bluuebunny/crossref_metadata_2025 huggingface dataset:
Access of Quaternary Ammonium Blockers to the Internal Pore of Cyclic Nucleotide-gated Channels: Implications for the Location of the Gate
Authors: Contreras Jorge E. , Holmgren Miguel
Published: April 2006

Cyclic nucleotide-gated (CNG) channels play important roles in the transduction of visual and olfactory information by sensing changes in the intracellular concentration of cyclic nucleotides. We have investigated the interactions between intracellularly applied quaternary ammonium (QA) ions and the α subunit of rod cyclic nucleotide-gated channels. We have used a family of alkyl-triethylammonium derivatives in which the length of one chain is altered. These QA derivatives blocked the permeation pathway of CNG channels in a concentration- and voltage-dependent manner. For QA compounds with tails longer than six methylene groups, increasing the length of the chain resulted in higher apparent affinities of ∼1.2 RT per methylene group added, which is consistent with the presence of a hydrophobic pocket within the intracellular mouth of the channel that serves as part of the receptor binding site. At the single channel level, decyltriethyl ammonium (C10-TEA) ions did not change the unitary conductance but they did reduce the apparent mean open time, suggesting that the blocker binds to open channels. We provide four lines of evidence suggesting that QA ions can also bind to closed channels: (1) the extent of C10-TEA blockade at subsaturating [cGMP] was larger than at saturating agonist concentration, (2) under saturating concentrations of cGMP, cIMP, or cAMP, blockade levels were inversely correlated with the maximal probability of opening achieved by each agonist, (3) in the closed state, MTS reagents of comparable sizes to QA ions were able to modify V391C in the inner vestibule of the channel, and (4) in the closed state, C10-TEA was able to slow the Cd2+ inhibition observed in V391C channels. These results are in stark contrast to the well-established QA blockade mechanism in Kv channels, where these compounds can only access the inner vestibule in the open state because the gate that opens and closes the channel is located cytoplasmically with respect to the binding site of QA ions. Therefore, in the context of Kv channels, our observations suggest that the regions involved in opening and closing the permeation pathways in these two types of channels are different.
ArrayCluster: an analytic tool for clustering, data visualization and module finder on gene expression profiles
Authors: Yoshida Ryo , Higuchi Tomoyuki , Imoto Seiya , Miyano Satoru
Published: April 2006

Summary: One of the significant challenges in gene expression analysis is to find unknown subtypes of several diseases at the molecular levels. This task can be addressed by grouping gene expression patterns of the collected samples on the basis of a large number of genes. Application of commonly used clustering methods to such a dataset however are likely to fail owing to over-learning, because the number of samples to be grouped is much smaller than the data dimension which is equal to the number of genes involved in the dataset. To overcome such difficulty, we developed a novel model-based clustering method, referred to as the mixed factors analysis. The ArrayCluster is a freely available software to perform the mixed factors analysis. It provides us some analytic tools for clustering DNA microarray experiments, data visualization and an automatic detector for module transcriptional of genes that are relevant to the calibrated molecular subtypes and so on.

Availability: The ArrayCluster can be used free of charge for non-commercial and academic use and downloaded from

Contact:  yoshidar@ims.u-tokyo.ac.jp
A comprehensive catalog of human KRAB-associated zinc finger genes: Insights into the evolutionary history of a large family of transcriptional repressors
Authors: Huntley Stuart , Baggott Daniel M. , Hamilton Aaron T. , Tran-Gyamfi Mary , Yang Shan , Kim Joomyeong , Gordon Laurie , Branscomb Elbert , Stubbs Lisa
Published: April 2006

Krüppel-type zinc finger (ZNF) motifs are prevalent components of transcription factor proteins in all eukaryotes. KRAB-ZNF proteins, in which a potent repressor domain is attached to a tandem array of DNA-binding zinc-finger motifs, are specific to tetrapod vertebrates and represent the largest class of ZNF proteins in mammals. To define the full repertoire of human KRAB-ZNF proteins, we searched the genome sequence for key motifs and then constructed and manually curated gene models incorporating those sequences. The resulting gene catalog contains 423 KRAB-ZNF protein-coding loci, yielding alternative transcripts that altogether predict at least 742 structurally distinct proteins. Active rounds of segmental duplication, involving single genes or larger regions and including both tandem and distributed duplication events, have driven the expansion of this mammalian gene family. Comparisons between the human genes and ZNF loci mined from the draft mouse, dog, and chimpanzee genomes not only identified 103 KRAB-ZNF genes that are conserved in mammals but also highlighted a substantial level of lineage-specific change; at least 136 KRAB-ZNF coding genes are primate specific, including many recent duplicates. KRAB-ZNF genes are widely expressed and clustered genes are typically not coregulated, indicating that paralogs have evolved to fill roles in many different biological processes. To facilitate further study, we have developed a Web-based public resource with access to gene models, sequences, and other data, including visualization tools to provide genomic context and interaction with other public data sets.
Evolutionary expansion and divergence in the ZNF91 subfamily of primate-specific zinc finger genes
Authors: Hamilton Aaron T. , Huntley Stuart , Tran-Gyamfi Mary , Baggott Daniel M. , Gordon Laurie , Stubbs Lisa
Published: April 2006

Most genes are conserved in mammals, but certain gene families have acquired large numbers of lineage-specific loci through repeated rounds of gene duplication, divergence, and loss that have continued in each mammalian group. One such family encodes KRAB-zinc finger (KRAB-ZNF) proteins, which function as transcriptional repressors. One particular subfamily of KRAB-ZNF genes, includingZNF91,has expanded specifically in primates to comprise more than 110 loci in the human genome. Genes of the ZNF91 subfamily reside in large gene clusters near centromeric regions of human chromosomes 19 and 7 with smaller clusters or isolated copies in other locations. Phylogenetic analysis indicates that many of these genes arose before the split between the New and Old World monkeys, but the ZNF91 subfamily has continued to expand and diversify throughout the evolution of apes and humans. Paralogous loci are distinguished by divergence within their zinc finger arrays, indicating selection for proteins with different regulatory targets. In addition, many loci produce multiple alternatively spliced transcripts encoding proteins that may serve separate and perhaps even opposing regulatory roles because of the modular motif structure of KRAB-ZNF genes. The tissue-specific expression patterns and rapid structural divergence of ZNF91 subfamily genes suggest a role in determining gene expression differences between species and the evolution of novel primate traits.
Unbiased location analysis of E2F1-binding sites suggests a widespread role for E2F1 in the human genome
Authors: Bieda Mark , Xu Xiaoqin , Singer Michael A. , Green Roland , Farnham Peggy J.
Published: April 2006

The E2F family of transcription factors regulates basic cellular processes. Here, we take an unbiased approach towards identifying E2F1 target genes by examining localization of E2F1-binding sites using high-density oligonucleotide tiling arrays. To begin, we developed a statistically-based methodology for analysis of ChIP-chip data obtained from arrays that represent 30 Mb of the human genome. Using this methodology, we identified regions bound by E2F1, MYC, and RNA Polymerase II (POLR2A). We found a large number of binding sites for all three factors; extrapolation suggests there may be ∼20,000–30,000 E2F1- and MYC-binding sites and ∼12,000–17,000 active promoters in HeLa cells. In contrast to our results for MYC, we find that the majority of E2F1-binding sites (>80%) are located in core promoters and that 50% of the sites overlap transcription starts. Only a small fraction of E2F1 sites possess the canonical binding motif. Surprisingly, we found that ∼30% of genes in the 30-Mb region possessed an E2F1 binding site in a core promoter and E2F1 was bound near to 83% of POLR2A-bound sites. To determine if these results were representative of the entire human genome, we performed ChIP-chip analyses of ∼24,000 promoters and confirmed that greater than 20% of the promoters were bound by E2F1. Our results suggest that E2F1 is recruited to promoters via a method distinct from recognition of the known consensus site and point toward a new understanding of E2F1 as a factor that contributes to the regulation of a large fraction of human genes.
Using stable isotope ratios as a tracer of feeding adaptation in released Japanese flounder Paralichthys olivaceus
Authors: Watanabe S. , Isshiki T. , Kudo T. , Yamada A. , Katayama S. , Fukuda M.
Published: April 2006

Release‐recapture experiments were conducted to examine temporal changes of the carbon and nitrogen stable isotope (δ13C and δ15N) ratios in the muscle tissue of artificially produced Japanese flounder Paralichthys olivaceus, juveniles. About 9000 juveniles (mean ± s.d. 43·3 ± 5·2 mm in standard length and 1·07 ± 0·37 g, n = 15) were released in each of three coastal areas: Chojagasaki, Arasaki and Jogashima with different geographical conditions, along Sagami Bay, Pacific coast of central Japan. Recapture efforts were made on 4, 11, 18, 40 and 55 days after the release. The stable isotope ratios, RNA:DNA ratio, stomach content mass (per body mass Msc) and condition factor (K) of recaptured individuals were measured. The mean ± s.d. δ13C and δ15N values (n = 15) were −18·3 ± 0·2‰ and 12·2 ± 0·2‰, respectively at the release. Wild Japanese flounder juveniles were captured only in Chojagasaki, and the δ13C and δ15N values (n = 6) were −14·0 ± 0·4‰ and 13·2 ± 0·7‰, respectively; these values were considered to represent the wild diet. Nutritional conditions of the released and recaptured juveniles as determined by the RNA : DNA ratio, MSC and K were indicated to be the best in Chojagasaki, in which the stable isotope ratios gradually shifted towards and reached the wild values within 40 days. This result along with stomach content analyses suggested that the released juveniles had acquired a wild feeding habit. In Arasaki and Jogashima, nutritional conditions of the recaptured juveniles were poorer, with no clear changes in the stable isotope ratios. Greatly varied stable isotope ratio values were observed in the juveniles recaptured in Chojagasaki 11 days after the release, ranging from the release levels to the wild levels. The extent of changes in the stable isotope ratios had a positive correlation to the RNA : DNA ratio and K of these juveniles (r = 0·87, n = 10 and r = 0·83, n = 18, respectively). The analyses of stable isotope ratios coupled with nutritional condition were considered to be an effective tool to examine post‐release feeding adaptation of Japanese flounder juveniles.
Effects of cyclic and constant hydrostatic pressure on norepinephrine and epinephrine levels in the brain of flounder
Authors: Damasceno‐Oliveira A. , Fernández‐Durán B. , Gonçalves J. , Serrão P. , Soares‐Da‐Silva P. , Reis‐Henriques M. A. , Coimbra J.
Published: April 2006

The effects of cyclic and constant hydrostatic pressure on the norepinephrine and epinephrine content in discrete regions of the brain of European flounder Platichthys flesus were studied. After a 14 day exposure to cyclic hydrostatic pressure with a tidal period of 12·4 h and with a maximum peak of 800 kPa (range 200–800 kPa of absolute hydrostatic pressure), fish showed a highly significant decrease in norepinephrine content when compared to control animals held at constant atmospheric pressure. No changes were detected in fish submitted to a constant hydrostatic pressure of 800 kPa.
Sensory‐motor function of human periodontal mechanoreceptors*
Authors: TRULSSON M.
Published: April 2006

summary  Natural teeth are equipped with periodontal mechanoreceptors that signal information about tooth loads. In the present review, the basic force‐encoding properties of human periodontal receptors will be presented along with a discussion about their likely functional role in the control of human mastication. Microneurographic recordings from single nerve fibres reveal that human periodontal receptors adapt slowly to maintained tooth loads. Most receptors are broadly tuned to the direction of force application, and about half respond to forces applied to more than one tooth. Populations of periodontal receptors, nevertheless, reliably encode information about both the teeth stimulated, and the direction of forces applied to the individual teeth. Information about the magnitude of tooth loads is made available in the mean firing rate response of periodontal receptors. Most receptors exhibit a markedly curved relationship between discharge rate and force amplitude, featuring the highest sensitivity to changes in tooth load at very low force levels (below 1 N for anterior teeth and 4 N for posterior teeth). Thus, periodontal receptors efficiently encode tooth load when subjects contact and gently manipulate food using the teeth. It is demonstrated that signals from periodontal receptors are used in the fine motor control of the jaw and it is clear from studies of various patient groups (e.g. patients with dental implants) that important sensory‐motor functions are lost or impaired when these receptors are removed during the extraction of teeth.
Protective role of supplement with foreign Bifidobacterium and Lactobacillus in experimental hepatic ischemia‐reperfusion injury
Authors: Xing Hui‐Chun , Li Lan‐Juan , Xu Kai‐Jin , Shen Tian , Chen Yun‐Bo , Sheng Ji‐Fang , Chen Yu , Fu Su‐Zhen , Chen Chun‐Lei , Wang Jian‐Guo , Yan Dong , Dai Fang‐Wei , Zheng Shu‐Sen
Published: April 2006

Background and Aim:  Intestinal microflora play a crucial role in some severe liver diseases. The purpose of this study was to evaluate the effects of a Lactobacillus strain and a Bifidobacterium strain on ischemia‐reperfusion (I/R) liver injury.

Methods:  Rats were divided into six groups. Each group received either Bifidobacterium Catenulatum ZYB0401; Lactobacillus Fermentum ZYL0401; a mixture of these two bacterial strains; gentamicin; or saline by daily gavage for 7 days. On the sixth day, all rats, except those in the control group, were subjected to 20 min of liver ischemia. After 22 h of hepatic reperfusion, liver enzymes and histology, malondialdehyde (MDA), superoxide dismutase (SOD), endotoxemia, serum tumor necrosis factor‐α (TNF‐α), intestinal bacteria, intestinal mucosal ultrastructure, and bacterial translocation were studied.

Results:  All administered bacteria increased intestinal Bifidobacterium and Lactobacillus, decreased endotoxemia (P < 0.01), alanine aminotransferase (ALT) (P < 0.01), and markedly ameliorated liver histology and intestinal mucosal ultrastructure. Only rats treated with Bifidobacterium Catenulatum ZYB0401 and Lactobacillus Fermentum ZYL0401 showed reduced incidence of bacterial translocation to the kidney (P < 0.05), associated with decreased serum TNF‐α and liver MDA (P < 0.05) and increased liver SOD (P < 0.05) compared to the I/R group. Gentamicin decreased almost all kinds of intestinal bacteria (P < 0.01) and decreased ALT (P < 0.01) and serum TNF‐α, but failed to reduce both endotoxemia and the incidence of bacterial translocation and had no effects on liver MDA and SOD.

Conclusion:  Bifidobacterium Catenulatum ZYB0401 in combination with Lactobacillus Fermentum ZYL0401 could be useful in restoring intestinal microflora and in preventing liver injury in hepatic I/R of rats.
Extranodal conjunctival Hodgkin's‐like lymphoma in a cat
Authors: Holt Elaine , Goldschmidt Michael H. , Skorupski Katherine
Published: April 2006

A seven‐year‐old female spayed Domestic Short‐haired cat was brought for examination following a four‐month history of conjunctivitis in the right eye. The superior palpebral conjunctiva was diffusely swollen and firm, displacing the right globe ventrally and preventing full closure of the eyelids. The right popliteal lymph node was enlarged as were several other peripheral lymph nodes. An incisional biopsy of the conjunctival swelling revealed a lymphoid neoplasm, the cellular make up of which suggested features of feline Hodgkin's‐like lymphoma. Although the neoplasm was poorly responsive to standard chemotherapeutic protocols for lymphoma, radiation therapy rapidly reduced its size. Three years following the initial diagnosis, there has been no recurrence of the conjunctival neoplasm. To the authors’ knowledge, there are no previous reports of extranodal or adnexal (conjunctiva, eyelid, orbit) Hodgkin's‐like lymphoma in the veterinary literature.
Calcification associated with the nasolacrimal system of a horse: case report and mineralogic composition
Authors: Cassotis Nicholas J. , Schiffman Peter
Published: April 2006

A 12‐year‐old Paso Fino mare was evaluated for a chronic nasal and ocular discharge. A calcification was identified eroding through the nasal mucosa of the middle meatus. Differential considerations for this mass included dacryolith, nasal calculus, or calcified tooth root abscess. Anatomical location and case history and progression supported a dacryolith. Following removal, the calculus was submitted for mineralogic analysis. The calculus was primarily carbonate hydroxylapatite (Ca10(PO4)3(CO3)3(OH)2) with a minor NaCl halite constituent. Dacryoliths, or nasolacrimal calculi, are an uncommon occurrence in animals, and sparsely reported in humans. The etiopathogenesis of dacryolith formation is unknown. The objective of this article was to report the first case report of an equine nasolacrimal system dacryolith and its mineralogic composition.
Interspecies variation in orbital bone structure of psittaciform birds (with emphasis on Psittacidae)
Authors: Machado Marcello , Dos Santos Schmidt Elizabeth Moreira , Montiani‐Ferreira Fabiano
Published: April 2006

Objective  This text presents an anatomical study of the normal bony orbital structure of a sample of different bird species belonging to the order Psittaciformes.

Procedures  The bony anatomy of Psittaciformes’ skulls was examined and described using cadavers of birds that were presented already dead to the Federal University of Paraná, Brazil or had been euthanized for humane reasons. Dissections of the orbital cavity were performed under 2–4 × magnification, and descriptions of the orbital bones were made from observations of macerated skulls that had been boiled and cleaned. The present paper discusses the main features of the bony orbit of psittaciform birds, describing known anatomical information but also bringing new information, mainly concerning species differences that might help not only veterinary anatomists but also zoologists, clinicians, researchers, and students of veterinary ophthalmology to better comprehend this order of birds.

Results and conclusions  Variations in the anatomic conformation of the bony elements of the orbit were observed in different species of Psittaciformes. Based on these differences, Psittaciformes were classified into two different groups. The first group of Psittaciformes shows an enclosed (complete) bony orbit formed by the junction of the orbital with the postorbital processes, creating a suborbital arch. The second group of Psittaciformes essentially lacked a suborbital arch, presenting an open (incomplete) bony orbit, typical of most modern birds. In the latter group, orbital and postorbital processes are present.
Topical effect of various agents on gelatinase activity in the tear film of normal dogs
Authors: Couture Simon , Doucet Michèle , Moreau Maxime , Carrier Michel
Published: April 2006

Objective  To evaluate the topical effect of various agents, currently used in the treatment of melting ulcers, on gelatinase activity present in the tear film of normal dogs.

Animal studied  Eight normal adult beagles.

Procedures  Each animal received the following agents: cyclosporine A 1%, N‐acetylcysteine 10%, ciprofloxacin 0.3%, ethylenediaminetetraacetic acid (EDTA) 1%, doxycycline 0.001%, polysulfated glycosaminoglycans (PSGAG) 5%, autoserum, and artificial tears during a 48‐h period following a Latin square design. Tear samples were collected with micro‐capillary pipettes following a corneal surface irrigation of each eye with sterile saline on four different occasions. Basal and total gelatinase activities were evaluated by optical density after processing in a commercial gelatinase activity assay. From the optical density ratio, a semi‐quantitative measure of gelatinase activity was obtained. Basal and total activities were measured in all samples.

Results  The lowest total gelatinase activity, representing a percent decline in the enzyme activity although not significant, was observed 1 h after the last treatment in seven out of the eight ophthalmic agents; EDTA (68%), ciprofloxacin (76%), cyclosporine A (68%), doxycycline (47%), artificial tears (26%), PSGAG (25%), and N‐acetylcysteine (20%). However, only the reduction observed with EDTA 6 h after the last treatment was significantly lower compared to the reduction observed with the artificial tears.

Conclusion  This study indicated that only EDTA was able to significantly reduce the gelatinase activity in a persistent manner in the tear film of normal canine eyes. Further studies will be required to evaluate the effect of EDTA under ulcerative conditions and to more accurately ascertain the potential in vivo effect of the other agents.
PrimaryAspergillusandFusariumkeratitis in a Holstein cow
Authors: Elligott Colleen R. , Wilkie David A. , Kuonen Vanessa J. , Bras I. Dineli , Neihaus Andrew
Published: April 2006

A 5‐year‐old female Holstein cow was examined for ocular discharge, periorbital swelling, an area of full‐thickness corneal cellular infiltrate, fibrin, hypopyon, diffuse corneal edema, and miosis. The patient was diagnosed with a corneal stromal abscess and secondary anterior uveitis. Histopathology, mycotic culture, and polymerase chain reaction positive forAspergillusandFusariumDNA confirmed the presence of fungal infection. Response to therapy was adequate, and follow‐up with the patient 1 year after diagnosis revealed a focal area of corneal fibrosis.
Semantic learning designs: recording assumptions and guidelines
Authors: Sicilia Miguel‐Angel
Published: April 2006

Recent developments in the standardisation of learning technology have resulted in models of learning activities and resources including descriptive metadata and definitions of conditional flows for multirole activities. Nonetheless, such learning designs are actually representations of the results of the design process and do not provide information about the rationale of the design, ie, about the theoretical standpoints, assumptions or guidelines applied to come up with the concrete arrangement of activities. These latter elements are critical not only for informative reasons, but as a medium towards the end of connecting theories and hypotheses to actual practice and analysing the resulting empirical data as a form of inquiry on the validity of theoretical assumptions. This paper delineates the main aspects of a schema for the recording of such design rationales using an ontological approach. The method for the engineering of the schema was based on connecting the definitions provided with an existing large ontological base, thus reusing a large amount of common sense knowledge. Two paradigmatic example positions of the range of aspects that could be covered by the representation language are described as an illustration. The resulting ontological definitions can be used as a foundation for the refinement of theoretical positions and for their comparative assessment.
TM4L: Creating and browsing educational topic maps
Authors: Dicheva Darina , Dichev Christo
Published: April 2006

In this article, we describe TM4L, an environment for building, maintaining and using standards‐based, ontology‐aware e‐learning repositories. It is based on the idea that concept‐driven access to learning material implemented as a topic map can bridge the gap between a learner and targeted knowledge. One of the driving goals of this work is to increase the reusability of available educational resources by enabling the use of a developed subject ontology with courses on the same subject with different stricture. Another goal of TM4L is to support an efficient context‐based retrieval of learning content tailored to the needs of a learner working on an educational task. The paper focuses on three aspects of the TM4L environment: domain modelling, editing capabilities and the interface for exploring the learning collection. The key features of the TM4L functionality are illustrated with some examples.
e‐Learning for depth in the Semantic Web
Authors: Shafrir Uri , Etkind Masha
Published: April 2006

In this paper, we describe concept parsing algorithms, a novel semantic analysis methodology at the core of a new pedagogy that focuses learners’ attention on deep comprehension of the conceptual content of learned material. Two new e‐learning tools are described in some detail: interactive concept discovery learning and meaning equivalence reusable learning objects. These semantic technologies were developed at the Ontario Institute for Studies in Education and Adaptive Technology Resource Centre of Faculty of Information Studies (ATRC/FIS) at the University of Toronto; they were tested since 2001 in several academic institutions in Canada and at the Russian Academy of Sciences (patents pending: US patent 6,953,344 B2, USPO ♯20050149510; Copyright 2005, PARCEP Inc.). We describe the rationale for developing these instructional tools, their main characteristics and results of several evaluative implementations that show their potential to enhance learning outcomes and to provide authentic, credible, evidence‐based formative assessments of learning processes.
Towards a semantic e‐learning theory by using a modelling approach
Authors: Yli‐Luoma Pertti V. J. , Naeve Ambjörn
Published: April 2006

In the present study, a semantic perspective on e‐learning theory is advanced and a modelling approach is used. This modelling approach towards the new learning theory is based on the four SECI phases of knowledge conversion: Socialisation, Externalisation, Combination and Internalisation, introduced by Nonaka in 1994, and involving two levels of knowledge—tacit and explicit. In the Socialisation phase, the teacher–student interaction activates the exploratory learning behaviour. This phase is emotionally and socially loaded. The Externalisation phase is partly emotional but a cognitive dimension is also needed, which requires creativity. This phase works optimally if it is collaborative in nature. In the Combination phase, an ability for hypothetical–deductive thinking is needed for the modelling approach. During the Internalisation phase, the learning process requires that students engage in seeking to understand and explain natural phenomena, which further demands testing of the theoretical concepts.
Semantic e‐learning: synthesising fantasies
Authors: Lytras Miltiadis , Naeve Ambjörn
Published: April 2006

When the subject of scientific analysis is learning, the research needs to be anchored in various nonmonolithic pillars. Several disciplines require a common ground of convergence. An objective observer of the domain can easily conclude that semantic e‐learning brings together the three different worlds of learners, pedagogues and technologists.

In this short concluding paper of the special issue, we criticise the monolithic approaches to technology‐enhanced learning. We argue that semantic e‐learning presents a critical research challenge to move towards extended openness, meaning exploitation and unforeseen learning opportunities for the global community.

The concluding remark is a call for a new learning generation primer. Synthesizing fantasies is in fact an invitation to semantically define our commitment to collaborate and to agree on the technology‐enabled services that bring learning to the forefront. The promotion of the knowledge‐and‐learning‐society requires an integration of the demand and supply side of knowledge and learning.
Holding the Line: Human Rights Defenders in the Age of Terror
Authors: Landman Todd
Published: April 2006

Human rights defenders have received renewed attention in the current period owing to new institutional and normative developments at the international level and renewed targeting by states at the domestic level. Human rights NGOs have begun to argue more forcefully that human rights defenders are more at risk from attack by their governments under the guise of the ‘war on terror’, an assertion that is supported by the fact that an increasing number of states have enacted anti-terror legislation. Using a cross-national data set of 195 countries for the period 1997 to 2003, this article explores the main factors that account for the cross-national variation in acts of abuse against human rights defenders in the post 9/11 era, including the presence of anti-terror legislation. In addition to the examination of the effects of democracy, economic development, intra-state war, population size and US overseas aid, the analysis shows that while reported abuse against human rights defenders has indeed increased since 2001, this increase is not attributable to the enactment of anti-terror legislation, a finding that is further mediated by the fact that just over half of the countries that have enacted such legislation are democracies.
What Does ‘Efficiency’ Mean in the Context of the Global Refugee Regime?
Authors: Betts Alexander
Published: April 2006

The language of ‘efficiency’ has increasingly been used as a rhetorical device to legitimate new approaches to refugee policy; in particular, extraterritorial processing and ‘protection-in-regions-of-origin’. This article aims to explore what ‘efficiency’ might mean from the perspective of the global refugee regime in order to, firstly, expose the hidden assumptions implicit in the use of the ‘efficiency’ discourse in the current debate and, secondly, to explore what the concept might offer in defining the normative contours of a future regime structure. Although the concept is acknowledged to be inevitably political and to carry epistemological assumptions, reconstructing the concept by drawing on economic theory is argued to offer a means to improve the quality of debate on the allocation of resources within the refugee regime. Indeed, a critical application of the concepts of productive, allocative and dynamic efficiency is shown to offer far more nuanced insights for sustainable refugee protection than is implied by the contemporary debate's political manipulation of the term. The article assesses both the theoretical and policy implications that derive from a more rigorous conceptualisation of the meaning of efficiency.
Rating 20th-Century British Prime Ministers
Authors: Theakston Kevin , Gill Mark
Published: April 2006

This article reports the results of a 2004 survey of academics, specialising in British politics and/or modern British history, asking them to rate all the 20th-century British prime ministers in terms of their success in office and also asking them to assess the key characteristics of successful prime ministers. The top-ranked PMs were (in order) Attlee, Churchill, Lloyd George and Thatcher. In contrast to the many and regular surveys of American academics ranking US presidents, this is the first large-scale exercise of this type in British political science. Analysis of the findings in terms of the characteristics of the survey respondents helps shed light on the survey results.
Global Production and Currency Devaluation*
Authors: Zhao Laixun , Xing Yuqing
Published: April 2006

We model the production allocation choices of a multinational enterprise (MNE) in a three‐country framework—one northern country and two southern ones. Products made in the South are of lower quality than those made in the North. Substitutability between goods differs due to variations in product quality. We investigate how exchange rates affect production, employment, and welfare, and find that currency devaluation from different countries brings contrasting results. In particular, an appreciation in the southern country (X) producing the lowest‐quality good with the least cost may reduce production (employment) in the North, while an appreciation in the other southern currency (Y) always does the opposite. A northern depreciation against both southern currencies may increase production in country X, but always reduces that in country Y. These arise because the MNE shifts production globally to minimize costs. Northern welfare always falls following currency appreciation in southern countries.
Strategic Exports and R&D with Internationally Mobile Skilled Labor and Exchange Rate Volatility*
Authors: Lahiri Sajal , Mesa Fernando
Published: April 2006

This paper extends the Spencer and Brander (1983) model of strategic exports and R&D by introducing exchange rate volatility and R&D activities that require internationally mobile skilled labor. We find that an increased volatility reduces both the levels of optimal export subsidy and R&D tax. We also find that the endogeneity of skilled wage increases the level of export subsidy and reduces the level of R&D tax if the country is an exporter of skilled labor.
Investment under Trade Policy Uncertainty: an Empirical Investigation*
Authors: Sudsawasd Sasatra , Moore Robert E.
Published: April 2006

The link between trade policy uncertainty and the share of investment in GDP per capita is investigated using panel data drawn from over a hundred countries for the period 1960–2000. Five indicators of trade policy are used. Two specifications of volatility for each of the trade policy indicators are constructed as measures of trade policy uncertainty. Panel regression results suggest a robust correlation between the volatility of trade policy indicators and the investment share. A significant negative impact of trade policy volatility on the investment share is found in most trade policy indicators with an exception—the volatility of the trade share indicator more closely associated with volatility in quantity than in prices has a significant positive impact on the investment share.
DO WEALTH DIFFERENCES AFFECT FAIRNESS CONSIDERATIONS?*
Authors: Armantier Olivier
Published: April 2006

The influence of relative wealth on fairness considerations is analyzed in an ultimatum game experiment in which participants receive large and widely unequal initial endowments. Subjects initially demonstrate a concern for fairness. With time however, behavior becomes at odds with both subgame perfection and fairness. Evidence of learning is detected for both proposers and receivers in the estimation of a structural reinforcement learning model. The estimation results suggest that, guided by foregone best responses and an acquired sense of deservingness, rich subjects become more selfish, whereas poor subjects, influenced only by their own experience, learn to tolerate this behavior.
COHABITATION, MARRIAGE, AND DIVORCE IN A MODEL OF MATCH QUALITY*
Authors: Brien Michael J. , Lillard Lee A. , Stern Steven
Published: April 2006

The objective of this research is to further our understanding of how and why individuals enter and leave coresidential relationships. We develop and estimate an economic model of nonmarital cohabitation, marriage, and divorce that is consistent with current data on the formation and dissolution of relationships. Jovanovic's (Journal of Political Economy 87 (1979), 972–90) theoretical matching model is extended to help explain household formation and dissolution behavior. Implications of the model reveal what factors influence the decision to start a relationship, what form this relationship will take, and the relative stability of the various types of unions. The structural parameters of the model are estimated using longitudinal data from a sample of female high school seniors from the United States. New numerical methods are developed to reduce computational costs associated with estimation. The empirical results have interesting interpretations given the structural model. They show that a significant cause of cohabitation is the need to learn about potential partners and to hedge against future bad shocks. The estimated parameters are used to conduct several comparative dynamic experiments. For example, we show that policy experiments changing the cost of divorce have little effect on relationship choices.
Evaluation of a Waiting List Initiative in a Child and Adolescent Mental Health Service
Authors: Clemente Carmen , McGrath Rita , Stevenson Clare , Barnes Jacqueline
Published: April 2006

Background:  The aim of the study was to evaluate Initial Assessment (IA), a new system for managing referrals. The system is designed to: reduce waiting times, reduce ‘did not attend’ (DNA) rates, and improve multi‐disciplinary team working and team morale, compared to the existing referral procedure.

Method:  A comparison was made between a child mental health service using IA and a second centre using the existing system over a 6‐month period, based on administrative records, a child functioning measure, staff and user questionnaires.

Results:  The Initial Assessment system was associated with a significantly shorter average waiting time for the first appointment (9 weeks) and a lower DNA rate (10%) in the intervention centre. The populations seen under the new and existing systems were similar in terms of the severity of cases. Staff reported a positive impact overall on team working and team morale, despite a reported individual increase in time pressure; users reported acceptance of the system.

Conclusions:  Findings suggest that the increase in team morale and support from colleagues associated with the new system may have mediated against any negative impact of the increased time pressure. Substantial cost savings to the NHS are indicated.
Recent Developments in Anorexia Nervosa
Authors: Bryant‐Waugh Rachel
Published: April 2006

Background:  This review summarises recent clinical developments, topics of debate, and research findings in relation to anorexia nervosa in children and adolescents. Following an update of diagnostic and prevalence issues, recent developments in treatment approaches are discussed. These cover recommendations for the medical management of anorexia nervosa in young people, as well as psychological interventions for children, adolescents and their families. The question of which type of service setting is most appropriate for the treatment of young people with anorexia nervosa remains a subject of discussion, and recent guidance and work in this area is presented. Finally, the ongoing relatively poor prognosis in terms of general mental health associated with anorexia nervosa is highlighted and the implications for CAMHS practitioners discussed.
Neurofibromatosis and Attentional Deficits: An Illustrative Example of the Common Association of Medical Causes with Behavioural Syndromes, Implications for General Child Mental Health Services
Authors: Philip Rebecca , Turk Jeremy
Published: April 2006

Background:   Neurofibromatosis type 1 (NF1) is a common autosomal dominant gene disorder. In addition to well described physical and cognitive features certain behavioural patterns have been reported. Clear association has been shown between NF1 and attention deficit hyperactivity disorder (ADHD), with up to half of children with NF1 fulfilling DSM‐IV diagnostic criteria for ADHD. This article aims to increase awareness among child mental health workers of the common link between genetic conditions (like NF1) and ADHD, thus improving diagnosis and intervention.
Morphometric Parameters of Purkinje Dendritic Networks after Ethanol Treatment during Aging
Authors: Pentney R. J. , Quigley P. J.
Published: April 2006

Spine densities on terminal branches of Purkinje cell dendrites of Fischer 344 rats were significantly altered by ethanol treatment and aging processes. An effect of the control liquid diet on the lengths of terminal branches and an interaction effect of this diet with age on the numbers of terminal branches/cell also occurred, but there were no detectable interaction effects of ethanol with age on dendritic parameters. Changes in spine density on terminal branches, which accounted for 63–67% of the total dendritic length/cell, represented a major quantitative modulation of synaptic input to these neurons during age and following ethanol treatment.
Relationship between Acute Ethanol‐related Responses in Long‐Sleep and Short‐Sleep Mice
Authors: Baker Rodney C. , Smolen Andrew , Smolen Toni N. , Deitrich R. A.
Published: April 2006

Long sleep (LS) and short sleep (SS) lines of mice were derived from a heterogeneous stock of mice (HS) and have been selectively bred on the basis of the time the animals were devoid of the righting reflex (sleep time) following acute ethanol administration. We have tested a large group of the HS mice for sleep time response to ethanol. Animals were then selected from the extremes of the HS sleep time response and designated short sleep (HS‐SS) or long sleep (HS‐LS). The ED50 value for loss of righting reflex was compared between these mice (HS‐SS and HS‐LS) and animals that had undergone 25 generations of selection (SS and LS mice). The ED50 value was not significantly different for the HS‐LS (1.9 g/kg) and LS (2.17 g/kg) mice but was markedly different between HS‐SS (3.02 g/kg) and SS (4.21 g/kg) mice. The ED50 values for the eight inbred strains that constituted the HS stock ranged only from 2.33 to 2.78 g/kg. The value for LD50 one hour after ethanol administration was found to be 9.03 g/kg and for SS mice 6.94 g/kg for LS mice, in contrast to our previous findings of no difference in LD50 values between SS and LS mice when ascertained 24 hr after the ethanol dose.

Since the two lines were selected only for a sleep time difference, a differential sensitivity to other consequences of acute ethanol exposure, such as the lethal dose, would not be expected unless the effects shared a common genetic mechanism of action with ethanol sleep time. The results also suggest that selection for loss of righting reflex was accomplished prior to complete divergence of sleep time. Comparison of the ethanol response distributions between the selected lines and the extremes of the HS stock indicate asymmetrical selection of both dose‐dependent initial loss of righting reflex and sleep time.
Covalent Binding of Acetaldehyde to Proteins: Participation of Lysine Residues
Authors: Tuma Dean J. , Newman Monte R. , Donohue Terrence M. , Sorrell Michael F.
Published: April 2006

The results of this study demonstrate that lysine is the major amino acid participating in the binding of acetaldehyde to proteins. The formation of both stable and unstable acetaldehyde‐albumin adducts was shown to occur via the reaction of acetaldehyde with lysine residues. This conclusion was based on the following experimental evidence: (a) the ratio of stable to unstable adducts of bovine serum albumin was similar to that observed for polylysine; (b) acetylation of albumin markedly reduced acetaldehyde binding; (c) the radioactivity profiles (obtained by high‐performance liquid chromatographic analysis) of [14C]acetaldehyde modified amino acids hydrolyzed from total and stable adducts of albumin were nearly identical to those of polylysine or α‐t‐boc‐lysine. Analysis of stable adducts of albumin indicated two major modified lysine residues; one residue was much more acidic and the other more basic than unmodified lysine. Unstable adducts were shown to be Schiff bases since NaBH4 treatment resulted in the formation of N‐ethyllysine residues. The reducing agents, NaCNBH3 and ascorbic acid, both increased stable adduct formation via increased binding to lysine residues; however, a different elution profile of modified lysine residues was observed for these reducing agents. NaCNBH3 increased the formation of N‐ethyllysine residues exclusively, whereas ascorbate increased the formation of the acidic adduct of lysine and also caused the formation of an additional modified lysine residue which was present only in the ascorbate‐treated polypeptides. In addition to their detection by radioactivity measurements, the acetaldehyde‐lysine adducts could also be detected by the fluorescence of their ophthalaldehyde derivatives. Therefore, the potential exists for the detection of acetalde‐hyde‐protein adducts in chronically ethanol‐fed animals and in alcoholic patients without the use of radioisotopes.
Essential Fatty Acids, Prostaglandins, and Alcoholism: An Overview
Authors: Horrobin David F.
Published: April 2006

Essential fatty acids (EFAs) are major structural components of the brain and through their effects on membrane properties can influence nerve conduction, transmitter release, and transmitter action. Prostaglandins (PCs) derived from EFAs have profound behavioral effects and are also able to modify conduction and transmitter function. Effects of alcohol on EFAs and PGs are therefore good candidates for explaining at least some of the actions of alcohol on brain function. Ethanol has three main known actions on EFA and PG metabolism: it reduces blood linoteic acid levels and induces or exaggerates EFA deficiency states; it blocks metabolism of linoteic acid to EFA metabolites which are known to be important in brain structure; and it enhances conversion of the linoteic acid metabolite, dihomo‐γ‐linolenic acid, to PGE1. This review demonstrates that some of the short‐term behavioral effects of ethanoi and some of its long‐term adverse effects on brain, liver, and other tissues may be partly explicable in terms of ethanoi actions on EFA and PG metabolism. Modification of such metabolism by dietary and other means has already been shown to influence the effects of alcohol and alcohol withdrawal in both humans and animals. This promises to be a fruitful source of investigation with substantial implications for the understanding and treatment of alcoholism.
Central Nervous System Prostaglandins and Ethanol
Authors: Anton Raymond F , Randall Carrie L
Published: April 2006

There is growing interest in the effect of ethanol on cellular membranes, generally, and neuronal membrane systems, in particular. Perturbations of membranes have led to numerous enzymatically mediated processes, one of which is prostaglandin production. This paper reviews the nature and role of prostaglandins in the central nervous system, and what is known about the effect of ethanol on prostaglandin production in brain. Areas of central nervous system physiological function in which prostaglandins may mediate the actions of ethanol are discussed. Methodological considerations and future directions for research in the area of ethanol and prostaglandins are highlighted.