bluuebunny/crossref_metadata_2025 huggingface dataset:
Antifungal and Antibacterial Activity of the Newly Synthesized 2‐Xanthone Derivatives
Authors: Marona Henryk , Szkaradek Natalia , Karczewska Elzbieta , Trojanowska Danuta , Budak Alicja , Bober Piotr , Przepiórka Waldemar , Cegla Marek , Szneler Edward
Published: December 2008

A series of 2‐substituted xanthone derivatives 8–20 containing selected allyl, cinnamyl, morpholine, and imidazole moieties were synthesized and tested for their antifungal and antibacterial in‐vitro properties. Of the newly synthesized derivatives, ten revealed antifungal activity especially against Trichophyton mentagrophytes (the biggest inhibition zones ranged 35 mm for 11 and 13). 2‐(3‐(Allylamino)propoxy)‐9H‐xanthen‐9‐one hydrochloride 9 inhibited growth of all of the examined fungal species. Significant efficacy against evaluated yeasts and dermatophytes was also observed for 6‐chloro‐2‐methyl‐9H‐xanthen‐9‐one derivatives 11–13 containing encyclic amine moieties. Additionally, compounds 9, 11, and 12 hindered development of bacteria species but in a lesser degree. They were efficacious against Staphylococcus aureus, Escherichia coli, and Enterococcus faecalis.
New 1H‐Pyrazole‐4‐Carboxamides with Antiplatelet Activity
Authors: Rehse Klaus , Kotthaus Joscha , Khadembashi Laleh
Published: December 2008

Nine title compounds were synthesized and investigated in the Born test for their antiplatelet activities against collagen, ADP, adrenaline, and platelet activating factor (PAF) as inducers of the aggregation. Using collagen three compounds with IC50 values below 100 μM were found (3b, 3e, 3i). Activities in nanomolar concentrations were observed against ADP (3b, IC50 = 9.4 nM), adrenaline (3i, IC50 = 5.8 nM), and platelet activating factor (3e, IC50 = 0.45 nM).
Efficacy of immobilized polyplexes and lipoplexes for substrate‐mediated gene delivery
Authors: Bengali Zain , Rea Jennifer C. , Gibly Romie F. , Shea Lonnie D.
Published: December 2008

Non‐viral gene delivery by immobilization of complexes to cell‐adhesive biomaterials, a process termed substrate‐mediated delivery, has many in vitro research applications such as transfected cell arrays or models of tissue growth. In this report, we quantitatively investigate the efficiency of gene delivery by surface immobilization, and compare this efficiency to the more typical bolus delivery. The ability to immobilize vectors while allowing cellular internalization is impacted by the biomaterial and vector properties. Thus, to compare this efficiency between vector types and delivery methods, transfection conditions were initially identified that maximized transgene expression. For surface delivery from tissue culture polystyrene, DNA complexes were immobilized to pre‐adsorbed serum proteins prior to cell seeding, while for bolus delivery, complexes were added to the media above adherent cells. Mathematical modeling of vector binding, release, and cell association using a two‐site model indicated that the kinetics of polyplex binding to cells was faster than for lipoplexes, yet both vectors have a half‐life on the surface of approximately 17 min. For bolus and surface delivery, the majority of the DNA in the system remained in solution or on the surface, respectively. For polyplexes, the efficiency of trafficking of cell‐associated polyplexes to the nucleus for surface delivery is similar or less than bolus delivery, suggesting that surface immobilization may decrease the activity of the complex. The efficiency of nuclear association for cell‐associated lipoplexes is similar or greater for surface delivery relative to bolus. These studies suggest that strategies to enhance surface delivery for polyplexes should target the vector design to enhance its potency, whereas enhancing lipoplex delivery should target the material design to increase internalization. Biotechnol. Bioeng. 2009;102: 1679–1691. © 2008 Wiley Periodicals, Inc.
Impact of varying electron donors on the molecular microbial ecology and biokinetics of methylotrophic denitrifying bacteria
Authors: Baytshtok Vladimir , Lu Huijie , Park Hongkeun , Kim Sungpyo , Yu Ran , Chandran Kartik
Published: December 2008

The goal of this study was to identify bacterial populations that assimilated methanol in a denitrifying sequencing batch reactor (SBR), using stable isotope probing (SIP) of 13C labeled DNA and quantitatively track changes in these populations upon changing the electron donor from methanol to ethanol in the SBR feed. Based on SIP derived 13C 16S rRNA gene clone libraries, dominant SBR methylotrophic bacteria were related to Methyloversatilis spp. and Hyphomicrobium spp. These methylotrophic populations were quantified via newly developed real‐time PCR assays. Upon switching the electron donor from methanol to ethanol, Hyphomicrobium spp. concentrations decreased significantly in accordance with their obligately methylotrophic nutritional mode. In contrast, Methyloversatilis spp. concentrations were relatively unchanged, in accordance with their ability to assimilate both methanol and ethanol. Direct assimilation of ethanol by Methyloversatilis spp. but not Hyphomicrobium spp. was also confirmed via SIP. The reduction in methylotrophic bacterial concentration upon switching to ethanol was paralleled by a significant decrease in the methanol supported denitrification biokinetics of the SBR on nitrate. In sum, the results of this study demonstrate that the metabolic capabilities (methanol assimilation and metabolism) and substrate specificity (obligately or facultatively methylotrophic) of two distinct methylotrophic bacterial populations contributed to their survival or washout in denitrifying bioreactors. Biotechnol. Bioeng. 2009;102: 1527–1536. © 2008 Wiley Periodicals, Inc.
Assessment of fetal canine cardiac myocyte survival in a dual‐side flow bioreactor with modeled hypoxia/reperfusion injury
Authors: Moore Sandra K. , Kleis Stanley J. , Geng Yong‐Jian
Published: December 2008

The present study introduces a new experimental model of hypoxia/reperfusion injury using a newly developed bioreactor system. The injury is introduced and kept localized via fluid dynamic manipulation. Using low Reynolds number fluid flow, regions of the culture can be injured while maintaining physiological conditions in the remaining culture. This approach enables both normal and injured cells within the same monolayer to be investigated side‐by‐side. The current study evaluated the ability of the model to induce localized reperfusion injury in a monolayer of fetal canine cardiomyocytes (FCCs). Significant apoptosis was found in the hypoxia/reperfusion‐injured but not normal‐flow regions of the myocyte cultures. The model holds the potential to help elucidate the fundamental mechanisms of hypoxic/reperfusion insults in myocardium. Biotechnol. Bioeng. 2009;103: 199–206. © 2008 Wiley Periodicals, Inc.
Governance and the decision to issue a profit warning
Authors: Francoeur Claude , Labelle Réal , Martinez Isabelle
Published: December 2008

The theoretical concept of agency costs developed by Jensen and Meckling (1976) and Jensen (2005) are used to study the relationship between the quality of a firm's governance and its decision to issue a profit warning (PW) when it is overvalued. Based on a sample of Canadian companies between 2000 and 2004, results were only partially supportive of the hypotheses. The characteristics of the board seem to play only a secondary role in the decision to issue a profit warning when the firm is overvalued. On the other hand, as expected, governance mechanisms that factor in market values to align the interests of managers and directors with those of shareholders are negatively related to the profit warning decision. Copyright © 2008 ASAC. Published by John Wiley & Sons, Ltd.
La gouvernance : quel impact sur la décision d'alerte aux résultats?
Authors: Francoeur Claude , Labelle Réal , Martinez Isabelle
Published: December 2008

The theoretical concept of agency costs developed by Jensen and Meckling (1976) and Jensen (2005) are used to study the relationship between the quality of a firm's governance and its decision to issue a profit warning (PW) when it is overvalued. Based on a sample of Canadian companies between 2000 and 2004, results were only partially supportive of the hypotheses. The characteristics of the board seem to play only a secondary role in the decision to issue a profit warning when the firm is overvalued. On the other hand, as expected, governance mechanisms that factor in market values to align the interests of managers and directors with those of shareholders are negatively related to the profit warning decision. Copyright © 2008 ASAC. Published by John Wiley & Sons, Ltd.
Sequential therapy with sorafenib and sunitinib in renal cell carcinoma
Authors: Dudek Arkadiusz Z. , Zolnierek Jakub , Dham Anu , Lindgren Bruce R. , Szczylik Cezary
Published: December 2008

BACKGROUND:

Sunitinib and sorafenib are small‐molecule tyrosine kinase inhibitors (TKI) with antitumor activity in advanced renal cell carcinoma. A retrospective study was conducted to assess the response of renal cell carcinoma to sequential treatment with these two agents.

METHODS:

Tumor response was evaluated by using Response Evaluation Criteria In Solid Tumors (RECIST) criteria in patients failing first‐line therapy with either sunitinib or sorafenib and subsequently receiving second‐line therapy with the other TKI agent.

RESULTS:

Twenty‐nine patients received sorafenib followed by sunitinib (Group A), and 20 patients received sunitinib followed by sorafenib (Group B). TKI drugs were terminated in 6 (12%) patients in Group A and 4 (8%) in Group B because of toxicity. Median duration of stable disease for Groups A and B was 20 and 9.5 weeks, respectively. Median time from starting first TKI to disease progression after second TKI (time to progression) in Groups A and B was 78 and 37 weeks, respectively. Multivariate analysis revealed that Group B had a shorter time to progression than Group A (risk ratio [RR] 3.0; P = .016). Median overall survival was 102 and 45 weeks in Groups A and B, respectively (P = .061).

CONCLUSIONS:

The longer duration of disease control in patients who received sorafenib followed by sunitinib warrants further investigation. Cancer 2009. © 2008 American Cancer Society.
Studies related to antibody fragment (Fab) production in Escherichia coli W3110 fed‐batch fermentation processes using multiparameter flow cytometry
Authors: Want Andrew , Thomas Owen R. T. , Kara Bo , Liddell John , Hewitt Christopher J.
Published: December 2008

Microbiology is important to industry therefore rapid and statistically representative measurements of cell physiological state, proliferation, and viability are essential if informed decisions about fermentation bioprocess optimization or control are to be made, because process performance will depend largely on the number of metabolically active viable cells. Samples of recombinant Escherichia coli W3110, containing the gene for the D1.3 anti‐lysozyme Fab fragment under the control of the lac‐based expression system, were taken at various stages from fed‐batch fermentation processes and stained with a mixture of bis‐(1,3‐dibutylbarbituric acid) trimethine oxonol and propidium iodide (PI/BOX). Where appropriate, measurements of dissolved oxygen tension (DOT), OD600nm and Fab concentration were made. Depending on time of induction the maximum amount of Fab accumulating in the supernatant varied quite markedly from 1 to 4 μg ml−1 as did subsequent cell physiological state with respect to PI/BOX staining with a concomitant drop in maximum biomass concentration. Depending on point of induction a fourfold increase in Fab production could be achieved accompanied by a ∼50% drop in maximum biomass concentration but with a higher proportion of viable cells as measured by multiparameter flow cytometry. © 2008 International Society for Advancement of Cytometry
Bio‐Inspired Bottom‐Up Assembly of Diatom‐Templated Ordered Porous Metal Chalcogenide Meso/Nanostructures
Authors: Zhou Han , Fan Tongxiang , Li Xufan , Ding Jian , Zhang Di , Li Xuesong , Gao Yahui
Published: December 2008

We put forward a novel and straightforward sonochemical process as a generic bottom‐up assembly routeto produce ordered porous metal chalcogenide meso/nanostructures by templating of diatom frustules. We work with one of the most beautiful species of diatoms, Coscinodiscus lineatus, as a representative of diatoms with central symmetry, and with ZnS as the prototype, as it is a high refractive index material and is a typical material widely used in optics and photonics. ZnS replicas have been successfully synthesized from the interaction between the reactive surfaces of the frustules and the precursors under ultrasound. The inorganic replicas copy the morphology of the ordered porous structure and inherit its optical property, such as the existence of the photonic bandgap of the diatom frustules. It is possible to achieve tunable photonic properties in the replicas by assembly of various metal chalcogenide semiconductors of different refractive indexes. This bio‐inspired discovery provides insight into the facile synthesis of elaborate meso/nanostructures from these marine microbes.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Unexpected Formation of Ferrocene‐Containing Indolizines by Tandem Cyclization–Activation Reactions Induced by Silver Salts
Authors: Aguado Javier E. , Cativiela Carlos , Gimeno M. Concepción , Jones Peter G. , Laguna Antonio , Sarroca Cristina
Published: December 2008

Silver salts are used as promoters for the cyclization to novel ferrocene‐containing indolizine systems in only one step and with the simultaneous activation of the 7‐position of theheterocyclic ring. The reaction of 2‐[3‐(ferrocenyl)‐1‐oxoprop‐2‐enyl]pyridine with [Ag(OTf)(PR3)] (OTf = trifluoromethylsulfonate; PR3 = PPh3, PPh2Me) occurs with the precipitation of metallic silver and formation of the indolizine system. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Optimal airfoil shapes for low Reynolds number flows
Authors: Srinath D. N. , Mittal S.
Published: December 2008

Flow over NACA 0012 airfoil is studied at α = 4∘ and 12∘ for Re⩽500. It is seen that the flow is very sensitive to Re. A continuous adjoint based method is formulated and implemented for the design of airfoils at low Reynolds numbers. The airfoil shape is parametrized with a non‐uniform rational B‐splines (NURBS). Optimization studies are carried out using different objective functions namely: (1) minimize drag, (2) maximize lift, (3) maximize lift to drag ratio, (4) minimize drag and maximize lift and (5) minimize drag at constant lift. The effect of Reynolds number and definition of the objective function on the optimization process is investigated. Very interesting shapes are discovered at low Re. It is found that, for the range of Re studied, none of the objective functions considered show a clear preference with respect to the maximum lift that can be achieved. The five objective functions result in fairly diverse geometries. With the addition of an inverse constraint on the volume of the airfoil the range of optimal shapes, produced by different objective functions, is smaller. The non‐monotonic behavior of the objective functions with respect to the design variables is demonstrated. The effect of the number of design parameters on the optimal shapes is studied. As expected, richer design space leads to geometries with better aerodynamic properties. This study demonstrates the need to consider several objective functions to achieve an optimal design when an algorithm that seeks local optima is used. Copyright © 2008 John Wiley & Sons, Ltd.
Shan‐and‐Chen‐type multiphase lattice Boltzmann study of viscous coupling effects for two‐phase flow in porous media
Authors: Huang Haibo , Li Zhitao , Liu Shuaishuai , Lu Xi‐yun
Published: December 2008

In this paper, the Shan–Chen‐type (SC) multiphase lattice Boltzmann model was used to study the viscous coupling effects for immiscible two‐phase flow in porous media. In the model, any typical equation of state can be incorporated and different contact angles of the gas–liquid interface at a solid wall can be obtained easily through adjusting the ‘density of wall’ (Benzi et al., Phys. Rev. E 2006; 74(2):021509). The viscous coupling effects due to capillary number, the viscosity ratio and the wetting angle were investigated. The two‐phase flows with density ratio as high as 56 in porous media were simulated. For different viscosity ratios and wettability, two‐phase flow patterns and relative‐permeability curves as a function of wetting saturation were obtained. It is observed that when the wetting phase is less viscous and covers the solid surface, the relative permeability of the non‐wetting phase may be greater than unity. Here, the SC model is demonstrated as a suitable tool to study the immiscible two‐phase flow in porous media because it is simple, easy to get the desired contact angle and able to simulate immiscible phase flow with high‐density ratio. Copyright © 2008 John Wiley & Sons, Ltd.
Retail default prediction by using sequential minimal optimization technique
Authors: Hu Yu‐Chiang , Ansell Jake
Published: December 2008

This paper employed sequential minimal optimization (SMO) to develop default prediction model in the US retail market. Principal components analysis is used for variable reduction purposes. Four standard credit scoring techniques—naïve Bayes, logistic regression, recursive partitioning and artificial neural network—are compared to SMO, using a sample of 195 healthy firms and 51 distressed firms over five time periods between 1994 and 2002. The five techniques perform well in predicting default particularly one year before financial distress. Furthermore, the prediction still remains sound even 5 years before default. No single methodology has the absolute best classification ability, as the model performance varies in terms of different time periods and variable groups. External influences have greater impacts on the naïve Bayes than other techniques. In terms of similarity with Moody's ranking, SMO excelled over other techniques in most of the time periods. Copyright © 2008 John Wiley & Sons, Ltd.
Identification of genes putatively involved in the pathogenesis of diffuse large B‐cell lymphomas by integrative genomics
Authors: Oudejans Joost J. , van Wieringen Wessel N. , Smeets Serge J. , Tijssen Marianne , Vosse Sjoerd J. , Meijer Chris J. L. M. , Meijer Gerrit A. , van de Wiel Mark A. , Ylstra Bauke
Published: December 2008

Diffuse large B‐cell lymphomas (DLBCL) are highly heterogeneous with regard to clinical presentation and outcome. DLBCL copy number aberrations have been identified previously, of which the deletion at 6q21‐24 was significantly associated with a highly favorable clinical response to chemotherapy. In this study, we aimed to identify genes implicated in this and other genomic regions with recurrent losses and/or gains. To identify implicated genes, we superimposed array comparative genomic hybridization (aCGH) data onto a microarray expression dataset of 42 clinically well‐characterized primary nodal DLBCL biopsies. We confirmed that loss of 6q21‐24 is significantly associated with a highly favorable clinical response to chemotherapy. Our approach identified 316 significant genes restricted to 32 chromosomal regions, including 24 genes identified at 6q21‐24. In an independent dataset, 18% of overexpressed genes in gained regions and 55% of down‐regulated genes in deleted regions were validated. In summary, using integrative genomics novel onco and tumor suppressor genes were identified in DLBCL that were not recognized by expression profiling alone. © 2008 Wiley‐Liss, Inc.
No genomic aberrations in Langerhans cell histiocytosis as assessed by diverse molecular technologies
Authors: da Costa Cristiana E. T. , Szuhai Karoly , van Eijk Ronald , Hoogeboom Manja , Sciot Raphael , Mertens Fredrik , Björgvinsdóttir Helga , Debiec‐Rychter Maria , de Krijger Ronald R. , Hogendoorn Pancras C. W. , Egeler R. Maarten , Annels Nicola E.
Published: December 2008

The etiology of Langerhans cell histiocytosis (LCH), a disease characterized by uncontrolled proliferation of Langerhans cells, is unknown. Although some believe that LCH is reactive, others support a neoplastic origin. We tested the hypothesis that LCH is neoplastic by investigating potential consistent chromosomal aberrations in LCH cells. We used multiparameter DNA flow cytometry to analyze the DNA ploidy LCH cells in 20 cases, performed karyotype analysis in 31 cases, array‐based comparative genomic hybridization (arrayCGH) and single nucleotide polymorphism (SNP) arrays with DNA from flow‐sorted CD1a‐positive and CD1a‐negative cells in 19 cases. Ploidy analysis revealed diploid DNA content in all cases. The karyotype of all patients analyzed was normal, excluding the presence of balanced translocations. ArrayCGH and SNP arrays did not show genome abnormalities. Despite positive TP53 protein immunohistochemical staining, sequencing of exon 5 to 8 of p53 gene showed no alterations in 7 cases. This study strongly suggests that gross chromosomal abnormalities do not cause LCH. Although we cannot exclude cryptic point mutations in as yet unidentified genes, this study of 72 LCH cases shows that LCH may be the result of restricted oligoclonal stimulation rather than unlimited neoplastic proliferation. © 2008 Wiley‐Liss, Inc.
Phosphorylation and lipid raft association of fibroblast growth factor receptor‐2 in oligodendrocytes
Authors: Bryant M. R. , Marta C. B. , Kim F. S. , Bansal R.
Published: December 2008

Fibroblast growth factors (FGFs) and their receptors (FGFRs) initiate diverse cellular responses that contribute to the regulation of oligodendrocyte (OL) function. To understand the mechanisms by which FGFRs elicit these cellular responses, we investigated the phosphorylation of signal transduction proteins and the role of cholesterol‐glycosphingolipid‐enriched “lipid raft” microdomains in differentiated OLs. Surprisingly, we found that the most abundant tyrosine‐phosphorylated protein in OLs was the 120‐kd isoform of FGFR2 and that it was phosphorylated even in the absence of FGF2, suggesting a potential ligand‐independent function for this receptor. Furthermore, FGFR2, but not FGFR1, was associated with lipid raft microdomains in OLs and myelin (but not in astrocytes). This provides the first evidence for the association of FGFR with TX‐100‐insoluble lipid raft fractions. FGFR2 phosphorylated the key downstream target, FRS2 in OLs. Raft disruption resulted in loss of phosphorylated FRS2 from lipid rafts, coupled with the loss of Akt but not of Mek or Erk phosphorylation. This suggests that FGFR2‐FRS2 signaling in lipid rafts operates via the PI3‐Kinase/Akt pathway rather than the Ras/Mek/Erk pathway, emphasizing the importance of microenvironments within the cell membrane. Also present in lipid rafts in OLs and myelin, but not in astrocytes, was a novel 52‐kd isoform of FGFR2 that lacked the extracellular ligand‐binding region. These results demonstrate that FGFR2 in OLs and myelin possess unique characteristics that are specific both to receptor type and to OLs and provide a novel mechanism to elicit distinct cellular responses that mediate both FGF‐dependent and ‐independent functions. © 2008 Wiley‐Liss, Inc.
Hepatitis B virus surface antigen levels: A guide to sustained response to peginterferon alfa-2a in HBeAg-negative chronic hepatitis B # †
Authors: Brunetto Maurizia Rossana , Moriconi Francesco , Bonino Ferruccio , Lau George K. K. , Farci Patrizia , Yurdaydin Cihan , Piratvisuth Teerha , Luo Kangxian , Wang Yuming , Hadziyannis Stephanos , Wolf Eva , McCloud Philip , Batrla Richard , Marcellin Patrick
Published: December 2008

We investigated the relationship between hepatitis B virus surface antigen (HBsAg) serum level decline and posttreatment response in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B from a large multinational study of pegylated interferon alfa-2a (peginterferon alfa-2a), with or without lamivudine, versus lamivudine alone. Serum HBsAg was quantified using the Architect assay (Abbott Diagnostics) at pretreatment, end of treatment (week 48), and 6 months after the end of treatment (week 72) in sera from 386 of the 537 patients who participated in the multinational study (peginterferon alfa-2a, 127; peginterferon alfa-2a plus lamivudine, 137; lamivudine monotherapy, 122). Pretreatment HBsAg levels varied according to genotype, with the highest levels present in patients infected with genotypes A (median, 4.11 log10 IU/mL) and D (median, 3.85 log10 IU/mL). Significant on-treatment decline in HBsAg was observed during treatment with peginterferon alfa-2a (alone or combined with lamivudine; mean decline at week 48, −0.71 and −0.67 log10 IU/mL, respectively, P < 0.001), but not during treatment with lamivudine alone (−0.02 log10 IU/mL). Significantly more patients treated with peginterferon alfa-2a (21%) or peginterferon alfa-2a plus lamivudine (17%) achieved HBsAg levels <100 IU/mL at the end of treatment compared with lamivudine (1%) (both P < 0.001 versus lamivudine). End-of-treatment HBsAg level correlated strongly with HBV DNA suppression to ≤400 copies/mL 6 months posttreatment. An HBsAg level <10 IU/mL at week 48 and on-treatment decline >1 log10 IU/mL were significantly associated with sustained HBsAg clearance 3 years after treatment (both P < 0.0001). Conclusion: On-treatment quantification of HBsAg in patients with HBeAg-negative chronic hepatitis B treated with peginterferon alfa-2a may help identify those likely to be cured by this therapy and optimize treatment strategies. (Hepatology 2009;49:1141–1150.)
Natural killer T cells regulate the homing of chemokine CXC receptor 3-positive regulatory T cells to the liver in mice #
Authors: Santodomingo-Garzon Tania , Han Jinglan , Le Tai , Yang Yang , Swain Mark G.
Published: December 2008

Natural killer T (NKT) cells and regulatory T cells (Tregs) are both found within the liver and are known to exhibit immune regulatory functions. Hepatic NKT cells are activated early during inflammatory responses and release cytokines, including interferon gamma (IFN-γ), which we speculated could regulate Treg recruitment to the liver. To examine this, we treated C57BL/6 mice with a specific NKT cell activating ligand α galactosyl-C18-ceramide (αGal-C18-Cer) and examined the hepatic recruitment of Tregs. We found a time-dependant increase in the hepatic recruitment of Tregs after NKT cell activation, which was absent in NKT cell–deficient mice. Most recruited Tregs expressed interleukin (IL) 10, and to a lesser extent transforming growth factor beta (TGF-β). Because IFN-γ induces the production of chemokine (C-X-C motif) ligand 10 (CXCL10), and Tregs can express the cognate receptor for CXCL10 (that is, CXCR3), we considered that CXCL10 might mediate the hepatic recruitment of Tregs after NKT cell activation. Hepatic CXCL10 levels were markedly increased after αGal-C18-Cer administration in wild-type but not in NKT cell–deficient mice. Moreover, approximately 50% of Tregs recruited to the liver after αGal-C18-Cer administration expressed CXCR3 and CXCR3+ Treg recruitment into the liver was significantly inhibited in IFN-γ KO mice, and after CXCL10 neutralization. In addition, prevention of CXCR3+ Treg recruitment into the liver enhanced inflammatory effector cell recruitment into the liver after αGal-C18-Cer treatment. Conclusion: These results show that activated NKT cells can induce the hepatic recruitment of Tregs through a cytokine-to-chemokine pathway, which could be relevant in the development of chemokine blocking or NKT cell activating strategies to treat liver diseases. (Hepatology 2009.)
Detection of novel biomarkers of liver cirrhosis by proteomic analysis #
Authors: Mölleken Christian , Sitek Barbara , Henkel Corinna , Poschmann Gereon , Sipos Bence , Wiese Sebastian , Warscheid Bettina , Broelsch Christoph , Reiser Markus , Friedman Scott L. , Tornφe Ida , Schlosser Anders , Klöppel Günter , Schmiegel Wolff , Meyer Helmut E. , Holmskov Uffe , Stühler Kai
Published: December 2008

Hepatic cirrhosis is a life-threatening disease arising from different chronic liver disorders. One major cause for hepatic cirrhosis is chronic hepatitis C. Chronic hepatitis C is characterized by a highly variable clinical course, with at least 20% developing liver cirrhosis within 40 years. Only liver biopsy allows a reliable evaluation of the course of hepatitis C by grading inflammation and staging fibrosis, and thus serum biomarkers for hepatic fibrosis with high sensitivity and specificity are needed. To identify new candidate biomarkers for hepatic fibrosis, we performed a proteomic approach of microdissected cirrhotic septa and liver parenchyma cells. In cirrhotic septa, we detected an increasing expression of cell structure associated proteins, including actin, prolyl 4-hydroxylase, tropomyosin, calponin, transgelin, and human microfibril–associated protein 4 (MFAP-4). Tropomyosin, calponin, and transgelin reflect a contribution of activated stellate cells/myofibroblasts to chronic liver injury. The expression of tropomyosin, transgelin, and MFAP-4, an extracellular matrix associated protein, were further evaluated by immunohistochemistry. Tropomyosin and MFAP-4 demonstrated high serum levels in patients with hepatic cirrhosis of different causes. Conclusion: A quantitative analysis of MFAP-4 serum levels in a large number of patients showed MFAP-4 as novel candidate biomarker with high diagnostic accuracy for prediction of nondiseased liver versus cirrhosis [area under receiver operating characteristic curve (AUC) = 0.97, P < 0.0001] as well as stage 0 versus stage 4 fibrosis (AUC = 0.84, P < 0.0001), and stages 0 to 3 versus stage 4 fibrosis (AUC = 0.76, P < 0.0001). (Hepatology 2009.)
Association study between glutathione S‐transferase GST‐M1, GST‐T1, and GST‐P1 polymorphisms and tardive dyskinesia
Authors: Kang Seung‐Gul , Lee Heon‐Jeong , Choi Jung‐Eun , An Hyonggin , Rhee MinKyu , Kim Leen
Published: December 2008

Objectives

Data from several studies suggest that oxidative stress may play a role in the pathophysiology of tardive dyskinesia (TD). Glutathione S‐transferase (GST) enzymes play important roles in protecting cells against oxidative stress. In the present study, we investigated the hypothesis that polymorphisms in genes for these detoxifying enzymes can influence susceptibility to TD in patients with schizophrenia.

Methods

The GST‐M1, GST‐T1, and GST‐P1 loci were analyzed by polymerase chain reaction (PCR)‐based methods in 83 schizophrenic patients with TD and 126 schizophrenic without TD who were matched for antipsychotic drug exposure and other relevant variables. The multifactor dimensionality reduction (MDR) approach was used to analyze gene–gene interactions.

Results

There were no significant differences in the distributions of the GST‐M1, GST‐T1, and GST‐P1 genotypes between the TD and non‐TD groups (p > 0.05). However, in comparison of the severity of TD among genotypes using Poisson regression showed that Ile/Ile genotype of GST‐P1 had higher AIMS score compared to Ile/Val + Val/Val genotypes (X2 = 7.13, p = 0.008). MDR analysis did not show a significant interaction between the three GST gene variants and susceptibility to TD (p > 0.05).

Conclusions

These results suggest that GST gene polymorphisms do not confer increased susceptibility to TD in patients with schizophrenia but TD severity might be related with GST‐P1 variants. Copyright © 2008 John Wiley & Sons, Ltd.
The t‐PA‐encapsulated PLGA nanoparticles shelled with CS or CS‐GRGD alter both permeation through and dissolving patterns of blood clots compared with t‐PA solution: An in vitro thrombolysis study
Authors: Wang Shoei‐Shen , Chou Nai‐Kuan , Chung Tze‐Wen
Published: December 2008

Accelerated thrombolysis by pressure‐driven permeation has been demonstrated in in vitro and in vivo animal models by using plasminogen activators (PAs) encapsulated liposomes or PEG microparticles. Recent reports have also described acceleration of thrombolysis using tissue type PA (t‐PA) encapsulated in PLGA nanoparticles (NPs) coated with chitosan (CS) or CS‐GRGD by interactions between the NPs and blood clots. However, the permeation through and dissolving patterns in thrombolysis with the aforementioned microparticles or NPs, which may be clinically relevant to the recovery status of the posttreatments, have not been reported. Therefore, this work studied such phenomena in thrombolysis with t‐PA encapsulated in NPs. The t‐PA solution and the NPs exhibited distinctly different permeation patterns of dissolved clots. Plasma permeates through clots showed a stream flow or burst flow phenomena when lyzed with NPs shelled with CS or CS‐GRGD, respectively, whereas a diffusion pattern was observed in those lyzed with t‐PA solution. At the outlet position of clots, the clots dissolved with PLGA/CS and PLGA/CS‐GRGD NPs revealed extremely rough surfaces to a depth of 100 μm, indicating that a cross‐permeation direction of clot lysis occurred, while those dissolved with t‐PA solution showed slightly rough surfaces to a depth of 12 μm. Permeation through and clot dissolution patterns of thrombolysis with t‐PA encapsulated in NPs shelled with CS or CS‐GRGD distinctly differed from those dissolved with t‐PA solutions in this in vitro thrombolysis model, These findings may be relevant to posttreatment of patients with conventional PA thrombolysis. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009
Investigations into the development of catalytic activity in anti‐acetylcholinesterase idiotypic and anti‐idiotypic antibodies
Authors: Johnson Glynis , Moore Samuel W.
Published: December 2008

We have previously described anti‐acetylcholinesterase antibodies that display acetylcholinesterase‐like catalytic activity. No evidence of contaminating enzymes was found, and the antibodies are kinetically and apparently structurally distinct from both acetylcholinesterase (AChE) and butyrylcholinesterase. We have also mimicked the antibody catalytic sites in anti‐anti‐idiotypic (Ab3) antibodies. Independently from us, similar acetylcholinesterase‐like antibodies have been raised as anti‐idiotypic (Ab2) antibodies against a non‐catalytic anti‐acetylcholinesterase antibody, AE‐2. In this paper, we describe an epitope analysis, using synthetic peptides in ELISA and competition ELISA, and a peptide array, of five catalytic anti‐acetylcholinesterase antibodies (Ab1s), three catalytic Ab3s, as well as antibody AE‐2 and a non‐catalytic Ab2. The catalytic Ab1s and Ab3s recognized three Pro‐ and Gly‐containing sequences (40PPMGPRRFL,78PGFEGTE, and258PPGGTGGNDTELVAC) on the AChE surface. As these sequences do not adjoin in the AChE structure, recognition would appear to be due to cross‐reaction. This was confirmed by the observation that the sequences superimpose structurally. The non‐catalytic antibodies, AE‐2 and the Ab2, recognized AChE's peripheral anionic site (PAS), in particular, the sequence70YQYVD, which contains two of the site's residues. The crystal structure of the AChE tetramer (Bourneet al., 1999) shows direct interaction and high complementarity between the257CPPGGTGGNDTELVAC sequence and the PAS. Antibodies recognizing the sequence and the PAS may, in turn, be complementary; this may account for the apparent paradox of catalytic development in both Ab1s and Ab2s. The PAS binds, but does not hydrolyze, substrate. The catalytic Ab1s, therefore, recognize a site that may function as a substrate analog, and this, together with the presence of an Arg‐Glu salt bridge in the epitope, suggests mechanisms whereby catalytic activity may have developed. In conclusion, the development of AChE‐like catalytic activity in anti‐AChE Ab1s and Ab2s appears to be the result of a combination of structural complementarity to a substrate‐binding site, charge complementarity to a salt bridge, and specific structural peculiarities of the AChE molecule. Copyright © 2008 John Wiley & Sons, Ltd.
Non‐stationary frequency analysis of extreme daily rainfall in Sao Paulo, Brazil
Authors: Sugahara Shigetoshi , da Rocha Rosmeri Porfírio , Silveira Reinaldo
Published: December 2008

This work is an assessment of frequency of extreme values (EVs) of daily rainfall in the city of Sao Paulo, Brazil, over the period 1933–2005, based on the peaks‐over‐threshold (POT) and Generalized Pareto Distribution (GPD) approach. Usually, a GPD model is fitted to a sample of POT values selected with a constant threshold. However, in this work we use time‐dependent thresholds, composed of relatively largepquantiles (for examplepof 0.97) of daily rainfall amounts computed from all available data. Samples of POT values were extracted with several values ofp. Four different GPD models (GPD‐1, GPD‐2, GPD‐3, and GDP‐4) were fitted to each one of these samples by the maximum likelihood (ML) method. The shape parameter was assumed constant for the four models, but time‐varying covariates were incorporated into scale parameter of GPD‐2, GPD‐3, and GPD‐4, describing annual cycle in GPD‐2, linear trend in GPD‐3, and both annual cycle and linear trend in GPD‐4. The GPD‐1 with constant scale and shape parameters is the simplest model. For identification of the best model among the four models we used rescaled Akaike Information Criterion (AIC) with second‐order bias correction. This criterion isolates GPD‐3 as the best model, i.e. the one with positive linear trend in the scale parameter. The slope of this trend is significant compared to the null hypothesis of no trend, for about 98% confidence level. The non‐parametric Mann–Kendall test also showed presence of positive trend in the annual frequency of excess over high thresholds, withp‐value being virtually zero. Therefore, there is strong evidence that high quantiles of daily rainfall in the city of Sao Paulo have been increasing in magnitude and frequency over time. For example, 0.99 quantiles of daily rainfall amount have increased by about 40 mm between 1933 and 2005. Copyright © 2008 Royal Meteorological Society
Spatio‐temporal rainfall patterns in Southern South America
Authors: Aravena Juan‐Carlos , Luckman Brian H.
Published: December 2008

The dominant spatial and temporal patterns of a network of 23 homogenous instrumental rainfall records of Southern South America were analysed and used to define four regional annual precipitation series: (1) Northwestern Patagonia (1950–2000) with nine stations from both side of the Andes between 41 and 44°S; (2) Central Patagonia (1950–2000) with five Chilean stations between 45 and 47°S; (3) Patagonian plains–Atlantic (1961–2000) with five Argentinean stations spread between 43 and 50°S and from the eastern foothills of the Andes to the Atlantic coast and (4) Southern Patagonia (1950–2000) with four stations east of the Andes, near the Strait of Magellan between 51 and 53°S. Unique patterns were also identified for two of the southernmost stations in Ushuaia and Evangelistas (EVA). Time series analysis of these regional patterns shows marked decadal variability for Northwestern and Central Patagonia, 3–7 years oscillations for the Patagonian plains–Atlantic region and a strong biannual oscillation mode for Southern Patagonia. Regional annual rainfall appears to be strongly influenced by Antarctic circulation modes (Antarctic Oscillation Index), whereas the El Niño‐Southern Oscillation (ENSO) influence on rainfall variability is less evident. Highly significant correlation of precipitation on the west coast of Patagonia with the pressure gradient between the subtropical eastern Pacific and the high‐latitude south eastern Pacific is confirmed. Copyright © 2008 Royal Meteorological Society
Vapor‐Based Polymer Gradients
Authors: Elkasabi Yaseen , Lahann Joerg
Published: December 2008

Chemical vapor deposition (CVD) co‐polymerization was used to fabricate polymer coatings, which comprise of reactive surface composition gradients. Two functionalized derivatives of [2.2]paracyclophane were fed into a two‐source CVD system at a 180 ° angle, then copolymerized and deposited as a polymer gradient. Infrared and X‐ray photoelectron spectroscopy (XPS) confirmed the compositional changes within the bulk polymer and at the surface. By manipulating process parameters, gradients of tailored compositional slope can be deposited on a wide range of substrates. We also were able to selectively immobilize fluorescence‐labeled ligands onto the reactive polymer gradients, making CVD‐based gradient surfaces a flexible platform for fabricating biomolecular substrates.

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Movement disturbances in the differential diagnosis of Creutzfeldt‐Jakob disease
Authors: Edler Jan , Mollenhauer Brit , Heinemann Uta , Varges Daniela , Werner Carola , Zerr Inga , Schulz‐Schaeffer Walter J.
Published: December 2008

Movement disturbances are common in dementia disorders and are a central feature of the clinical classification criteria of Creutzfeldt‐Jakob disease (CJD). Polymorphism at codon 129 of the prion protein gene is known to determine the clinical picture of CJD. The frequency and characteristics of movement disturbances in other dementing disorders, such as Alzheimer's disease (AD), is barely known and leads to misdiagnoses. We investigated the occurrence and characteristics of movement disturbances in 143 patients neuropathologically confirmed with CJD (n = 100), AD (n = 29), dementia with Lewy bodies (DLB) (n = 7), or other diagnoses (n = 7). All patients had been referred with the differential diagnosis of prion disease. Ataxia and dysmetria were significantly more frequent in CJD than in AD or DLB patients, whereas hypokinesia was up to five times more frequent in AD or DLB (P < 0.05). Using an ordered logistic regression to identify constellations of movement disturbances, the diagnosis of CJD was likely in patients presenting ataxia but not hypokinesia. The reverse situation was statistically associated with AD. Ataxia and cogwheel rigidity were associated with valine‐homozygosity and akinesia with methionine‐homozygosity in the CJD patients. Our results indicate that the careful assessment of movement disturbances may be helpful in the differential diagnosis of Creutzfeldt‐Jakob disease. © 2008 Movement Disorder Society
Numerical analysis of the response of battered piles to inclined pullout loads
Authors: Mroueh Hussein , Shahrour Isam
Published: December 2008

This paper presents a three‐dimensional finite element analysis of the response of battered piles to the combined lateral and vertical pullout loads. Analyses are carried out using an elastoplastic constitutive law based on the non‐associated Mohr–Coulomb criterion. The influence of the contact condition at the pile–soil interface is also investigated. Analyses show that the load's inclination with regard to the pile's axis affects both the lateral and axial response of the battered piles. Analyses also show that the pullout capacity of battered piles is affected by the pile's inclination regarding the vertical axis as well as the load's inclination regarding the pile's axis. The investigation of the influence of the contact condition at the soil–pile interface shows that the possibility of sliding at the soil–pile interface affects the response of battered piles subjected to loads with low inclination regarding the pile's axis. Copyright © 2008 John Wiley & Sons, Ltd.
Axial symmetric elasticity analysis in non‐homogeneous bodies under gravitational load by triple‐reciprocity boundary element method
Authors: Ochiai Yoshihiro , Sladek Vladimir , Sladek Jan
Published: December 2008

In general, internal cells are required to solve elasticity problems by involving a gravitational load in non‐homogeneous bodies with variable mass density when using a conventional boundary element method (BEM). Then, the effect of mesh reduction is not achieved and one of the main merits of the BEM, which is the simplicity of data preparation, is lost. In this study, it is shown that the domain cells can be avoided by using the triple‐reciprocity BEM formulation, where the density of domain integral is expressed in terms of other fields that are represented by boundary densities and/or source densities at isolated interior points. Utilizing the rotational symmetry, the triple‐reciprocity BEM formulation is developed for axially symmetric elasticity problems in non‐homogeneous bodies under gravitational force. A new computer program was developed and applied to solve several test problems. Copyright © 2008 John Wiley & Sons, Ltd.
Efficient preparation of novel fluoroalkyl end‐capped oligomers/titanium dioxide nanocomposites
Authors: Sawada Hideo , Sawada Eri , Kakehi Hiroshi , Kariya Takurou , Mugisawa Masaki , Chounan Yukiyasu , Miura Masashi , Isu Norifumi
Published: December 2008

Novel fluoroalky end‐capped oligomers/titanium dioxide nanocomposites were prepared by the hydrolysis of titanium isopropoxide in the presence of fluoroalkyl end‐capped N‐(1,1‐dimethyl‐3‐oxobutyl)acrylamide oligomer [RF‐(DOBAA)n‐RF], fluoroalkyl end‐capped N,N‐dimethylacrylamide oligomer [RF‐(DMAA)n‐RF], and fluoroalkyl end‐capped acrylic acid oligomer [RF‐(ACA)n‐RF] in tetrahydrofuran under mild conditions. In these fluorinated oligomers, RF‐(ACA)n‐RF oligomer is more effective for the preparation of the corresponding oligomers/titanium dioxide nanocomposites, and this oligomer can afford the expected fluorinated titanium dioxide nanocomposites in higher isolated yields. In addition, RF‐(ACA)n‐RF/titanium dioxide composites are nanometer size‐controlled very fine nanoparticles (14–48 nm), and exhibited a good dispersibility not only in water but also in traditional organic solvents. Fluoroalkyl end‐capped oligomers/titanium dioxide nanocomposites were also applied to the surface modification of the common organic polymers such as poly(methyl methacrylate) to exhibit a good oleophobic and hydrophilic characteristics on the surface. POLYM. COMPOS., 2009. © 2008 Society of Plastics Engineers.
Acaricidal activity of triketone analogues derived from Leptospermum scoparium oil against house‐dust and stored‐food mites
Authors: Jeong Eun‐Young , Kim Min‐Gi , Lee Hoi‐Seon
Published: December 2008

BACKGROUND: Various attempts to control the populations of house‐dust and stored‐food mites have been implemented using synthetic chemicals. Although effective, the repeated use of these chemicals has led to resistance owing to the mite's high reproductive potential and short life cycle. Therefore, this study aimed to develop natural acaricides using oils derived from Leptospermum scoparium JR & G Forst., which may affect the overall biological activity of a mite without adverse effects. Results were compared with those from using benzyl benzoate and N,N‐diethyl‐3‐methylbenzamide (DEET).

RESULTS: The LD50 values of L. scoparium oil were 0.54, 0.67 and 1.12 µg cm−2 against Dermatophagoides farinae (Hughes), D. pteronyssinus (Troussart) and Tyrophagus putrescentiae (Schrank) respectively. The active constituent isolated from L. scoparium was identified as leptospermone (6‐isovaleryl‐2,2,4,4‐tetramethyl‐1,3,5‐cyclohexanetrione) by spectroscopic analysis. Based on the LD50 values of leptospermone and its derivatives, the most toxic compound against D. farinae was leptospermone (0.07 µg cm−2), followed by 2,2,4,4,6,6‐hexamethyl‐1,3,5‐cyclohexanetrione (1.21 µg cm−2), benzyl benzoate (10.03 µg cm−2) and DEET (37.12 µg cm−2). Furthermore, similar results were observed when the leptospermone and its derivatives were tested against D. pteronyssinus and T. putrescentiae.

CONCLUSIONS: These results indicate that L. scoparium oil‐derived materials, particularly leptospermone and 2,2,4,4,6,6‐hexamethyl‐1,3,5‐cyclohexanetrione, have potential for development as new agents for the control of three species of mite. Copyright © 2008 Society of Chemical Industry
Fesoterodine (Toviaz): new option for overactive bladder
Authors: Chaplin Steve , Wagg Adrian
Published: December 2008

Fesoterodine, the prodrug of the active metabolite of tolterodine, has been launched in two strengths for the treatment of overactive bladder. In our New products review Steve Chaplin presents the clinical data relating to its efficacy and adverse effects, and Dr Adrian Wagg comments on its place in treatment. Copyright © 2008 Wiley Interface Ltd