bluuebunny/crossref_metadata_2025 huggingface dataset:
TIME VARYING RISK PREMIUM AND THE PREDICTIVE POWER OF THE AUSTRALIAN TERM STRUCTURE OF INTEREST RATES
Authors: Alles Lakshman A.
Published: February 2009

Using weekly data on bank accepted bills over the 1976 to 1993 period, this paper provides direct evidence of the presence of a term premium in the Australian term structure. The term premium is shown to vary over time and have an adverse effect on the predictive power of the term structure. The variance of the expected term premium is quantified in terms of its lower bound relative to the upper bound of the variance of the rational expectations error. This ratio is observed to vary over sample sub periods and rise to a high of one in some periods which include the period immediately prior to the market crash.
THE REINSURANCE DECISION IN LIFE INSURANCE FIRMS: AN EMPIRICAL TEST OF THE RISK‐BEARING HYPOTHESIS
Authors: Adams Mike
Published: February 2009

Several explanations have been advanced in the financial economics literature to explain the reinsurance decision in insurance firms. Prominent amongst these is the risk‐bearing hypothesis which holds that reinsurance is motivated by the ability of residual claimants to effectively hedge against operational risk. Since the efficiency of risk‐bearing is influenced by organisational factors, such as ownership structure and firm size, the amount of reinsurance should also vary according to the characteristics of insurance firms. This study tests empirically the hypothesis that reinsurance is related to firm‐specific factors. Using 1988–1993 data gathered from New Zealand's life insurance industry, a fixed‐effects covariance regression model is estimated. Consistent with expectations, the results indicate that reinsurance is associated with smaller and more highly leveraged life insurance entities, and companies with greater underwriting risk. However, contrary to predictions, it also appears that it is stocks and companies with diversified production that tend to reinsure. The risk‐bearing hypothesis thus receives only partial support.
Converting preference shares: An Australian capital structure innovation
Authors: Davis Kevin
Published: February 2009

Converting preference shares (prefs) are a hybrid security involving mandatory conversion into a fixed value of ordinary shares (although some issues have an option‐like conversion value payoff). This paper explains how prefs can be viewed as equivalent to an ordinary share issue plus a swap contract between “old” and “new” shareholders. This perspective is used to illustrate why prefs financing may be chosen when significant information asymmetries exist between management and outside investors. Other factors motivating the use of prefs are examined and their relevance for particular issuers and for the specific design of prefs securities analysed.
Efficient management remuneration plan design: A consideration of specific human capital investments
Authors: Deegan Craig
Published: February 2009

This paper investigates the contractual relationship between the manager and the firm. The results indicate that cross‐sectional variation in the components of management remuneration plans can be explained by variations in the specificity of both the manager's human capital investments and the firm's resources. Where the returns on the firm's resources are relatively more dependent upon (specific to) a particular manager, that manager is more likely to be able to negotiate his/her remuneration. The manager is also more likely to be paid on a long run contingent basis and to be offered deferred forfeitable remuneration. The results also indicate that the greater the firm‐specificity of a manager's human capital investments the greater the likelihood that the manager is offered termination compensation as part of the remuneration package.
The effects of microcomputers on the work of professional accountants
Authors: Ferguson Colin
Published: February 2009

A model of the interrelations between perceptions, anxieties, attitudes, microcomputer use and work outcomes of professional accountants is developed and tested on 157 Big Six accountants. The results show that job satisfaction of professional accountants is directly affected by their attitude toward using microcomputers and by microcomputer use itself. Job performance appears to be only directly affected by microcomputer attitudes, but microcomputer use does not directly affect job performance. Along with perceived ease of use and perceived usefulness, computer anxiety is shown to be an important determinant of microcomputer attitudes—higher levels of computer anxiety negatively affect these attitudes. Conversely, higher levels of perceived ease of use and perceived usefulness heighten individuals' positive attitudes toward using microcomputers. Perceived ease of use and perceived usefulness also indirectly affect microcomputer attitudes through their effect on computer anxiety. The results show that higher levels of perceived ease of use and perceived usefulness result in lower levels of computer anxiety. A surprising result from the study is that while perceived ease of use is shown to directly affect the level of microcomputer usage, perceived usefulness and attitude toward using microcomputers do not.
Determinants of voluntary disclosure of segment information: A re‐examination of the role of diversification strategy
Authors: Aitken Michael , Hooper Cameron , Pickering Joanne
Published: February 2009

This paper explores the determinants of management's decision to voluntarily disclose segment information. It is an extension of McKinnon and Dalimunthe (1993) who investigate the role of six hypothesised determinants. Their results indicate that firm size, industry membership, ownership diffusion, and the level of minority interest are related to the voluntary disclosure of segment information. However, they find that leverage and diversification into related versus unrelated industries are not related to this disclosure. It is the diversification finding that motivates our work. This paper explores the effect of differences in data, differences in samples, and differences in the measurement of diversification on the McKinnon and Dalimunthe (1993) results. Using an alternative definition of diversification, we find diversification strategy, firm size, and the level of minority interest to be related to segment disclosure while the results for ownership diffusion and industry are mixed. We find no support for a leverage effect.
Estimating unobservable valuation parameters for illiquid assets
Authors: Boyle Glenn , Guthrie Graeme , Quigley Neil
Published: February 2009

A problem that often arises in applied finance is one where decision‐makers need to choose a value for some parameter that will affect the cash flows between two parties involved in the operation of an illiquid asset. Because the values of the cash flows also depend on various unobservable parameters, identifying the value of the policy parameter that achieves the desired allocation between the parties is no simple task, often resulting in disputes and the invocation of ad hoc approaches. We show how this problem can be solved using an extension of the well‐known ‘implied volatility’ technique from option pricing, and apply it to the determination of equilibrium rental rates on ground leases of commercial land.
China's Emerging Neoliberal Urbanism: Perspectives from Urban Redevelopment
Authors: He Shenjing , Wu Fulong
Published: February 2009

Abstract: China's urbanization is undergoing profound neoliberal shifts, within which urban redevelopment has emerged in the forefront of neoliberalization. This study aims to understand China's emerging neoliberal urbanism by examining the association between urban redevelopment and neoliberalism. Rather than a deliberate design, neoliberalization in China is a response to multiple difficulties/crises and the desire for rapid development. The neoliberalization process is full of controversies and inconsistencies, which involve conflicts between neoliberal practices and social resistance, and tensions between central and local states. Nevertheless, China's neoliberal urbanism has a responsive and resilient system to cope with the contradictions and imbalances inherent in neoliberalism. Meanwhile, neoliberal urbanism is more tangible at the sub‐national scale, since the local state can most effectively assist neoliberal experiments and manage crises. This study not only contributes to the understanding of China's neoliberal urbanism, but also has multiple implications for neoliberalism studies in general. First, in examining the interrelationship between the state and market, it is the actual effect of legitimizing and facilitating market operation rather than the presence (or absence) of the state that matters. Second, a new nexus of governance has formed in the neoliberalization process. Not only the nation state but also the local state is of great significance in assisting and managing neoliberal projects. Third, this study further validates the importance and necessity of scrutinizing neoliberal practices, in particular the controversies and inconsistencies within the neoliberalization process.
Neoliberalism and the Aestheticization of New Middle‐Class Landscapes
Authors: Pow Choon‐Piew
Published: February 2009

Abstract: If according to Terry Eagleton (The Ideology of the Aesthetic1990:28), the aesthetic is from the start “a contradictory, double‐edged concept”, how are seemingly innocent acts of viewing and consuming aesthetically pleasing landscapes implicated in the neoliberal politics of urban restructuring? Using contemporary Shanghai as a case study, this paper critically examines the role of the aesthetic in the politics of exclusion and urban segregation in post‐Socialist Shanghai where the restructuring and commodification of erstwhile public welfare housing have led to the rapid development of private “middle‐class” gated enclaves. A central objective of this paper is to excavate the underlying cultural politics of neoliberalism and demonstrate how the aestheticization of urban spaces in Shanghai has become increasingly intertwined with and accentuated by neoliberal ideologies and exclusionary practices in the city. Imbricated in the pristine neighborhoods of Shanghai's gated communities are the fault lines of social division and class distinction that are rapidly transforming urban China.
The poorest and most vulnerable? On hazards, livelihoods and labelling of riverine communities in Bangladesh
Authors: Lein Haakon
Published: February 2009

Within the field of hazard research, vulnerability studies have been central to inducing a shift in the perspective on disasters as being primarily inflicted by geophysical events to that of apprehending disasters as destructive outcomes of particular social as well as hazardous environmental conditions. However, the inherent tendency within vulnerability studies to classify certain areas or people as ‘vulnerable’ may in some cases also serve to reinforce popular and/or ingrained prejudices, negative stereotypes and dubious explanations of the living conditions and fate of specific communities that become so labelled. The riverbanks and islands in river courses of Bangladesh have long been portrayed as home to the ‘poorest’ and most vulnerable communities, the widespread assumption being that people would only live in such riverine environments because they have no other options. Drawing on an examination of existing literature on char settlements in Bangladesh and data from a field site in the Jamuna River, this paper argues that the prevailing perceptions and labelling of char dwellers as ‘vulnerable’ people is based on a far too simplistic understanding of both rural migration patterns and the livelihoods obtained in these riverine areas.
To infinity and beyond?: workspace and the multi‐location worker
Authors: Hislop Donald , Axtell Caroline
Published: February 2009

The paper examines the spatial implications of multi‐location work considering how the spaces such workers travel through and work in shape the type of tasks they conduct, how they act to create a workspace in such locations and the implications that this type of working has for how the workplace is conceptualised.
Social workers' attitudes to the law: an Israeli perspective
Authors: Doron Israel , Karpel Mirit , Or‐Chen Keren
Published: February 2009

Doron I, Karpel M, Or‐Chen K. Social workers' attitudes to the law: an Israeli perspective Int J Soc Welfare 2010: 19: 95–103 © 2009 The Author(s), Journal compilation © 2009 Blackwell Publishing Ltd and the International Journal of Social Welfare.

In recent years, there has been a general shift towards integration and cooperation between lawyers and social workers, both professionally and ideologically. The goal of this study was to explore the general attitudes of social workers toward the law. The hypothesis was that, due to the recent legal and professional changes in Israel, social workers would express positive attitudes towards the law. For the purpose of this study, a closed questionnaire containing 25 statements regarding the law and its relationship to social work was used. The research population consisted of 202 social workers from Haifa and the Northern region of Israel. The findings of this study support the hypothesis that there is indeed a tendency to closer ideological and professional proximity between social work and the law in Israel. However, especially regarding courts and the litigation process, their attitudes in response to the statements were relatively less favourable.
God’sCampesinos? Mexico’s Revolutionary Church in the Countryside
Authors: BUTLER MATTHEW
Published: February 2009

While revolutionary attempts to eradicate religion have been well studied, this article explores a little‐known attempt to construct state hegemony within the religious sphere by founding a revolutionary Church (the Iglesia Católica Apostólica Mexicana, or Mexican Catholic and Apostolic Church) in 1925. The article first explores the agrarian ideology of the schism, conceived as a revolutionary form of spiritual modernisation. It then charts the popular reception of the schism in Mexico State and argues that some agrarianised communities appropriated the new religion because it was seen as the spiritual adjunct of land reform, a means of blending popular revolutionary and religious beliefs, and a sectarian political weapon.
Democratisation, External Exposure and State Food Distribution in The Dominican Republic
Authors: MITCHELL KENNETH
Published: February 2009

The Dominican Republic shares the island of Hispaniola with a ‘failed’ state, requires regular financial assistance from international funds and remains exposed to external economic pressures. State food distribution in the country, however, adheres to traditional statist policies and institutions that disappeared elsewhere in Latin America and the Caribbean during the 1980s and 1990s. Relevant literature arguably does not anticipate this outcome. This article proposes that political institutions associated with Dominican democratisation since the late 1970s, particularly strong presidentialism, a stable, non‐ideological party system and high voter turnout at elections, provide incentives for a status quo, clientelistic policy in this strategic area of social policy.
Dystopian Buenos Aires
Authors: RIERA MONICA
Published: February 2009

This article explores the dystopian presence of Buenos Aires in Roberto Arlt’s Los siete locos (The seven madmen) and its companion novel, Los lanzallamas (The flamethrowers). Both belong to a tradition of metropolitan narrative represented in Europe by authors such as Robert Musil, Alfred Döblin and James Joyce. Arlt’s work, however, has a distinctive character, since it connects the expectations and anxieties unleashed by modernity with a dystopian imagination which has origins in nineteenth‐century Argentina with its raison d’être being profoundly linked to the formation of an Argentine national identity.
HO‐1‐mediated macroautophagy: a mechanism for unregulated iron deposition in aging and degenerating neural tissues
Authors: Zukor Hillel , Song Wei , Liberman Adrienne , Mui Jeannie , Vali Hojatollah , Fillebeen Carine , Pantopoulos Kostas , Wu Ting‐Di , Guerquin‐Kern Jean‐Luc , Schipper Hyman M.
Published: February 2009

J. Neurochem. (2009)109, 776–791.

Oxidative stress, deposition of non‐transferrin iron, and mitochondrial insufficiency occur in the brains of patients with Alzheimer disease (AD) and Parkinson disease (PD). We previously demonstrated that heme oxygenase‐1 (HO‐1) is up‐regulated in AD and PD brain and promotes the accumulation of non‐transferrin iron in astroglial mitochondria. Herein, dynamic secondary ion mass spectrometry (SIMS) and other techniques were employed to ascertain (i) the impact of HO‐1 over‐expression on astroglial mitochondrial morphologyin vitro, (ii) the topography of aberrant iron sequestration in astrocytes over‐expressing HO‐1, and (iii) the role of iron regulatory proteins (IRP) in HO‐1‐mediated iron deposition. Astroglial hHO‐1 over‐expression induced cytoplasmic vacuolation, mitochondrial membrane damage, and macroautophagy. HO‐1 promoted trapping of redox‐active iron and sulfur within many cytopathological profiles without impacting ferroportin, transferrin receptor, ferritin, and IRP2 protein levels or IRP1 activity. Thus, HO‐1 activity promotes mitochondrial macroautophagy and sequestration of redox‐active iron in astroglia independently of classical iron mobilization pathways. Glial HO‐1 may be a rational therapeutic target in AD, PD, and other human CNS conditions characterized by the unregulated deposition of brain iron.
Neural progenitor cell death is induced by extracellular ATP via ligation of P2X7 receptor
Authors: Delarasse Cécile , Gonnord Pauline , Galante Micaela , Auger Rodolphe , Daniel Hervé , Motta Iris , Kanellopoulos Jean M.
Published: February 2009

J. Neurochem. (2009) 109, 846–857.

Neural progenitor cells (NPCs) are capable of self‐renewal and differentiation into neurons, astrocytes and oligodendrocytes, and have been used to treat several animal models of CNS disorders. In the present study, we show that the P2X7 purinergic receptor (P2X7R) is present on NPCs. In NPCs, P2X7R activation by the agonists extracellular ATP or benzoyl ATP triggers opening of a non‐selective cationic channel. Prolonged activation of P2X7R with these nucleotides leads to caspase independent death of NPCs. P2X7R ligation induces NPC lysis/necrosis demonstrated by cell membrane disruption accompanied with loss of mitochondrial membrane potential. In most cells that express P2X7R, sustained stimulation with ATP leads to the formation of a non‐selective pore allowing the entry of solutes up to 900 Da, which are reportedly involved in P2X7R‐mediated cell lysis. Surprisingly, activation of P2X7R in NPCs causes cell death in the absence of pore formation. Our data support the notion that high levels of extracellular ATP in inflammatory CNS lesions may delay the successful graft of NPCs used to replace cells and repair CNS damage.
Comparison of transduction efficiency of recombinant AAV serotypes 1, 2, 5, and 8 in the rat nigrostriatal system
Authors: McFarland Nikolaus R. , Lee Jeng‐Shin , Hyman Bradley T. , McLean Pamela J.
Published: February 2009

J. Neurochem. (2009) 109, 838–845.

Enhanced delivery and expression of genes in specific neuronal systems is critical for the development of genetic models of neurodegenerative disease and potential gene therapy. Recent discovery of new recombinant adeno‐associated viral (rAAV) capsid serotypes has resulted in improved transduction efficiency, but expression levels, spread of transgene, and potential toxicity can differ depending on brain region and among species. We compared the transduction efficiency of titer‐matched rAAV 2/1, 2/5, and 2/8 to the commonly used rAAV2/2 in the rat nigrostriatal system via expression of the reporter transgene, enhanced green fluorescent protein. Newer rAAV serotypes 2/1, 2/5, and 2/8 demonstrated marked increase in transduction and spread of enhanced green fluorescent protein expression in dopaminergic nigrostriatal neurons and projections to the striatum and globus pallidus compared to rAAV2/2 at 2 weeks post‐injection. The number of nigral cells transduced was greatest for rAAV2/1, but for serotypes 2/5 and 2/8 was still two‐ to threefold higher than that for 2/2. Enhanced transduction did not cause an increase in glial cell response or toxicity. New rAAV serotypes thus promise improved gene delivery to nigrostriatal system with the potential for better models and therapeutics for Parkinson disease and other neurodegenerative disorders.
Nicotine is neuroprotective when administered before but not after nigrostriatal damage in rats and monkeys
Authors: Huang Luping Z. , Parameswaran Neeraja , Bordia Tanuja , Michael McIntosh J. , Quik Maryka
Published: February 2009

J. Neurochem. (2009) 109, 826–837.

Nicotine reduces dopaminergic deficits in parkinsonian animals when administered before nigrostriatal damage. Here we tested whether nicotine is also beneficial when given to rats and monkeys with pre‐existing nigrostriatal damage. Rats were administered nicotine before and after a unilateral 6‐hydroxydopamine lesion of the medial forebrain bundle, and the results compared with those in which rats received nicotine only after lesioning. Nicotine pre‐treatment attenuated behavioral deficits and lessened lesion‐induced losses of the striatal dopamine transporter, and α6β2* and α4β2* nicotinic receptors (nAChRs). By contrast, nicotine administered 2 weeks after lesioning, when 6‐hydroxydopamine‐induced neurodegenerative effects are essentially complete, did not improve these same measures. Similar results were observed in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine‐lesioned monkeys. Nicotine did not enhance striatal markers when administered to monkeys with pre‐existing nigrostriatal damage, in contrast to previous data that showed improvements when nicotine was given to monkeys before lesioning. These combined findings in two animal models suggest that nicotine is neuroprotective rather than neurorestorative against nigrostriatal damage. Receptor studies with 125I‐α‐conotoxinMII and the α‐conotoxinMII analog E11A were next performed to determine whether nicotine treatment pre‐ or post‐lesioning differentially affected expression of α6α4β2* and α6(nonα4)β2* nAChR subtypes in striatum. The observations suggest that protection against nigrostriatal damage may be linked to striatal α6α4β2* nAChRs.
VIP down‐regulates the inflammatory potential and promotes survival of dying (neural crest‐derived) corneal endothelial cells ex vivo: necrosis to apoptosis switch and up‐regulation of Bcl‐2 and N‐cadherin
Authors: Koh Shay‐Whey M. , Cheng Jason , Dodson Rebecca M. , Ku Chao‐Yar T , Abbondandolo Cara J.
Published: February 2009

J. Neurochem. (2009) 109, 792–806.

The neuropeptide vasoactive intestinal peptide (VIP) is anti‐inflammatory and protective in the immune and nervous systems, respectively. This study demonstrated in corneal endothelial (CE) cells injured by severe oxidative stress (1.4 mM H2O2) in bovine corneal organ cultures that VIP pre‐treatment (0, 10−10, 10−8, and 10−6 M; 15 min), in a VIP concentration‐dependent manner, switched the inflammation‐causing necrosis to inflammation‐neutral apoptosis (showing annexin V‐binding, chromatin condensation, and DNA fragmentation) and upheld ATP levels in a VIP antagonist (SN)VIPhyb‐sensitive manner, while up‐regulated mRNA levels of the anti‐apoptotic Bcl‐2 and the differentiation marker N‐cadherin in a kinase A inhibitor‐sensitive manner. As a result, VIP, in a concentration‐dependent and VIP antagonist‐sensitive manners, promoted long‐term CE cell survival. ATP levels, a determining factor in the choice of apoptosis versus necrosis, measured after VIP pre‐treatment and 0.5 min post‐H2O2 were 39.6 ± 3.3, 50.8 ± 6.2, 60.1 ± 4.8, and 53.6 ± 5.3 pmoles/μg protein (mean ± SEM), respectively (p < 0.05, anova). VIP treatment alone concentration‐dependently increased levels of N‐cadherin (Koh et al. 2008), the phosphorylated cAMP‐responsive‐element binding protein and Bcl‐2, while10−8 M VIP, in a VIP antagonist (SN)VIPhyb‐sensitive manner, increased ATP level by 38% (p < 0.02) and decreased glycogen level by 32% (p < 0.02). VPAC1 (not VPAC2) receptor was expressed in CE cells. Thus, CE cell VIP/VPAC1 signaling is both anti‐inflammatory and protective in the corneal endothelium.
Post‐translational modifications of tubulin in the nervous system
Authors: Fukushima Nobuyuki , Furuta Daisuke , Hidaka Yuji , Moriyama Ryutaro , Tsujiuchi Toshifumi
Published: February 2009

J. Neurochem. (2009) 109, 683–693.

Many studies have shown that microtubules (MTs) interact with MT‐associated proteins and motor proteins. These interactions are essential for the formation and maintenance of the polarized morphology of neurons and have been proposed to be regulated in part by highly diverse, unusual post‐translational modifications (PTMs) of tubulin, including acetylation, tyrosination, detyrosination, Δ2 modification, polyglutamylation, polyglycylation, palmitoylation, and phosphorylation. However, the precise mechanisms of PTM generation and the properties of modified MTs have been poorly understood until recently. Recent PTM research has uncovered the enzymes mediating tubulin PTMs and provided new insights into the regulation of MT‐based functions. The identification of tubulin deacetylase and discovery of its specific inhibitors have paved the way to understand the roles of acetylated MTs in kinesin‐mediated axonal transport and neurodegenerative diseases such as Huntington’s disease. Studies with tubulin tyrosine ligase (TTL)‐null mice have shown that tyrosinated MTs are essential in normal brain development. The discovery of TTL‐like genes encoding polyglutamylase has led to the finding that polyglutamylated MTs which accumulate during brain development are involved in synapse vesicle transport or neurite outgrowth through interactions with motor proteins or MT‐associated proteins, respectively. Here we review current exciting topics that are expected to advance MT research in the nervous system.
Immigrant patients’ experiences and reflections pertaining to the consultation: a study on patients from Chile, Iran and Turkey in primary health care in Stockholm, Sweden
Authors: Wiking Eivor , Saleh‐Stattin Nuha , Johansson Sven‐Erik , Sundquist Jan
Published: February 2009

Our knowledge of the immigrant patient’s experiences and reflections regarding consultations in primary health care where interpreters are used is limited. Thus, the primary aim was to explore these experiences and reflections. The second aim was to study whether demographic and migration‐related factors are associated with the patient’s satisfaction with the consultation and feeling of consolation given by the general practitioner (GP). The third aim was to analyse whether these feelings are related to the time from the booking to the consultation, to self‐reported health, symptoms and the patient’s experiences. A questionnaire was distributed to 78 consecutive immigrant patients from Chile, Iran and Turkey at 12 primary healthcare centres around Stockholm. The respondents were asked about their background and health status, while open‐ended questions focused on their experiences and comments regarding the consultation and cross‐cultural communication in general. Ethical approval was obtained. The respondents consisted of 52 patients, 16 from Chile, nine from Iran and 27 from Turkey. Most of the answers concerned communication problems because of language and cultural differences between the GP and the patient and the GP’s ability to listen. Therefore, the importance of having a competent interpreter for a satisfactory consultation was stressed. Many of the respondents also felt that the GP’s ability to listen to them and understand them is crucial in the consultation. Background facts, including demographic and migration‐related factors, health status and factors related to the consultation, did not seem to be associated with the patient’s satisfaction and the feeling of consolation. One limitation is that the sample is small and not equally distributed. The use of authorized interpreters during the consultation is essential. The consultation must be based on a patient‐centred strategy and adjusted to the patient’s educational level. Cultural competence is needed when meeting immigrant patients.
Effects of tramadol and dexketoprofen on analgesia and gastrointestinal transit in mice
Authors: Miranda H.F. , Puig M.M. , Romero M.A. , Prieto J.C.
Published: February 2009

The purpose of the present study was to evaluate the nature of the antinociceptive interaction among dexketoprofen (DEX), a mixed inhibitor of the cyclo‐oxygenases, and tramadol (TRAM), a weak opioid with monoaminergic activity that inhibits norepinephrine and serotonin re‐uptake. We assessed antinociception in the acetic acid writhing test, the tail flick and the formalin (FT) tests, and gastrointestinal transit (GIT) after the administration of a charcoal meal. The analysis of the interaction was carried out using isobolograms and interaction indexes or the fixed‐dose method GIT. The administration of DEX or TRAM individually induced dose–dependent antinociception in all the algesiometric tests. In the three tests, TRAM was between 5.2 (FT, phase I) and 35 times (FT, Phase II) more potent than DEX. When testing combinations at different potency ratios (1 : 1, 1 : 3, 3 : 1), we could demonstrate synergy in all algesiometric tests, only when drugs were combined in a 1 : 1 proportion. Interestingly, the proportion of the drugs in the combination could change the type of interaction from synergy to antagonism. On the inhibition of GIT, a dose‐related inhibition was established for TRAM, but not for DEX. Using a fixed‐dose protocol, we could demonstrate antagonism between DEX and TRAM on the inhibition of GIT. The results of the present study suggest that a combination of DEX and TRAM in a 1 : 1 proportion could be adequate to use in future clinical trials in humans.
Interest of using genetically manipulated mice as models of depression to evaluate antidepressant drugs activity: a review
Authors: Gardier Alain M. , Guiard Bruno P. , Guilloux Jean‐Philippe , Repérant Christelle , Coudoré François , David Denis J.
Published: February 2009

Among the multiple possibilities to study human depressive disorders, animal models remain important preclinical tools. They allow the understanding of the mechanisms of action of antidepressant drugs. Primarily developed in rat, animal models of depression have been adapted to the mouse, an easy‐to‐use mammal with better genetic possibilities than rats. As an example, genetic manipulation of the serotoninergic 5‐hydroxytryptamine‐HT; (5‐HT) system provided important opportunities to investigate the role of this monoamine in mood disorders. The contribution of either constitutive knockout (KO), tissue specific, or inducible KO mice and animal models in the current knowledge of the pathophysiology and treatment of depression is unanimously recognized. The phenotype of genetically manipulated animals is strongly influenced by both the genetic background of the animal as well as environmental factors. For these reasons, it is necessary to underline that KO mice have been generated on various genetic backgrounds, which strongly influence the behavioral and neurochemical responses to the tests. The present review will thus focus on KO mice lacking G protein‐coupled monoaminergic receptors (e.g; 5‐HT1B, 5‐HT1A, and 5‐HT4 receptors) and the 5‐HT serotonin transporter, which is the main target of antidepressant drugs (or strategies). The importance of KO mice for neurotrophic factors, particularly for brain‐derived neurotrophic factor and its main receptor displaying a tyrosine kinase activity, will also be addressed to illustrate the fact that in preclinical studies, combination of genetic manipulations with pharmacological ones should allow further progress in the field of neuropsychopharmacology.
Tacrolimus pharmacokinetic drug interactions: effect of prednisone, mycophenolic acid or sirolimus
Authors: Park Sung‐In , Felipe Claudia R. , Pinheiro‐Machado Paula G. , Garcia Riberto , Fernandes Fernanda B. , Casarini Dulce E. , Tedesco‐Silva Helio , Medina‐Pestana Jose O.
Published: February 2009

This study was conducted to evaluate time‐dependent pharmacokinetic changes and drug interactions over the first 6 months after transplantation in kidney transplant recipients receiving tacrolimus (TAC), prednisone (PRED) and mycophenolate mofetil (MMF) or sirolimus (SRL). Pharmacokinetic assessments were carried out at day 7 and months 1, 3, and 6 in kidney transplant recipients receiving TAC plus PRED with either MMF (2 g/day,n = 13) or SRL (15 mg loading dose, 5 mg for 7 days followed by 2 mg/day,n = 12). There were no differences in the main demographic characteristics or in mean PRED doses during the first 6 months after transplant. From day 7 to month 6, there was a 65% increase in TAC dose corrected exposure (dose corrected area under the curve; AUC) in patients receiving MMF (P = 0.005) and a 59% increase in TAC dose corrected exposure in patients receiving SRL (P = 0.008). From day 7 to month 6, there was a 72% increase in mycophenolate dose corrected exposure (P = 0.001) and a 65% increase in SRL dose corrected exposure (P = 0.008). TAC dose corrected exposure was 23% lower in patients receiving SRL compared with MMF (P = 0.012) on average over the study period. PRED dose reduction was associated with increase in TAC (in patients receiving SRL,P = 0.040) and mycophenolic acid (MPA) (P = 0.070) drug exposures. Tercile distribution of TAC drug exposure showed a positive correlation with mean SRL exposures (P = 0.016). Conversely, tercile distribution of SRL drug exposure showed a positive correlation with mean TAC exposures (P = 0.004). Time‐dependent increases in TAC, MPA and SRL drug exposures occur up to 6 months after transplantation. Drug‐to‐drug interactions indicate that intense therapeutic drug monitoring is required to avoid under‐ or over‐immunosuppression.
Interactions between ingested kaolinite and the intestinal mucosa in rat: proteomic and cellular evidences
Authors: Reichardt François , Habold Caroline , Chaumande Bertrand , Ackermann Alain , Ehret‐Sabatier Laurence , Le Maho Yvon , Angel Fabielle , Liewig Nicole , Lignot Jean‐Hervé
Published: February 2009

Although some of the effects of clay ingestion by humans and animals, such as gastrointestinal wellness and the increase in food efficiency are well known, the underlying mechanisms are not yet fully understood. Therefore, the interactions between the intestinal mucosa and kaolinite particles and their effects on mucosal morphology were observed using light microscopy (LM), transmission electron microscopy (TEM), conventional (CSEM) and environmental (ESEM) scanning electron microscopy combined with an EDX micro‐analysis system. Kaolinite consumption, given with free access to rats, varied considerably from one animal to the other but was regular through time for each individual. Some kaolinite particles appeared chemically dissociated in the lumen and within the mucus barrier. Aluminium (Al) originating from ingested clay and present in the mucus layer could directly cross the intestinal mucosa. A significant increase in the thickness of the villi with large vacuoles at the base of the mucosal cells and a decrease in the length of enterocyte microvilli characterized complemented animals. The proteomic analyses of the intestinal mucosa of complemented rats also revealed several modifications in the expression level of cytoskeleton proteins. In summary, kaolinite particles ingested as food complement interact with the intestinal mucosa and modify nutrient absorption. However, these data, together with the potential neurotoxicity of Al, need further investigation.
Antiplatelet ‘resistance’ and ‘non‐responders’: what do these terms really mean?
Authors: Serebruany Victor L. , Eisert Christian , Atar Dan , Ferguson James J.
Published: February 2009

The term ‘resistance’ should be restricted to very specialized physiologic circumstances, if not abandoned altogether. The term ‘non‐responder’ needs to be placed in the context of the question: ‘Non‐responder to what?’ Even if we would somehow magically know what an optimal response to antiplatelet therapy was, it will still be challenging to demonstrate an ‘inadequate’ response to antiplatelet therapy. At present there are two alternatives – give more drug or give additional drugs. Both strategies may work in further inhibiting platelet function, but both strategies can also be associated with an increased risk of bleeding. The trick, for the future, much as with our antihypertensive and lipid‐lowering armamentaria, will be to know in whom to do what with which drug, and why. Single isolated measurements are not useful – if you don't know where you started, how we would know that antiplatelet drug is producing an ‘adequate’ clinical effect? There is no evidence of any sort of absolute ‘threshold’ that must be exceeded for treatment to be effective, and in the absence of this, if we are to evaluate the effect of a given drug, we have to have baseline values (off drug), therapeutic values (on drug), and some sort of assessment of both resting (unstimulated) and agonist‐provoked (stimulated) platelet function. Moreover, given all of the different things that platelets do, the ideal assessment of platelet function and drug responsiveness will need to incorporate more than one agonist and some sort of assessment of both platelet activation and platelet aggregation. No one man (or test) tells us everything; it is the totality of the information that gives us the most complete picture. And, ultimately, we need to more firmly establish how the variability in platelet function and drug‐associated changes in that function correlates with long‐term, hard‐endpoint clinical events.
Characterisation of Strength Behaviour of Aluminium Foam Sandwiches Under Static Load
Authors: Vogel J. , Keller J. , Sviridov A. , Feige H.‐J. , Kreyssig K. , Auersperg J. , Plass P. , Walter H.
Published: February 2009

Abstract:  Cellular metals, particularly aluminium foams, are increasingly used in automotive, railcar and aircraft industries due to their advantages such as low density, comparatively high stiffness, noise damping or non‐flammability. From this point of view a new powder‐compact forming and foaming technique has been developed to manufacture 3D‐aluminium foam sandwich (AFS) parts for components of railcars without glued joint between the foamed core layer and both cover sheets. Three different stages of foam expansion have been analysed to describe the material properties. We have characterised samples made of plane AFS panels by compression, bending and shear tests. The shear strain is optically measured by digital image correlation to estimate the shear modulus of foamed sandwiches. Furthermore, these experimentally determined values and curves are the basis for the verification and optimisation of finite element models by design of experiments. As a result of this work, recommendations could be derived for improving technological parameters.
Interlaminar Fracture Toughness of Carbon Fibre‐Reinforced Polymer Laminates With Nano‐ and Micro‐Fillers
Authors: Kostopoulos V. , Karapappas P. , Loutas T. , Vavouliotis A. , Paipetis A. , Tsotra P.
Published: February 2009

Abstract:  Vapour growth carbon nanofibres (CNF) and lead zirconate titanate (PZT) piezoelectric particles were added in the matrix of carbon fibre‐reinforced polymer laminates. The fracture toughness of the modified composites was measured under mode I and mode II loading and compared with plain epoxy carbon fibre‐reinforced composites. The mode I fracture toughness of the composites improved with the incorporation of the carbon nanofibres and deteriorated with the incorporation of PZT piezoelectric particles. When both fillers were added in the composite matrix, the mode I fracture toughness improved but to a lesser extend. The mode II fracture toughness of the modified composites was improved in all three cases. The aforementioned behaviour was attributed to competing fracture mechanisms instigated by the different fillers, and backed by fractographic evidence from the failed composite coupons; during the tests, the acoustic emission activity of the coupons was monitored and classified in three major energy absorbing mechanisms which were attributed to the failure of distinct composite phases.
Effects of four tillage systems on soil structure and soil microbial biomass in organic farming
Authors: Vian J. F. , Peigne J. , Chaussod R. , Roger‐Estrade J.
Published: February 2009

Tillage modifies soil structure and crop residue distribution and in turn affects the ability of soil micro‐organisms to degrade soil organic matter and release nutrients for crop growth. In organic farming, soil microbiological activity is of primary importance as nutrient supply is mainly dependent on the degradation of soil organic matter by soil micro‐organisms. The aim of this work was therefore to study, in organic farming, the effects of four tillage systems [mouldboard ploughing (MP), shallow mouldboard ploughing (SMP), reduced tillage (RT) and shallow soil tillage (ST)] on soil structure, soil microbial biomass (SMB) and its potential activity (Cmin) during the first year following the treatments. To study simultaneously the effects of soil structure modifications and crop residue distribution on SMB and Cmin, we adopted a sampling scheme based on a morphological description of soil profiles. We distinguished and sampled compacted and non‐compacted clods (Δ and Γ clods) at three depths (0–5, 5–15 and 15–30 cm). This method enabled us to have a precise estimation of the effects of tillage treatments on SMB and Cmin. MP reduced compacted zones and limited unfavourable conditions for microbial growth and enabled a homogenous distribution of SMB in the soil profile. At the opposite, the ST increased compacted zones in the soil profile and limited SMB development below the top few centimetres. The SMP and the RT systems appeared as intermediate techniques. RT seemed to be a conservation tillage technique which could be used in organic farming.
Effect of different management strategies on soil quality of citrus orchards in Southern Italy
Authors: Canali S. , Di Bartolomeo E. , Trinchera A. , Nisini L. , Tittarelli F. , Intrigliolo F. , Roccuzzo G. , Calabretta M. L.
Published: February 2009

Twenty‐six soil samples were collected from 13 paired orchards (organically vs. conventionally managed) homogeneous for age, rootstock and cultivars, belonging to the Eastern Sicily Organic Citrus farm Network. The soil quality was evaluated by chemical and biochemical indicators. The total organic C, humification parameters and isoelectric focusing of extracted organic matter were measured to quantify the size of relevant soil C pools. In addition, C turnover was evaluated by determining microbial C mineralization, C microbial biomass and by calculating the mineralization and metabolic quotient (qCO2). The results obtained demonstrated that organic citrus soils were characterized by a general increase in all the organic matter pools, which means a greater C supply for soil metabolic processes. This observed trend did not directly influence the organic matter turnover, indicating that the organic approach could act as a soil C‐sink. The soil microflora of organically managed soils showed an improved efficiency in use of energy and organic resources, corresponding to an increased ability of soils under organic management to sustain biological productivity in the long term.
Participatory soil survey: experience in working with a Mesoamerican indigenous community
Authors: Barrera‐Bassols N. , Zinck J. A. , Van Ranst E.
Published: February 2009

In traditional rural societies that still represent the majority of small farmers worldwide, the use of conventional soil survey information frequently fails because it does not take into account or underestimates soil knowledge and experience of local people. Innovative approaches have been proposed to utilize the soil knowledge of rural communities through the participation of local farmers. This paper reports experience of participatory soil survey in the Purhépecha community of San Francisco Pichátaro in the volcanic highlands of central Mexico. Ethnographic and ethnopedologic techniques were applied to acquire soil and land data. Local soil knowledge was incorporated through plenary workshops designed to produce a participatory soil map based on a Purhépecha soil classification. This soil map reflects farmers’ soil–landscape understanding and correlates fairly well with a scientific soil map of the same area because in both approaches terrain plays a key role in the delineation of soil units. Participatory soil mapping promoted cooperation between local and external participants and formed the basis for an agreed land‐use plan.
Inositol trisphosphate‐dependent Ca2+ stores and mitochondria modulate slow wave activity arising from the smooth muscle cells of the guinea pig prostate gland
Authors: Exintaris Betty , Nguyen Dan‐Thanh T , Lam Michelle , Lang Richard J
Published: February 2009

Background and purpose:  Changes in smooth muscle tone of the prostate gland are involved in aetiology of symptomatic prostatic hyperplasia, however the control mechanisms of prostatic smooth muscle are not well understood. Here, we have examined the role of internal Ca2+ compartments in regulating slow wave activity in the guinea pig prostate.

Experimental approach:  Standard intracellular membrane potential recording techniques were used.

Key results:  The majority (89%) of impaled cells displayed ‘slow wave’ activity. Cyclopiazonic acid (10 µmol·L−1) transiently depolarized (3–9 mV) the membrane potential of the prostatic stroma and transiently increased slow wave frequency. Thereafter, slow wave frequency slowly decreased over 20–30 min. Ryanodine transiently increased slow wave frequency, although after 30 min exposure slow wave frequency and time course returned to near control values. Caffeine (1 mmol·L−1) reduced slow wave frequency, accompanied by membrane depolarization of about 8 mV. Blockade of inositol trisphosphate receptor (IP3R)‐mediated Ca2+ release with 2‐aminoethoxy‐diphenylborate (60 µmol·L−1) or Xestospongin C (3 µmol·L−1) or inhibiting phospholipase C and IP3 formation using U73122 (5 µmol·L−1) or neomycin (1 and 4 mmol·L−1) reduced slow wave frequency, amplitude and duration. The mitochondrial uncouplers, p‐trifluoromethoxy carbonyl cyanide phenyl hydrazone (1–10 µmol·L−1), carbonyl cyanide m‐chlorophenylhydrazone (1–3 µmol·L−1) or rotenone (10 µmol·L−1), depolarized the membrane (8–10 mV) before abolishing electrical activity.

Conclusion and implications:  These results suggest that slow wave activity was dependent on the cyclical release of Ca2+ from IP3‐controlled internal stores and mitochondria. This implies that intracellular compartments were essential in the initiation and/or maintenance of the regenerative contractile activity in the guinea pig prostate gland.