bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of SU11248 on gastrointestinal stromal tumor‐T1 cells: Enhancement of growth inhibition via inhibition of 3‐kinase/Akt/mammalian target of rapamycin signaling
Authors: Ikezoe Takayuki , Yang Yang , Nishioka Chie , Bandobashi Kentaro , Nakatani Hajime , Taguchi Takahiro , Koeffler H. Phillip , Taguchi Hirokuni
Published: June 2006

SU11248 is an orally available type III and V receptor tyrosine kinase inhibitor. Clinical studies have shown the efficacy of SU11248 in individuals with gastrointestinal stromal tumors (GIST); however, the molecular mechanisms by which SU11248 inhibits the proliferation of these tumor cells remains to be fully elucidated. Taking advantage of GIST‐T1 cells, which possess an activating mutation in exon 11 of the c‐KIT gene, we examined the medicinal action of SU11248 in GIST cells. Clonogenic and MTT assays showed that SU11248 potently inhibited the proliferation of GIST‐T1 cells with IC50 of approximately 1 nM and 40 nM, respectively. SU11248 (10 or 20 nM, 48 h) activated caspase‐3 and induced apoptosis of GIST‐T1 cells as measured by caspase assay, annexin V staining and cleavage of poly (ADP‐ribose) polymerase. Western blot analyses found that SU11248 blocked autophosphorylation of c‐KIT in association with inhibition of its downstream effectors, including Akt and extracellular signal‐regulated kinase, but not signal transducers and activators of transcription. Interestingly, when phosphatidylinositol 3‐kinase/Akt/mammalian target of rapamycin signaling was blocked simultaneously by either LY294002 or rapamycin, growth inhibition mediated by SU11248 was potentiated. Taken together, this study supports clinical studies of SU11248 for individuals with GIST, and the combination of SU11248 and inhibitors of 3‐kinase/Akt/mammalian target of rapamycin signaling represents a promising novel treatment strategy. (Cancer Sci 2006; 97: 945–951)
Predictive factors for response to docetaxel in human breast cancers
Authors: Noguchi Shinzaburo
Published: June 2006

Docetaxel has come into wide use recently for the treatment of breast cancer in neoadjuvant, adjuvant and metastatic settings. Docetaxel binds to β‐tubulin and causes kinetic abnormalities in the dynamics of microtubules by increasing their polymerization and inhibiting their depolymerization, resulting in elevated levels of microtubule formation. During metaphase, defective spindle formation induced by docetaxel activates the mitotic checkpoint and leads to cell cycle arrest, culminating in apoptosis. However, docetaxel is not effective for all breast cancers. For example, in metastatic settings, the response rate to docetaxel reportedly ranges from 30 to 50%. It is therefore very important to develop a diagnostic method with high accuracy for the prediction of sensitivity to docetaxel in order to avoid unnecessary treatment. Currently it is impossible to identify, before the initiation of therapy, the patients for whom docetaxel will be effective. Various biological parameters have been studied clinically for their ability to predict response to docetaxel, such as parameters related to: (1) efflux (p‐glycoprotein) and metabolism (CYP3A4); (2) β‐tubulin (somatic mutation of β‐tubulin and changes in β‐tubulin isotypes levels); (3) cell cycle (HER2, BRCA1 and Aurora‐A); and (4) apoptosis (p53, BCL2 and thioredoxin). More recently, gene expression profiling techniques have been used for the development of a prediction model for response to docetaxel. In the present paper, clinical studies that have been conducted recently to identify predictive factors for response to docetaxel are reviewed together with a presentation of our recent work in this field. (Cancer Sci 2006; 97: 813–820)
Trade‐offs within the immune systems of female White‐footed Mice, Peromyscus leucopus
Authors: MARTIN II L. B. , WEIL Z. M. , KUHLMAN J. R. , NELSON R. J.
Published: June 2006

In many vertebrates, immune activity is compromised when other expensive activities are concurrent. One explanation for such patterns includes trade‐offs between immune activity and other expensive physiological processes. Trade‐offs among different immune responses themselves may also occur, but thus far few data exist to substantiate them.

We predicted that immune activity in female White‐footed Mice, Peromyscus leucopus, would be weak (relative to sham‐treated controls) if another immune response was already ongoing. To test this hypothesis, we examined (i) the effects of inflicting a cutaneous wound on cell‐mediated immune activity one day after wounding, and (ii) the effects of inducing cell‐mediated immune activity on the cutaneous wound‐healing process when wounds were inflicted one day after the immune challenge.

Prior wounding dampened cell‐mediated immune responses and induction of cell‐mediated immune activity altered progression of wound healing. Immune challenges did not affect reproductive tissue masses, however, as has been detected in males of this species. Also, concentrations of circulating glucocorticoids, which are known modulators of immune activity, were not dramatically different between treatment and sham groups.

In sum, our results provide evidence that some immune responses can negatively influence other recent immunological activity. Further study is warranted, however, to pinpoint the molecular mechanisms underlying these apparent trade‐offs and determine whether induction of immune activity may sometimes prime instead of hinder subsequent immune responses.
Higher stress protein levels are associated with lower humoral and cell‐mediated immune responses in Pied Flycatcher females
Authors: MORALES J. , MORENO J. , LOBATO E. , MERINO S. , TOMÁS G. , MARTÍNEZ DE LA PUENTE J. , MARTÍNEZ J.
Published: June 2006

The proper functioning of immune defences may be traded‐off against protecting the organism from physiological stress through the induction of stress protein (HSP) synthesis. Immune function could also be negatively affected by haemoparasite infections.

We studied whether two induced immune responses (the humoral response to a tetanus vaccine and the T‐cell‐mediated response to phytohaemaglutinin (PHA) injection) were associated with the levels of two stress proteins (HSP60, HSP70), with haemoparasite infection and with condition in Pied Flycatcher,Ficedula hypoleucaPallas, females. HSP levels, haemoparasite infection and condition were assessed on days 1 and 11 of nestling age, prior to tetanus and PHA challenges, respectively.

Females with higher HSP60 levels prior to tetanus challenge mounted lower humoral responses. Females parasitized byHaemoproteusshowed lower humoral responses, when controlling for HSP60 levels. No association was detected for HSP70 levels.

Females with higher HSP60 and HSP70 levels prior to PHA challenge, independently ofHaemoproteusinfection, showed lower cell‐mediated responses, when correcting for laying date. Female condition was not associated with immune responses.

These results suggest that synthesizing more HSPs to mitigate stress may be traded‐off against mounting humoral and cell‐mediated immune responses, and agree with immune defences being costly.
Immunocompetence and flea parasitism of a desert rodent
Authors: GOÜY DE BELLOCQ J. , KRASNOV B. R. , KHOKHLOVA I. S. , GHAZARYAN L. , PINSHOW B.
Published: June 2006

Immunocompetence is the general capacity of an organism to mount an immune response against pathogens and parasites. We studied the relationship between the immunocompetence of a rodent host,Meriones crassus(Sundevall's Jird) and parasitism by the fleaXenopsylla ramesis. We hypothesized that flea parasitism affects physiological and immunological variables of the host, and that the host's level of immunocompetence affects fitness components in the flea parasite. We wanted to find out (a) the effect of flea parasitism on the haematocrit (Hct), leucocyte concentration (LC) and response to phytohaemagglutinin (PHA) of the host; (b) if and how the level of immunocompetence of the host is related to the fitness of fleas exploiting it; and (c) the relationship between the immunological and behavioural defences of the host.

We measured Hct and LC and response to PHA before and after 16 days of flea infestation in Sundevall's Jird and compared these variables between jirds subjected to flea parasitism and non‐parasitized (control) animals. We evaluated egg production and hatching success in fleas exploiting hosts with different levels of immunocompetence.

The effect of flea parasitism on Hct and LC of rodents was manifested by an increase in among‐host variation in the temporal changes of these variables. Response to PHA injection was significantly lower in parasitized than in control animals.

Flea egg production and hatching success were not related to either LC, prior to experimental treatments, or to the PHA response of rodents. However, both of these flea fitness traits were negatively correlated with changes in LC between the 1st and the 16th days of infestation.

At the end of the experiment, blood consumption of fleas was measured in jirds of both treatment groups. Fleas consumed significantly more blood when they fed on previously parasitized than on non‐parasitized animals. Among fleas that fed on previously parasitized animals, blood consumption was positively correlated with the initial LC of the hosts, and negatively correlated with differences in LC between the 1st and the 16th days of flea infestation. We found no correlation between blood consumption in fleas that fed on control animals and either immunological variable of the hosts.

No trade‐off was found between behavioural and immune defences of the rodent hosts.
Caching as a strategy for surviving periods of resource scarcity; a comparative study of two species of Neotoma
Authors: POST D. M. , SNYDER M. V. , FINCK E. J. , SAUNDERS D. K.
Published: June 2006

Energy management has been studied in migrators and hibernators but little is know about energy management in cachers.

We investigated the energy management behaviour of two species of cachers, Neotoma floridana and Neotoma micropus. We also investigated differences in energy management of these two species that experience different environmental conditions during the period of food scarcity.

Results show that both species decrease body mass from autumn to winter and increase mass from winter to spring. Both species decrease body fat from autumn to winter but only N. floridana increases body fat from winter to spring. Plasma protein follows the same pattern as body mass in N. floridana. Plasma lipids decrease from autumn to winter but do not increase from winter to spring.

Results indicate that cachers, unlike hibernators or migrators, are able to use the food cache to increase body mass and body fat when new resources are not being produced in the environment.

Results suggest that environmental conditions alter resource management and the species that experiences more severe conditions stores more energy as fat.
Assessing larval food quality for phytophagous insects: are the facts as simple as they appear?
Authors: MOREAU J. , BENREY B. , THIERY D.
Published: June 2006

We argue here that host plant quality affects many life‐history traits of herbivorous insects and these traits often interact. Studies that look only at a limited number of traits often fail to determine the overall effect of plant quality on larval performance and adult fitness. Parameters such as mating success and adult longevity are frequently neglected even though they are affected by larval feeding and are crucial to overall fitness.

To illustrate this, we examined a whole suite of life‐history traits of the moth Lobesia botrana after rearing larvae of this grape pest on three different grape cultivars.

Development time, mating success, fecundity, egg size and fertility were differentially affected by the cultivar on which the larvae were reared. Our results highlight that decreased fecundity can be balanced by an increase in egg size and fertility.

Throughout this study, we emphasize that drawing conclusions about larval food quality can be spurious when based on too few life‐history traits. Therefore, it is essential to study all fitness related life‐history traits to fully understand the effects of larval food quality on herbivore fitness.
Several components of global change alter nitrifying and denitrifying activities in an annual grassland
Authors: BARNARD R. , LE ROUX X. , HUNGATE B. A. , CLELAND E. E. , BLANKINSHIP J. C. , BARTHES L. , LEADLEY P. W.
Published: June 2006

The effects of global change on below‐ground processes of the nitrogen (N) cycle have repercussions for plant communities, productivity and trace gas effluxes. However, the interacting effects of different components of global change on nitrification or denitrification have rarely been studied in situ.

We measured responses of nitrifying enzyme activity (NEA) and denitrifying enzyme activity (DEA) to over 4 years of exposure to several components of global change and their interaction (increased atmospheric CO2 concentration, temperature, precipitation and N addition) at peak biomass period in an annual grassland ecosystem. In order to provide insight into the mechanisms controlling the response of NEA and DEA to global change, we examined the relationships between these activities and soil moisture, microbial biomass C and N, and soil extractable N.

Across all treatment combinations, NEA was decreased by elevated CO2 and increased by N addition. While elevated CO2 had no effect on NEA when not combined with other treatments, it suppressed the positive effect of N addition on NEA in all the treatments that included N addition. We found a significant CO2–N interaction for DEA, with a positive effect of elevated CO2 on DEA only in the treatments that included N addition, suggesting that N limitation of denitrifiers may have occurred in our system. Soil water content, extractable N concentrations and their interaction explained 74% of the variation in DEA.

Our results show that the potentially large and interacting effects of different components of global change should be considered in predicting below‐ground N responses of Mediterranean grasslands to future climate changes.
Sexual selection, growth compensation and fast‐start swimming performance in Green Swordtails, Xiphophorus helleri
Authors: ROYLE N. J. , METCALFE N. B. , LINDSTRÖM J.
Published: June 2006

Fast‐start swimming provides an integrated physiological index of performance and a measure of ability to escape predators, so may be expected to covary with other important composite life‐history traits such as growth rate.

Variation in resource availability during growth and development is common, and organisms may show compensatory responses (such as catch‐up growth) to periods of low food availability. However, such responses usually carry costs.

We examined fast‐start performance in adult Green Swordtails in relation to growth regime experienced as a juvenile. In contrast to previous studies we found that conditions experienced early in life did not significantly affect fast‐start swimming performance, indicating that escape ability is at a premium in green swordtails.

Fish raised on ad libitum food had similar performance to fish raised on a restricted diet and fish experiencing compensatory growth, controlling for body size.

Body depth was positively related to fast‐start performance in both males and females, with males having faster escape responses than females for a given body depth.

Remarkably, males with the relatively longest sexual ornaments (‘swords’) had the greatest escape ability, suggesting that sword length may be a good indicator of quality among males of similar age.
Nuptial feeding is reflected in tissue nitrogen isotope ratios of female katydids
Authors: VOIGT C. C. , LEHMANN G. U. C. , MICHENER R. H. , JOACHIMSKI M. M.
Published: June 2006

During copulation male katydids transfer a protein‐rich nuptial gift to females, which is ingested by the female. We hypothesized that female katydids are built at least partly from proteins assimilated from nuptial gifts.

We measured the ratio of nitrogen isotopes (δ15N) in the diet and tissue of sexually reproducing Isophya kraussii and obligate parthenogenetically reproducing Poecilimon intermedius. We used the δ15N of muscles as an indicator of the most recent diet and the δ15N of the cuticula as an indicator of the larval diet.

In free‐ranging I. kraussi, muscular and cuticular δ15N of adult males was low, suggesting a plant diet. Cuticular δ15N did not differ between sexes, indicating that immatures of both sexes fed on similar diets. Female muscles were significantly more enriched in nitrogen‐15 than female cuticula and also than male muscles, suggesting that adult females incorporated animal proteins and immature females plant material.

Female I. kraussii that were kept with males in captivity had higher δ15N in muscular tissue than in cuticula. Muscular δ15N of these females was also higher than that of muscle and cuticula of females held isolated from males, suggesting that incorporated nitrogen originated from nuptial gifts.

In parthenogenetically reproducing P. intermedius muscular and cuticular δ15N was almost identical, suggesting no additional uptake of insect proteins in the absence of nuptial gifts.

We therefore conclude that female I. kraussii substantially assimilate spermatophylax compounds for both egg production and body homeostasis.
Moving towards acceleration for estimates of activity‐specific metabolic rate in free‐living animals: the case of the cormorant
Authors: WILSON RORY P. , WHITE CRAIG R. , QUINTANA FLAVIO , HALSEY LEWIS G. , LIEBSCH NIKOLAI , MARTIN GRAHAM R. , BUTLER PATRICK J.
Published: June 2006

Time and energy are key currencies in animal ecology, and judicious management of these is a primary focus for natural selection. At present, however, there are only two main methods for estimation of rate of energy expenditure in the field, heart rate and doubly labelled water, both of which have been used with success; but both also have their limitations.

The deployment of data loggers that measure acceleration is emerging as a powerful tool for quantifying the behaviour of free‐living animals. Given that animal movement requires the use of energy, the accelerometry technique potentially has application in the quantification of rate of energy expenditure during activity.

In the present study, we test the hypothesis that acceleration can serve as a proxy for rate of energy expenditure in free‐living animals. We measured rate of energy expenditure as rates of O2 consumption () and CO2 production () in great cormorants (Phalacrocorax carbo) at rest and during pedestrian exercise. and were then related to overall dynamic body acceleration (ODBA) measured with an externally attached three‐axis accelerometer.

Both and were significantly positively associated with ODBA in great cormorants. This suggests that accelerometric measurements of ODBA can be used to estimate and and, with some additional assumptions regarding metabolic substrate use and the energy equivalence of O2 and CO2, that ODBA can be used to estimate the activity specific rate of energy expenditure of free‐living cormorants.

To verify that the approach identifies expected trends in from situations with variable power requirements, we measured ODBA in free‐living imperial cormorants (Phalacrocorax atriceps) during foraging trips. We compared ODBA during return and outward foraging flights, when birds are expected to be laden and not laden with captured fish, respectively. We also examined changes in ODBA during the descent phase of diving, when power requirements are predicted to decrease with depth due to changes in buoyancy associated with compression of plumage and respiratory air.

In free‐living imperial cormorants, ODBA, and hence estimated , was higher during the return flight of a foraging bout, and decreased with depth during the descent phase of a dive, supporting the use of accelerometry for the determination of activity‐specific rate of energy expenditure.
Effects of parental effort on blood stress protein HSP60 and immunoglobulins in female blue tits: a brood size manipulation experiment
Authors: MERINO SANTIAGO , MORENO JUAN , TOMÁS GUSTAVO , MARTÍNEZ JAVIER , MORALES JUDITH , MARTÍNEZ‐DE LA PUENTE JOSUÉ , OSORNO JOSÉ LUIS
Published: June 2006

Physiological stress in animals may impose a limit for investment in current reproduction in the wild. A brood manipulation experiment was conducted in a population of blue titsCyanistes caeruleusto study the effect of parental effort on changes in two types of proteins related with stress: the blood stress protein HSP60 and the plasma immunoglobulins.

Levels of HSP60 were reduced across the experiment for females attending reduced broods, and females attending enlarged broods experienced a reduction of immunoglobulin levels. Moreover, the overall changes in the levels of both proteins were positively related.

By controlling for the change in immunoglobulin levels we found an increase in HSP60 for females in the enlarged treatment, presumably to offset deleterious effects derived from increased effort.

Maternal effort was able to partially compensate for the effect of treatment as nestlings did not differ in mass and levels of immunoglobulins and HSP60 among treatments.

Physiological stress as reflected in stress and immunoglobulin proteins may limit maternal effort in breeding blue tits.
Species resistance and community response to wind disturbance regimes in northern temperate forests
Authors: PAPAIK M. J. , CANHAM C. D.
Published: June 2006

Severe winds are the predominant cause of natural disturbance in temperate forests of north‐eastern and north‐central North America. Conceptual models of the effects of wind disturbance have traditionally focused on the impacts of catastrophic disturbances and have painted a simple picture of how disturbance acts to maintain tree species diversity. These models ignore variation among species characteristics that could have important consequences for both resistance to and recovery from disturbance.

We integrated an empirically parameterized, mechanistic model of windstorm mortality (WINDSTORM) and a seed‐mass‐based dispersal and recruitment model into a spatially explicit, individual tree model of forest dynamics (SORTIE) in order to create simulated long‐term ‘experiments’ designed to explore the sensitivity of forest composition and structure to species‐specific resistance to and recovery from disturbance.

We found that species‐specific variation in resistance to wind mortality interacted strongly with: (i) shade tolerance characteristics, (ii) the medium‐term history of disturbances, (iii) the long‐term average severity of the disturbance regime and (iv) seedbed substrate dynamics to influence tree population dynamics and successional trajectories.

We also examined how local and long‐distance dispersal affect response to wind disturbance. Ignoring differences among local dispersal characteristics overestimates the importance of dispersal‐limited species. Our results show that long‐distance immigration maintains species coexistence only if the immigration rate is very high relative to local dispersal. Despite this, stand‐scale models that ignore long‐distance dispersal can underestimate population dynamics of dispersal‐limited species.

Our results indicate that landscape‐scale heterogeneity in structure and species composition in these forests is facilitated by synergisms between the stochastic nature of wind disturbance and complex interactions between species traits that govern: (i) resistance to disturbance, (ii) local dispersal and seedling establishment and (iii) competitive (i.e. growth/survival) traits that do not adhere to strict tradeoffs.

We conclude that wind disturbance has much more complex and variable effects on long‐term dynamics of forest structure and composition than suggested by previous models. In particular, non‐catastrophic disturbances can generate important variation in forest dynamics that can either lead to dominance by a single or small number of species, or facilitate species coexistence.
Bayesian identification of admixture events using multilocus molecular markers
Authors: CORANDER JUKKA , MARTTINEN PEKKA
Published: June 2006

Bayesian statistical methods for the estimation of hidden genetic structure of populations have gained considerable popularity in the recent years. Utilizing molecular marker data, Bayesian mixture models attempt to identify a hidden population structure by clustering individuals into genetically divergent groups, whereas admixture models target at separating the ancestral sources of the alleles observed in different individuals. We discuss the difficulties involved in the simultaneous estimation of the number of ancestral populations and the levels of admixture in studied individuals’ genomes. To resolve this issue, we introduce a computationally efficient method for the identification of admixture events in the population history. Our approach is illustrated by analyses of several challenging real and simulated data sets. The software (baps), implementing the methods introduced here, is freely available at http://www.rni.helsinki.fi/~jic/bapspage.html.
Sub‐lethal responses of the large pine weevil, Hylobius abietis, to the pyrethroid insecticide lambda‐cyhalothrin
Authors: ROSE D. , MATTHEWS G. A. , LEATHER S. R.
Published: June 2006

Abstract The response of the large pine weevil (Hylobius abietis) to the pesticide lambda‐cyhalothrin, a pyrethroid, is investigated. Both behavioural (feeding preferences) and nutritional and physiological (lipid content) responses are recorded. Hylobius abietis shows both a significant avoidance of pesticide‐treated food sources and a decrease in lipid content after exposure, but a full recovery after feeding on untreated food. It is proposed that the mechanism for the pesticide avoidance and altered lipid levels is due to an anti‐feedant effect of the pesticide. Implications for pest management programmes are described.
Antennal olfactory sensitivity in response to task‐related odours of three castes of the ant Atta mexicana (hymenoptera: formicidae)
Authors: LÓPEZ‐RIQUELME GERMÁN OCTAVIO , MALO EDI A. , CRUZ‐LÓPEZ LEOPOLDO , FANJUL‐MOLES MARíA LUISA
Published: June 2006

Abstract The relationship between scent composition and antennal sensitivity in different castes of Atta mexicana is investigated under laboratory conditions. Extracts of dead ants are analysed by gas chromatography‐mass spectrometry to identify the compounds presumably responsible for the specific undertaking behaviour. Oleic acid is identified as one compound that triggers undertaking behaviour. To determine differences in odour reception between workers of different castes (i.e. foragers, undertakers and soldiers), further antennal sensitivity to task‐related odours is tested using electroantennographic techniques. Soldiers are the most specialized caste because of their low response to all odours, except odourants related to alarm pheromones. The behavioural specialization of soldiers and their reduced behavioural repertoire are discussed.
Long‐term growth of soybean at elevated [CO2] does not cause acclimation of stomatal conductance under fully open‐air conditions
Authors: LEAKEY ANDREW D. B. , BERNACCHI CARL J. , ORT DONALD R. , LONG STEPHEN P.
Published: June 2006

Accurately predicting plant function and global biogeochemical cycles later in this century will be complicated if stomatal conductance (gs) acclimates to growth at elevated [CO2], in the sense of a long‐term alteration of the response of gs to [CO2], humidity (h) and/or photosynthetic rate (A). If so, photosynthetic and stomatal models will require parameterization at each growth [CO2] of interest. Photosynthetic acclimation to long‐term growth at elevated [CO2] occurs frequently. Acclimation of gs has rarely been examined, even though stomatal density commonly changes with growth [CO2]. Soybean was grown under field conditions at ambient [CO2] (378 µmol mol−1) and elevated [CO2] (552 µmol mol−1) using free‐air [CO2] enrichment (FACE). This study tested for stomatal acclimation by parameterizing and validating the widely used Ball et al. model (1987, Progress in Photosynthesis Research, vol IV, 221–224) with measurements of leaf gas exchange. The dependence of gs on A, h and [CO2] at the leaf surface was unaltered by long‐term growth at elevated [CO2]. This suggests that the commonly observed decrease in gs under elevated [CO2] is due entirely to the direct instantaneous effect of [CO2] on gs and that there is no longer‐term acclimation of gs independent of photosynthetic acclimation. The model accurately predicted gs for soybean growing under ambient and elevated [CO2] in the field. Model parameters under ambient and elevated [CO2] were indistinguishable, demonstrating that stomatal function under ambient and elevated [CO2] could be modelled without the need for parameterization at each growth [CO2].
Extensional tectonics and volcano lateral collapses: insights from Ollagüe volcano (Chile‐Bolivia) and analogue modelling
Authors: Tibaldi Alessandro , Bistacchi Andrea , Pasquarè Federico Aligi , Vezzoli Luigina
Published: June 2006

Understanding the process of volcanic lateral collapse, which may be governed by numerous possible factors, can be significantly improved by identifying the role of each factor. Here we test the perturbation induced in a volcano by tectonic normal faulting in the basement, magma inflation and multiple flank deformation, based on fieldwork and analogue experiments. Ollagüe Volcano (Chile‐Bolivia) provides a good example of a sector collapse with exposed substrate extensional tectonics, and our experiments have been done with conditions consistent with field data. Results show that none of the possible tectonic conditions led to complete lateral failure; in agreement also with the field data, sector collapse of the model cone occurred only when a shallow magmatic intrusion within the volcano was reproduced. We also found out that volcano flank deformation is enhanced if a previous flank destabilization occurred, interleaved by new cone growth.

Terra Nova, 18, 282–289, 2006
NSAID‐induced gastrointestinal damage: Current clinical management and recommendations for prevention
Authors: LANAS Angel , FERRANDEZ Angel
Published: June 2006

Gastrointestinal toxicity is a common adverse effect of traditional non‐steroidal anti‐inflammatory drugs (NSAIDs) and patients at risk should receive prevention therapies. Selective cyclooxygenase‐2 (COX‐2) inhibitors (coxibs) are safer to the gastrointestinal tract than traditional NSAIDs. Current prevention strategies in patients who need NSAIDs should also take into account the presence of cardiovascular risk factors, as coxibs and probably most traditional NSAIDs increase the incidence of serious cardiovascular events. Patients without risk factors should be treated with traditional NSAIDs, whereas patients at risk may receive cotherapy with a proton pump inhibitor (PPI) or misoprostol, or a coxib alone. However, patients with a previous bleeding ulcer should receive the combination of a coxib plus a PPI, and Helicobacter pylori should be tested for and treated if present. Coxib and NSAID therapy should be prescribed with caution in patients with increased cardiovascular risk and should be prescribed at the lowest possible dose and for the shortest period of time. These patients will probably be treated with low‐dose aspirin or other antiplatelet agents, which puts them at increased risk of upper gastrointestinal complications. The risk of gastrointestinal toxicity with combined therapy of aspirin and coxib may be lower than that with traditional NSAIDs plus aspirin, but all these patients may benefit from PPI cotherapy. When the lower gastrointestinal tract is of concern, coxib instead of NSAID therapy should be considered. Coxib therapy has better gastrointestinal tolerance than traditional NSAIDs and PPI therapy is effective both in the treatment and prevention of NSAID‐induced dyspepsia and should be considered in patients who develop dyspepsia during NSAID or coxib therapy.
Additional bedtime H2‐receptor antagonist for the control of nocturnal gastric acid breakthrough: A Cochrane systematic review
Authors: PAN Tao , WANG Yi Ping , LIU Fu Cheng , YANG Jin Lin
Published: June 2006

OBJECTIVES:  To assess the effectiveness and safety of additional bedtime H2‐receptor antagonists (H2RAs) in suppressing nocturnal gastric acid breakthrough (NAB) via a systematic review.

METHODS:  Eligible trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL) (Cochrane Library Issue 2, 2004), MEDLINE (January 1966–June 2004), EMBASE (January 1980–June 2004) and CINAHL (January 1982–June 2004). Additional hand‐searching was conducted on the proceedings of correlated conferences, eight important Chinese journals and references of all included trials. All randomized controlled trials evaluating H2RAs for the control of NAB were eligible for inclusion. The systematic review was conducted using methods recommended by The Cochrane Collaboration.

RESULTS:  Only two randomized crossover studies, comprising 32 participants, met the inclusion criteria. Because the design, dosage and duration of the treatments were different between the studies, it was not possible to conduct meta‐analysis. There were no consistent conclusions found between the two included studies in evaluating H2RAs for the control of NAB.

CONCLUSIONS:  No implications for practice at this stage can be concluded. Appropriately designed large‐scale randomized controlled trials with long‐term follow up are needed to determine the effects of additional bedtime H2RAs in suppressing NAB.
Differentiation potential of bone marrow stromal cells to enteric neurons in vitro
Authors: GAO Yuan Jun , QIAN Wei , WANG Bu Hai , LIN Rong , HOU Xiao Hua
Published: June 2006

OBJECTIVE:  To investigate whether bone marrow stromal cells (BMSC) can be induced to differentiate into enteric neurons and to produce more nerve growth factor (NGF) and glial cell line‐derived neurotrophic factor (GDNF).

METHODS:  Bone marrow stromal cells were harvested from male Sprague–Dawley rats and cultured in Dulbecco's modified eagle medium supplemented with 20% fetal bovine serum. The BMSC were passaged six times and characterized by flow cytometry. The BMSC were pre‐induced by basic fibroblast growth factor (10 ng/mL) for 24 h, then induced with GDNF in fetal gut condition medium (FGCM) for 10 days. The expressions of neuronal markers neural specific enolase (NSE), neurofilament (NF), glial cell marker, glial fibrillary acedic protein (GFAP), and enteric neuronal marker protein gene product 9.5 (PGP9.5), neural nitric oxide synthase (nNOS), and enteric neural transmitter vasoactive intestinal polypeptide (VIP) were detected by fluorescent immunohistochemistry. Expression levels of GDNF and NGF mRNA were determined by RT‐PCR.

RESULTS:  The cultured BMSC were CD90 (99.7%) positive and CD45 negative on flow cytometry. At day 10 of induction, 58.5 ± 10.8% cells adopted neuron‐like morphological changes and showed expression of NSE (47.6 ± 7.5%), NF (75.6 ± 8.4%), GFAP (negative), PGP9.5 (57.7 ± 6.5%), nNOS (46.6 ± 5.4%) and VIP (72.3 ± 6.7%) by immunofluorescence. The BMSC expressed low levels of NGF and GDNF mRNA; however, after induction of GDNF in FGCM, the expression levels of NGF and GDNF mRNA were significantly increased.

CONCLUSION:  Bone marrow stromal cells have the potential to be induced to differentiate into enteric neurons, express enteric neural transmitters, and produce more NGF and GDNF. Therefore, BMSC could be used as new method to treat gastrointestinal motility disorders associated with enteric neural lesions.
Alteration of the pancreatic endocrine component in the early stage of acute necrotic pancreatitis in rats
Authors: LI Yong Yu , ZHU Guo Ying , GAO Yong Xin , YANG Zhi Yong , WANG Zhu Yi
Published: June 2006

OBJECTIVE:  To investigate alterations of the pancreatic endocrine component in the early stage of acute necrotic pancreatitis (ANP) in rats.

METHODS:  Thirty‐six Sprague–Dawley rats were randomly allocated to two groups: ANP group (n = 18) and sham‐operated (control) group (n = 18). ANP was induced by retrograde injection of 4% sodium deoxycholate (40 mg/kg, 0.1 mL/min) into the biliopancreatic duct and the severity of pancreatitis induced was assessed by histopathological examination and level of plasma amylase. The pancreatic endocrine function was assessed by measuring the levels of plasma glucose and insulin and by measuring the insulin content in pancreatic β cells by immunofluorescence and immunocytochemistry.

RESULTS:  Five hours after operation, the pancreas of rats in the ANP group showed pathological changes with edema, hemorrhage, fatty necrosis, acinar destruction and leukocyte infiltration in the exocrine portion of the pancreas. Plasma amylase activity increased significantly (P < 0.01) and bloody ascites appeared in the abdominal cavity. Nevertheless the endocrine islets appeared normal and the β cells contained intensive labeling of insulin. Levels of glucose and insulin in plasma increased significantly. In the ANP group, 5 h after operation the plasma level of glucose was 8.18 ± 2.26 mmol/L vs 6.39 ± 1.26 mmol/L, and of insulin was 23.27 ± 3.50 MIU/L vs 18.40 ± 3.98 MIU/L. In the control group, 5 h after operation the plasma level of glucose was 9.39 ± 0.62 mmol/L vs 5.89 ± 0.62 mmol/L, and of insulin was 26.28 ± 4.77 MIU/L vs 12.89 ± 2.05 MIU/L; there was no significant difference between these two groups (P > 0.05). After a bolus injection of glucose, however, a much higher level of insulin was found in the control group (35.30 ± 5.05 MIU/L) than that in the ANP group (23.91 ± 4.62 MIU/L, P < 0.05).

CONCLUSIONS:  There may be an impaired ability of insulin release in response to glucose stimulation in the early stage of ANP, although the morphology of the pancreatic endocrine component remains intact.
Histopathological study of vascular changes after intra‐arterial and intravenous injection of N‐butyl‐2‐cyanoacrylate
Authors: WANG Yan Mei , CHENG Liu Fang , LI Nan
Published: June 2006

OBJECTIVE:  To assess the histopathological vascular changes after injection of N‐butyl‐2‐cyanoacrylate into the vessels of adult rabbits.

METHODS:  The animals used were 42 pure‐blood New Zealand white rabbits weighing 2–3 kg. 0.2 mL cyanoacrylate with lipiodol was injected into the external jugular vein and femoral artery of each rabbit. Tissue specimens were obtained for histopathological study at 3 days, 7 days, 2 weeks, 3 weeks, 4 weeks, 2 months and 3 months after injection.

RESULTS:  The vessels were obliterated immediately after the injection. The main manifestation of histopathology at 3 days to 2 weeks was an acute inflammatory reaction; this progressed to subacute vasculitis at 3 weeks and a chronic granulomatous foreign body reaction developed at 4 weeks. The glue mass essentially disappeared in 2–3 months, replaced by fibrotic tissue with partial vascular recanalization. At 3 weeks after injection, the elastic fibrils of the arterial wall proliferated distinctly, resulting in narrowing of the lumen with subsequent obliteration, whereas the venous wall still showed inflammation and necrosis without hyperplasia of elastic fibrils. Extrusion of glue was observed over 1–3 months in both arteries and veins and was obvious in the latter.

CONCLUSIONS:  The histopathological changes after injection of N‐butyl‐2‐cyanoacrylate were similar in the arteries and the veins with the exception of hyperplasia of elastic fibrils in the arterial wall and inflammation and necrosis in the venous wall at 2–3 weeks. Glue extrusion was seen in both arteries and veins.
An antibody derivative expressed from viral vectors passively immunizes pigs against transmissible gastroenteritis virus infection when supplied orally in crude plant extracts
Authors: Monger Wendy , Alamillo Josefa M. , Sola Isabel , Perrin Yolande , Bestagno Marco , Burrone Oscar R. , Sabella Patricia , Plana‐Duran Joan , Enjuanes Luis , Garcia Juan A. , Lomonossoff George P.
Published: June 2006

To investigate the potential of antibody derivatives to provide passive protection against enteric infections when supplied orally in crude plant extracts, we have expressed a small immune protein (SIP) in plants using two different plant virus vectors based on potato virus X (PVX) and cowpea mosaic virus (CPMV). The ɛSIP molecule consisted of a single‐chain antibody (scFv) specific for the porcine coronavirus transmissible gastroenteritis virus (TGEV) linked to the ɛ‐CH4 domain from human immunoglobulin E (IgE). In some constructs, the sequence encoding the ɛSIP molecule was flanked by the leader peptide from the original murine antibody at its N‐terminus and an endoplasmic reticulum retention signal (HDEL) at its C‐terminus to allow the expressed protein to be directed to, and retained within, the endoplasmic reticulum. Western blot analysis of samples from Nicotiana clevelandii or cowpea tissue infected with constructs revealed the presence of SIP molecules which retained their ability to dimerize. The analysis of crude plant extracts revealed that the plant‐expressed ɛSIP molecules could bind to and neutralize TGEV in tissue culture, the levels of binding and neutralization reflecting the level of expression. Oral administration of crude extracts from SIP‐expressing plant tissue to 2‐day‐old piglets demonstrated that the extracts which showed the highest levels of in vitro neutralization could also provide in vivo protection against challenge with TGEV.
ESTIMATION IN RICKER'S TWO‐RELEASE METHOD: A BAYESIAN APPROACH
Authors: Lee Shen‐Ming , Chen Cathy W.S. , Gerlach Richard H. , Huang Li‐Hui
Published: June 2006

The Ricker's two‐release method is a simplified version of the Jolly‐Seber method, from Seber's Estimation of Animal Abundance (1982), used to estimate survival rate and abundance in animal populations. This method assumes there is only a single recapture sample and no immigration, emigration or recruitment. In this paper, we propose a Bayesian analysis for this method to estimate the survival rate and the capture probability, employing Markov chain Monte Carlo methods and a latent variable analysis. The performance of the proposed method is illustrated with a simulation study as well as a real data set. The results show that the proposed method provides favourable inference for the survival rate when compared with the modified maximum likelihood method.
THE CASE FOR PARITY AND BIRTH‐ORDER STATISTICS
Authors: Corr Patrick , Kippen Rebecca
Published: June 2006

Parity refers to the number of (live) births that a woman (or man) has had. Birth order refers to whether a birth is the first, second, third or higher‐order birth of the parent. In the context of low and shifting fertility, parity and birth‐order statistics are becoming increasingly important for understanding fertility trends and patterns, for policy, and for carrying out projections of future fertility.

In Australia, the main sources of demographic data are birth, death and marriage registers, and the five‐yearly national census. Both the birth registers and the census are ideally placed to collect data required to calculate parity and birth‐order statistics. However not all Australian states and territories collect or code the necessary information in the birth registers, and the parity question ‘For each female, how many babies has she ever had?’ is only asked every second census; that is, once every 10 years. In this paper, we outline the importance and uses of parity and birth‐order statistics. We discuss the Australian data available at present and their gaps and shortcomings. We then describe the ‘gold standard’ of parity and birth‐order statistics and how Australia can achieve this standard through some minor changes to the data collection process.
ESTIMATING THE NUMBER OF VISITS TO THE DOCTOR
Authors: Berzel Andreas , Heller Gillian Z. , Zucchini Walter
Published: June 2006

The frequency of doctor consultations has direct consequences for health care budgets, yet little statistical analysis of the determinants of doctor visits has been reported. We consider the distribution of the number of visits to the doctor and, in particular, we model its dependence on a number of demographic factors. Examination of the Australian 1995 National Health Survey data reveals that generalized linear Poisson or negative binomial models are inadequate for modelling the mean as a function of covariates, because of excessive zero counts, and a mean‐variance relationship that varies enormously over covariate values. A negative binomial model is used, with parameter values estimated in subgroups according to the discrete combinations of the covariate values. Smoothing splines are then used to smooth and interpolate the parameter values. In effect the mean and the shape parameters are each modelled as (different) functions of gender, age and geographical factors. The estimated regressions for the mean have simple and intuitive interpretations. However, the dependence of the (negative binomial) shape parameter on the covariates is more difficult to interpret and is subject to influence by extreme observations. We illustrate the use of the model by estimating the distribution of the number of doctor consultations in the Statistical Local Area of Ryde, based on population numbers from the 1996 census.
BAYESIAN ANALYSIS OF THE ADDITIVE MIXED MODEL FOR RANDOMIZED BLOCK DESIGNS
Authors: Wang Jenting , Hsu John S.J.
Published: June 2006

This paper deals with the Bayesian analysis of the additive mixed model experiments. Consider b randomly chosen subjects who respond once to each of t treatments. The subjects are treated as random effects and the treatment effects are fixed. Suppose that some prior information is available, thus motivating a Bayesian analysis. The Bayesian computation, however, can be difficult in this situation, especially when a large number of treatments is involved. Three computational methods are suggested to perform the analysis. The exact posterior density of any parameter of interest can be simulated based on random realizations taken from a restricted multivariate t distribution. The density can also be simulated using Markov chain Monte Carlo methods. The simulated density is accurate when a large number of random realizations is taken. However, it may take substantial amount of computer time when many treatments are involved. An alternative Laplacian approximation is discussed. The Laplacian method produces smooth and very accurate approximates to posterior densities, and takes only seconds of computer time. An example of a pipeline cracks experiment is used to illustrate the Bayesian approaches and the computational methods.
Presidential IQ, Openness, Intellectual Brilliance, and Leadership: Estimates and Correlations for 42 U.S. Chief Executives
Authors: Simonton Dean Keith
Published: June 2006

Individual differences in intelligence are consistently associated with leader performance, including the assessed performance of presidents of the United States. Given this empirical significance, IQ scores were estimated for all 42 chief executives from George Washington to G. W. Bush. The scores were obtained by applying missing‐values estimation methods (expectation‐maximization) to published assessments of (a) IQ (Cox, 1926; n = 8), (b) Intellectual Brilliance (Simonton, 1986c; n = 39), and (c) Openness to Experience (Rubenzer & Faschingbauer, 2004; n = 32). The resulting scores were then shown to correlate with evaluations of presidential leadership performance. The implications for George W. Bush and his presidency were then discussed.