bluuebunny/crossref_metadata_2025 huggingface dataset:
NOX2‐CONTAINING NADPH OXIDASE AND XANTHINE OXIDASE ARE SOURCES OF SUPEROXIDE IN MOUSE TRACHEA
Authors: Westover Alana , Harrison Craig B , Selemidis Stavros
Published: November 2008

Superoxide anion plays an important role in host defence against invading pathogens and in the inflammation that arises in lungs. The aim of the present study was to elucidate whether the two key candidate superoxide‐producing enzymes in mammalian cells, namely Nox2‐containing NADPH oxidase and xanthine oxidase, are responsible for superoxide production in mouse trachea.

Superoxide production by isolated trachea, as measured by L‐012‐dependent chemiluminescence, was markedly reduced by superoxide dismutase (300 U/mL) and the xanthine oxidase inhibitor allopurinol (100 µmol/L). Tracheas from Nox2−/– mice had significantly lower levels (~60%) of superoxide than control mice.

These novel findings suggest that superoxide production by mouse trachea is attributed to both Nox2‐containing NADPH oxidase and xanthine oxidase.
Effect of being overweight on postoperative morbidity and long‐term surgical outcomes in proximal gastric carcinoma1
Authors: Oh Sung Jin , Hyung Woo Jin , Li Chen , Song Jyewon , Rha Sun Young , Chung Hyun Cheol , Choi Seung Ho , Noh Sung Hoon
Published: November 2008

Background and Aim:  The prevalence of being overweight has risen remarkably in Korea. This study sought to clarify the relationship between being overweight and surgical outcomes in gastric cancer patients.

Methods:  A total of 410 patients who underwent curative total gastrectomies with D2 dissection from January 2000 to December 2003 were retrospectively studied from a prospectively designed database. The patients were assigned to two groups based upon their body mass index (BMI): non‐overweight, BMI < 25 kg/m2; overweight, BMI ≥ 25 kg/m2. Perioperative surgical outcomes, postoperative morbidity, mortality, recurrence, and prognosis were analyzed.

Results:  The overweight group had longer operation time and more postoperative complications than the non‐overweight group. The two groups were similar in terms of transfusion volumes, postoperative bowel movement, time to initiation of a soft diet, and postoperative hospital stay. Patterns of recurrence and cumulative survival rates were similar for each group. Multivariate analysis showed that being overweight was not a risk factor for recurrence or poor prognosis.

Conclusion:  Although being overweight was associated with increased operation time and higher risk of complications in gastric cancer patients undergoing curative total gastrectomy, it had no effect on recurrence or long‐term survival.
The bone histology of osteoderms in temnospondyl amphibians and in the chroniosuchianBystrowiella
Authors: Witzmann Florian , Soler‐Gijón Rodrigo
Published: November 2008

Witzmann, F. and Soler‐Gijón, R. 2010. The bone histology of osteoderms in temnospondyl amphibians and in the chroniosuchianBystrowiella. —Acta Zoologica(Stockholm)91: 96–114

Bone histology of osteoderms in the armoured temnospondylPeltobatrachus, plagiosaurids (Gerrothorax,Plagiosuchus) and dissorophids (Aspidosaurus,Cacops,Platyhystrix), as well as in the chroniosuchianBystrowiella, is studied. The massive osteoderms ofPeltobatrachusandGerrothoraxconsist of homogeneous parallel‐fibred bone, whereas in dissorophids, a lightly built, trabecular middle region is mantled by a thin cortex that is composed of a plywood‐type structure. InBystrowiellaandPlagiosuchus, the osteoderms consist to a large degree of interwoven primary fibres and have cell lacunae that bear stumpy canaliculi. The differences in the histological structure of dissorophids and plagiosaurids suggest an iterative evolution of osteoderms. Furthermore, histology inPlagiosuchusindicates a metaplastic development of the osteoderms, whereas the osteoderms ofGerrothoraxrepresent periosteal ossifications as in dissorophids. This suggests a convergent origin of osteoderms also within plagiosaurids. The extensive armour inGerrothoraxprobably constituted a calcium reservoir, indicated by cyclical resorption events preserved in the external cortex and interpreted as a physiological response to periodic changes in salinity of the aquatic environment. In contrast, the unique osteoderm structure of dissorophids provides maximum stability and minimum bone mass, and is coherent with the interpretation that the osteoderms served to strengthen the vertebral column during terrestrial locomotion.
Targeting and post‐translational processing of human α1‐antichymotrypsin in BY‐2 tobacco cultured cells†
Authors: Benchabane Meriem , Saint‐Jore‐Dupas Claude , Bardor Muriel , Faye Loïc , Michaud Dominique , Gomord Véronique
Published: November 2008

The post‐translational processing of human α1‐antichymotrypsin (AACT) in Bright Yellow‐2 (BY‐2) tobacco cells was assessed in relation to the cellular compartment targeted for accumulation. As determined by pulse‐chase labelling experiments and immunofluorescence microscopy, AACT sent to the vacuole or the endoplasmic reticulum (ER) was found mainly in the culture medium, similar to a secreted form targeted to the apoplast. Unexpectedly, AACT expressed in the cytosol was found in the nucleus under a stable, non‐glycosylated form, in contrast with secreted variants undergoing multiple post‐translational modifications during their transit through the secretory pathway. All secreted forms of AACT were N‐glycosylated, with the presence of complex glycans as observed naturally on human AACT. Proteolytic trimming was also observed for all secreted variants, both during their intracellular transit and after their secretion in the culture medium. Overall, the targeting of human AACT to different compartments of BY‐2 tobacco cells led to the production of two protein products: (i) a stable, non‐glycosylated protein accumulated in the nucleus; and (ii) a heterogeneous mixture of secreted variants resulting from post‐translational N‐glycosylation and proteolytic processing. Overall, these data suggest that AACT is sensitive to resident proteases in the ER, the Golgi and/or the apoplast, and that the production of intact AACT in the plant secretory pathway will require innovative approaches to protect its structural integrity in vivo. Studies are now needed to assess the activity of the different AACT variants, and to identify the molecular determinants for the nuclear localization of AACT expressed in the cytosol.
Using the antisaccade task to investigate the relationship between the development of inhibition and the development of intelligence
Authors: Michel Fiona , Anderson Mike
Published: November 2008

A number of authors have proposed models of cognitive development that explain improvements in intelligence over the course of childhood via changes in the efficiency of inhibitory processes (Anderson, 2001; Bjorklund & Harnishfeger, 1990; Dempster, 1991, 1992; Dempster & Corkill, 1999a; Harnishfeger, 1995; Harnishfeger & Bjorklund, 1993). A review of the literature reveals little empirical support for the thesis. This is largely due to a failure to distinguish between age‐related and non‐age‐related changes in both inhibitory ability and intelligence. Empirical evidence is presented from a developmental study employing the antisaccade task to provide support for the role of inhibitory processes in the development of intelligence. Additionally, a case is made for a functional difference underlying antisaccade errors that are subsequently corrected and those that remain uncorrected.
Age‐related changes in transient and oscillatory brain responses to auditory stimulation during early adolescence
Authors: Poulsen Catherine , Picton Terence W. , Paus Tomáš
Published: November 2008

Maturational changes in the capacity to process quickly the temporal envelope of sound have been linked to language abilities in typically developing individuals. As part of a longitudinal study of brain maturation and cognitive development during adolescence, we employed dense‐array EEG and spatiotemporal source analysis to characterize maturational changes in the timing of brain responses to temporal variations in sound. We found significant changes in the brain responses compared longitudinally at two time points in early adolescence, namely 10 years (65 subjects) and 11.5 years (60 of the 65 subjects), as well as large differences between adults, studied with the same protocol (Poulsen, Picton & Paus, 2007), and the children at 10 and 11.5 years of age. The transient auditory evoked potential to tone onset showed decreases in the latency of vertex and T‐complex components, and a highly significant increase in the amplitude of the N1 wave with increasing age. The auditory steady state response to a 40‐Hz frequency‐modulated tone increased in amplitude with increasing age. The peak frequency of the envelope‐following response to sweeps of amplitude‐modulated white noise also increased significantly with increasing age. These results indicate persistent maturation of the cortical mechanisms for auditory processing from childhood into middle adulthood.
Holistic processing for faces and cars in preschool‐aged children and adults: evidence from the composite effect
Authors: Cassia Viola Macchi , Picozzi Marta , Kuefner Dana , Bricolo Emanuela , Turati Chiara
Published: November 2008

The current study compared the development of holistic processing for faces and non‐face visual objects by testing for the composite effect for faces and frontal images of cars in 3‐ to 5‐year‐old children and adults in a series of four experiments using a two‐alternative forced‐choice recognition task. Results showed that a composite effect for faces was present as early as

years, and none of the age groups tested showed signs of a composite effect for cars. These findings provide the first demonstration that holistic processing is already selective for faces in early childhood, and confirm existing evidence that sensitivity to holistic information in faces does not increase from 4 years to adulthood.
THE VALUE OF CHOICE IN PUBLIC POLICY
Authors: DOWDING KEITH , JOHN PETER
Published: November 2008

Conceptualizing and measuring choice is problematic both in theory and in practice. Measuring by counting the alternatives seems counter‐intuitive as a smaller set of better or more diverse alternatives seems to provide more choice than one that is simply larger. However, concentrating upon better alternatives leads to choice being defined by welfare or utility which is also counter‐intuitive. The implications of this paradox are considered in relation to examples drawn from the choice agenda in British social policy. Empirical difficulties in measuring the welfare gains through implementing greater choice at a time of other central‐led policy initiatives such as targets are discussed, and the extant evidence discussed. Criteria for judging whether or not choice has been welfare‐enhancing are suggested. It is argued that ‘soft choice’ where service providers provide information and explain different options is preferable to ‘hard’ choice of simplistic targets to increase choice by ticking target boxes.
MODERNIZATION AND SPORT: THE REFORM OF SPORT ENGLAND AND UK SPORT
Authors: HOULIHAN BARRIE , GREEN MICK
Published: November 2008

This article evaluates the impact of New Labour’s ‘modernization project’ on two key non‐departmental public bodies for sport, Sport England and UK Sport. Our analysis concentrates on identifying the sources of the general momentum for modernization in the sport sector, how it has been interpreted by government in relation to the two organizations, the nature and consequences of modernization for both organizations, and the future of modernization. The analysis is informed by a range of public documents produced by government and by the two sports agencies, together with a series of seven interviews conducted with senior staff and members of Sport England and UK Sport and with senior civil servants in the Department for Culture, Media and Sport. Our conclusions suggest that modernization has resulted in a narrowing of the two organizations’ objectives, the adoption of business‐like principles and a ‘command and control’ regime in relationships with key frontline delivery partners.
Does Raising the Principal's Wage Improve the School's Outcomes? Quasi‐experimental Evidence from an Unusual Policy Experiment in Israel
Authors: Lavy Victor
Published: November 2008

This paper reports estimates of the causal effects of a 50 percent increase in the salary of headmasters of high schools in Israel. The results suggest that the program led to significant improvements in twelfth‐grade students' academic achievements. However, the effect was relatively modest, comprising increases of about 5–10 percent in the school mean matriculation rate, average score and number of subjects and credit units taken in matriculation programs. Based on these results and the lack of evidence regarding the effect of increasing teachers' salary, it seems that priority should be given to paying higher wages to school principals.
Quasi‐experimental Estimates of the Effect of Class Size on Achievement in Norway*
Authors: Leuven Edwin , Oosterbeek Hessel , Rønning Marte
Published: November 2008

Using a comprehensive Norwegian administrative database, we exploit independent quasi‐experimental methods to estimate the effect of class size on student achievement at the end of lower‐secondary school. Identification based on maximum class‐size rules and population variation (and variations on these methods) give very similar estimates. We cannot reject that the class‐size effect is equal to zero, and can rule out effects as small as 1.5 percent of a standard deviation for a one‐student change in class size during three consecutive years.
Returns to Apprenticeship Training in Austria: Evidence from Failed Firms*
Authors: Fersterer Josef , Pischke Jörn‐Steffen , Winter‐Ebmer Rudolf
Published: November 2008

In the German‐speaking countries, little is known about the payoffs to apprenticeship training for the participants. OLS estimates suggest that the returns are similar to those of other types of schooling. However, there is considerable heterogeneity in the quality of apprenticeships offered, and institutional descriptions suggest that there might be an important element of selection in who obtains an apprenticeship, and what type. In order to overcome the resulting ability bias, we estimate returns to apprenticeship training for apprentices in small Austrian firms which cease to operate. When a firm fails, current apprentices cannot complete their training in this firm. Since apprentices will be at different stages in their apprenticeship at that time, the failure of a firm will manipulate the length of the apprenticeship period completed for some apprentices. The time to firm failure can therefore serve as an instrument for the length of the apprenticeship completed both at the original firm and at other firms. We find instrumental variables returns which are similar or larger than the OLS returns in our sample, indicating relatively little selection.
Proxying Ability by Family Background in Returns to Schooling Estimations is Generally a Bad Idea*
Authors: Mellander Erik , Sandgren‐Massih Sofia
Published: November 2008

When schooling is measured with error and data on ability are lacking, return to schooling estimates will be subject to positive omitted variable bias (OVB) and negative measurement error bias (MEB). We investigate how these biases are affected when ability is proxied by family background variables. We show that the effect on OVB is uncertain, while MEB invariably increases in magnitude. Our empirical analysis demonstrates that MEB generally dominates OVB. With more background variables or increased measurement error, the total bias rapidly becomes negative and increasing in magnitude, thereby driving the return estimate further and further away from the true value.
SEXTUS EMPIRICUS ON THE POSSIBILITY OF INQUIRY
Authors: GRGIC FILIP
Published: November 2008

Abstract: In this paper I discuss Sextus Empiricus’ response to the dogmatists’ objection that the skeptics cannot inquire into philosophical theories and at the same time suspend judgment about everything. I argue that his strategy consists in putting the burden of proof on the dogmatists: it is they, and not the skeptics, who must justify the claim to be able to inquire into the nature of things. Sextus’ arguments purport to show that if we consider the dogmatists’ inquiry, we should conclude either that it is impossible or that it does not supply the skeptics with satisfactory starting‐points for further inquiry.
KAUFMAN'S RESPONSE TO LUCRETIUS
Authors: JOHANSSON JENS
Published: November 2008

Abstract:  The symmetry argument is an objection to the ‘deprivation approach’– the account of badness favored by nearly all philosophers who take death to be bad for the one who dies. Frederik Kaufman's recent response to the symmetry argument is a development of Thomas Nagel's suggestion that we could not have come into existence substantially earlier than we in fact did. In this paper, I aim to show that Kaufman's suggestion fails. I also consider several possible modifications of his theory, and argue that they are unsuccessful as well.
WHAT WILLIAMSON'S ANTI‐LUMINOSITY ARGUMENT REALLY IS*
Authors: WONG WAI‐HUNG
Published: November 2008

Abstract:  Williamson argues that when one feels cold, one may not be in a position to know that one feels cold. He thinks this argument can be generalized to show that no mental states are such that when we are in them we are in a position to know that we are in them. I argue that his argument is a sorites argument in disguise because it relies on the implicit premise that warming up is gradual. Williamson claims that his argument is not a sorites argument; I explain why he has not given us any reason to accept the claim.
Petrosal anatomy in the fossil mammal Necrolestes: evidence for metatherian affinities and comparisons with the extant marsupial mole
Authors: Ladevèze Sandrine , Asher Robert J. , Sánchez‐Villagra Marcelo R.
Published: November 2008

We present reconstructions of petrosal anatomy based on high‐resolution X‐ray computed tomography scans for the fossil mammal Necrolestes and for the marsupial mole Notoryctes sp. Compared with other mammals, Necrolestes exhibits a mosaic of plesiomorphic and derived characters, but most of the evidence supports its metatherian status. We revised previous descriptions and report on features of phylogenetic or functional significance. Necrolestes exhibits features that support metatherian affinities, such as the presence of a short and lateral prootic canal, and the loss of the stapedial artery in adults. A deep groove at the anterior pole of the promontorium is present in front of the cochlear housing, a variant on the extrabullar pathway of the internal carotid artery. The promontorium is laterally bordered by a large bony projection resembling the eutherian tegmen tympani [De Beer GR (1937) The Development of the Vertebrate Skull, Oxford, Clarendon Press, p. 391]. Posteromedial to the secondary facial foramen and anterolateral to the fenestra vestibuli is a pronounced fossa for the tensor tympani muscle. On the medial part of the pars canalicularis there is a great inflation of the medial side of the caudal tympanic process, a structure of unknown function. The internal acoustic meatus exhibits a broad transverse septum and is bordered laterally by a broad prefacial commissure. The cochleae of Necrolestes and of Notoryctes have fewer spiral turns (1.1 and 1.6, respectively) than most marsupials. The lateral semicircular canal is more expanded than the posterior semicircular canal in Necrolestes but not in Notoryctes. Both Necrolestes and Notoryctes have a second crus commune, i.e. the lateral semicircular canal opens into the ampulla of the posterior semicircular canal. A stylomastoid foramen enclosed anterodorsally by both the pars cochlearis and pars canalicularis is present in Dasyuridae, Dromiciops gliroides and Notoryctes.
A three‐dimensional microcomputed tomographic study of site‐specific variation in trabecular microarchitecture in the human second metacarpal
Authors: Lazenby Richard A. , Angus Sarah , Cooper David M. L. , Hallgrímsson Benedikt
Published: November 2008

Variation in trabecular microarchitecture is widely accepted as being regulated by both functional (mechanical loading) and genetic parameters, although the relative influence of each is unclear. Studies reporting inter‐site differences in trabecular morphology (volume, number and structure) reveal a complex interaction at the gene–environment interface. We report inter‐ and intra‐site variation in trabecular anatomy using a novel model of contralateral (left vs right) and ipsilateral (head vs base) comparisons for the human second metacarpal in a sample of n = 29 historically known 19th century EuroCanadians. Measures of bone volume fraction, structure model index, connectivity, trabecular number, spacing and thickness as well as degree of anisotropy were obtained from 5‐mm volumes of interest using three‐dimensional microcomputed tomography. We hypothesized that: (i) the more diverse loading environment of metacarpal heads should produce a more robust trabecular architecture than corresponding bases within sides and (ii) the ipsilateral differences between epiphyses will be larger on the right side than on the left side, as a function of handedness. Analysis of covariance (Side × Epiphysis) with Age as covariate revealed a clear dichotomy between labile and constrained architectures within and among anatomical sites. The predicted variation in loading was accommodated by changes in trabecular volume, whereas trabecular structure did not vary significantly by side or by epiphysis within sides. Age was a significant covariate only for females. We conclude that environmental and genetic regulation of bone adaptation may act through distinct pathways and local anatomies to ensure an integrated lattice of sufficient mass to meet normal functional demands.
Morphology of deltoid origin and end tendons – a generic model
Authors: Leijnse J. N. A. L. , Han S.‐H. , Kwon Y. H.
Published: November 2008

This study provides a model of the complex deltoid origin and end tendons, as a basis for further anatomical, biomechanical and clinical research. Although the deltoid is used in transpositions with upper limb paralysis, its detailed morphology and segmentation has not been object of much study. Morphologically, the deltoid faces two distinct challenges. It closely envelops a ball joint, and it reduces its width over a short distance from a very wide origin along clavicle, acromion and spina scapula, to an insertion as narrow as the humerus. These challenges necessitate specific morphological tendon adaptations. A qualitative model for these tendons is developed by the stepwise transformation of a unipennate muscle model into a functional deltoid muscle. Each step is the solution to one of the mentioned morphological challenges. The final model is of an end tendon consisting of a continuous succession of bipennate end tendon blades centrally interspaced by unipennate tendon parts. The origin tendon consists of lamellae that interdigitate with the end tendon blades, creating a natural segmentation. The model is illustrated by qualitative dissection results. In addition, in view of a proliferation of terms found in the literature to describe deltoid tendons, tendon concepts are reviewed and the systematic use of the unique and simple terminology of ‘origin and end tendons’ is proposed.
Caenorhabditis elegansglutamate transporter deletion induces AMPA‐receptor/adenylyl cyclase 9‐dependent excitotoxicity
Authors: Mano Itzhak , Driscoll Monica
Published: November 2008

In stroke and several neurodegenerative diseases, malfunction of glutamate (Glu) transporters causes Glu accumulation and triggers excitotoxicity. Many details on the cascade of events in the neurodegenerative process remain unclear. As molecular components of glutamatergic synapses are assembled inCaenorhabditis elegansand as many fundamental cellular processes are conserved from nematodes to humans, we studied Glu‐induced necrosis inC. elegansand probed its genetic requirements. We combinedΔglt‐3, a Glu transporter‐null mutation, with expression of a constitutively active form of the alpha subunit of the G protein Gs. While neitherΔglt‐3nor expression of the constitutively active form of the alpha subunit of the G protein Gs is severely toxic toC. eleganshead interneurons, their combination induces extensive neurodegeneration.Δglt‐3‐dependent neurodegeneration acts through Ca2+‐permeable Glu receptors of the α‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazolepropionic acid (AMPA) subtype, requires calreticulin function, and is modulated by calcineurin and type‐9 adenylyl cyclase (AC9). We further show that mammalian AC9 hyperactivates mammalian AMPA‐receptors (AMPA‐Rs) in aXenopusoocyte expression system, supporting that the relationship between AMPA‐Rs hyperactivation and AC9 might be conserved between nematodes and mammals. AMPA‐Rs–AC9 synergism is thus critical for nematode excitotoxicity and could potentially be involved in some forms of mammalian neurodegeneration.
Mechanism of okadaic acid‐induced neuronal death and the effect of estrogens
Authors: Yi Kun Don , Covey Douglas F. , Simpkins James W.
Published: November 2008

Serine/threonine protein phosphatases are important mediators of general cellular function as well as neurodegenerative processes. We have previously shown inhibition of protein phosphatases to be as neurotoxic as glutamate‐induced neuronal death but resistant to neuroprotection by estrogens. In this study, the mechanism by which phosphatase inhibition via okadaic acid (OA) induced neurotoxicity is explored. Neurons were exposed to OA or glutamate in the presence or absence of various protein kinases inhibitors, and/or one of four estrogens. Both OA and glutamate induced cell death via increased reactive oxygen species, protein carbonylation, lipid peroxidation, caspase‐3 activity, and mitochondrial dysfunction. All estrogens attenuated glutamate‐mediated responses, but not OA‐induced responses. In addition, inhibition of protein kinase C and mitogen‐activated protein kinase pathway was neuroprotective against glutamate but not OA toxicity. Interestingly, inhibition of mitogen‐activated protein kinase pathway with PD98096 or U0126 caused a decrease in reactive oxygen species production suggesting that activation of ERK1/2 could further exacerbate the oxidative stress caused by glutamate‐induced toxicity; however, these inhibitors had no effect on OA‐induced toxicity. Collectively, these results indicate that both glutamate and OA neurotoxicities are mediated by persistent activation of ERK1/2 and/or protein kinase C and a resulting oxidative stress, and that protein phosphatase activity is an important and necessary aspect of estrogen‐mediated neuroprotection.
Gating deficits in isolation‐reared rats are correlated with alterations in protein expression in nucleus accumbens
Authors: Roncada Paola , Bortolato Marco , Frau Roberto , Saba Pierluigi , Flore Giovanna , Soggiu Alessio , Pisanu Salvatore , Amoresano Angela , Carpentieri Andrea , Devoto Paola
Published: November 2008

The isolation‐rearing (IR) paradigm, consisting of the social deprivation for 6–9 weeks after weaning, induces a spectrum of aberrant behaviors in adult rats. Some of these alterations such as sensorimotor gating deficits are reminiscent of the dysfunctions observed in schizophrenia patients. Although gating impairments in IR rats have been linked to impairments in the cortico‐mesolimbic system, the specific molecular mechanisms underlying this relation are unclear. To elucidate the neurochemical modifications underlying the gating disturbances exhibited by IR rats, we compared their pre‐pulse inhibition (PPI) of the acoustic startle reflex with that of socially reared (SR) controls, and correlated this index to the results of proteomic analyses in prefrontal cortex and nucleus accumbens from both groups. As expected, IR rats exhibited significantly lower startle amplitude and PPI than their SR counterparts. Following behavioral testing, IR and SR rats were killed and protein expression profiles of their brain regions were examined using two‐dimensional electrophoresis based proteomics. Image analysis in the Coomassie blue‐stained gel revealed that three protein spots were differentially expressed in the nucleus accumbens of IR and SR rats. Mass spectrometry (matrix‐assisted laser desorption ionization‐time of flight and MS/MS) identified these spots as heat shock protein 60 (HSP60), α‐synuclein (α‐syn), and 14‐3‐3 protein ζ/δ. While accumbal levels of HSP60 was decreased in IR rats, α‐syn and 14‐3‐3 proteins were significantly increased in IR in comparison with SR controls. Notably, these two last alterations were significantly correlated with different loudness intensity‐specific PPI deficits in IR rats. In view of the role of these proteins in synaptic trafficking and dopaminergic regulation, these findings might provide a neurochemical foundation for the gating alterations and psychotic‐like behaviors in IR rats.
Na+/K+‐ATPase‐mediated signal transduction and Na+/K+‐ATPase regulation
Authors: Zhang Linan , Zhang Zhe , Guo Huicai , Wang Yongli
Published: November 2008

A number of studies suggest that Na+/K+‐ATPase in caveolae interacts with neighboring membrane proteins and organizes cytosolic cascades of signaling proteins to send messages to intracellular organelles in different tissues, mostly in cardiac myocytes. Low concentration of ouabain binding to Na+/K+‐ATPase activates Src/epidermal growth factor receptor complex to initiate multiple signal pathways, which include PLC/IP3/CICR, PI3K, reactive oxygen species (ROS), PLC/DG/PKC/Raf/MEK/ERK1/2, and Ras/Raf/MEK/ERK1/2 pathways. In cardiac myocytes, the resulting downstream events include the induction of some early response proto‐oncogenes, activation of transcription factors, activator protein‐1, and nuclear factor‐κB, the regulation of a number of cardiac growth‐related genes, and the stimulation of protein synthesis and myocyte hypertrophy and apoptosis. Conversely, several factors acting through signal pathways, such as protein kinases, Ca2+, ROS, etc., can modulate the activity of the Na+/K+‐ATPase.
Solanum indicum ssp. distichum extract is effective against l‐NAME‐induced hypertension in rats
Authors: Bahgat Ashraf , Abdel‐Aziz Heba , Raafat Mohamed , Mahdy Amina , El‐Khatib Aiman S. , Ismail Ahmed , Khayyal Mohamed T.
Published: November 2008

Solanum indicum ssp. distichum is used as a vegetable in some parts of Africa and claimed in folk medicine to guard against cardiovascular disorders. It was of interest to study the potential blood pressure lowering effects of a standardized extract of the fruit. An ethanolic extract of the fruit, standardized to contain > 0.15% chlorogenic acids, was tested orally in both normotensive rats and in those rendered hypertensive by twice daily intraperitoneal injection of NW‐nitro‐l‐arginine methylester (l‐NAME) for 1 week. The extract was either given at the same time as l‐NAME or after the establishment of hypertension. The systolic blood pressure (SBP) was measured non‐invasively using a tail cuff computer‐aided monitoring device. Treatment of normotensive rats with the extract (30–300 mg/kg) for 4 weeks showed no hypotensive effect. Giving the extract (100 and 300 mg/kg) orally once daily during the 1 week hypertension induction period with l‐NAME prevented the development of hypertension. Administration of the extract orally for 1 week after the establishment of hypertension tended to normalize the blood pressure. Pharmacological evidence for the antihypertensive activity of S. distichum is hereby reported for the first time. The extract showed good prophylactic as well as curative effect against l‐NAME‐induced hypertension, whereby its content of chlorogenic acids may play a minor role. Other constituents may be responsible for the antihypertensive action. The findings support further development of the extract as a potential therapeutically useful antihypertensive agent.
Population approaches in paediatrics
Authors: Chatelut Etienne
Published: November 2008

Population pharmacokinetic (PK) approach is now often used to evaluate PK characteristics of a new compound during its clinical development. Recently, new legislation governing the development and authorization of medicines for use in children aged 0–17 years was introduced in the European Union. Among the strategies proposed in relation to clinical aspects, use of population PKs is stated. In this manuscript, comparison between standard PK and population PK methods will be briefly addressed to understand why the second is particularly adapted to perform PK studies in paediatrics. Then, specific patients’ characteristics (covariates) in paediatrics will be presented. Examples of PK and PK–pharmacodynamic (PK–PD) studies will be finally given. The number of population PK studies published still exceeds largely those of PK–PD.
Minutes from the round table held at Paris on July 6, 2007†
Authors: Laveille Christian , Vis Peter
Published: November 2008

A symposium called “Contribution of modelling in the paediatric drug development” was organized at Paris on July 5‐6, 2007 under the auspices of INSERM. The following issues were highlighted and discussed by the participants at the end of the meeting during a round table:

• What is the place of modelling at a preclinical stage in the paediatric development?

• What is the place of modelling at a clinical stage in the paediatric development?

• What are the requirements for an evaluation based on modelling?

• What are the recommendations and guidelines need to be established to facilitate the use of modelling techniques in paediatrics?

This paper summarizes the discussion around these four questions.
Vibration Phase‐Based Ordering of Vibration Patterns Acquired With a Shearing Speckle Interferometer and Pulsed Illumination
Authors: Somers P. A. A. M. , Bhattacharya N.
Published: November 2008

Abstract:  A method for both temporal and spatial characterisation of harmonic vibrations is presented. The method is based on simultaneous acquisition of phase‐stepped speckle interference patterns using a shearing speckle interferometer and the vibration phase for a series of vibration states within the vibration period. An unsynchronised free‐running pulse laser is used for illuminating a vibrating object yielding speckle interference patterns in random vibration phase order. Two π/2 phase‐stepped speckle interference patterns are acquired simultaneously for each recorded vibration state. The data set is sorted using vibration phase as the sorting key. The sorted speckle interference patterns are processed using a two‐bucket algorithm for the calculation of phase difference and by applying temporal phase unwrapping to finally obtain unwrapped phase distributions for any vibration state of the vibration cycle.
Application of Double‐Focus Speckle Interferometry for Non‐Destructive Testing
Authors: Bruno L. , Poggialini A.
Published: November 2008

Abstract:  This paper deals with the application of a speckle interferometer, which works on the new operating principle of double‐focusing presented by the authors in recent studies, to the field of non‐destructive testing (NDT). Using this interferometer, the components of displacement given by holographic interferometry can be measured, but with no need for an external reference beam. The implementation of this interferometry can be indifferently carried out by adopting a Michelson or a Mach–Zender configuration. In the paper a double‐focus interferometer based on the Michelson design and sensitive to out‐of‐plane displacements was implemented and applied to a metallic specimen which simulates the deformations of a typical debonding.
A Note on Tensile Testing of Poled and Unpoled Piezoelectric Ceramics
Authors: Motola Y. , Banks‐Sills L. , Fourman V.
Published: November 2008

Abstract:  Tensile tests were carried out on unpoled and poled soft lead zirconate titanate (PZT) ceramic materials: APC #855 (APC International) and PZT‐5H (Morgan Electro Ceramics). The tests were performed on a dog‐bone specimen with holes at its edges. A methodology is presented for carrying out these tests. A tensile stress was applied by means of Kevlar strings through the specimen holes. The poling direction was perpendicular to the longitudinal specimen axis. For the poled specimens, two electrical boundary conditions were applied, namely, E = 0 and D = 0. Strains were measured at four points on the sample. For each specimen, the bending percentage was calculated. For all specimens, stress–strain curves were found to be initially linear; at a strain of approximately 0.0001, the curves became nonlinear. Young’s modulus was measured in the linear region of the stress–strain curve. Young’s modulus values were highest for the poled material with an open circuit boundary condition (D = 0) and lowest for the unpoled material.
An Understanding of the Width Effect in FRP–Concrete Debonding
Authors: Subramaniam K. V. , Carloni C. , Nobile L.
Published: November 2008

Abstract:  The scaling of the ultimate load in fibre‐reinforced polymer (FRP)–concrete debonding with the relative width of the FRP is experimentally investigated in this paper. Shear debonding tests are performed to evaluate the cohesive stress transfer between the adherents during the interface crack growth which produces debonding. Concrete specimens with two different widths and different widths of FRP are used in the experimental programme. The nominal stress at debonding increases with the FRP‐to‐concrete width ratio. For a given width of FRP composite sheet, lower debonding stress is obtained from concrete specimens with a larger width. The strain distribution on the FRP and concrete free surface at different stages of debonding was determined using a full‐field optical technique known as digital image correlation. The contribution of the two factors, the boundary effect and the restraint from the surrounding concrete, was studied from the measured strain distribution. The strain distributions across the FRP composite sheet and the concrete within the cohesive stress transfer zone associated with the interface crack are shown to be very inhomogeneous. A region of constant width associated with high shear strains is found at the edge of the FRP sheet during the entire debonding process. The increase in the ultimate nominal stress at debonding is shown to be due to the decrease in the proportion of the total width of the FRP occupied by the edge region. It is shown that the boundary region within the FRP is of a fixed width. The width of concrete close to the edge of the FRP involved in stress transfer, however, increases with the width of FRP. It is established that when the FRP‐to‐concrete width ratio is smaller than 0.5, the level of restraint from concrete increases with the FRP width.
Eccrine Nevus Presenting as a Hypopigmented Patch
Authors: Salama Hania , Shwayder Tor
Published: November 2008

Abstract:  A 14‐month‐old Caucasian male presented with a hypopigmented patch associated with increased perspiration on the right side of his back, flank, and abdomen. Starch iodide test and biopsy revealed an eccrine nevus. The truncal presentation and light color both were unique presentations of this rare hamartoma.
Pyoderma Gangrenosum in Association with Autoimmune Neutropenia of Infancy
Authors: Mehta Anisha J. , Charman Carolyn R.
Published: November 2008

Abstract:  We report the case of a 10‐month‐old girl who presented with a spontaneous ulcer on the left buttock which failed to heal despite antibiotic therapy. Histology showed changes consistent with pyoderma gangrenosum and the ulcer resolved rapidly with super‐potent topical steroids under occlusion. Blood tests revealed a persistent neutropenia. Immunoglobulin G (IgG) antineutrophil antibodies were detected in the serum, directed against human neutrophil antigen (HNA)‐1a. Bone marrow studies showed normocellular marrow with no evidence of dysplasia. T and B cell subsets and karotype analysis were normal. Autoimmune neutropenia is an uncommon self‐limiting condition in young children. Pyoderma gangrenosum is rare in infants, although the buttocks are a common site of involvement in this age group. Pyoderma gangrenosum in infancy can be associated with systemic disease as in adults, particularly myelodysplasia and leukemia, arthritis and inflammatory bowel disease. However, the association of pyoderma gangrenosum and autoimmune neutropenia of infancy has not previously been reported.
Differences in Acne Treatment Prescribing Patterns of Pediatricians and Dermatologists: An Analysis of Nationally Representative Data
Authors: Yentzer Brad A. , Irby Cynthia E. , Fleischer Jr. Alan B. , Feldman Steven R.
Published: November 2008

Abstract:  Background: Acne vulgaris is a very common disease process that is seen frequently by both pediatricians and dermatologists. However, treatment may be different depending on specialty. Objectives: To compare pediatricians’ and dermatologists’ patterns of treatment for acne vulgaris. Methods: National Ambulatory Medical Care Survey data on office visits to pediatricians and dermatologists for acne vulgaris were analyzed from 1996 to 2005. Results: During this 10‐year time period, dermatologists managed an estimated 18.1 million acne visits and pediatricians managed an estimated 4.6 million acne visits. Dermatologists prescribed topical retinoids considerably more frequently than did pediatricians (46.1% of acne visits for dermatologists vs 12.1% for pediatricians). Conclusions: There is an opportunity for pediatricians to play a greater role in the management of patients with acne. A shift toward greater use of topical retinoids by pediatricians would be more in line with the practice of dermatologists and with current acne treatment consensus guidelines.
Gianotti‐Crosti Syndrome Following Hepatitis A Vaccination
Authors: KOLIVRAS ATHANASSIOS , ANDRÉ JOSETTE
Published: November 2008

Abstract:  We report a case of Gianotti‐Crosti syndrome in a child following hepatitis A vaccination in order to insist that currently available hepatitis A vaccines are highly immunogenic and that Gianotti‐Crosti syndrome is a possible minor adverse reaction.
Assessing the Market Value of Real Estate Property with a Geographically Weighted Stochastic Frontier Model
Authors: Samaha Stephen A. , Kamakura Wagner A.
Published: November 2008

In this study we consider the problem of sellers, buyers and real estate appraisers in determining the price for a house, taking into account the characteristics of the house and its location as well as the goals of these three different parties. The appraiser's job is to determine the fair market value of the house, while the buyer and seller want to find, respectively, the lowest and highest feasible price for it. We combine recent developments in geography and econometrics to develop an approach that determines local estimates of property values from the perspectives of the buyer, seller and appraiser, taking into account the characteristics of the house as well as its location. We illustrate our approach analyzing closing prices in one residential real estate market.
Induction of Cell Wall Thickening by the Antifungal Compound Dihydromaltophilin Disrupts Fungal Growth and is Mediated by Sphingolipid Biosynthesis
Authors: LI SHAOJIE , CALVO ANA M. , YUEN GARY Y. , DU LIANGCHENG , HARRIS STEVEN D.
Published: November 2008

ABSTRACT. Dihydromaltophilin (heat‐stable antifungal factor [HSAF]) is an antifungal metabolite produced in Lysobacter enzymogenes biocontrol strain C3. This compound induces cell wall thickening in Aspergillus nidulans. Here we show that the cell wall thickening is a general response to HSAF in diverse fungal species. In the A. nidulans model, the thickened cell wall negatively affects hyphal growth. Growth of HSAF‐pre‐treated hyphae failed to resume at hyphal tips with thick cell wall and the actin cable could not re‐polarize at the thickened region of the cell wall, even after the treated hyphae were transferred to drug‐free medium. Moreover, HSAF‐induced cell wall thickening is mediated by sphingolipid synthesis: HSAF failed to induce cell wall thickening in the absence of ceramide synthase BarA and the sphingolipid synthesis inhibitor myriocin was able to suppress HSAF‐induced cell wall thickening. The thickened cell wall could be digested by chitinase suggesting that chitin contributes to the HSAF‐induced thickening. Furthermore, HSAF treatment activated the transcription of two chitin synthase encoding genes chsB and chsC.
PCR‐Based Diversity Estimates of Artificial and Environmental 18S rRNA Gene Libraries
Authors: POTVIN MARIANNE , LOVEJOY CONNIE
Published: November 2008

ABSTRACT. Environmental clone libraries constructed using small subunit ribosomal RNA (rRNA) or other gene‐specific primers have become the standard molecular approach for identifying microorganisms directly from their environment. This technique includes an initial polymerase chain reaction (PCR) amplification step of a phylogenetically useful marker gene using universal primers. Although it is acknowledged that such primers introduce biases, there have been few studies if any to date systematically examining such bias in eukaryotic microbes. We investigated some implications of such bias by constructing clone libraries using several universal primer pairs targeting rRNA genes. Firstly, we constructed artificial libraries using a known mix of small cultured pelagic arctic algae with representatives from five major lineages and secondly we investigated environmental samples using several primer pairs. No primer pair retrieved all of the original algae in the artificial clone libraries and all showed a favorable bias toward the dinoflagellate Polarella glacialis and a bias against the prasinophyte Micromonas and a pennate diatom. Several other species were retrieved by only one primer pair tested. Despite this, sequences from nine environmental libraries were diverse and contained representatives from all major eukaryotic clades expected in marine samples. Further, libraries from the same sample grouped together using Bray–Curtis clustering, irrespective of primer pairs. We conclude that environmental PCR‐based techniques are sufficient to compare samples, but the total diversity will probably always be underestimated and relative abundance estimates should be treated with caution.
Variable Bax antigenicity is linked to keratinocyte position within epidermal strata and UV‐induced apoptosis
Authors: Zuliani Thomas , Obriot Hélène , Tual Martine , Lachman‐Weber Nadège , Dumas Marc , Formstecher Pierre , Polakowska Renata , Ratinaud Marie‐Hélène
Published: November 2008

Abstract:  Pro‐ and anti‐apoptotic members of the Bcl‐2 family are fundamental in the control of apoptosis. Among them, Bax plays a key role in apoptosis induction by mediating the release of apoptogenic factors from mitochondria to the cytosol. In this report, we investigated, by immunohistofluorescence, the in vivo distribution of Bax in normal human epidermis before and 24 h after exposure to solar‐simulated radiation. Bax expression was evaluated with three different, Western blot pretested, anti‐Bax antibodies (Ab) and correlated with markers of keratinocyte differentiation and apoptosis using anti‐β1 integrin and anti‐active caspase‐3 Abs respectively. Using anti‐Bax N20 and A‐3533 polyclonal Ab, we found that, whereas undifferentiated keratinocytes of the basal proliferative compartment contained Bax in the cytosol, the differentiated suprabasal cells had Bax mainly in the nucleus. This immunoreactivity pattern was not modified by skin irradiation. Interestingly, the well known apoptosis‐related Bax redistribution to mitochondria in response to a cell death signal, could be detected only with yet another, the 2D2 monoclonal Ab. This relocalization occurred specifically in apoptotic, active caspase‐3 positive cells of irradiated epidermis. Our data highlight the differentiation‐ and apoptosis‐associated changes in the pattern of Bax subcellular and cellular distribution as uncovered by different anti‐Bax Abs and suggest that Bax undergoes successive activation that progresses in parallel with keratinocyte differentiation and apoptosis.