bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyaline Fibromatosis Syndrome inducing mutations in the ectodomain of anthrax toxin receptor 2 can be rescued by proteasome inhibitors
Authors: Deuquet Julie , Lausch Ekkehart , Guex Nicolas , Abrami Laurence , Salvi Suzanne , Lakkaraju Asvin , Ramirez Maria Celeste M. , Martignetti John A. , Rokicki Dariusz , Bonafe Luisa , Superti‐Furga Andrea , van der Goot Françoise G.
Published: February 2011

Hyaline Fibromatosis Syndrome (HFS) is a human genetic disease caused by mutations in the anthrax toxin receptor 2 (or cmg2) gene, which encodes a membrane protein thought to be involved in the homeostasis of the extracellular matrix. Little is known about the structure and function of the protein or the genotype–phenotype relationship of the disease. Through the analysis of four patients, we identify three novel mutants and determine their effects at the cellular level. Altogether, we show that missense mutations that map to the extracellular von Willebrand domain or the here characterized Ig‐like domain of CMG2 lead to folding defects and thereby to retention of the mutated protein in the endoplasmic reticulum (ER). Mutations in the Ig‐like domain prevent proper disulphide bond formation and are more efficiently targeted to ER‐associated degradation. Finally, we show that mutant CMG2 can be rescued in fibroblasts of some patients by treatment with proteasome inhibitors and that CMG2 is then properly transported to the plasma membrane and signalling competent, identifying the ER folding and degradation pathway components as promising drug targets for HFS.
Survey on power system stabilizers control and their prospective applications for power system damping using Synchrophasor‐based wide‐area systems
Authors: Chompoobutrgool Yuwa , Vanfretti Luigi , Ghandhari Mehrdad
Published: February 2011

Power system oscillation damping remains as one of the major concerns for secure and reliable operation of large power systems, and is of great current interest to both industry and academia. The principal reason for this is that the inception of poorly‐damped low‐frequency inter‐area oscillations (LFIOs) when power systems are operating under stringent conditions may lead to system‐wide breakups or considerably reduce the power transfers over critical corridors. With the availability of high‐sampling rate phasor measurement units (PMUs), there is an increasing interest for effectively exploiting conventional damping control devices, such as power system stabilizers (PSSs), by using these measurements as control input signals. In this paper, we provide a comprehensive overview of distinct elements (or “building blocks”) necessary for wide‐area power system damping using synchrophasors and PSSs. These building blocks together shape a tentative methodical framework, and are disposed as follows: (1) fundamental understanding of the main characteristics of inter‐area oscillations, (2) wide‐area measurement and control systems (WAMS and WACS) and wide‐area damping control (WADC), (3) advanced signal processing techniques for mode property identification, (4) methods for model‐based small‐signal analysis, (5) control input signals selection, and (6) methods for PSS control design. We also describe the latest developments in the implementation of synchrophasor measurements in WAMS and WACS as well as their prospectives for WADC applications. This paper serves both to abridge the state‐of‐the‐art in each of these elements, and to accentuate aspiring ideas in each building block. Copyright © 2011 John Wiley & Sons, Ltd.
Application of interactive multiple models in thermal modeling of power transformers
Authors: Akbari Asghar , Allahbakhshi Mehdi , Golpari Reza
Published: February 2011

Power transformers are one of the most expensive equipments in power systems. The efficiency and optimal utilization of these equipments are very important issues. Some factors, like temperature, moisture and oxidation can affect the solid and liquid insulations and reduce the useful life of power transformer. Temperature of a power transformer depends on the ambient temperature, present and past loading and cooling classes. Proper thermal model is essential to predict temperature in different conditions of cooling system. Such model leads to analyze useful life and improve loading and utilization of a power transformer.

In this contribution a thermal model for power transformers based on the new technique of Interactive Multiple Modeling (IMM) is suggested to predict the top‐oil temperature. Practical validation is carried out with measured load and temperature data of a power transformer. Consequently the prediction error for the conventional thermal model and the new suggested model based on IMM technique are compared. Copyright © 2011 John Wiley & Sons, Ltd.
Coordination of multilateral trades in electricity markets via power vectors
Authors: Balagopalan Sudha , Ashok S. , Mohandas K. P.
Published: February 2011

A transmission restructure model is presented, which resolves line abuse, conflict of incentives and information asymmetry in electricity markets. It uses market compatible game theory, graph theory, market mechanism, multilateral trade structure, etc. rather than conventional tools. The model is useful to emulate any active, competitive transmission sector. It has more relevance in countries like India with high T&D loss and power deficit problems. Cooperative game theory (CGT) is holistically applied in organizational, operational, commercial and planning aspects of restructure. A three phase CGT environment to model entity interactions, an elastic transmission service charge (TSC) to penalize abuse and a powerful power vector to resolve information asymmetry are some proposals developed in this context. In the scheme, Discos use power vectors to play the game and negotiate for agreeable TSC share and engineer fruitful mergers. A stable set of coalitions contracting optimal trades at lowest TSC is finally obtained. The method is illustrated on a 5 bus and successfully tested on a 24 bus Indian power system. The outcome is that agents aggregate sequentially, to safeguard network security as a common agenda, despite market activities starting at diverse locations. These results are important because transmission is the most difficult zone to model in electricity markets due to several issues and this model addresses most of them. Copyright © 2011 John Wiley & Sons, Ltd.
Combined operation of converter‐based distributed generation unit in DC distribution system in order to have premium power quality
Authors: Noroozian Reza , Gharehpetian Gevorg B.
Published: February 2011

This paper studies a DC distribution system, which has been supplied by utility AC grid and converter‐based distributed generation (DG) in order to provide an overall solution to power quality problems. The power flow control in DC distribution systems is achieved by network and storage converters, which have DC voltage controllers. A control strategy for these converters has been presented, which is based on DC voltage droop controller and a novel instantaneous power regulation scheme. Furthermore, this paper presents a simple DC bus voltage controller, which can be used for DC system voltage determination. Also, a novel control system has been proposed for DG and load converters. The simulation results, based on PSCAD/EMTDC software, show that DC distribution system including converter‐based DG unit can provide the premium power quality. Copyright © 2011 John Wiley & Sons, Ltd.
A third‐order velocity correction scheme obtained at the discrete level
Authors: Owen H. , Codina R.
Published: February 2011

In this work we explore a velocity correction method that introduces the splitting at the discrete level. In order to do so, the algebraic continuity equation is transformed into a discrete pressure Poisson equation and a velocity extrapolation is used. In Badia et al. (IJNMF, 2008, p. 351), where the method was introduced, the discrete Laplacian that appears in the pressure Poisson equation is approximated by a continuous one using an extrapolation for the pressure. In this work we explore the possibility of actually solving the discrete Laplacian. This introduces significant differences because the pressure extrapolation is avoided and only a velocity extrapolation is needed. Our numerical results indicate that it is the second‐order pressure extrapolation which makes third‐order methods unstable. Instead, second‐order velocity extrapolations do not lead to instabilities. Avoiding the pressure extrapolation allows to obtain stable solutions in problems that become unstable when the Laplacian is approximated. A comparison with a pressure correction scheme is also presented to verify the well‐known fact that the use of a second order pressure extrapolation leads to instabilities. Therefore we conclude that it is the combination of a velocity correction scheme with a discrete Laplacian that allows to obtain a stable third‐order scheme by avoiding the pressure extrapolation. Copyright © 2011 John Wiley & Sons, Ltd.
Three‐dimensional wave impact on a rigid structure using smoothed particle hydrodynamics
Authors: Cummins S. J. , Silvester T. B. , Cleary P. W.
Published: February 2011

Navier–Stokes computations of a wave–structure interaction are performed with the aim of assessing the potential of smoothed particle hydrodynamics to accurately estimate impact loading time history. A three‐dimensional dam‐break flow with a rectangular column located downstream is considered. The net force and impulse exerted on the column is monitored throughout the simulation with the results correlating well with existing experimental data. Initial and boundary conditions and numerical parameters are varied and their effect on the column load investigated. The column load is found to be most sensitive to the choice of boundary treatment. Copyright © 2011 John Wiley & Sons, Ltd.
The Role of Financial Variables in predicting economic activity
Authors: Espinoza Raphael , Fornari Fabio , Lombardi Marco J.
Published: February 2011

Previous research found that the US business cycle leads the European one by a few quarters, and can therefore be useful in predicting euro area gross domestic product (GDP). In this paper we investigate whether additional predictive power can be gained by adding selected financial variables belonging to either the USA or the euro area. We use vector autoregressions (VARs) that include the US and euro area GDPs as well as growth in the Rest of the World and selected combinations of financial variables. Out‐of‐sample root mean square forecast errors (RMSEs) evidence that adding financial variables produces a slightly smaller error in forecasting US economic activity. This weak macro‐financial linkage is even weaker in the euro area, where financial indicators do not improve short‐ and medium‐term GDP forecasts even when their timely availability relative to GDP is exploited. It can be conjectured that neither US nor European financial variables help predict euro area GDP as the US GDP has already embodied this information. However, we show that the finding that financial variables have no predictive power for future activity in the euro area relates to the unconditional nature of the RMSE metric. When forecasting ability is assessed as if in real time (i.e. conditionally on the information available at the time when forecasts are made), we find that models using financial variables would have been preferred in several episodes and in particular between 1999 and 2002. Copyright   2011 John Wiley & Sons, Ltd.
The effect of job loss and unemployment duration on suicide risk in the United States: a new look using mass‐layoffs and unemployment duration
Authors: Classen Timothy J. , Dunn Richard A.
Published: February 2011

We examine the link between employment status and suicide risk using a panel of US states from 1996 to 2005 with monthly data on suicides, the duration of unemployment spells and the number of job losses associated with mass‐layoff events. The use of aggregate data at the monthly level along with the distribution of unemployment duration allows us to separate the effect of job loss from the effect of unemployment duration, an important distinction for policy purposes, especially for the timing of potential interventions. Our results are consistent with unemployment duration being the dominant force in the relationship between job loss and suicide. Nevertheless, mass‐layoffs may be powerful localized events where suicide risk increases shortly afterward. Implications for the design of unemployment insurance are discussed. Copyright © 2011 John Wiley & Sons, Ltd.
Expression of CD147 is associated with prostate cancer progression
Authors: Zhong Wei‐de , Liang Yu‐xiang , Lin Sharron X. , Li Ling , He Hui‐chan , Bi Xue‐cheng , Han Zhao‐dong , Dai Qi‐shan , Ye Yong‐kang , Chen Qing‐biao , Wang Yue‐sheng , Zeng Guo‐hua , Zhu Gang , Zhang Zheng , Chen Zhi‐nan , Wu Chin‐Lee
Published: February 2011

Novel molecular markers that are associated with prostate cancer (PCa) progression will provide valuable information in the diagnosis and treatment of the disease. Extracellular matrix metalloproteinase inducer (CD147) has been demonstrated to be involved in tumor invasion, metastasis, growth and survival. In our study, we examined whether the expression of CD147 can be used as a prognostic marker for predicting PCa progression. Tissue samples from 240 patients who received radical prostatectomy for PCa were obtained. CD147 expression in these samples was evaluated using immunohistochemical staining with a monoclonal antibody specifically against CD147. Increased expression of CD147 was correlated with higher Gleason scores (GS), positive surgical margin, prostate‐specific antigen (PSA) failure, metastasis and reduced overall survival. Both univariate Cox regression analysis and multivariate analysis including competing biological variables demonstrated that increased CD147 expression was associated with increased risk for reduced PSA failure‐free, metastasis‐free and overall survival. Kaplan–Meier survival curves showed that the CD147 overexpression was a significant predictor for the PSA failure‐free, metastasis‐free and the overall survival in both pT2 and pT3 PCa patients. More significantly, higher expression of CD147 can serve as an independent prognostic predictor for PSA failure‐free survival in PCa patients when they are stratified by GS. Our study results demonstrate the involvement of CD147 in PCa progression and suggest its potential role as an independent predictor of biochemical recurrence, development of metastasis and reduced overall survival in PCa.
The shape of gaseous n‐butylbenzene: Assessment of computational methods and comparison with experiments
Authors: Halbert Stéphanie , Clavaguéra Carine , Bouchoux Guy
Published: February 2011

Conformational landscape of neutral and ionized n‐butylbenzene has been examined. Geometries have been optimized at the B3LYP/6‐31G(d), B3LYP/6‐31+G(d,p), B3LYP‐D/6‐31+G(d,p), B2PLYP/6‐31+G(d,p), B2PLYP‐D/6‐31+G(d,p), B97‐D/6‐31+G(d,p), and M06‐2X/6‐31+G(d,p) levels. This study is complemented by energy computations using 6‐311++G(3df,2p) basis set and CBS‐QB3 and G3MP2B3 composite methods to obtain accurate relative enthalpies. Five distinguishable conformers have been identified for both the neutral and ionized systems. Comparison with experimentally determined rotational constants shows that the best geometrical parameters are provided by B3LYP‐D and M06‐2X functionals, which include an explicit treatment of dispersion effects. Composite G3MP2B3 and CBS‐QB3 methods, and B2PLYP‐D, B3LYP‐D, B97‐D, and M06‐2X functionals, provide comparable relative energies for the two sets of neutral and ionized conformers of butyl benzene. An exception is noted however for conformer V+ the stability of which being overestimated by the B3LYP‐D and B97‐D functionals. The better stability of neutral conformers I, III, and IV, and of cation I+, demonstrated by our computations, is in perfect agreement with conclusions based on micro wave, fluorescence, and multiphoton ionization experiments. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Fast construction of assembly trees for molecular graphs
Authors: Artemova Svetlana , Grudinin Sergei , Redon Stephane
Published: February 2011

A number of modeling and simulation algorithms using internal coordinates rely on hierarchical representations of molecular systems. Given the potentially complex topologies of molecular systems, though, automatically generating such hierarchical decompositions may be difficult. In this article, we present a fast general algorithm for the complete construction of a hierarchical representation of a molecular system. This two‐step algorithm treats the input molecular system as a graph in which vertices represent atoms or pseudo‐atoms, and edges represent covalent bonds. The first step contracts all cycles in the input graph. The second step builds an assembly tree from the reduced graph. We analyze the complexity of this algorithm and show that the first step is linear in the number of edges in the input graph, whereas the second one is linear in the number of edges in the graph without cycles, but dependent on the branching factor of the molecular graph. We demonstrate the performance of our algorithm on a set of specifically tailored difficult cases as well as on a large subset of molecular graphs extracted from the protein data bank. In particular, we experimentally show that both steps behave linearly in the number of edges in the input graph (the branching factor is fixed for the second step). Finally, we demonstrate an application of our hierarchy construction algorithm to adaptive torsion‐angle molecular mechanics. © 2011 Wiley Periodicals, Inc. J Comput Chem , 2011.
Predicting protein folding rates using the concept of Chou's pseudo amino acid composition
Authors: Guo Jianxiu , Rao Nini , Liu Guangxiong , Yang Yong , Wang Gang
Published: February 2011

One of the most important challenges in computational and molecular biology is to understand the relationship between amino acid sequences and the folding rates of proteins. Recent works suggest that topological parameters, amino acid properties, chain length and the composition index relate well with protein folding rates, however, sequence order information has seldom been considered as a property for predicting protein folding rates. In this study, amino acid sequence order was used to derive an effective method, based on an extended version of the pseudo‐amino acid composition, for predicting protein folding rates without any explicit structural information. Using the jackknife cross validation test, the method was demonstrated on the largest dataset (99 proteins) reported. The method was found to provide a good correlation between the predicted and experimental folding rates. The correlation coefficient is 0.81 (with a highly significant level) and the standard error is 2.46. The reported algorithm was found to perform better than several representative sequence‐based approaches using the same dataset. The results indicate that sequence order information is an important determinant of protein folding rates. ©2011 Wiley Periodicals, Inc. J Comput Chem 2011.
Pharmacophore alignment search tool: Influence of scoring systems on text‐based similarity searching
Authors: HÄhnke Volker , Schneider Gisbert
Published: February 2011

The text‐based similarity searching method Pharmacophore Alignment Search Tool is grounded on pairwise comparisons of potential pharmacophoric points between a query and screening compounds. The underlying scoring matrix is of critical importance for successful virtual screening and hit retrieval from large compound libraries. Here, we compare three conceptually different computational methods for systematic deduction of scoring matrices: assignment‐based, alignment‐based, and stochastic optimization. All three methods resulted in optimized pharmacophore scoring matrices with significantly superior retrospective performance in comparison with simplistic scoring schemes. Computer‐generated similarity matrices of pharmacophoric features turned out to agree well with a manually constructed matrix. We introduce the concept of position‐specific scoring to text‐based similarity searching so that knowledge about specific ligand‐receptor binding patterns can be included and demonstrate its benefit for hit retrieval. The approach was also used for automated pharmacophore elucidation in agonists of peroxisome proliferator activated receptor gamma, successfully identifying key interactions for receptor activation. © 2011 Wiley Periodicals, Inc. J Comput Chem 2011.
Specific interactions between lactose repressor protein and DNA affected by ligand binding: Ab initio molecular orbital calculations
Authors: Ohyama Tatsuya , Hayakawa Masato , Nishikawa Shin , Kurita Noriyuki
Published: February 2011

Transcription mechanisms of gene information from DNA to mRNA are essentially controlled by regulatory proteins such as a lactose repressor (LacR) protein and ligand molecules. Biochemical experiments elucidated that a ligand binding to LacR drastically changes the mechanism controlled by LacR, although the effect of ligand binding has not been clarified at atomic and electronic levels. We here investigated the effect of ligand binding on the specific interactions between LacR and operator DNA by the molecular simulations combined with classical molecular mechanics and ab initio fragment molecular orbital methods. The results indicate that the binding of anti‐inducer ligand strengthens the interaction between LacR and DNA, which is consistent with the fact that the binding of anti‐inducer enhances the repression of gene transcription by LacR. It was also elucidated that hydrating water molecules existing between LacR and DNA contribute to the specific interactions between LacR and DNA. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Infinite basis set extrapolation for double hybrid density functional theory 1: Effect of applying various extrapolation functions
Authors: Chuang Yao‐Yuan , Chen Sheng‐Min
Published: February 2011

We applied the Infinite Basis (IB) set extrapolation and Double Hybrid Density Functional Theory (DHDF) to calculate the databases of atomization energies, ionization energies, electron affinities, reaction barrier heights, proton affinities, alkyl bond dissociation energies, and noncovalent interactions. The Complete Basis Set (CBS) limit is estimated by extrapolating the hybrid density functional theory and PT2 energies using extrapolation functions including exponential, inverse power, modified exponential, and the combination of the these functions. We found that the combination of B2KPLYP/cc‐pV[D|T]Z (which is the extrapolation based on the energies calculated in cc‐pVDZ and cc‐pVTZ) gives results in quadruple‐ζ quality. However, if we want to reach the ∼2 kcal/mol chemical accuracy limit, the cc‐pV[T|Q]Z is required. Similar results with various extrapolation functions obtained, because the IB parameters were determined by minimizing the averaged mean unsigned error of the calculated databases. We generalized the IB set extrapolation to include more than two basis sets, but we found that extrapolation with two basis sets is satisfactory to give reasonable results. The largest error occurred in the databases of the electron affinities and the weak interactions between the noble gas and the nonpolar molecules. We expect that performing the DHDF‐IB scheme with the basis sets augmented by diffuse basis functions will further improve the results. © 2011 Wiley Periodicals, Inc. J Comput Chem , 2011.
Reply to the comment by Sheppard and Henkelman on the nudged elastic band method
Authors: Quapp Wolfgang , Bofill Josep Maria
Published: February 2011

We reject a comment of Sheppard and Henkelman. © 2011 Wiley Periodicals, Inc. J Comput Chem , 2011.
Engineering a mammalian super producer
Authors: Dietmair Stefanie , Nielsen Lars K. , Timmins Nicholas E.
Published: February 2011

Mammalian cells are the preferred host for the manufacture of a wide range of biopharmaceuticals, but production costs are high owing to low productivity. A range of rational engineering strategies have been pursued in order to increase volumetric product titres from mammalian cells, such as delaying apoptosis, manipulation of the cell cycle, and improving metabolism and protein processing. Unfortunately, outcomes from these strategies have been mixed, with few instances where significant improvements in product yield have been achieved. This article reviews and contrasts many of the engineering strategies attempted to date, highlighting the variability and context specificity in outcome. The paper argues that this is a reflection of the complexity of mammalian cells, and that a deeper understanding of the biology underpinning protein production for biotechnological purposes is required. Copyright © 2011 Society of Chemical Industry
Development of a control algorithm for air‐scour reduction in membrane bioreactors for wastewater treatment
Authors: Ferrero Giuliana , Monclús Hector , Buttiglieri Gianluigi , Gabarron Sara , Comas Joaquim , Rodríguez‐Roda Ignasi
Published: February 2011

BACKGROUND: Membrane bioreactors are used in an increasing number of wastewater treatment facilities because of their compactness and efficiency in solid‐liquid separation, but energy requirements are still higher than other competitive technologies such as conventional activated sludge.

RESULTS: In this paper the development of an air‐scour control algorithm based on short‐term and long‐term membrane permeability evolution is presented. An open loop calibration and partial validation was carried out in a semi‐industrial scale pilot plant where manual changes in air‐scour flow had been previously carried out. The control system was successfully tested in closed loop in an industrial scale pilot plant, defining a maximum daily air‐scour decrease or increase of 6% of the air‐scour recommended by membranes suppliers. An average air‐scour saving of 13% and a maximum of 20%, calculated in terms of air flow saved, were achieved during the validation test without any apparent long‐term effect on membrane permeability.

CONCLUSION: It was proven that the air‐scour control system is an important tool capable of reducing operational costs in MBR systems. Copyright © 2011 Society of Chemical Industry
Testing evolutionary hypotheses about the phylotypic period of zebrafish
Authors: Schmidt Kai , Starck J. Matthias
Published: February 2011

Vertebrate embryos pass through a period of morphological similarity, the phylotypic period. Since Haeckel's biogenetic law of recapitulation, proximate and ultimate evolutionary causes of such similarity of embryos were discussed. We test predictions about changes in phenotypic and genetic variances that were derived from three hypotheses about the evolutionary origin of the phylotypic stage, i.e. random, epigenetic effects, and stabilizing selection. The random hypothesis predicts increasing values for phenotypic variances and stable or increasing values for genetic variances; the epigenetic effects hypothesis predicts declining values for phenotypic variances but stable or increasing values of genetic variances, and the stabilizing selection predicts stable phenotypic variances but decreasing genetic variances. We studied zebrafish as a model species, because it can be bred in large numbers as necessary for a quantitative genetics breeding design. A half‐sib breeding scheme provided estimates of additive genetic variances from 11 embryonic characters from 12 through to 24 hr after fertilization, i.e. before, during (15–19 hr), and after the phylotypic period. Because additive genetic variances are size dependent, we calculated narrow‐sense heritabilities as a size independent gauge of genetic contributions to the phenotype. The results show declining phenotypic variances and stable heritabilities. In conclusion, we reject the random and the stabilizing selection hypotheses and favor ideas about epigenetic effects that constrain the early embryonic development. Additive genetic variance during the phylotypic stage makes it accessible for evolution, thus explaining in a simple and straightforward way why the phylotypic period differs among vertebrates in timing, duration, and morphologies.J. Exp. Zool. (Mol. Dev. Evol.) 316:319–329, 2011. © 2011 Wiley‐Liss, Inc.
Complete restoration of phenylalanine oxidation in phenylketonuria mouse by a self‐complementary adeno‐associated virus vector
Authors: Yagi Hiroya , Ogura Tsuyoshi , Mizukami Hiroaki , Urabe Masashi , Hamada Hiromi , Yoshikawa Hiroyuki , Ozawa Keiya , Kume Akihiro
Published: February 2011

Background

Classical phenylketonuria (PKU) arises from a deficiency of phenylalanine hydroxylase (PAH) that catalyses phenylalanine oxidation in the liver. Lack of PAH activity causes massive hyperphenylalaninemia and consequently severe brain damage. Preclinical studies showed that conventional adeno‐associated virus (AAV) vectors could correct hyperphenylalaninemia in a mouse model of PKU, although limitations such as very large dose requirement and relative inefficiency in female animals were recognized.

Method

An AAV8‐pseudotyped vector was constructed with a self‐complementary AAV (scAAV) genome for efficient liver transduction and expression. Following vector injection to PKU mice, blood Phe was periodically measured by an enzymatic fluorometric assay. In vivo Phe oxidation was evaluated by a non‐invasive breath test using [1‐13C]Phe. Vector copy number in the host tissues was determined by quantitative polymerase chain reaction.

Results

A single injection of 1 × 1011–1 × 1012 particles of the scAAV8 vector resulted in a reduction of blood Phe to normal or near‐normal levels for more than 1 year in both genders. The treated animals showed normal level of in vivo Phe oxidation. The presence of > 1 copy of vector DNA per diploid genome in the liver was associated with normal blood Phe in the AAV‐treated PKU mice.

Conclusions

Complete phenotypic correction of PKU mice was achieved by the scAAV8 vector for the longest duration reported to date. The vector overcame the female‐specific disadvantage in AAV‐mediated liver transduction; thus, it offers a promising platform of long‐lasting gene therapy for PKU. Copyright © 2011 John Wiley & Sons, Ltd.
Sustained inhibition of IL‐6 and IL‐8 expression by decoy ODN to NF‐κB delivered through respirable large porous particles in LPS‐stimulated cystic fibrosis bronchial cells
Authors: De Stefano Daniela , Ungaro Francesca , Giovino Concetta , Polimeno Antonio , Quaglia Fabiana , Carnuccio Rosa
Published: February 2011

Background

Cystic fibrosis (CF) is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Neutrophil‐dominated inflammation and chronic bacterial infection are still considered the primary cause of bronchioectasis, respiratory failure and consequent death in CF patients. Activation of nuclear factor (NF)‐κB is responsible for overproduction of cytokines, such as interleukin (IL)‐6 and IL‐8, in airways of CF patients. Thus, decoy oligodeoxynucleotides against NF‐κB (dec‐ODN) may limit lung inflammation in CF. In the present study, we studied the effects of dec‐ODN delivered through biodegradable and respirable poly(D,L‐lactide‐co‐glycolide) large porous particles (LPP) on IL‐6 and IL‐8 mRNA expression as well as NF‐κB/DNA binding activity in cystic fibrosis cells stimulated with lipopolysaccharide (LPS) from Pseudomonas aeruginosa.

Methods

dec‐ODN LPP were prepared by a modified double emulsion technique and characterized in terms of size, morphology, tapped density and dec‐ODN loading. Human epithelial bronchial IB3‐1 (CFTR‐mutated) as well as S9 (CFTR‐corrected) were stimulated with LPS from P. aeruginosa for 24 and 72 h in the absence or presence of naked dec‐ODN or dec‐ODN LPP.

Results

Stimulation of cells with LPS from P. aeruginosa caused an increase of IL‐6 and IL‐8 mRNA levels, which were significantly inhibited by dec‐ODN LPP at 24 and 72 h, whereas naked dec‐ODN inhibited those only at 24 h. Similar effects were exhibited by dec‐ODN LPP or naked dec‐ODN on NF‐κB/DNA binding activity.

Conclusions

Our observations indicate that respirable biodegradable dec‐ODN LPP may represent a promising strategy for inhibiting NF‐κB transcriptional activity and related gene expression and, thus, reduce lung chronic inflammation in CF patients. Copyright © 2011 John Wiley & Sons, Ltd.
Wettability, surface microstructure and mechanical properties of films based on phosphorus oxychloride‐treated zein
Authors: Wu Lei‐Yan , Wen Qi‐Biao , Yang Xiao‐Quan , Xu Ming‐Sheng , Yin Shou‐Wei
Published: February 2011

BACKGROUND: Zein, the predominant protein in corn, has been extensively studied as an alternative packaging material in edible and biodegradable films. However, films made from 100% zein are brittle under normal conditions. The aim of this investigation was to improve the film‐forming properties of zein by chemical phosphorylation. The surface hydrophobicity, surface microstructure and mechanical properties of films based on untreated and phosphorus oxychloride (POCl3)‐treated zein were evaluated and compared. The effect of POCl3 treatment on the rheological properties of zein solutions was also studied.

RESULTS: POCl3 treatment, especially at pH 7 and 9, led to an increase in the apparent viscosity of zein solutions. Atomic force microscopy (AFM) analysis showed that the film based on POCl3‐treated zein at pH 7 had a stone‐like surface microstructure with a higher roughness (Rq) than the untreated zein film. The AFM data may partially account for the phenomenon that this film exhibited high surface hydrophobicity (H0). POCl3 treatment diminished the tensile strength (TS) of zein films from 4.83–6.67 to 1.3–2.29 MPa. However, the elongation at break (EAB) of the films at pH 7 and 9 increased from 3.0–4.5% (control film) to 150.1–122.7% (POCl3‐treated film), indicating the potential application of zein films in wrapping foods or in non‐food industries such as sugar, fruit or troche that need good extension packing materials.

CONCLUSION: The data presented suggest that the properties of zein films could be modulated by chemical phosphorylation treatment with POCl3 at an appropriate pH value. Copyright © 2011 Society of Chemical Industry
Effect of amino acid level in the pig diet during growing and early finishing on growth response during the late finishing phase of lean meat type gilts
Authors: Millet Sam , Langendries Karolien , Aluwé Marijke , De Brabander Daniël L
Published: February 2011

BACKGROUND: This experiment examined the influence of different amino acid levels during the growing and early finishing diet and the late finishing diet on growth performance and carcass quality of a lean meat type gilt. In a two by two factorial trial, 96 gilts were divided over four treatments. The two factors were (1) amino acid level in growing and early finishing and (2) amino acid level in late finishing. For the low amino acid diets we lowered the lysine, methionine, threonine and tryptophan levels by 20% and 30% in the growing and two finishing phases, respectively.

RESULTS: Restricting amino acid levels in growing and early finishing led to a decreased growth rate but improved efficiency of amino acid use, which lasted into the subsequent phase. Pigs on a high amino acid diet in late finishing pigs were able to compensate to a large extent for amino acid restriction in growing and early finishing. Amino acid content in late finishing determined carcass quality.

CONCLUSION: In the lean meat type gilts used in this experiment, restricting amino acid concentrations by 20% in the growing and 30% in the early finishing phase increased the growth rate and efficiency of growth in the subsequent late finishing phase. In order to obtain good carcass quality, it is crucial to provide the animals with a balanced diet during the late finishing phase. Copyright © 2011 Society of Chemical Industry
Effects of feeding salt‐tolerant forage cultivated in saline‐alkaline land on rumen fermentation, feed digestibility and nitrogen balance in lamb
Authors: Wang Cong , Hu Dong Kuan , Liu Qiang , Yang Wen Zhu , Zhao Xiang , Liu Sheng Qiang , Ting He Ting , Yu Liu Zhuang
Published: February 2011

BACKGROUND: Mixing salt‐tolerant plants with other plants may affect rumen fermentation, which could result in an increase of feed conversion rate. The objective of this study was to evaluate the effects of partially or entirely replacing the corn stover with a mixture of salt‐tolerant forage (Dahurian wildrye grass, weeping alkaligrass and erect milkvetch) in the diet of lambs on ruminal fermentation, feed digestibility and nitrogen (N) balance. Ratios of corn stover to the mixture of salt‐tolerant forages in the four experimental diets were 100:0, 67:33, 33:67 and 0:100, respectively, for control, low (LF), medium (MF) and high (HF).

RESULTS: Ruminal pH was lower (P = 0.048) with LF and MF than with control and HF diets. Total VFA concentration was consistently higher (P = 0.039) for LF and MF than for control and HF with increasing amount of salt‐tolerant forage. Ratio of acetate to propionate was linearly (P = 0.019) decreased due to the decrease in acetate production. Digestibilities of OM, NDF and CP in the whole tract linearly (P < 0.002) decreased with increasing amount of salt‐tolerant forage. Similarly, retained N and ratio of retained N to digestible N also linearly (P < 0.005) decreased.

CONCLUSION: Feeding salt‐tolerant forage cultivated in saline‐alkaline land improved rumen fermentation with increased total VFA production, and changed the rumen fermentation pattern to increased butyrate production. However, the decreased feed digestibility in the whole digestive tract of lamb may reduce nutrient availability to animals and thus adversely affect animal productivity. Additionally, feeding salt‐tolerant forages may require more protein supplement to meet animal requirements, because of the low protein content and low protein digestibility of the salt‐tolerant forages. Copyright © 2011 Society of Chemical Industry
Functionalized polymeric stationary phases for ion chromatography
Authors: Buszewski Bogusław , Jaćkowska Magdalena , Bocian Szymon , Kosobucki Przemysław , Gawdzik Barbara
Published: February 2011

Synthesis and properties of the multilayered stationary phases, which contain quaternary amine functional groups for the analysis of anions by ion chromatography, are described. The bonded phases were characterized by elemental analysis, solid‐state 13C NMR spectroscopy and chromatographic methods. The surface of 1,4‐di(2‐hydroxy‐3‐methacryloyloxypropoxy)phenol (solid support) was coated with polymeric layers formed by condensation polymerization of primary amine with diepoxide. Each layer of the anion exchange stationary phase consists of copolymer of methylamine (MA) and 1,4‐butanedioldiglycidyl ether (BDDE). A series of stationary phases with different numbers of polymerized layers were tested. The separation of an inorganic anions sample (F–, Cl−, NO2− Br−, NO3−, additionally HPO42− and SO42−) was performed. In the measurement, a hydroxide, carbonate, bicarbonate and their mixture were used as mobile phases.
Fast, accurate, and convenient analysis of bed densities for columns packed with fine reversed‐phase particles
Authors: Jung Stephanie , Stoeckel Daniela , Tallarek Ulrich
Published: February 2011

We determine the interparticle porosities of commercially available, analytical, reversed‐phase HPLC columns by Donnan exclusion of a small, unretained, co‐ionic tracer (nitrate ions). The columns contained packings of C18‐modified, endcapped, silica particles, which differed in their nominal particle diameters (1.8–5 μm) and construction (fully porous or core‐shell). Experiments were carried out by monitoring the elution volumes of nitrate samples in a mobile phase of acetonitrile/water 80:20 v/v at increasing concentrations of Tris‐HCl buffer (pH 8.1) from 0.01 to 60 mM. At low buffer concentrations, nitrate ions are completely electrostatically excluded from the intraparticle mesopore space, which is reflected by a plateau region in the elution curves. The elution volume in the plateau region equals the interparticle void volume. Clearly defined plateau regions were observed for all columns, even those densely packed with core‐shell and sub‐2 μm particles, enabling the accurate determination of interparticle porosities to three decimal places in a fast and convenient way.
Tribological properties of powder metallurgical tool steels used in powder compaction pressing dies
Authors: Hatami Sepehr , Armada Sergio , Laurent Annabelle , Nyborg Lars , Olsson Mikael
Published: February 2011

The tribological properties of two powder metallurgical (PM) tool steels, high and low nitrogen containing, are investigated by means of three different wear tests: ball‐on‐disc, rubber wheel and scratch test. The ball‐on‐disc tests showed two distinct friction curves corresponding to each material. In order to simulate the tribosystem existing in metal powder compaction dies, the rubber wheel and the scratch test were modified. The rubber wheel test was performed using ferrous powder instead of sand, and scratch testing was carried out by sliding a powder compact over the tool steels. The scratch tests indicated a higher steady‐state coefficient of friction for the low nitrogen containing PM steel as compared with the high nitrogen containing alloy. Additionally, the results from the rubber wheel tests were in agreement with industrial experiences, showing the low nitrogen containing tool steel to suffer from severe galling. Copyright © 2011 John Wiley & Sons, Ltd.
Expression and association of TRPC1 with TRPC3 during skeletal myogenesis
Authors: Cheung Kwok‐Kuen , Yeung Simon S. , Au Shannon W. , Lam Levina S. , Dai Zhong‐Quan , Li Ying‐Hui , Yeung Ella W.
Published: February 2011

Introduction: TRPC1 and TRPC3 proteins are widely expressed in skeletal muscles in forming calcium‐permeable channels. Herein we characterize the expression pattern of TRPC transcripts during skeletal myogenesis in C2C12 myoblasts. Methods: We used polymerase chain reaction and Western blotting to detect expression levels, immunohistochemistry for subcellular localization, and co‐immunoprecipitation techniques to assess interaction. Results: TRPC1 localizes to the cytoplasm and is enriched in the perinuclear region in undifferentiated myoblasts. Expression of TRPC1 increases significantly during myogenesis and resides mainly in differentiated myocytes and myotubes. TRPC3 is absent in undifferentiated myoblasts, is dramatically upregulated in differentiated culture, and is preferentially expressed in myotubes. Physical interaction of TRPC1–TRPC3 was observed, suggesting the possible existence of heteromers. Conclusions: Expression of TRPC1 and TRPC3 is tightly regulated during myogensis. Evidence of TRPC1–TRPC3 interaction was first demonstrated in a muscle cell line. The functional consequences of this interaction remain to be established. Muscle Nerve 44: 358–365, 2011
Brachial plexopathy as a rare presenting manifestation of scorpion envenomation
Authors: Rubin Devon I. , Vavra Michael
Published: February 2011

We report a patient who experienced a rare manifestation of an acute, severe brachial plexopathy as the initial complication of scorpion (presumed Hemiscorpius lepturus species) envenomation. Features suggesting conduction block, due to either proximal demyelination or ion channel dysfunction, along with axonal loss were seen on serial electrophysiological studies. Possible mechanisms of the brachial plexopathy include direct compression from tissue edema or a toxic effect on the membrane channels along the nerve. Muscle Nerve 44: 131–135, 2011
An indirect approach for automatic generation of quadrilateral meshes with arbitrary line constraints
Authors: Liu Yan , Xing H. L. , Guan Zhenqun
Published: February 2011

A new approach to the automatic generation of a quadrilateral mesh with arbitrary line constraints is proposed in this paper. It is an indirect all‐quad mesh generation and presented in the following steps: (1) discretizing the constrained lines within the domain; (2) converting the above domain to a triangular mesh together with the line constraints; (3) transforming the generated triangular mesh with line constraints to an all‐quad mesh through performing an advancing front algorithm from the line constraints, which enables the construction of quadrilaterals layer by layer, and roughly keeps the feature of the initial triangular mesh; (4) optimizing the topology of the quadrilateral mesh to reduce the number of irregular nodes; (5) smoothing the generated mesh toward high‐quality all‐quad mesh generation. Finally, a few application examples are given to demonstrate the reliability and usefulness of the proposed algorithm. Copyright © 2011 John Wiley & Sons, Ltd.
Perspectives on quality and content of information on the internet for adolescents with cancer
Authors: Stinson Jennifer N. , White Meghan , Breakey Vicky , Chong Amy Lee , Mak Isabella , Low Kazuo Koekebakker , Low Anja Koekebakker
Published: February 2011

Objectives

To assess the quality and content of Internet information about cancer from the perspectives of adolescents with cancer (AWC), their parents and healthcare professionals (HCP).

Methods

Key words relevant to pediatric cancer were searched across 6 search engines. Quality of information was appraised using the DISCERN tool. Website content completeness, accuracy, readability, cultural sensitivity, and desirability were assessed.

Results

Only 29 websites had DISCERN scores above 50 (indicating fair quality; mean 55.76 ± 8.23, range 42.50–70.5). The majority of sites targeted parents and only four (14%) were specific to AWC. Overall completeness of the sites was rated 11.46 out of 20 (±3.60; range 4–17.5) and accuracy was rated 4/4, indicating high accuracy with moderate completeness. The average SMOG score was 11.87 (±2.51, range 7.7–18.67) and the Flesch Reading Ease score was 57.44 (±16.94, range 9.1–92.4) indicating that the material was too difficult to read. The average cultural sensitivity scores for the Format, Written message and Visual material scales were 3.08/4 (±0.53, range 2–4), 3.48/4 (±0.41, range 2.6–4) and 2.84/4 (±1.03, range 0–4) indicating the websites were adequately culturally sensitive. On Average, websites had 4/21 features from the desirability checklist, indicating the sites had low desirability.

Conclusion

Given the paucity of high quality Internet health information at an appropriate reading level for AWC there is a critical need for HCP's to develop Internet programs to meet their unique needs. Pediatr Blood Cancer 2011;57:97–104. © 2011 Wiley‐Liss, Inc.
Disparities in cancer outcomes: Lessons learned from children with cancer
Authors: Bhatia Smita
Published: February 2011

Disparities in cancer burden by race/ethnicity have been reported, primarily in adults with cancer. However, there appear to be gaps in the pediatric oncology literature with regards to a comprehensive overview on this topic. Extant literature is used to highlight the results of studies focusing on racial and ethnic disparities in outcome observed in selected childhood cancers. A comprehensive approach is utilized to understand possible underlying causes of disparities in cancer outcomes, and to highlight the gaps that currently exist. This review helps define areas of future research that could help develop targeted, disease‐specific approaches to eliminate the disparities. Pediatr Blood Cancer 2011;56:994–1002. © 2011 Wiley‐Liss, Inc.