bluuebunny/crossref_metadata_2025 huggingface dataset:
Optimized compact filtering schemes for computational aeroacoustics
Authors: Zhanxin Liu , Qibai Huang , Li Hu , Jixuan Yuan
Published: September 2008

Spurious waves are inevitably introduced in the simulation of computational aeroacoustics problems by finite difference schemes. Filters are proposed to damp the spurious waves as soon as they are generated. A family of filtering schemes, both interior and boundary, are optimized in this paper. The transfer functions of the filters are approximated to modified Gaussian functions and sharp spectral cutoffs are obtained. The advanced sequential quadratic programming method is employed to get the approximation. Although all of the optimized filters are stable and perform well in the computation, we find that the optimized fourth‐order filters are sufficient for different kinds of requirements. The improvements of the accuracy and convenient application of the optimized filters are demonstrated when applied to one‐ and two‐dimensional problems. Copyright © 2008 John Wiley & Sons, Ltd.
Solution of fully developed free convection of a micropolar fluid in a vertical channel by homotopy analysis method
Authors: Bataineh A. Sami , Noorani M. S. M. , Hashim I.
Published: September 2008

In this paper, we reconsider the problem of fully developed natural convection heat and mass transfer of a micropolar fluid in a vertical channel with asymmetric wall temperatures and concentrations. The resulting boundary‐value problem is solved analytically by the homotopy analysis method. The accuracy of the present solution is found to be in excellent agreement with the solutions of Cheng (Int. Commun. Heat Mass Transfer 2006; 33:627–635). Copyright © 2008 John Wiley & Sons, Ltd.
Testing the martingale hypothesis for futures prices: Implications for hedgers
Authors: de Ville de Goyet Cédric , Dhaene Geert , Sercu Piet
Published: September 2008

The martingale hypothesis for futures prices is investigated using a nonparametric approach where it is assumed that the expected futures returns depend (nonparametrically) on a linear combination of predictors. We first collapse the predictors into a single‐index variable where the weights are identified up to scale, using the average derivative estimator proposed by T. Stoker (1986). We then use the Nadaraya–Watson kernel estimator to calculate (and visually depict) the relationship between the estimated index and the expected futures returns. We discuss implications of this finding for a noninfinitely risk‐averse hedger. © 2008 Wiley Periodicals, Inc. Jrl Fut Mark 28:1040–1065, 2008
Age‐related brain structural alterations in children with specific language impairment
Authors: Soriano‐Mas Carles , Pujol Jesús , Ortiz Héctor , Deus Joan , López‐Sala Anna , Sans Anna
Published: September 2008

Previous neuroimaging studies have suggested that children with specific language impairment (SLI) may show subtle anatomical alterations in specific brain regions. We aimed to characterize structural abnormalities in children with SLI using a voxel‐wise analysis over the whole brain. Subjects covered a wide age range (5–17 years) in order to assess the dynamic nature of the disorder across childhood. Three‐dimensional MRIs were collected from 36 children with SLI and from a comparable group of healthy controls. Global gray and white matter measurements were obtained for each subject, and voxel‐based morphometry (VBM) was used to evaluate between‐group differences in regional brain anatomy. Possible age‐related changes were assessed in separate analyses of younger (below 11 years of age) and older children. SLI patients showed larger global gray and white matter volumes, particularly in the younger subgroup. Voxel‐wise analyses of the whole sample showed two regions of increased gray matter volume in SLI: the right perisylvian region and the occipital petalia. Age‐group analyses suggested a more extended pattern of volume increases in the younger subjects, which included entorhinal, temporopolar, caudate nucleus, motor‐precentral and precuneus gray matter, and white matter of the frontal and temporal lobes. Our results suggest that in the SLI brain there are enduring anatomical alterations that exist across a wide age range, as well as a distributed pattern of abnormalities that appear to normalize with development. They also suggest that the neuroanatomical basis of SLI may be better characterized by considering the dynamic course of the disorder throughout childhood. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.
The human mirror neuron system in a population with deficient self‐awareness: An fMRI study in alexithymia
Authors: Moriguchi Yoshiya , Ohnishi Takashi , Decety Jean , Hirakata Makiko , Maeda Motonari , Matsuda Hiroshi , Komaki Gen
Published: September 2008

The mirror neuron system (MNS) is considered crucial for human imitation and language learning and provides the basis for the development of empathy and mentalizing. Alexithymia (ALEX), which refers to deficiencies in the self‐awareness of emotional states, has been reported to be associated with poor ability in various aspects of social cognition such as mentalizing, cognitive empathy, and perspective‐taking. Using functional magnetic resonance imaging (fMRI), we measured the hemodynamic signal to examine whether there are functional differences in the MNS activity between participants with ALEX (n = 16) and without ALEX (n = 13), in response to a classic MNS task (i.e., the observation of video clips depicting goal‐directed hand movements). Both groups showed increased neural activity in the premotor and the parietal cortices during observation of hand actions. However, activation was greater for the ALEX group than the non‐ALEX group. Furthermore, activation in the left premotor area was negatively correlated with perspective‐taking ability as assessed with the interpersonal reactivity index. The signal in parietal cortices was negatively correlated with cognitive facets assessed by the stress coping inventory and positively correlated with the neuroticism scale from the NEO five factor personality scale. In addition, in the ALEX group, activation in the right superior parietal region showed a positive correlation with the severity of ALEX as measured by a structured interview. These results suggest that the stronger MNS‐related neural response in individuals scoring high on ALEX is associated with their insufficient self‐other differentiation. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.
Collaborative computational anatomy: An MRI morphometry study of the human brain via diffeomorphic metric mapping
Authors: Miller Michael I. , Priebe Carey E. , Qiu Anqi , Fischl Bruce , Kolasny Anthony , Brown Timothy , Park Youngser , Ratnanather J. Tilak , Busa Evelina , Jovicich Jorge , Yu Peng , Dickerson Bradford C. , Buckner Randy L.
Published: September 2008

This article describes a large multi‐institutional analysis of the shape and structure of the human hippocampus in the aging brain as measured via MRI. The study was conducted on a population of 101 subjects including nondemented control subjects (n = 57) and subjects clinically diagnosed with Alzheimer's Disease (AD, n = 38) or semantic dementia (n = 6) with imaging data collected at Washington University in St. Louis, hippocampal structure annotated at the Massachusetts General Hospital, and anatomical shapes embedded into a metric shape space using large deformation diffeomorphic metric mapping (LDDMM) at the Johns Hopkins University. A global classifier was constructed for discriminating cohorts of nondemented and demented subjects based on linear discriminant analysis of dimensions derived from metric distances between anatomical shapes, demonstrating class conditional structure differences measured via LDDMM metric shape (P < 0.01). Localized analysis of the control and AD subjects only on the coordinates of the population template demonstrates shape changes in the subiculum and the CA1 subfield in AD (P < 0.05). Such large scale collaborative analysis of anatomical shapes has the potential to enhance the understanding of neurodevelopmental and neuropsychiatric disorders. Hum Brain Mapp, 2009. © 2008 Wiley‐Liss, Inc.
Pathobiology of biliary epithelia and cholangiocarcinoma: Proceedings of the Henry M. and Lillian Stratton basic research single-topic conference
Authors: Sirica Alphonse E. , Nathanson Michael H. , Gores Gregory J. , LaRusso Nicholas F.
Published: September 2008

In June 2008, the American Association for the Study of Liver Diseases (AASLD) sponsored the Henry M. and Lillian Stratton Basic Research Single-Topic Conference on the Pathobiology of Biliary Epithelia and Cholangiocarcinoma, which was held in Atlanta, GA. Attendees from 12 different countries participated in this conference, making it a truly international scientific event. Both oral and poster presentations were given by multidisciplinary experts, who highlighted important areas of current basic and translational research on biliary epithelial cell biology and pathophysiology, and on the etiology, cellular and molecular pathogenesis, and target-based therapy of cholangiocarcinoma. The specific goals and objectives of the conference were: (1) to advance knowledge of basic and molecular mechanisms underlying developmental and proliferative disorders of the biliary tract; (2) to foster a better and more comprehensive understanding of mechanisms regulating biliary epithelial (cholangiocyte) growth and transport, signaling, cell survival, and abnormalities that result in disease; and (3) to understand basic mechanisms of cholangiocarcinoma development and progression, with the added goal of identifying and exploiting potentially critical molecular pathways that may be targeted therapeutically. A number of interrelated themes emerged from the oral and poster sessions that affected current understandings of the complex organization of transcriptional and signaling mechanisms that regulate bile duct development, hepatic progenitor cell expansion, cholangiocyte secretory functions and proliferation, and mechanisms of cholangiocarcinogenesis and malignant cholangiocyte progression. Most notable were the critical questions raised as to how best to exploit aberrant signaling pathways associated with biliary disease as potential targets for therapy. (Hepatology 2008;48:2040-2046.)
Patients with Epstein Barr virus‐positive lymphomas have decreased CD4+ T‐cell responses to the viral nuclear antigen 1
Authors: Heller Kevin N. , Arrey Frida , Steinherz Peter , Portlock Carol , Chadburn Amy , Kelly Kara , Münz Christian
Published: September 2008

Epstein Barr virus (EBV) causes lymphomas in immune competent and, at increased frequencies, in immune compromised patients. In the presence of an intact immune system, EBV‐associated lymphomas express in most cases only 3 or fewer EBV antigens at the protein level, always including the nuclear antigen 1 of EBV (EBNA1). EBNA1 is a prominent target for EBV‐specific CD4+ T cell and humoral immune responses in healthy EBV carriers. Here we demonstrate that patients with EBV‐associated lymphomas, primarily Hodgkin's lymphoma, lack detectable EBNA1‐specific CD4+ T‐cell responses and have slightly altered EBNA1‐specific antibody titers at diagnosis. In contrast, the majority of EBV‐negative lymphoma patients had detectable IFNγ expression and proliferation by CD4+ T cells in response to EBNA1, and carry EBNA1‐specific immunoglobulins at levels similar to healthy virus carriers. Other EBV antigens, which were not present in the tumors, were recognized in less EBV positive, than negative lymphoma patients, but detectable responses reached similar CD8+ T cell frequencies in both cohorts. Patients with EBV‐positive and ‐negative lymphomas did not differ in T‐cell responses in influenza‐specific CD4+ T cell proliferation and in antibody titers against tetanus toxoid. These data suggest a selective loss of EBNA1‐specific immune control in EBV‐associated lymphoma patients, which should be targeted for immunotherapy of these malignancies. © 2008 Wiley‐Liss, Inc.
Organ‐specific profiles of genetic changes in cancers caused by activation‐induced cytidine deaminase expression
Authors: Morisawa Toshiyuki , Marusawa Hiroyuki , Ueda Yoshihide , Iwai Akio , Okazaki Il‐mi , Honjo Tasuku , Chiba Tsutomu
Published: September 2008

Various molecular changes characterizing organ‐specific carcinogenesis have been identified in human tumors; however, the molecular mechanisms of the genomic changes specific for each cancer are not well defined. A transgenic (Tg) mouse model with constitutive expression of the nucleotide‐editing enzyme, activation‐induced cytidine deaminase (AID), develops tumors in various organs as a result of the mutagenic activities of AID. This phenotypic character of AID Tg mice allowed us to analyze the organ‐specific genetic changes in tumor‐related genes commonly triggered by AID‐mediated mutagenesis. Among the 80 AID Tg mice analyzed, 11 mice developed hepatocellular carcinomas, and 7 developed lung cancers. In addition, 1 developed the gastric cancer and 3 developed gastric adenomas. Organ‐specific preferences for nucleotide changes were observed in some of the tumor‐related genes in each epithelial tissue of the AID Tg mice. Of note, the c‐myc and K‐ras genes were the preferential targets of the mutagenic activity of AID in lung and stomach cancers, respectively, whereas mutations in the p53 and β‐catenin genes were commonly observed in all 3 organs. Quantitative RT‐PCR analyses revealed that alpha‐fetoprotein, insulin‐like growth factor2 and cyclin D1 genes were specifically upregulated in HCC, whereas upregulation of the matrix metalloproteinase7 gene was more marked in lung cancer. Our findings suggest that AID, a DNA mutator that plays a critical role linking inflammation to human cancers, might be involved in the generation of organ‐specific genetic diversity in oncogenic pathways during cancer development. © 2008 Wiley‐Liss, Inc.
Dietary intakes of ω‐6 and ω‐3 polyunsaturated fatty acids and the risk of breast cancer
Authors: Thiébaut Anne C.M. , Chajès Véronique , Gerber Mariette , Boutron‐Ruault Marie‐Christine , Joulin Virginie , Lenoir Gilbert , Berrino Franco , Riboli Elio , Bénichou Jacques , Clavel‐Chapelon Françoise
Published: September 2008

Experimental studies suggest detrimental effects of ω‐6 polyunsaturated fatty acids (PUFA), and beneficial effects of ω‐3 PUFAs on mammary carcinogenesis, possibly in interaction with antioxidants. However, PUFA food sources are diverse in human diets and few epidemiologic studies have examined whether associations between dietary PUFAs and breast cancer risk vary according to food sources or antioxidant intakes. The relationship between individual PUFA intakes estimated from diet history questionnaires and breast cancer risk was examined among 56,007 French women. During 8 years of follow‐up, 1,650 women developed invasive breast cancer. Breast cancer risk was not related to any dietary PUFA overall; however, opposite associations were seen according to food sources, suggesting other potential effects than PUFA per se. Breast cancer risk was inversely associated with α‐linolenic acid (ALA) intake from fruit and vegetables [highest vs. lowest quintile, hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.63, 0.88; p trend < 0.0001], and from vegetable oils (HR 0.83; 95% CI 0.71, 0.97; p trend 0.017). Conversely, breast cancer risk was positively related to ALA intake from nut mixes (p trend 0.004) and processed foods (p trend 0.068), as was total ALA intake among women in the highest quintile of dietary vitamin E (p trend 0.036). A significant interaction was also found between ω‐6 and long‐chain ω‐3 PUFAs, with breast cancer risk inversely related to long‐chain ω‐3 PUFAs in women belonging to the highest quintile of ω‐6 PUFAs (p interaction 0.042). These results emphasize the need to consider food sources, as well as interactions between fatty acids and with antioxidants, when evaluating associations between PUFA intakes and breast cancer risk. © 2008 Wiley‐Liss, Inc.
EBAG9 is a tumor‐promoting and prognostic factor for bladder cancer
Authors: Kumagai Jinpei , Urano Tomohiko , Ogushi Tetsuo , Takahashi Satoru , Horie‐Inoue Kuniko , Fujimura Tetsuya , Azuma Kotaro , Muramatsu Masami , Ouchi Yasuyoshi , Kitamura Tadaichi , Inoue Satoshi
Published: September 2008

Upregulation of EBAG9 expression has been observed in several malignant tumors such as advanced breast and prostate cancers, indicating that EBAG9 may contribute to tumor proliferation. In the present study, we assess the role of EBAG9 in bladder cancer. We generated human bladder cancer EJ cells stably expressing FLAG‐tagged EBAG9 (EJ‐EBAG9) or empty vector (EJ‐vector), and investigated whether EBAG9 overexpression modulates cell growth and migration in vitro as well as the in vivo tumor formation of EJ transfectants in xenograft models of BALB/c nude mice. EBAG9 overexpression promoted EJ cell migration, while the effect of EBAG9 to cultured cell growth was rather minimal. Tumorigenic experiments in nude mice showed that the size of EJ‐EBAG9‐derived tumors was significantly larger than EJ‐vector‐derived tumors. Loss‐of‐function study for EBAG9 using small interfering RNA (siRNA) in xenografts with parental EJ cells showed that the intra‐tumoral injection of EBAG9 siRNA markedly reduced the EJ tumor formation compared with control siRNA. Furthermore, immunohistochemical study for EBAG9 expression was performed in 60 pathological bladder cancer specimens. Intense and diffuse cytoplasmic immunostaining was observed in 45% of the bladder cancer cases. Positive EBAG9 immunoreactivity was closely correlated with poor prognosis of the patients (p = 0.0001) and it was an independent prognostic predictor for disease‐specific survival in multivariate analysis (p = 0.003). Our results indicate that EBAG9 would be a crucial regulator of tumor progression and a potential prognostic marker for bladder cancer. © 2008 Wiley‐Liss, Inc.
A prospective investigation of serum 25‐hydroxyvitamin D and risk of lymphoid cancers
Authors: Lim Unhee , Freedman D. Michal , Hollis Bruce W. , Horst Ronald L. , Purdue Mark P. , Chatterjee Nilanjan , Weinstein Stephanie J. , Morton Lindsay M. , Schatzkin Arthur , Virtamo Jarmo , Linet Martha S. , Hartge Patricia , Albanes Demetrius
Published: September 2008

Studies indicate that higher sun exposure, especially in the recent past, is associated with reduced risk of non‐Hodgkin lymphoma (NHL). Ultraviolet radiation‐derived vitamin D may be protective against lymphomagenesis. We examined the relationship between prediagnostic serum 25‐hydroxyvitamin D (25(OH)D) and lymphoid cancer risk in a case–control study nested within the Alpha‐Tocopherol Beta‐Carotene Cancer Prevention Study cohort (1985–2002) of 29,133 Finnish male smokers (ages 50–69). We identified 270 incident lymphoid cancer cases and matched them individually with 538 controls by birth‐year and month of fasting blood draw at baseline. In conditional logistic regression models for 10 nmol/L increments or tertile comparisons, serum 25(OH)D was not associated with the risk of overall lymphoid cancers, NHL (n = 208) or multiple myeloma (n = 41). Odds ratios (OR) for NHL for higher tertiles were 0.75 (95% confidence interval (CI), 0.50, 1.14) and 0.82 (95% CI, 0.53, 1.26). The 25(OH)D‐NHL association, however, differed by follow‐up duration at diagnosis. Cases diagnosed less than 7 years from the baseline showed an inverse association (OR for highest vs. lowest tertile = 0.43; 95% CI: 0.23, 0.83; p for trend = 0.01), but not later diagnoses (OR = 1.52; 95% CI: 0.82, 2.80; p for trend = 0.17). The inverse association found for close exposure to diagnosis was not confounded by other risk factors for lymphoma or correlates of 25(OH)D. Although our findings suggest that circulating 25(OH)D is not likely associated with overall lymphoid cancer, they indicate a potentially protective effect on short‐term risk of NHL. © 2008 Wiley‐Liss, Inc.
The DNA repair proteins BRCA1 and ERCC1 as predictive markers in sporadic ovarian cancer
Authors: Weberpals Johanne , Garbuio Kyla , O'Brien Anna , Clark‐Knowles Katherine , Doucette Steve , Antoniouk Olga , Goss Glenwood , Dimitroulakos Jim
Published: September 2008

This study compares Breast Cancer 1 (BRCA1) and excision repair cross complementation group 1 (ERCC1) expression as predictive markers and evaluates the in vitro enhancement of platinum sensitivity using targeted agents in sporadic ovarian cancer (OC). A retrospective study was performed of advanced stage OC patients receiving platinum‐based chemotherapy. BRCA1 and ERCC1 mRNA expression was determined from frozen tissue of 51 patients. Median overall survival (OS) was longer for patients with lower BRCA1 vs. higher BRCA1 (46 vs.33 months, p = 0.03). High BRCA1 was predictive of poorer OS specifically in patients with residual disease (RD) <2 cm (p = 0.03). There was a non‐significant association for patients with lower ERCC1 and RD <2 cm in favor of improved OS and time to progression. Patients who expressed higher levels of both BRCA1 and ERCC1 mRNA had a shorter OS compared to patients with lower levels of either or both transcript (33 vs.46 months, p = 0.04). When Cox proportional modeling was used by representing BRCA1 and ERCC1 mRNA expression as a continuous variable, both emerge as potential predictors of survival. OC cell lines were exposed to chemotherapy in combination with DNA repair pathway inhibitors and cell viability was assessed. In vitro histone deacetylase (HDAC) inhibition increased the sensitivity of A2780s/cp cells to cisplatin and carboplatin but not to taxol, coincident with a significant decrease in BRCA1 and ERCC1 expression, suggesting that this compound directly targets DNA repair. In summary, this study shows that low BRCA1 and ERCC1 expression correlate with improved survival in advanced OC and HDAC inhibition induces synergistic cytotoxicity with platinum in vitro. © 2008 Wiley‐Liss, Inc.
Expression of the putative tumor suppressor genePTPN13/PTPL1is an independent prognostic marker for overall survival in breast cancer
Authors: Révillion Françoise , Puech Carole , Rabenoelina Fanja , Chalbos Dany , Peyrat Jean‐Philippe , Freiss Gilles
Published: September 2008

Although it is well established that some protein tyrosine kinases have a prognostic value in breast cancer, the involvement of protein tyrosine phosphatases (PTPs) is poorly substantiated for breast tumors. Three of these enzymes (PTP‐gamma, LAR, and PTPL1) are already known to be regulated by estrogens or their antagonists in human breast cancer cells. We used a real‐time reverse transcriptase polymerase chain reaction method to test the expression levels of PTP‐gamma, LAR and its neuronal isoform, and PTPL1 in a training set of RNA from 59 breast tumors. We sought correlations between levels of these molecular markers, current tumor markers, and survival. We then quantified the expression level of the selected phosphatase in 232 additional samples, resulting in a testing set of 291 breast tumor RNAs from patients with a median follow‐up of 6.4 years. The Spearman nonparametric test revealed correlations between PTPL1 expression and differentiation markers. Cox univariate analysis of the overall survival studies demonstrated that PTPL1 is a prognostic factor [risk ratio (RR) = 0.45], together with the progesterone receptor (PR) (RR = 0.52) and node involvement (RR = 1.58). In multivariate analyses, PTPL1 and PR retained their prognostic value (RRs of 0.48 and 0.55, respectively). This study demonstrates for the first time that PTPL1 expression level is an independent prognostic indicator of favorable outcome for patients with breast cancer. In conjunction with our mechanistic studies, this finding identifies PTPL1 as an important regulatory element of human breast tumor aggressiveness and sensitivity to treatments such as antiestrogens and antiaromatase. © 2008 Wiley‐Liss, Inc.
Overexpression of PLK1 is associated with poor survival by inhibiting apoptosis via enhancement of survivin level in esophageal squamous cell carcinoma
Authors: Feng Yan‐Bin , Lin De‐Chen , Shi Zhi‐Zhou , Wang Xiao‐Chun , Shen Xiao‐Ming , Zhang Yu , Du Xiao‐Li , Luo Man‐Li , Xu Xin , Han Ya‐Ling , Cai Yan , Zhang Zi‐Qiang , Zhan Qi‐Min , Wang Ming‐Rong
Published: September 2008

PLK1 is essential for the maintenance of genomic stability during mitosis. In our study, we found that overexpression of PLK1 was an independent prognostic factor (RR = 4.253, p = 0.020) and significantly correlated with survivin, an antiapoptotic protein, in esophageal squamous cell carcinoma (ESCC). Reverse transcription‐polymerase chain reaction and fluorescence in situ hybridization (FISH) revealed upregulation of PLK1 mRNA and amplification of PLK1 gene, respectively. Depletion of PLK1 activated the intrinsic apoptotic pathway, which was substantiated by loss of mitochondrial membrane potential, reduction of Mcl‐1 and Bcl‐2 as well as activation of caspase‐9. Coimmunoprecipitation and confocal microscopy displayed that PLK1 was associated with survivin and PLK1 depletion led to downregulation of survivin. Cotransfection of survivin constructs could partially reverse PLK1‐depletion‐induced apoptosis. These data suggest that PLK1 might be a useful prognostic marker and a potential therapeutic target for ESCC. Survivin is probably involved in antiapoptotic function of PLK1. © 2008 Wiley‐Liss, Inc.
Inhibition of the sarcoplasmic/endoplasmic reticulum Ca2+‐ATPase by flavonoids: A quantitative structure‐activity relationship study
Authors: Ogunbayo Oluseye A. , Harris Robert M. , Waring Rosemary H. , Kirk Christopher J. , Michelangeli Francesco
Published: September 2008

Flavonoids are commonly found in fruit and vegetables and have been shown to reach concentrations of several micromolars in human blood plasma. Flavonoids are also believed to have cancer chemoprotective properties. One hypothesis is that flavonoids are able to initiate apoptosis, especially in cancer cells, via a Ca2+‐dependent mitochondrial pathway. This pathway can be activated through an exaggerated elevation of cytosolic [Ca2+], and sarcoplasmic/endoplasmic reticulum Ca2+‐ATPases (SERCA) play an essential role in ameliorating such changes. In this study, we demonstrate that flavonoids (especially flavones) can inhibit the activity of Ca2+‐ATPases isoforms SERCA1A and SERCA2B in the micromolar concentration range. Of the 25 flavonoids tested, 3,6‐dihydroxyflavone (IC50, 4.6 μM) and 3,3′,4′,5,7‐pentahydroxyflavone (quercetin) (IC50, 8.9 μM) were the most potent inhibitors. We show that polyhydroxylation of the flavones are important for inhibition, with hydroxylation at position 3 (for SERCA1A) and position 6 (for SERCA2B) being particularly relevant. © 2008 IUBMB IUBMB Life, 60(12): 853–858, 2008
Activation of HIF‐1α in exponentially growing cells via hypoxic stimulation is independent of the Akt/mTOR pathway
Authors: Dayan Frédéric , Bilton Rebecca L. , Laferrière Julie , Trottier Eric , Roux Danièle , Pouyssegur Jacques , Mazure Nathalie. M.
Published: September 2008

Accumulation of HIF‐1α during normoxic conditions at high cell density has previously been shown to occur and can be used to stabilize HIF‐1α protein in the absence of a specific anaerobic chamber. However, the impact and origin of this pool of HIF‐1α, obtained under normoxia, has been underestimated. In this study, we have systematically compared the related pools of HIF‐1α stabilized in normoxia by high cell density to those obtained at low density in hypoxia. At first glance, these two stimuli appear to have similar outcomes: HIF‐1α stabilization and induction of HIF‐1‐dependent genes. However, upon careful analysis, we observed that molecular mechanisms involved are different. We clearly demonstrate that density‐dependant HIF‐1α accumulation during normoxia is due to the cells high consumption of oxygen, as demonstrated by using a respiration inhibitor (oligomycin) and respiratory‐defective mutant cells (GSK3). Finally and most importantly, our data indicate that a decrease in AKT activity followed by a total decrease in p70S6K phosphorylation reflecting a decrease in mTOR activity occurs during high oxygen consumption, resulting from high cell density. In contrast, hypoxia, even at severe low O2 levels, only slightly impacts upon the mTOR pathway under low cell density conditions. Thus, activation of HIF‐1α in exponentially growing cells via hypoxic stimulation is independent of the Akt/mTOR pathway whereas HIF‐1α activation obtained in high confluency is totally dependent on mTOR pathway as rapamycin totally impaired (i) HIF‐1α stabilization and (ii) mRNA levels of CA9 and BNIP3, two HIF‐target genes. J. Cell. Physiol. 218: 167–174, 2009. © 2008 Wiley‐Liss, Inc.
Skin toxicity caused by EGFR antagonists—An autoinflammatory condition triggered by deregulated IL‐1 signaling?
Authors: Rodeck Ulrich
Published: September 2008

Acneiform skin eruptions associated with sterile inflammation frequently accompany pharmacological inhibition of signaling through the epidermal growth factor receptor (EGFR) in cancer patients. Here we discuss possible pathogenic mechanisms for this phenomenon linked to control of inflammatory mediators by EGFR blockade in keratinocytes of the outer root sheath of the hair follicle. This discussion is focused on the putative role of EGFR activation in restraining interleukin (IL)‐1‐dependent inflammatory networks at the hair follicle. J. Cell. Physiol. 218: 32–34, 2009. © 2008 Wiley‐Liss, Inc.
Blockade of sphingosine‐1‐phosphate reduces macrophage influx and retinal and choroidal neovascularization
Authors: Xie Bing , Shen Jikui , Dong Aling , Rashid Aymen , Stoller Glenn , Campochiaro Peter A.
Published: September 2008

Sphingosine‐1‐phosphate (S1P) is a bioactive lipid molecule that stimulates endothelial cell migration, proliferation, and survival in vitro, and tumor angiogenesis in vivo. In this study, we used a humanized monoclonal antibody (sonepcizumab) that selectively binds S1P to investigate its role in retinal and choroidal neovascularization (NV). Intraocular injection of sonepcizumab significantly reduced macrophage influx into ischemic retina and strongly suppressed retinal NV in mice with oxygen‐induced ischemic retinopathy. In mice with laser‐induced rupture sites in Bruch's membrane, intraocular injection of sonepcizumab significantly reduced the area of choroidal NV and concomitantly reduced fluorescein leakage from the remaining choroidal NV. Four weeks after intraocular injection of up to 1.8 mg of the sonepcizumab in non‐human primates, electroretinograms and fluorescein angiograms were normal, and light microscopy of ocular sections showed no evidence of structural damage. These data show for the first time that S1P stimulates both choroidal and retinal NV and suggest that sonepcizumab could be considered for evaluation in patients with choroidal or retinal NV. J. Cell. Physiol. 218: 192–198, 2009. © 2008 Wiley‐Liss, Inc.
Cloning, sequencing and analysis of dnaK ‐dnaJ gene cluster of Bacillus megaterium
Authors: Bao Fangming , Gong Lei , Shao Weilan
Published: September 2008

The DNA fragment of heat shock genes (hrcA‐grpE‐dnaK‐dnaJ) containing complete hrcA‐grpE‐dnaK operon and the transcription unit of dnaJ was cloned, sequensed and analyzed from Bacillus megaterium RF5. The sequence of hrcA, grpE and dnaJ were first time reported, and their coding products exibit 60%, 63% and 81% of identities to the homologs of B. subtilis. A σA‐type promoter of Gram‐positive bacteria (PA1) and a terminator were located upstream of the hrcA and downstream of dnaK, and a Controlling inverted repeat of chaperone expression element (CIRCE) was identified between PA1 and hrcA. Another σA‐type promoter (PA2) and a terminator were found upstream and downstream of dnaJ, indicating B. megaterium has a transcription unit containing a single gene dnaJ. The structure of dnaJ transcription unit is more similar to that of Listeria monocytogenes than other species of Bacillus. A partial protein‐based phylogenetic tree, derived from Gram‐positive bacteria using HrcA sequence, indicated a closer phylogenetic relationship between B. megaterium and Geobacillus species than other two Bacillus species. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Fermentation of cocoa beans: influence of microbial activities and polyphenol concentrations on the flavour of chocolate
Authors: Camu Nicholas , De Winter Tom , Addo Solomon K , Takrama Jemmy S , Bernaert Herwig , De Vuyst Luc
Published: September 2008

BACKGROUND: Spontaneous cocoa bean fermentation is characterised by a succession of microbial activities. Cocoa flavour precursors are developed during fermentation and drying of cocoa beans. Polyphenols and alkaloids contribute to astringency and bitterness of cocoa and chocolate.

RESULTS: Population dynamics, metabolite target analyses, and chocolate production were performed for seven independent spontaneous cocoa bean heap fermentations in Ghana. Although the same micro‐organisms were involved in these heaps, carried out at different farms or in different seasons, heap temperatures and microbial metabolite concentrations were different. This could be due to heterogeneity and size of the heaps, but was mainly ascribed to microbial variability. Indeed, differences in microbial activity could be linked with the flavour of chocolates made from the corresponding dried, fermented cocoa beans. Whereas the polyphenol and alkaloid contents of cocoa beans were crop‐ and heap‐dependent, epicatechin and theobromine levels decreased during fermentation due to diffusion out of the bean cotyledons and polyphenol oxidation and condensation. Residual levels were responsible for the degree of bitterness of the final chocolates.

CONCLUSION: Differences in microbial activities between different heap fermentations can result in dried fermented cocoa beans and chocolates with different flavour characteristics. Hence, fermentation control may direct the flavour of chocolate. Copyright © 2008 Society of Chemical Industry
Revalorisation of vine trimming wastes using Lactobacillus acidophilus and Debaryomyces hansenii
Authors: Portilla Oscar M , Rivas Beatriz , Torrado Ana , Moldes Ana B , Domínguez José M
Published: September 2008

BACKGROUND: Mild acid treatments of vine‐shoot trimmings result in the hydrolysis of hemicellulosic sugars that can be utilised by Lactobacillus acidophilus CECT‐4179 (ATCC 832) and Debaryomyces hansenii NRRL Y‐7426 as carbon sources to obtain food additives. Since the high content of glucose in these hydrolysates reduces the effective bioconversion of xylose into xylitol by D. hansenii, the use of Lactobacillus acidophilus, one of the main probiotic species, allows this problem to be solved by the selective consumption of glucose. In order to use both sugars (glucose and xylose), hemicellulosic vine‐shoot trimming hydrolysates can be sequentially fermented by both micro‐organisms.

RESULTS: It was found that, in the first step, L. acidophilus generated almost exclusively lactic acid (32.7 g of lactic acid L−1, QLA = 1.363 g L−1 h−1, YLA/S = 0.72 g g−1) by homofermentative degradation of sugars (mainly glucose), and in the second step, the remaining hemicellulosic sugars were transformed primarily into xylitol by Debaryomyces hansenii (31.3 g of xylitol L−1, QXylitol = 0.708 g L−1 h−1, YXylitol/S = 0.66 g g−1). Furthermore, L. acidophilus proved to be a strong cell‐bounded biosurfactant producer. Cell extracts were able to reduce the surface tension (ST) of PBS in 18 mN m−1 units. Lactobacillus acidophilus cells showed no difference in viability before or after PBS extraction of biosurfactants, achieving values of 0.9 × 109 colony‐forming units (CFU) mL−1 in both cases.

CONCLUSIONS: These results have made a serious contribution to the re‐evaluation of a useless and pollutant residue, producing a wide range of natural food additives. Copyright © 2008 Society of Chemical Industry
Effect of nitric oxide on reactive oxygen species and antioxidant enzymes in kiwifruit during storage
Authors: Zhu Shuhua , Sun Lina , Liu Mengchen , Zhou Jie
Published: September 2008

BACKGROUND: The accumulation of reactive oxygen species (ROS) in kiwifruit can cause oxidative damage during storage. Little research has been carried out on the effects of nitric oxide (NO) on oxidative damage to kiwifruit. Therefore the aim of the present study was to evaluate the ability of 0.5, 1 and 2 µmol L−1 NO aqueous solutions to alleviate oxidative damage to kiwifruit during storage.

RESULTS: The most marked effect was obtained with 1 µmol L−1 NO solution, which significantly reduced the accumulation of malondialdehyde, superoxide and hydrogen peroxide, delayed the decrease in vitamins C and E, maintained the content of soluble solids, inhibited the activity of lipoxygenase and peroxidase and increased the activity of superoxide dismutase and catalase in kiwifruit during storage. The 0.5 µmol L−1 NO solution was too weak to significantly affect the content of ROS and the activity of enzymes. However, treatment with 2 µmol L−1 NO solution promoted the accumulation of ROS, decreased the activity of antioxidant enzymes and accelerated peroxidation in kiwifruit during storage.

CONCLUSION By increasing the activity of antioxidant enzymes and maintaining the content of vitamins C and E, treatment with 1 µmol L−1 NO aqueous solution could protect kiwifruit against oxidative damage caused by ROS during storage. Copyright © 2008 Society of Chemical Industry
Preparation of trypsin‐immobilised chitosan beads and their application to the purification of soybean trypsin inhibitor
Authors: Zhang Li , Zhang Bin , Lin Hong , Liu Pei‐Pei , Yu Li‐Na , Wang Dong‐Feng
Published: September 2008

BACKGROUND: Trypsin inhibitors are among the most important antinutritional factors in legumes. Recent research has shown that soybean trypsin inhibitor (SBTI) exhibits multiple bioactivities, but very few studies on the purification of SBTI are available. Enzymes are commonly used as biospecific ligands in affinity purification of their substrates or inhibitors. The aim of the present study was to prepare trypsin (EC 3.4.21.4)‐immobilised chitosan beads and use them to purify trypsin inhibitor from soybean whey.

RESULTS: Compared with free trypsin, the immobilised trypsin had higher thermal and pH stability. The adsorption ratio of SBTI from crude SBTI aqueous solution by trypsin‐immobilised chitosan beads was 33.3%. The purified SBTI obtained by affinity chromatography was characterised by sodium dodecyl sulfate polyacrylamide gel electrophoresis as a single polypeptide band with an Mr of 8.3 kDa belonging to the Bowman–Birk family.

CONCLUSION: Trypsin‐immobilised chitosan beads were effectively used in the affinity separation of trypsin inhibitor from soybean seeds, thus indicating that immobilised trypsin may have practical application in the soybean‐processing industry. The results of this study provide a background for further investigation of potential applications of soybean bioactive constituents in the areas of agriculture and food. Copyright © 2008 Society of Chemical Industry
Milk production of dairy goats fed diets with different legume seeds: Effects of amino acid composition of the rumen undegradable protein fraction
Authors: Morales E Ramos , Alcaide E Molina , Sampelayo MR Sanz
Published: September 2008

BACKGROUND: To establish the effect of the nature of four different legume seeds, lupins (L), faba beans (FB), bitter vetch (BV) and vetch (V) on the production and composition of goat milk, we studied the ruminal degradation of these legumes, and the amino acid (AA) composition of the seeds and that of the undegradable fractions of the protein sources. Four isonitrogenous and isoenergetic diets were designed, and in each case 30% of the protein was supplied by one of the different legume seeds. A group of eight Granadina goats was used to study the utilisation of these diets for milk production. The goats were allocated to a replicated 4 × 4 Latin square.

RESULTS: Ruminal fermentation modified the AA profile of the protein of the legume seeds which was different in each case. However, milk production remained unchanged irrespective of the diet consumed. On the contrary, and despite the high level of degradability of the protein in the different legumes, the concentration of total protein, casein (CN) and overall αS1‐CN and αS2‐CN in milk depended on the protein source used.

CONCLUSION: The concentration of total protein in milk, as well as its composition, was apparently determined by the AA composition of the corresponding fraction of the rumen‐undegradable protein. Copyright © 2008 Society of Chemical Industry
Models of growing season weather impacts on breadmaking quality of spring wheat from producer fields in western Canada
Authors: Jarvis Chad K , Sapirstein Harry D , Bullock Paul R , Naeem Hamid A , Angadi Sangamesh V , Hussain Akhtar
Published: September 2008

BACKGROUND: The purpose of this study was to quantify growing season weather and wheat quality at individual producer fields to understand weather impacts and develop weather‐based models of spring wheat quality.

RESULTS: Ninety‐six hard red spring wheat samples of two genotypes supplied by western Canadian producers in 2003 and 2004 underwent comprehensive analysis for breadmaking quality. For each individual field, daily rainfall, maximum and minimum air temperature were observed and used to calculate several measures of heat. Modeled water use, demand and stress were also calculated and all weather variables were accumulated over different phenological stages. Relationships between weather variables and wheat quality variables were determined by multivariate regression analysis separated into four steps, each adding more complex information into the models. There was substantial variation in weather conditions and wheat quality between years with generally higher quality and stronger dough in the warmer and drier year, 2003. The two genotypes displayed many differences in response to the environment. Prediction of wheat quality improved with increasing complexity of weather models and close to 50% of the variation in quality could be explained by multivariate models.

CONCLUSIONS: Results showed that even for top‐grade milling wheat of similar protein content, significant differences exist in breadmaking quality of wheat from different farms. The improvement in r2 when using modeled environmental variables indicates that crop water use and water stress are important for wheat quality. The development of Canada Western Red Spring quality prediction models for western Canada based on growing season weather shows promise. Copyright © 2008 Society of Chemical Industry
Ruminal micro‐organisms do not adapt to increase utilization of poly‐phenol oxidase protected red clover protein and glycerol‐based lipid
Authors: Lee Michael RF , Tweed John KS , Scollan Nigel D , Sullivan Michael L
Published: September 2008

BACKGROUND: The enzyme polyphenol oxidase (PPO) reduces the extent of proteolysis and lipolysis within red clover fed to ruminants with subsequent increases in the efficiency of N utilization and the level of beneficial polyunsaturated fatty acids in their products (meat and milk). It has also been reported that red clover feeding alters the rumen microbial population compared to grass feeding. This study investigated whether the observed shifts in the microbial population of the rumen when ruminants are fed red clover silage (RC) as opposed to grass silage (G) represented an adaptation by the micro‐organisms to increase the utilization of PPO‐protected protein and glycerol‐based lipid.

RESULTS: The experiment consisted of two periods where ruminally fistulated dairy cows were offered either RC or G for 2 weeks, followed by collection of rumen fluid, which was then used in in vitro incubations to investigate lipolysis and proteolysis over time in plant material derived from red clover plants with either wild type PPO expression (PPO+) or PPO expression reduced to undetectable levels by gene silencing (PPO−). Proteolysis and lipolysis (P < 0.05) were lower after 24 h of incubation in the PPO+ treatment than the PPO− treatment irrespective of rumen fluid. Biohydrogenation of C18 polyunsaturated fatty acids was also lower on the PPO+ treatment than the PPO− treatment, with no effect of rumen fluid.

CONCLUSION: These results suggest that microbial changes to red clover feeding did not result in an increased ability of the micro‐organisms in the present study to utilize either PPO‐protected protein or glycerol‐based lipid. Copyright © 2008 Society of Chemical Industry
Simultaneous determination of alkali, alkaline earths and ammonium in natural waters by ion chromatography
Authors: Bruzzoniti Maria Concetta , De Carlo Rosa Maria , Fungi Martino
Published: September 2008

An ion chromatographic method has been developed for the determination of alkali (Li+, Na+, K+), alkaline earths (Ca2+, Mg2+, Ba2+, Sr2+) and ammonium ion in waters. The usual difficulties encountered during traditional cation‐exchange separations (incomplete resolution for Na+ and NH4+ present in disproportionate concentration ratios) have been overcome tuning the selectivity of the separation by the introduction of 18‐crown‐6 ether in the mobile phase using an IonPac CS12A (150×3 mm id) column. After a detailed study of the effect of mobile phase components on separation, a gradient elution from 26 mM methanesulphonic acid (MSA) with a step change at 9 min to 60 mM MSA (0.5 mM 18‐crown‐6) provided the required baseline separation for the eight selected analytes. The method developed provides the advantage of the determination, in the same analytical run, also of strontium and barium, which is usually performed by spectroscopic techniques. Within‐day and between‐day repeatability have been assessed, observing between‐day RSD included between 0.3 and 1.8% for retention times and 0.6 and 7.2% for peak areas. The method has been finally tested for the analysis of water samples of different provenience (well, tanks, water system) and results compared with those obtained by the laboratory in charge of the control of drinking water for the city of Torino (Italy).
The integration of film‐induced tourism and destination branding in Yorkshire, UK
Authors: O'Connor Noelle , Flanagan Sheila , Gilbert David
Published: September 2008

This paper identifies the integration of film induced tourism and destination branding on destinations featured in television series' such as Yorkshire, which is the film location for many popular English television series'. The review of the existing literature identified a gap in previous investigations and in response, a tourist survey and strategic conversations with the key stakeholders were an initial attempt to fill this gap. The issues which arose from these and the literature review highlighted some implications for the future development of these destinations, namely the use of destination branding in the promotion of a film location. Copyright © 2008 John Wiley & Sons, Ltd.
Human resource development issues for the hotel sector in Libya: a government perspective
Authors: Naama Ahmed , Haven‐Tang Claire , Jones Eleri
Published: September 2008

The Libyan government emphasises the importance of tourism in economic diversification through its Libyan Tourism Master Plan identifying various initiatives to develop the Libyan tourism industry, including human resource development (HRD). Hotels are key to an internationally competitive industry and human resources critical to perceptions of service quality. This paper analyses issues relating to the Libyan hotel sector, including the need to strengthen the private sector; to match education/training programmes to industrial needs, and to address cultural and religious dimensions which exacerbate poor industry image. The paper identifies a partnership approach between governmental, educational and hotel sectors to address HRD issues through workforce planning. Copyright © 2008 John Wiley & Sons, Ltd.