bluuebunny/crossref_metadata_2025 huggingface dataset:
Daniel, the Three Youths fragment and the transmission of Old English verse
Authors: Remley Paul G.
Published: May 2003

The theories of oral-formulaic composition advanced by Albert B. Lord, his
mentor and collaborator Milman Parry, and their later twentieth-century followers
have been adduced frequently in studies of Old English verse, elements of
whose language must go back ultimately to an oral tradition. After decades of
research, however, scholars have yet to find conclusive answers to some basic
questions: did literate Anglo-Saxons continue to practise techniques of extemporaneous
versification? If so, did they continue to develop the mnemonic skills
attributed to oral poets? It is clear that the monuments of Old English verse
reveal many examples of formulaic language (for example, se mæra maga
Healfdenes, se mæra mago Healfdenes and se mæra maga Ecgðeowes); but should we
regard this language as a reliable witness to oral-formulaic versification or,
perhaps, as a hybrid, ‘literary-formulaic’ idiom? Finally, if we accept the synchronic
(or achronic) models of the formulaic ‘word-hoard’ that inform many
Old English studies, is it pointless even to speculate about poetic influence, direction of borrowing and similar concerns? If so, how should we regard, say,
two parallel uses of the unusual phrase enge anpaðas, occurring verbatim in
Beowulf and the poetic Exodus but nowhere else among the surviving monuments?
Must we view these parallels as isolated outcroppings in the trackless
expanse of the Old English poetic corpus? Largely as a result of the scarcity of
verse preserved in multiple copies, such questions have remained debatable into
the present century.
2. RECENT RESEARCH ON LANGUAGE MAINTENANCE
Authors: García MaryEllen
Published: May 2003

From its beginnings to the present, research in the field of language maintenance and shift has advocated the preservation of ethnic minority and immigrant languages. This review of current published literature, which continues that advocacy, focuses on a narrow time frame (approximately 1998–2002) in order to provide broad, worldwide coverage of different language contact situations. The discussion largely excludes questions of language policy and planning, but includes studies that use traditional as well as newer methodologies to illuminate how educational institutions, the media, ethnic language literacy, family relationships, and friendship networks—to name the more significant factors in maintenance—can be employed to encourage maintenance and language revitalization. After considering recent theoretical and critical works, this review surveys various countries in which research within ethnic and minority language communities illuminates language maintenance, or shift, or revitalization for that group. Current research suggests that use of the ethnic language in the family and friendship networks and its transgenerational transmission are still of crucial importance, as are the conditions in the greater society that provide support for its linguistic viability as a means of communication within and outside the immediate community.
6. EDUCATION AS A SITE OF LANGUAGE CONTACT
Authors: Baker Colin
Published: May 2003

This chapter reviews the multidimensional research on bilingual education, covering contexts where bilingual children are in transitional classrooms as well as schools where curriculum content is experienced in two (or more) languages. Bilingual education has become a major tool in language reversal planning, since language transmission within families within minority languages typically provides a considerable shortfall in language reproduction. To play its part in language reversal, bilingual education needs to show its relative effectiveness, both as an educational approach and for language maintenance planning. Immersion and dual language approaches have increasingly demonstrated such success. However, bilingual education is neither a universal panacea for language planners, nor is it effective purely due to dual language classroom approaches, as recent research reveals. Such research locates the political nature of bilingual education, not only at the level of policy making, but also in qualitative research in classrooms. It illuminates how language and literacy practices can latently legitimate and reproduce unequal relations between language majorities and minorities. Emerging directions in bilingual education research include trilingual education, the bilingual education of deaf students, the consequences of information technologies for bilingual classrooms, and the effect of the internationalization of English on language contact in schools. This reflects an international interest for research at the varying levels of philosophy, policy, provision, practice, and not least the politics of education as a site of language contact.
7. PARTICIPATION OF SECOND LANGUAGE AND SECOND DIALECT SPEAKERS IN THE LEGAL SYSTEM
Authors: Eades Diana
Published: May 2003

Manipulation of language is the key to all participation in the legal system. While linguists, especially sociolinguists, have been researching legal contexts for some two decades, there is still a considerable paucity of research on what happens when second language (L2) and second dialect (D2) speakers come into contact with the ‘language’ of the law. This chapter overviews the current state of theory and research on this topic. As with studies of L1 speakers, most of the studies have analyzed language in courtrooms, where access to data is much easier than in other legal settings, such as police interviews, mediation sessions or lawyer-client interviews. Most such research addresses one or more of the following questions, with the greatest concentration of research on the second and third of these: (a) What are the interpreting needs of second language speakers? (b) How are these needs being addressed? (c) What are the challenges to the provision of language services to second language speakers? And (d) How do dialectal differences affect the participation of second dialect speakers? The discussion concludes by highlighting a number of questions of crucial legal concern that need to be addressed by applied linguistics research.
An Integrated Navigation System For Suez Canal (SCINS)
Authors: EL-Kader Farouk Abd , EL-Soud M. Samy Abo , EL-Serafy Kamel , Hassan Ezzat A.
Published: May 2003

This paper offers a designed Integrated Navigation System that will permit vessels to transit safely through the Suez Canal avoiding collision and grounding in all weather environments instead of being directed to anchor, thus keeping the Canal open at all times for ship transits. The Suez Canal Integrated Navigation System (SCINS) includes Differential Global Positioning System (DGPS), Suez Canal LORAN-C system, and Vessel Traffic Management System (VTMS). The combination of DGPS and LORAN-C systems would provide real-time DGPS corrections that could be used to calibrate the Loran fix; this can be achieved by means of portable integrated DGPS/LORAN-C sets installed aboard the vessels. The addition of VTMS provides significant capability for preserving system accuracy during periods of GPS outages. Due to the interface between LORAN-C and VTMS systems, the SCINS will be able to solve the problem of targets that cannot be tracked by VTMS radars in the shadow areas behind the new bridges along the Canal. The SCINS automates position fixing in real-time, offers a designed algorithm to return the ship to the middle of the Canal and computes the cross-track error (XTE) and the ship squat. Kalman Filter design and system level performance predictions for the SCINS are briefly described. Simulation results show that the SCINS offers superior performance and better position accuracy than current integrated systems.
Formal and cultural constraints on optional objects in Bislama
Authors: Meyerhoff Miriam
Published: May 2003

Bislama allows phonetically overt and phonetically null noun
phrases (NPs) in argument positions. This article explores
constraints on the occurrence of null NPs in direct object
position. Discourse factors (given/new status of referent,
antecedent's form) and syntactic factors (antecedent's
grammatical role, identification by a transitive suffix) are
investigated. Morphosyntactic and semantic features that might
transfer from substrate languages (referent's animacy,
(in)alienable possession) and social factors (age, sex, language
of education) are also examined. Strong priming effects for
grammatical role of the antecedent and form of the antecedent
are identified. Also salient are inalienable possession and
semantic type of the verb. The effect of inalienable possession
shows the highly abstract transfer of substrate features, raising
questions about the modularity of grammar. It is argued that
a key motivation for such transfer is not just linguistic
availability, but the social and cultural significance of different
kinds of possession in Melanesia.
Language variation and change in the urban midwest: The case
of St. Louis, Missouri
Authors: Murray Thomas E.
Published: May 2003

St. Louis, Missouri, though located in the central Midlands,
is a complex city dialectally. Nevertheless, over the past 50
years most dialectologists and sociolinguists have identified
the area as primarily a Northern or Northern/North Midland
speech island in a sea of Southern and especially South Midland
forms. This article is concerned with whether the city's
strong affinity for the Northern/North Midland dialect
continues into the 21st century. Small pieces of evidence presented
over the last generation regarding the evolution of the area's
language have shown that different features of its pronunciation,
grammar, and lexicon are variously shifting both toward and
away from a Northern/North Midland standard. More comprehensive
evidence from a dialectological/sociolinguistic survey
completed in 1982–1983 and replicated in 2001, however,
suggests that overall the Northern/North Midland standard
has been not only preserved, but greatly strengthened.
Research assessment under the microscope: disturbing findings and distorting effects
Authors: Steadman Philip , Hillier Bill
Published: May 2003

The Research Assessment Exercise (RAE) to which every research-active UK university department has to submit every five years has fundamental resourcing implications for teaching and research – and thus, in the case of architecture, for the profession itself. Within the RAE, Architecture has always sat uneasily in a Built Environment ‘unit of assessment’ which appears to be dominated by construction and surveying – an unrepresentative state of affairs which can no longer be ignored. Leaders and letters in recent issues of arq (5/4, 6/1 and 2) have revealed the deep unease with which the results of the latest Exercise have been received. Now that full details of all RAE submissions have been published on the Web (www.hero.ac.uk/rae/ under ‘Submissions’), a fully informed analysis is at last possible. This article has been written in the light of this latest information.
Casbah: a brief history of a design concept
Authors: Oxman Robert , Shadar Hadas , Belferman Ehud
Published: May 2003

The Casbah concept was developed by a group of younger
European architects in the late 1950s. It flourished over a period
of no more than ten years but its influence continues to this day.
Three views on the RAE Design and the computer. Archigram's invisible university
Authors: Tabor Phil
Published: May 2003

My student years, 1961–67, exactly coincide with Archigram's first and best flourishing and, just as Jon Harris, in my Cambridge Architecture year, was the Cambridge salesman for the first issue of Private Eye, I was the Cambridge salesman for the first issue of Archigram. From this contemporary though partial viewpoint, Simon Sadler's article arq 6/3, pp247–255) seems historically convincing. I might, though, nuance the emphasis on Archigram ‘cultivating the anti-establishment reputation of 1960s youth’ and ‘an ill-tempered generation gap in early 1960s British architecture’. Most people, especially when young, proclaim themselves as outside the establishment tent, pissing in. So it's surely not noticeably ‘ironic’ that pre-War AA students did too. But there seems to me a world of difference between the soft ‘youthquake’ of early 1960s Britain (Quant, Bailey, the other Peter Cook, etc) and the leftist atmosphere of post-1965, the delayed echo in Britain of America's Vietnam and Civil Rights struggles. The first ethos – aesthetic, chirpy, self-mocking, and largely apolitical – nurtured the surrealist technophilia of Archigram's most interesting projects. The second, which really was ill-tempered and anti-establishment, made Archigram seem irrelevant or worse, as the article points out.
THE DYNAMICS OF KEYNESIAN MONETARY GROWTH
Authors: Chiarella Carl , Flaschel Peter , Wells Graeme
Published: May 2003

The objective of this book is to provide “a systematic theory of endogenous business fluctuations and growth with a hierarchical structure of integrated macro-dynamical models” (p. 372). The starting point is Tobin's neoclassical model of monetary growth, and successive chapters show how Tobin's model can be extended in various “realistic” directions while preserving the relevant adding-up and balance-sheet constraints of a macro model. The work reported here is squarely in an ongoing European theoretical tradition that eschews the stochastic, representative-agent, approach to macroeconomic modeling. Absent stochastic disturbances, the authors provide a qualitative analysis of dynamic behavior for a variety of closed-economy models—a variety that, as the authors themselves point out, is closely related to three prototype models studied in Part I of Sargent's 1977 book, Macroeconomic Theory.
Comparing error frequencies in monolingual and bilingual acquisition
Authors: DE HOUWER ANNICK
Published: May 2003

Natascha Müller's article concerns the acquisition of word order in German subclauses by young bilingual children. Müller's basic argument as I understand it runs as follows:

(1) In the acquisition of word order in German subclauses some children make errors and others do not;

(2) there are some monolingual and some bilingual children who do not make errors;

(3) there are some monolingual and some bilingual children who do make errors, and the errors are qualitatively similar for monolingual and bilingual children;

(4) when children do make errors, they occur more frequently in bilingual than in monolingual children;

(5) the errors in both monolingual and bilingual children are due to the misprojection of a separate functional category;

(6) in addition, the errors in bilingual children (but not in monolingual children) are due to influence from the other language they are simultaneously acquiring. The reason for positing this is that bilingual children's errors are more frequent than monolingual children's errors.
Cross-linguistic influence, input and the young bilingual child
Authors: LANZA ELIZABETH
Published: May 2003

The field of bilingual first language acquisition has focused on several important and interrelated issues: whether or not the young child acquiring two languages simultaneously differentiates his or her two languages from the onset of acquisition, what role the input plays in the acquisition of two languages, and whether the path of acquisition is similar to that of monolingual peers (see De Houwer, 1990). As a member of the DUFDE team, Natascha Müller has in previous work argued forcefully and convincingly for the bilingual child's separate development of his or her two languages, and hence how language-acquiring bilinguals behave like monolinguals. In her keynote article, Müller invokes the notion of transfer, a well-known term from research into second language acquisition, and proposes to consider transfer from the perspective of the input to which the young bilingual child is exposed. When this input is ambiguous, so that is there is variation in the input regarding one of the languages, the child will resort to transfer from the other language as a so-called relief strategy. In the following, I address the issue of cross-linguistic influence in language development and highlight the implications Müller's proposals may have for the field of bilingual first language acquisition. In conclusion I will relate these issues to the complexity of the notion of input in early bilingualism.
Transfer versus coexistent systems
Authors: TRACY ROSEMARIE
Published: May 2003

Compared with the wealth of investigations on monolingual language acquisition, research on early bilingualism still has some catching up to do. Papers such as the one by Natascha Müller show us what may be gained if results from both areas are integrated within one theoretical framework, in this case current generative theory.
One vs. two systems in early bilingual syntax: Two versions of the question
Authors: DEUCHAR MARGARET , QUAY SUZANNE
Published: May 2003

This paper identifies two versions of the question as to whether there is a single initial system in the syntax of developing bilinguals. Version 1 asks whether there are early mixed utterances, and if so, attributes this to a single initial system. Version 2 asks whether the utterances containing words from one of the child's languages exhibit the same syntax as the utterances containing words from the child's other language. We argue with reference to our own data (from an English-Spanish bilingual from ages 1;7 to 1;9) that Version 1 is not tenable because of the paucity of lexical resources when the child begins to produce two-word utterances. However, we argue that the early two-word utterances in our data do seem to exhibit a single rudimentary syntax, based on a predicate-argument structure found in all utterance types, mixed and non-mixed. We then argue in relation to Version 2 of the question, that it can only be answered once the child's utterances can be identified as language-specific in the two languages, and that this is not possible before the emergence of morphological marking. This is illustrated by an analysis of our data from ages 1;8 to 2;3. We argue that language-specific morphology allows us to identify the language of the utterances in our data and to see evidence for the appearance of two differentiated morphosyntactic systems.
Die Forderung nach Internationalisierung der deutschen Psychologie am Beispiel der Zeitschrift für Pädagogische Psychologie
Authors: Borkenhagen Ada , Schumacher Jörg , Brähler Elmar
Published: May 2003

Zusammenfassung: Ausgehend von der aktuellen Debatte einer Internationalisierung der deutschen Psychologie wurden die letzten beiden Jahrgänge der Zeitschrift für Pädagogische Psychologie einer bibliometrischen Analyse unterzogen, um die Auswirkungen dieser Forderung auf ein anwendungsorientiertes Fach wie die Pädagogische Psychologie und eines ihrer zentralen deutschsprachigen Publikationsorgane zu untersuchen. Die Strategie der Herausgeber der Zeitschrift für Pädagogische Psychologie, auch unter dem Eindruck der Forderung einer Revision des deutschsprachigen wissenschaftlich-psychologischen Zeitschriftensystems an der Publikationssprache Deutsch festzuhalten, ist angesichts der Resonanz (Impact), die die Zeitschrift für Pädagogische Psychologie in der Scientific Community und den “Flagschiffjournalen” der Pädagogischen Psychologie erfährt, als grundsätzlich erfolgreich anzusehen, wobei jedoch Verbesserungsmöglichkeiten bestehen. In der Untersuchung wurde sowohl die Resonanz, die die letzten beiden Jahrgänge der Zeitschrift für Pädagogische Psychologie auf die übrigen relevanten Fachjournale ausgeübt haben, wie auch die Rezeption des internationalen Forschungsstandes durch die Autoren der Zeitschrift für Pädagogische Psychologie detailliert analysiert.
Benthic macroinvertebrates in Swedish streams: community structure, taxon richness, and environmental relations
Authors: Sandin Leonard
Published: May 2003

Spatial scale, e.g. from the stream channel, riparian zone, and catchment to the regional and global scale is currently an important topic in running water management and bioassessment. An increased knowledge of how the biota is affected by human alterations and management measures taken at different spatial scales is critical for improving the ecological quality of running waters. However, more knowledge is needed to better understand the relationship between environmental factors at different spatial scales, assemblage structure and taxon richness of running water organisms. In this study, benthic macroinvertebrate data from 628 randomly selected streams were analysed for geographical and environmental relationships. The dataset also included 100 environmental variables, from local measures such as in‐stream substratum and vegetation type, catchment vegetation and land‐use, and regional variables such as latitude and longitude. Cluster analysis of the macroinvertebrate data showed a continuous gradient in taxonomic composition among the cluster groups from north to south. Both locally measured variables (e.g. water chemistry, substratum composition) and regional factors (e.g. latitude, longitude, and an ecoregional delineation) were important for explaining the variation in assemblage structure and taxon richness for stream benthic macroinvertebrates. This result is of importance when planning conservation and management measurements, implementing large‐scale biomonitoring programs, and predicting how human alterations (e.g. global warming) will affect running water ecosystems.
Synchrony of woodland bird populations: the effect of landscape structure
Authors: Bellamy P. E. , Rothery P. , Hinsley S. A.
Published: May 2003

The influence of environmental stochasticity and dispersal in producing patterns in population synchrony was examined for 53 woods censused annually from 1990 to 1999 for nine resident bird species (wrenTroglodytes troglodytes, dunnockPrunella modularis, robinErithacus rubecula, blackbirdTurdus merula, song thrushTurdus philomelos, long‐tailed titAegithalos caudatus, blue titParus caeruleus, great titParus major, and chaffinchFringilla coelebs) and four migrant bird species (garden warblerSylvia borin, blackcapSylvia atricapilla, chiffchaffPhylloscopus collybitaand willow warblerPhylloscopus trochilus). Twelve species showed global synchrony of population counts due to regional population trends and widespread annual population fluctuations. There was a clear link between population fluctuations and winter weather for wren, and three other species showed their largest population declines after the coldest winters. Eight species showed a decline in synchrony with distance between woods, and there was evidence for dispersal causing this pattern in three species. Landscape structure affected patterns of synchrony in several species, with lower synchrony in landscapes with less woodland. For three species, this difference in synchrony across a landscape gradient of decreasing woodland cover accounted for the decline in synchrony over distance. Three species showed greater synchrony between woods with similar amounts of hedgerow in the surrounding landscape, suggesting that the surroundings of a wood influence the population dynamics of some species breeding in the wood. Habitat fragmentation can alter the processes contributing to population synchrony. Loss of woodland reduces the relative abundance of woodland bird species. The remaining patches of habitat are smaller, more isolated and are set in a more hostile landscape, all of which may disrupt dispersal between patches and alter the population dynamics within woods.
Epidemiology of Vitiligo and Associated Autoimmune Diseases in Caucasian Probands and Their Families
Authors: Alkhateeb Asem , Fain Pamela R. , Thody Anthony , Bennett Dorothy C. , Spritz Richard A.
Published: May 2003

Generalized vitiligo is an autoimmune disorder characterized by acquired white patches of skin and overlying hair, the result of loss of melanocytes from involved areas. The most common disorder of pigmentation, vitiligo occurs with a frequency of 0.1–2.0% in various populations. Family clustering of cases is not uncommon, in a non‐Mendelian pattern suggestive of multifactorial, polygenic inheritance. We surveyed 2624 vitiligo probands from North America and the UK regarding clinical characteristics, familial involvement, and association with other autoimmune disorders, the largest such survey ever performed. More than 83% of probands were Caucasians, and the frequency of vitiligo appeared approximately equal in males and females. The frequency of vitiligo in probands' siblings was 6.1%, about 18 times the population frequency, suggesting a major genetic component in disease pathogenesis. Nevertheless, the concordance of vitiligo in monozygotic twins was only 23%, indicating that a non‐genetic component also plays an important role. Probands with earlier disease onset tended to have more relatives affected with vitiligo, suggesting a greater genetic component in early onset families. The frequencies of six autoimmune disorders were significantly elevated in vitiligo probands and their first‐degree relatives: vitiligo itself, autoimmune thyroid disease (particularly hypothyroidism), pernicious anaemia, Addison's disease, systemic lupus erythematosus, and probably inflammatory bowel disease. These associations indicate that vitiligo shares common genetic aetiologic links with these other autoimmune disorders. These results suggest that genomic analysis of families with generalized vitiligo and this specific constellation of associated autoimmune disorders will be important to identify the mechanisms of genetic susceptibility to autoimmunity.
The Role of Melanocortin‐1 Receptor Polymorphism in Skin Cancer Risk Phenotypes
Authors: Sturm Richard A. , Duffy David L. , Box Neil F. , Chen Wei , Smit Darren J. , Brown Darren L. , Stow Jennifer L. , Leonard J. Helen , Martin Nicholas G.
Published: May 2003

We have examined melanocortin‐1 receptor (MC1R) variant allele frequencies in the general population and in a collection of adolescent dizygotic and monozygotic twins to determine statistical associations of pigmentation phenotypes with increased skin cancer risk. This included hair and skin color, freckling, mole count and sun exposed skin reflectance. Nine variants were studied and designated as either strong R (OR = 63; 95% CI 32–140) or weak r (OR = 5; 95% CI 3–11) red hair alleles. Penetrance of each MC1R variant allele was consistent with an allelic model where effects were multiplicative for red hair but additive for skin reflectance. To assess the interaction of the brown eye color gene BEY2/OCA2 on the phenotypic effects of variant MC1R alleles we imputed OCA2 genotype in the twin collection. A modifying effect of OCA2 on MC1R variant alleles was seen on constitutive skin color, freckling and mole count. In order to study the individual effects of these variants on pigmentation phenotype we have established a series of human primary melanocyte strains genotyped for the MC1R receptor. These include strains which are MC1R wild‐type consensus, variant heterozygotes, and homozygotes for strong R alleles Arg151Cys and Arg160Trp. Ultrastructural analysis demonstrated that only consensus strains contained stage III and IV melanosomes in their terminal dendrites whereas Arg151Cys and Arg160Trp homozygous strains contained only immature stage I and II melanosomes. Such genetic association studies combined with the functional analysis of MC1R variant alleles in melanocytic cells should provide a link in understanding the association between pigmentary phototypes and skin cancer risk.
Inheritance of cleft palate in South America: evidence for a major locus recessive
Authors: Vieira AR , Romitti PA , Orioli IM , Castilla EE
Published: May 2003

Structured Abstract

Authors – Vieira AR, Romitti PA, Orioli IM, Castilla EE

Objectives – Determine the model of inheritance of non‐syndromic cleft palate in humans.

Design – Complex segregation analysis performed in families of consecutive newborns affected with non‐syndromic cleft palate.

Setting and Sample Population – The Latin American Collaborative Study of Congenital Malformations (ECLAMC). Four hundred and seven consecutive newborns affected with non‐syndromic cleft palate registered during the period 1967–97.

Outcome Measure – Likelihood ratio test and Akaike information criterion (AIC) values.

Results – The single major locus recessive model provided a significantly better explanation of the data. It was the most parsimonious and had the smallest AIC value of the six models tested with approximately the same likelihood as the general model (χ2 = 2.44, p = 0.5).

Conclusions – To have defined a genetic model for non‐syndromic cleft palate and provided evidence for a single major locus inheritance suggests that genetic linkage studies could be implemented.
Actions of LY341495 on metabotropic glutamate receptor‐mediated responses in the neonatal rat spinal cord
Authors: Howson Patrick A , Jane David E
Published: May 2003

The group II metabotropic glutamate (mGlu) receptor antagonist (2S,1′S,2′S)‐2‐(2‐carboxycyclopropyl)‐2‐(9H‐xanthen‐9‐yl)glycine (LY341495) also has activity at group I and III mGlu receptors at higher concentrations and can be used to discriminate between mGlu receptor subtypes. We report the antagonist action of LY341495 on glutamate receptors expressed in the neonatal rat spinal cord preparation and the use of this antagonist to investigate the group III mGlu receptor subtypes responsible for mediating the depression of synaptic transmission in the spinal cord mediated by the group III mGlu receptor agonists (S)‐2‐amino‐4‐phosphonobutanoic acid ((S)‐AP4) and (1S,3R,4S)‐1‐aminocyclopentane‐1,2,4‐tricarboxylic acid (ACPT‐I).

LY341495 antagonised mGlu receptor agonist‐induced responses in the spinal cord with a rank order of potency of group II > group III > group I, which is the same as that observed in human cloned mGlu receptor cell lines. Antagonism of group II and III mGlu receptor‐mediated effects were time dependent when low‐nanomolar concentrations of LY341495 were used. Although the rank order of potency of LY341495 was the same on native rat and cloned human mGlu receptors, there was a compression in the selectivity between group II and III mGlu receptors, expressed in the spinal cord.

In agreement with a previous study on cloned ionotropic glutamate receptors 100 μM LY341495 had little or no effect on N‐methyl‐D‐aspartate, (S)‐2‐amino‐3‐(3‐hydroxy‐5‐methylisoxazol‐4‐yl) propionic acid or kainate receptor‐mediated responses on motoneurones.

LY341495 exhibited low‐nanomolar potency antagonist activity against (S)‐AP4 and ACPT‐I suggesting that these agonists are activating predominantly mGlu8 and that mGlu4 receptors do not play a role in modulating synaptic transmission in the pathways stimulated in the experiments described here.

British Journal of Pharmacology (2003) 139, 147–155. doi:10.1038/sj.bjp.0705230
Inhibition of lipopolysaccharide‐inducible nitric oxide synthase, TNF‐α and COX‐2 expression by sauchinone effects on I‐κBα phosphorylation, C/EBP and AP‐1 activation
Authors: Lee Ae Kyung , Sung Sang Hyun , Kim Young Choong , Kim Sang Geon
Published: May 2003

Sauchinone, a lignan isolated from Saururus chinensis (Saururaceae), is a diastereomeric lignan with cytoprotective and antioxidant activities in cultured hepatocytes. The effects of sauchinone on the inducible nitric oxide synthase (iNOS), tumor necrosis factor‐α (TNF‐α) and cyclooxygenase 2 (COX‐2) gene expression and on the activation of transcription factors, nuclear factor‐κB (NF‐κB), CCAAT/enhancer‐binding protein (C/EBP), activator protein‐1 (AP‐1) and cAMP‐response element‐binding protein (CREB) were determined in Raw264.7 cells as part of the studies on its anti‐inflammatory effects.

Expression of the iNOS, TNF‐α and COX‐2 genes was assessed by Northern and Western blot analyses. NO production was monitored by chemiluminescence detection using a NO analyzer. To identify the transcriptional factors affected by sauchinone, the extents of NF‐κB, C/EBP, AP‐1 and CREB activation were measured. Activation of the transcription factors was monitored by gel mobility shift assay, whereas p65 and I‐κBα were analyzed by immunocytochemical and immunoblot analyses.

Sauchinone inhibited the induction of iNOS, TNF‐α and COX‐2 by lipopolysaccharide (LPS) (IC5010 μM) with suppression of the mRNAs.

Sauchinone (1–30 μM) inhibited LPS‐inducible nuclear NF‐κB activation and nuclear translocation of p65, which was accompanied by inhibition of I‐κBα phosphorylation.

LPS‐inducible increase in the intensity of C/EBP binding to its consensus sequence was also inhibited by sauchinone. The AP‐1, but not CREB, DNA binding activity was weakly inhibited by sauchinone.

These results demonstrate that sauchinone inhibits LPS‐inducible iNOS, TNF‐α and COX‐2 expression in macrophages through suppression of I‐κBα phosphorylation and p65 nuclear translocation and of C/EBP and/or AP‐1 activation, which may constitute anti‐inflammatory effects of the lignan.

British Journal of Pharmacology (2003) 139, 11–20. doi:10.1038/sj.bjp.0705231
PPAR‐α and ‐γ but not ‐δ agonists inhibit airway inflammation in a murine model of asthma: in vitro evidence for an NF‐κB‐independent effect
Authors: Trifilieff Alexandre , Bench Anne , Hanley Marcus , Bayley Debbie , Campbell Emma , Whittaker Paul
Published: May 2003

Peroxisome proliferator‐activated receptors (PPARs) are ligand‐activated transcription factors that have been proposed to regulate inflammation by antagonising the nuclear factor‐κB (NF‐κB) signalling pathway. We investigated the role of PPARs using synthetic agonists in murine models of airway inflammation, and addressed the possible effect on NF‐κB signalling in vitro using a human epithelial cell line, A549.

Sensitised BALB/c mice exposed to an aerosol solution of ovalbumin had an increased number of airway eosinophils, neutrophils and lymphocytes. When given intranasally an hour before the aerosol challenge, a PPAR‐α (GW 9578) and PPAR‐γ (GI 262570) selective agonist as well as a dual PPAR‐α/γ (GW 2331) agonist selectively inhibited allergen‐induced bronchoalveolar lavage eosinophil and lymphocyte but not neutrophil influx. In contrast, a PPAR‐δ agonist (GW 501516) was inactive.

When given intranasally an hour before challenge, PPAR‐α and PPAR‐γ selective agonists as well as a dual PPAR‐α/γ agonist did not inhibit lipopolysaccharide‐induced bronchoalveolar lavage neutrophil influx or tumour necrosis factor‐α (TNF‐α) and KC production.

In A549 cells, selective agonists for PPAR‐α, ‐γ and ‐δ did not inhibit intracellular adhesion molecule‐1 expression following stimulation with proinflammatory cytokines. In addition, IL‐8 release and the activation of an NF‐κB‐responsive reporter gene construct were inhibited only at micromolar concentrations, suggesting that these effects were not PPAR‐mediated.

Our in vivo data show that agonists of PPAR‐α and ‐γ, but not ‐δ, inhibit allergen‐induced bronchoalveolar lavage eosinophil and lymphocyte influx. In vitro data suggest that this effect might not be mediated by antagonism of the NF‐κB pathway.

British Journal of Pharmacology (2003) 139, 163–171. doi:10.1038/sj.bjp.0705232
Effect of resiniferatoxin on the noxious heat threshold temperature in the rat: a novel heat allodynia model sensitive to analgesics
Authors: Almási Róbert , Pethö Gábor , Bölcskei Kata , Szolcsányi János
Published: May 2003

An increasing‐temperature hot plate (ITHP) was introduced to measure the noxious heat threshold (45.3±0.3°C) of unrestrained rats, which was reproducible upon repeated determinations at intervals of 5 or 30 min or 1 day.

Morphine, diclofenac and paracetamol caused an elevation of the noxious heat threshold following i.p. pretreatment, the minimum effective doses being 3, 10 and 200 mg kg−1, respectively.

Unilateral intraplantar injection of the VR1 receptor agonist resiniferatoxin (RTX, 0.048 nmol) induced a profound drop of heat threshold to the innocuous range with a maximal effect (8–10°C drop) 5 min after RTX administration. This heat allodynia was inhibited by pretreatment with morphine, diclofenac and paracetamol, the minimum effective doses being 1, 1 and 100 mg kg−1 i.p., respectively.

The long‐term sensory desensitizing effect of RTX was examined by bilateral intraplantar injection (0.048 nmol per paw) which produced, after an initial threshold drop, an elevation (up to 2.9±0.5°C) of heat threshold lasting for 5 days.

The VR1 receptor antagonist iodo‐resiniferatoxin (I‐RTX, 0.05 nmol intraplantarly) inhibited by 51% the heat threshold‐lowering effect of intraplantar RTX but not α,β‐methylene‐ATP (0.3 μmol per paw). I‐RTX (0.1 or 1 nmol per paw) failed to alter the heat threshold either acutely (5–60 min) or on the long‐term (5 days). The heat threshold of VR1 receptor knockout mice was not different from that of wild‐type animals (45.6±0.5 vs 45.2±0.4°C).

In conclusion, the RTX‐induced drop of heat threshold measured by the ITHP is a novel heat allodynia model exhibiting a high sensitivity to analgesics.

British Journal of Pharmacology (2003) 139, 49–58. doi:10.1038/sj.bjp.0705234
Immunocontraception for population control: Will resistance evolve?
Authors: Magiafoglou Andréa , Schiffer Michele , Hoffmann Ary A , McKechnie Stephen W
Published: May 2003

The prospect for successful biocontrol using immunocontraception is threatened if there is adaptation to the vaccine through natural selection of individuals that are genetically resistant to the contraceptive agent. To assess this possibility we examined the literature and found that little relevant data are available for any species on the appropriate trait, fertility variation among immunized individuals, or about appropriate population and genetic parameters influencing the likelihood of a selection response. Some data are available on variation in antibody response to immunocontraceptives, but the relationship between antibody response and fertility levels is poorly documented. The antibody response data indicate low heritability for this trait suggesting that fertility levels of contraceptive‐resistant individuals will also have a low heritability. Slow evolution of contraception resistance might therefore be anticipated. The absence of information about relevant parameters makes the construction of quantitative models premature. We discuss factors in particular need of investigation if predictions about resistance evolution are to be made. These include: 1. the genetic basis of fertility retention, 2. the proportion of the population resistant to the contraceptive agent and how this is affected by gene flow from refuge populations, 3. the genetically‐based fitness tradeoffs of resistant individuals that often accompany selection, 4. cross‐generation effects that can thwart the effects of selection, and 5. the efficiency of delivery of the contraceptive agent. An understanding of the above for particular species, and the development of appropriate divergently acting multiple vaccines that can be used in temporal rotation or in mixtures, should facilitate the development of management options to minimize resistance evolution.
Cancer immunotherapy: The past, the present and the future
Authors: Parish Christopher R
Published: May 2003

One of the most controversial issues in immunology for over a century has been whether an effective immune response can be elicited against malignant tumours. Whether the immunology community has believed cancer immunotherapy is feasible or impossible has been largely determined by the prevailing immunological paradigms at that time. In fact, during the last 110 years it is possible to trace at least five dramatic fluctuations in attitude towards cancer immunotherapy. It now appears, however, that overwhelming evidence is available to support the view that both the innate and adaptive immune responses can recognize and eliminate tumours. On the other hand, it remains to be seen if these immune responses can be harnessed to control cancer as, at the time of diagnosis, many tumours have already been immunoselected to be highly resistant to immune elimination. Based on these observations it is argued that immunotherapy approaches, other than the generation of tumour‐specific cytotoxic T lymphocytes, must be explored. Alternative strategies include recruiting tumouricidal myeloid cells into tumours, generating antiangiogenic immune responses and directing innate immunity to hypoxia‐induced ligands on tumour cells.
Amniotic fluid index in normal pregnancy: An assessment of gestation specific reference values among Indian women
Authors: Khadilkar Suvarna S. , Desai Sabita S. , Tayade Sadhana M. , Purandare Chittaranjan N.
Published: May 2003

Aim:  To obtain a gestational reference range for the amniotic fluid index (AFI) among Indian women.

Methods:  An analysis of AFI estimations was undertaken in 517 Indian women with normal pregnancy between 16 and 42 weeks of gestation. It was a prospective, cross‐sectional study conducted in a university teaching hospital. Women with fetal anomalies, pregnancy‐induced hypertension, diabetes mellitus, and other maternal complications were excluded from the study. The median, the 5th and the 95th percentile values were calculated for each gestational week and these values were compared with other studies.

Results:  The median reached its peak at the 27th week of gestation. We observed ∼ 6 cm as the lower limit of normal (5th percentile) and ∼ 18 cm (95th percentile) as upper limit of normal AFI at term for our population, whereas in the Caucasian population, the values were ∼ 7 cm and ∼ 20 cm, respectively. All gestation specific AFI values were lower in the studied population of Indian women compared with other studies on Caucasian population (P < 0.01 for 5th percentile & P < 3.26 × 10−7 for 95th percentile), but slightly higher than the Chinese population.

Conclusion:  Amniotic fluid index values differ in different populations. We standardized the reference values for normal AFI in Indian women. We found that they are lower in the population studied compared with reported values in the Caucasian population, but slightly higher than the Chinese population.
The clinical efficacy and efficiency of a 100‐IU starting dose of recombinant follicle stimulating hormone (Puregon®) in Korean women undergoing in vitro fertilization and embryo transfer
Authors: Moon Shin Yong , Kim Seok Hyun , Ku Seung Yup , Jee Byoung Chul , Choi Young Min , Lee Jin Yong
Published: May 2003

Aim:  A prospective, non‐comparative study was conducted to evaluate the efficacy and efficiency of a starting dose of 100 IU recombinant follicle stimulating hormone (rhFSH, Puregon®) in women undergoing ovarian stimulation prior to in vitro fertilization (IVF).

Methods:  A total of 40 women were down‐regulated with gonadotropin releasing hormone agonist (long protocol), then treated with a fixed dose of 100 IU rhFSH for the first 4 days, and the dose of gonadotropin administration was adjusted according to patient's response thereafter. A maximum number of 3 embryos were transferred in 32 patients.

Results:  Nine patients were treated with intracytoplasmic sperm injection, and 24 with conventional IVF. The duration of stimulation was 10.8 ± 1.8 days, serum estradiol concentration on human chorionic gonadotropin day was 1693.0 ± 1651.2 pg/mL, and 1480 ± 450 IU rhFSH was used. A mean number of 8.4 ± 5.7 oocytes were retrieved, 4.9 ± 4.3 embryos obtained, 2.4 ± 0.9 embryos transferred, and 3.5 ± 3.2 embryos cryopreserved. The proportion of mature oocytes was 71.6%, and the fertilization rate was 86.4%. Clinical pregnancy was achieved in 8 patients (25.0%), and all of these pregnancies are ongoing or delivered. There were 3 cases of twin gestations (37.5%). The implantation rate was 13.1% (11/84). There was one case of moderate ovarian hyperstimulation syndrome, however, the patient recovered within 7 days without any complications.

Conclusion:  The starting dose of 100 IU rhFSH has a good safety profile, and is adequate in controlled ovarian hyperstimulation for IVF with a small amount of gonadotropin administered.
Effects of methylergometrine and oxytocin on thoracic epidural pressure during cesarean section
Authors: Kikutani Takehiko , Shimada Yoichi
Published: May 2003

Aim:  The effects of oxytocics on thoracic epidural pressure during cesarean section were studied in 60 parturients, (American Society of Anesthesiologist physical status, class I or II) after obtaining informed consent.

Methods:  The subjects were randomized to either a ergometrine (n = 30) or oxytocin treatment group (n = 30). The subjects were anesthetized with 11–12 mg of intrathecal isobaric bupivacaine (0.5%), and an epidural catheter was placed at Th 11/12, and was connected to a pressure transducer to continuously monitor thoracic epidural pressure. We analyzed epidural pressure, blood pressure, and heart rate 5 min after administering intrathecal bupivacaine (SAB5m), immediately before skin incision (pre‐incision), immediately after delivery of the placenta (placenta‐del), and 5 min after delivery of the fetus (CS5m).

Results:  In both groups, epidural pressures were found to be elevated after delivery compared with their levels before the skin incisions were made, (P < 0.0001). Epidural pressures at placenta‐del (P = 0.0055) and CS5m (P < 0.0001) were higher than at SAB5m in the ergometrine group. Epidural pressures at placenta‐del were also higher than at SAB5m in the oxytocin group (P < 0.0001). Epidural pressures at placenta‐del were lower in the ergometrine group compared with the oxytocin group (P = 0.0122), but epidural pressures at CS5m were higher in the ergometrine group compared with the oxytocin group (P < 0.0001).

Conclusions:  We conclude that there is an increase in thoracic epidural pressure after fetal delivery, which appears to be associated with uterine contraction.
The regulation of the Na+,K+ pump in contracting skeletal muscle
Authors: NIELSEN O.B. , HARRISON A.P.
Published: May 2003

Increased passive Na+,K+ fluxes necessitate an efficient activation of the Na+,K+ pump in working muscles to limit the rundown of the Na+,K+ chemical gradients and ensuing loss of excitability. Several studies have demonstrated an increase in Na+,K+‐pump rate in working muscles, and in electrically stimulated muscles up to a 22‐fold increase in active Na+,K+ transport has been observed. Excitation‐induced increase in intracellular Na+ is believed to be the primary stimulus for Na+,K+ pumping in a contracting muscle. In muscles recovering from electrical stimulation, however, the activity of the pump may stay elevated even after intracellular Na+ has been reduced to below the resting level. Moreover, in rat soleus muscles 10‐s stimulation at 60 Hz induced a 5‐fold increase in the activity of the Na+,K+ pump although mean intracellular [Na+] was unchanged. These findings strongly suggest that a substantial part of the excitation‐induced increase in Na+,K+‐pump activity is caused by mechanisms other than increased intracellular [Na+]. The mechanism behind this activation is not clear, but may involve a change in the affinity of the Na+,K+ pump for intracellular Na+. In addition to intracellular [Na+], the Na+,K+ pump may be stimulated in contracting muscles by other factors such as catecholamines, calcitonin gene‐related peptide (CGRP), free fatty acids and cytoskeletal links. Together, this activation may form a feed forward mechanism protecting muscles from loss of excitability during periods of contraction by increasing Na+,K+‐pump activity prior to erosion of the Na+,K+ chemical gradients. During exercise of high intensity, however, intracellular [Na+] increases substantially constituting an additional stimulus for the pump.