bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of observed variability and trends in numbers of frost days in Turkey for the period 1950–2010
Authors: Erlat Ecmel , Türkeş Murat
Published: August 2011

This study examines the climatology of annual frost days, and analyses the size and behaviour of the long‐term variability and trends in annual numbers of frost day at the 72 stations over Turkey from 1950 to 2010. The main results are summarized as follows: (1) The annual number of frost days has evidently decreased at most of the stations with some observed regional differences, (2) The decreasing trends are largest over the Eastern Anatolia, the Marmara regions and along the Mediterranean coastline. The meteorological stations located in the continental northeast and the easternmost parts of the Anatolian Peninsula, including Ardahan, Iǧdır and Van, show a negative linear trend with a rate of four days per decade, (3) As in other regions of the Earth, changes in number of frost days are very likely associated with changes in minimum air temperatures and increasing growing season lengths in Turkey, (4) The decreasing trends in number of frost days also indicated considerable decadal‐scale variability. This variability is very likely attributable to the large‐scale atmospheric circulation and atmospheric oscillations such as the Arctic Oscillation (AO) or North Atlantic Oscillation (NAO) and the North Sea‐Caspian Pattern, (5) Consequently, the long‐winter (DJFM) composites of number of frost days were examined for extreme phases of the AO index during the period 1950–2010 in order to assess the influence of atmospheric oscillations on year‐to‐year variability in number of frost days. According to the Cramer's tk test, winter number of frost days tended to increase significantly during the high (positive) index AO phase, while they tended to decrease significantly during the low (negative) index AO phase. These relationships are statistically significant at the 1% level at the majority of stations. Copyright © 2011 Royal Meteorological Society
Morphology of the human vertebral endplate
Authors: Rodriguez Azucena G. , Rodriguez‐Soto Ana E. , Burghardt Andrew J. , Berven Sigurd , Majumdar Sharmila , Lotz Jeffrey C.
Published: August 2011

It is presumed that poor intervertebral disc cell nutrition is a contributing factor in degeneration, and is exacerbated by vertebral endplate sclerosis. Yet, quantitative relationships between endplate morphology and degeneration are unavailable. We investigated how endplate bone microstructure relates to indices of disc degeneration, such as morphologic grade, proteoglycan content, and cell density. Intervertebral core samples [n = 96, 14 subjects, L1–L5 level, ages 35–85 (64 ± 16 years), degeneration grade 1 (n = 4), grade 2 (n = 32), grade 3 (n = 44), grade 4 (n = 10), grade 5 (n = 6)] that included subchondral bone, cartilage endplate, and adjacent nucleus were harvested from human cadaveric lumbar spines. The morphology of the vertebral endplate was analyzed using µCT and the adjacent nucleus tissue was collected for biochemical and cellular analyses. Relationships between vertebral endplate morphology and adjacent disc degeneration were analyzed. Contrary to the prevailing notion, vertebral endplate porosity increased between 50% and 130% and trabecular thickness decreased by between 20% and 50% with advancing disc degeneration (p < 0.05). We also observed that nucleus cell density increased (R2 = 0.33, p < 0.05) and proteoglycan content decreased (R2 = 0.47, p < 0.05) as the endplate became more porous. Our data suggest that endplate sclerosis is not a fundamental factor contributing to disc degeneration. Rather, the opposite was observed in our samples, as the endplate became progressively more porous with age and degeneration. Since ischemic disc cell behavior is commonly associated with degenerative change, this may be related to other factors such as the quality of vertebral capillaries, as opposed to decreased permeability of intervening tissues. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:280–287, 2012
Patients with patellofemoral pain exhibit elevated bone metabolic activity at the patellofemoral joint
Authors: Draper Christine E. , Fredericson Michael , Gold Garry E. , Besier Thor F. , Delp Scott L. , Beaupre Gary S. , Quon Andrew
Published: August 2011

Patellofemoral pain is characterized by pain behind the kneecap and is often thought to be due to high stress at the patellofemoral joint. While we cannot measure bone stress in vivo, we can visualize bone metabolic activity using 18F NaF PET/CT, which may be related to bone stress. Our goals were to use 18F NaF PET/CT to evaluate whether subjects with patellofemoral pain exhibit elevated bone metabolic activity and to determine whether bone metabolic activity correlates with pain intensity. We examined 20 subjects diagnosed with patellofemoral pain. All subjects received an 18F NaF PET/CT scan of their knees. Uptake of 18F NaF in the patella and trochlea was quantified by computing the standardized uptake value and normalizing by the background tracer uptake in bone. We detected increased tracer uptake in 85% of the painful knees examined. We found that the painful knees exhibited increased tracer uptake compared to the pain‐free knees of four subjects with unilateral pain (P = 0.0006). We also found a correlation between increasing tracer uptake and increasing pain intensity (r2 = 0.55; P = 0.0005). The implication of these results is that patellofemoral pain may be related to bone metabolic activity at the patellofemoral joint. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 30:209–213, 2012
Evaluation of copper–1,3,5‐benzenetricarboxylate metal–organic framework (Cu‐MOF) as a selective sorbent for Lewis‐base analytes
Authors: Harvey Scott D. , Eckberg Alison D. , Thallapally Praveen K.
Published: August 2011

The metal–organic framework copper–1,3,5‐benzenetricarboxylate (Cu‐BTC) was evaluated for its ability to selectively interact with Lewis‐base analytes by examining retention on gas‐chromatographic columns packed with Chromosorb W HP that contained 3.0% SE‐30 along with various loadings of Cu‐BTC. Scanning electron microscopy images of the support material showed the characteristic Cu‐BTC crystals embedded in the SE‐30 coating on the diatomaceous support. The results indicated that the Cu‐BTC‐containing stationary phase had limited thermal stability (220°C) and strong general retention for analytes. Kováts index calculations showed selective retention (amounting to about 300 Kováts units) relative to n‐alkanes for many small Lewis‐base analytes on a column that contained 0.75% Cu‐BTC compared with an SE‐30 control. Short columns that contained lower loadings of Cu‐BTC (0.10%) allowed elution of nitroaromatics; however, selectivity was not observed for aromatic compounds (including nitroaromatics) or nitroalkanes. Observed retention characteristics are discussed.
Preparative separation of minor saponins from Platycodi Radix by high‐speed counter‐current chromatography
Authors: Ha In J. , Kang Minseok , Na Yun C. , Park Youmie , Kim Yeong S.
Published: August 2011

Platycosides (PSs), the saponins found in the root of Platycodon grandiflorum (Jacq.) A. DC. (Platycodi Radix), are typically composed of oleanene backbones with two side chains; one is a 3‐O‐glucose linked by a glycosidic bond, and the other is a 28‐O‐arabinose‐rhamnose‐xylose‐apiose linked by an ester bond. Minor saponins, acetylated isomers of the major saponin on either the 2″ or 3″ position of rhamnose, were isolated from Platycodi Radix using a multi‐step process including high‐speed counter‐current chromatography (HSCCC) and preparative reversed‐phase high‐performance liquid chromatography (RP‐HPLC). After the separation of the major components, the enriched minor saponin fraction was used for this study. A two‐phase solvent system consisting of chloroform–methanol–isopropanol–water (3:2:2:3, v/v) was used for HSCCC. HSCCC separation of the enriched minor saponin fraction yielded 2″‐O‐acetylplatycodin D, 3″‐O‐acetylpolygalacin D, 2″‐O‐acetylpolygalacin and a mixture of 3″‐O‐acetylplatycodin D and polygalacin D. The mixture fraction from HSCCC separation was further purified by preparative RP‐HPLC, giving 3″‐O‐acetylplatycodin D and polygalacin D at a purity of over 98.9%. The developed method provides the preparative and rapid separation of minor saponins in the crude extract of Platycodi Radix. To the best of our knowledge, this is the first on the separation of acetylated PSs by HSCCC.
Molecularly imprinted polymer microspheres for solid‐phase extraction of protocatechuic acid in Rhizoma homalomenae
Authors: Chen Fang‐Fang , Wang Guo‐Ying , Shi Yan‐Ping
Published: August 2011

Molecularly imprinted polymers (MIPs) had been prepared by precipitation polymerization method using acrylamide as the functional monomer, ethylene glycol dimethacrylate as the cross‐linker, acetonitrile as the porogen solvent and protocatechuic acid (PA), one of phenolic acids, as the template molecule. The MIPs were characterized by scanning electron microscopy and Fourier transform infrared, and their performance relative to non‐imprinted polymers was assessed by equilibrium binding experiments. Six structurally similar phenolic acids, including p‐hydroxybenzoic acid, gallic acid, salicylic acid, syringic acid, vanillic acid, ferulic acid were selected to assess the selectivity and recognition capability of the MIPs. The MIPs were applied to extract PA from the traditional Chinese medicines as a solid‐phase extraction sorbent. The resultant cartridge showed that the MIPs have a good extraction performance and were able to selectively extract almost 82% of PA from the extract of Rhizoma homalomenae. Thus, the proposed molecularly imprinted‐solid phase extraction‐high performance liquid chromatography method can be successfully used to extract and analyse PA in traditional Chinese medicines.
A characterization of retracts in certain Fraïssé limits
Authors: Dolinka Igor
Published: August 2011

Assuming certain conditions on a class \documentclass{article}\usepackage{amssymb,amsmath,mathrsfs}\begin{document}\pagestyle{empty}$\mathscr{C}$\end{document} of finitely generated first‐order structures admitting the model‐theoretical construction of a Fraïssé limit, we characterize retracts of such limits as algebraically closed structures in a class naturally related to \documentclass{article}\usepackage{amssymb,amsmath,mathrsfs}\begin{document}\pagestyle{empty}$\mathscr{C}$\end{document}. In this way we generalize an earlier description of retracts of the countably infinite random graph.
The PLA2G6 gene in early‐onset Parkinson's disease
Authors: Kauther Kai Michael , Höft Christine , Rissling Ida , Oertel Wolfgang H. , Möller Jens Carsten
Published: August 2011

Background:

The definite etiology of neurodegenerative disorders such as Parkinson's disease (PD) is still unknown. Because of its role in the generation of reactive oxygen species and its association with neurodegeneration with brain iron accumulation, a possible involvement of calcium‐independent group VI phospholipase A2 (iPLA2‐VI) in the pathogenesis of PD has been proposed.

Methods:

In this study we analyzed all 17 exons of the PLA2G6 gene encoding iPLA2‐VI in a group of 102 discordant pairs with early‐onset Parkinson's disease (EOPD) and an additional sample of 166 EOPD patients and 155 unrelated controls.

Results:

The nonsynonymous single‐nucleotide polymorphisms (SNPs) 2339A>G (n = 2) and 2341G>A (n = 1) in 2 neighboring codons were found in 3 patients with typical L‐dopa‐responsive sporadic EOPD and in none of our controls, indicating a possible role of PLA2G6 in the pathogenesis of EOPD in rare cases.

Conclusions:

Future studies should investigate the prevalence of these SNPs in other PD populations and larger control groups and also address possible genetic alterations in the remaining parts of the PLA2G6 gene. © 2011 Movement Disorder Society
The Importance of Descriptor‐Based Clusterization in QSAR Models Development: Tyrosine Kinases Inhibitors as a Key Study
Authors: Marzaro Giovanni , Tonus Francesca , Brun Paola , Castagliuolo Ignazio , Guiotto Adriano , Chilin Adriana
Published: August 2011

Quantitative Structure Activity Relationship (QSAR) is a well known cheminformatic tool for the discovery of novel biologically active compounds. However, when large and heterogeneous datasets are mined, it is not possible to derive a QSAR equation able to predict in a satisfactory manner the activity of the compounds. Thus, QSAR models are often inadequate for virtual screening purpose. Herein we present a novel approach to multitarget classification QSAR models, useful to assess the selectivity profile of the tyrosine kinases inhibitors. A descriptor‐based clusterization process was employed, that allowed the generation of models with high accuracies and independent from the chemical classification of the compounds (i.e. from the scaffold type). The herein proposed methodology can lead to QSAR models useful for virtual screening processes.
Mass spectrometry‐based quantification of myocardial protein adducts with acrolein in an in vivo model of oxidative stress
Authors: Wu Jianyong , Stevens Jan F. , Maier Claudia S.
Published: August 2011

Acrolein (ACR) exposure leads to the formation of protein–ACR adducts. Protein modification by ACR has been associated with various chronic diseases including cardiovascular and neurodegenerative diseases. Here, we report an analytical strategy that enables the quantification of Michael‐type protein adducts of ACR in mitochondrial proteome samples using liquid chromatography in combination with tandem mass spectrometry and selected ion monitoring (LC‐MS/MS SRM) analysis. Our approach combines site‐specific identification and relative quantification at the peptide level of protein–ACR adducts in relation to the unmodified protein thiol pool. Treatment of 3‐month‐old rats with CCl4, an established in vivo model of acute oxidative stress, resulted in significant increases in the ratios of distinct ACR‐adducted peptides to the corresponding unmodified thiol‐peptides obtained from proteins that were isolated from cardiac mitochondria. The mitochondrial proteins that were found adducted by ACR were malate dehydrogenase, NADH dehydrogenase [ubiquinone] flavoprotein 1, cytochrome c oxidase subunit VIb isoform 1, ATP synthase d chain, and ADP/ATP translocase 1. The findings indicate that protein modification by ACR has potential value as an index of mitochondrial oxidative stress.
The preemptive swapping problem on a tree
Authors: Anily Shoshana , Gendreau Michel , Laporte Gilbert
Published: August 2011

This article considers the swapping problem on a tree. In this problem at most one object of some type is available at each vertex, and each vertex also requests at most one object of a given type. The total demand and the total supply of each object type are identical. The problem is to determine a minimum cost routing plan starting and ending at a prespecified vertex which is the depot, for a single vehicle of unit capacity and m object types, so that all vertex requests are satisfied. We consider the preemptive mode in which objects may be temporarily dropped along the way. It is shown that this problem is NP‐hard. A heuristic with a worst‐case performance ratio of 1.5 is developed. Finally, it is shown that the case where m = 1 is polynomially solvable. © 2011 Wiley Periodicals, Inc. NETWORKS, 2011
Scheduling two chains of unit jobs on one machine: A polyhedral study
Authors: Arbib Claudio , Labbé Martine , Servilio Mara
Published: August 2011

We investigate polyhedral properties of the following scheduling problem: given two sets of unit, indivisible jobs and revenue functions of the jobs completion times, find a one‐machine schedule maximizing the total revenue under the constraint that the schedule of each job set respects a prescribed chain‐like precedence relation. A solution to this problem is an order preserving assignment of the jobs to a set of time‐slots. We study the convex hull of the feasible assignments and provide families of facet‐defining inequalities in two cases: (i) each job must be assigned to a time‐slot and (ii) a job does not need to be assigned to any time‐slot. © 2011 Wiley Periodicals, Inc. NETWORKS, 2011
Online traveling salesman problems with service flexibility
Authors: Jaillet Patrick , Lu Xin
Published: August 2011

The traveling salesman problem is a well‐known combinatorial optimization problem. We are concerned here with online versions of this problem defined on metric spaces. One novel aspect in this article is the introduction of a sound theoretical model to incorporate “yes‐no” decisions on which requests to serve, together with an online strategy to visit the accepted requests. To do so, we assume that there is a penalty for not serving a request. Requests for visit of points in the metric space are revealed over time to a server, initially at a given origin, who must decide in an online fashion which requests to serve to minimize the time to serve all accepted requests plus the sum of the penalties associated with the rejected requests. We first look at the special case of the non‐negative real line. After providing a polynomial time algorithm for the offline version of the problem, we propose and prove the optimality of a 2‐competitive polynomial time online algorithm based on reoptimization approaches. We also consider the impact of advanced information (lookahead) on this optimal competitive ratio. We then consider the generalizations of these results to the case of the real line. We show that the previous algorithm can be extended to an optimal 2‐competitive online algorithm. Finally we consider the case of a general metric space and propose an original c ‐competitive online algorithm, where
\documentclass{article}\usepackage{mathrsfs, amsmath, amsfonts, amssymb}\pagestyle{empty}\begin{document} $c = \sqrt{({17+5})}/{4} \approx 2.28$ \end{document}. We also give a polynomial‐time (1.5ρ + 1) ‐competitive online algorithm which uses a polynomial‐time ρ ‐approximation for the offline problem. © 2011 Wiley Periodicals, Inc. NETWORKS, 2011
Collection and storage of human blood and adipose for genomic analysis of clinical samples
Authors: Cashion Ann K. , Umberger Reba A. , Goodwin Shirlean B. , Sutter Thomas R.
Published: August 2011

In this methods article, we describe collection and storage of clinically acquired blood and adipose samples for transcript analysis in an ongoing study exploring obesity in renal transplant recipients. Total ribonucleic acid (RNA) was isolated from whole blood using the LeukoLOCK™ Total RNA Isolation System (n = 4), and comparisons between fresh and frozen samples were made. Abdominal subcutaneous adipose samples (n = 4) were obtained during kidney transplantation, flash frozen, and stored at −80°C. Adipose RNA was extracted using either the STAT‐60 method modified for lipids or Trizol plus RNeasy extraction. Affymetrix HG‐U133 plus 2.0 arrays and Affymetrix Human Gene 1.0 ST arrays were used for both blood and adipose transcriptome analysis. Purity, quality, and quantity of RNA were high with comparable results using both array platforms. © 2011 Wiley Periodicals, Inc. Res Nurs Health 34:408–418, 2011
HPLC Analysis of Oxindole Alkaloids in Uncaria Tomentosa: Sample Preparation and Analysis Optimisation by Factorial Design
Authors: Bertol Gustavo , Franco Luzia , de Oliveira Brás Heleno
Published: August 2011

Introduction

Uncaria tomentosa (“cat's claw”) is widely used for the treatment of some infectious and inflammatory diseases. Oxindole alkaloids are regarded as the most important components responsible for the biological activities attributed to the plant. Their analysis require efficient sample preparation and suitable reference standards but few are commercially available.

Objective

To develop and validate a HPLC analytical method for oxindole alkaloids in Uncaria tomentosa with emphasis on sample preparation.

Method

Factorial experimental designs were used for the optimisation of both sample preparation and chromatographic separation. The optimised sample preparation involved extraction with aqueous ethanol, and the granulometry of the powdered plant material significantly influenced extraction yields. Mitraphylline was used as a calibration reference for the determination of total alkaloids.

Results

The method was fully validated and showed good selectivity, linearity (r2 ≥ 0.9996), accuracy (≥ 96%) and precision (RSD < 2.4%). Detection and quantification limits for mitraphylline were 0.8 and 2.4 ppm, respectively.

Conclusion

The optimised chromatographic method, using organic buffer in the mobile phase, provided baseline separation of tetracyclic and pentacyclic alkaloids in the samples. Calibration using mitraphylline provided more accurate estimates of total alkaloid content when compared to other available reference alkaloids. Copyright © 2011 John Wiley & Sons, Ltd.
Resisting Everything except Temptation: Evidence and an Explanation for Domain–specific Impulsivity
Authors: Tsukayama Eli , Duckworth Angela Lee , Kim Betty
Published: August 2011

We propose a model of impulsivity that predicts both domain–general and domain–specific variance in behaviours that produce short–term gratification at the expense of long–term goals and standards. Specifically, we posit that domain–general impulsivity is explained by domain–general self–control strategies and resources, whereas domain–specific impulsivity is explained by how tempting individuals find various impulsive behaviours, and to a lesser extent, in perceptions of their long–term harm. Using a novel self–report measure, factor analyses produced six (non–exhaustive) domains of impulsive behaviour (Studies 1–2): work, interpersonal relationships, drugs, food, exercise and finances. Domain–general self–control explained 40% of the variance in domain–general impulsive behaviour between individuals, reffect = .71. Domain–specific temptation ( reffect = .83) and perceived harm ( reffect = −.26) explained 40% and 2% of the unique within–individual variance in impulsive behaviour, respectively (59% together). In Study 3, we recruited individuals in special interest groups (e.g. procrastinators) to confirm that individuals who are especially tempted by behaviours in their target domain are not likely to be more tempted in non–target domains. Copyright © 2011 John Wiley & Sons, Ltd.
A high intake of industrial or ruminant trans fatty acids does not affect the plasma proteome in healthy men
Authors: de Roos Baukje , Wanders Anne J. , Wood Sharon , Horgan Graham , Rucklige Garry , Reid Martin , Siebelink Els , Brouwer Ingeborg A.
Published: August 2011

Consumption of industrial trans fat raises the risk of cardiovascular disease, but it is unclear whether cis9,trans11‐conjugated linoleic acid (CLA) – a trans fatty acid in dairy products – modulates disease development. We investigated the effects of complete diets providing 7% of energy as industrial trans fat or cis9, trans11 CLA, compared with oleic acid, on regulation of plasma proteins in 12 healthy men. Diets were provided for 3 wk each, in random order. Plasma was collected at the end of each 3 wk intervention period, depleted of its 12 most abundant proteins and analyzed by 2‐DE. Principal component analysis of protein spot intensity values revealed that the nature of the dietary intervention did not significantly affect the plasma proteome. The intervention provided in the 1st period produced a significant treatment effect compared with the interventions provided in the other two periods, and there was a significant subject effect. In conclusion, the nature of an extreme dietary intervention, i.e. 7% of energy provided by industrial trans fat or cis9,trans11 CLA, did not markedly affect the plasma proteome. Thus plasma proteomics using 2‐DE appears, by and large, an unsuitable approach to detect regulation of plasma proteins due to changes in the diet.
Clinimetric properties of breath‐stacking technique for assessment of inspiratory capacity
Authors: de Sá Feitosa Larissa Andrade , Barbosa Paula Antas , Pessoa Maíra Floretino , Rodrigues‐Machado Maria da Glória , de Andrade Armèle Dornelas
Published: August 2011

Background and Purpose

Breath stacking (BS) is used as an alternative method for lung expansion therapy and the assessment of inspiratory capacity in uncooperative patients. The aims of the present study were to identify the reproducibility of the BS technique in healthy volunteers and to compare BS with conventional spirometry with regard to inspiratory capacity.

Methods

A cross‐sectional study was carried out. Eighty‐five healthy volunteers (21.78 ± 2.79 years; 41 men, 44 women) underwent spirometry and BS. Lung function, anthropometric and cardiopulmonary parameters were evaluated prior to the intervention. BS was performed with a unidirectional inspiratory valve by two different examiners. The order of each examiner was randomized. Spirometric tests were performed three times, and the BS manoeuvre was evaluated three times by each examiner. Respiratory rate, heart rate and peripheral arterial oxygen saturation were determined before, during and following the manoeuvre.

Results

There were no statistically significant differences in the intra‐examiner and inter‐examiner analyses for the volume mobilized during BS, respiratory rate, duration of BS manoeuvre or perceived effort index (p > 0.05). The intra‐class correlation coefficient was greater than 0.7 for all variables analysed. Maximal volumes achieved using the BS technique were significantly higher than those achieved with conventional spirometry (p < 0.0001).

Conclusion

Data from both the intra‐examiner and inter‐examiner analyses suggest that the BS technique is reproducible. This technique mobilizes greater lung volumes than conventional spirometry. Copyright © 2011 John Wiley & Sons, Ltd.
The X‐ray crystallographic structure and specificity profile of HAD superfamily phosphohydrolase BT1666: Comparison of paralogous functions in B. thetaiotaomicron
Authors: Lu Zhibing , Dunaway‐Mariano Debra , Allen Karen N.
Published: August 2011

Analysis of the haloalkanoate dehalogenase superfamily (HADSF) has uncovered homologues occurring within the same organism that are found to possess broad, overlapping substrate specificities, and low catalytic efficiencies. Here we compare the HADSF phosphatase BT1666 from Bacteroides thetaiotaomicron VPI‐5482 to a homologue with high sequence identity (40%) from the same organism BT4131, a known hexose‐phosphate phosphatase. The goal is to find whether these enzymes represent duplicated versus paralogous activities. The X‐ray crystal structure of BT1666 was determined to 1.82 Å resolution. Superposition of the BT1666 and BT4131 structures revealed a conserved fold and identical active sites suggestive of a common physiological substrate. The steady‐state kinetic constants for BT1666 were determined for a diverse panel of phosphorylated metabolites to define its substrate specificity profile and overall level of catalytic efficiency. Whereas BT1666 and BT4131 are both promiscuous, their substrate specificity profiles are distinct. The catalytic efficiency of BT1666 (kcat/Km = 4.4 × 102M−1 s−1 for the best substrate fructose 1,6‐(bis)phosphate) is an order of magnitude less than that of BT4131 (kcat/Km = 6.7 × 103M−1 s−1 for 2‐deoxyglucose 6‐phosphate). The seemingly identical active‐site structures point to sequence variation outside the active site causing differences in conformational dynamics or subtle catalytic positioning effects that drive the divergence in catalytic efficiency and selectivity. The overlapping substrate profiles may be understood in terms of differential regulation of expression of the two enzymes or a conferred advantage in metabolic housekeeping functions by having a larger range of possible metabolites as substrates. Proteins 2011;. © 2011 Wiley‐Liss, Inc.
The structure, molecular dynamics, and energetics of centrin–melittin complex
Authors: Sosa Liliana del Valle , Alfaro Elisa , Santiago Jorge , Narváez Daniel , Rosado Marie Cely , Rodríguez Aslin , Gómez Ana María , Schreiter Eric R. , Pastrana‐Ríos Belinda
Published: August 2011

Centrin is a calcium binding protein (CaBP) belonging to the EF‐hand superfamily. As with other proteins within this family, centrin is a calcium sensor with multiple biological target proteins. We chose to study Chlamydomonas reinhardtii centrin (Crcen) and its interaction with melittin (MLT) as a model for CaBP complexes due to its amphipathic properties. Our goal was to determine the molecular interactions that lead to centrin–MLT complex formation, their relative stability, and the conformational changes associated with the interaction, when compared to the single components. For this, we determined the thermodynamic parameters that define Crcen–MLT complex formation. Two‐dimensional infrared (2D IR) correlation spectroscopy were used to study the amide I′, I′*, and side chain bands for 13C‐Crcen, MLT, and the 13C‐Crcen–MLT complex. This approach resulted in the determination of MLT's increased helicity, while centrin was stabilized within the complex. Herein we provide the first complete molecular description of centrin–MLT complex formation and the dissociation process. Also, discussed is the first structure of a CaBP–MLT complex by X‐ray crystallography, which shows that MLT has a different binding orientation than previously characterized centrin‐bound peptides. Finally, all of the experimental results presented herein are consistent with centrin maintaining an extended conformation while interacting with MLT. The molecular implications of these results are: (1) the recognition of hydrophobic contacts as requirements for initial binding, (2) minimum electrostatic interactions within the C‐terminal end of the peptide, and (3) van der Waals interactions within MLTs N‐terminal end are required for complex formation. Proteins 2011; © 2011 Wiley‐Liss, Inc.
Elastic network model‐based normal mode analysis reveals the conformational couplings in the tripartite AcrAB‐TolC multidrug efflux complex
Authors: Wang Beibei , Weng Jingwei , Fan Kangnian , Wang Wenning
Published: August 2011

The AcrAB‐TolC drug efflux system, energized by proton movement down the transmembrane electrochemical gradient, is responsible for the resistance of the organism to a wide range of drugs. Experimental data suggest functional roles of each part of the assembly, but the detailed working mechanism of this machinery remains elusive. We used elastic network‐based normal mode analysis (NMA) to explore the conformational dynamics of the AcrAB‐TolC complex. The intrinsic flexibilities of the pore domain in AcrB monomer conform to the previously proposed three‐step functionally rotating mechanism for asymmetric AcrB trimer. Conformational couplings across monomers in the AcrB trimer were observed, and the coupling between the transmembrane domain and the other parts of AcrB are strengthened through trimeric assembly. In the tripartite AcrAB‐TolC assembly obtained through molecular docking, concerted motions were observed not only at the direct contact interfaces between various components but also between distant parts of the whole complex. The presence of AcrA was shown to significantly strengthen the motional couplings between AcrB and TolC. Overall, NMA revealed an allosteric network in the AcAB‐TolC efflux system, which provides hints to our understanding of its detailed working mechanism. Proteins 2011; © 2011 Wiley‐Liss, Inc.
Phosphorylation alters backbone conformational preferences of serine and threonine peptides
Authors: Kim Su‐Yeon , Jung Youngae , Hwang Geum‐Sook , Han Hogyu , Cho Minhaeng
Published: August 2011

Despite the notion that a control of protein function by phosphorylation works mainly by inducing its conformational changes, the phosphorylation effects on even small peptide conformation have not been fully understood yet. To study its possible effects on serine and threonine peptide conformations, we recently carried out pH‐ and temperature‐dependent circular dichroism (CD) as well as 1H NMR studies of the phosphorylated serine and threonine peptides and compared them with their unphosphorylated analogs. In the present article, by performing the self‐consistent singular value decomposition analysis of the temperature‐dependent CD spectra and by analyzing the 3J(HN,Hα) coupling constants extracted from the NMR spectra, the populations of the polyproline II (PPII) and β‐strand conformers of the phosphorylated Ser and Thr peptides are determined. As temperature is increased, the β‐strand populations of both phosphorylated serine and threonine peptides increase. However, the dependences of PPII/β‐strand population ratio on pH are different for these two cases. The phosphorylation of the serine peptide enhances the PPII propensity, whereas that of the threonine peptide has the opposite effect. This suggests that the serine and threonine phosphorylations can alter the backbone conformational propensity via direct but selective intramolecular hydrogen‐bonding interactions with the peptide NH groups. This clearly indicates that the phosphoryl group actively participates in modulating the peptide backbone conformations. Proteins 2011; © 2011 Wiley‐Liss, Inc.
Effects of the Val211Gly substitution on molecular dynamics of the CMY‐2 cephalosporinase: Implications on hydrolysis of expanded‐spectrum cephalosporins
Authors: Kotsakis Stathis D. , Tzouvelekis Leonidas S. , Petinaki Efthymia , Tzelepi Eva , Miriagou Vivi
Published: August 2011

CMY‐30, a naturally occurring class C β‐lactamase differing from the Citrobacter freundii‐derived CMY‐2 by a Val211Gly substitution in the Ω‐loop, exhibits increased hydrolytic efficiency against ceftazidime and cefotaxime. Kinetic constants of CMY‐2 and CMY‐30 against the latter substrates suggested that the improved efficiency of the Gly211 variant was due to an increase in kcat. The structural basis of the increased turn‐over rates of oxyimino‐cephalosporins caused by Val211Gly was studied using 5 ns molecular dynamics simulations of CMY‐2 and CMY‐30 in their free forms and in covalent complexes with ceftazidime (acyl‐enzyme) as well as a boronic acid analogue of ceftazidime (deacylation transition state). Analysis of thermal factors indicated that Val211Gly increased the flexibility of the Ω‐loop/H7‐helix and the Q120‐loop formed by amino acids 112–125, and also altered the vibrations of the H10‐helix/R2‐loop. Structural elements containing the catalytic residues remained relatively rigid except Tyr150 in acyl‐enzyme species. Regions exhibiting altered flexibility due to the substitution appear to move in a concerted manner in both enzymes. This movement was more intense in CMY‐30 and also at directions different to those observed for CMY‐2. Additionally, it appeared that the Val211Gly increased the available space for the accommodation of the R1 side chain of ceftazidime. These findings are likely associated with the significantly increased vibrations of the bound compounds observed in CMY‐30 complexes. Therefore, the extended spectrum properties of CMY‐30 seem to arise through a complex process implicating changes in protein movement and in the mode of substrate accommodation. Proteins 2011;. © 2011 Wiley‐Liss, Inc.
Mycobacterium tuberculosis Rv0899 defines a family of membrane proteins widespread in nitrogen‐fixing bacteria
Authors: Marassi Francesca M.
Published: August 2011

The Mycobacterium tuberculosis membrane protein Rv0899 confers adaptation of the bacterium to acidic environments. Due to strong sequence homology of its C‐terminus to bacterial OmpA‐like domains, Rv0899 has been proposed to constitute an outer membrane porin of M. tuberculosis. However, OmpA‐like domains are widespread in a wide variety of bacterial proteins with different functions. Furthermore, the three‐dimensional structure of Rv0899 does not contain a transmembrane β‐barrel, and recent evidence demonstrates that it does not have porin activity. Instead, the rv0899 gene is part of an operon (rv0899‐rv0901) that is required for fast ammonia secretion, pH neutralization, and growth of M. tuberculosis in acidic environments. The mechanism whereby these functions are accomplished is not known. To gain further functional insights, a targeted search of the genomic databases was performed for proteins with sequence similarity beyond the OmpA‐like C‐terminus. The results presented here, show that Rv0899‐like proteins are widespread in bacteria with functions in nitrogen metabolism, adaptation to nutrient poor environments, and/or establishing symbiosis with the host organism, and appear to form a protein family. These findings suggest that M. tuberculosis Rv0899 may also assist similar processes and lend further support to its role in ammonia secretion and M. tuberculosis adaptation to the host environment. Proteins 2011; © 2011 Wiley‐Liss, Inc.
Inhibition of α‐synuclein aggregation by small heat shock proteins
Authors: Bruinsma Ilona B. , Bruggink Kim A. , Kinast Karsten , Versleijen Alexandra A. M. , Segers‐Nolten Ine M. J. , Subramaniam Vinod , Bea Kuiperij H. , Boelens Wilbert , de Waal Robert M. W. , Verbeek Marcel M.
Published: August 2011

The fibrillization of α‐synuclein (α‐syn) is a key event in the pathogenesis of α‐synucleinopathies. Mutant α‐syn (A53T, A30P, or E46K), each linked to familial Parkinson's disease, has altered aggregation properties, fibril morphologies, and fibrillization kinetics. Besides α‐syn, Lewy bodies also contain several associated proteins including small heat shock proteins (sHsps). Since α‐syn accumulates intracellularly, molecular chaperones like sHsps may regulate α‐syn folding and aggregation. Therefore, we investigated if the sHsps αB‐crystallin, Hsp27, Hsp20, HspB8, and HspB2B3 bind to α‐syn and affect α‐syn aggregation. We demonstrate that all sHsps bind to the various α‐syns, although the binding kinetics suggests a weak and transient interaction only. Despite this transient interaction, the various sHsps inhibited mature α‐syn fibril formation as shown by a Thioflavin T assay and atomic force microscopy. Interestingly, HspB8 was the most potent sHsp in inhibiting mature fibril formation of both wild‐type and mutant α‐syn. In conclusion, sHsps may regulate α‐syn aggregation and, therefore, optimization of the interaction between sHsps and α‐syn may be an interesting target for therapeutic intervention in the pathogenesis of α‐synucleinopathies. Proteins 2011; © 2011 Wiley‐Liss, Inc.
Simulation of the β‐ to α‐sheet transition results in a twisted sheet for antiparallel and an α‐nanotube for parallel strands: Implications for amyloid formation
Authors: Hayward Steven , James Milner‐White E.
Published: August 2011

α‐sheet has been proposed to be the main constituent of the toxic amyloid intermediate. Molecular dynamics simulations on proteins known to be involved in amyloid diseases have demonstrated that β‐sheet can, under certain conditions, spontaneously convert to α‐sheet via ββ→αRαL peptide‐plane flipping. Using torsion‐angle driving to simulate this flip the transition has been investigated for parallel and antiparallel sheets. Concerted and sequential flipping processes were simulated, the former allowing direct calculation of helical parameters. For antiparallel sheet, the strands tend to splay apart during the transition. This can be understood by consideration of the geometry of repeating dipeptide conformations. At the end of the transition antiparallel α‐sheet is slightly twisted, comprising gently curving strands. In parallel sheet, the strands maintain identical conformations and stay hydrogen bonded during the transition as they curl up to suggest a hitherto unseen structure, the multi‐helix α‐nanotube. Intriguingly, the α‐nanotube has some of the characteristics of the parallel β‐helix, a single‐helix structure also implicated in amyloid. Unlike the β‐helix, α‐nanotube formation could involve identical strands aligning with each other in register as in most amyloids. Proteins 2011;. © 2011 Wiley‐Liss, Inc.
Molecular dynamics modeling of tubulin C‐terminal tail interactions with the microtubule surface
Authors: Freedman Holly , Luchko Tyler , Luduena Richard F. , Tuszynski Jack A.
Published: August 2011

Tubulin, an α/β heterodimer, has had most of its 3D structure analyzed; however, the carboxy (C)‐termini remain elusive. Importantly, the C‐termini play critical roles in regulating microtubule structure and function. They are sites of most of the post‐translational modifications of tubulin and interaction sites with molecular motors and microtubule‐associated proteins. Simulated annealing was used in our molecular dynamics modeling to predict the interactions of the C‐terminal tails with the tubulin dimer. We examined differences in their flexibility, interactions with the body of tubulin, and the existence of structural motifs. We found that the α‐tubulin tail interacts with the H11 helix of β‐tubulin, and the β‐tubulin tail interacts with the H11 helix of α‐tubulin. Tail domains and H10/B9 loops interact with each other and compete for interactions with positively‐charged residues of the H11 helix on the neighboring monomer. In a simulation in which α‐tubulin's H10/B9 loop switches on sub‐nanosecond intervals between interactions with the C‐terminal tail of α‐tubulin and the H11 helix of β‐tubulin, the intermediate domain of α‐tubulin showed more fluctuations compared to those in the other simulations, indicating that tail domains may cause shifts in the position of this domain. This suggests that C‐termini may affect the conformation of the tubulin dimer which may explain their essential function in microtubule formation and effects on ligand binding to microtubules. Our modeling also provides evidence for a disordered‐helical/helical double‐state system of the T3/H3 region of the microtubule, which could be linked to depolymerization following GTP hydrolysis. Proteins 2011; © 2011 Wiley‐Liss, Inc.
A spin‐calorics device based on La0.7Sr0.3MnO3/SrRuO3 superlattices
Authors: Ziese M.
Published: August 2011

High quality La0.7Sr0.3MnO3/SrRuO3 superlattices with ultrathin individual layers were grown by pulsed laser deposition and were studied by magnetometry and magnetoresistance measurements. Depending on layer thickness and structural quality, exchange biasing could be observed both in magnetization and magnetotransport. In this regime the superlattice magnetization forms an exchange spring that leads to a reversible field dependence of the magnetoresistance and the magnetic work. It is shown that the magnetic work and the magnetocaloric effect can be tuned by the SrRuO3 layer thickness. This opens up the possibility of fabricating spin‐caloric devices from wedge‐shaped superlattices with self‐sustaining Seebeck effect. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
An arrayed nanoantenna for broadband light emission and detection
Authors: Miroshnichenko Andrey E. , Maksymov Ivan S. , Davoyan Arthur R. , Simovski Constantin , Belov Pavel , Kivshar Yuri S.
Published: August 2011

We suggest a broadband optical unidirectional arrayed nanoantenna consisting of equally spaced nanorods of gradually varying length. Each nanorod can be driven by near‐field quantum emitters radiating at different frequencies or, according to the reciprocity principle, by an incident light at the same frequency. Broadband unidirectional emission and reception characteristics of the nanoantenna open up novel opportunities for subwavelength light manipulation and quantum communication, as well as for enhancing the performance of photoactive devices such as photovoltaic detectors, light‐emitting diodes, and solar cells. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Verification of objective sensitivity climatologies of Mediterranean intense cyclones: test against human judgement
Authors: Garcies L. , Homar V.
Published: August 2011

A variety of sensitivity climatologies of Mediterranean intense cyclones have been recently built owing to the growing international interest in contributing to the basic understanding and the short‐range forecasting of high‐impact weather events. The verification of these climatologies is essential to ensure the reliability of the sensitivity products and ultimately provide robust guidance to policy‐makers on plans to redefine routine observational strategies. This work tackles the arduous task of verifying the available (an adjoint‐based and two different ensemble‐based) sensitivity climatologies of Mediterranean intense cyclones. We perform Observing System Simulation Experiments (OSSE) with the WRF ARW model for 25 of the most intense Mediterranean cyclones detected in the ERA‐40 database to test the ability of each method in identifying areas where perturbations in the initial conditions derived from the sensitivity fields lead to a greater impact on the forecast of intense cyclones. For the sake of a sensible reference, the performance of the available sensitivity climatologies is tested against the judgement of an experienced severe weather meteorologist. In addition, a control measure of the background random response is also carried out. The impact on the prediction of intense Mediterranean cyclones of prescribed perturbations to the initial conditions is evaluated comparing each perturbed experiment with a control simulation. Furthermore, a quantitative study of the linearity of the evolution of the perturbations is performed using twin perturbations. Results confirm a statistically significant superior skill of the human and adjoint sensitivity fields against both ensemble sensitivity climatologies. Climatological ensemble sensitivities only show a noticeable improvement upon non‐sensitivity experiments when an ad hoc classification of cyclones is used. This reveals one fundamental limitation of the ensemble sensitivity technique in climatological mode when it is applied to rare events insufficiently sampled in the available datasets. Copyright © 2011 Royal Meteorological Society
Modified dynamic anti‐windup through deferral of activation
Authors: Sajjadi‐Kia Solmaz , Jabbari Faryar
Published: August 2011

We consider the dynamic anti‐windup design problem for linear systems with saturating actuators. The basic idea proposed here is to apply anti‐windup only when the performance of saturated system faces substantial degradation. We provide synthesis LMIs to obtain the gains of the dynamic anti‐windup compensator in a structure that delays the activation of the anti‐windup. Benefits of the proposed design method over the immediate activation of the anti‐windup are demonstrated using a well‐known example. Copyright © 2011 John Wiley & Sons, Ltd.
Robust H ∞  control of discrete‐time Markovian jump systems in the presence of incomplete knowledge of transition probabilities and saturating actuator
Authors: Wang Yijing , Sun Yunna , Zuo Zhiqiang , Chen Michael Z.Q.
Published: August 2011

This paper deals with the problem of robust H ∞  control for a class of discrete‐time Markovian jump systems subject to both actuator saturation and incomplete knowledge of transition probability. Different from the previous results where the transition probability is completely known, a more general situation where only partial information on the exact values of elements in transition probability matrix is considered. By introducing some free parameters to express the relationship for the known and the unknown elements of transition probability matrix in stability analysis, a criterion is established to guarantee the stochastic stability of the closed‐loop system as well as an H ∞  performance index. The concept of domain of attraction in mean square sense is used to analyze the closed‐loop stability, and the mode‐dependent H ∞  state‐feedback controller is designed. It is shown that, even in the absence of actuator saturation, the obtained result is less conservative than the existing one. A numerical example is provided to illustrate the effectiveness of the proposed method. Copyright © 2011 John Wiley & Sons, Ltd.