bluuebunny/crossref_metadata_2025 huggingface dataset:
Silencing DJ‐1 reveals its contribution in paraquat‐induced autophagy
Authors: González‐Polo Rosa A. , Niso‐Santano Mireia , Morán José M. , Ortiz‐Ortiz Miguel A. , Bravo‐San Pedro José M. , Soler Germán , Fuentes José M.
Published: March 2009

J. Neurochem. (2009) 109, 889–898.

The role of autophagy as a survival strategy of cells constitutes an emerging topic in the study of the pathogenesis of several diseases with autophagic changes being described in a number of age‐related neurodegenerative disorders, including Parkinson’s disease (PD). Although the etiology of PD is still unknown, both environmental (for example, paraquat exposure) and genetic factors have been investigated as putative causes of the disease. In the latter case, mutations or changes in the protein DJ‐1 have been reported to be associated with autosomal recessive, early‐onset parkinsonism. In this paper we established a model system to study the involvement of the DJ‐1 protein in paraquat‐induced autophagy. When human neuroblastoma SH‐SY5Y cells were transfected with DJ‐1‐specific small interfering RNAs and exposed to paraquat, we observed (i) sensitization additive with paraquat‐induced apoptotic cell death, (ii) inhibition of the cytoplasmic accumulation of autophagic vacuoles as well as the recruitment of LC3 fusion protein to the vacuoles, (iii) exacerbation of apoptotic cell death in the presence of the autophagy inhibitor 3‐methyladenine, and (iv) an increase in mammalian target of rapamycin phosphorylation. Taken together, these findings suggest an active role for DJ‐1 in the autophagic response produced by paraquat, providing evidence for the role of PD‐related proteins in the autophagic degradation pathway, a factor that should be considered in the design of potential therapies for the treatment of the disease.
Inducible over‐expression of wild type α‐synuclein in human neuronal cells leads to caspase‐dependent non‐apoptotic death
Authors: Vekrellis Kostas , Xilouri Maria , Emmanouilidou Evangelia , Stefanis Leonidas
Published: March 2009

Alpha‐synuclein (ASYN) is central in Parkinson’s disease pathogenesis. Converging pieces of evidence suggest that the levels of ASYN expression play a critical role in both familial and sporadic Parkinson’s disease. To elucidate the mechanism underlying wild type (WT) ASYN‐mediated neurotoxicity, we have generated a novel Tet‐Off SHSY‐5Y cell line, conditionally expressing WT ASYN. Induction of human WT ASYN in retinoic acid‐differentiated SHSY‐5Y cells leads to accumulation of soluble ASYN oligomers, in the absence of inclusions, and to gradual cellular degeneration. Morphologically, the death observed is non‐apoptotic. Caspases other than caspase 3, including caspase 9, are activated and caspase inhibition diminishes death by acting at a point upstream of cytochrome c release. Application of Scyllo‐inositol, an oligomer‐stabilizing compound, prevents neuronal death in this model. These findings are consistent with a model in which oligomeric ASYN triggers the initial activation of the apoptotic pathway, which is however blocked downstream of the mitochondrial checkpoint, thus leading to a death combining in a unique fashion both apoptotic and non‐apoptotic features. This novel inducible cell model system may prove valuable in the deciphering of WT ASYN‐induced pathogenic effects and in the assessment and screening of potential therapeutic strategies.
Bioenergetic analysis of isolated cerebrocortical nerve terminals on a microgram scale: spare respiratory capacity and stochastic mitochondrial failure
Authors: Choi Sung W. , Gerencser Akos A. , Nicholls David G.
Published: March 2009

Pre‐synaptic nerve terminals (synaptosomes) require ATP for neurotransmitter exocytosis and recovery and for ionic homeostasis, and are consequently abundantly furnished with mitochondria. Pre‐synaptic mitochondrial dysfunction is implicated in a variety of neurodegenerative disorders, although there is no precise definition of the term ‘dysfunction’. In this study, we test the hypothesis that partial restriction of electron transport through Complexes I and II in synaptosomes to mimic possible defects associated with Parkinson’s and Huntington’s diseases respectively, sensitizes individual terminals to mitochondrial depolarization under conditions of enhanced proton current utilization, even though these stresses are within the respiratory capacity of the synaptosomes when averaged over the entire population. We combine two novel techniques, firstly using a modification of a plate‐based respiration and glycolysis assay that requires only microgram quantities of synaptosomal protein, and secondly developing an improved method for fluorescent imaging and statistical analysis of single synaptosomes. Conditions are defined for optimal substrate supply to the in situ mitochondria within mouse cerebrocortical synaptosomes, and the energetic demands of ion cycling and action‐potential firing at the plasma membrane are additionally determined.
Chronic stress elicits prolonged activation of α‐MSH secretion and subsequent degeneration of melanotroph
Authors: Ogawa Tokiko , Shishioh‐Ikejima Nobue , Konishi Hiroyuki , Makino Tetsuya , Sei Hiroyoshi , Kiryu‐Seo Sumiko , Tanaka Masaaki , Watanabe Yasuyoshi , Kiyama Hiroshi
Published: March 2009

Prolonged stress affects homeostasis in various organs and induces stress‐associated disorders. We examined the cellular changes of pituitary gland under the continuous stress condition using a rat model in which rats were kept in a cage filled with water to a height of 1.5 cm for up to 5 days. Among the pituitary hormone mRNAs, proopiomelanocortin mRNA was up‐regulated specifically in the intermediate lobe (IL) of this rat model. Additionally, the peripheral blood levels of α‐melanocyte stimulating hormone (α‐MSH), a major product of proopiomelanocortin in IL were increased. The α‐MSH secreting cells, melanotrophs, showed a markedly developed endoplasmic reticulum and Golgi apparatus in the early phase of the experiment. Subsequent continuous stress caused remarkable dilation of the endoplasmic reticulum, disruption of the Golgi structure, and the degeneration of some melanotrophs. In addition the dopaminergic nerve fibers from hypothalamus were markedly decreased in IL. A dopamine antagonist elicited the similar morphologic changes of melanotroph in normal rat. These findings suggest that prolonged stress suppressed hypothalamus‐derived dopamine release in IL, which elicited over‐secretion of α‐MSH from the melanotrophs. The present study also suggests that prolonged hyperactivation of endocrine cells could lead to disorder of secretion mechanisms and eventual degeneration.
Dynamic chromatin remodeling events in hippocampal neurons are associated with NMDA receptor‐mediated activation of Bdnf gene promoter 1
Authors: Tian Feng , Hu Xian‐Zhang , Wu Xuan , Jiang Hong , Pan Hongna , Marini Ann M. , Lipsky Robert H.
Published: March 2009

To determine the epigenetic events associated with NMDA receptor‐mediated activation of brain‐derived neurotrophic factor gene (Bdnf) promoter 1 by hippocampal neurons in culture, we screened 12 loci across 4.5 kb of genomic DNA 5′ of the transcription start site (TSS) of rat Bdnf for specific changes in histone modification and transcription factor binding following NMDA receptor stimulation. Chromatin immunoprecipitation (ChIP) assays showed that NMDA receptor stimulation produced a durable, time‐dependent decrease in histone H3 at lysine 9 dimethylation (H3K9me2), within 3 h after NMDA treatment across multiple loci. Concomitant increases in H3K4me2 and H3K9/14 acetylation (H3AcK9/14) were associated with transcriptional activation, but occurred at fewer sites within the promoter. The decrease in H3K9me2 was associated with release of HDAC1, MBD1, MeCP2, and REST from specific locations within promoter 1, although with different kinetics. In addition, occupancy of sites proximal to and distal to the TSS by the transcription factors NF‐κB, CREB‐binding protein (CBP), and cAMP‐response element‐binding protein were correlated with increased occupancy of RNA polymerase II at two loci proximal to the TSS following NMDA receptor stimulation. These temporal changes in promoter occupancy could occur thousands of base pairs 5′ of the TSS, suggesting a mechanism that produces waves of Bdnf transcription.
The Eocene Arctic Azolla bloom: environmental conditions, productivity and carbon drawdown
Authors: SPEELMAN E. N. , VAN KEMPEN M. M. L. , BARKE J. , BRINKHUIS H. , REICHART G. J. , SMOLDERS A. J. P. , ROELOFS J. G. M. , SANGIORGI F. , DE LEEUW J. W. , LOTTER A. F. , SINNINGHE DAMSTÉ J. S.
Published: March 2009

Enormous quantities of the free‐floating freshwater fern Azolla grew and reproduced in situ in the Arctic Ocean during the middle Eocene, as was demonstrated by microscopic analysis of microlaminated sediments recovered from the Lomonosov Ridge during Integrated Ocean Drilling Program (IODP) Expedition 302. The timing of the Azolla phase (~48.5 Ma) coincides with the earliest signs of onset of the transition from a greenhouse towards the modern icehouse Earth. The sustained growth of Azolla, currently ranking among the fastest growing plants on Earth, in a major anoxic oceanic basin may have contributed to decreasing atmospheric pCO2 levels via burial of Azolla‐derived organic matter. The consequences of these enormous Azolla blooms for regional and global nutrient and carbon cycles are still largely unknown. Cultivation experiments have been set up to investigate the influence of elevated pCO2 on Azolla growth, showing a marked increase in Azolla productivity under elevated (760 and 1910 ppm) pCO2 conditions. The combined results of organic carbon, sulphur, nitrogen content and 15N and 13C measurements of sediments from the Azolla interval illustrate the potential contribution of nitrogen fixation in a euxinic stratified Eocene Arctic. Flux calculations were used to quantitatively reconstruct the potential storage of carbon (0.9–3.5 1018 gC) in the Arctic during the Azolla interval. It is estimated that storing 0.9 1018 to 3.5 1018 g carbon would result in a 55 to 470 ppm drawdown of pCO2 under Eocene conditions, indicating that the Arctic Azolla blooms may have had a significant effect on global atmospheric pCO2 levels through enhanced burial of organic matter.
The Jews in the Medieval Polish Economy: Some Thoughts on the Historiography of the Twentieth Century
Authors: Komornicka Jolanta N.
Published: March 2009

This essay was runner‐up in the 2007History CompassGraduate Essay Prize, Europe Section.

The historiography of medieval Jewry has often by‐passed the place of Jews in Poland, leaving that region for early modern scholars to tackle. Yet Poland had a significant Jewish population by the thirteenth century, though ascertaining its origins has been an issue of considerable debate among scholars and one heavily influenced by modern prejudices. As the scholarship has pulled itself from the anti‐Semitic morass of the early twentieth century, gradually greater weight has been given to the place of Jews in Polish communities apart from the stereotyped role of moneychanger and royal financer. Yet East and West have still to come together to provide a better nuanced understanding of both the Jews in Europe and the growth of cities and communes along the eastern border of the Latin West.
Lack of effect of norfloxacin on hyperdynamic circulation in bile duct‐ligated rats despite reduction of endothelial nitric oxide synthase function: result of unchanged vascular Rho‐kinase?
Authors: Hennenberg Martin , Trebicka Jonel , Buecher Doris , Heller Jörg , Sauerbruch Tilman
Published: March 2009

Background/Aims: In cirrhosis, portal hypertension is maintained by splanchnic vasodilation owing to overproduction of the vasodilator nitric oxide (NO) and defective contractile signalling by Rho‐kinase. NO overproduction is partially caused by bacterial translocation from the gut to mesenteric lymph nodes. However, the effects of intestinal bacterial decontamination on hyperdynamic circulation or vascular contractility are unknown. We investigated the haemodynamic and vascular effects of norfloxacin in rats with secondary biliary cirrhosis.

Methods: Cirrhosis was induced by bile duct ligation (BDL). One group was treated with norfloxacin (20 mg/kg/day, 5 days, orally). Bacterial growth in the lymph nodes was determined on blood agar plates. Invasive haemodynamic measurements were combined with coloured microspheres. Aortic contractility was assessed myographically. Protein expression/phosphorylation was examined by Western blot analysis.

Results: Norfloxacin treatment of BDL rats abolished bacterial translocation to mesenteric lymph nodes. BDL rats had hyperdynamic circulation, including portal hypertension and splanchnic vasodilation. None of these parameters was changed by norfloxacin, although norfloxacin reduced endothelial NO synthase expression and phosphorylation. The latter was associated with a diminished activity of protein kinase G (PKG), which mediates NO‐induced vasodilation. However, norfloxacin had no effect on aortic contractility to methoxamine or Ca2+, or the aortic expression of RhoA, Rho‐kinase and β‐arrestin 2, or the phosphorylation of the Rho‐kinase substrate moesin.

Conclusions: Short‐term treatment of BDL rats with norfloxacin does not change hyperdynamic circulation or vascular contractility, despite reduction of PKG activity.
Partial epilepsy syndrome in a Gypsy family linked to 5q31.3‐q32
Authors: Angelicheva Dora , Tournev Ivailo , Guergueltcheva Velina , Mihaylova Violeta , Azmanov Dimitar N. , Morar Bharti , Radionova Melania , Smith Shelagh J. , Zlatareva Dora , Stevens John M. , Kaneva Radka , Bojinova Veneta , Carter Kim , Brown Matthew , Jablensky Assen , Kalaydjieva Luba , Sander Josemir W.
Published: March 2009

Purpose:  The restricted genetic diversity and homogeneous molecular basis of Mendelian disorders in isolated founder populations have rarely been explored in epilepsy research. Our long‐term goal is to explore the genetic basis of epilepsies in one such population, the Gypsies. The aim of this report is the clinical and genetic characterization of a Gypsy family with a partial epilepsy syndrome.

Methods:  Clinical information was collected using semistructured interviews with affected subjects and informants. At least one interictal electroencephalography (EEG) recording was performed for each patient and previous data obtained from records. Neuroimaging included structural magnetic resonance imaging (MRI). Linkage and haplotype analysis was performed using the Illumina IVb Linkage Panel, supplemented with highly informative microsatellites in linked regions and Affymetrix SNP 5.0 array data.

Results:  We observed an early‐onset partial epilepsy syndrome with seizure semiology strongly suggestive of temporal lobe epilepsy (TLE), with mild intellectual deficit co‐occurring in a large proportion of the patients. Psychiatric morbidity was common in the extended pedigree but did not cosegregate with epilepsy. Linkage analysis definitively excluded previously reported loci, and identified a novel locus on 5q31.3‐q32 with an logarithm of the odds (LOD) score of 3 corresponding to the expected maximum in this family.

Discussion:  The syndrome can be classified as familial temporal lobe epilepsy (FTLE) or possibly a new syndrome with mild intellectual deficit. The linked 5q region does not contain any ion channel–encoding genes and is thus likely to contribute new knowledge about epilepsy pathogenesis. Identification of the mutation in this family and in additional patients will define the full phenotypic spectrum.
Asymmetric seizure termination in primary and secondary generalized tonic–clonic seizures
Authors: Walser Gerald , Unterberger Iris , Dobesberger Judith , Embacher Norbert , Falkenstetter Tina , Larch Julia , Kuchukhidze Giorgi , Gotwald Thaddaeus , Ortler Martin , Bauer Gerhard , Trinka Eugen
Published: March 2009

Purpose: In temporal lobe epilepsies an asymmetric termination (AST) of the clonic phase of secondary generalized tonic–clonic seizures (sGTCS) reliably lateralizes the side of seizure onset. The last clonic activity occurs ipsilateral to the side of the seizure onset zone. We compared the prevalence and lateralizing value of AST in sGTCS of frontal and temporal lobe origin as well as in primary generalized tonic–clonic seizures (pGTCS).

Methods: We analyzed 177 seizures in 84 consecutive patients. Forty‐one patients had temporal lobe epilepsy (TLE), 24 frontal lobe epilepsy (FLE), and 19 had nonfocal (primary) generalized epilepsies (GE). All patients underwent intensive video‐EEG (electroencephalography) monitoring, high‐resolution magnetic resonance imaging (MRI), neuropsychological testing, and single photon emission computed tomography/positron emission tomography (SPECT/PET) when feasible. Two investigators blinded for diagnosis, EEG, and imaging data assessed frequency and side of the last clonic jerk.

Results: AST occurred in 63% of patients with TLE (47% of seizures), in 71% with FLE (60% of seizures), and in 42% with GE (21% of seizures). These results were not significant for patients, but significant for seizures in TLE versus GE and in FLE versus GE (p < 0.001). The positive predictive value (PPV) for the side of seizure onset was 74% (p = 0.003) in TLE and 75% (p = 0.008) in FLE.

Discussion: AST in sGTCS lateralizes the side of seizure onset in TLE and in FLE to the ipsilateral hemisphere with a high PPV. However, AST was also observed in GE. Therefore, asymmetric clinical signs should not inevitably lead to the assumption of focal epilepsy syndromes.
Cardiac function and antiepileptic drug treatment in the elderly: A comparison between lamotrigine and sustained‐release carbamazepine
Authors: Saetre Erik , Abdelnoor Mikael , Amlie Jan Peder , Tossebro Morten , Perucca Emilio , Taubøll Erik , Anfinsen Ole Gunnar , Isojärvi Jouko , Gjerstad Leif
Published: March 2009

Purpose:  To investigate the comparative effects of carbamazepine (CBZ) and lamotrigine (LTG) on electrocardiography (ECG) parameters in elderly patients with newly diagnosed epilepsy.

Methods:   The study was conducted in the Norwegian subcohort (n = 108) of an international randomized double‐blind 40‐week trial, which compared the efficacy and tolerability of LTG and sustained‐release CBZ in patients aged 65 and older with newly diagnosed epilepsy. Target maintenance doses were 400 mg/day for CBZ and 100 mg/day for LTG, with adjustments based on clinical response. Patients with significant unpaced atrioventricular (AV) conduction defect were excluded. Resting 12‐lead ECG recordings were made under standardized conditions at pretreatment (baseline) and at the 40‐week study visit (treatment visit). Changes in QRS interval (primary endpoint), heart rate (HR), PQ, and QTc (HR‐corrected QT) intervals were assessed and compared between groups.

Results:  Of the 108 patients randomized, 33 discontinued prematurely because of adverse events (n = 24, none of which was cardiac) or other reasons (n = 9), and 15 were nonevaluable due to incomplete ECG data. None of the assessed ECG parameters differed significantly between groups at baseline. No significant ECG changes were recorded between baseline and treatment visit for QRS duration and QTc intervals, whereas HR fell and PQ intervals increased slightly on both treatments. However, there were no differences between groups in changes from baseline to treatment visit. There were no significant relationships between individual ECG changes and serum drug concentrations, except for QTc intervals, which decreased slightly with increasing CBZ concentrations. The proportion of patients with ECG parameters outside the normal range at treatment visit was similar to that recorded at baseline.

Discussion:  Clinically significant ECG changes are not common during treatment with CBZ or LTG in elderly patients with no preexisting significant AV conduction defects.
Effects of Prenatal Ethanol Exposure on Hypothalamic‐Pituitary‐Adrenal Function Across the Estrous Cycle
Authors: Lan Ni , Yamashita Fiona , Halpert Alison G. , Sliwowska Joanna H. , Viau Victor , Weinberg Joanne
Published: March 2009

Background: Rats prenatally exposed to ethanol (E) typically show increased hypothalamic‐pituitary‐adrenal (HPA) responses to stressors in adulthood. Importantly, prenatal ethanol may differentially alter stress responsiveness in male and female offspring, suggesting a role for the gonadal hormones in mediating the effects of ethanol on HPA activity. We investigated the role of ethanol‐induced changes in hypothalamic‐pituitary‐gonadal (HPG) activity in the differential HPA regulation observed in E compared to control females across the estrous cycle.

Methods: Peripheral hormones and changes in central neuropeptide mRNA levels were measured across the estrous cycle in adult female offspring from E, pair‐fed (PF) and ad libitum‐fed control (C) dams.

Results: Ethanol females showed normal estrous cyclicity (vaginal smears) but delayed sexual maturation (vaginal opening). Both HPG and HPA activity were differentially altered in E (and in some cases, PF) compared to control females as a function of estrous cycle stage. In relation toHPG activity,E and PF females had higher basal and stress estradiol (E2) levels in proestrus compared to other phases of the cycle, and decreased GnRH mRNA levels compared to C females in diestrus. Further, E females had greater variation in LH than PF and C females across the cycle, and in proestrus, only E females showed a significant LH increase following stress. In relation toHPA activity, both basal and stress CORT levels and overall ACTH levels were greater in E than in C females in proestrus. Furthermore, AVP mRNA levels were increased overall in E compared to PF and C females.

Conclusions: These data demonstrate ethanol‐induced changes in both HPG and HPA activity that are estrous phase‐specific, and support the possibility that changes in HPA activity in E females may reflect differential sensitivity to ovarian steroids. E females appear to have an increased HPA sensitivity to E2, and a possible shift toward AVP regulation of HPA activity. That PF were similar to E females on some measures suggests that nutritional effects of diet or food restriction played a role in mediating at least some of the changes observed.
Altering the Relative Abundance of GABAAReceptor Subunits Changes GABA‐ and Ethanol‐Responses inXenopusOocytes
Authors: Hurley Joyce H. , Ballard Carrie J. , Edenberg Howard J.
Published: March 2009

Background: Variations inGABRA2andGABRG3, genes encoding the α2 and γ3 subunits of the pentameric GABAAreceptor, are associated with the risk of developing alcoholism in adults, conduct disorder at younger ages, and with differences in electroencephalographic power in the β frequency range. The SNPs associated with alcoholism did not alter the coding of these genes, and extensive DNA sequencing ofGABRA2did not find coding changes in the high‐risk haplotypes. Therefore, we hypothesize that the associations arise from differences in gene expression.

Methods: Here we report studies inXenopusoocytes to examine the functional effects of altering the relative abundance of these 2 receptor subunits on GABA current and response to ethanol, as a model of potential effects of regulatory differences.

Results: When human α2β2γ3 subunits are co‐expressed, increasing the amount of the α2 subunit mRNA increased GABA current; in contrast, increasing the amount of the γ3 subunit decreased GABA currents. Acute ethanol treatment of oocytes injected with a 1:1:1 or 2:2:1 ratio of α2:β2:γ3 subunit mRNAs resulted in significant potentiation of GABA currents, whereas ethanol inhibited GABA currents in cells injected with a 6:2:1 ratio. Overnight treatment with ethanol significantly reduced GABA currents in a manner dependent on the ratio of subunits.

Conclusions: These studies demonstrate that changes in relative expression of GABAAreceptor subunits alter the response of the resulting channels to GABA and to ethanol.
SIAM‐Like Phenomenon Caused by Low Doses of Alcohol
Authors: Shimamoto Akiko , Liu Jin‐Yao , Fujimiya Tatsuya
Published: March 2009

Background: Swift increase in alcohol metabolism (SIAM) is usually evoked by a large dose of ethanol, which is often demonstrated by an abrupt increase in oxygen uptake. SIAM was induced by low doses of ethanol and evaluated by pharmacokinetic analyses of ethanol and its metabolites.

Methods: Rabbits were initially administered 1.0 g/kg of ethanol solution and the same dose was given to the bolus group 6 hours after the first injection. The infusion group was administered 0.25 g/kg/h of ethanol 2 hours after the first injection. Blood concentrations of ethanol, acetaldehyde, and acetate were then determined and comparisons were made using pharmacokinetic parameters.

Results: A significantly higher ethanol elimination rate was observed after re‐administration of ethanol to the bolus group. Other pharmacokinetic parameters were unaffected. The concentration at steady state (Css) for the infusion group was stable. A significantly higher level of mean residence time (MRT) in blood acetaldehyde was observed for the bolus group, whereas no MRT changes were observed for the infusion group. A significantly higher level of blood acetate Css was observed after re‐administration of ethanol to the bolus group, following the changes in area under concentration and MRT. No Css changes were observed for the infusion group. The Css of acetate at stage 2 was significantly higher for the bolus group, compared to the infusion group.

Conclusion: Low doses of ethanol enhanced alcohol metabolism in rabbits, according to a pharmacokinetic analysis of circulating ethanol concentrations. Simultaneous analyses of its metabolites followed the kinetic of ethanol.
A Conjoint‐Hazard Model of the Timing of Buyers' Upgrading to Improved Versions of High‐Technology Products*
Authors: Kim Sang‐Hoon , Srinivasan V.
Published: March 2009

Understanding consumers' upgrading behavior is essential to product planning. Product managers would like to know what fraction of customers would upgrade to new and improved versions, and how fast. This paper presents a method to forecast the sales path of an improved version of a high‐technology product defined in terms of its price path and multiattribute product specification. The approach is potentially useful to managers to answer what‐if questions on the effects of alternative price paths and product specifications of the upgrade on when and what fraction of customers will upgrade. By doing such analysis for several product options under consideration, managers can choose the best feature specification and price path for the upgrade. The proposed approach integrates an individual‐level conjoint utility model with a hazard function specification. The first stage of estimation (i.e., conjoint analysis) measures individual‐level multiattribute utility functions, and the second stage (i.e., duration analysis) calibrates the coefficients of predictor variables of the time to upgrade via maximum likelihood. An illustrative application in the personal digital assistant (PDA) category confirms the predictive validity and potential usefulness of the proposed approach. Among the empirical findings are that higher upgrade costs and expectation of faster product improvement tend to delay buyers' upgrading decisions. The roles of other predictor variables such as product category characteristics, consumer characteristics, and peer pressure were also confirmed.
Incorporating Network Externalities into the Technology Acceptance Model*
Authors: Song Michael , Parry Mark E. , Kawakami Tomoko
Published: March 2009

Research on network externalities has identified a number of product categories in which the market performance of an innovation (e.g., unit sales and revenues) is an increasing function of that innovation's installed base and the availability of complementary products. Innovation scholars have attributed these findings to the positive impact of network externality variables on consumer perceptions of innovation attributes. This paper provides the first empirical examination of these perceptual linkages by extending the Technology Acceptance Model to include consumer perceptions of network externality variables. The authors hypothesize that, when direct and indirect network externalities exist, consumer purchase intentions and consumer perceptions of an innovation's usefulness and ease of use will positively reflect perceptions of installed base size and the availability of complementary products. To test this reasoning, the authors developed new measures of consumer perceptions of network externality variables. These measures were incorporated into a survey that explored the attitudes in Japan of potential adopters toward digital music (DM) players at an early stage in the product life cycle. Findings reveal a direct positive relationship between ease of use and the perceived availability of digital music. The authors also find positive and significant relationships between both purchase intention and perceived usefulness and (1) the perceived size of the DM player installed base and (2) the perceived availability of digital music. An application of the Baron‐Kenny test for mediating variables reveals that (1) ease of use partially mediates the relationship between the perceived availability of digital music and perceived usefulness and (2) perceived usefulness partially mediates the relationship between the perceived availability of digital music and purchase intention. The research has important implications for future research on new product adoption and for the management of innovations that involve network externalities. The conceptual model provides a framework for testing alternative explanations of observed variations in the impact of network externalities within and across product categories. The empirical analysis provides guidance for managers who wish to manage the impact of network externalities on adoption. In addition to stimulating the size of the installed base and the variety of complementary products, executives must also manage consumer awareness of network externality variables and consumer understanding of the relationship between those variables and innovation attributes. Finally, traditional adoption models link consumer adoption decisions to perceptions of innovation attributes. The findings provided here imply that predictive accuracy of these models can be improved by including consumer perceptions of network externality variables.
Exploring the Relationships Between Product Development and Environmental Turbulence: The Case of Mobile TLC Services*
Authors: Buganza Tommaso , Dell'Era Claudio , Verganti Roberto
Published: March 2009

Managing innovation in turbulent environments (e.g., in environments with extreme uncertainty and complexity in market needs and technological opportunities) is a major challenge. A recent stream of studies in the management literature has suggested that when facing turbulent environments, firms should deploy more flexible development processes. This paper approaches this issue by looking at the Italian mobile telecommunications (TLC) industry. Nine in‐depth case studies were conducted in five different companies. Data analysis showed some important results. First of all environmental turbulence should be considered to be project specific rather than company or industry specific. Moreover, it can come from both shift in the market needs and in the technology. Nevertheless, it seems clear that having rapid changes is not enough to have environmental turbulence. If rapid changes can be somehow foreseen, there is no turbulence at all. Hence, when approaching projects in potentially turbulent environments, managers should assess both rapidity and unpredictability of the environment. Finally, looking at the in‐depth cases, the paper points out what of the main practices to increase flexibility that are described in literature are actually adopted by companies. In case of turbulence (both in the market and/or in the technology) companies delay concept freezing point. Moreover, in the case of technological turbulence, they also leverage on rapid project iterations, whereas in case of market turbulence they more likely adopt early experiments involving customers, formal and cross‐functional project teams, and flat organizational structures.
Identification of Lead Users for Consumer Products via Virtual Stock Markets*
Authors: Spann Martin , Ernst Holger , Skiera Bernd , Soll Jan Henrik
Published: March 2009

Newly launched products in the consumer goods and services markets show high failure rates. To reduce the failure rates, companies can integrate innovative and knowledgeable customers, the so‐called lead users, into the new product development process. However, the detection of such lead users is difficult, especially in consumer product markets with very large customer bases. A new and potentially valuable approach toward the identification of lead users involves the use of virtual stock markets, which have been proposed and applied for political and business forecasting but not for the identification of experts such as lead users. The basic concept of virtual stock markets is bringing a group of participants together via the Internet and allowing them to trade shares of virtual stocks. These stocks represent a bet on the outcome of future market situations, and their value depends on the realization of these market situations. In this process, a virtual stock market elicits and aggregates the assessments of its participants concerning future market developments. Virtual stock markets might also serve as a feasible instrument to filter out lead users, primarily for the following two reasons. First, a self‐selection effect might occur because sophisticated consumers with a higher involvement in the product of interest decide to participate in virtual stock markets. Second, a performance effect is likely to arise because well‐performing participants in virtual stock markets show a better understanding of the market than their (already self‐selected) fellow participants. So far, only limited information exists about these two effects and their relation to lead user characteristics. The goal of this paper is to analyze the feasibility of virtual stock markets for the identification of lead users. The results of this empirical study show that virtual stock markets can be an effective instrument to identify lead users in consumer products markets. Furthermore, the results show that not all lead users perform well in virtual stock markets. Hence, virtual stock markets allow identifying lead users with superior abilities to forecast market success.
Does Familiarity with Technology Predict Successful Use of an External Loop Recorder? The Loop Recorder Technology Cognition Study (LOCO)
Authors: GULA LORNE J. , KLEIN GEORGE J. , ZURAWSKA URSZULA , MASSEL DAVID , YEE RAYMOND , SKANES ALLAN C. , KRAHN ANDREW D.
Published: March 2009

Background:

The diagnosis of presyncope, syncope, and palpitations is facilitated by successful documentation of the cardiac rhythm during symptoms. We prospectively assessed technological familiarity using a Technology Cognition Questionnaire to determine influence on proper and effective use of an external loop recorder (ELR).

Methods:

Patients with palpitations, presyncope, or syncope were assessed for familiarity with technology and provided an ELR for a period of 6 weeks. Proper use of the device was demonstrated to the patient and test transmissions were sent by analog telephone line on a weekly basis. Patients were instructed to activate the device to record cardiac rhythm when symptoms recurred, and to send these recordings via telephone transmission.

Results:

Ninety‐two patients were prospectively enrolled, with mean age 54.9 ± 20.9 and 42 males (46%). Sixty‐five patients (71%) had recurrence of symptoms during the 6‐week monitoring period. Among these patients, 40 (62%) were successful in recording and transmitting data such that a diagnosis was made at a median of 8 days (IQR 12.5, range 0–30). Among patients with symptoms during the monitoring period, 36 (55%) had at least one failed recording or transmission. On multivariate analysis, failed symptom recording/transmission was less likely among patients able to program a home video recorder (odds ratio [OR] 0.25 [0.07–0.93]), and more likely among patients who failed a test transmission (OR 3.45 [1.04–11.7]). No variables were independently associated with successful diagnosis.

Conclusions:

Familiarity with technology correlates with successful use of the ELR, but does not necessarily correlate with the ability to reach a diagnosis.
Repolarization Spatial‐Time Current Abnormalities in Patients with Coronary Heart Disease
Authors: OGATA KUNIOMI , KANDORI AKIHIKO , WATANABE YASUSHI , SUZUKI AKIHIRO , TANAKA KIMIO , OKA YUJI , TAKAKI HIROSHI , KANZAKI HIDEAKI , NAKATANI SATOSHI , MIYATAKE KUNIO , WATANABE SHIGEYUKI , YAMAGUCHI IWAO , MIYASHITA TSUYOSHI , KAMAKURA SHIRO
Published: March 2009

Background:Magnetocardiography (MCG) is a new technique for visualizing a current distribution in the myocardium. In recent years, current distribution parameters (CDPs) have been developed based on the distribution. The CDPs reflect spatial‐time current abnormalities in patients with coronary heart disease (CHD). However, the criteria and scoring method of the abnormalities using CDPs are still controversial.

Method:We measured MCG signals for 101 normal controls and 56 CHD patients (single‐, double‐, and triple‐vessel diseases) using a MCG system. The CDPs (maximum current vector [MCV], total current vector [TCV], current integral map, and current rotation) during ventricular repolarization were analyzed. To evaluate the CDPs that are effective in distinguishing between normal controls and CHD patients, the areas under the receiver operating characteristic curve (Az) are calculated. Furthermore, the total scores (“0” to “4”) of four CDPs with high Azvalues are also calculated.

Results:MCV and TCV angles at the T‐wave peak had the highest Azvalue. Furthermore, TCV angular differences between the ST‐T segment also had high Azvalues. Using the four CDPs, the averaged total score for patients with triple‐vessel disease was the highest (“2.67”) compared to the other groups (normal controls: 0.53). Furthermore, based on the assumption that subjects with a total score over “1” were suspected of having CHD, sensitivity and specificity were 85.7% and 74.3%, respectively.

Conclusion:We concluded that the score and criteria using MCV and TCV during repolarization in CHD patients can reflect lesion areas and time changes of electrical activation dispersion due to ischemia.
“Cold Can for a Hot Case”: Use of a Coronary Sinus Shocking Lead in Association with Cold Can to Achieve Successful Defibrillation
Authors: HAMID SHOAIB , KHAN SITARA , RINALDI CHRISTOPHER A.
Published: March 2009

Attaining an adequate defibrillation threshold is critical in the functioning of an implantable cardioverter‐defibrillator. This is achieved in a majority of implants but in those where this does not occur, reprogramming, lead repositioning, and ultimately placement of a subcutaneous array lead may be necessary.
Health‐Affecting Compounds in Brassicaceae
Authors: Jahangir Muhammad , Kim Hye K. , Choi Young H. , Verpoorte Robert
Published: March 2009

ABSTRACT:  Brassicaceae vegetables are considered to be a staple food in many areas all over the world. Brassica species are not only known for their high fat and protein contents for human and animal consumption, but Brassicaceae vegetables are recognized as a rich source of nutrients such as vitamins (carotenoids, tocopherol, ascorbic acid, folic acid), minerals (Cu, Zn, P, Mg, among others), carbohydrates (sucrose and glucose), amino acids (for example, L‐alanine, L‐aspartic acid, L‐glutamic acid, L‐glutamine, L‐histidine, L‐methionine, L‐phenylalanine, L‐threonine, L‐tryptophan, and L‐valine), and different groups of phytochemicals such as indole phytoalexins (brassinin, spirobrassinin, brassilexin, camalexin, 1‐methoxyspirobrassinin, 1‐methoxyspirobrassinol, and methoxyspirobrassinol methyl ether), phenolics (such as feruloyl and isoferuloylcholine, hydroxybenzoic, neochlorogenic, chlorogenic, caffeic, p‐coumaric, ferulic, and sinapic acids, anthocyanins, quercetin, and kaempferol), and glucosinolates (mainly glucoiberin, glucoraphanin, glucoalyssin, gluconapin, glucobrassicanapin, glucobrassicin, gluconasturtiin, and neoglucobrassicin). All of these phytochemicals contribute to the reported antioxidant, anticarcinogenic, and cardiovascular protective activities of Brassica vegetables. However, not all members of this family are equal from a nutritional viewpoint, since significant qualitative variations in the phytochemical profiles of Brassica species and varieties suggest differences in the health‐promoting properties among these vegetables. In this article, Brassica phytochemicals with their nutritional value and health‐promoting activities are discussed to give an overview of the literature for Brassica as a staple crop.
PUFAs in Fish: Extraction, Fractionation, Importance in Health
Authors: Sahena F. , Zaidul I.S.M. , Jinap S. , Saari N. , Jahurul H.A. , Abbas K.A. , Norulaini N.A.
Published: March 2009

ABSTRACT: Polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are currently in demand in the pure form and actively being studied to understand their potential roles in human health. Arachidonic acid, 20:4 (n‐6), and DHA, 22:6 (n‐3), are important in normal neurodevelopment and visual function. Infants fed formula often have low blood lipid 20:4 (n‐6) and 22:6 (n‐3). Consumption of fish oils may increase the 20:5 (n‐3) (EPA) and 22:6 (n‐3) (DHA) in human blood. Some marine fish oils contain higher amounts of arachidonic acid, EPA, and DHA. PUFA contents in different marine fishes and methods for their extraction and fractionation, in terms of fatty acid constituents in the form of methyl esters, are covered in this review. Emphasis is given to the fractionations of EPA and DHA by means of supercritical fluid extractions (SFE). The advantages of SFE compared to conventional methods are discussed in this review. PUFAs are usually extracted at about 10 to 30 MPa and at 40 to 80 °C. SFE is a promising and currently the best technique to extract PUFAs, especially EPA and DHA, from marine and freshwater fish.
Pectins in Processed Fruit and Vegetables: Part I—Stability and Catalytic Activity of Pectinases
Authors: Duvetter T. , Sila D.N. , Van Buggenhout S. , Jolie R. , Van Loey A. , Hendrickx M.
Published: March 2009

ABSTRACT:  Pectinases catalyze numerous pectin conversion reactions strongly impacting on the quality of fruits, vegetables, and the related intermediate and end products. The effect of processing on the stability and catalytic activity of pectinases is of prime importance to food processors since desirable and/or deleterious reactions can be tailored (accelerated or inhibited) meeting specific quality targets. Of the multiple endogenous enzymes involved in the modification and degradation of pectin, pectinmethylesterase (PME), and polygalacturonase (PG) have been widely investigated in the context of fruit and vegetable processing. This review covers the stability and catalytic activity of endogenous plant PME and PG including the quantitative approaches applied in inactivating and/or boosting the catalytic activity of the enzymes in purified and real food systems. This will be discussed in the context of both traditional and novel food processing technologies.
Pectins in Processed Fruits and Vegetables: Part II—Structure–Function Relationships
Authors: Sila D.N. , Van Buggenhout S. , Duvetter T. , Fraeye I. , De Roeck A. , Van Loey A. , Hendrickx M.
Published: March 2009

ABSTRACT: Pectin represents a very heterogeneous biopolymer whose functionality remains largely puzzling. The link between the pectin fine structure and functional properties with relevance to plant growth and development, as well as food processing, is continually being explored. This review describes the current knowledge of pectin structure–function relationships. Key mechanisms dictating pectin structure–function relationships are discussed, including the polymer biosynthesis, cross‐linking mechanisms, enzymatic and nonenzymatic conversion reactions, solubility properties, and more. Insight into the polymer structure–function relationships is highlighted by examining traditional and advanced methodologies used in pectin research. The role of pectin in modulating the quality characteristics of plant‐based foods is underlined while pin‐pointing some of the main challenges and perspectives. An integrated approach using the pectin structure–function relationship in the precision engineering of mechanical properties of tissue‐based systems is proposed.
Pectins in Processed Fruits and Vegetables: Part III—Texture Engineering
Authors: Van Buggenhout S. , Sila D.N. , Duvetter T. , Van Loey A. , Hendrickx M.
Published: March 2009

ABSTRACT:  Current interest in controlling the textural and rheological properties of processed fruit and vegetable products has stimulated research on the biochemistry of the cell wall, with particular reference to pectin and its degradation. This review covers the literature over the last decade with respect to pectin engineering in the field of fruit and vegetable processing. Several applications, illustrating that refined manipulation of chemical and/or enzymatic pectin degradation can be used as a tool to improve the texture/rheology of thermally processed and frozen fruit and vegetable products, are described. The discussion includes an evaluation of the role of novel technologies such as high‐pressure processing in pectin engineering of processed fruits and vegetables. Furthermore, the possible role of pectin‐related enzymes other than pectin methylesterase (PME) and polygalacturonase (PG) and of the nontraditional, ferulic acid‐mediated cross‐linking process is discussed. Finally, new trends, challenges, and suggestions for future pectin engineering research are covered in this review.
Both Sides of the Collecting Encounter: The George W. Harley Collection at the Peabody Museum of Archaeology and Ethnology, Harvard University
Authors: Adams Monni
Published: March 2009

The Peabody Museum of Archaeology and Ethnology holds a large collection of wooden facemasks from the Dan and Mano peoples of Northeast Liberia. Made for ritual use, most of these masks were sold in the 1930s to George W. Harley, a medical missionary who worked in the region. This article explores Harley's training, methods, and motives, and the socio‐political conditions under which he collected. Beginning with the notes that Harley provided on the reasons that owners gave for selling their masks, I examine the collection itself for clues to the choices made on the other side of the collecting encounter.
Grain‐Boundary Characterization in a Nonstoichiometric Fine‐Grained Magnesium Aluminate Spinel: Effects of Defect Segregation at the Space‐Charge Layers
Authors: Nuns Nicolas , Béclin Franck , Crampon Jacques
Published: March 2009

The grain‐boundary chemistry of fine‐grained spinel MgO·nAl2O3 (mean grain size below micron) has been investigated by STEM microanalysis. We have quantified the concentration of each element across the grain boundaries. Stoichiometry variations are observed from the grain‐boundary region to the bulk. The Al/Mg ratio increases from 2.1 in the bulk to 2.35 at the grain‐boundary regions. X‐ray quantification allows us to reveal and to characterize the space‐charge layer in the subgrain boundary. The grain‐boundary cores are negatively charged due to

vacancies in excess, and in the subgrain‐boundary region, an opposite, positive space‐charge layer is obtained. The point defect composition and the characteristic (sign, space‐charge potential Φ∞) of the space‐charge layer are discussed.