bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimicrobial combined action of terpenes against the food‐borne microorganisms Escherichia coli, Staphylococcus aureus and Bacillus cereus
Authors: Gallucci M. N. , Oliva M. , Casero C. , Dambolena J. , Luna A. , Zygadlo J. , Demo M.
Published: September 2009

The aims of this work were to study the antimicrobial activity of nine monoterpenes and the synergistic or antagonistic associations between them, and to relate water solubility, H‐bonding and pKa values with antimicrobial activity. The minimum inhibitory concentrations (MICs) and minimum bactericidal concentration (MBCs) were determined. The MIC of carvacrol against S. aureus was 3.2 g/l and of thymol was 7.5 g/l. E. coli was resistant. Carvacrol and thymol were bactericidal. The associations geraniol/menthol against S. aureus and B. cereus and thymol/menthol against B. cereus were totally synergistic. Eugenol/geraniol displayed partial synergism against B. cereus. The other groups did not show any synergistic effect. Eugenol had the lowest pKa, followed by thymol and carvacrol. Eugenol had the highest total area and polar area and intermolecular and intramolecular hydrogen‐bonding capacity, while carvacrol and thymol only had intermolecular hydrogen‐bonding capacity. The terpenes alone and in combination were effective against microorganisms. Phenolic compounds were the most active terpenes. Associations between terpenes were related to the chemical structure. Studies on the antimicrobial activity of associations of terpenes will advance the search for new alternatives for food preservation. Copyright © 2009 John Wiley & Sons, Ltd.
A volume‐based discrete test filter for conducting large eddy simulations with application to physiological flow in a constricted tube
Authors: Bahramian F. , Straatman A. G.
Published: September 2009

A discrete test‐filtering operation that takes advantage of a volume‐averaging procedure, as opposed to the more popular line‐interpolation technique, has been developed to enable mixed‐scale and dynamic LES simulations on general unstructured grids. Simulations of fully developed turbulent flow in a square duct show that the proposed test filter gives the results of similar accuracy to the best modern filters developed for non‐uniform orthogonal grids, but a second‐order correction is required to produce solutions of sufficient accuracy. The discrete filter technique is also used to simulate stationary and pulsatile turbulent flow in a 75% constricted tube, in which the flow undergoes transition to turbulence. Comparisons to previous published results confirm that the results obtained using the proposed discrete test filter are in a good agreement with the existing experimental and numerical results. Copyright © 2009 John Wiley & Sons, Ltd.
Forecasting volatility with support vector machine‐based GARCH model
Authors: Chen Shiyi , Härdle Wolfgang K. , Jeong Kiho
Published: September 2009

Recently, support vector machine (SVM), a novel artificial neural network (ANN), has been successfully used for financial forecasting. This paper deals with the application of SVM in volatility forecasting under the GARCH framework, the performance of which is compared with simple moving average, standard GARCH, nonlinear EGARCH and traditional ANN‐GARCH models by using two evaluation measures and robust Diebold–Mariano tests. The real data used in this study are daily GBP exchange rates and NYSE composite index. Empirical results from both simulation and real data reveal that, under a recursive forecasting scheme, SVM‐GARCH models significantly outperform the competing models in most situations of one‐period‐ahead volatility forecasting, which confirms the theoretical advantage of SVM. The standard GARCH model also performs well in the case of normality and large sample size, while EGARCH model is good at forecasting volatility under the high skewed distribution. The sensitivity analysis to choose SVM parameters and cross‐validation to determine the stopping point of the recurrent SVM procedure are also examined in this study. Copyright © 2009 John Wiley & Sons, Ltd.
Evaluating volatility dynamics and the forecasting ability of Markov switching models
Authors: Parikakis George S. , Merika Anna
Published: September 2009

This paper uses Markov switching models to capture volatility dynamics in exchange rates and to evaluate their forecasting ability. We identify that increased volatilities in four euro‐based exchange rates are due to underlying structural changes. Also, we find that currencies are closely related to each other, especially in high‐volatility periods, where cross‐correlations increase significantly. Using Markov switching Monte Carlo approach we provide evidence in favour of Markov switching models, rejecting random walk hypothesis. Testing in‐sample and out‐of‐sample Markov trading rules based on Dueker and Neely (Journal of Banking and Finance, 2007) we find that using econometric methodology is able to forecast accurately exchange rate movements. When applied to the Euro/US dollar and the euro/British pound daily returns data, the model provides exceptional out‐of‐sample returns. However, when applied to the euro/Brazilian real and the euro/Mexican peso, the model loses power. Higher volatility exercised in the Latin American currencies seems to be a critical factor for this failure.  Copyright © 2009 John Wiley & Sons, Ltd.
Long-Term Efficacy of Rosiglitazone in Nonalcoholic Steatohepatitis: Results of the Fatty Liver Improvement by Rosiglitazone Therapy (Flirt 2) Extension Trial
Authors: Ratziu Vlad , Charlotte Fréderic , Bernhardt Carole , Giral Philippe , Halbron Marine , LeNaour Gilles , Hartmann-Heurtier Agnès , Bruckert Eric , Poynard Thierry
Published: September 2009

Short-term trials of glitazones in nonalcoholic steatohepatitis (NASH) yielded controversial histological results. Longer treatment might result in additional improvement. After a 1-year randomized trial, 53 patients underwent a control liver biopsy and were enrolled in an open-label extension trial of rosiglitazone (RSG), 8 mg/day for 2 additional years. In all, 44 completed the extension phase including 40 with a third liver biopsy. Of these, 22 received placebo (PLB) in the randomized phase (PLB-RSG), and 18 RSG (RSG-RSG). During the 2-year extension phase serum insulin decreased by 26%, homeostasis model assessment (HOMA) by 30%, and alanine aminotransferase (ALT) by 24%. However, there was no significant change in the mean NASH activity score (NAS) (3.8 ± 2.11 versus 3.68 ± 1.8), ballooning score, fibrosis stage (1.76 ± 1.18 versus 1.85 ± 1.19), or area of fibrosis by micromorphometry (4.43% ± 0.68 to 5.54% ± 0.68). In the PLB-RSG group steatosis significantly decreased after 2 years of RSG (median decrease of 15%); in the RSG-RSG group, after an initial decline in the first year of 20%, 2 additional years of RSG did not result in further improvement. Likewise, there was no improvement in the NAS score, ballooning, intralobular inflammation, fibrosis stage, or area of fibrosis with 2 additional years of RSG in the RSG-RSG group.

Conclusion:

Rosiglitazone has a substantial antisteatogenic effect in the first year of treatment without additional benefit with longer therapy despite a maintained effect on insulin sensitivity and transaminase levels. This suggests that improving insulin sensitivity might not be sufficient in NASH and that additional targets of therapy for liver injury should be explored. (Hepatology 2009.)
Interleukin-17–Producing Cd4+ T Cells Increase With Severity of Liver Damage in Patients With Chronic Hepatitis B
Authors: Zhang Ji-Yuan , Zhang Zheng , Lin Fang , Zou Zheng-Sheng , Xu Ruo-Nan , Jin Lei , Fu Jun-Liang , Shi Feng , Shi Ming , Wang Hui-Fen , Wang Fu-Sheng
Published: September 2009

Interleukin-17 (IL-17)-producing CD4+ T cells (Th17)-mediated immune response has been demonstrated to play a critical role in inflammation-associated disease; however, its role in chronic hepatitis B virus (HBV) infection remains unknown. Here we characterized peripheral and intrahepatic Th17 cells and analyzed their association with liver injury in a cohort of HBV-infected patients including 66 with chronic hepatitis B (CHB), 23 with HBV-associated acute-on-chronic liver failure (ACLF), and 30 healthy subjects as controls. The frequency of circulating Th17 cells increased with disease progression from CHB (mean, 4.34%) to ACLF (mean, 5.62%) patients versus healthy controls (mean, 2.42%). Th17 cells were also found to be largely accumulated in the livers of CHB patients. The increases in circulating and intrahepatic Th17 cells positively correlated with plasma viral load, serum alanine aminotransferase levels, and histological activity index.

In vitro

, IL-17 can promote the activation of myeloid dendritic cells and monocytes and enhance the capacity to produce proinflammatory cytokines IL-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-23 in both CHB patients and healthy subjects. In addition, the concentration of serum Th17-associated cytokines was also increased in CHB and ACLF patients.

Conclusion:

Th17 cells are highly enriched in both peripheral blood and liver of CHB patients, and exhibit a potential to exacerbate liver damage during chronic HBV infection. (Hepatology 2009.)
Randomized Controlled Trial Testing the Effects of Weight Loss on Nonalcoholic Steatohepatitis
Authors: Promrat Kittichai , Kleiner David E. , Niemeier Heather M. , Jackvony Elizabeth , Kearns Marie , Wands Jack R. , Fava Joseph L. , Wing Rena R.
Published: September 2009

Nonalcoholic steatohepatitis (NASH) is a chronic progressive liver disease that is strongly associated with obesity. Currently, there is no approved therapy for NASH. Weight reduction is typically recommended, but efficacy data are lacking. We performed a randomized controlled trial to examine the effects of lifestyle intervention using a combination of diet, exercise, and behavior modification, with a goal of 7% to 10% weight reduction, on clinical parameters of NASH. The primary outcome measure was the change in NASH histological activity score (NAS) after 48 weeks of intervention. Thirty-one overweight or obese individuals (body mass index [BMI], 25–40 kg/m2) with biopsy-proven NASH were randomized in a 2:1 ratio to receive intensive lifestyle intervention (LS) or structured education (control). After 48 weeks of intervention, participants assigned to LS lost an average of 9.3% of their weight versus 0.2% in the control group (

P

= 0.003). A higher proportion of participants in the LS group had a reduction of NAS of at least 3 points or had posttreatment NAS of 2 or less as compared with the control group (72% versus 30%,

P

= 0.03). NAS improved significantly in the LS group (from 4.4 to 2.0) in comparison with the control group (from 4.9 to 3.5) (

P

= 0.05). Percent weight reduction correlated significantly with improvement in NAS (

r

= 0.497,

P

= 0.007). Participants who achieved the study weight loss goal (≥7%), compared with those who lost less than 7%, had significant improvements in steatosis (−1.36 versus −0.41,

P

< 0.001), lobular inflammation (−0.82 versus −0.24,

P

= 0.03), ballooning injury (−1.27 versus −0.53,

P

= 0.03) and NAS (−3.45 versus −1.18,

P

< 0.001).

Conclusion:

Weight reduction achieved through lifestyle intervention leads to improvements in liver histology in NASH. (Hepatology 2009.)
Long-Term Outcomes of Positive Fluorescence in Situ Hybridization Tests in Primary Sclerosing Cholangitis
Authors: Bangarulingam Sanjay Y. , Bjornsson Einar , Enders Felicity , Barr Fritcher Emily G. , Gores Gregory , Halling Kevin C. , Lindor Keith D.
Published: September 2009

Patients with primary sclerosing cholangitis (PSC) are at increased risk for developing cholangiocarcinoma (CCA). Fluorescence

in situ

hybridization (FISH) is a cytological test designed to enhance early CCA diagnosis. The long-term outcome of PSC patients with a positive FISH test (polysomy, trisomy/tetrasomy) are unclear. All PSC patients with at least one FISH test were identified and defined to have CCA if they had a positive tissue biopsy, positive cytology, or evidence of cancer in the explant after liver transplantation. A total of 235 PSC patients had at least one FISH test performed, and 56 patients had CCA on histopathology (n = 35) or cytology (n = 21). Overall, 120 of 235 (51%) of PSC patients tested for FISH were positive, but only one third of these positive patients had CCA. Sensitivity and specificity for FISH polysomy were 46% and 88%, and for trisomy/tetrasomy they were 25% and 67%, respectively. Survival analysis showed that patients with FISH polysomy had an outcome similar to patients with CCA; whereas FISH trisomy/tetrasomy patients had an outcome similar to patients with negative FISH tests. The FISH polysomy patients without cancer compared with those with CCA had lower serum bilirubin, lower carbohydrate antigen 19-9 (CA 19-9), lower Mayo risk score, and lower occurrence of dominant strictures.

Conclusion:

In PSC patients, the presence of a dominant stricture plus FISH polysomy has a specificity of 88% for CCA. Patients with FISH showing trisomy or tetrasomy have a similar outcome to patients with negative FISH. FISH testing should be used selectively in patients with other signs indicating CCA and not as a screening tool in all PSC patients undergoing endoscopic retrograde cholangiopancreatography (ERCP). (Hepatology 2009.)
Apolipoprotein E Interacts With Hepatitis C Virus Nonstructural Protein 5A and Determines Assembly of Infectious Particles
Authors: Benga Wagane J. A. , Krieger Sophie E. , Dimitrova Maria , Zeisel Mirjam B. , Parnot Marie , Lupberger Joachim , Hildt Eberhard , Luo Guangxiang , McLauchlan John , Baumert Thomas F. , Schuster Catherine
Published: September 2009

Chronic hepatitis C virus (HCV) infection is a major cause of liver disease worldwide. Restriction of HCV infection to human hepatocytes suggests that liver-specific host factors play a role in the viral life cycle. Using a yeast-two-hybrid system, we identified apolipoprotein E (apoE) as a liver-derived host factor specifically interacting with HCV nonstructural protein 5A (NS5A) but not with other viral proteins. The relevance of apoE–NS5A interaction for viral infection was confirmed by co-immunoprecipitation and co-localization studies of apoE and NS5A in an infectious HCV cell culture model system. Silencing apoE expression resulted in marked inhibition of infectious particle production without affecting viral entry and replication. Analysis of particle production in liver-derived cells with silenced apoE expression showed impairment of infectious particle assembly and release. The functional relevance of the apoE–NS5A interaction for production of viral particles was supported by loss or decrease of apoE–NS5A binding in assembly-defective viral mutants.

Conclusion:

These results suggest that recruitment of apoE by NS5A is important for viral assembly and release of infectious viral particles. These findings have important implications for understanding the HCV life cycle and the development of novel antiviral strategies targeting HCV–lipoprotein interaction. (Hepatology 2010)
Increased Caffeine Consumption Is Associated With Reduced Hepatic Fibrosis
Authors: Modi Apurva A. , Feld Jordan J. , Park Yoon , Kleiner David E. , Everhart James E. , Liang Jake T. , Hoofnagle Jay H.
Published: September 2009

Although coffee consumption has been associated with reduced frequency of liver disease, it is unclear whether the effect is from coffee or caffeine and whether there is an effect on hepatic fibrosis specifically. This study was undertaken to use a food-frequency instrument for dietary caffeine consumption to evaluate the relationship between caffeine intake and liver fibrosis. Patients undergoing liver biopsy completed a detailed caffeine questionnaire on three occasions over a 6-month period. Caffeine intake was compared between patients with mild and advanced liver fibrosis (bridging fibrosis/cirrhosis). Logistic regression was used to evaluate the association between caffeine consumption and hepatic fibrosis. One hundred seventy-seven patients (99 male, 104 white, 121 with chronic hepatitis C virus [HCV] infection) undergoing liver biopsy completed the caffeine questionnaire on up to three occasions. Results from repeated questionnaires were consistent. Daily caffeine consumption above the 75th percentile for the cohort (308 mg = approximately 2.25 cups of coffee equivalents) was associated with reduced liver fibrosis (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.14-0.80;

P

= 0.015) and the protective association persisted after controlling for age, sex, race, liver disease, body mass index, and alcohol intake in all patients (OR, 0.25; 95% CI, 0.09-0.67;

P

= 0.006), as well as the subset with HCV infection (OR, 0.19; 95% CI, 0.05-0.66;

P

= 0.009). Despite a modest trend, consumption of caffeine from sources other than coffee or of decaffeinated coffee was not associated with reduced liver fibrosis. A reliable tool for measurement of caffeine consumption demonstrated that caffeine consumption, particularly from regular coffee, above a threshold of approximately 2 coffee-cup equivalents per day, was associated with less severe hepatic fibrosis. (Hepatology 2010;51:201–209.)
Cyclosporine A inhibits hepatitis C virus nonstructural protein 2 through cyclophilin A #
Authors: Ciesek Sandra , Steinmann Eike , Wedemeyer Heiner , Manns Michael P. , Neyts Johann , Tautz Norbert , Madan Vanesa , Bartenschlager Ralf , von Hahn Thomas , Pietschmann Thomas
Published: September 2009

Numerous anti-hepatitis C virus (HCV) drugs targeting either the viral nonstructural 3 (NS3) protease or NS5B polymerase are currently in clinical testing. However, rapid resistance development is a major problem and optimal therapy will clearly require a combination of multiple mechanisms of action. Cyclosporine A (CsA) and its nonimmunosuppressant derivatives are among the more promising drugs under development. Based on work with subgenomic HCV replicons it has been thought that they act as NS5B-inhibitors. In this study we show that CsA inhibits replication of full-length HCV Japanese Fulminant Hepatitis (JFH1) genomes about 10-fold more efficiently than subgenomic replicons. This effect is dependent on the presence of NS2 in the viral polyprotein and mediated through cellular cyclophilin A. NS2 is either an additional target for CsA-dependent inhibition or modulates the antiviral activity against NS3 to NS5B proteins. CsA is thus the first anti-HCV drug shown to act through NS2. Conclusion: CsA inhibits replication of JFH1 full-length genomes much more efficiently than subgenomic replicons by targeting cleavage at the NS2/NS3 junction and possibly other nonreplication lifecycle steps. (Hepatology 2009.)
Diagnosis of Fibrosis and Cirrhosis Using Liver Stiffness Measurement in Nonalcoholic Fatty Liver Disease
Authors: Wong Vincent Wai-Sun , Vergniol Julien , Wong Grace Lai-Hung , Foucher Juliette , Chan Henry Lik-Yuen , Le Bail Brigitte , Choi Paul Cheung-Lung , Kowo Mathurin , Chan Anthony Wing-Hung , Merrouche Wassil , Sung Joseph Jao-Yiu , de Lédinghen Victor
Published: September 2009

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in affluent countries. Accurate noninvasive tests for liver injury are urgently needed. The aim of this study was to evaluate the accuracy of transient elastography for the diagnosis of fibrosis and cirrhosis in patients with NAFLD and to study factors associated with discordance between transient elastography and histology. Two hundred forty-six consecutive patients from two ethnic groups had successful liver stiffness measurement and satisfactory liver biopsy specimens. The area under the receiver-operating characteristics curve (AUROC) of transient elastography for F3 or higher and F4 disease was 0.93 and 0.95, respectively, and was significantly higher than that of the aspartate aminotransferase–to–alanine aminotransferase ratio, aspartate aminotransferase–to–platelet ratio index, FIB-4, BARD, and NAFLD fibrosis scores (AUROC ranged from 0.62 to 0.81,

P

< 0.05 for all comparisons). At a cutoff value of 7.9 kPa, the sensitivity, specificity, and positive and negative predictive values for F3 or greater disease were 91%, 75%, 52%, and 97%, respectively. Liver stiffness was not affected by hepatic steatosis, necroinflammation, or body mass index. Discordance of at least two stages between transient elastography and histology was observed in 33 (13.4%) patients. By multivariate analysis, liver biopsy length less than 20 mm and F0-2 disease were associated with discordance.

Conclusion:

Transient elastography is accurate in most NAFLD patients. Unsatisfactory liver biopsy specimens rather than transient elastography technique account for most cases of discordance. With high negative predictive value and modest positive predictive value, transient elastography is useful as a screening test to exclude advanced fibrosis. Liver biopsy may be considered in NAFLD patients with liver stiffness of at least 7.9 kPa. (Hepatology 2010;51:454–462.)
In vitro and in vivo platelet targeting by cyclic RGD‐modified liposomes
Authors: Srinivasan Rekha , Marchant Roger E. , Gupta Anirban Sen
Published: September 2009

Cell‐selective delivery using ligand‐decorated nanoparticles is a promising modality for treating cancer and vascular diseases. We are developing liposome nanoparticles surface‐modified by RGD peptide ligands having targeting specificity to integrin GPIIb‐IIIa. This integrin is upregulated and stimulated into a ligand‐binding conformation on the surface activated platelets. Activated‐platelet adhesion and aggregation are primary events in atherosclerosois, thrombosis, and restenosis. Hence, platelet‐targeted nanoparticles hold the promise of vascular site‐selective delivery of drugs and imaging probes. Here, we report in vitro and ex vivo microscopy studies of platelet‐targeting by liposomes surface‐modified with a cyclic RGD peptide. The peptide‐modified liposomes were labeled either with a lipophilic fluorophore or with lipid‐tethered Nanogold®. For in vitro tests, coverslip‐adhered activated human platelets were incubated with probe‐labeled liposomes, followed by analysis with fluorescence microscopy, phase contrast microscopy, and scanning electron microscopy (SEM). For in vivo tests, the liposomes were introduced within a catheter‐injured carotid artery restenosis model in rats and post‐euthanasia, the artery was imaged ex vivo by fluorescence microscopy and SEM. All microscopy results showed successful platelet‐targeting by the peptide‐modified liposomes. The in vitro SEM results also enabled visualization of nanoscopic liposomes attached to activated platelets. The results validate our nanoparticle design for site‐selective vascular delivery. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Friction properties of novel PVP/PVA blend hydrogels as artificial cartilage
Authors: Ma Ruyin , Xiong Dangsheng , Miao Feng , Zhang Jinfeng , Peng Yan
Published: September 2009

In this work, novel polyvinylpyrrolidone (PVP)/polyvinylalcohol (PVA) blend hydrogels were prepared by repeated freezing‐thawing cycles. The factors that influenced friction properties of blend hydrogels, such as PVP content, contact load, sliding speed, and lubrication condition, were mainly studied by sliding with stainless steel ball. The results showed that friction coefficients of the PVP/PVA blend hydrogels were definitely dependent on such influence factors. The friction system consisting of blend hydrogel and stainless steel ball nearly exhibited a mixed lubrication regime especially under bovine serum lubrication, and it can be proposed as a promising method to reduce wear of the prosthesis. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res, 2010
Computer simulation of flow‐sheets for the solvent extraction of uranium: a new route to delay the effect of chemical degradation of the organic phase during uranium recovery from acidic sulfate media
Authors: Chagnes Alexandre , Courtaud Bruno , Thiry Jacques , Cote Gérard
Published: September 2009

BACKGROUND: The extractants used in solvent extraction processes undergo degradation under thermal, chemical and radiolytical stresses. In the case of uranium plants, tri‐n‐octylamine, used as an extractant, slowly degrades into di‐n‐octylamine. Such degradation causes a gradual depletion of the uranium extraction isotherms and as a result, of the efficiency of uranium recovery from feed solutions. The present work highlights a new route to delay this depletion of the extraction efficiency, merely by optimizing the flow‐sheets involved in the process. Five flow‐sheets have been compared for uranium recovery from acidic sulfate media by a solution of 0.146 mol L−1 tri‐n‐octylamine in kerosene modified with 5% w/w 1‐tridecanol and stripping with a 199 g L−1 Na2CO3 solution. These five flow‐sheets include the classical counter‐current flow‐sheet with four mixers–settlers in extraction and three mixers–settlers in stripping and four unusual combined solvent extraction flow‐sheets with two independent extraction stripping loops and with one or two feed inlets.

RESULTS: Computer simulation supplied evidence of the strong influence of the studied flow‐sheets on the sturdiness of the process. More precisely, the unusual combined solvent extraction flow‐sheets appeared to be significantly more efficient than the classical counter‐current one and it is shown that an advantage of this can be to delay the negative impact of gradual degradation of tri‐n‐octylamine on uranium recovery efficiency from acidic sulfate media.

CONCLUSION: The replacement of classical counter‐current flow‐sheets with a unique extraction‐stripping loop in unusual combined flow‐sheets with two or more independent extraction‐stripping loops and with one or more feed inlets is a fruitful approach to delay the periodic addition of fresh tri‐n‐octylamine necessary for counter‐balancing the progressive degradation of the extraction solvent and, as a result, to delay the gradual depletion of the efficiency of uranium recovery. Copyright © 2009 Society of Chemical Industry
When does benevolent leadership lead to creativity? The moderating role of creative role identity and job autonomy
Authors: Wang An‐Chih , Cheng Bor‐Shiuan
Published: September 2009

The present study identified creative role identity and job autonomy as two moderators that influence the relationship between benevolent leadership, a leadership style that prevails in paternalistic contexts, and creativity. Using 167 dyads of supervisor and subordinate as a sample, we found that both creative role identity and job autonomy have significant moderating effects: When each moderator is high, the positive relationship between benevolent leadership and creativity is stronger; when each moderator is low, this relationship is weaker. Our results suggest that the effect of benevolent leadership upon creativity is dependent on the coexistence of important individual and contextual factors. Copyright © 2009 John Wiley & Sons, Ltd.
Micro Raman spectroscopy for monitoring alterations between human skin keratinocytes HaCaT and their tumorigenic derivatives A5RT3—toward a Raman characterization of a skin carcinoma model
Authors: Donfack P. , Rehders M. , Brix K. , Boukamp P. , Materny A.
Published: September 2009

Raman scattering provides molecular information about biochemical differences between healthy and cancerous cells in a non‐invasive and non‐destructive fashion. We have monitored such changes for the human skin keratinocyte cell line HaCaT and its cancerogenic counterpart A5RT3 at 514.5 and 647 nm excitations, with either fixed‐cell droplets or adherent fixed and living cells for repeated preparations over time in order to discriminate intrinsic characteristic changes. Cell droplets yielded average but rather reproducible information and helped to rapidly determine such changes. The Raman spectra show differences in the relative intensity ratios of the protein amide I band at 1656 cm−1 and amide III bands around 1250 cm−1 and of the phenylalanine ring mode at 1003.6 cm−1 to the CH2 deformation band at 1448 cm−1, which are considerably greater for HaCaT cells than A5RT3 cells. Interestingly, these observations were accompanied by severe and consistent changes in the amide III region and in the collagen marker region around 936 cm−1, therefore providing an unambiguous evidence of protein degradation and changes in the essential amino acid phenylalanine and in the lipid components in tumorigenic A5RT3 cells. Ultimately, in light of these intrinsic changes, the present findings are consistent with the passage number of the non‐tumorigenic HaCaT cells, because low pass HaCaT showed less pronounced alterations than high pass HaCaT, suggesting a correlation of tumorigenic transformation with primarily genetic instabilities in HaCaT cells. This work represents the first Raman spectroscopy discrimination of the skin carcinoma model cell lines, the non‐tumorigenic HaCaT and the cancerous A5RT3 cells, addressing the importance of delineating nonspecific variations from intrinsic characteristic changes and giving a spectroscopic indication for the influence of the passage number of HaCaT cells on the tumorigenic development. Copyright © 2009 John Wiley & Sons, Ltd.
Insights into phase stability of anhydrous/hydrate systems: a Raman‐based methodology
Authors: Nolasco Mariela M. , Amado Ana M. , Ribeiro‐Claro Paulo J. A.
Published: September 2009

FT‐Raman spectroscopy turns out to be a powerful technique to evaluate the amount of polymorphic and pseudopolymorphic forms in crystalline samples—which is particularly relevant in pharmaceutical sciences. This paper presents a methodology that allows successful quantitative evaluation of the solid‐state hydration and dehydration processes, using FT‐Raman spectroscopy. All the steps required for a reliable evaluation of the hydration/dehydration process are illustrated for the caffeine system, a particularly challenging system presenting limited spectral differences between the pseudopolymorphs. The hydration process of caffeine was found to occur in a single‐step process with a half‐life time of ca 13 h, while the dehydration occurs through a two‐step mechanism. The critical relative humidity was found to be at ca 81 and 42% for anhydrous and hydrate caffeine forms, respectively. Copyright © 2009 John Wiley & Sons, Ltd.
Genetic dissection of amino acid content in rice grain
Authors: Lu Kaiyang , Li Lanzhi , Zheng Xingfei , Zhang Zhihong , Mou Tongmin , Hu Zhongli
Published: September 2009

BACKGROUND: Protein content and amino acid composition in rice are the most important components of rice nutrient quality. However, there have been few reports on the mapping of quantitative trait loci (QTLs) for the contents of protein and amino acids in rice grain and other crops (soybean, corn). In this study a population of 241 recombinant inbred lines (RILs) from a cross between Zhenshan 97 and Minghui 63 (the parents of the most widely grown hybrid rice in China) was constructed to detect the main effect and epistatic effect QTLs for amino acid content (AAC) as characterised by individual AACs, total essential AAC and total AAC.

RESULTS: Using a linkage map covering a total of 1796 centimorgan (cM) based on 221 molecular marker loci, a total of 12 QTLs were identified for ten traits mapped on chromosomes 1, 4, 6, 7 and 11. The QTL cluster (flanked by C904, R2632 and C39) on chromosome 1 was associated with the content of eight amino acids. The phenotypic variation explained by individual QTLs ranged from 3.4 to 48.8%. Eighty‐one digenic interactions were resolved that involved 143 loci distributed on all 12 chromosomes. The amount of variation explained by main effect QTLs was lower than that explained by QTLs involved in epistatic interactions.

CONCLUSION: The findings showed that most main effect QTLs for AACs detected tended to be co‐localised within the genome. Thus, if a breeder were interested in changing the concentration of only one amino acid, this might be difficult to achieve. Meanwhile, the prevalent epistasis for the loci involved appeared to hold true for the content of amino acids. The information reported in the present study is expected to be useful for future breeding programmes targeting the development of improved rice amino acid composition for human nutrition. Copyright © 2009 Society of Chemical Industry
Massive trauma and the healing role of reparative justice
Authors: Danieli Yael
Published: September 2009

In this article, the author focuses on victims/survivors' experiences of justice processes after massive trauma. Reparative justice insists that every step throughout the justice experience—from the first moment of the court's encounter with a potential witness, to the follow‐up of witnesses after their return home, to the aftermath of the completion of the case—presents an opportunity for redress and healing. Conversely, this experience may present a risk of missing opportunities for healing and reintegrating victims into their societies, or, worse, (re)victimizing and (re)traumatizing them. Although restitution, rehabilitation, or compensation may come only after this process has concluded, opportunities exist throughout. Although not sufficient in itself, reparative justice is a necessary component among the healing processes after massive trauma.
Human rights and the trauma model: Genuine partners or uneasy allies?
Authors: Steel Zachary , Bateman Steel Catherine R. , Silove Derrick
Published: September 2009

Since World War II, a comprehensive body of international law has developed to protect and promote human rights. Three generations of rights can be delineated: civil and political; economic, social and cultural; and collective rights. The convergence of a medical rights‐based campaign in the late 1970s with the emergence of the new trauma model resulted in mental health professionals playing a prominent role in documenting and protecting civil and political rights. Economic, social, and cultural rights also emerged as being pivotal, particularly in the Australian context as mental health professionals began to work with excluded populations such as asylum seekers. Consideration of third‐generation rights raises important questions about the responsibilities facing mental health professionals applying the trauma model to non‐Western settings.
Differential inhibitory effects of inotilone on inflammatory mediators, inducible nitric oxide synthase and cyclooxygenase‐2, in LPS‐stimulated murine macrophage
Authors: Kuo Yu‐Ching , Lai Ching‐Shu , Wang Ju‐Ming , Badmaev Vladimir , Nagabhushanam Kalyanam , Ho Chi‐Tang , Pan Min‐Hsiung
Published: September 2009

The inhibitory effects of inotilone and methylinotilone on the induction of inducible nitric oxide synthase (iNOS) and cyclooxygenase‐2 (COX‐2) in murine RAW 264.7 cells activated with LPS were investigated. The results show that both hydroxyl groups on the benzene ring of the inotilone molecule are required for better anti‐inflammatory effect. Western blotting and RT‐PCR analyses demonstrated that inotilone blocked protein and mRNA expression of iNOS but not COX‐2. Instead, inotilone inhibited prostaglandin E2 production through decreasing the enzyme activity of COX‐2. The repression of iNOS but not COX‐2 expression may come from the differential effect of inotilone on nuclear factor‐κB (NFκB) and CCAAT/enhancer‐binding protein beta Treatment with inotilone resulted in the reduction of LPS‐induced nuclear translocation of NFκB subunit and the NFκB‐dependent transcriptional activity by blocking phosphorylation of inhibitor κB(IκB)α and p65 and subsequent degradation of inhibitor κBα. Inotilone also inhibited LPS‐induced activation of PI3K/Akt and extracellular signal‐regulated kinase 1/2 and p38 mitogen‐activated protein kinase. Our results suggest that inotilone may have potential to be developed into an effective anti‐inflammatory agent.
Purified berry anthocyanins but not whole berries normalize lipid parameters in mice fed an obesogenic high fat diet
Authors: Prior Ronald L. , Wu Xianli , Gu Liwei , Hager Tiffany , Hager Aaron , Wilkes Sam , Howard Luke
Published: September 2009

Male C57BL/6 mice received diets with either 10% of kcal from fat, or a high fat diet [45% (HF45) or 60% (HF60) kcal from fat]. Diets were prepared with or without freeze‐dried powders (10%) from whole blueberries (BB), strawberries (SB), Concord grape or black raspberry. In the 2nd study, purified anthocyanins (ACNs) from SB or BB were added to the drinking water of the treatments fed the HF60 diet. In Study 1, serum triglycerides were increased by feeding the HF45 diet but were elevated further when black raspberry or BB was included in the HF45 diet. Liver total lipids and triglycerides were increased in mice fed HF45 diet and inclusion of any of the berry powders in the HF45 diet did not alter concentrations compared to HF45 controls. In the 2nd study, mice fed the HF60 diet plus purified ACNs from BB in the water had lower body weight gains and body fat than the HF60 fed. Serum cholesterol and triglyceride levels were elevated with the HF60 diet and decreased to control levels when ACNs from either SB or BB were included in the drinking water. Serum leptin levels were consistently decreased to control low fat levels in those ACN treatments in which measures of body fat were decreased. Administering purified ACNs from BB and strawberry via drinking water prevented the development of dyslipidemia and obesity in mice, but feeding diets containing whole berries or purple corn (PC) ACNs did not alter the development of obesity.
Impaired active demethylation of the paternal genome in pronuclear‐stage rat zygotes produced by in vitro fertilization or intracytoplasmic sperm injection
Authors: Yoshizawa Yusuke , Kato Megumi , Hirabayashi Masumi , Hochi Shinichi
Published: September 2009

This study was designed to investigate the effect of in vitro production systems of rat zygotes such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) on demethylation dynamics of the paternal genome. Immunostaining with anti‐5‐methylcytosine indicated that in vivo derived zygotes harvested at 20 hr post‐hCG injection had no active demethylation of paternal genomes as a mean relative methylation (RM) value, total fluorescence in the paternal genome divided by that in maternal one, at 1.17. Leaving zygotes in vivo or in culture for an additional 4 or 8 hr resulted in significant decreases of RM values to 0.14–0.31. Since in vitro‐derived zygotes were produced using oocytes harvested at 14 hr post‐hCG injection, zygotes at 6 hr after IVF or ICSI were considered developmentally comparable to the in vivo derived zygotes harvested at 20 hr post‐hCG injection, with RM values at 1.04 and 0.92, respectively. At 10 hr post‐IVF and ICSI, the RM values of the in vitro derived zygotes decreased significantly, but to a lesser extent compared with in vivo derived zygotes, to 0.53 and 0.62, respectively, without further decreases at 14 hr. Treatment of IVF‐derived zygotes with 5‐aza‐2′‐deoxycytidine (5‐azadC; an inhibitor for methylation) or trichostatin A (TSA; an inhibitor for deacetylation) resulted in the decreased RM values at 14 hr post‐IVF. However, developmental potential of the 5‐azadC‐ or TSA‐treated IVF zygotes up to the blastocyst stage was not improved. Thus, the demethylation dynamics of the paternal genome in pronuclear‐stage rat zygotes was impaired by routine protocols for in vitro embryo production such as IVF and ICSI. Mol. Reprod. Dev. 77: 69–75, 2010. © 2009 Wiley‐Liss, Inc.
Administration of a mutated myostatin propeptide to neonatal mice significantly enhances skeletal muscle growth
Authors: Li Zicong , Zhao Baoping , Kim Yong Soo , Hu Ching Yuan , Yang Jinzeng
Published: September 2009

Myostatin is a dominant inhibitor of skeletal muscle development and growth. As transgenic over‐expression of myostatin propeptide dramatically enhanced muscle mass, we hypothesized that administration of myostatin propeptide will increase muscle growth. In this study, the wild‐type form of porcine myostatin propeptide and its mutated form at the cleavage site of metalloproteinases of BMP‐1/TLD family were produced from insect cells. In vitro A204 cells reporter assays showed that both wild‐type and the mutated propeptides depressed myostatin activity. The recombinant propeptides at four‐fold myostatin concentration can effectively block myostatin function during co‐incubation with A204 cells. In particular, the mutated propeptide appeared much more effective than wild‐type propeptide over a long period during the in vitro co‐incubation. Administration of the mutated propeptide to neonatal mice at the age of 11 and 18 days was tested and showed significant increase in growth performance by 11–15% from the age of 25 to 57 days (P < 0.05). The major skeletal muscles of mice that were injected with mutated propeptide were 13.5–24.8% heavier than the control group (P < 0.05) as a result of muscle fiber hypertrophy. In conclusion, administration of the mutated myostatin propeptide during the neonatal period is an effective way for promoting muscle growth. Mol. Reprod. Dev. 77: 76–82, 2010. © 2009 Wiley‐Liss, Inc.
”Mein Verhältnis zur GDCh ist emotional“
Authors: Guggolz Ernst , Remenyi Christian
Published: September 2009

Die Amtszeit von Klaus Müllen als GDCh‐Präsident endet in diesem Jahr. Die Nachrichten aus der Chemie fragen ihn, was ihn mit der GDCh verbindet und auf welchem Weg er die Gesellschaft sieht.
Die dreidimensionale Welt der Moleküle
Authors: Koch Oliver
Published: September 2009

Die Cambridge Strukturdatenbank ist in ein System von Programmen eingebettet, um Molekülgeometrien und ‐interaktionen innerhalb von Molekülkristallstrukturen zu analysieren.
”Bereiten Sie sich auf den Aufschwung vor — der kommt“
Authors: Erbslöh Carl Hugo , Guggolz Ernst
Published: September 2009

Wirtschaftskrise, Finanzkrise, echter Export, Reach, Shareholder‐Value, Tierversuche: Carl Hugo Erbslöh spricht mit den Nachrichten aus der Chemie über das, was aktuell nicht nur den Mittelstand umtreibt.
Stencil reduction algorithms for the local discontinuous Galerkin method
Authors: Castillo Paul E.
Published: September 2009

The problem of reducing the stencil of the local discontinuous Galerkin method applied to second‐order differential operator is discussed. Heuristic algorithms to minimize the total number of non‐zero blocks of the reduced stiffness matrix are presented and tested on a wide variety of unstructured and structured grids in 2D and 3D. Copyright © 2009 John Wiley & Sons, Ltd.
The fixed‐mesh ALE approach applied to solid mechanics and fluid–structure interaction problems
Authors: Baiges Joan , Codina Ramon
Published: September 2009

In this paper we propose a method to solve Solid Mechanics and fluid–structure interaction problems using always a fixed background mesh for the spatial discretization. The main feature of the method is that it properly accounts for the advection of information as the domain boundary evolves. To achieve this, we use an Arbitrary Lagrangian–Eulerian (ALE) framework, the distinctive characteristic being that at each time step results are projected onto a fixed, background mesh. For solid mechanics problems subject to large strains, the fixed‐mesh (FM)‐ALE method avoids the element stretching found in fully Lagrangian approaches. For FSI problems, FM‐ALE allows for the use of a single background mesh to solve both the fluid and the structure. Copyright © 2009 John Wiley & Sons, Ltd.
Safety, efficacy, and pharmacokinetics of intravenous busulfan in children undergoing allogeneic hematopoietic stem cell transplantation
Authors: Wall Donna A. , Chan Ka Wah , Nieder Michael L. , Hayashi Robert J. , Yeager Andrew M. , Kadota Richard , Przepiorka Donna , Mezzi Khaled , Kletzel Morris
Published: September 2009

Purpose

To determine the safety, efficacy, and PK profile of intravenous busulfan (Bu) in the context of a Bu and cyclophosphamide (IVBuCy) preparative regimen in children undergoing allogeneic hematopoietic stem cell transplantation (HSCT).

Methods

Twenty‐four children were enrolled in an open‐label, multicenter trial of IVBuCy as the preparative regimen for HLA‐matched sibling allogeneic HSCT. IVBu was administered q6 hr for 16 doses with a targeted area under the curve (AUC) of 900–1,350 µMol‐min. The initial dose was 0.8 mg/kg for children >4 years of age and 1 mg/kg for those <4 years of age. PK of the first dose IVBu was determined to calculate a single dosage adjustment, and with the 9th and 13th doses to confirm steady‐state PK.

Results

The targeted AUC was achieved with the first dose in 17/24 (71%) of the children using the age‐adjusted dosing approach. Dosing was increased in five patients, and reduced in two patients to achieve target values. After dose adjustment based on PK, 91% of the children had an AUC within the target range at steady state (AUCss). Median final dosing and clearance (CL) of IVBu were 1.1 mg/kg and 4.1 ml/min/kg in patients ≤4 years, and 0.9 mg/kg and 2.9 ml/min/kg in patients >4 years. All children were engrafted with documented donor chimerism. No late rejections or graft failures occurred. Four patients had veno‐occlusive disease, three of which resolved within 2 weeks of onset. Two children died from transplant‐related causes unrelated to Bu.

Conclusion

IVBu is a safe and effective and offers the benefit of predictable and consistent systemic exposure. Pediatr Blood Cancer 2010;54:291–298. © 2009 Wiley‐Liss, Inc.
Community acquired influenza requiring hospitalization: Vaccine status is unrelated to morbidity in children with cancer
Authors: Kersun Leslie S. , Coffin Susan E. , Leckerman Kateri H. , Ingram Mary , Reilly Anne F.
Published: September 2009

Background

Community acquired influenza can be severe and there are few data regarding hospitalization for children with cancer and influenza. Association between prior vaccination and infection severity has not been studied, although vaccination is standard practice.

Procedure

Patients with malignancy or prior stem cell transplant (SCT) were identified using a database of children with laboratory confirmed influenza (2000–2005). Other data collected included receipt of vaccine, absolute neutrophil count (ANC) and absolute lymphocyte count (ALC). These were compared with intensive care unit (ICU) stay, respiratory complications and hospital days.

Results

There were 39 patients with laboratory‐confirmed influenza with a median age of 6.9 years. Twenty‐four (62%) were on cancer therapy at time of infection and 18 (46%) had received the influenza vaccination that season. Measures of immune status included ANC at time of infection (median 1,530 cells/µl; inter‐quartile range, 315, 4347), presence of graft versus host disease 2 (5%) and steroid therapy 4 (10%) patients. All had a low ALC (median 448 cells/µl; IQR 189, 861). Respiratory complications occurred in 8 (20%), ICU admissions in 4 (10%) and death in 2 (5%) patients. Median hospital stay was 2 days. All ICU admissions occurred in unvaccinated patients (P = 0.1). Vaccine status, ANC (<1,000 cells/µl vs. >1,000) and ALC (<500 cells/µl vs. >500) were not associated with length of stay or respiratory complications.

Conclusions

Influenza infection can be severe in children with cancer and complications occur despite vaccination. Prospective evaluation of vaccine response is worthy of future study. Pediatr Blood Cancer 2010; 54:79–82. © 2009 Wiley‐Liss, Inc.