (N = 253) the effects of favourable outcomes at the individual and group levels on the relations between members of high (nondisabled) and low (disabled) status groups. Consistent with past research, the results show that, overall, high‐status group members are more likely than low‐status group members to display ingroup bias. Furthermore, as hypothesized on the basis of the role of relative gratification in intergroup relations, a favourable group outcome led high‐status group members to derogate the low‐status outgroup. On the other hand, as predicted from the assumption that outgroup favouritism reflects a strategy of individual mobility, a favourable individual outcome led low‐status group members to display an evaluative bias in favour of, and to identify with, the high‐status outgroup. The implications of these findings for the explanation of outgroup favouritism and outgroup derogation are discussed. Copyright © 2002 John Wiley & Sons, Ltd.
Sources of distinctiveness: position, difference and separateness in the identities of Anglican parish priests
Authors: Vignoles Vivian L. , Chryssochoou Xenia , Breakwell Glynis M.
Published: November 2002

We investigated the implications of three sources of distinctiveness—position, difference and separateness—for identity and subjective well‐being in a survey of 149 Anglican parish priests. Distinctiveness was examined within parish and clergy comparative contexts. Each source contributed substantially and uniquely to ratings of the distinctiveness associated with identity elements in each context. Parish‐context position was emphasised within identity and was positive for affect, while parish‐context separateness was negative for affect. Distinctiveness in the clergy context was not emphasised within identity and was unrelated to affect. This shows that distinctiveness is not a unitary construct: extending existing theories (Breakwell, 1993; Brewer, 1991; Triandis, 1995), we argue that different forms of distinctiveness will have different implications for identity and well‐being according to culture and context. Copyright © 2002 John Wiley & Sons, Ltd.
Ethnic minority identity and group context: self‐descriptions, acculturation attitudes and group evaluations in an intra‐ and intergroup situation
Authors: Verkuyten Maykel , de Wolf Angela
Published: November 2002

In an experimental questionnaire study among Chinese participants living in the Netherlands, it was found that self‐descriptions, acculturation attitudes and ingroup evaluation were affected by the comparative group context. Following self‐categorization theory, different predictions were tested and supported. Self‐ratings on trait adjectives systematically differed between an intragroup (Chinese) and an intergroup (Chinese versus Dutch) context. Furthermore, ethnic self‐categorization turned out to be related to self‐descriptions in the intragroup context, whereas ethnic self‐esteem showed an effect on self‐descriptions in the intergroup context. Acculturation attitudes and ingroup favouritism were also affected by the comparative context. In the intergroup context, participants were more strongly in favour of heritage culture maintenance and reported higher ingroup favouritism than in the intragroup context. It is concluded that studies on ethnic minorities should consider the important and often neglected intragroup processes and comparisons in addition to the familiar minority–majority group comparisons. Copyright © 2002 John Wiley & Sons, Ltd.
Spill‐over effects of intermittent costs for defection in social dilemmas
Authors: Eek Daniel , Loukopoulos Peter , Fujii Satoshi , Gärling Tommy
Published: November 2002

This research investigates the role of intermittent monetary costs in restraining individuals from defection in social dilemmas. In Experiment 1, 104 car owners made fictitious choices between a slow and a fast travel mode in the context of a continuous social dilemma. There were four different conditions of monetary costs for choosing the fast mode (defection): no cost, low cost, high cost to self, or high cost to others. Participants defected most when there was no cost and least when they themselves were charged a high cost. A spill‐over effect was obtained such that when others were charged a high cost to defect, defection rates were lower than under no cost. Experiment 2 used 36 undergraduates as participants in an iterated decision task with real groups. The results replicated the major results of Experiment 1. Furthermore, whereas prosocials were strongly affected by intermittent costs for defection (i.e. showed large spill‐over effects), proselfs seemed to be unaffected. Possible explanations of this interaction effect between social value orientation and intermittent punishment for defection are provided. Copyright © 2002 John Wiley & Sons, Ltd.
Sex differences in the jealousy‐evoking effect of rival characteristics
Authors: Dijkstra Pieternel , Buunk Bram P.
Published: November 2002

Four studies examined sex differences in the jealousy‐evoking nature of rival characteristics. Study 1, among 130 undergraduates, made an inventory of all relevant rival characteristics that were spontaneously mentioned when asked about a rival to whom one's partner might feel attracted. On the basis of these findings, in Study 2, among 240 undergraduates, a questionnaire was constructed, containing 56 rival characteristics. A factor analysis distinguished five dimensions of rival characteristics, i.e. Social Dominance, Physical Attractiveness, Seductive Behaviors, Physical Dominance, and Social Status. In line with the predictions, men reported more jealousy when a rival was high in Social Dominance, Physical Dominance, and Social Status, whereas women reported more jealousy when a rival was high in Physical Attractiveness. Study 3 largely replicated these findings in a community sample of 144 heterosexuals. Study 4 showed that gay men (n = 80) reported more jealousy than lesbian women (n = 73) when the rival was high in Physical Dominance, and more jealousy than heterosexual men when the rival was high in Social Dominance. Lesbian women reported more jealousy than heterosexual women when the rival was high in Physical Attractiveness. In Studies 2–4, favorable rival characteristics evoked more jealousy among those high in Social Comparison Orientation, particularly among women. Copyright © 2002 John Wiley & Sons, Ltd.
The bystander effect and social control behavior: the effect of the presence of others on people's reactions to norm violations
Authors: Chekroun Peggy , Brauer Markus
Published: November 2002

Observers of deviant social behavior sometimes communicate disapproval directly or indirectly to the perpetrator of a deviant act. This reaction has been termed ‘social control’. Three field studies were conducted to explore the influence of the number of bystander‐observers on the likelihood of social control. We predicted that the presence of others would inhibit people's tendency to communicate their disapproval to the deviant but only if personal implication was low. In the first study, we measured participants' perceptions of two fictive situations, one in which a deviant draws graffiti in an elevator of a shopping center and one in which a deviant litters in a small neighborhood park by throwing a plastic bottle in the bushes. As expected, participants considered both behaviors to be equally counternormative but felt personally more implicated by the littering behavior in the park. In Studies 2 and 3, the two situations were enacted with confederates of the experimenter. Naïve bystanders served as participants, and social control was the primary dependent variable. Consistent with our hypothesis, we found evidence for a bystander effect in the low personal implication situation (‘graffiti in the elevator’) but not in the high personal implication situation (‘littering in park’). These results make clear that perceived personal implication moderates the extent to which people are inhibited by the presence of others when they decide whether they should exert social control or not. Copyright © 2002 John Wiley & Sons, Ltd.
On the nature of attitude–behavior relations: the strong guide, the weak follow
Authors: Holland Rob W. , Verplanken Bas , Van Knippenberg Ad
Published: November 2002

This study investigated the role of attitude strength as a moderator variable with regard to the direction of the relation between attitudes and behavior. The hypothesis was tested that strong attitudes guide behavior, whereas weak attitudes follow behavior in accordance with self‐perception principles. The study (N = 106) consisted of two sessions. In session 1, attitudes and attitude strength (certainty, importance, centrality) towards Greenpeace were measured. One week later, participants returned to the laboratory (session 2) and were given the opportunity to donate money to Greenpeace. After the participants' decision to donate money or not, attitudes towards Greenpeace were measured again. The results were consistent with the predictions. First, strong attitudes were more predictive of donation behavior than weak attitudes. Moreover, session 2 attitudes of weak attitude participants were influenced by their donation behavior, whereas no such effect was found among strong attitude participants. Finally, strong attitudes were also found to be more stable over time than weak attitudes. The results provide a complete overview of the moderating role of attitude strength with regard to the bi‐directional attitude‐behavior relationship. Results are discussed in the light of attitude retrieval versus attitude‐construction processes. Copyright © 2002 John Wiley & Sons, Ltd.
Univariate and multivariate family‐based association analysis of the IL‐13 ARG130GLN polymorphism in the Childhood Asthma Management program
Authors: DeMeo D.L. , Lange c. , Silverman E.K. , Senter J.M. , Drazen J.M. , Barth M.J. , Laird N. , Weiss S.T.
Published: November 2002

Interleukin 13 (IL‐13) has been demonstrated to have a crucial role in animal models of allergy and asthma. In human case‐control genetic‐association studies, the Arg130Gln polymorphism has been associated with elevated total serum IgE and an asthma diagnosis in atopic and nonatopic individuals (Graves et al. [2000] J. Allergy Clin. Immunol. 105:506–513; Heinzmann et al. [2000] Hum. Mol. Genet. 9:549–559). To apply family‐based association methods, we obtained DNA samples from 685 asthmatic children from 640 sibships and their parents in the Childhood Asthma Management Program (CAMP). Six hundred and sixty‐six asthmatic children had complete phenotypic information and were used for this analysis. We performed quantitative association analysis using the transmission disequilibrium test (TDT) on 22 individual phenotypes and 5 grouped phenotypes relating to allergy, airway responsiveness, pulmonary function, bronchodilator responsiveness, and asthma severity, using genotypes at the Arg130Gln polymorphism of the IL‐13 gene. A positive association was obtained between Arg130Gln and a grouped phenotype of allergy (consisting of the individual phenotypes of eosinophils, IgE, and positive skin tests), using FBAT‐GEE, a multivariate extension of the family‐based association test (Lange et al. [2002] Biostatistics 1:1–15). The three phenotypes were then evaluated individually and revealed a significant association between total eosinophil count and the Arg130Gln locus; there was a trend for association between total IgE and the Arg130Gln polymorphism. The Arg130Gln polymorphism is associated with an elevated eosinophil count as well as with a grouped allergy phenotype, in children with mild to moderate asthma. No evidence for association was found between Arg130Gln and airway responsiveness, asthma diagnosis, or asthma severity. Genet. Epidemiol. 23:335–348, 2002. © 2002 Wiley‐Liss, Inc.
Preferential transmission of type 1 diabetes from parents to offspring: fact or artifact?
Authors: Guo Sun‐Wei , Tuomilehto Jaakko
Published: November 2002

It has been widely reported that men with type 1 diabetes (T1D) tend to be more likely to transmit the disease to their offspring than their female counterparts in Caucasoid populations. Several theories to explain this preferential transmission have been proposed, but so far none of them has been unequivocally proven. Whatever the mechanism, confirmation or refutation of this observation is nonetheless important and practical to the design of future genetic studies of T1D. We carried out some statistical modeling of the preferential transmission. The well‐established fact that males have higher a prevalence of T1D than females, an apparent sex difference in fecundity, and a possible misclassification of gestational diabetes mellitus (GDM) as T1D in women have been considered. We demonstrated, first, that the ascertainment of study families through the affected offspring with T1D would generate a higher proportion of fathers than mothers having T1D, even though there was no preferential transmission at all. This can be explained by the male preponderance in T1D prevalence as compared with females, coupled with a greater likelihood of being selected and/or recruited for study in families with T1D fathers due to the fecundity difference. Second, when the study population is ascertained through affected parents, misclassification of mothers with GDM as T1D, and the existence of male/female difference in fecundity in conjunction with a birth order effect, can contribute to the observed preferential transmission, even though there was none. In light of the plausibility of assumptions employed in the analysis and, in particular, an apparent failure to critically examine the effects of these causes of bias in earlier studies, it is perhaps prudent to say that the jury for the existence of preferential transmission in T1D is still out. Genet. Epidemiol. 23:323–334, 2002. © 2002 Wiley‐Liss, Inc.
Relative efficiency of ambiguous vs. directly measured haplotype frequencies
Authors: Schaid Daniel J.
Published: November 2002

Haplotypes are useful for both fine‐mapping of susceptibility loci and evaluation of sequence variation at multiple sites along a chromosome. However, they are difficult to directly measure over long stretches of DNA in diploid organisms. Consequently, multiple genetic markers are typically measured, without linkage phase information, giving rise to a subject's diplotype. From diplotype data, haplotypes are often inferred by pedigree information, or treated as partially missing data when haplotype frequencies are estimated among unrelated subjects. This latter ambiguity can increase the variance of the estimated haplotype frequencies. Douglas et al. ([2001] Nat. Genet. 28:361–364) recently quantified the relative efficiency of estimating haplotype frequencies from the diplotypes of unrelated subjects, relative to directly measured haplotypes via somatic cell hybrids (conversion technology), and demonstrated that unknown linkage phase can lead to a large loss of efficiency. However, their results were based on linkage equilibrium among marker loci, which may not be realistic for closely linked markers. We extend their relative efficiency calculations by several aspects: 1) allowance for linkage disequilbrium (LD) among marker loci; 2) evaluation of different patterns of LD; and 3) evaluation of nuclear families with and without parents. We show that although the loss in efficiency of haplotype frequencies among unrelated subjects decreases as LD increases to its maximum value, the general conclusions of Douglas et al. ([2001] Nat. Genet. 28:361–364) hold true for a variety of LD patterns and magnitudes. However, our results also demonstrate that trios of parents+one child are highly efficient for haplotype frequency estimation, that additional children offer little information, and that siblings without parents can be grossly inefficient. Genet. Epidemiol. 23:426–443, 2002. © 2002 Wiley‐Liss, Inc.
Segregation analysis of 389 Icelandic pedigrees with Breast and prostate cancer
Authors: Baffoe‐Bonnie Agnes B. , Kiemeney Lambertus A.L.M. , Beaty Terri H. , Bailey‐Wilson Joan E. , Schnell Audrey H. , Sigvaldason Helgi , Ólafsdóttir Guriur , Tryggvadóttir Laufey , Tulinius Hrafn
Published: November 2002

Breast cancer and prostate cancer are the most commonly occurring cancers in females and males, respectively. The objective of this project was to test the hypothesis that breast cancer in females and prostate cancer in males represent homologous cancers that may be controlled by one or more common unidentified genes that may explain some of the observed familial aggregation. We modeled the transmission of a breast‐prostate cancer phenotype in 389 pedigrees ascertained through a breast cancer proband drawn from the Icelandic Cancer Registry. Assuming that age at diagnosis of this combined phenotype followed a logistic distribution, segregation analyses were performed to evaluate residual parental effects, a sibship covariate, and a dichotomous cohort effect. The most parsimonious model was a Mendelian codominant model, which could partly explain the familial aggregation of both cancers. Inheritance of a putative high‐risk allele (A) predicted gender‐specific mean ages of onset for females as 53.8 years, 59.7 years, and 65.6 years for the putative AA, AB, and BB genotypes, respectively. Similarly, the predicted means were 73.7 years, 75.6 years, and 78.3 years, respectively, among males. Under this codominant model, the lifetime risk of a woman being affected was 19% by age 80 years. This implies that when prostate cancer among male relatives of breast cancer probands (unselected for family history or early‐onset disease) is considered a pleiotrophic effect of the same gene that increases the risk for breast cancer, women are predicted to have a less than 1 in 5 risk of developing breast cancer when they carry the putative high‐risk allele. However, this is a higher risk than in the general Icelandic population. Our results suggest that BRCA2 mutations alone are inadequate to explain all of the excess clustering of prostate cancer cases in families of breast cancer probands, and that additional genes conferring excess risk to both breast and prostate cancer may exist in this population. Genet. Epidemiol. 23:349–363, 2002. © 2002 Wiley‐Liss, Inc.
Evidence that BCL3 plays a role in the etiology of nonsyndromic oral clefts in Brazilian families
Authors: Gaspar D.A. , Matioli S.R. , Pavanello R.C. , Araújo B.C. , André M. , Steman S. , Otto P.A. , Passos‐Bueno M.R.
Published: November 2002

The BCL3 gene has been considered a susceptibility locus for nonsyndromic cleft lip with or without cleft palate (NSCL/P), based on association and linkage studies in some populations. We evaluated an intragenic marker at the BCL3 gene and the microsatellite D19S178 (1.1 cM distant from the BCL3 gene) among 98 infants born with NSCL/P and their parents, using the transmission disequilibrium test (TDT) and a method for haplotype analysis. Our analysis, based on BCL3 alleles, revealed the existence of a marginal association of allele 135pb of the BCL3 gene with NSCL/P (χ2=3.60; P=0.058; 1 df), with a major effect in female (χ2=5.77; P=0.016; 1 df) and in familial cases (χ2=3.79; P=0.051; 1 df). However, the haplotype analysis detected no significant segregation distortion, even if the alleles of the D19S178 were grouped into two classes. These findings support previous findings that BCL3 plays a role in the etiology of NSCL/P as an allele of low penetrance or as a modifier locus. We hypothesize that there might be more than one mutation in this gene associated with NSCL/P, or alternatively, that more than one mutation has arisen associated with the 135‐bp allele. Genet. Epidemiol. 23:364–374, 2002 © 2002 Wiley‐Liss, Inc.
Impact of parental relationships in maximum lod score affected sib‐pair method
Authors: Leutenegger Anne‐Louise , Génin Emmanuelle , Thompson Elizabeth A. , Clerget‐Darpoux Françoise
Published: November 2002

Many studies are done in small isolated populations and populations where marriages between relatives are encouraged. In this paper, we point out some problems with applying the maximum lod score (MLS) method (Risch, [1990] Am. J. Hum. Genet. 46:242–253) in these populations where relationships exist between the two parents of the affected sib‐pairs. Characterizing the parental relationships by the kinship coefficient between the parents (f), the maternal inbreeding coefficient (αm, and the paternal inbreeding coefficient (αp), we explored the relationship between the identity by descent (IBD) vector expected under the null hypothesis of no linkage and these quantities. We find that the expected IBD vector is no longer (0.25, 0.5, 0.25) when f, αm, and αp differ from zero. In addition, the expected IBD vector does not always follow the triangle constraints recommended by Holmans ([1993] Am. J. Hum. Genet. 52:362–374). So the classically used MLS statistic needs to be adapted to the presence of parental relationships. We modified the software GENEHUNTER (Kruglyak et al. [1996] Am. J. Hum. Genet. 58: 1347–1363) to do so. Indeed, the current version of the software does not compute the likelihood properly under the null hypothesis. We studied the adapted statistic by simulating data on three different family structures: (1) parents are double first cousins (f=0.125, αm=αp=0), (2) each parent is the offspring of first cousins (f=0, αm=αp=0.0625), and (3) parents are related as in the pedigree from Goddard et al. ([1996] Am. J. Hum. Genet. 58:1286–1302) (f=0.109, αm=αp=0.0625). The appropriate threshold needs to be derived for each case in order to get the correct type I error. And using the classical statistic in the presence of both parental kinship and parental inbreeding almost always leads to false conclusions. Genet. Epidemol. 23:413–425, 2002. © 2002 Wiley‐Liss, Inc.
Dietary folate and colorectal cancer
Authors: La Vecchia Carlo , Negri Eva , Pelucchi Claudio , Franceschi Silvia
Published: November 2002

Folate may be inversely related to colorectal cancer risk, possibly in combination with low methionine and high alcohol consumption. We considered, therefore, the relation between folate and colorectal cancer in a multicentric case‐control study of 1,953 cases and 4,154 controls from Italy, i.e., a population with frequent regular alcohol drinking. In the overall data set, the odds ratio (OR) was 0.72 for the highest quintile of folate, and the continuous OR per 100 μg was 0.86. The inverse relation was similar in men and women and somewhat stronger for the rectum (OR = 0.59 for the highest quintile) compared to the colon (OR = 0.81). It was also somewhat stronger in the highest tertile of alcohol drinking (OR = 0.65), though trends were not heterogeneous across strata of alcohol, whereas no appreciable difference was observed across strata of methionine intake. Compared to subjects reporting low alcohol, high methionine and high folate intake, the OR was 1.83 for those reporting high alcohol, low methionine and low folate intake. The present findings support a favorable role of folate in colorectal carcinogenesis. © 2002 Wiley‐Liss, Inc.
Interference with TGF‐β1 and ‐β3 in tumor stroma lowers tumor interstitial fluid pressure independently of growth in experimental carcinoma
Authors: Lammerts Ellen , Roswall Pernilla , Sundberg Christian , Gotwals Philip J. , Koteliansky Victor E. , Reed Rolf K. , Heldin Nils‐Erik , Rubin Kristofer
Published: November 2002

A high tumor interstitial fluid pressure (TIFP) is a pathologic characteristic distinguishing the stroma of carcinomas from normal interstitial loose connective tissues. The role of TGF‐β1 and ‐β3 in generating a high TIFP was investigated in xenografted experimental anaplastic thyroid carcinoma (ATC) derived from the human ATC cell line KAT‐4. A single intravenous injection of a soluble recombinant TGF‐β receptor type II‐murine Fc:IgG2A chimeric protein that specifically inhibits TGF‐β1 and ‐β3, significantly lowered TIFP in a time and concentration dependent manner but did not change total tissue water content in the tumors. Tumor growth rate was higher in tumors treated with the TGF‐β1 and ‐β3 inhibitor compared to control tumors during the first 10 days after administration of the inhibitor. The apoptotic index of carcinoma cells, and expression of the cell cycle inhibitor p27Kip1, were, however, increased in TGF‐β1 and ‐β3 inhibitor‐treated tumors. Prolonged treatment periods and administration of a second dose of the inhibitor decreased tumor growth rate. The TGF‐β1 and ‐β3 inhibitor did not affect proliferation or expression of phosphorylated Smad2 protein in KAT‐4 cells cultured in vitro. Our results indicate that members of the TGF‐β family are potential targets for novel anti‐cancer treatment directed to the stroma. First by controlling TIFP and by that potentially the uptake of anticancer drugs into tumors and second by their suggested role in maintaining a supportive tumor stroma. © 2002 Wiley‐Liss, Inc.
Targeting of RGD‐modified proteins to tumor vasculature: A pharmacokinetic and cellular distribution study
Authors: Schraa Astrid J. , Kok Robbert J. , Moorlag Henk E. , Bos Erwin J. , Proost Johannes H. , Meijer Dirk K.F. , de Leij Lou F.M.H. , Molema Grietje
Published: November 2002

Angiogenesis‐associated integrin αvβ3 represents an attractive target for therapeutic intervention because it becomes highly upregulated on angiogenic endothelium and plays an important role in the survival of endothelial cells. Cyclic RGD peptides were prior shown to have a high affinity for αvβ3 and can induce apoptosis of endothelial cells. In our laboratory, monocyclic RGD peptides (cRGDfK) were chemically coupled to a protein backbone. Previous results demonstrated that the resulting RGDpep‐HuMab conjugate bound with increased avidity to αvβ3/αvβ5 on endothelial cells. In our present study, RGDpep‐HuMab was injected intravenously and intraperitoneally in B16.F10 tumor‐bearing mice to determine its pharmacokinetics and organ distribution. In the tumor, the RGDpep‐HuMab conjugate specifically localized at the endothelium as was demonstrated by immunohistochemistry. The control RADpep‐HuMab conjugate was not detected in the tumor. Besides tumor localization RGDpep‐HuMab was found in liver and spleen associated with macrophages. This uptake by macrophages is probably responsible for the more rapid clearance of RGDpep‐HuMab from the circulation than HuMab and RADpep‐HuMab. The half‐life of RGDpep‐HuMab (90 min) was still considerably longer than that of free RGD peptides (<10 min). This prolonged circulation time may be favorable for drug targeting strategies because the target cells are exposed to the conjugate for a longer time period. Taken together these results indicate that RGD‐modified proteins are suitable carriers to deliver therapeutic agents into tumor or inflammation induced angiogenic endothelial cells. © 2002 Wiley‐Liss, Inc.
Replication efficiency and sequence analysis of full‐length hepatitis B virus isolates from hepatocellular carcinoma tissues
Authors: Lin Xu , Ma Zhang‐Mei , Yao Xin , Zhang Yan‐Ping , Wen Yu‐Mei
Published: November 2002

Prolonged replication of hepatitis B virus (HBV) in liver tissues of hepatitis B patients has been considered as an important risk factor for the development of malignancy. Few studies on full‐length HBV sequencing in association with the replication efficiency of isolates from HCC tissues have been reported. To study the structural and functional genomics of HBV isolates from Chinese hepatocellular carcinoma (HCC) patients, full‐length HBV genomes were amplified from 6 HBV‐marker positive HCC tissues and used to transfect HepG2 cells. Five of 6 isolates showed high replicative efficiency. All isolates were of genotype C and “hot‐spots” mutations were detected in the B cell and T helper (Th) cell epitopes of the envelope and the core region. In addition, the X region of 2 isolates contained a stop‐codon mutation that was predicted to result in a truncated X protein. High replicative HBV immune escape mutants that persist in infected hepatocytes could be 1 of the important factors to initiate pathological processes for the development of HCC in Chinese patients. © 2002 Wiley‐Liss, Inc.
Identification of HLA‐A3‐restricted CD8+ T cell epitopes derived from mammaglobin‐A, a tumor‐associated antigen of human breast cancer
Authors: Jaramillo Andrés , Majumder Kanchana , Manna Partha P. , Fleming Timothy P. , Doherty Gerard , Dipersio John F. , Mohanakumar Thalachallour
Published: November 2002

Mammaglobin‐A is highly overexpressed in breast cancer cell lines and primary breast tumors. This pattern of expression is restricted to mammary epithelium and metastatic breast tumors. Thus, mammaglobin‐A‐specific T cell immune responses may provide an important approach for the design of breast cancer‐specific immunotherapy. The purpose of our study was to define the T cell‐mediated immune response to mammaglobin‐A. We determined that the frequency of mammaglobin‐A‐reactive CD8+ and CD4+ T cells in breast cancer patients is significantly higher than that observed in healthy female controls using limiting dilution analyses (p = 0.026 and p = 0.02, respectively). We identified 8 mammaglobin‐A‐derived 9‐mer peptides with the highest binding affinity for the HLA‐A3 molecule (Mam‐A3.1–8) using a computer‐assisted analysis of the mammaglobin‐A protein sequence. Subsequently, we determined that CD8+ T cells from breast cancer patients reacted to peptides Mam‐A3.1 (23–31, PLLENVISK), Mam‐A3.3 (2–10, KLLMVLMLA), Mam‐A3.4 (55–63, TTNAIDELK) and Mam‐A3.8 (58–66, AIDELKECF) using an IFN‐γ enzyme‐linked immunospot assay. A CD8+ T cell line generated in vitro against HLA‐A*0301‐transfected TAP‐deficient T2 cells loaded with these peptides showed significant cytotoxic activity against the Mam‐A3.1 peptide. This CD8+ T cell line showed a significant HLA‐A3‐restricted cytotoxic activity against mammaglobin‐A‐positive but not mammaglobin‐A‐negative breast cancer cells. In summary, our study identified four HLA‐A3‐restricted mammaglobin‐A‐derived epitopes naturally expressed by breast cancer cells, indicating the immunotherapeutic potential of this novel antigen for the treatment and prevention of breast cancer. © 2002 Wiley‐Liss, Inc.