bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality in services for disabled children and their families: what can theory, policy and research on children's and parents' views tell us?
Authors: Mitchell Wendy , Sloper Patricia
Published: August 2002

Many discourses surround the concept of ‘service quality’, however, it continues to remain partial and ambiguous. This paper seeks to unpack ‘quality’ in services for disabled children and their families. Theoretical models are initially reviewed and then considered in relation to key policy guidelines, empirical data drawing upon parents' and children's experiences of ‘quality’ in services are presented. This paper demonstrates the many different levels within the concept of ‘quality’ and highlights the importance of recognising and respecting that children and parents frequently value different aspects of ‘quality’. Copyright © 2001 John Wiley & Sons, Ltd.
Stereochemical terminology and its discontents
Authors: Mislow Kurt
Published: August 2002

Scrutiny of the purported misuse of some current stereochemical terms shows that obsolescence and faulty syntax may be less of a problem than previously assumed. Furthermore, changes in stereochemical terminology over time are not always due to obsolescence or to novel developments in chemical technology; for example, technical developments played no role whatsoever in the semantic transmutations over time of the terms “diastereomer” and “pseudoasymmetry.” Finally, definitions of many stereochemical terms acquire meaning only within a given context and therefore cannot always be easily formulated. A prime example is the definition of “chirality,” the concept at the heart of stereochemistry and, not coincidentally, the name of the journal in which this essay appears in print. Chirality 14:126–134, 2002. © 2002 Wiley‐Liss, Inc.
Cyclic AMP‐dependent protein kinase A plays a role in the directed migration of human keratinocytes in a DC electric field
Authors: Pullar Christine E. , Isseroff R. Rivkah , Nuccitelli Richard
Published: August 2002

Skin wound healing requires epithelial cell migration for re‐epithelialization, wound closure, and re‐establishment of normal function. We believe that one of the earliest signals to initiate wound healing is the lateral electric field generated by the wound current. Normal human epidermal keratinocytes migrate towards the negative pole, representing the center of the wound, in direct currents of a physiological strength, 100 mV/mm. Virtually nothing is known about the signal transduction mechanisms used by these cells to sense the endogenous electric field. To elucidate possible protein kinase (PK) involvement in the process, PK inhibitors were utilized. Two important findings have been described. Firstly, addition of 50 nM KT5720, an inhibitor of PKA, resulted in a 53% percent reduction in the directional response of keratinocytes in the electric field, while not significantly affecting general cell motility. The reduction was dose‐dependent, there was a gradual decrease in the directional response from 5 to 50 nM. Secondly, addition of 1 μM ML‐7, a myosin light chain kinase inhibitor, resulted in an approximate 31% decrease in the distance the cells migrated without affecting directional migration. The PKC inhibitors GF109203X at 4 μM and H‐7 at 20 μM and W‐7, a CaM kinase inhibitor, did not significantly alter either directed migration or cell migration, although they all resulted in a slight reduction in directional migration. D‐erythro‐sphingosine at 15 μM, a PKC inhibitor, had virtually no effect on either migration distance or directed migration. These findings demonstrate that divergent kinase signaling pathways regulate general cell motility and sustained directional migration and highlight the complexity of the signal transduction mechanisms involved. The inhibitor studies described in this paper implicate a role for PKA in the regulation of the directional migratory response to applied electric fields, galvanotaxis. Cell Motil. Cytoskeleton 50:207–217, 2001. © 2001 Wiley‐Liss, Inc.
Initiation of cell locomotility is a morphogenetic checkpoint in thyroid epithelial cells regulated by ERK and PI3‐kinase signals
Authors: Yap Alpha S.
Published: August 2002

Epithelial locomotility is a fundamental determinant of tissue patterning that is subject to strict physiological regulation. The current study sought to identify cellular signals that initiate cell migration in cultured thyroid epithelial cells. Porcine thyroid cells cultured as 3‐dimensional follicles convert to 2‐dimensional monolayers when deprived of agents that stimulate cAMP/PKA signaling. This morphogenetic event is driven by the activation of cell‐on‐substrate locomotility, providing a convenient assay for events that regulate the initiation of locomotion. In this system, the extracellular signal regulated kinase (ERK) pathway became activated as follicles converted to monolayer, as demonstrated by immunoblotting for activation‐specific phosphorylation and nuclear accumulation of ERK. Inhibition of ERK activation using the drug PD98059 effectively prevented cells from beginning to migrate. PD98059 inhibited cell spreading, actin filament reorganization and the assembly of focal adhesions, cellular events that mediate the initiation of thyroid cell locomotility. Akt (PKB) signaling was also activated during follicle‐to‐monolayer conversion and the phosphoinositide 3‐kinase (PI3‐kinase) inhibitor, wortmannin, also blocked the initiation of cell movement. Wortmannin did not, however, block activation of ERK signaling. These findings, therefore, identify the ERK and PI3‐kinase signaling pathways as important stimulators of thyroid cell locomotility. These findings are incorporated into a model where the initiation of thyroid cell motility constitutes a morphogenetic checkpoint regulated by coordinated changes in stimulatory (ERK, PI3‐kinase) and tonic inhibitory (cAMP/PKA) signaling pathways. Cell Motil. Cytoskeleton 49:93–103, 2001. © 2001 Wiley‐Liss, Inc.
Vascular endothelial growth factor overexpression is correlated with von Hippel‐Lindau tumor suppressor gene inactivation in patients with sporadic renal cell carcinoma
Authors: Igarashi Hiroshi , Esumi Mariko , Ishida Hajime , Okada Kiyoki
Published: August 2002

BACKGROUND

A high frequency of genetic alterations of the von Hippel‐Lindau (VHL) gene and overexpression of the vascular endothelial growth factor (VEGF) gene have been observed independently in human sporadic renal cell carcinoma (RCCs), but to the authors' knowledge the association between the two has not been characterized in primary sporadic RCC. In the current study the authors report the simultaneous comparison of the biallelic inactivation status of the VHL gene and VEGF expression levels in patients with sporadic RCC.

METHODS

DNA and RNA were extracted from 27 sporadic RCC samples. Mutation was analyzed by direct sequencing of the amplified VHL DNA and cDNA. Loss of heterozygosity (LOH) of the gene was analyzed at three polymorphic markers. The VEGF mRNA was measured using Northern blot analysis.

RESULTS

Mutations of the VHL gene were found in 14 of 27 RCC samples (51.9%). LOH analysis by a VHL‐intragenic polymorphic marker and 2 extragenic microsatellite markers, D3S1560 and D3S1317, showed that LOH occurred in 10 of 15 RCC samples (66.7%). Overexpression of VEGF mRNA was observed in 17 of 27 RCC cases (63.0%): 15 of the 18 RCC samples estimated to have at least 1 hit, but only 2 of the 6 RCC samples with 0‐1 hit, and none of the 3 RCC samples in which the VHL gene was not inactivated.

CONCLUSIONS

VEGF overexpression was found to be correlated with both monoallelic and biallelic VHL inactivation. Alteration of the VHL gene is believed to cause angiogenesis in RCC cases through the overexpression of VEGF. Cancer 2002;95:47–53. © 2002 American Cancer Society.

DOI 10.1002/cncr.10635
Connection from cortical area V2 to MT in macaque monkey
Authors: Anderson John C. , Martin Kevan A.C.
Published: August 2002

The extrastriate visual area of the macaque monkey called MT or V5, receives its input from multiple sources. We have previously examined the synaptic connections made by V1 cells that project to MT (Anderson et al., 1998). Here, we provide a similar analysis of the projection from V2 to MT. The major target of the V2 projection in MT is layer 4, where it forms clusters of asymmetric (excitatory) synapses. Unlike the V1 projection, it also forms synapses in layers 1 and 2 and does not form synapses in layer 6. The most frequently encountered targets of boutons labeled from V2 were spines (67% in layer 4; 82% in layer 2/3). Unusually, only 5/12 boutons examined in layer 1 actually formed synapses. Unlike the V1 projection, multisynaptic boutons were rare (mean, 1.1 synapses per bouton vs. 1.7 for the V1 projection). Like the V1 projection, the input to MT from any point in V2 is sparse (contributing approximately 4–6% of the asymmetric synapses in the densest clusters in layer 4). The synapses of the V2 projection were similar in size to those of the V1 projection (0.1 μm2 vs. 0.09 μm2) and both formed more complex postsynaptic densities on spines than on dendritic shafts. The clear differences between the V1 and V2 projection to MT indicate that their functions are complementary rather than completely overlapping. J. Comp. Neurol. 443:56–70, 2002. © 2002 Wiley‐Liss, Inc.
Immunohistochemical localization of three different prepro‐GnRHs in the brain and pituitary of the European sea bass (Dicentrarchus labrax) using antibodies to the corresponding GnRH‐associated peptides
Authors: González‐Martínez David , Zmora Nilli , Mañanos Evaristo , Saligaut Dany , Zanuy Silvia , Zohar Yonathan , Elizur Abigail , Kah Olivier , Muñoz‐Cueto José Antonio
Published: August 2002

The distribution of the cells expressing three prepro‐gonadotrophin‐releasing hormones (GnRH), corresponding to salmon GnRH (sGnRH), seabream GnRH (sbGnRH), and chicken GnRH‐II (cGnRH‐II) forms, was studied in the brain and pituitary of the sea bass (Dicentrarchus labrax) by using immunohistochemistry. To circumvent the cross‐reactivity problems of antibodies raised to GnRH decapeptides, we used specific antibodies generated against the different sea bass GnRH‐associated peptides (GAP): salmon GAP (sGAP), seabream GAP (sbGAP), and chicken‐II GAP (cIIGAP). The salmon GAP immunostaining was mostly detected in terminal nerve neurons but also in ventral telencephalic and preoptic perikarya. Salmon GAP‐immunoreactive (ir) fibers were observed mainly in the forebrain, although sGAP‐ir projections were also evident in the optic tectum, mesencephalic tegmentum, and ventral rhombencephalon. The pituitary only receives a few sGAP‐ir fibers. The seabream GAP‐ir cells were mainly detected in the preoptic area. Nevertheless, sbGAP‐ir neurons were also found in olfactory bulbs, ventral telencephalon, and ventrolateral hypothalamus. The sbGAP‐ir fibers were only observed in the ventral forebrain, innervating strongly the pituitary gland. Finally, chicken‐II GAP immunoreactivity was only detected in large synencephalic cells, which are the origin of a profuse innervation reaching the telencephalon, preoptic area, hypothalamus, thalamus, pretectum, posterior tuberculum, mesencephalic tectum and tegmentum, cerebellum, and rhombencephalon. However, no cIIGAP‐ir fibers were detected in the hypophysis. These results corroborate the overlapping of sGAP‐ and sbGAP‐expressing cells in the forebrain of the sea bass, and provide, for the first time, unambiguous information on the distribution of projections of the three different GnRH forms expressed in the brain of a single species. J. Comp. Neurol. 446:95–113, 2002. © 2002 Wiley‐Liss, Inc.
Neonatally elevated serotonin levels alter terminal arbors of individual retinal ganglion cells in superior colliculus of hamsters
Authors: Crnko‐Hoppenjans Tracy A. , Mooney Richard D. , Rhoades Robert W.
Published: August 2002

Previous studies from this laboratory showed that sprouting of serotoninergic (5‐HT) axons in the hamster's superior colliculus (SC), induced by a single subcutaneous injection of 5,7‐dihydroxytryptamine (5,7‐DHT) at birth (postnatal day 0 [P‐0]), resulted in an increased terminal distribution of the uncrossed retinocollicular projection that was not associated with any changes in the number or distribution of ipsilaterally projecting retinal ganglion cells. The present study was undertaken to determine what effect this manipulation had on the terminal arbors of such axons. Retinocollicular axons of normal and 5,7‐DHT‐treated animals were anterogradely labeled with small intraretinal injections of the lipophilic dye 1,1′‐dioctadecyl‐3,3,3′,3′‐tetramethylindocarbocyanine perchlorate (DiI) on P‐16. After tissue processing on P‐19, single retinocollicular axon arbors were reconstructed by using confocal microscopy. Quantitative analysis indicated that arbors from 5,7‐DHT‐treated hamsters had significantly greater total fiber lengths, areas, and volumes than those from normal animals. There were no differences between axons from the two groups in number of branch points, distribution of relative branch lengths, and numbers of bouton‐like swellings. These results support the hypothesis that increased SC concentrations of 5‐HT alter development of the uncrossed retinocollicular pathway such that a greater territory is covered by individual terminal arbors but that the number of synaptic contacts per arbor remains constant. This may explain, at least in part, the abnormally widespread distribution of the aggregate ipsilateral projection. J. Comp. Neurol. 432:528–536, 2001. © 2001 Wiley‐Liss, Inc.
Target‐derived BDNF (brain‐derived neurotrophic factor) is essential for the survival of developing neurons in the isthmo‐optic nucleus
Authors: Von Bartheld Christopher S. , Johnson James E.
Published: August 2002

Neurons in the peripheral nervous system depend on single neurotrophic factors, whereas those in the brain are thought to utilize many different trophic factors. This study examined whether some neurons in the brain critically depend on a single trophic factor during development. Neurons in the isthmo‐optic nucleus (ION) of chick embryos respond to exogenous brain‐derived neurotrophic factor (BDNF). Relatively high concentrations of endogenous BDNF were present in the ION of 14–18‐day‐old chick embryos. ION target cells in the retina were immunolabeled for BDNF but showed surprisingly low levels of BDNF mRNA. These data suggest that ION target cells derive some BDNF from other retinal sources. No BDNF mRNA was detected in the ION itself. ION neurons had a very efficient retrograde transport system for BDNF and exogenous BDNF arrived in the ION intact. When the ION was deprived of endogenous trkB ligands by injection of trkB fusion proteins in the eye, cell death of ION neurons was enhanced, and this effect was mimicked by BDNF‐specific blocking antibodies in the eye. TrkB fusion proteins in the retina induced cell death of ION neurons prior to visible effects on ION target cells in the retina. Immunolabel for endogenous BDNF was sparse in pyknotic ION neurons, suggesting that ION neurons with low BDNF content were eliminated by apoptosis. These data show that BDNF is an essential target‐derived trophic factor for developing ION neurons and thereby validate the neurotrophic hypothesis for at least one neuronal population in the brain. J. Comp. Neurol. 433:550–564, 2001. © 2001 Wiley‐Liss, Inc.
Complementary finite element methods applied to the numerical homogenization of 3D absolute permeability
Authors: Trykozko Anna , Zijl Wouter
Published: August 2002

To be able to use a limited number of relatively large grid cells in numerical oil reservoir simulators and groundwater models, upscaling of the absolute permeability is frequently applied. The spatial fine‐scale permeability distribution, which is generally obtained from geological and geostatistical models, is incorporated in the relatively large grid cells of the numerical model. If the porous medium may be approximated as a periodic medium, upscaling can be performed by the homogenization method. Numerical homogenization gives rise to an approximation error. The complementarity between the conformal–nodal finite element method and the mixed–hybrid finite element method has been used to quantify this error. The two methods yield, respectively, upper and lower bounds for the eigenvalues of the coarse‐scale permeability tensor. Results of numerical experiments obtained using tetrahedral meshes are shown both in the far field and in the near well region. Copyright © 2001 John Wiley & Sons, Ltd.
A Monte Carlo simulation of the determination of mean particle volume using the Cavalieri estimator
Authors: Hammel Ilan , Lagunoff David
Published: August 2002

Background

A common morphometric problem is the determination of an estimate of the size of biological particles obtained from measurements made on a sample of profiles observed in sections. Results are reported typically in terms of mean caliper diameter or mean volume of the particle.

Methods

We have investigated the use of the Cavalieri estimator for obtaining estimates of mean particle volume using a Monte Carlo simulation. Samples of spherical and ellipsoidal particles were generated by computer and serially sectioned at a fixed mean thickness with a small, imposed random variation. The area of each profile was determined and the volume of the particle was calculated according to the Cavalieri estimator. The influence on the estimate of the mean particle volume and its 95% confidence interval was evaluated for several variables: the shape of the particles, the standard deviation of the particle volume in the population, the section thickness, and the standard deviation of the section thickness.

Results

The results obtained with the Cavalieri estimator correspond favorably with those obtained with previously reported alternative methods. This leads to a recommendation for the strong consideration for the use of the Cavalieri estimator in cases in which it is technically feasible to obtain at least three sections through the individual particles. Graphs are provided, which relate the confidence interval for the mean volume to the number of particles measured. Cytometry 47:138–141, 2002. © 2002 Wiley‐Liss, Inc.
Therapeutic use of nucleotides in respiratory and ophthalmic diseases
Authors: Yerxa Benjamin R.
Published: August 2002

Nucleotide agonists of P2Y2 receptors are potentially useful therapeutics for treating respiratory diseases such as chronic bronchitis and cystic fibrosis, and for treating ophthalmic indications such as dry eye and retinal detachment. INS365 is a chemically stable nucleotide P2Y2 agonist that, when inhaled, enhances mucociliary clearance of the airways and thus may be useful for treating chronic bronchitis in which retained mucus is a hallmark. On the ocular mucosa, P2Y2 agonists stimulate the secretion of salt, water, and mucus. This mechanism of basal tear secretion forms the scientific basis for the clinical investigation of INS365 as a tear film secretagogue for the treatment of dry eye disease. INS365 ophthalmic solution is currently in Phase II clinical trials in the US. INS37217, a next‐generation nucleotide P2Y2 agonist with enhanced metabolic stability and a potentially longer duration of action, is being developed for the treatment of cystic fibrosis and retinal detachment. In cystic fibrosis, P2Y2 agonists activate an alternative chloride channel, thereby restoring hydration of the airway surface and promoting mucociliary clearance. In experimental models of retinal detachment, INS37217 injected into the back of the eye activates P2Y2 receptors on the retinal pigmented epithelium, promoting fluid absorption in the subretinal space and thus facilitating retinal reattachment. Since receptors for nucleotides are found throughout the body, nucleotides and their analogs have great therapeutic promise when administered locally to the desired site of action. Drug Dev. Res. 52:196–201, 2001. © 2001 Wiley‐Liss, Inc.
Corpus cavernosum dysfunction in diabetic rats: effects of combined α‐lipoic acid and γ‐linolenic acid treatment
Authors: Keegan Alan , Cotter Mary A. , Cameron Norman E.
Published: August 2002

Background

The effects of streptozotocin‐induced diabetes on nitric oxide (NO)‐mediated relaxation of rat corpus cavernosum smooth muscle to neurogenic and endothelial stimulation was examined. The aim was to assess the effects of treatment with low doses of the antioxidant, α‐lipoic acid, and the ω‐6 essential fatty acid, γ‐linolenic acid, either separately or in combination.

Methods

Treatment was preventive from diabetes induction or corrective over 4 weeks after 4 weeks of untreated diabetes. Corpus cavernosum responses were examined in vitro.

Results

Neither diabetes nor treatment affected contractile responses to transmural electrical field stimulation of noradrenergic nerves. Stimulation of phenylephrine precontracted cavernosa in the presence of guanethidine and atropine caused relaxation via the nitrergic innervation. Maximum relaxation responses were 40% and 46% decreased after 4 and 8 weeks of diabetes, respectively. α‐Lipoic acid, γ‐linolenic acid combination treatment fully prevented this deficit, and partially (52%) corrected the effect of 4 weeks of untreated diabetes. Neither α‐lipoic acid nor γ‐linolenic components alone had significant effects, which suggests that there were synergistic interactions between the drugs. Both 4 and 8 weeks of untreated diabetes reduced maximum endothelium‐dependent relaxation of phenylephrine precontracted cavernosa to acetylcholine by approximately 40%. While α‐lipoic acid or γ‐linolenic acid were ineffective, joint treatment fully prevented and corrected this diabetic endothelial deficit. Neither diabetes nor treatment affected endothelium‐independent relaxation to the NO donor, sodium nitroprusside.

Conclusion

The data show that α‐lipoic acid and γ‐linolenic acid interact synergistically to improve NO‐mediated neurogenic and endothelium‐dependent relaxation of corpus cavernosum in experimental diabetes. Copyright © 2001 John Wiley & Sons, Ltd.
No role of calcium‐ and ATP‐dependent potassium channels in insulin‐induced vasodilation in humans in vivo
Authors: Abbink Evertine J. , Walker Annabel J. , van der Sluijs Henk A. , Tack Cees J. , Smits Paul
Published: August 2002

The mechanism of insulin‐induced vasodilation has not been completely clarified, but could be important in future treatment strategies of insulin resistance. Recently, a role for calcium‐dependent and ATP‐dependent potassium (KCa and KATP) channels in insulin‐induced vasodilation has been demonstrated in in vitro studies. A role for these channels has never been confirmed in humans in vivo. Therefore, we investigated the role of these channels in insulin‐induced vasodilation in humans in vivo. A hyperinsulinemic euglycemic clamp was combined with intra‐arterial infusion of placebo, tetraethylammonium (blocker of KCa channels) or glibenclamide (blocker of KATP channels) in three groups of 12 healthy volunteers. Bilateral forearm blood flow was measured with venous occlusion plethysmography. Systemic hyperinsulinemia induced a 20±9% vasodilation (p=0.001). Neither tetraethylammonium nor glibenclamide reduced this vasodilation as compared to placebo. According to the results of the present study, insulin‐induced vasodilation seems not to be mediated by the opening of KCa and KATP channels in humans in vivo. Copyright © 2002 John Wiley & Sons, Ltd.
Comparative localization of Dax‐1 and Ad4BP/SF‐1 during development of the hypothalamic‐pituitary‐gonadal axis suggests their closely related and distinct functions
Authors: Ikeda Yayoi , Takeda Yoshie , Shikayama Tatsuji , Mukai Tokuo , Hisano Setsuji , Morohashi Ken‐Ichirou
Published: August 2002

Two nuclear receptors, Ad4BP/SF‐1 and Dax‐1, are essential regulators for development and function of the mammalian reproductive system. Similarity in expression sites, such as adrenal glands, gonads, pituitary, and hypothalamus, suggests a functional interaction, and the phenotype similarities were manifested in Ad4BP/SF‐1‐deficient mice and in cases of natural human mutations of Dax‐1. In this study, quantitative reverse transcriptase polymerase chain reaction analyses revealed that expression profiles of Dax‐1 in embryonic gonads are different between the two sexes and also from those of Ad4BP/SF‐1. Immunohistochemical analyses clarified the spatial and temporal expressions of the Dax‐1 protein during development of tissues composing the hypothalamic‐pituitary‐gonadal axis. During gonadal development, Dax‐1 occurred after Ad4BP/SF‐1 exhibiting a sexually dimorphic expression pattern at indifferent stages, indicating a possibility of Dax‐1 involvement in earliest sex differentiation. When cord formation begins in the testis at embryonic day 12.5 (E12.5), Dax‐1 was expressed strongly in Sertoli cells, but its expression level markedly decreased in Sertoli cells and increased in interstitial cells between E13.5 and E17.5. In the female, Dax‐1 was strongly expressed in the entire ovarian primordium from E12.5 until E14.5, and then its expression level was decreased and limited to cells near the surface epithelium between E17.5 and postnatal day 0 (P0). During postnatal development of the testis, the variable staining of Dax‐1 in Sertoli cells was detected as early as P7 and Dax‐1‐expressing Leydig cells became rare. In the postnatal ovary, Dax‐1 expression was detected in granulosa cells with variable staining intensity, and occasionally in interstitial cells. During pituitary organogenesis, Dax‐1 but not Ad4BP/SF‐1 was expressed in the dorsal part of Rathke's pouch from E9.5. Later in development after E14.5, the distribution of Dax‐1 overlapped with that of Ad4BP/SF‐1, being restricted to gonadotropic cells in the anterior pituitary. In the ventromedial hypothalamus (VMH), Dax‐1 and Ad4BP/SF‐1 were mostly colocalized throughout the embryonic and postnatal development. Thus, the coexpression of Dax‐1 and Ad4BP/SF‐1 indicates their closely related functions in the development of the reproductive system. Furthermore, we noticed the presence of cells that express Dax‐1 but not Ad4BP/SF‐1, further indicating additional functions of Dax‐1 in an Ad4BP/SF‐1‐independent molecular mechanism. © 2001 Wiley‐Liss, Inc.
Agouti signaling protein and other factors modulating differentiation and proliferation of immortal melanoblasts
Authors: Sviderskaya Elena V. , Hill Simon P. , Balachandar Divya , Barsh Gregory S. , Bennett Dorothy C.
Published: August 2002

The melanocyte lineage potentially forms an attractive model system for studies in cell differentiation, developmental genetics, cell signaling, and melanoma, because differentiated cells produce the visible pigment melanin. Immortal lines of murine melanoblasts (melanocyte precursors) have been described previously, but induction of differentiation involved a complex culture system with keratinocyte feeder cells. Here we describe conditions for both growth and induced differentiation of the melanoblast line melb‐a, without feeder cells, and analyze factors that directly control proliferation and differentiation of these pure melanoblasts. Several active factors are products of developmental and other coat color genes, including stem cell factor (SCF), melanocyte‐stimulating hormone (αMSH), and agouti signaling protein (ASP), a natural antagonist at the MSH receptor (melanocortin 1 receptor, MC1R) encoded by the agouti gene. A stable analog of αMSH (NDP‐MSH) stimulated differentiation and inhibited growth. ASP in excess inhibited both effects of NDP‐MSH, that is, ASP could inhibit pigmentation and stimulate growth. These effects provide an explanation for the interactions in mice of melanocyte developmental mutations with yellow agouti and Mc1r alleles, and a role for embryonic expression patterns of ASP. © 2001 Wiley‐Liss, Inc.
Are RAN‐ and phonological awareness‐deficits additive in children with reading disabilities?
Authors: Compton Donald L. , Defries John C. , Olson Richard K.
Published: August 2002

The double‐deficit hypothesis (Wolf, M. and Bowers, P.G. (1999) The double‐deficit hypothesis for the developmental dyslexias. Journal of Educational Psychology, 91, 415–438) proposes that deficits in phonological processing and rapid automatized naming (RAN) are separable sources of reading dysfunction. Further, the double‐deficit hypothesis predicts that the presence of deficits in both phonological processing and RAN have an additive negative influence on reading performance above and beyond that of a single deficit. The purpose of this study was to examine the additive nature of phonological awareness (PA)‐ and RAN‐deficits on written language skill in children with reading disabilities (RD). Concurrent relationships between PA, RAN, and written language skills were examined in 476 children with RD, ranging in age from 8 to 18 years of age. Hierarchical regression analysis revealed that PA and RAN skill have an additive effect on a majority of the reading and spelling measures. When participants were classified into three deficit subtypes based on the double‐deficit model (i.e. phonological‐, rate‐, and double‐deficit), comparisons across the subtypes confirmed that individuals with double‐deficits performed below the single‐deficit groups on both subtyping variables (RAN and PA) and all measures of written language. When the double‐ and single‐deficit groups were matched on the subtyping variable (i.e. double‐ and rate‐deficit groups matched on RAN and double‐ and phonological‐deficit groups matched on PA) differences between the double‐ and rate‐deficit groups remained in non‐word reading, whereas differences between the double‐ and phonological‐deficit groups remained in timed word recognition and reading comprehension. These results support an additive model in which RAN‐deficits primarily affect tasks that require speeded/fluent response, and PA‐deficits primarily affect tasks that emphasize phonological processing skill. Results are also presented that illustrate several statistical problems associated with the formation of deficit groups by dichotomizing the RAN and PA variables. Copyright © 2001 John Wiley & Sons, Ltd.
Women's perceptions of the outcome of weight loss diets: A Signal detection approach
Authors: Heffernan Dorothy D. , Harper Susan M. , McWilliam Donna
Published: August 2002

Objective

Evolutionary psychology suggests that body shape is as important as body size and that, in women, certain body shapes are considered more attractive, specifically a waist‐to‐hip ratio (WHR) of about 0.70. Research has shown that the WHR does not change as a result of weight loss diets although it may be that women who diet do not appreciate this. We hypothesized that women would report diet outcomes that included shape change. This was investigated using a signal detection paradigm.

Method

Two groups of female participants (high and low WHRs) were presented with images with high and low WHRs and were asked to choose images they could resemble through dieting.

Results

Both groups of women selected low WHR images as the outcome of their diets, supporting theories of evolutionary psychology.

Discussion

We conclude that women in the high WHR group may find adherence to diets problematic because the desired change in shape does not occur. © 2002 by Wiley Periodicals, Inc. Int J Eat Disord 31: 339–343, 2002; DOI 10.1002/eat.10007
Prevention of eating disorders: Challenges and opportunities
Authors: Pearson Jane , Goldklang Dorothy , Striegel‐Moore Ruth H.
Published: August 2002

Objective and Methods

On April 25, 2000, the National Institute of Mental Health (NIMH) convened a Roundtable on the Prevention of Eating Disorders to review the state of prevention science in eating disorders and formulate recommendations regarding future steps to be taken in this area of research.

Results and Discussion

This report summarizes the roundtable discussion. The discussion focused on four major areas: the state of the art of risk factors research, translational research, prevention research in related fields, and cutting‐edge efforts in eating disorder prevention.

Conclusions

The report concludes with specific recommendations. © 2002 by Wiley Periodicals, Inc. Int J Eat Disord 31: 233–239, 2002; DOI 10.1002/eat.10014
Reducing risk factors for eating disorders: Targeting at‐risk women with a computerized psychoeducational program
Authors: Zabinski Marion F. , Pung Meredith A. , Wilfley Denise E. , Eppstein Dori L. , Winzelberg Andrew J. , Celio Angela , Taylor C. Barr
Published: August 2002

Objective

This controlled study evaluated whether an 8‐week program offered over the Internet would significantly decrease body image dissatisfaction, disordered eating patterns, and preoccupation with shape/weight among women at high risk for developing an eating disorder.

Method

Fifty‐six college women were recruited on the basis of elevated scores (≥110) on the Body Shape Questionnaire (BSQ). Psychological functioning, as measured by the Eating Disorder Inventory Drive for Thinness (EDI‐DT) subscale, Eating Disorder Examination‐Questionnaire (EDE‐Q), and the BSQ, was assessed at baseline, posttreatment, and at 10‐week follow‐up.

Results

All participants improved over time on most measures, although effect sizes suggest that the program did impact the intervention group.

Discussion

Findings suggest that technological interventions may be helpful for reducing disordered eating patterns and cognitions among high‐risk women. Future research is needed to assess whether such programs are effective over time for prevention of and reduction in eating disorder symptomatology. © 2001 by John Wiley & Sons, Inc. Int J Eat Disord 29: 401–408, 2001.
Numerical Dispersion and Stability Condition of the Nonstandard FDTD Method
Authors: Kudo Hironori , Kashiwa Tatsuya , Ohtani Tadao
Published: August 2002

In order to reduce the phase error in the FDTD analysis, Cole proposed the NS‐FDTD method. However, in the paper by Cole, numerical dispersion characteristics and accurate stability condition were not presented. Also, definition was given only for cubic lattices. In this paper, the NS‐FDTD method is extended to the rectangular lattices and the numerical dispersion characteristic and the stability condition are derived. From the analysis for the stability condition, it is found that the stability condition in the present method is larger than those for the FDTD method and the FDTD(2, 4) method. From the analysis of the dispersion characteristic, it is shown that the present method has much higher accuracy than the FDTD method whether the lattices are cubic or rectangular. An analysis of a waveguide model is carried out in which the NS‐FDTD method and the FDTD method are mixed. © 2001 Scripta Technica, Electron Comm Jpn Pt 2, 85(1): 22–30, 2002
Determining the costs to industry of environmental regulation
Authors: Haq Gary , Bailey Peter D. , Chadwick Michael J. , Forrester John , Kuylenstierna Johan , Leach Gerald , Villagrasa Delia , Fergusson Malcolm , Skinner Ian , Oberthur Sebastian
Published: August 2002

During the negotiation of international and European environmental regulations, the industry sector typically raises the issue of the cost of compliance. It is often maintained that the cost of complying with environmental regulations restricts business profitability and competitiveness. This paper provides an overview of the cost of compliance by considering the arguments, strategies and cost estimates that were presented by industry during the negotiations of several different environmental regulations in Europe and North America, and at the global level. It examines the difficulties associated with comparing costs using pre‐ and post‐regulation cost data and discusses the strategies adopted during the negotiations of the regulation and once the regulation was implemented. The paper concludes that although some proposals for regulation may impose burdens on industry, which it will oppose, industry has come to recognize that environmental regulation does not necessarily mean increased costs at the level anticipated. While regulation cannot guarantee innovation or lead to greater competitiveness and higher productivity for all firms, those that seize the opportunities will usually gain benefits. The paper reinforces the view that the EU should give careful consideration to the costs presented by industry as in the past it has tended to overestimate costs of compliance and underestimate the potential for the development of new technology. The introduction of independent cost assessments and technology assessments may be one way of overcoming this problem. Copyright © 2001 John Wiley & Sons, Ltd. and ERP Environment
Genotoxicity of iron chelators in L5178Y mouse lymphoma cells
Authors: Whittaker Paul , Seifried Harold E. , San Richard H.C. , Clarke Jane J. , Dunkel Virginia C.
Published: August 2002

To further study the mechanism of observed iron mutagenicity and cellular toxicity, a number of different iron chelators were evaluated to select a compound that was not mutagenic and had limited toxicity to mouse lymphoma cells. A series of iron chelators including those used clinically, those under development for clinical applications, and those used in nonclinical applications were evaluated. The mutagenic activity of the iron chelators was assessed in L5178Y mouse lymphoma cells. Eight of the 12 iron chelators that were tested induced mutagenic responses both with and without the addition of S9. Among those chelators used clinically or developed for clinical use, the only compound that did not induce a mutagenic response was the starch deferoxamine conjugate. In contrast, deferoxamine mesylate showed the highest toxicity in this group of chemicals and the concentrations leading to toxicity and mutagenicity between the activated and nonactivated assays were not significantly different. The other three chelators that were not mutagenic were Na2EDTA, phytic acid, and ferrozine. Environ. Mol. Mutagen. 38:347–356, 2001. Published 2001 Wiley‐Liss, Inc.
Models for the estimation of a ‘no effect concentration’
Authors: Pires Ana M. , Branco João A. , Picado Ana , Mendonça Elsa
Published: August 2002

The use of a no effect concentration (NEC), instead of the commonly used no observed effect concentration (NOEC), has been advocated recently. In this article models and methods for the estimation of an NEC are proposed and it is shown that the NEC overcomes many of the objections to the NOEC. The NEC is included as a threshold parameter in a non‐linear model. Numerical methods are then used for point estimation and several techniques are proposed for interval estimation (based on bootstrap, profile likelihood and asymptotic normality). The adequacy of these methods is empirically confirmed by the results of a simulation study. The profile likelihood based interval has emerged as the best method. Finally the methodology is illustrated with data obtained from a 21 day Daphnia magna reproduction test with a reference substance, 3,4‐dichloroaniline (3,4‐DCA), and with a real effluent. Copyright © 2002 John Wiley & Sons, Ltd.
A preliminary prediction of seismic damage‐based degradation in RC structures
Authors: Gupta Vinay K. , Nielsen Søren R. K. , Kirkegaard Poul H.
Published: August 2002

Estimation of structural damage from a known increase in the fundamental period of a structure after an earthquake or prediction of degradation of stiffness and strength for a known damage requires reliable correlations between these response functionals. This study proposes a modified Clough–Johnston single‐degree‐of‐freedom oscillator to establish these correlations in the case of a simple elasto‐plastic oscillator. It is assumed that the proposed oscillator closely models the response of a given multi‐degree‐of‐freedom system in its fundamental mode throughout the duration of the excitation. The proposed model considers the yield displacement level and ductility supply ratio‐related parameter as two input parameters which must be estimated over a narrow range of ductility supply ratio from a frequency degradation curve. This curve is to be identified from a set of recorded excitation and response time‐histories. Useful correlations of strength and stiffness degradation with damage have been obtained wherein a simple damage index based on maximum and yield displacements and ductility supply ratio has been considered. As an application, the proposed model has been used to demonstrate that ignoring the effects of aftershocks in the case of impulsive ground motions may lead to unsafe designs. Copyright © 2001 John Wiley & Sons, Ltd.
Same pie, different portions: shape and weight‐based self‐esteem and eating disorder symptoms in a Georgian sample
Authors: Tchanturia Ketevan , Troop Nicholas A. , Katzman Melanie
Published: August 2002

Objective:

Current diagnostic criteria for eating disorders emphasize the importance of issues concerning weight and shape for self‐esteem and self‐worth. However, this requirement is based on patients presenting at clinics in Western countries and it is not clear whether such overvaluation of weight and shape is also a feature of eating pathology in non‐Western women.

Method:

Two hundred and forty‐five women from Georgia (part of the former Soviet Union) completed a number of questionnaires measuring eating pathology, anxiety and depression. In addition, participants completed two measures concerning their evaluation of weight and shape (overvaluation of weight/shape and shape‐ and weight‐based self‐esteem).

Results:

Both overvaluation of weight and shape and shape‐ and weight‐based self‐esteem were significantly correlated with measures of eating pathology, even after partialling out the effects of anxiety and depression. In addition, the majority of these women desired a thinner body shape. Despite the associations between weight/shape‐based self‐esteem and eating pathology, the overall degree to which women based their self‐esteem on weight and shape was less than that reported in other studies using Western samples.

Conclusion:

Despite differences in culture, language and location, the women of Georgia appear to share with Western women their dissatisfaction with body shape. In addition, processes that underlie eating pathology may also be similar (namely overvaluation of weight/shape and shape‐ and weight‐based self‐esteem). Given that Georgian women have had differing exposure to western consumerism and marketing it is interesting that the same processes may be operating. With increasing exposure to a Western ideal of thinness portrayed in films, fashion and advertising, we can perhaps expect an increase in the prevalence of pathological eating syndromes. Copyright © 2001 John Wiley & Sons, Ltd and Eating Disorders Association.
Numerical modelling of gas–solid fluidized beds using the two‐fluid approach
Authors: Pain C. C. , Mansoorzadeh S. , de Oliveira C. R. E. , Goddard A. J. H
Published: August 2002

This paper details an approach to modelling gas–solid fluidized beds using the two‐fluid granular temperature model. Details concerning the difficulties associated with the boundary conditions, particularly for curved boundaries, are described along with a novel means of obtaining the internal stress of the solid‐phase, in part, by solving an implicit equation. This results in a scheme that is stable even when the solid volume fraction is close to maximum packing. A transient, mixed finite element discretization is used to solve the multi‐phase equations with a discontinuous finite element representation of the granular temperature and continuity equations. A new solution method is proposed to solve the coupled momentum and continuity equations based on Arnoldi iteration. Two fluidized beds are modelled, one in the bubbling regime and the other in the slugging regime. These simulations are compared with experiments. Copyright © 2001 John Wiley & Sons, Ltd.
Reexpression of a cluster of silenced transgenes is associated with their rearrangement
Authors: McBurney Michael W. , Lau Stephen , Jardine Karen , Yang Xiaofeng , Davies Bryan
Published: August 2002

Irreversible inactivation or silencing of tumor suppressor genes occurs frequently in the development of cancer. A similar process of silencing can occur after the integration of transfected or microinjected genes into the genomes of recipient cells. The inactivation of transfected genes seems particularly efficient in cells with stem cell characteristics. We have been studying the inactivation of genes transfected into cultured P19 embryonal carcinoma cells and found that the CpG‐rich sequence comprising the coding region of the lacZ reporter gene becomes extensively methylated after integration into the genome. 5‐Aza‐2′‐deoxycytidine (5AdC), an inhibitor of DNA methylation, induced the reexpression of silent transgenes in one clone of P19 cells studied in detail. However, the reexpressed genes remained heavily methylated over the lacZ coding sequence. We used pulsed‐field gel electrophoresis to analyze the structure of the transgenic locus in the parental and in 5AdC‐treated cells and found that, in each of the cells reexpressing the transgene, the cluster of transgenes had been rearranged. Each clone had undergone a different rearrangement that appeared to involve recombination within the tandemly repeated copies of the transgene. Our data seem consistent with the idea that 5AdC induces efficient DNA recombination between tandemly repeated genes and that the reexpression of silenced genes induced by 5AdC might be triggered by the chromatin reorganization at the site of DNA recombination. © 2001 Wiley‐Liss, Inc.
Marine and estuarine reservoir effects in central Queensland, Australia: Determination of ΔR values
Authors: Ulm Sean
Published: August 2002

As a component of archaeological investigations on the central Queensland coast, a series of five marine shell specimens live‐collected between A.D. 1904 and A.D. 1929 and 11 shell/charcoal paired samples from archaeological contexts were radiocarbon dated to determine local ΔR values. The object of the study was to assess the potential influence of localized variation in marine reservoir effect in accurately determining the age of marine and estuarine shell from archaeological deposits in the area. Results indicate that the routinely applied ΔR value of −5 ± 35 for northeast Australia is erroneously calculated. The determined values suggest a minor revision to Reimer and Reimer's (2000) recommended value for northeast Australia from ΔR = +11 ± 5 to +12 ± 7, and specifically for central Queensland to ΔR = +10 ± 7, for near‐shore open marine environments. In contrast, data obtained from estuarine shell/charcoal pairs demonstrate a general lack of consistency, suggesting estuary‐specific patterns of variation in terrestrial carbon input and exchange with the open ocean. Preliminary data indicate that in some estuaries, at some time periods, a ΔR value of more than −155 ± 55 may be appropriate. In estuarine contexts in central Queensland, a localized estuary‐specific correction factor is recommended to account for geographical and temporal variation in 14C activity. © 2002 Wiley Periodicals, Inc.
Expression pattern of the Brachyury gene in the arrow worm paraspadella gotoi (chaetognatha)
Authors: Takada Norio , Goto Taichiro , Satoh Nori
Published: August 2002

Summary: Arrow worms (the phylum Chaetognatha), which are among the major marine planktonic animals, are direct developers and exhibit features characteristic of both deuterostomes and protostomes. In particular, the embryonic development of arrow worms appears to be of the deuterostome type. Brachyury functions critically in the formation of the notochord in chordates, whereas the gene is expressed in both the blastopore and stomodeum invagination regions in embryos of hemichordates and echinoderms. Here we analyzed the expression of Brachyury (Pg‐Bra) in the arrow worm Paraspadella gotoi and showed that Pg‐Bra is expressed in the blastopore region and the stomodeum region in the embryo and then around the mouth opening region at the time of hatching. The expression of Pg‐Bra in the embryo resembles that of Brachyury in embryos of hemichordates and echinoderms, whereas that in the mouth opening region in the hatchling appears to be novel. genesis 32:240–245, 2002. © 2002 Wiley‐Liss, Inc.