bluuebunny/crossref_metadata_2025 huggingface dataset:
Phase II clinical trial of parenteral hydroxyurea and hyperfractionated, accelerated external beam radiation therapy in patients with advanced squamous cell carcinoma of the head and neck: Toxicity and efficacy with continuous ribonucleoside reductase inhibition
Authors: Beitler Jonathan J. , Smith Richard V. , Owen Randall P. , Silver Carl E. , Mazumdar Madhu , Wadler Scott
Published: September 2006

Background

Almost all concurrent chemoradiation regimens for head and neck are platinum based; however, cisplatin is associated with severe renal, oto‐, and neurotoxicity. Hydroxyurea (HU) has been associated with fewer irreversible toxicities. We obtained HU in parenteral form to be administered continually during the radiation treatment. Intravenous HU promised better pharmacokinetics and cell cycle blockade.

Methods

Participants had biopsy‐proven, untreated squamous cell carcinoma of the oral cavity, oropharynx (stage IV) and hypopharynx (stages II–IV). Radiation therapy consisted initially of 74.4 Gy administered in twice daily 1.2‐Gy fractions. After 20 patients, the radiation dose was reduced to 60.0 Gy, and another 16 patients were enrolled.

Results

Patients received HU by Continuous Ambulatory Drug Delivery (CADD) pump on a daily ×5 schedule during radiation therapy. Because of persistent long‐term dysphagia, after 20 patients, the dose of external beam radiation therapy was reduced from 74 to 60 Gy, and the duration of concurrent HU was correspondingly reduced. The new regimen was much better tolerated. The median survival for the group as a whole was 30 months. Within this small study, there were no significant differences in survival, regional control, or local control between the 2 groups.

Conclusions

Lower doses of concurrent parenteral HU and hyperfractionated radiation therapy are tolerable and promising. © 2006 Wiley Periodicals, Inc. Head Neck, 2006
Asymmetry of neuron numbers in the hippocampal formation of prenatally malnourished and normally nourished rats: A stereological investigation
Authors: Lister James P. , Tonkiss John , Blatt Gene J. , Kemper Thomas L. , DeBassio William A. , Galler Janina R. , Rosene Douglas L.
Published: September 2006

There is considerable evidence for lateralization of hippocampal function and hemispheric asymmetry in humans. In the rat, studies have reported asymmetries in the thicknesses of layers, the volumes of hippocampal subfields, and the density of cells at specific points along the septotemporal axis. To determine if there is an asymmetry of neuron numbers and whether prenatal malnutrition affects any asymmetries, 90‐day old male Sprague–Dawley rats that were either normally nourished or malnourished prenatally were perfused with 4% paraformaldehyde and the brains cut into 30‐μm sections. One interrupted series of sections through the entire hippocampus was analyzed stereologically to estimate the total number of neurons in the hilus of the dentate gyrus, the CA3/CA2 stratum pyramidale (SP), the CA1 SP, and the SP of the prosubiculum/subiculum of both hemispheres. Significant asymmetries (P < 0.05) were found in the CA1 and CA3/CA2 subfields, with the right hemisphere containing 21 and 6% fewer neurons, respectively. Malnutrition reduced neuron numbers in the CA1 subfield by 12%, but did not alter the hemispheric asymmetry. Our findings agree with previous reports of left dominant asymmetries in the rat brain and suggest that this may result from differences in total numbers of neurons. © 2006 Wiley‐Liss, Inc.
The role of strategic health planning processes in the development of health care reform policies: a comparative study of Eritrea, Mozambique and Zimbabwe
Authors: Green Andrew , Collins Charles , Stefanini Angelo , Ferrinho Paulo , Chapman Glyn , Hagos Besrat , Adams Yussuf , Omar Mayeh
Published: September 2006

This paper reports on comparative analysis of health planning and its relationship with health care reform in three countries, Eritrea, Mozambique and Zimbabwe. The research examined strategic planning in each country focusing in particular on its role in developing health sector reforms. The paper analyses the processes for strategic planning, the values that underpin the planning systems, and issues related to resources for planning processes. The resultant content of strategic plans is assessed and not seen to have driven the development of reforms; whilst each country had adopted strategic planning systems, in all three countries a more complex interplay of forces, including influences outside both the health sector and the country, had been critical forces behind the sectoral changes experienced over the previous decade. The key roles of different actors in developing the plans and reforms are also assessed. The paper concludes that a number of different conceptions of strategic planning exist and will depend on the particular context within which the heatlh system is placed. Whilst similarities were discovered between strategic planning systems in the three countries, there are also key differences in terms of formality, timeframes, structures and degrees of inclusiveness. No clear leadership role for strategic planning in terms of health sector reforms was discovered. Planning appears in the three countries to be more operational than strategic. Copyright © 2006 John Wiley & Sons, Ltd.
Biocompatibility evaluation of surface‐treated AISI 316L austenitic stainless steel in human cell cultures
Authors: Martinesi M. , Bruni S. , Stio M. , Treves C. , Bacci T. , Borgioli F.
Published: September 2006

The effects of AISI 316L austenitic stainless steel, tested in untreated state or subjected to glow‐discharge nitriding (at 10 or 20 hPa) and nitriding + post‐oxidizing treatments, on human umbilical vein endothelial cells (HUVEC) and on peripheral blood mononuclear cells (PBMC) were evaluated. All the treated samples showed a better corrosion resistance in PBS and higher surface hardness in comparison with the untreated alloy. In HUVEC put in contact for 72 h with the sample types, proliferation and apoptosis decreased and increased, respectively, in the presence of the nitrided + post‐oxidized samples, while only slight differences in cytokine (TNF‐α, IL‐6, and TGF‐β1) release were registered. Intercellular adhesion molecule‐1 (ICAM‐1) increased in HUVEC incubated with all the treated samples, while vascular cell adhesion molecule‐1 (VCAM‐1) and E‐selectin increased in the presence of all the sample types. PBMC incubated for 48 h with the samples showed a decrease in proliferation and an increase in apoptosis in the presence of the untreated samples and the nitrided + post‐oxidized ones. All the sample types induced a remarkable increase in TNF‐α and IL‐6 release in PBMC culture medium, while only the untreated sample and the nitrided at 10 hPa induced an increase in ICAM‐1 expression. In HUVEC cocultured with PBMC, previously put in contact with the treated AISI 316L samples, increased levels of ICAM‐1 were detected. In HUVEC coincubated with the culture medium of PBMC, previously put in contact with the samples under study, a noteworthy increase in ICAM‐1, VCAM‐1, and E‐selectin levels was always registered, with the exception of VCAM‐1, which was not affected by the untreated sample. In conclusion, even if the treated samples do not show a marked increase in biocompatibility in comparison with the untreated alloy, their higher corrosion resistance may suggest a better performance as the contact with physiological environment becomes longer. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007
18β‐glycyrrhetinic acid promotes src interaction with connexin43 in rat cardiomyocytes
Authors: Chung Tun‐Hui , Wang Seu‐Mei , Chang Yun‐Chieh , Chen Yuh‐Lien , Wu Jiahn‐Chun
Published: September 2006

The mechanism by which 18β‐glycyrrhetinic acid regulates gap junction intercellular communication (GJIC) remains poorly understood. In this study, treatment of cultured rat neonatal cardiomyocytes with 18β‐glycyrrhetinic acid resulted in dose‐dependent inhibition of GJIC as assessed by fluorescent dye transfer analysis. 18β‐Glycyrrhetinic acid induced time‐dependent serine/threonine dephosphorylation and redistribution of connexin43 (Cx43) in cardiomyocytes and the induced Cx43 dephosphorylation was prevented by the protein phosphatase inhibitor, calyculin A. However, functional analyses showed that the inhibitory effect of 18β‐glycyrrhetinic acid on dye spreading among cardiomyocytes was not blocked by calyculin A, but was blocked by the Src‐selective tyrosine kinase inhibitor, PP2. 18β‐Glycyrrhetinic acid also induced an increase in the levels of phosphorylated Src, and this effect was prevented by PP2. Immunoprecipitation using anti‐Cx43 and anti‐p‐Src antibodies showed that 18β‐glycyrrhetinic acid increased the association between p‐Src and Cx43 and induced tyrosine phosphorylation of Cx43. We conclude that the inhibitory effect of 18β‐glycyrrhetinic acid on GJIC in cardiomyocytes involves Src‐mediated tyrosine phosphorylation of Cx43. J. Cell. Biochem. 100: 653–664, 2007. © 2006 Wiley‐Liss, Inc.
Acetyl‐coenzyme A carboxylases: Versatile targets for drug discovery
Authors: Tong Liang , Harwood H. James
Published: September 2006

Acetyl‐coenzyme A carboxylases (ACCs) have crucial roles in fatty acid metabolism in humans and most other living organisms. They are attractive targets for drug discovery against a variety of human diseases, including diabetes, obesity, cancer, and microbial infections. In addition, ACCs from grasses are the targets of herbicides that have been in commercial use for more than 20 years. Significant progresses in both basic research and in drug discovery have been made over the past few years in the studies on these enzymes. At the basic research level, the crystal structures of the biotin carboxylase (BC) and the carboxyltransferase (CT) components of ACC have been determined, and the molecular basis for ACC inhibition by small molecules are beginning to be understood. At the drug discovery level, a large number of nanomolar inhibitors of mammalian ACCs have been reported and the extent of their therapeutic potential is being aggressively explored. This review summarizes these new progresses and also offers some prospects in terms of the future directions for the studies on these important enzymes. J. Cell. Biochem. 99: 1476–1488, 2006. © 2006 Wiley‐Liss, Inc.
Large‐scale plant protein subcellular location prediction
Authors: Chou Kuo‐Chen , Shen Hong‐Bin
Published: September 2006

Current plant genome sequencing projects have called for development of novel and powerful high throughput tools for timely annotating the subcellular location of uncharacterized plant proteins. In view of this, an ensemble classifier, Plant‐PLoc, formed by fusing many basic individual classifiers, has been developed for large‐scale subcellular location prediction for plant proteins. Each of the basic classifiers was engineered by the K‐Nearest Neighbor (KNN) rule. Plant‐PLoc discriminates plant proteins among the following 11 subcellular locations: (1) cell wall, (2) chloroplast, (3) cytoplasm, (4) endoplasmic reticulum, (5) extracell, (6) mitochondrion, (7) nucleus, (8) peroxisome, (9) plasma membrane, (10) plastid, and (11) vacuole. As a demonstration, predictions were performed on a stringent benchmark dataset in which none of the proteins included has ≥25% sequence identity to any other in a same subcellular location to avoid the homology bias. The overall success rate thus obtained was 32–51% higher than the rates obtained by the previous methods on the same benchmark dataset. The essence of Plant‐PLoc in enhancing the prediction quality and its significance in biological applications are discussed. Plant‐PLoc is accessible to public as a free web‐server at http://202.120.37.186/bioinf/plant. Furthermore, for public convenience, results predicted by Plant‐PLoc have been provided in a downloadable file at the same website for all plant protein entries in the Swiss‐Prot database that do not have subcellular location annotations, or are annotated as being uncertain. The large‐scale results will be updated twice a year to include new entries of plant proteins and reflect the continuous development of Plant‐PLoc. J. Cell. Biochem. 100: 665–678, 2007. © 2006 Wiley‐Liss, Inc.
Numerical characterization of DNA sequences based on the k‐step Markov chain transition probability
Authors: Dai Qi , Liu Xiao‐Qing , Wang Tian‐Ming
Published: September 2006

A DNA sequence can be regarded as a discrete‐time Markov chain. Based on k‐step transition probabilities, we construct a series of 4 × 4 k‐step transition matrices to characterize the DNA primary sequences. According to the properties of Markov chains, we obtain distributions of A, T, C and G, and analyze the changes among them from yesterday to tomorrow. We can calculate the probabilities of nucleotide triples of DNA primary sequences. Finally, we introduce a correlation of this kind of transition matrices and consider it as an invariant to analyze the similarities/dissimilarities of DNA sequences. © 2006 Wiley Periodicals, Inc. J Comput Chem, 2006
Transition metal–boron complexes BnM: From bowls (n = 8–14) to tires (n = 14)
Authors: Li Si‐Dian , Miao Chang‐Qing , Guo Jin‐Chang , Ren Guang‐Ming
Published: September 2006

Transition metal–boron complexes BnM have been predicted at density functional theory level to be molecular bowls (n = 8–14) hosting a transition metal atom (M) inside or molecular tires (n = 14) centered with a transition metal atom. Small Bn clusters prove to be effective inorganic ligands to all the VB–VIIIB transition metal elements in the periodic table. Density functional evidences obtained in this work strongly suggest that bowl‐shaped fullerene analogues of Bn units exist in small BnM complexes and the bowl‐to‐tire structural transition occur to the first‐row transition metal complexes BnM (M = Mn, Fe, Co) at n = 14, a size obviously smaller than n = 20 where the 2D‐3D structural transition occurs to bare Bn. The half‐sandwich‐type B12Cr (C3v), full sandwich‐type (B12)2Cr (D3d), bowl‐shaped B14Fe (C2), and tire‐shaped B14Fe (D7d) and B14Fe− (C7v) are the most interesting prototypes to be targeted in future experiments. These BnM complexes may serve as building blocks to form extended boron‐rich BnMm tubes or cages (m ≥ 2) or as structural units to be placed inside carbon nanotubes with suitable diameters. © 2006 Wiley Periodicals, Inc. J Comput Chem, 2006
An iterative knowledge‐based scoring function to predict protein–ligand interactions: I. Derivation of interaction potentials
Authors: Huang Sheng‐You , Zou Xiaoqin
Published: September 2006

Using a novel iterative method, we have developed a knowledge‐based scoring function (ITScore) to predict protein–ligand interactions. The pair potentials for ITScore were derived from a training set of 786 protein–ligand complex structures in the Protein Data Bank. Twenty‐six atom types were used based on the atom type category of the SYBYL software. The iterative method circumvents the long‐standing reference state problem in the derivation of knowledge‐based scoring functions. The basic idea is to improve pair potentials by iteration until they correctly discriminate experimentally determined binding modes from decoy ligand poses for the ligand‐protein complexes in the training set. The iterative method is efficient and normally converges within 20 iterative steps. The scoring function based on the derived potentials was tested on a diverse set of 140 protein–ligand complexes for affinity prediction, yielding a high correlation coefficient of 0.74. Because ITScore uses SYBYL‐defined atom types, this scoring function is easy to use for molecular files prepared by SYBYL or converted by software such as BABEL. © 2006 Wiley Periodicals, Inc. J Comput Chem, 2006
Importance of individual side chains for the stability of a protein fold: Computational alanine scanning of the insulin monomer
Authors: Zoete Vincent , Meuwly Markus
Published: September 2006

A new computational approach is proposed to probe the importance of residue side chains for the stability of a protein fold. Computational mutations to estimate protein stability (CMEPS) is based on the notion that the binding free energy corresponding to the complexation of a given side chain, considered as a “pseudo‐ligand” of the wild type protein, reflects the importance of this side chain to the thermodynamic stability of the protein. The contribution of a particular side chain to the folding energy is estimated according to the molecular mechanics‐generalized born surface area MM‐GBSA approach, using a single molecular dynamics simulation trajectory of the wild type protein. CMEPS is a first principles method which does not contain any adjustable parameter that could be fitted to experimental data. The approach is first validated for Barnase and the B1 domain of protein L, for which a correlation coefficient R = 0.73, between experimental and CMEPS calculated ΔΔG values, is found and then applied to the insulin monomer. In the present application, CMEPS replaces each amino acid by an alanine residue. Therefore, most mutations lead to cavities in the protein. From this the change in stability can be correlated with increased cavity volume. For insulin, this correlation is very similar compared with data previously analyzed for T4 lysozyme from an experiment for buried apolar side chains. There, the increased cavity volume has been related to the hydrophobic effect. However, since CMEPS uses the energetics in terms of electrostatic and van der Waals interactions (and not the hydrophobic effect which is difficult to relate to physical interactions), it is possible to study the effect of mutations of polar and solvent accessible side chains. According to CMEPS, residues Leu A16, Tyr A19, Leu B11, Leu B15, and Arg B22 are most important for the stability of the monomeric insulin fold. This is in agreement with experimental data. As a consequence, mutation of these residues may lead to misfolded and inactive insulin analogues. © 2006 Wiley Periodicals, Inc. J Comput Chem, 2006
On the mechanism of ion formation from the aqueous solutions irradiated with 3 µm IR laser pulses under atmospheric pressure
Authors: Laiko Victor V. , Taranenko Nelli I. , Doroshenko Vladimir M.
Published: September 2006

The mechanism of atmospheric pressure (AP) laser ionization of water and water/glycerol liquid samples at a 3‐µm wavelength is studied experimentally. For the ion desorption, an in‐house built Yb : YAG‐pumped optical parametric oscillator (OPO) infrared (IR) laser has been coupled with AP MALDI ion source interfaced to an ion trap mass spectrometer (MS). It has been shown that water is primarily responsible for ion generation in water/glycerol samples, while glycerol increases the solution viscosity and decreases the water evaporation rate and sample losses. In contrast to AP UV‐MALDI, the electric field in the case of AP IR‐MALDI does not assist in ion production. It was found that the absence of the electrical field provides the optimum ionization condition both for water and water/glycerol liquid samples at the 3‐µm laser irradiation. A two‐stage ion formation mechanism, which includes the initial emission of microdroplets and release of molecular ions at the second stage, can explain the experimentally observed ion signal dependencies upon the voltage applied between MS inlet and the MALDI sample plate. Postionization using additional corona discharge APCI increases the observed signal by approximately 50%, which indicates that some portion of the analyte is desorbed in the form of neutral molecules. Copyright © 2006 John Wiley & Sons, Ltd.
Neuroprotective effect of N‐acetylcysteine on neuronal apoptosis induced by a synthetic gingerdione compound: Involvement of ERK and p38 phosphorylation
Authors: Lin Chia‐Ho , Kuo Sheng‐Chu , Huang Li‐Jiau , Gean Po‐Wu
Published: September 2006

Besides being used as a spice, ginger has been applied in oriental medicine to ameliorate symptoms such as inflammatory, rheumatic disorders, and gastrointestinal discomforts. The effects of ginger on neuronal cells, however, have not been explored. We investigate the effect of 1‐(3,4‐dimethoxyphenyl)‐3,5‐dodecenedione (I6), a derivative of gingerdione, on cultured cortical neurons. After a 5‐day maturation period in vitro, cortical neurons were treated with I6 for 24 hr and cell viability was assessed using MTT assay. I6 induced neuronal death in a concentration‐dependent manner. Hoechst 33342, propidium iodide (PI), and TUNEL staining confirmed that the reduced cell viability by I6 was due to apoptosis. Pre‐treatment of cell with N‐acetylcysteine (NAC) prevented cell death in a concentration‐dependent manner. N‐acetylcysteine increased phosphorylated levels of p42 and p44 extracellular signal‐regulated kinases (ERKs). In parallel, farnesyltransferase and MEK inhibitors blocked ERK phosphorylation and neuroprotective effect of NAC. Unexpectedly, NAC also increased phosphorylated level of p38 mitogen‐activated protein kinase (MAPK) and p38 specific inhibitors dose‐dependently attenuated the effect of NAC. Farnesyltransferase and MEK inhibitors completely abolished NAC‐induced p38 phosphorylation whereas p38 inhibitor did not influence NAC‐induced ERK phosphorylation. These results show that NAC serially activates ERKs and p38 MAPK, and ERKs and p38 work together to mediate the neuroprotective effect of NAC. © 2006 Wiley‐Liss, Inc.
Inhibition of EphA7 up‐regulation after spinal cord injury reduces apoptosis and promotes locomotor recovery
Authors: Figueroa Johnny D. , Benton Richard L. , Velazquez Ixane , Torrado Aranza I. , Ortiz Cristina M. , Hernandez Carmen M. , Diaz Juan J. , Magnuson David S. , Whittemore Scott R. , Miranda Jorge D.
Published: September 2006

Functional impairment after spinal cord injury (SCI) is partially attributed to neuronal cell death, with further degeneration caused by the accompanying apoptosis of myelin‐forming oligodendrocytes. The Eph receptor protein tyrosine kinase family and its cognate ligands, the ephrins, have been identified to be involved in axonal outgrowth, synapse formation, and target recognition, mainly mediated by repulsive activity. Recent reports suggest that ephrin/Eph signaling might also play a role as a physiological trigger for apoptosis during embryonic development. Here, we investigated the expression profile of EphA7, after SCI, by using a combination of quantitative real‐time PCR (QRT‐PCR) and immunohistochemical techniques. QRT‐PCR analysis showed an increase in the expression of full‐length EphA7 at 7 days postinjury (DPI). Receptor immunoreactivity was shown mostly in astrocytes of the white matter at the injury epicenter. In control animals, EphA7 expression was observed predominantly in motor neurons of the ventral gray matter, although some immunoreactivity was seen in white matter. Furthermore, blocking the expression of EphA7 after SCI using antisense oligonucleotides resulted in significant acceleration of hindlimb locomotor recovery at 1 week. This was a transient effect; by 2 weeks postinjury, treated animals were not different from controls. Antisense treatment also produced a return of nerve conduction, with shorter latencies than in control treated animals after transcranial magnetic stimulation. We identified EphA7 receptors as putative regulators of apoptosis in the acute phase after SCI. These results suggest a functional role for EphA7 receptors in the early stages of SCI pathophysiology. © 2006 Wiley‐Liss, Inc.
pH is an intracellular effector controlling differentiation of oligodendrocyte precursors in culture via activation of the ERK1/2 pathway
Authors: Bernard Frédéric , Vanhoutte Peter , Bennasroune Amar , Labourdette Gérard , Perraut Martine , Aunis Dominique , Gaillard Stéphane
Published: September 2006

We reported previously that onset of oligodendrocyte precursor cell (OPC) differentiation is accompanied by an increase in intracellular pH (pHi). We show that OPC differentiation is dependent primarily on a permissive pHi value. The highest differentiation levels were observed for pHi values around 7.15 and inhibition of differentiation was observed at slightly more acidic or alkaline values. Clamping the pHi of OPCs at 7.15 caused a transient activation of ERK1/2 that was not observed at more acidic or alkaline values. Furthermore, inhibition of ERK activation with the UO126 compound totally prevented OPC differentiation in response to pHi shift. These results indicate that pHi, acting through the ERK1/2 pathway, is a key determinant for oligodendrocyte differentiation. We also show that this pHi pathway is involved in the process of retinoic acid‐induced OPC differentiation. © 2006 Wiley‐Liss, Inc.
Morphine upregulates functional expression of neurokinin‐1 receptor in neurons
Authors: Wan Qi , Douglas Steven D. , Wang Xu , Kolson Dennis L. , O'Donnell Lauren A. , Ho Wen‐Zhe
Published: September 2006

Neuronkinin‐1 receptor (NK‐1R), the neuropeptide substance P (SP) preferring receptor, is highly expressed in areas of the central nervous system (CNS) that are especially implicated in depression, anxiety, and stress. Repeated exposure to opioids may sensitize neuronal systems involved in stress response. We examined the effects of morphine, the principal metabolite of heroin, on the functional expression of NK‐1R in the cortical neurons. NK‐1R and mu‐opioid receptor (MOR) are co‐expressed in the cortical neurons. Morphine enhanced NK‐1R expression in the cortical neurons at both the mRNA and protein levels. The upregulated NK‐1R by morphine had functional activity, because morphine‐treated cortical neurons had greater SP‐induced Ca2+ mobilization than untreated neurons. Blocking opioid receptors on the cortical neurons by naltrexone or CTAP (a μ‐opioid receptor antagonist) abolished the morphine action. Investigation of the mechanism(s) responsible for the morphine action showed that morphine activated NK‐1R promoter and induced the phosphorylation of p38 MAPK protein in the cortical neurons. These in vitro data provide a plausible cellular mechanism for opioid‐mediated neurological disorders. © 2006 Wiley‐Liss, Inc.
Termination Kinetics of tert‐Butyl Methacrylate and of n‐Butyl Methacrylate Free‐Radical Bulk Homopolymerizations
Authors: Buback Michael , Junkers Tanja
Published: September 2006

Summary: Termination kinetics in tert‐butyl methacrylate (tert‐BMA) and n‐butyl methacrylate (n‐BMA) bulk homopolymerizations has been studied via the single pulse‐pulsed laser polymerization‐near infrared (SP‐PLP‐NIR) method between 40 and 80 °C at pressures from 500 to 2 250 bar. Toward increasing monomer conversion, the chain‐length averaged termination rate coefficient, 〈kt〉, for both monomers exhibits the methacrylate‐specific sequence of an initial plateau region, assigned to control by segmental diffusion, followed by a steep decrease of 〈kt〉 at intermediate conversion, which is assigned to translational diffusion control, and a weaker decrease of 〈kt〉, associated with reaction‐diffusion control, at still higher degrees of monomer conversion. Despite this similarity, the two isomeric monomers clearly differ in absolute size of 〈kt〉 and in the monomer concentration ranges where the transitions between the different types of diffusion control occur. The differences are assigned to effects of chain mobility which is hindered to a larger extent in tert‐BMA than in n‐BMA. As a consequence, the 〈kt〉 behavior of tert‐BMA at 80 °C is close to the one of n‐BMA at 40 °C. Investigations into the chain‐length dependence of kt, in particular into kt(i,i), the rate coefficient for termination of two radicals of identical size, support the evidence on the different types of diffusion control that operate as a function of monomer conversion. In the initial conversion range, the power‐law exponent which characterizes the chain‐length dependence of larger (entangled) radicals, is found for both monomers to be close to the theoretical value of α = 0.16.

Dependence of log(〈kt〉/kp) on monomer conversion, X, for n‐BMA and tert‐BMA bulk homopolymerizations at 2 000 bar and 70 °C. Circles and triangles represent independent data sets obtained from separate experiments.

magnified image

Dependence of log(〈kt〉/kp) on monomer conversion, X, for n‐BMA and tert‐BMA bulk homopolymerizations at 2 000 bar and 70 °C. Circles and triangles represent independent data sets obtained from separate experiments.
DNA‐Synthetic Polymer Conjugates
Authors: Ono Akira
Published: September 2006

Summary: By conjugating functional moieties of biopolymers to artificial polymers, novel functional materials can be developed, since such conjugated polymers could combine the functions of the biopolymers and the functions, solidity, and economical advantages of the artificial polymers. This article reviews studies for developing novel materials from DNA and their analogues, and discusses a recent report by Wang and co‐workers (Macromol. Rapid Commun. 2006, 207, 389) that describes the preparation of a thymine‐poly(thiophene) conjugate, a novel conjugated polymer that carries a nucleobase. In addition, they demonstrate that the conjugated polymer is useful for detecting HgII ions. Thus, the report indicates that developing conjugated polymers, which have the functions of DNA on a stable polymer backbone, is one of the promising ways to synthesize practical functional polymers.

A schematic representation of the DNA duplex structure and a poly(thiophene) carrying a thymine residue.

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A schematic representation of the DNA duplex structure and a poly(thiophene) carrying a thymine residue.
Electronic Conductive Microporous Polymer‐Based Structures
Authors: Yakisir Dinçer , Mighri Frej , Bousmina Mosto
Published: September 2006

Summary: This study aims at developing a highly electronic conductive microporous structure from thermoplastic polymers filled with carbon black (CB) and graphite (GR). The matrix was a low viscosity poly(propylene) (PP) and the conductive additives were composed of high specific surface area CB and synthetic flake GR. Conductive blends were first developed using a corotating twin‐screw extruder. Rheological properties and conductivities of these blends were then characterized as a function of blend composition. Blends that show the best compromise between electronic conductivity and processability were subsequently extruded through a sheet die to obtain films of around 500 µm in thickness. These films were then stretched in two successive steps under controlled temperature and stretching rate to generate a film of controlled microporous structure.

TEM of film made from a 50 wt.‐% PP/25 wt.‐% CB/25 wt.‐% GR blend after stretching.

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TEM of film made from a 50 wt.‐% PP/25 wt.‐% CB/25 wt.‐% GR blend after stretching.
Risk tolerance in the present and the future: an experimental study
Authors: Noussair Charles , Wu Ping
Published: September 2006

We design an experiment to study the consistency of risk preferences between lotteries that are resolved and paid in the present versus in the future. The results show that a substantial fraction of subjects (38.6%) exhibits a greater level of risk aversion for lotteries resolved and paid in the present than in the future. Additional treatments suggest that the effect is neither specific to gambles that are realized immediately, nor is due to steep discounting of future payoffs. Our experiment suggests that risk tolerance increases the farther in the future the gamble is realized. Copyright © 2006 John Wiley & Sons, Ltd.
Price‐setting power and information asymmetry in sealed bidding
Authors: Parco James E.
Published: September 2006

Diverging from the historical precedent of using a midpoint rule (k=½) to experimentally structure two‐person bargaining under incomplete information, extreme values of k (k={0, 1}) are invoked in an asymmetric information environment endowing one player with exclusive price‐setting power and the other player with veto‐only power. Theoretical analysis suggests that regardless of who possesses an information advantage, expected profits for a seller (buyer) decrease (increase) in k. Yet, experimental results show that under conditions of dramatic information asymmetry, not only is the observed share of the surplus is much smaller than predicted for the player with price‐setting power, but also the player with the information advantage is unable to garner a greater share of the surplus as has been consistently demonstrated in previous studies providing a boundary test of Daniel et al.'s Information Disparity Hypothesis (1998). Published in 2006 by John Wiley & Sons, Ltd.
On‐the‐job leisure as a cause of asymmetric observed‐effort distributions
Authors: Dickinson David L.
Published: September 2006

When employers observe imperfect measures of worker effort, theorists typically assume that observed effort is unimodal and symmetrically distributed. Though observable effort may be distributed in different ways within a work day, for example, available field data on these effort distributions are rare. The symmetry assumption is largely untestable as a result. This paper presents empirical data from two experimental work environments that question the validity of such assumptions. For these piece‐rate work environments the author finds that observed effort is significantly negatively‐skew (i.e. modal>mean effort). The author's hypothesis is that on‐the‐job leisure causes this skewness in observed effort distributions. There are both theoretical and practical implications of this asymmetry. Some implications from the theoretical agency literature that we discuss include: self‐selection into rank‐order tournaments, optimal wage spreads in rank‐order tournaments, and optimal wage contracts with asymmetric information. Copyright © 2006 John Wiley & Sons, Ltd.
An experimental examination of demand reduction in multi‐unit versions of the Uniform‐price, Vickrey, and English auctions
Authors: Porter David , Vragov Roumen
Published: September 2006

Demand reduction in Uniform‐price and English auctions are strategic reactions by participants to reduce price and thus increase potential profits. Laboratory experiments similar to the field experiments performed by List and Reiley (Am. Econ. Rev. 2000; 9(4): 961–972) in which two individuals with demands for two units vie for two units through a Uniform‐price, English or Vickrey auction are conducted. We find strong support for demand reduction in both the English and Uniform‐price auctions, with significantly more dramatic reductions in the English auction. However, there is significant overbidding in both the Vickrey and Uniform‐price auction. This overbidding solves a puzzle found by List and Reiley in their field experiment data. Copyright © 2006 John Wiley & Sons, Ltd.
Low expression of HER2 protein in breast cancer is biologically significant
Authors: Tovey SM , Reeves JR , Stanton P , Ozanne BW , Bartlett JMS , Cooke TG
Published: September 2006

HER2 status is routinely tested using immunohistochemistry or FISH following the licensing of a therapeutic agent targeting HER2. However, neither of these methods provides quantitative information relating to the 70–80% of patients with levels of expression lower than the assay detection thresholds. In this study, radioimmunohistochemistry was used to detect quantitative HER2 protein expression in 178 breast cancers. Survival analysis was performed, as were correlations with known prognostic variables and with overexpression of other HER family members. It is demonstrated that the populations expressing very high and very low levels of HER2 are each associated with increased risk of cancer‐specific death on survival analysis (p = 0.0043). The group with low levels of HER2 was more likely to be of higher grade, EGFR‐positive and ER/HER3/HER4‐negative. HER2‐positive cases were frequently ER‐negative/HER3‐positive, whilst cases with normal HER2 expression were often ER‐positive/HER4‐positive. The aggressive nature of the tumour group with low HER2 expression may be explained by actions of other HER family members, particularly EGFR, but whether these or other factors have a negative regulatory effect on HER2 expression remains to be determined. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Differential capacity of anti‐RAP and anti‐megalin antibodies to produce progressive passive Heymann nephritis — implications for the pathogenesis of idiopathic human membranous glomerulonephritis
Authors: Makker SP , Tramontano A
Published: September 2006

Passive Heymann nephritis (PHN) induced with heterologous antisera has been described according to various criteria, which may or may not include induction of chronic disease and proteinuria. Characteristics of the glomerular immune deposits determined by the antigenic specificities of the antisera presumably account for differences in disease outcome. In this study, the clinical and immunohistological features in the model produced with monospecific antisera were compared against megalin or receptor associated protein (RAP), two proteins that have been implicated as target antigens in PHN. Rats injected with either anti‐megalin or anti‐RAP antiserum developed typical glomerular immune deposits of PHN when examined after 7 days. Although the deposits stained for complement, none of the animals had abnormal proteinuria in this time frame. Over a longer time course (7–16 weeks), immune deposits persisted and proteinuria increased to pathological levels in all animals injected with anti‐megalin serum. By contrast, immune deposits had cleared from the kidneys of rats injected with anti‐RAP antiserum when examined at 7–8 weeks post‐injection and the proteinuria levels observed up to 13 weeks remained in the normal range. Additional doses of anti‐RAP antiserum given 4 and 17 days after the first injection did not prolong the duration of glomerular immune deposits. These results demonstrate a clear divergence in pathogenic potential of antisera generated against the two renal antigens, which suggest differences in the immune deposits linked to a soluble antigen that is non‐covalently bound to the podocyte membrane versus those linked to an integral membrane antigen. These observations could provide clues to the nature of the unknown glomerular autoantigen of idiopathic membranous glomerulonephritis in humans. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Contact allergy to topical drugs: prevalence in a clinical setting and estimation of frequency at the population level
Authors: Menezes de Pádua C. A. , Uter W. , Schnuch A.
Published: September 2006

Objectives

To estimate the prevalence of contact allergy (CA) to a set of topical drugs patch tested in the research network IVDK (Information Network of Departments of Dermatology; www.ivdk.org) between 1995 and 2004, and to extrapolate these clinical data to the German population.

Methods

Clinical data comprised results of allergy patch tests with topical drugs in patients with suspected CA. Clinical epidemiology and drug utilization research (CE‐DUR) methods were employed to grossly estimate the incidence of CA to these topical drugs during two 5‐year periods (1995–1999 and 2000–2005) in the German general population. To estimate the number of persons eligible for patch testing (with the topical drugs) on a general population level, sales data of patch test material were obtained. By relating this denominator to the CA frequency observed in the IVDK, the incidence of CA to selected topical drugs in the German general population was crudely estimated.

Results

In general, topical aminoglycosides showed the highest CA frequencies and, except for gentamicin sulfate, frequencies of CA to all other allergens tested were lower in the 2nd period of analysis. According to the medium model, 1‐year incidence rates ranged from 1 (hydrocortisone‐17‐butyrate) to 29 persons/100 000 (neomycin sulfate) in the general population (1995–1999).

Conclusion

The CE‐DUR approach yielded incidence estimates of CA to relevant topical drugs in the German general population, which, despite their limited precision in absolute terms, illustrate the relative frequency of this particular adverse effect. However, comparative risk assessment should preferably take exposure information into account. Copyright © 2006 John Wiley & Sons, Ltd.
Effectiveness and safety of ritodrine hydrochloride for the treatment of preterm labour: a systematic review
Authors: Yaju Yukari , Nakayama Takeo
Published: September 2006

Purpose

To analyse the available data on the effectiveness and safety of ritodrine hydrochloride in delaying delivery and in decreasing the incidence of preterm birth.

Methods

Systematic review of randomised controlled trials (RCTs) that compared the effectiveness and safety of ritodrine hydrochloride with a placebo or with no treatment. Main outcome measures were relative risks (RRs) for perinatal mortality, neonatal respiratory distress syndrome (RDS), delivery within 48 hours or 7 days, preterm birth before 37 weeks gestation and low birth weight. We searched computerised databases (MEDLINE, CENTRAL, Ichushi Web) from their inception to October 2004, and searched the references of eligible trials.

Results

Seventeen RCTs were included and meta‐analysis was conducted. Pooled RRs relative to placebo for delivery within 48 hours or 7 days for parenteral ritodrine hydrochloride were 0.74 (95%CI (confidential interval): 0.56, 0.97), 0.85 (95%CI: 0.74, 0.97). There was no significant decrease in perinatal mortality, the proportion of RDS, preterm birth and low birth weight infants. Maternal side‐effects significantly increased in patients receiving ritodrine with respect to those receiving a placebo. Pooled RRs relative to placebo for oral ritodrine hydrochloride showed no significant decrease in primary and secondary endpoints.

Conclusions

The effectiveness of parenteral ritodrine hydrochloride for tocolysis in preterm labour is limited to short‐range prolongation of gestation. The effectiveness of maintenance tocolytic therapy with oral ritodrine hydrochloride was not proved. Copyright © 2006 John Wiley & Sons, Ltd.
A call for international harmonization in therapeutic risk management
Authors: Hirst Ceri , Cook Suzanne , Dai Wanju , Perez‐Gutthann Susana , Andrews Elizabeth
Published: September 2006

Therapeutic risk management is required to ensure that the benefits of a particular drug outweigh the risks in general practice. Current risk management strategies and handling of risk management and pharmacovigilance issues differ across borders. Differences in key regulatory decisions on the same product around the world, including the handling of safety issues with cisapride, dofetilide, and isotretinoin, bring into question the robustness of these decisions and the procedures currently in place to manage the risks to the public of products with potentially unfavorable risk‐benefit balances. These differences may be partly due to differences in health care systems, regulatory requirements and procedures, and cultures. Greater international harmonization in approaches to risk management potentially would improve safety of medicines around the world by developing a greater uniformity in acquiring and interpreting risk‐benefit evidence. The appropriateness and effectiveness of risk management interventions in different regions should be examined, and international strategies should be ‘fine‐tuned’ for each regional health care setting. Recently issued international guidance on risk management and pharmacovigilance may help to improve consistency of decision‐making around the world and promote better international communication and collaboration. Copyright © 2006 John Wiley & Sons, Ltd.
Polymer‐nanofiber composites: Enhancing composite properties by nanofiber oxidation
Authors: Rasheed Asif , Dadmun Mark D. , Britt Phillip F.
Published: September 2006

Nanocomposites of styrene and vinyl phenol copolymers, which contain varying (10, 20, and 40 mol %) vinyl phenol content, were prepared with 1 wt % unoxidized, 1 wt % oxidized, and 5 wt % oxidized carbon nanofibers. Dynamic mechanical analysis and differential scanning calorimetry indicate that the composites prepared from oxidized nanofibers exhibit improved thermal and structural properties relative to those prepared from unoxidized nanofibers. The optimum enhancement in the mechanical and thermal properties was observed for the composite containing oxidized nanofibers and the 20% vinyl phenol copolymer. These results are in excellent agreement with our previous work on carbon nanotube–polymer composites and suggest that the presence of intermolecular interactions between the copolymer matrix and nanofibers are responsible for the observed property enhancement. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 44: 3053–3061, 2006
Analysis of novel angiotensin‐I‐converting enzyme inhibitory peptides from protease‐hydrolyzed marine shrimp Acetes chinensis
Authors: Hai‐Lun HE , Xiu‐Lan Chen , Cai‐Yun Sun , Yu‐Zhong Zhang , Bai‐Cheng Zhou
Published: September 2006

Acetes chinensis is an underutilized shrimp species thriving in the Bo Hai Gulf of China. In a previous study, we had used the protease from Bacillus sp. SM98011 to digest this kind of shrimp and found that the oligopeptide‐enriched hydrolysate possessed antioxidant activity and high angiotensin I‐converting enzyme (ACE) inhibitory activity with an IC50 value of 0.97 mg/ml. In this paper, by ultrafiltration, gel permeation chromatography and reversed‐phase high‐performance liquid chromatography (RP‐HPLC), five peptides with high ACE inhibitory activity were purified from the shrimp hydrolysates and their sequences were identified by amino acid composition analysis and molecular weight (MW) analysis. Three of them, FCVLRP (a), IFVPAF (f) and KPPETV (j), were novel ACE inhibitory peptides. Their IC50 values were 12.3 µM, 3.4 µM and 24.1 µM, respectively, and their recoveries were 30 mg/100 g (solid basis of shrimp), 19 mg/100 g and 33 mg/100 g, respectively. Lineweaver‐Burk plots for the three novel peptides showed that they are all competitive inhibitors. To test the ACE inhibitory activity of peptide a, f, j after they were digested by digestive enzymes in vivo, 12 derived peptides from FCVLRP and IFVPAF were synthesized based on their amino acid sequences and the cleavage sites of digestive enzymes. No digestive enzyme cleavage site was found in KPPETV. The IC50 values of the derived peptides were determined and the result showed that except for VPAF, FC and FCVL, the ACE inhibitory activity of the other nine derived peptides did not significantly change when compared with their original peptides. Surprisingly, five peptides had lower IC50 values than their original peptides, particularly for RP (IC50 value = 0.39 µM), which is about 30 times lower than its original peptide and almost the lowest IC50 value for ACE inhibitory peptides reported. Therefore, the novel peptides identified from A. chinensis hydrolysates probably still maintain a high ACE inhibitory activity even if they are digested in vivo. This is the first report about novel ACE inhibitory peptides from hydrolysates of marine shrimp A. chinensis. The novel peptides from hydrolysate of A. chinensis and some of their derived peptides with high ACE inhibitory activity probably have potential in the treatment of hypertension or in clinical nutrition. Copyright © 2006 European Peptide Society and John Wiley & Sons, Ltd.
Determination of glyoxylyl‐peptide concentration using oxime chemistry and RP‐HPLC analysis
Authors: Garcia Jean‐Michel , Far Samia , Diesis Eric , Melnyk Oleg
Published: September 2006

Glyoxylyl‐peptides are useful peptide derivatives in the context of hydrazone, oxime or thiazolidine ligations. We describe a method for the determination of glyoxylyl‐peptide concentration based on the reaction of the α‐oxo aldehyde group with an excess of O‐benzylhydroxylamine. The amount of O‐benzylhydroxylamine necessary to convert the α‐oxo aldehyde group into the corresponding O‐benzyloxime was determined by RP‐HPLC analysis and corresponded to the quantity of glyoxylyl‐peptide used in the experiment. The method is rapid, sensitive, accurate and allows the automated analysis of several samples. Copyright © 2006 European Peptide Society and John Wiley & Sons, Ltd.