bluuebunny/crossref_metadata_2025 huggingface dataset:
Metal Coordination and Aggregation Properties of Chiral Polythiophenes and Polythienylethynylenes
Authors: Matthews James R. , Goldoni Francesca , Kooijman Huub , Spek Anthony L. , Schenning Albertus P. H. J. , Meijer E. W.
Published: August 2007

A series of chiral thio‐ and oxo‐substituted polythiophenes and polythienylethynylenes has been synthesised and investigated. The replacement of an oxo‐linkage by a thio‐linkage distorts and/or inhibits the helical aggregation behaviour. The quenching of fluorescence upon coordination to palladium is also radically different depending on the presence of oxo‐ or thio‐substitution of the thiophene units. The alkylthio‐substituted polythiophenes and polythienylethynylenes do act as sensors for palladium by quenching of their fluorescence to a significantly greater extent than the quenching observed for nonthio functionalised polythiophenes and polythienylethynylenes.

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Shielding Effects in Polymer‐Polymer Reactions, 1
Authors: Fröhlich Markus G. , Vana Philipp , Zifferer Gerhard
Published: August 2007

Shielding effects of the surrounding arms and chains on the reactive centers taking part in RAFT four‐arm star polymerization following the Z‐group approach are calculated by means of exact enumeration of star/chain samples prepared by Monte Carlo techniques. The shielding effect, which can be relieved when using expanded core moieties, increases with increasing chain (arm) lengths. This leads to a reduction of the contact probability according to a power law with an exponent of −0.4 to −0.45. Additionally, characteristic chain properties and shape parameters are calculated as a function of the distance between the center of the star and the end of the linear chain in order to gain deeper insight into the mechanism of contact formation preceding the actual reaction.

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Dynamic competition in pharmaceuticals: cross‐national evidence from new drug diffusion
Authors: Berndt Ernst R. , Danzon Patricia M. , Kruse Gregory B.
Published: August 2007

We report on an exploratory examination of the extent of differences across fifteen countries and three therapeutic classes (antihypertensives, antidepressants and antiepileptics) in the rate at which medicines in general and new medicines in particular are promoted and then diffuse, as well as relative new/old drug prices. We find substantial heterogeneity across classes and countries in promotion and diffusion. In terms of diffusion, relative prices of old vs. new drugs, and intensity of detailing physicians, we find that somewhat surprisingly, the US is often “in the middle” relative to other countries, and is not an outlier. However, differences across classes are striking. Overall, new drug quantity elasticities with respect to own price are negative, ranging from about −0.75 to −1.1, while cross‐price (new drug quantity with respect to old drug price) are positive but small. Total promotion effects on total utilization are generally positive, particularly antidepressants. Promotion of new drugs positively affects the new drug share, while promotion of old drugs negatively affects the new drug share. Promotion of old drugs is surprisingly substantial in some classes and countries. Copyright © 2007 John Wiley & Sons, Ltd.
‘Branded Generics’ as a strategy to limit cannibalization of pharmaceutical markets
Authors: Reiffen David , Ward Michael R.
Published: August 2007

This paper demonstrates how, by introducing a generic version of its previously patented product, a branded firm can influence the equilibrium in the generic segment of the market for the product. This in turn can increase the firm's profits from selling the branded version. We then use structural estimates from previous literature to calculate the magnitude of the effects in the generic and branded segments. Copyright © 2007 John Wiley & Sons, Ltd.
Determinants of drug prices and expenditures
Authors: Comanor William S. , Schweitzer Stuart O.
Published: August 2007

The process by which pharmaceuticals are bought and sold is exceedingly complex. The major reason is that most consumers do not pay directly for the drugs they consume. Intermediaries are generally present who purchase pharmaceuticals from their manufacturers and have them provided to their subscribers or affiliates. The products themselves, however, are generally supplied by the same pharmacies used by cash purchasers. The purpose of this paper is to describe and examine these markets. Copyright © 2007 John Wiley & Sons, Ltd.
An industrial organization perspective on the influenza vaccine shortage
Authors: Scherer F.M.
Published: August 2007

This paper analyzes reasons advanced for the recent shortage of influenza vaccine in the United States and numerous other similar shortages in recent years. Explanations have included high regulatory costs, inadequate profitability, and mergers. Using Census data, it shows that vaccine producers realize unusually high price‐cost margins, but are probably also unusually capital‐intensive. Applying theories of scale economies to existing information, it identifies the extent to which, for diverse types of vaccines, economies of scale limit the number of vaccine producers, exposing the nation to stochastic shortage risk. A benefit/cost analysis explores whether it is economically worthwhile to maintain additional production sources with surge capacity. It is found that under plausible demand, external benefit, and stochastic supply failure conditions, such multiple sourcing yields more benefits than its cost. Copyright © 2007 John Wiley & Sons, Ltd.
Product differentiation, competition and regulation of new drugs: the case of statins in four European countries
Authors: Kanavos Panos , Font Joan Costa , McGuire Alistair
Published: August 2007

This paper examines the determinants of competition in the statins market across four European countries over the 1991–2002 period. Using IMS data from the UK, Germany, France and the Netherlands, the paper analyses the potential existence of competition between branded statins prior to patent expiry. Against a conceptual background of Cournot type quantity competition with product differentiation a demand function is estimated using panel data analysis for the first and second entrants on the market. The results indicate substitutability across the initial market entrants and the subsequent entrant only. This is consistent with potential price sensitivity in the branded market for statins, even when the overall size of market is growing. The results are indicative due to empirical issues surrounding endogeniety of the price variable. Copyright © 2007 John Wiley & Sons, Ltd.
Microvascular breast reconstruction pedicle thrombosis: How long can we wait?
Authors: Vijan Sandeep S. , Tran Nho V.
Published: August 2007

Re‐exploration plays a key role in salvaging vascularly compromised free flaps. A retrospective review of 290 free flaps in breast reconstruction was performed to determine whether the time delay between thrombosis detection and surgical re‐exploration had any effect on flap salvage. Overall flap success was 97.6%. Postoperative thrombosis requiring re‐exploration was documented in 6.2% cases. Fifty‐five percent of take‐back flaps were salvaged and 45% were lost. The median time between detection of flap compromise to surgical incision was 128 min in our saved flaps, and 228 min in the lost flap group. Our preliminary data suggests that re‐exploration within 188 min may improve flap salvage. © 2007 Wiley‐Liss, Inc. Microsurgery, 2007.
Concentration decrease of nitric oxide in the postischemic muscle is not only caused by the generation of O
Authors: Stoffels Felix , Lohöfener Felix , Beisenhirtz Moritz , Lisdat Fred , Büttemeyer Rolf
Published: August 2007

Reperfusion of ischemic skeletal muscle is associated with an alteration of the concentrations of O and NO. In this study, the influence of epigallocatechin‐3‐gallate (EGCG), a known radical scavenger, on the balance of O and NO has been measured online in the skeletal muscle of Wistar rats. The hind limb of 14 male rats had been exposed to ischemic stress for 2 h. Seven rats received an infusion of 1.5 μmol EGCG/kg 5 min before reperfusion. O, NO, and temperature were measured during reperfusion. The concentration of O declined under the influence of EGCG from 156.5 to 72.2 nmol/l (P = 0.01). The level of NO was found to decrease; this decrease was not significantly changed by EGCG (−175 nmol/l vs. – 227 nmol/l; P = 0.33). Thus the different superoxide concentrations did not correspond to different levels of NO, and the interaction of both radicals is not the only reason for the concentration decrease of NO in the reperfusion period. We conclude that EGCG protects skeletal muscle from I/R‐injury without influencing the NO concentration profile to a large extent. © 2007 Wiley‐Liss, Inc. Microsurgery, 2007.
Case ascertainment of alcohol dependence in general population surveys: ‘gated’ versus ‘ungated’ approaches
Authors: Degenhardt Louisa , Bohnert Kipling M. , Anthony James C.
Published: August 2007

Social role impairment and other forms of maladaptation are referenced explicitly in the case definitions for the drug use disorders within DSM‐IV‐TR, but there is continuing debate about whether and how to include these manifestations of ‘clinical significance’ in diagnostic criteria and assessment protocols. When a ‘gated’ approach (based on impairment or other maladaptation) has been taken during recent large scale psychiatric surveys with coverage of drug dependence (e.g. to reduce participant fatigue or burden), the net effect may include (a) a reduced number of identified cases, and (b) biases in the estimates of association linked to the occurrence of drug dependence. In this report focused on alcohol dependence, we probe these issues, making use of data from the cross‐sectional US National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), a household survey with 44,093 adult participants. NESARC alcohol dependence assessments were ‘ungated’, but allowed simulation of a ‘gated’ approach; the end result was a robust decrement in the estimated prevalence of this condition. Nonetheless, patterns of association linking suspected background characteristics to prevalence of alcohol dependence were not appreciably different when the gated and ungated estimates were contrasted. In summary, there are reasons to take the ungated approach in detailed research on alcohol use and dependence. Nevertheless, in panoramic mental health surveys, the inefficiency of an ungated approach must be balanced against the anticipated yield of cases who have experienced alcohol dependence without alcohol related social role impairments or other maladaptation, particularly when the dependence syndromes without these consequences are sometimes thought to lack clinical significance. Copyright © 2007 John Wiley & Sons, Ltd.
Emulsifier‐Free Emulsion Copolymerization of Vinyl Acetate and 3‐Dimethyl(methacryloyloxyethyl)ammonium Propanesulfonate and Swelling Behavior of their Copolymer Matrices
Authors: Kamenska Elena , Kostova Bistra , Ivanov Ivo , Rachev Dimitar , Georgiev George
Published: August 2007

Stable poly{(vinyl acetate)‐co‐[3‐dimethyl(methacryloyloxyethyl)ammonium propanesulfonate]} latexes with different compositions were synthesized by emulsifier‐free emulsion copolymerization. An unusual “overshooting” behavior of the copolymer tablets is explained based on the formation of specific clusters of oppositely oriented dipoles. The variation of their concentration with the zwitterionic monomer unit fraction, ionic strength and temperature is responsible for the differences in the swelling kinetics established. The results show that these parameters can be used to control swelling degree of copolymer matrices and their sustained drug delivery.

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SANISAND: Simple anisotropic sand plasticity model
Authors: Taiebat Mahdi , Dafalias Yannis F.
Published: August 2007

SANISAND is the name used for a family of simple anisotropic sand constitutive models developed over the past few years within the framework of critical state soil mechanics and bounding surface plasticity. The existing SANISAND models use a narrow open cone‐type yield surface with apex at the origin obeying rotational hardening, which implies that only changes of the stress ratio can cause plastic deformations, while constant stress‐ratio loading induces only elastic response. In order to circumvent this limitation, the present member of the SANISAND family introduces a modified eight‐curve equation as the analytical description of a narrow but closed cone‐type yield surface that obeys rotational and isotropic hardening. This
modification enables the prediction of plastic strains during any type of constant stress‐ratio loading, a feature lacking from the previous SANISAND models, without losing their well‐established predictive capability for all other loading conditions including the cyclic. In the process the plausible assumption is made that the plastic strain rate decomposes in two parts, one due to the change of stress ratio and a second due to loading under constant stress ratio, with isotropic hardening depending on the volumetric component of the latter part only. The model formulation is presented firstly in the triaxial stress space and subsequently its multiaxial generalization is developed following systematically the steps of the triaxial one. A detailed calibration procedure for the model constants is presented, while successful simulation of both drained and undrained behavior of sands under constant and variable stress‐ratio loadings at various densities and confining pressures is obtained by the model. Copyright © 2007 John Wiley & Sons, Ltd.
A supply chain design model with unreliable supply
Authors: Qi Lian , Shen Zuo‐Jun Max
Published: August 2007

Uncertainties abound within a supply chain and have big impacts on its performance. We propose an integrated model for a three‐tiered supply chain network with one supplier, one or more facilities and retailers. This model takes into consideration the unreliable aspects of a supply chain. The properties of the optimal solution to the model are analyzed to reveal the impacts of supply uncertainty on supply chain design decisions. We also propose a general solution algorithm for this model. Computational experience is presented and discussed. © 2007 Wiley Periodicals, Inc. Naval Research Logistics, 2007
Campus cultural and artistic activity effects evaluation model: a study of universities in Taiwan
Authors: Wu Shwu‐Ing
Published: August 2007

This research examines three types of universities in Taiwan to discuss the factors that influence campus cultural and artistic activity effects and establishes a structure model. In this research, university students are the target group for nonprofit organizations (NPOs) that regard cultural and artistic activities as products or services. The study used message contact, emotion, cognition, message evaluation, and attitude toward the activity as the influence factors. The relationships among these factors along with student participatory intention, participation behavior, and activity effect were then explored. The results show that each influence factor affects student willingness to participate, which leads to different levels of participation and effectiveness. Moreover, there are hierarchical relationships between the influence factors and effects.

Copyright © 2007 John Wiley & Sons, Ltd.
Gift giving: an interdisciplinary review
Authors: Sargeant Adrian , Woodliffe Lucy
Published: August 2007

The issue of why individuals choose to support charity has been the focus of considerable research in the disciplines of economics, psychology, social psychology, sociology, anthropology and more recently, management and marketing. This paper draws together extant work, developing a content model of giving behavior that fundraisers may use to inform their professional practice. A number of specific propositions are developed from the literature to assist in this goal. The paper provides summary tables of existing empirical studies categorized by the dimensions of the model, explores ambiguity in research findings, and concludes by highlighting opportunities for further research

Copyright © 2007 John Wiley & Sons, Ltd.
In the frame: investigating the use of mobile phone photography in museums
Authors: Leighton Debra
Published: August 2007

The ubiquitous use of mobile phone technology to capture photographic images has rapidly become an accepted feature of our social and cultural lifestyle. From the capture of photographic images in a social setting to the evening news reports of the 7/7 suicide bombings that led with phone video footage taken by a member of the public, mobile phone photography has rapidly become embedded in everyday life and presents a new set of challenges for marketers in all sectors. Within the heritage sector, mobile phone photography presents new methods for visitors to interact with and interpret historic sites, buildings and artefacts. This paper explores the use of mobile phone photography within the museum setting through an empirical study conducted at the National Football Museum in Preston, UK. It discusses the role of mobile phone photography in the visitor experience, in formal and informal learning provision, in stimulating the motivation to learn and in encouraging social interaction with visitor groups. The paper concludes with the identification of potential marketing opportunities for the museum and wider heritage sector.

Copyright © 2007 John Wiley & Sons, Ltd.
Genome‐wide expression analysis of Middle Eastern papillary thyroid cancer reveals c‐MET as a novel target for cancer therapy
Authors: Siraj AK , Bavi P , Abubaker J , Jehan Z , Sultana M , Al‐Dayel F , Al‐Nuaim A , Alzahrani A , Ahmed M , Al‐Sanea O , Uddin S , Al‐Kuraya KS
Published: August 2007

In an attempt to find genes that may be of importance in malignant progression of papillary thyroid carcinoma (PTC) in the Middle East, which therefore can be targeted in cancer therapy, we screened and validated the global gene expression in PTC using cDNA expression arrays and immunohistochemistry (IHC) on tumour tissue microarrays. Twenty‐nine PTC tissue specimens were compared with seven non‐cancerous thyroid specimens by use of cDNA microarray. Results for selected genes were confirmed by quantitative real‐time PCR. Protein expression of selected genes was further studied using a tissue microarray consisting of 536 PTCs and compared with histologically non‐cancerous tissue samples. One hundred and ninety‐six genes were overexpressed in PTC tissues relative to non‐cancerous thyroid tissues. The genes that were up‐regulated in PTC were involved in cell cycle regulation, cell signaling, and oncogenesis. Among these genes, c‐MET was identified by immunohistochemical methods as a protein that is overexpressed in 37% of PTCs and was significantly associated with more aggressive behaviour, eg higher stage, nodal involvement, and tall cell variant (p value = 0.01, 0.01 and 0.04, respectively). In this study, 55% of the PTC cases expressed activated AKT (P‐AKT), which suggests that activated AKT may play an important role in PTC tumourigenesis. The fact that most of the PTC cases that had activated AKT showed overexpression of c‐MET (p = 0.027) leads us to hypothesize that c‐MET may be an alternative mechanism of AKT activation in Middle Eastern PTCs. Finally, our data suggest that c‐MET dysregulation is associated with aggressive behaviour and may serve as a molecular biomarker and potential therapeutic target in this disease. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Predictive blood group genetics in hemolytic disease of the fetus and newborn: a 10‐year review of a laboratory evaluation of amniotic fluid‐derived DNA
Authors: Seto Eva , Fernandes Bernard J. , Wang Chen , Denomme Gregory A.
Published: August 2007

Objective

To identify the types of requests, the patterns of testing, and the error rates associated with the genetic identification of fetuses at risk for immune‐mediated hemolytic disease.

Method

Retrospective review of the laboratory information system for all fetal blood group genotyping tests performed at Mount Sinai Hospital, Toronto, Canada from January 1997 to December 2006.

Results

Amniotic fluid‐derived DNA, from 220 women (243 pregnancies), was tested for one or more antigens (279 tests) when the father was heterozygous for the inferred blood group antigen or was unavailable. The PCR amplification failure rate of amniotic fluid‐derived DNA was 5.0%. When the father was considered hemizygous for RHD or was not available, the fetus was positive in 68.6% and 72.7% of cases, respectively. Two amniotic fluid‐derived DNA KEL1 SSP‐PCR results did not correlate with the result determined from cultured amniocyte DNA.

Conclusions

Paternal RHD hemizygosity may be overestimated. Thus, we recommend that RHD zygosity be established by molecular analysis of the RHD breakpoint. Cultured amniocytes should be reserved for testing if the amniotic fluid‐derived DNA is inconclusive due to PCR amplification failure. We use PCR‐RFLP genotyping methods for RHCE*E/RHCE*e (Rh E/e), KEL1/KEL2 (K/k), FYA/FYB (Fya/b), and JKA/JKB (Jka/b). Copyright © 2007 John Wiley & Sons, Ltd.
Endoscopic laser surgery in severe second‐trimester twin‐twin transfusion syndrome: a three‐year experience from a Latin American center
Authors: Sepulveda Waldo , Wong Amy E. , Dezerega Victor , Devoto Juan C. , Alcalde Juan L.
Published: August 2007

Objective

In order to assess the outcome of pregnancies complicated by severe second trimester twin‐twin transfusion syndrome (TTTS) undergoing treatment with endoscopic laser surgery, we reviewed our experience following the implementation of an institutional fetal surgery program.

Methods

Patients presenting with monochorionic‐diamniotic twin pregnancies complicated by severe TTTS before 26 weeks of gestation were offered endoscopic laser surgery to coagulate placental vascular anastomoses. Using regional anesthesia and guided by real‐time sonography, anastomoses were identified and selectively coagulated. At the end of the procedure, amniodrainage was performed to restore normal amniotic fluid volume. Follow‐up and delivery were carried out at the referring institutions. Six‐month follow‐up was performed in all cases.

Results

During a 3‐year period from September 2003 to December 2006, 33 consecutive cases of severe TTTS were operated on at a median gestational age of 21 weeks (range 17–25). Nine (27.3%) cases were classified as stage II, 21 (63.6%) as stage III, and three (9.1%) as stage IV. The placenta was anterior or predominantly anterior in 15 (45.5%) of the cases. Overall, both twins were born alive in 16 (48.5%) cases, only one twin was born alive in 11 (33.3%), and neither was born alive in the remaining six (18.2%). Therefore, 81.8% (27 of 33) of the pregnancies resulted in at least one liveborn infant. Among them, the mean gestational age at delivery was 32 weeks (range 23–38) and the mean birthweight of the liveborn infants was 1591 g (range 350–3800). Thirty‐four infants survived the perinatal period, yielding an overall perinatal survival rate of 51.5%, with 75.8% (25 of 33) of the pregnancies resulting in at least one perinatal survivor. All neonatal deaths were associated with extreme prematurity.

Conclusions

This preliminary experience suggests that selective laser coagulation appears to be a good treatment option in cases of monochorionic twin pregnancies complicated by severe TTTS. However, technical skills and adequate equipment are required for implementing a fetal surgery program. Auditing outcomes during the learning curve would help in identifying potential problems. Copyright © 2007 John Wiley & Sons, Ltd.
Applying quantitative methods for detecting new drug safety signals in pharmacovigilance national database
Authors: Shalviri Gloria , Mohammad Kazem , Majdzadeh Reza , Gholami Kheirollah
Published: August 2007

Objectives

To applies three different methods of signal detection to the registered adverse events in Iranian Pharmacovigilance database over the period of 1998–2005.

Methods

All adverse drug reactions (ADRs) reported to Iranian Pharmacovigilance Center (IPC) from March 1998 through January 2005, were used for the analysis. The data were analysed based on three different signal detection methods including reporting odds ratios (RORs), information component (IC) and proportional reporting ratios (PRRs). The signals detected were categorised based on the number of reports per drug‐adverse event combination, severity of the event and labelled or unlabelled ADRs.

Results

During the study period, 6353 cases of ADR reports describing 11 130 reactions were received by IPC. The dataset involved 4975 drug‐adverse event combinations. The count of drug‐event combinations was 1, 2 and 3 or more for 3470, 726 and 779 combinations, respectively. According to PRRs, there were 2838, 872 and 488 drug‐event combinations known as a signal for the pairs with the reporting frequency of 1, 2 and 3 reports, respectively. The results of estimating RORs showed that 2722, 862 and 481 drug‐adverse event combinations were detected to be signal for the pairs with the reporting frequency of 1, 2 and 3 reports, respectively, while measuring IC and IC‐2SD detected 1120, 378 and 235 for the same reporting frequencies. Diclofenac‐induced paralysis and tramadol‐induced severe reactions were the most important signals.

Conclusion

Applying quantitative signal detection methods to the database of national pharmacovigilance centres is necessary to early detection of drug safety alerts. Copyright © 2007 John Wiley & Sons, Ltd.
Discovering functions and revealing mechanisms at molecular level from biological networks
Authors: Zhang Shihua , Jin Guangxu , Zhang Xiang‐Sun , Chen Luonan
Published: August 2007

With the increasingly accumulated data from high‐throughput technologies, study on biomolecular networks has become one of key focuses in systems biology and bioinformatics. In particular, various types of molecular networks (e.g., protein–protein interaction (PPI) network; gene regulatory network (GRN); metabolic network (MN); gene coexpression network (GCEN)) have been extensively investigated, and those studies demonstrate great potentials to discover basic functions and to reveal essential mechanisms for various biological phenomena, by understanding biological systems not at individual component level but at a system‐wide level. Recent studies on networks have created very prolific researches on many aspects of living organisms. In this paper, we aim to review the recent developments on topics related to molecular networks in a comprehensive manner, with the special emphasis on the computational aspect. The contents of the survey cover global topological properties and local structural characteristics, network motifs, network comparison and query, detection of functional modules and network motifs, function prediction from network analysis, inferring molecular networks from biological data as well as representative databases and software tools.
Proteomic applications in ecotoxicology
Authors: Monsinjon Tiphaine , Knigge Thomas
Published: August 2007

Within the growing body of proteomics studies, issues addressing problems of ecotoxicology are on the rise. Generally speaking, ecotoxicology uses quantitative expression changes of distinct proteins known to be involved in toxicological responses as biomarkers. Unlike these directed approaches, proteomics examines how multiple expression changes are associated with a contamination that is suspected to be detrimental. Consequently, proteins involved in toxicological responses that have not been described previously may be revealed. Following identification of key proteins indicating exposure or effect, proteomics can potentially be employed in environmental risk assessment. To this end, bioinformatics may unveil protein patterns specific to an environmental stress that would constitute a classifier able to distinguish an exposure from a control state. The combined use of sets of marker proteins associated with a given pollution impact may prove to be more reliable, as they are based not only on a few unique markers which are measured independently, but reflect the complexity of a toxicological response. Such a proteomic pattern might also integrate some of the already established biomarkers of environmental toxicity. Proteomics applications in ecotoxicology may also comprise functional examination of known classes of proteins, such as glutathione transferases or metallothioneins, to elucidate their toxicological responses.
Analysis of protein phosphorylation on a proteome‐scale
Authors: Collins Mark O. , Yu Lu , Choudhary Jyoti S.
Published: August 2007

Phosphorylation, the most intensively studied and common PTM on proteins, is a complex biological phenomenon. Its complexity manifests itself in the large numbers of proteins that attach it, remove it and recognise it as a protein code. Since the first report of protein phosphorylation on vitellin 100 years ago, a wide variety of biochemical and analytical chemical approaches have been developed to enrich and detect protein phosphorylation. The last 5 years have witnessed a renaissance in methodologies capable of characterising protein phosphorylation on a proteome‐scale. These technological advances have allowed identification of hundreds to thousands of phosphorylation sites in a proteome and have resulted in a profound paradigm shift. For the first time, using quantitative MS, the topology and significance of global phosphorylation networks may be investigated, marking a new era of cell signalling research. This review addresses recent technological advances in the purification of phosphorylated proteins and peptides and current MS‐based strategies used to qualitatively and quantitatively probe these enriched phosphoproteomes. In addition, we review the application of complementary array‐based technologies to derive signalling networks from kinase–substrate interactions and discuss future challenges in the field.
Subcellular shotgun proteomics in plants: Looking beyond the usual suspects
Authors: Haynes Paul A. , Roberts Thomas H.
Published: August 2007

In this review we examine the current state of analytical methods used for shotgun proteomics experiments in plants. The rapid advances in this field in recent years are discussed, and contrasted with experiments performed using current widely used procedures. We also examine the use of subcellular fractionation approaches as they apply to plant proteomics, and discuss how appropriate sample preparation can produce a great increase in proteome coverage in subsequent analysis. We conclude that the conjunction of these two techniques represents a significant advance in plant proteomics, and the future of plant biology research will continue to be enriched by the ongoing development of proteomic analytical technology.
Variation of the temperature‐dependent substituent effects with solvent in alkaline hydrolysis of substituted phenyl and alkyl benzoates and phenyl tosylates
Authors: Nummert Vilve , Piirsalu Mare , Koppel Ilmar A.
Published: August 2007

The second‐order rate constantskfor the alkaline hydrolysis of eight substituted alkyl benzoates have been measured spectrophotometrically in aqueous 5.3 M NaClO4and 0.5 Mn‐Bu4NBr at various temperatures. Variation of the substituent effect with temperature in alkaline hydrolysis ofortho‐,meta‐, andpara‐substituted phenyl benzoates, phenyl tosylates, and alkyl benzoates in various solvents (water, aqueous 0.5 M Bu4NBr, 80% (v/v) DMSO, 2.25 M Bu4NBr, and 5.3 M NaClO4) was studied. The susceptibility to temperature variation of themetaandparapolar substituent effect, theorthoinductive effect, and the alkyl polar effect for various media showed good correlation with the solvent electrophilicity,ES, which characterizes the hydrogen‐bond donating power of the solvent. The variation of the temperature‐dependentorthoinductive effect with solvent hydrogen‐bond donor capacity (electrophilicity) was found to be nearly twice smaller than that formetaandparapolar effect. The temperature‐dependent alkyl polar substituent effect was found to vary withESnearly by the same extent as the polar effect ofmetaandparasubstituents. The dependences of theρvalues (altogether 109 values ofρ) on the (1/T) term for various media were found to cross nearly at the same isosolvent temperature (1/βisosolv ≈ 2 × 10−3) formeta‐,para‐,ortho‐, and alkyl‐substituted esters. AtT = βisosolvthe difference (ρ)S − (ρ)Waterbecomes zero for all polar substituent effects in all media considered and the additional inductive effect from theorthoposition (compared withparaderivatives) disappears for all solvents studied. Copyright © 2007 John Wiley & Sons, Ltd.
Synthesis and characterization of poly(vinyl alcohol)‐graft‐[poly(D,L‐lactide)/poly(D,L‐lactide‐co‐glycolide)] hydrogels
Authors: Vidović Elvira , Klee Doris , Höcker Hartwig
Published: August 2007

Poly(D,L‐lactide) and poly(D,L‐lactide‐co‐glycolide) with various composition and with one methacrylate and one carboxylate end group were synthesized and grafted onto poly(vinyl alcohol) (PVA) via the carboxylate group. The graft copolymers were crosslinked via the methacrylate groups using a free radical initiator. The polymer networks were characterized by means of NMR and studied qualitatively by means of IR spectroscopy. The influence of the glycolide content in the polyester grafts and of the number of ester units in the grafts on thermal properties and swellability were studied as well. The high swellability in water is characteristic of all hydrogels. Differential scanning calorimetry (DSC) showed a single glass transition temperature that occurs in the range between 51 and 69 °C. Thermogravimetric analysis (TGA) of the networks showed the main loss in weight in the temperature range between 290 and 370 °C. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4536–4544, 2007
High‐efficiency poly(phenylenevinylene)‐co‐fluorene copolymers incorporating a triphenylamine as the end group for white‐light‐emitting diode applications
Authors: Kuo Chao‐Hui , Cheng Wei‐Kang , Lin Kun‐Rung , Leung Man‐Kit , Hsieh Kuo‐Huang
Published: August 2007

We have synthesized a series of PPV copolymers and investigated the relationships between their chemical structures, thermal stabilities, and optoelectronic properties. Initially, we monitored the effects of the end group and the molecular weight on the behavior of polymer light emitting diodes (PLEDs) prepared from a series of oligo(phenylenevinylene) (OPV)‐fluorene luminescent copolymers. We found that the nature of the end‐capping group was an important factor affecting the luminescence properties of devices, which were improved especially when applying a triphenylamine end group. The molecular weight mainly affected the film quality of the manufactured device; that is, it improved to a certain degree when the molecular weight increased. Based on the luminescence conversion mechanism, we used a simple spin‐coating process to fabricate a high‐efficiency LED displaying white‐light CIE 1931 (coordinates of 0.31, 0.34). The device exhibited a high current‐efficiency of 3.5 cd/A and a brightness of 973 cd/m2. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4504–4513, 2007
Synthesis and properties of various poly(diarylacetylenes) containing siloxy and hydroxy groups
Authors: Hu Yanming , Shiotsuki Masashi , Masuda Toshio
Published: August 2007

Diarylacetylene monomers (1b−f) containing siloxy and either naphthyl, fluorenyl, or biphenyl groups were polymerized with TaCl5–n‐Bu4Sn catalyst, and 1b, 1c, and 1f provided high molecular weight polymers. Free‐standing membranes of polymers 2b, 2c, and 2f were fabricated by casting from toluene solution. Desilylation of these polymer membranes was carried out with trifluoroacetic acid to afford poly (diarylacetylenes) membranes having hydroxy groups (3b and 3c). According to thermogravimetric analysis (TGA), both siloxy‐containing and hydroxy‐containing polymers exhibited high thermal stability, and the onset temperatures of weight loss in air were ∼370 °C and ∼430 °C, respectively. The CO2 permeability coefficients of these membranes were in the range of 65–640 barrers. The points of 3b and 3c in the PCO2 versus PCO2/PCH4 plot were located above Robeson's upper bound. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4487–4495, 2007
On Depth Profiling of Polymers by Argon Ion Sputtering
Authors: Holländer Andreas , Haupt Michael , Oehr Christian
Published: August 2007

Organic polymers readily react after the impact of energetic ions as used in sputter depth profiling. The resulting chemical composition (elemental concentrations, structural features) is different from the original one. These alterations are observed after a short time exposure of polyethylene (PE) and poly(ethylene terephthalate) (PET). The XPS data of the C1s and the O1s regions changed dramatically. Electron spin resonance measurements support the assumption that radicals are involved in the reactions. The chemical surface composition of these polymers was changed by the ion bombardment in a way that it is virtually impossible to tell anything about the original structure. The depth profile is mostly an artefact.

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Observation of rapid drainage system development by thermal erosion of ice wedges on Bylot Island, Canadian Arctic Archipelago
Authors: Fortier Daniel , Allard Michel , Shur Yuri
Published: August 2007

Rapid development of a new drainage system was observed on Bylot Island. A 750‐m long gully system was eroded in four years. The process was initiated by the formation of sinkholes eroded in ice wedges by runoff flowing into open frost cracks. The sinkholes evolved into underground tunnels cut in the ice‐wedge network and the ice‐rich permafrost. Widening of tunnels was followed by subsidence and collapse of their roofs and the development of open gullies. The drainage generally developed as the shortest line along the regional slope with some deviations caused by collapse of blocks of soil which temporarily obstructed the water flow. Retrogressive scarps exposed to flowing water retreated at maximum rates of up to 5 m/day for a total of 15 to 50 m during the summer. Scarps exposed to atmospheric heat and solar radiation retreated between 2.5 and 40 m over four summers with a mean of 15.5 m. Such slopes had nearly stabilised after four years with a retreat rate of only a few centimetres per year in the last year of observation. Copyright © 2007 John Wiley & Sons, Ltd.
Thermal regime of three low elevation scree slopes in central Europe
Authors: Zacharda Miloslav , Gude Martin , Růžička Vlastimil
Published: August 2007

External air temperature (EAT) and the interior temperature of the talus (IT) were measured for one year at two low elevation scree slopes in the Sudeten Mountains, central Europe. Similar measurements were made at an ‘ice‐cave’ beneath a talus and supplemented by cave‐floor temperature (CGT). The year‐round interplay between EAT, IT and CGT can be subdivided into four periods: (1) winter cooling linked with ascending exhalations and downslope cool airflows; (2) spring warming linked with ice formation from meltwater refreezing between the blocks; (3) summer linked to a prolonged zero‐curtain period; (4) autumnal increases of IT at the same time as EAT decreases. The differences between EAT and IT cause continual air circulation between the scree voids. Patchy permafrost probably occurs at these scree locations in spite of mean annual air temperatures of 6.8–7.5°C. Copyright © 2007 John Wiley & Sons, Ltd.
A better understanding of molecular mechanisms underlying human disease
Authors: Bermúdez‐Crespo José , López José Luis
Published: August 2007

This review summarises and discusses the degree to which proteomics is contributing to medical care, providing examples and signspots for future directions. Why do genomic approaches provide a limited view of gene expression? Because of the multifactorial nature of many diseases, proteomics enables us to understand the molecular basis of disease, not only at the organism, whole‐cell or tissue levels, but also in subcellular structures, protein complexes and biological fluids. The application of proteomics in medicine is expected to have a major impact by providing an integrated view of individual disease processes. This review describes several proteomic platforms and examines the role of proteomics as a tool for clinical biomarker discovery, the identification of prognostic and earlier diagnostic markers, their use in monitoring the effects of drug treatments and eventually find more efficient and safer therapeutics for a wide range of pathologies.
Quantitative proteomics for identification of cancer biomarkers
Authors: Chaerkady Raghothama , Pandey Akhilesh
Published: August 2007

Quantitative proteomics can be used for the identification of cancer biomarkers that could be used for early detection, serve as therapeutic targets, or monitor response to treatment. Several quantitative proteomics tools are currently available to study differential expression of proteins in samples ranging from cancer cell lines to tissues to body fluids. 2‐DE, which was classically used for proteomic profiling, has been coupled to fluorescence labeling for differential proteomics. Isotope labeling methods such as stable isotope labeling with amino acids in cell culture (SILAC), isotope‐coded affinity tagging (ICAT), isobaric tags for relative and absolute quantitation (iTRAQ), and 18O labeling have all been used in quantitative approaches for identification of cancer biomarkers. In addition, heavy isotope labeled peptides can be used to obtain absolute quantitative data. Most recently, label‐free methods for quantitative proteomics, which have the potential of replacing isotope‐labeling strategies, are becoming popular. Other emerging technologies such as protein microarrays have the potential for providing additional opportunities for biomarker identification. This review highlights commonly used methods for quantitative proteomic analysis and their advantages and limitations for cancer biomarker analysis.
Culture requirements of prostatic epithelial cell lines for acinar morphogenesis and lumen formation in vitro: Role of extracellular calcium
Authors: Tyson Darren R. , Inokuchi Junichi , Tsunoda Toshiyuki , Lau Alice , Ornstein David K.
Published: August 2007

BACKGROUND

Three‐dimensional (3D) culture of benign prostatic epithelial cell lines can recapitulate acinar morphogenesis in vitro, but the broad applicability of this approach has not been described. The present studies examine the culture conditions important for prostatic acinar morphogenesis in vitro and the role of extracellular calcium in this process.

METHODS

With optimized culture conditions, RWPE‐1, pRNS‐1‐1, PZ‐HPV‐7, PNT1A, BPH‐1, and PrEC were analyzed for their ability to undergo acinar morphogenesis in 3D culture and by immunoblotting. RWPE‐1 cells were further examined for the effects of calcium on morphology, E‐cadherin membrane localization and multicellular layering in 2D culture and for acinar morphogenesis, luminal apoptosis, and luminal filling in 3D.

RESULTS

Cell lines grown in low‐calcium medium have the ability to form acinar structures with lumens, which correlates with E‐cadherin expression, but low calcium is not required for this process. Adding CaCl2 to the medium strongly inhibits lumen formation, luminal apoptosis and induces luminal filling, and luminal filling is blocked by an interfering antibody.

CONCLUSIONS

Optimized medium composition allows nearly all seeded RWPE‐1 cells to undergo acinar morphogenesis, forming consistent structures representative of normal adult prostate glands. Low‐calcium‐containing medium appears selective for cells capable of undergoing acinar morphogenesis in vitro, and branching and luminal space within the acini are strongly influenced by extracellular calcium levels, likely through the actions of E‐cadherin. These results provide important information about a relevant in vitro model with which to study prostate development and carcinogenesis and highlight the importance of extracellular calcium in regulating 3D morphology. Prostate 67: 1601–1613, 2007. © 2007 Wiley‐Liss, Inc.
Signal transducer and activator of transcription‐6 (STAT6) is a constitutively expressed survival factor in human prostate cancer
Authors: Das Susobhan , Roth Cherice P. , Wasson Lori M. , Vishwanatha Jamboor K.
Published: August 2007

BACKGROUND

Signal transducer and activator of transcription (STAT)‐6 is a member of the STAT family of latent transcription factors. In this investigation, we examined STAT6 expression in clinical prostate cancer tissue specimen and determined its role in prostate cell proliferation and migration.

METHODS

STAT6 expression in cell lines and tissues was analyzed by RT‐PCR, IHC and/or immunoblot analyses. Down‐regulation of STAT6 expression was achieved by STAT6 siRNA and its effect on cell migration and apoptosis was measured.

RESULTS

STAT6 is highly expressed in the fibromuscular stroma of prostate cancer specimens. STAT6 is also expressed in the malignant epithelial layer and prostate intraepithelial neoplasia (PIN). STAT6 expression was significantly correlated with high histological grades of prostate cancer as well as with tumor size. Our data indicate deregulated STAT6 mRNA and protein expression in prostate cancer cells with high levels in the non‐cancerous HPV 18C‐1 and cancerous DU145 cell lines and low levels in PC3 and LNCaP cells. Phosphorylated STAT6 was expressed in all three cancer cell lines DU145, PC3, and LNCaP. Down‐regulation of STAT6 using siRNA leads to the induction of early apoptosis in DU145 cells and inhibits migration of these cells. Significant reduction in cell viability and transcriptional down‐regulation of the anti‐apoptotic protein Bcl‐XL was observed followed by STAT6 down‐regulation in DU145 cells. Interestingly STAT6 also regulates transcription of 15‐lipoxygenase‐1 gene in DU145 cells.

CONCLUSIONS

Our data suggest that STAT6 is a survival factor in prostate cancer and regulates the genetic transcriptional program that is responsible for prostate cancer progression. Prostate 67: 1550–1564, 2007. © 2007 Wiley‐Liss, Inc.
Epigallocatechin‐3‐Gallate suppresses early stage, but not late stage prostate cancer in TRAMP mice: Mechanisms of action
Authors: Harper Curt E. , Patel Brijesh B. , Wang Jun , Eltoum Isam A. , Lamartiniere Coral A.
Published: August 2007

BACKGROUND

Prostate cancer (PCa) is the second leading cause of cancer‐related death in men in the United States. Many men have implemented purported chemopreventive agents into their daily diet in an attempt to delay the early onset of a PCa. Green tea polyphenols, one such agent, has been shown to be chemopreventive in skin, breast, and prostate cancers. We hypothesized that Epigallocatechin‐3‐Gallate (EGCG), the major polyphenol found in green tea, will exert its chemopreventive effect in the prostate via regulation of sex steroid receptor, growth factor‐signaling, and inflammatory pathways.

METHODS

Five‐week‐old male TRAMP (Transgenic Adenocarcinoma Mouse Prostate) offspring were fed AIN‐76A diet and 0.06% EGCG in tap water. Animals were sacrificed at 28 weeks of age and the entire prostates were scored histopathologically. In addition, animals were sacrificed at 12 weeks of age and ventral (VP) and dorsolateral (DLP) prostates were removed for histopathological evaluation and immunoblot analyses or ELISA.

RESULTS

EGCG, inhibited early but not late stage PCa in the current study. In the VP, EGCG significantly reduced cell proliferation, induced apoptosis, and decreased androgen receptor (AR), insulin‐like growth factor‐1 (IGF‐1), IGF‐1 receptor (IGF‐1R), phospho‐extracellular signal‐regulated kinases 1 and 2 (phospho‐ERKs 1 and 2), cyclooxygenase‐2 (COX‐2), and inducible nitric oxide synthase (iNOS).

CONCLUSIONS

The attenuation of the AR, the down‐regulation of potent growth factor IGF‐1, modulation of inflammation biomarkers, and decrease in the MAPK signaling may contribute to the reduction in cell proliferation and induction of apoptosis and hence provide a biochemical basis for EGCG suppressing PCa without toxicity. Prostate 67: 1576–1589, 2007. © 2007 Wiley‐Liss, Inc.