bluuebunny/crossref_metadata_2025 huggingface dataset:
Business transformation in heterogeneous environments: The impact of market development and firm strength on retrenchment and growth reconfiguration
Authors: Chakrabarti Abhirup , Vidal Elena , Mitchell Will
Published: May 2011

Asset reconfiguration by both growth and divestiture underlies business transformation, but reconfiguration remains poorly understood in countries with limited market infrastructure. We argue that more developed infrastructure facilitates resource reconfiguration, assisting weak firms' attempts to retrench and strong firms' attempts to grow; in turn, market development shapes the impact of reconfiguration by enhancing the benefits of adding assets and limiting the benefits of divestitures. We examine reconfiguration activity by 1,256 firms based in eight South East Asian economies—Hong Kong, Indonesia, Korea, Malaysia, the Philippines, Singapore, Taiwan, and Thailand—from 1990 to 1999. The study contributes to theories of business dynamics in varied settings of market‐based socioeconomic development.
The geographic scope of the MNC and its alliance portfolio: Resolving the paradox of distance
Authors: Zaheer Akbar , Hernandez Exequiel
Published: May 2011

Some research suggests that knowledge transfer and performance suffer when entities are distant from each other, while other work emphasizes that distance is beneficial by allowing firms to access novel and diverse knowledge. We resolve this paradox by focusing on the differing roles of MNC subsidiaries and headquarters vis‐à‐vis its alliances: distance between technology alliance partners and subsidiaries hurts MNC performance, but MNCs benefit when such partners are located afar from headquarters. We find support for these ideas in a longitudinal sample (2002 to 2006) of 126 Fortune 500 firms. Our work broadens the concept of the geographic scope of the firm, and suggests that MNCs gain by searching globally but collaborating locally.
Bringing corporate governance to international joint ventures
Authors: Reuer Jeffrey J. , Klijn Elko , van den Bosch Frans A.J. , Volberda Henk W.
Published: May 2011

Large gaps appear to exist between the evolving corporate governance practices of organizations and those of international joint ventures (IJVs). Some of these gaps might well be appropriate given some of the unique features of IJVs, while others might require new consideration and attention by organizations engaged in alliances. The expansive literatures on corporate governance and IJVs have developed separately from one another, and there are important opportunities to combine them. We argue that a need exists for a new generation of IJV governance research that considers IJVs' boards of directors as well as other dimensions of governance. We highlight some research opportunities that are illustrative for the research agenda that we are calling for that builds bridges between the literatures on corporate governance and IJVs.
The mentalizing network orchestrates the impact of parochial altruism on social norm enforcement
Authors: Baumgartner Thomas , Götte Lorenz , Gügler Rahel , Fehr Ernst
Published: May 2011

Parochial altruism—a preference for altruistic behavior towards ingroup members and mistrust or hostility towards outgroup members—is a pervasive feature in human society and strongly shapes the enforcement of social norms. Since the uniqueness of human society critically depends on the enforcement of norms, the understanding of the neural circuitry of the impact of parochial altruism on social norm enforcement is key, but unexplored. To fill this gap, we measured brain activity with functional magnetic resonance imaging (fMRI) while subjects had the opportunity to punish ingroup members and outgroup members for violating social norms. Findings revealed that subjects' strong punishment of defecting outgroup members is associated with increased activity in a functionally connected network involved in sanction‐related decisions (right orbitofrontal gyrus, right lateral prefrontal cortex, right dorsal caudatus). Moreover, the stronger the connectivity in this network, the more outgroup members are punished. In contrast, the much weaker punishment of ingroup members who committed the very same norm violation is associated with increased activity and connectivity in the mentalizing‐network (dorsomedial prefrontal cortex, bilateral temporo‐parietal junction), as if subjects tried to understand or justify ingroup members' behavior. Finally, connectivity analyses between the two networks suggest that the mentalizing‐network modulates punishment by affecting the activity in the right orbitofrontal gyrus and right lateral prefrontal cortex, notably in the same areas showing enhanced activity and connectivity whenever third‐parties strongly punished defecting outgroup members. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.
Hepatocyte proliferation and hepatomegaly induced by phenobarbital and 1,4-bis [2-(3,5-dichloropyridyloxy)] benzene is suppressed in hepatocyte-targeted glypican 3 transgenic mice
Authors: Lin Chih-Wen , Mars Wendy M. , Paranjpe Shirish , Donthamsetty Shashikiran , Bhave Vishakha S. , Kang Liang-I , Orr Anne , Bowen William C. , Bell Aaron W. , Michalopoulos George K.
Published: May 2011

Glypican 3 (GPC3) is a family of glycosylphosphatidylinositol-anchored, cell-surface heparan sulfate proteoglycans. Loss-of-function mutations of GPC3 cause Simpson-Golabi-Behmel syndrome characterized by overgrowth of multiple organs, including liver. Our previous study showed that in GPC3 transgenic (TG) mice, hepatocyte-targeted overexpression of GPC3 suppresses hepatocyte proliferation and liver regeneration after partial hepatectomy and alters gene expression profiles and potential cell cycle-related proteins. This study investigates the role of GPC3 in hepatocyte proliferation and hepatomegaly induced by the xenobiotic mitogens phenobarbital (PB) and TCPOBOP (1, 4-bis [2-(3, 5-dichloropyridyloxy)] benzene). Wildtype (WT) and GPC3 TG mice were given 0.1% PB in drinking water for 10 days or a single dose of TCPOBOP (3 mg/kg) by oral gavage. At day 5 the WT mice showed a 2.2- and 3.0-fold increase in liver weight, whereas the GPC3 TG mice showed a 1.3- and 1.6-fold increase in liver weight after PB and TCPOBOP administration, respectively. There was a significant suppression of proliferative response in the GPC3 TG mice, as assessed by percent of Ki67-positive hepatocyte nuclei. Moreover, gene array analysis showed a panel of changes in the gene expression profile of TG mice, both before and after administration of the xenobiotic mitogens. Expression of cell cycle-related genes in the TG mice was also decreased compared to the WT mice.

Conclusion:

Our results indicate that in GPC3 TG mice, hepatocyte-targeted overexpression of GPC3 plays an important role for regulation of liver size and termination of hepatocyte proliferation induced by the xenobiotic mitogens PB and TCPOBOP, comparable to the effects seen in the GPC3 TG mice during liver regeneration after partial hepatectomy. (Hepatology 2011;)
Toll-like receptor 4 and myeloid differentiation factor 88 provide mechanistic insights into the cause and effects of interleukin-6 activation in mouse liver regeneration
Authors: Vaquero Javier , Campbell Jean S. , Haque Jamil , McMahon Ryan S. , Riehle Kimberly J. , Bauer Renay L. , Fausto Nelson
Published: May 2011

Partial hepatectomy (PH) consistently results in an early increase of circulating interleukin-6 (IL-6), which is thought to play a major role in liver regeneration. Activation of this cytokine after PH requires the adaptor protein, MyD88, but the specific MyD88-related receptors involved remain unidentified. It is also unknown whether the magnitude of IL-6 elevation determines the extent of subsequent hepatocyte proliferation. Here, we uncovered artifacts in the assessment of circulating IL-6 levels when using cardiac puncture in mice after PH. By using retro-orbital bleed sampling, we show that the circulating levels of IL-6 after PH were not directly correlated with the extent of hepatocyte DNA synthesis in individual mice. The IL-6 increase after PH was attenuated in all lipopolysaccharide-hyporesponsive mouse strains studied (e.g., C3H/HeJ,

Tlr4

null,

Cd14

null,

Tlr2,4,9

null, and

Tlr2,4-Caspase1

null) and was severely abrogated in

Myd88

null mice. Despite attenuated IL-6 levels,

Tlr4

null mice showed normal signaling downstream of IL-6 and normal hepatocyte proliferation. In contrast,

Myd88

null mice showed severe impairments in signal transducer and activator of transcription 3 phosphorylation and

Socs3

induction, but had enhanced and prolonged extracellular signal-related kinase 1 and 2 phosphorylation in the first 6 hours after PH. Unexpectedly, these changes were associated with accelerated initiation of hepatocyte proliferation, as assessed by hepatocyte bromodeoxyuridine incorporation, phospho-histone H3 immunostaining, and cyclin E and A protein expression.

Conclusion:

TLR-4 signaling contributes to IL-6 activation after PH, but the

Tlr4

-independent component appears sufficient for ensuring intact signaling downstream of IL-6. The lack of correlation between IL-6 levels and hepatocyte proliferation after PH, and the accelerated start of hepatocyte proliferation in

Myd88

null mice despite abrogated cytokine activation, may highlight relevant antiproliferative effects of IL-6 signaling, possibly via

Socs3
, in the regulation of liver regeneration. (Hepatology 2011;)
Genomewide microRNA down-regulation as a negative feedback mechanism in the early phases of liver regeneration
Authors: Shu Jingmin , Kren Betsy T. , Xia Zhilian , Wong Phillip Y.-P. , Li Lihua , Hanse Eric A. , Min Michael X. , Li Bingshan , Albrecht Jeffrey H. , Zeng Yan , Subramanian Subbaya , Steer Clifford J.
Published: May 2011

The liver is one of the few organs that have the capacity to regenerate in response to injury. We carried out genomewide microRNA (miRNA) microarray studies during liver regeneration in rats after 70% partial hepatectomy (PH) at early and mid time points to more thoroughly understand their role. At 3, 12, and 18 hours post-PH ˜40% of the miRNAs tested were up-regulated. Conversely, at 24 hours post-PH, ˜70% of miRNAs were down-regulated. Furthermore, we established that the genomewide down-regulation of miRNA expression at 24 hours was also correlated with decreased expression of genes, such as

Rnasen
,
Dgcr8
,
Dicer
,
Tarbp2
, and

Prkra
, associated with miRNA biogenesis. To determine whether a potential negative feedback loop between miRNAs and their regulatory genes exists, 11 candidate miRNAs predicted to target the above-mentioned genes were examined and found to be up-regulated at 3 hours post-PH. Using reporter and functional assays, we determined that expression of these miRNA-processing genes could be regulated by a subset of miRNAs and that some miRNAs could target multiple miRNA biogenesis genes simultaneously. We also demonstrated that overexpression of these miRNAs inhibited cell proliferation and modulated cell cycle in both Huh-7 human hepatoma cells and primary rat hepatocytes. From these observations, we postulated that selective up-regulation of miRNAs in the early phase after PH was involved in the priming and commitment to liver regeneration, whereas the subsequent genomewide down-regulation of miRNAs was required for efficient recovery of liver cell mass.

Conclusion:

Our data suggest that miRNA changes are regulated by negative feedback loops between miRNAs and their regulatory genes that may play an important role in the steady-state regulation of liver regeneration. (Hepatology 2011;)
Idiopathic noncirrhotic portal hypertension
Authors: Schouten Jeoffrey N.L. , Garcia-Pagan Juan C. , Valla Dominique C. , Janssen Harry L.A.
Published: May 2011

Idiopathic noncirrhotic portal hypertension (INCPH) is characterized by an increased portal venous pressure gradient in the absence of a known cause of liver disease and portal vein thrombosis. In contrast to the high prevalence of this disorder in India, INCPH is a rare disease in the Western world. The etiology of INCPH can be divided in five categories: chronic infections, exposure to medication or toxins, thrombophilia, immunological disorders, and genetic disorders. Multifactorial etiology can also be encountered. Chronic abdominal infection is incriminated as the most important etiological factor in Eastern patients and thrombophilia in Western patients. The majority of patients with INCPH initially present with signs or complications of portal hypertension (mainly variceal bleeding and splenomegaly). These patients usually have preserved liver function. Liver function impairment occurs mainly in the context of intercurrent conditions. Patients with INCPH are often clinically and radiologically misdiagnosed as liver cirrhosis, so that a liver biopsy is indispensable to discriminate cirrhosis from INCPH. Histopathological characteristics of INCPH are heterogeneous, demonstrating overlap between several pathological entities (e.g., hepatoportal sclerosis, nodular regenerative hyperplasia, and incomplete septal cirrhosis). Even though hemodynamical changes in INCPH patients are not comparable to those in cirrhotics, prophylaxis and treatment of variceal bleeding are recommended to be similar. Anticoagulation therapy must be considered only in patients who develop portal vein thrombosis. INCPH has been considered a disorder with a relatively benign disease course. However, liver failure, hepatic encephalopathy, and hepatopulmonary syndrome can occur and are considered indications for liver transplantation. (HEPATOLOGY 2011;)
Characterization of fecal microbial communities in patients with liver cirrhosis
Authors: Chen Yanfei , Yang Fengling , Lu Haifeng , Wang Baohong , Chen Yunbo , Lei Dajiang , Wang Yuezhu , Zhu Baoli , Li Lanjuan
Published: May 2011

Liver cirrhosis is the pathologic end stage of chronic liver disease. Increasing evidence suggests that gut flora is implicated in the pathogenesis of liver cirrhosis complications. The aim of this study was to characterize the fecal microbial community in patients with liver cirrhosis in comparison with healthy individuals. We recruited 36 patients with liver cirrhosis and 24 healthy controls. The fecal microbial communities was analyzed by way of 454 pyrosequencing of the 16S ribosomal RNA V3 region followed by real-time quantitative polymerase chain reaction. Community-wide changes of fecal microbiota in liver cirrhosis were observed compared with healthy controls. The proportion of phylum

Bacteroidetes

was significantly reduced (

P

=
0.008), whereas

Proteobacteria

and

Fusobacteria

were highly enriched in the cirrhosis group (

P

= 0.001 and 0.002, respectively).

Enterobacteriaceae
(
P

= 0.001),

Veillonellaceae
(
P

= 0.046), and

Streptococcaceae
(
P

= 0.001) were prevalent in patients with cirrhosis at the family level. A positive correlation was observed between Child-Turcotte-Pugh (CTP) score and

Streptococcaceae
(
R

= 0.386,

P

= 0.02).

Lachnospiraceae

decreased significantly in patients with cirrhosis (

P

= 0.004) and correlated negatively with CTP score (

R

= −0.49,

P

= 0.002). Using partial least square discriminate analysis, we identified 149 operational taxonomic units (OTUs) as key phylotypes that responded to cirrhosis, most of which were

Lachnospiraceae

(65 OTUs),

Streptococcaceae

(23 OTUs), and

Veillonellaceae

(21 OTUs).

Conclusion:

Fecal microbial communities are distinct in patients with cirrhosis compared with healthy individuals. The prevalence of potentially pathogenic bacteria, such as

Enterobacteriaceae

and

Streptococcaceae
, with the reduction of beneficial populations such as

Lachnospiraceae

in patients with cirrhosis may affect prognosis. (Hepatology 2011;)
Dendritic cell depletion exacerbates acetaminophen hepatotoxicity
Authors: Connolly Michael K. , Ayo Diego , Malhotra Ashim , Hackman Michael , Bedrosian Andrea S. , Ibrahim Junaid , Cieza-Rubio Napoleon E. , Nguyen Andrew H. , Henning Justin R. , Dorvil-Castro Monica , Pachter Leon H. , Miller George
Published: May 2011

Acetaminophen (APAP) overdose is one of the most frequent causes of acute liver failure in the United States and is primarily mediated by toxic metabolites that accumulate in the liver upon depletion of glutathione stores. However, cells of the innate immune system, including natural killer (NK) cells, neutrophils, and Kupffer cells, have also been implicated in the centrilobular liver necrosis associated with APAP. We have recently shown that dendritic cells (DCs) regulate intrahepatic inflammation in chronic liver disease and, therefore, postulated that DC may also modulate the hepatotoxic effects of APAP. We found that DC immune-phenotype was markedly altered after APAP challenge. In particular, liver DC expressed higher MHC II, costimulatory molecules, and Toll-like receptors, and produced higher interleukin (IL)-6, macrophage chemoattractant protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-α). Conversely, spleen DC were unaltered. However, APAP-induced centrilobular necrosis, and its associated mortality, was markedly exacerbated upon DC depletion. Conversely, endogenous DC expansion using FMS-like tyrosine kinase 3 ligand (Flt3L) protected mice from APAP injury. Our mechanistic studies showed that APAP liver DC had the particular capacity to prevent NK cell activation and induced neutrophil apoptosis. Nevertheless, the exacerbated hepatic injury in DC-depleted mice challenged with APAP was independent of NK cells and neutrophils or numerous immune modulatory cytokines and chemokines.

Conclusion:

Taken together, these data indicate that liver DC protect against APAP toxicity, whereas their depletion is associated with exacerbated hepatotoxicity. (HEPATOLOGY 2011;)
Effect of vitamin K2 on the recurrence of hepatocellular carcinoma
Authors: Yoshida Haruhiko , Shiratori Yasushi , Kudo Masatoshi , Shiina Shuichiro , Mizuta Toshihiko , Kojiro Masamichi , Yamamoto Kyosuke , Koike Yukihiro , Saito Kenichi , Koyanagi Nozomu , Kawabe Takao , Kawazoe Seiji , Kobashi Haruhiko , Kasugai Hiroshi , Osaki Yukio , Araki Yasuyuki , Izumi Namiki , Oka Hiroko , Tsuji Kunihiko , Toyota Joji , Seki Toshihito , Osawa Toshiya , Masaki Naohiko , Ichinose Masao , Seike Masataka , Ishikawa Akihisa , Ueno Yoshiyuki , Tagawa Kazumi , Kuromatsu Ryoko , Sakisaka Shotaro , Ikeda Hiroshi , Kuroda Hidekatsu , Kokuryu Hiroyuki , Yamashita Tatsuya , Sakaida Isao , Katamoto Tetsuo , Kikuchi Kentaro , Nomoto Minoru , Omata Masao
Published: May 2011

Hepatocellular carcinoma (HCC) is characterized by frequent recurrence, even after curative treatment. Vitamin K2, which has been reported to reduce HCC development, may be effective in preventing HCC recurrence. Patients who underwent curative ablation or resection of HCC were randomly assigned to receive placebo, 45 mg/day, or 90 mg/day vitamin K2 in double-blind fashion. HCC recurrence was surveyed every 12 weeks with dynamic computed tomography/magnetic resonance imaging, with HCC-specific tumor markers monitored every 4 weeks. The primary aim was to confirm the superiority of active drug to placebo concerning disease-free survival (DFS), and the secondary aim was to evaluate dose-response relationship. Disease occurrence and death from any cause were treated as events. Hazard ratios (HRs) for disease occurrence and death were calculated using a Cox proportional hazards model. Enrollment was commenced in March 2004. DFS was assessed in 548 patients, including 181 in the placebo group, 182 in the 45-mg/day group, and 185 in the 90-mg/day group. Disease occurrence or death was diagnosed in 58, 52, and 76 patients in the respective groups. The second interim analysis indicated that vitamin K2 did not prevent disease occurrence or death, with an HR of 1.150 (95% confidence interval: 0.843-1.570, one-sided;

P

= 0.811) between the placebo and combined active-drug groups, and the study was discontinued in March 2007.

Conclusion:

Efficacy of vitamin K2 in suppressing HCC recurrence was not confirmed in this double-blind, randomized, placebo-controlled study. (Hepatology 2011;)
Prediction of the arrival of peak nitrate concentrations at the water table at the regional scale in Great Britain
Authors: Wang L. , Stuart M. E. , Bloomfield J. P. , Butcher A. S. , Gooddy D. C. , McKenzie A. A. , Lewis M. A. , Williams A. T.
Published: May 2011

A simple process‐based approach to predict regional‐scale loading of nitrate at the water table was implemented in a GIS for Great Britain. This links a nitrate input function, unsaturated zone thickness, and lithologically dependent rate of nitrate unsaturated zone travel to estimate arrival time of nitrate at the water table. The nitrate input function is the loading at the base of the soil and has been validated using unsaturated zone porewater profiles. The unsaturated zone thickness uses groundwater levels based on regional‐scale observations infilled by interpolated river base levels. Estimates of the rate of unsaturated zone travel are attributed from regional‐scale hydrogeological mapping. The results indicate that peak nitrate loading may have already arrived at the water table for many aquifers, but that it has not where the unsaturated zone is relatively thick There are contrasting outcomes for the two main aquifers which have similar unsaturated zone velocities, the predominantly low relief Permo‐Triassic sandstones, and the Chalk, which forms significant topographic features. For about 60% of the Chalk, the peak input has not yet reached the water table and will continue to arrive over the next 60 years. The methodology is readily transferable and provides a robust method for estimating peak arrival time for any diffuse conservative pollutant where an input function can be defined at a regional scale and requires only depth to groundwater and a hydrogeological classification. The methodology is extendable in that if additional information is available this can easily be incorporated into the model scheme. British Geology Survey © NERC 2011. Hydrological Process © 2011 John Wiley & Sons, Ltd
Optical biosensors to analyze novel biomarkers in oncology
Authors: Donzella Valentina , Crea Francesco
Published: May 2011

Many cancer types are characterized by poor survival and unpredictable therapy response. Easy‐to‐perform molecular analyses may help patient stratification and treatment tailoring. Several integrated devices have been proposed to overcome current analysis equipment limitations. They offer improved sensitivity and easy availability of parallel detection. Particularly, unlabelled optical biosensors combine the manifold advantages of integrated sensors (e.g. easy handling, portability and low‐volume requirement) with detection of target molecules in their original form. Here, we review integrated optical biosensor current features, and discuss their possible application to the detection of protein variants from body fluids, with particular regard to histone modifications. Indeed, histone post‐translational modifications are a set of epigenetic markers frequently deregulated in cancer. Available technology does not allow a comprehensive analysis of all histone modifications in a single patient. Thus, label‐free optical biosensors may pave the way to the discovery and detection of a novel class of biomarkers in oncology. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A green method for the synthesis of thiochromene derivatives in ionic liquids
Authors: Wang Xiang‐Shan , Wu Jian‐Rong , Zhou Jie , Zhang Mei‐Mei
Published: May 2011

Controlling the pH value by changing the negative ion of ionic liquids, the same reactions of aromatic aldehyde, 2‐(2,3‐dihydrothiochromen‐4‐ylidene) malononitrile and malononitrile product unaromatized and aromatized 6H‐benzo[c]thiochromene derivatives in high yields. The nice features of these procedures include mild reactions condition, simple operations, high yields, and environmentally benign. J. Heterocyclic Chem., (2011).
Headspace solid‐phase microextraction with on‐fiber derivatization for the determination of aldehydes in algae by gas chromatography–mass spectrometry
Authors: Ma Jiping , Xiao Ronghui , Li Jinhua , Li Jie , Shi Benzhang , Liang Yanjuan , Lu Wenhui , Chen Lingxin
Published: May 2011

A simple, fast, sensitive and cost‐effective method based on headspace solid‐phase microextraction (HS‐SPME) with on‐fiber derivatization coupled with gas chromatography–mass spectrometry was developed for the determination of six typical aldehydes, 2E‐hexenal, heptanal, 2E‐heptenal, 2E,4E‐heptadienal, 2E‐decenal and 2E,4E‐decadienal in laboratory algae cultures. As derivatization reagent, O‐2,3,4,5,6‐(pentafluorobenzyl) hydroxylamine hydrochloride, was loaded onto the poly(dimethylsiloxane)/divinylbenzene fiber for aldehydes on‐fiber derivatization prior to HS‐SPME. Various influence factors of extraction efficiency were systematically investigated. Under optimized extraction conditions, excellent method performances for all the six aldehydes were attained, such as satisfactory extraction recoveries ranging from 67.1 to 117%, with the precision (relative standard deviation) within 5.3–11.1%, and low detection limits in the range of 0.026–0.044 μg/L. The validated method was successfully applied for the analysis of the aldehydes in two diatoms (Skeletonema costatum and Chaetoceros muelleri), two pyrrophytas (Prorocentrum micans and Scrippsiella trochoidea) and Calanus sinicus eggs (feeding on the two diatoms above).
Use of different stationary phases for separation of isoniazid, its metabolites and vitamin B6 forms
Authors: Pasáková Ivana , Gladziszová Marcela , Charvátová Jana , Stariat Ján , Klimeš Jiří , Kovaříková Petra
Published: May 2011

The ability of different stationary phases developed for the analysis of polar compounds (ZIC‐HILIC, ZIC‐pHILIC and Zorbax SB‐Aq) to separate isoniazid, its metabolites (acetylisonazid, pyridoxal isonicotinoyl hydrazone, pyridoxal isonicotinoyl hydrazone 5‐phosphate), pyridoxine, pyridoxal and pyridoxal 5‐phosphate under MS compatible conditions was systematically investigated using HPLC‐UV. The mobile phase strength, pH and buffer concentration were modified to assess their impact on the retention of these compounds. The best available separation of the compounds was achieved using 1 mM ammonium formate (pH≈6) and ACN (20:80, v/v) on ZIC‐HILIC and employing 5 mM ammonium formate (pH 3.0) and ACN (40:60, v/v) on ZIC‐pHILIC. A gradient profile using 0.5 mM ammonium formate (pH≈6) and MeOH (0–12 min: 10% MeOH, 12–15 min: 10–50% MeOH, 15–35 min: 50% MeOH, 35.0–35.2 min: 50–10% MeOH, 35.2–45.0 min: 10% MeOH) provided the best separation of the compounds on Zorbax SB‐Aq. Subsequent LC‐MS analysis demonstrated that ZIC‐HILIC is useful for the analysis of pyridoxine, pyridoxal and pyridoxal isonicotinoyl hydrazone. However, the chromatographic conditions developed for the analysis of the compounds on Zorbax SB‐Aq are capable of achieving the best separation of all compounds in this study with the higher sensitivity for most of the analytes.
Tetrafluoroethylene Copolymers with Sulfonyl Fluoride Pendants: Syntheses in Supercritical Carbon Dioxide, Polymerization Behaviors, and Properties
Authors: Xu Anhou , Zhao Junhong , Yuan Wang Zhang , Li Hong , Zhang Heng , Wang Li , Zhang Yongming
Published: May 2011

Copolymerizations of tetrafluoroethylene (TFE) and perfluoro(3,6‐dioxa‐4‐methyl‐7‐octen)sulfonyl fluoride (PSVE) initiated by bis(perfluoro‐2‐n‐propoxypropionyl) peroxide in supercritical carbon dioxide are investigated. The reactivity ratios for TFE (rTFE) and PSVE (rPSVE) are calculated to be 7.85, 0.079 and 7.92, 0.087 according to Fineman–Ross and Kelen–Tudos methods, respectively. The glass transition temperatures of the copolymers increase with increasing in PSVE content. Comparison studies on above copolymers and another fluorinated sample prepared in emulsion show that the copolymers have comparable properties to the fluorinated one, thus offering an economic way to improve the properties of TFE–PSVE copolymers for their applications in diverse fields.

magnified image
Simple and Rapid Fabrication of Large‐Scale Polymer‐Immobilized Colloidal Crystals by Spray Coating
Authors: Ishii Masahiko , Narita Takeshi , Hayata Yuki , Nishimura Akira , Tachi Kazuyuki
Published: May 2011

Polymer‐immobilized colloidal crystal films have been fabricated by conventional spray coating and UV curing of silica–acrylic monomer suspensions. Controlling both the viscosity of the suspensions and the wettability of substrates enabled colloidal crystal films with smooth surfaces and brilliant structural colors due to Bragg diffraction. The structural colors could be controlled by particle concentrations in addition to particle diameter. The wettability influenced the thickness of the coated film and it consequently affected the Bragg reflection intensity of the film. Silhouette figures were textured on a substrate having regions with different wettabilities by single spray coating.

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Phantom Ring‐Closing Condensation Polymerization: Towards Antibacterial Oligoguanidines
Authors: Mattheis Claudia , Schwarzer Martin C. , Frenking Gernot , Agarwal Seema
Published: May 2011

The first example of phantom ring‐closing condensation polymerization for the synthesis of oligoguanidines is presented. A new oligoguanidine with a ring structure was achieved in one step by the condensation reaction of a triamine, like diethylenetriamine, with guanidine hydrochloride. The condensation reaction proceeded by selective ring‐closure towards the formation of five‐membered rings in the oligomer backbone. The resulting polymer repeat unit structure was different from the starting monomers (phantom polymer) and was formed by elimination of three molecules of ammonia per repeat unit. The inter‐, intra‐, and inter‐molecular reaction sequences led to the new structure as proved by different spectroscopic techniques (atmospheric pressure chemical‐ionization mass spectrometry, and one‐dimensional and two‐dimensional homo‐ and heteronuclear correlation NMR experiments) as well as supported by quantum chemical investigations. Preliminary results regarding antibacterial use of the resulting oligoguanidine were also promising and showed its effect within 15–30 min as an antibacterial material.

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Silibinin inhibits the invasion and migration of renal carcinoma 786‐O cells in vitro, inhibits the growth of xenografts in vivo and enhances chemosensitivity to 5‐fluorouracil and paclitaxel
Authors: Chang Horng‐Rong , Chen Pei‐Ni , Yang Shun‐Fa , Sun Ying‐Sui , Wu Sheng‐Wen , Hung Tung‐Wei , Lian Jong‐Da , Chu Shu‐Chen , Hsieh Yih‐Shou
Published: May 2011

Silibinin is a flavonoid antioxidant that is widely used for its anti‐hepatotoxic properties. It exerts a dose‐dependent inhibition on the invasion and migration of 786‐O renal cell carcinoma (RCC) cells in the absence of cytotoxicity. 786‐O cells were treated with silibinin at various concentrations, up to 50 µM, for a defined period and then subjected to gelatin zymography, casein zymography, and Western blot to investigate the impacts of silibinin on metalloproteinase (MMP) ‐2, ‐9, urokinase plasminogen activator (u‐PA), and MAPK pathway signaling proteins, respectively. The results showed that silibinin decreased MMP‐2, MMP‐9, u‐PA, p‐p38, and p‐Erk1/2 expressions in a concentration‐dependent manner. The reduced expressions of MMP‐2 and u‐PA, as well as inhibition of cell invasion were obtained in the cultures pre‐treated with PD98059 (Erk1/2 inhibitor) and SB203580 (p38 inhibitor). An in vivo anti‐tumor study with a nude mice xenograft model by a subcutaneous inoculation of 786‐O cells demonstrated small solid tumors after eight days following cell inoculation. There was a 70.1% reduction in tumor volume and 69.7% reduction in tumor weight by silibinin feeding on day 44, compared to those of controls. Moreover, combination treatment with silibinin and 5‐fluorouracil, paclitaxel, vinblastine, or RAD‐001 enhanced the chemosensitivity of 5‐fluorouracil and paclitaxel. In conclusion, silibinin inhibits the invasion and migration of 786‐O cells in vitro, inhibits the growth of xenografts in vivo, and enhances chemosensitivity to 5‐fluorouracil and paclitaxel. © 2011 Wiley‐Liss, Inc.
Quality of life in young‐ compared with late‐onset Parkinson's disease
Authors: Knipe M. Duleeka W. , Wickremaratchi Mirdhu M. , Wyatt‐Haines Emma , Morris Huw R. , Ben‐Shlomo Yoav
Published: May 2011

The impact of Parkinson's disease on quality of life may vary depending on age at onset. We investigated the effect of age at onset on quality of life in a large Parkinson's disease population (n = 426) using a disease‐specific rating scale (PDQ‐39) and with careful adjustment for confounding and intermediary factors. We also explored the relationship between depression and excessive daytime sleepiness by age at onset and compared this with the general population. We found that a younger age at onset was significantly associated with worse overall quality of life scores (odds ratio, 2.66; 95% confidence interval, 1.39–5.09; P = .003), but this was attenuated by adjustment for depression as an intermediary factor (odds ratio, 1.86; 95% confidence interval, 0.84–4.11; P = .13). Younger onset was also a risk factor for poor emotional well‐being independent of depression status. Risk of depression and excessive daytime sleepiness were elevated in patients with Parkinson's disease compared with controls (odds ratio, 2.99; 95% confidence interval, 1.93–4.65; P < .001; and odds ratio, 3.84; 95% confidence interval, 2.56–5.75; P < .001, respectively), with similar findings seen in both early‐ and late‐onset groups. Our study highlights the need for accurate diagnosis and treatment of depression in younger‐onset patients in order to improve quality of life. © 2011 Movement Disorder Society
Sperm storage in the female reproductive tract of Scotophilus heathii: Role of androgen
Authors: Roy Vikas Kumar , Krishna Amitabh
Published: May 2011

The aim of the present study was to investigate the mechanism of androgen‐mediated, prolonged sperm‐storage in the female reproductive tract of the bat, Scotophilus heathii. The bat treated in vivo with flutamide, an androgen antagonist, showed loss of spermatozoa at the storage site, utero‐tubal junction. Immunocytochemistry and Western blot analysis revealed the presence of increased expression of Bcl2 in the epithelial cell lining of the utero‐tubal junction during the period of sperm‐storage. Treatment with testosterone in vitro caused a significant dose‐dependent increase in expression of the survival factor Bcl2, whereas treatment with flutamide together with testosterone caused a significant decline in Bcl2 in the utero‐tubal junction of S. heathii. Together with the expression of Bcl2, the utero‐tubal junction also expresses the death signal, caspase3. Expression of caspase3 decreased during January, but increased in February during the late stage of sperm storage. Androgen stimulated Bcl2 synthesis in the utero‐tubal junction via the non‐genomic MAP kinase signaling pathway. In conclusion, this study suggests that androgen promotes sperm storage in S. heathii by stimulating the survival factor Bcl2 in the utero‐tubal junction. It is further hypothesized that a balance between the survival factor, Bcl2, and the death signal, caspase3, determines the duration of sperm storage in S. heathii. Mol. Reprod. Dev. 78:477–487, 2011. © 2011 Wiley‐Liss, Inc.
Full‐length phrenic nerve transfer as the treatment for brachial plexus avulsion injury to restore wrist and finger extension
Authors: Lin Haodong , Hou Chunlin , Chen Desong
Published: May 2011

Introduction: The functional restoration of wrist and finger extension after complete brachial plexus avulsion injury remains an unsolved problem. We conducted a prospective study to elucidate a new method for resolving this injury. Methods: Six patients with complete brachial plexus avulsion injury underwent a new surgical procedure in which the full‐length phrenic nerve was transferred to the medial portion of the radial nerve at the level of the latissimus dorsi insertion via endoscopic thoracic surgery. Results: In 5 patients, extensor carpi ulnaris and extensor carpi radialis strength recovered to Medical Research Council grade ≥M3, and in 4 patients extensor digitorum strength recovered to ≥M3. Conclusions: Neurotization of phrenic nerve to the medial portion of the radial nerve at the level of latissimus dorsi insertion is a feasible means of restoring wrist and finger extension in cases of complete brachial plexus avulsion injury. Muscle Nerve 45: 39–42, 2012
Muscle function in monozygotic female twin pairs discordant for hormone replacement therapy
Authors: Finni Taija , Noorkoiv Marika , Pöllänen Eija , Ronkainen Paula H.A. , Alén Markku , Kaprio Jaakko , Kovanen Vuokko , Sipilä Sarianna
Published: May 2011

Introduction: Postmenopausal monozygotic twin pairs discordant for hormone replacement therapy (HRT) provide an advantageous study design controlling for genetic background for elucidating the relationships between aging, sex hormone levels, muscle strength, contractile capacity, and fatigability. Methods: Thirteen postmenopausal monozygotic twin pairs discordant for HRT were measured for maximal voluntary torque (MVC) and twitch characteristics using electrical stimulation before and after intermittent dynamic plantarflexor exercise until exhaustion. Results: Peak twitch torque was 32% higher in HRT users than in their non‐HRT, genetically identical sisters (P = 0.002), but MVC did not differ. There were no differences in the activation level or twitch time characteristics between the co‐twins. Fatigue caused decreases in MVC (P = 0.001), twitch torque (P = 0.001), time to peak (P = 0.013), and half‐relaxation time (P = 0.001) similarly in HRT users and non–HRT users. Conclusion: In early postmenopausal women, involuntary but not voluntary force‐generating mechanisms of the plantarflexors are augmented by the use of HRT. Muscle Nerve, 2011
MRI & MRS assessment of the role of the tumour microenvironment in response to therapy
Authors: Bell Leanne K. , Ainsworth Nicola L. , Lee Shen‐Han , Griffiths John R.
Published: May 2011

MRI and MRS techniques are being applied to the characterisation of various aspects of the tumour microenvironment and to the assessment of tumour response to therapy. For example, kinetic parameters describing tumour blood vessel flow and permeability can be derived from dynamic contrast‐enhanced MRI data and have been correlated with a positive tumour response to antivascular therapies. The ongoing development and validation of noninvasive, high‐resolution anatomical/molecular MR techniques will equip us with the means to detect specific tumour biomarkers early on, and then to monitor the efficacy of cancer treatments efficiently and reliably, all within a clinically relevant time frame. Reliable tumour microenvironment imaging biomarkers will provide obvious advantages by enabling tumour‐specific treatment tailoring and potentially improving patient outcome. However, for routine clinical application across many disease types, such imaging biomarkers must be quantitative, robust, reproducible, sufficiently sensitive and cost‐effective. These characteristics are all difficult to achieve in practice, but image biomarker development and validation have been greatly facilitated by an increasing number of pertinent preclinical in vivo cancer models. Emphasis must now be placed on discovering whether the preclinical results translate into an improvement in patient care and, therefore, overall survival. Copyright © 2011 John Wiley & Sons, Ltd.
Membrane color and gas permeability of 6FDA‐TeMPD polyimide membranes prepared with various membrane preparation protocols
Authors: Kanehashi Shinji , Sato Shuichi , Nagai Kazukiyo
Published: May 2011

The relations among polyimide membrane colors, their gas transport and separation properties, and their fluorescence spectra were systematically investigated using fluorine‐containing aromatic polyimide, 6FDA‐TeMPD {[4,4‐(hexafluoroisopropylidene) diphthalic anhydride] [(6FDA)‐2,3,5,6‐tetramethyl‐1,4‐phenylene‐diamine (TeMPD)]}, which was used in electronic device and gas separation materials. Different molecular ordering structures of 6FDA‐TeMPD polyimides were prepared by controlling kinds of casting solvents and dry conditions. This difference was based on the effect of charge transfer (CT) interaction formed by π electrons of ring structures in polyimide. Membrane color measured using spectrophotometer determined colors as intrinsic parameters without sample collection. The permeability coefficients of oxygen and nitrogen of the 6FDA‐TeMPD polyimide membranes were correlated with membrane color index parameters such as L*, a*, b*, and ΔE*, and fluorescence properties such as maximum peak emission wavelength λmax and intensity Imax, which reflect molecular ordering affected by CT interaction in polyimide membranes. POLYM. ENG. SCI., 2011. © 2011 Society of Plastics Engineers
Experimental identification of the deformation mechanisms during sintering of cold compacted polytetrafluoroethylene powders
Authors: Canto Rodrigo Bresciani , Schmitt Nicolas , De Carvalho Jonas , Billardon René
Published: May 2011

The influence of the cooling rate after melting on the crystalline weight fraction of pure poly(tetrafluoroethylene) (PTFE) was derived from differential scanning calorimetry tests. Specimens made of pure or filled PTFE were manufactured by isostatic or constrained uniaxial cold pressing, up to different values of the porosity. Dilatometry tests were carried out on these specimens while imposing various heating–cooling treatments. The deformations recorded during these tests strongly depend on the mode and level of compaction. The original procedures presented, herein, made it possible to identify that these macroscopic deformations, which are strongly anisotropic for uniaxially pressed specimens, result from the combination of different independent mechanisms. The mechanisms that were distinguished are reversible thermal expansion, void closure, crystalline to amorphous and vice versa transformations, and recovery, which were not observed for isostatically pressed specimens. It was also shown that, after being subjected to a standard sintering treatment, anisotropically pressed specimens still exhibit anisotropic crystallization strains. POLYM. ENG. SCI., 2011. © 2011 Society of Plastics Engineers
Use of seed layers for structure, optical, and electronic transport measurements on microcrystalline silicon on glass
Authors: Ross C. , Mai Y. , Carius R. , Finger F.
Published: May 2011

A detailed structural analysis is provided by which the benefits of thin undoped ‘seed layers’ for the preparation of microcrystalline silicon on glass for material characterization are demonstrated. Raman spectroscopy and photothermal deflection spectroscopy (PDS) results reveal that ‘seed layers’ are not only effective for the growth of structurally homogenous films and for an extension of the range of deposition parameters in which highly crystalline material is grown, but also allow for preparing material on glass with properties very close to that of functional layers in thin film solar cells. Films which have successfully been tailored in this way are characterized with respect to electrical conductivity and optical absorption. Regarding conductivity, hydrogenated microcrystalline silicon material grown on a ‘seed layer’ exhibits a structure‐dependent behaviour which is very similar to that observed for material grown on bare glass. Regarding optical absorption spectra, residual interference fringes, which indicate structural non‐uniformities, can be successfully removed by means of ‘seed layers’. As a result, more information is obtainable from PDS, and the data gained in this way are in good agreement with Raman spectroscopy results. Copyright © 2011 John Wiley & Sons, Ltd.
Context‐dependent resistance to proteolysis of intrinsically disordered proteins
Authors: Suskiewicz Marcin J. , Sussman Joel L. , Silman Israel , Shaul Yosef
Published: May 2011

Intrinsically disordered proteins (IDPs), also known as intrinsically unstructured proteins (IUPs), lack a well‐defined 3D structure in vitro and, in some cases, also in vivo. Here, we discuss the question of proteolytic sensitivity of IDPs, with a view to better explaining their in vivo characteristics. After an initial assessment of the status of IDPs in vivo, we briefly survey the intracellular proteolytic systems. Subsequently, we discuss the evidence for IDPs being inherently sensitive to proteolysis. Such sensitivity would not, however, result in enhanced degradation if the protease‐sensitive sites were sequestered. Accordingly, IDP access to and degradation by the proteasome, the major proteolytic complex within eukaryotic cells, are discussed in detail. The emerging picture appears to be that IDPs are inherently sensitive to proteasomal degradation along the lines of the “degradation by default” model. However, available data sets of intracellular protein half‐lives suggest that intrinsic disorder does not imply a significantly shorter half‐life. We assess the power of available systemic half‐life measurements, but also discuss possible mechanisms that could protect IDPs from intracellular degradation. Finally, we discuss the relevance of the proteolytic sensitivity of IDPs to their function and evolution.
Crystal structure of the bifunctional tRNA modification enzyme MnmC from Escherichia coli
Authors: Kitamura Aya , Sengoku Toru , Nishimoto Madoka , Yokoyama Shigeyuki , Bessho Yoshitaka
Published: May 2011

Post‐transcriptional modifications of bases within the transfer RNAs (tRNA) anticodon significantly affect the decoding system. In bacteria and eukaryotes, uridines at the wobble position (U34) of some tRNAs are modified to 5‐methyluridine derivatives (xm5U). These xm5U34‐containing tRNAs read codons ending with A or G, whereas tRNAs with the unmodified U34 are able to read all four synonymous codons of a family box. In Escherichia coli (E.coli), the bifunctional enzyme MnmC catalyzes the two consecutive reactions that convert 5‐carboxymethylaminomethyl uridine (cmnm5U) to 5‐methylaminomethyl uridine (mnm5U). The C‐terminal domain of MnmC (MnmC1) is responsible for the flavin adenine dinucleotide (FAD)‐dependent deacetylation of cmnm5U to 5‐aminomethyl uridine (nm5U), whereas the N‐terminal domain (MnmC2) catalyzes the subsequent S‐adenosyl‐L‐methionine‐dependent methylation of nm5U, leading to the final product, mnm5U34. Here, we determined the crystal structure of E.coli MnmC containing FAD, at 3.0 Å resolution. The structure of the MnmC1 domain can be classified in the FAD‐dependent glutathione reductase 2 structural family, including the glycine oxidase ThiO, whereas the MnmC2 domain adopts the canonical class I methyltransferase fold. A structural comparison with ThiO revealed the residues that may be involved in cmnm5U recognition, supporting previous mutational analyses. The catalytic sites of the two reactions are both surrounded by conserved basic residues for possible anticodon binding, and are located far away from each other, on opposite sides of the protein. These results suggest that, although the MnmC1 and MnmC2 domains are physically linked, they could catalyze the two consecutive reactions in a rather independent manner.
Selection and characterization of a 7‐mer peptide binding to divalent cations
Authors: Han Daeyoung , Huh Seong , Myung Heejoon
Published: May 2011

A 7‐mer peptide (S‐T‐L‐P‐L‐P‐P) that bound to various divalent cations was selected from a phage display peptide library. Isothermal calorimetric analysis revealed that the peptide bound to Pb2+, Cd2+, Hg2+, and Cu2+. Through the use of CD studies, no secondary structural changes were observed for the peptide upon binding to divalent cations. Ala scanning mutant peptides bound to Hg2+ with a reduced affinity. However, no single substitution was shown to affect the overall affinity. We suggest that Pro residues chelate divalent cations, while the structure formed by the peptide is also important for the binding process. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.