bluuebunny/crossref_metadata_2025 huggingface dataset:
A microwell array device with integrated microfluidic components for enhanced single‐cell analysis
Authors: Lindström Sara , Mori Kiichiroh , Ohashi Toshiro , Andersson‐Svahn Helene
Published: November 2009

Increasing awareness of the importance of cell heterogeneity in many biological and medical contexts is prompting increasing interest in systems that allow single‐cell analysis rather than conventional bulk analysis (which provides average values for variables of interest from large numbers of cells). Recently, we presented a microwell chip for long‐term, high‐throughput single‐cell analysis. The chip has proved to be useful for purposes such as screening individual cancer and stem cells for protein/gene markers. However, liquids in the wells can only be added or changed by manually rinsing the chip, or parts of it. This procedure has several well‐known drawbacks – including risks of cross‐contamination, large dead volumes and laboriousness – but there have been few previous attempts to integrate liquid rinsing/switching channels in “ready‐to‐use” systems for single‐cell analysis. Here we present a microwell system designed (using flow simulations) for single‐cell analysis with integrated microfluidic components (microchannels, magnetically driven micropumps and reservoirs) for supplying the cell culture wells with reagents, or rinsing, thus facilitating controlled, directed liquid handling. It can be used totally independently, since tubing is not essential. The practical utility of the integrated system has been demonstrated by culturing endothelial cells in the microwells, and successfully applying live‐cell Calcein AM staining. Systems such as this combining high‐density microwell chips with microfluidic components have great potential in numerous screening applications, such as exploring the important, but frequently undetected, heterogeneity in drug responses among individual cells.
Traumatic events, posttraumatic stress symptomatology and somatoform symptoms in eating disorder patients
Authors: Tagay Sefik , Schlegl Sandra , Senf Wolfgang
Published: November 2009

Objective

The central aim of the study was to assess the frequency of traumatic events and comorbid posttraumatic stress disorder (PTSD) in women with eating disorders (EDs). In addition, the frequency of somatoform complaints was investigated in patients with PTSD compared to those without PTSD.

Method

101 ED patients (26.4 years, SD = 7.4) from an outpatient department were investigated by means of standardized questionnaires.

Results

63.3% of the anorexic and 57.7% of the bulimic patients had experienced at least one trauma in their life. 10% of the anorexic and 14.1% of the bulimic patients fulfilled the study definition for a current diagnosis of PTSD. Patients with a comorbid PTSD reported somatoform symptoms more frequently than patients without PTSD (p < 0.001).

Discussion

These findings provide additional support for the association between somatization and PTSD in ED patients. In addition, clinical interventions for traumatized ED patients may benefit from a focus on posttraumatic stress symptomatology. Copyright © 2009 John Wiley & Sons, Ltd and Eating Disorders Association.
Multistage analysis strategies for genome‐wide association studies: summary of group 3 contributions to Genetic Analysis Workshop 16
Authors: Neuman Rosalind J. , Sung Yun Ju
Published: November 2009

This contribution summarizes the work done by six independent teams of investigators to identify the genetic and non‐genetic variants that work together or independently to predispose to disease. The theme addressed in these studies is multistage strategies in the context of genome‐wide association studies (GWAS). The work performed comes from Group 3 of the Genetic Analysis Workshop 16 held in St. Louis, Missouri in September 2008. These six studies represent a diversity of multistage methods of which five are applied to the North American Rheumatoid Arthritis Consortium rheumatoid arthritis case‐control data, and one method is applied to the low‐density lipoprotein phenotype in the Framingham Heart Study simulated data. In the first stage of analyses, the majority of studies used a variety of screening techniques to reduce the noise of single‐nucleotide polymorphisms purportedly not involved in the phenotype of interest. Three studies analyzed the data using penalized regression models, either LASSO or the elastic net. The main result was a reconfirmation of the involvement of variants in the HLA region on chromosome 6 with rheumatoid arthritis. The hope is that the intense computational methods highlighted in this group of papers will become useful tools in future GWAS.Genet. Epidemiol. 33 (Suppl. 1):S19–S23, 2009. © 2009 Wiley‐Liss, Inc.
Phenotype definition and development—contributions from Group 7
Authors: Wilcox Marsha A. , Paterson Andrew D.
Published: November 2009

The papers in Genetic Analysis Workshop 16 Group 7 covered a wide range of topics. The effects of confounder misclassification and selection bias on association results were examined by one group. Another focused on bias introduced by various methods of accounting for treatment effects. Two groups used related methods to derive phenotypic traits. They used different analytic strategies for genetic associations with non‐overlapping results (but because they used different sets of single‐nucleotide polymorphisms (SNPs) and significance criteria, this is not surprising). Another group relied on the well‐characterized definition of type 2 diabetes to show benefits of a novel predictive test. Transmission‐ratio distortion was the focus of another paper. The results were extended to show a potential secondary benefit of the test to identify potentially mis‐called SNPs. Genet. Epidemiol. 33 (Suppl. 1):S40–S44, 2009. © 2009 Wiley‐Liss, Inc.
Genome‐wide association studies: quality control and population‐based measures
Authors: Ziegler Andreas
Published: November 2009

Genome‐wide association studies, using hundreds of thousands of single‐nucleotide polymorphism (SNP) markers, have become a standard approach for identifying disease susceptibility genes. The change in the technology poses substantial computational and statistical challenges that have been addressed in the quality control, imputation, and population‐based measure groups of the Genetic Analysis Workshop 16. The computational challenges pertain to efficient memory management and computational speed of the statistical procedures, and we discuss an approach for efficient SNP storage. Accuracy and computational speed is relevant for genotype calling, and the results from a comparison of three calling algorithms are discussed. The first statistical challenge is related to statistical quality control, and we discuss two novel quality control procedures. These low‐level analyses have an effect on subsequent preparatory steps for high‐level analyses, e.g., the quality of genotype imputation approaches. After the conduct of a genome‐wide association study with successful replication and/or validation, measures of diagnostic accuracy, including the area under the curve, are investigated. The area under the curve can be constructed from summary data in some situations. Finally, we discuss how the population‐attributable risk of a genetic variant that is only measured in a reference data set can be determined. Genet. Epidemiol. 33 (Suppl. 1):S45–S50, 2009. © 2009 Wiley‐Liss, Inc.
Machine learning in genome‐wide association studies
Authors: Szymczak Silke , Biernacka Joanna M. , Cordell Heather J. , González‐Recio Oscar , König Inke R. , Zhang Heping , Sun Yan V.
Published: November 2009

Recently, genome‐wide association studies have substantially expanded our knowledge about genetic variants that influence the susceptibility to complex diseases. Although standard statistical tests for each single‐nucleotide polymorphism (SNP) separately are able to capture main genetic effects, different approaches are necessary to identify SNPs that influence disease risk jointly or in complex interactions. Experimental and simulated genome‐wide SNP data provided by the Genetic Analysis Workshop 16 afforded an opportunity to analyze the applicability and benefit of several machine learning methods. Penalized regression, ensemble methods, and network analyses resulted in several new findings while known and simulated genetic risk variants were also identified. In conclusion, machine learning approaches are promising complements to standard single‐and multi‐SNP analysis methods for understanding the overall genetic architecture of complex human diseases. However, because they are not optimized for genome‐wide SNP data, improved implementations and new variable selection procedures are required. Genet. Epidemiol. 33 (Suppl. 1):S51–S57, 2009. © 2009 Wiley‐Liss, Inc.
Inclusion of a priori information in genome‐wide association analysis
Authors: Tintle Nathan , Lantieri Francesca , Lebrec Jérémie , Sohns Melanie , Ballard David , Bickeböller Heike
Published: November 2009

Genome‐wide association studies (GWAS) continue to gain in popularity. To utilize the wealth of data created more effectively, a variety of methods have recently been proposed to include a priori information (e.g., biologically interpretable sets of genes, candidate gene information, or gene expression) in GWAS analysis. Six contributions to Genetic Analysis Workshop 16 Group 11 applied novel or recently proposed methods to GWAS of rheumatoid arthritis and heart disease related phenotypes. The results of these analyses were a variety of novel candidate genes and sets of genes, in addition to the validation of well‐known genotype‐phenotype associations. However, because many methods are relatively new, they would benefit from further methodological research to ensure that they maintain type I error rates while increasing power to find additional associations. When methods have been adapted from other study types (e.g., gene expression data analysis or linkage analysis), the lessons learned there should be used to guide implementation of techniques. Lastly, many open research questions exist concerning the logistic details of the origin of the a priori information and the way to incorporate it. Overall, our group has demonstrated a strong potential for identifying novel genotype‐phenotype relationships by including a priori data in the analysis of GWAS, while also uncovering a series of questions requiring further research. Genet. Epidemiol. 33 (Suppl. 1):S74–S80, 2009. © 2009 Wiley‐Liss, Inc.
Use of longitudinal data in genetic studies in the genome‐wide association studies era: summary of Group 14
Authors: Kerner Berit , North Kari E. , Fallin M. Daniele
Published: November 2009

Participants analyzed actual and simulated longitudinal data from the Framingham Heart Study for various metabolic and cardiovascular traits. The genetic information incorporated into these investigations ranged from selected single‐nucleotide polymorphisms to genome‐wide association arrays. Genotypes were incorporated using a broad range of methodological approaches including conditional logistic regression, linear mixed models, generalized estimating equations, linear growth curve estimation, growth modeling, growth mixture modeling, population attributable risk fraction based on survival functions under the proportional hazards models, and multivariate adaptive splines for the analysis of longitudinal data. The specific scientific questions addressed by these different approaches also varied, ranging from a more precise definition of the phenotype, bias reduction in control selection, estimation of effect sizes and genotype associated risk, to direct incorporation of genetic data into longitudinal modeling approaches and the exploration of population heterogeneity with regard to longitudinal trajectories. The group reached several overall conclusions: (1) The additional information provided by longitudinal data may be useful in genetic analyses. (2) The precision of the phenotype definition as well as control selection in nested designs may be improved, especially if traits demonstrate a trend over time or have strong age‐of‐onset effects. (3) Analyzing genetic data stratified for high‐risk subgroups defined by a unique development over time could be useful for the detection of rare mutations in common multifactorial diseases. (4) Estimation of the population impact of genomic risk variants could be more precise. The challenges and computational complexity demanded by genome‐wide single‐nucleotide polymorphism data were also discussed. Genet. Epidemiol. 33 (Suppl. 1):S93–S98, 2009. © 2009 Wiley‐Liss, Inc.
Summary of contributions to GAW Group 15: family‐based samples are useful in identifying common polymorphisms associated with complex traits
Authors: Knight Stacey , Uh Hae‐Won , Martinez Maria
Published: November 2009

Traditionally, family‐based samples have been used for genetic analyses of single‐gene traits caused by rare but highly penetrant risk variants. The utility of family‐based genetic data for analyzing common complex traits is unclear and contains numerous challenges. To assess the utility as well as to address these challenges, members of Genetic Analysis Workshop 16 Group 15 analyzed Framingham Heart Study data using family‐based designs ranging from parent—offspring trios to large pedigrees. We investigated different methods including traditional linkage tests, family‐based association tests, and population‐based tests that correct for relatedness between subjects, and tests to detect parent‐of‐origin effects. The analyses presented an assortment of positive findings. One contribution found increased power to detect epistatic effects through linkage using ascertainment of sibships based on extreme quantitative values or presence of disease associated with the quantitative value. Another contribution found four single‐nucleotide polymorphisms (SNPs) showing a maternal effect, two SNPs with an imprinting effect, and one SNP having both effects on a binary high blood pressure trait. Finally, three contributions illustrated the advantage of using population‐based methods to detect association to complex binary or quantitative traits. Our findings highlight the contribution of family‐based samples to the genetic dissection of complex traits. Genet. Epidemiol. 33 (Suppl. 1):S99–S104, 2009. © 2009 Wiley‐Liss, Inc.
Gene‐ or region‐based analysis of genome‐wide association studies
Authors: Beyene Joseph , Tritchler David , Asimit Jennifer L. , Hamid Jemila S.
Published: November 2009

With rapid advances in genotyping technologies in recent years and the growing number of available markers, genome‐wide association studies are emerging as promising approaches for the study of complex diseases and traits. However, there are several challenges with analysis and interpretation of such data. First, there is a massive multiple testing problem, due to the large number of markers that need to be analyzed, leading to an increased risk of false positives and decreased ability for association studies to detect truly associated markers. In particular, the ability to detect modest genetic effects can be severely compromised. Second, a genetic association of a given single‐nucleotide polymorphism as determined by univariate statistical analyses does not typically explain biologically interesting features, and often requires subsequent interpretation using a higher unit, such as a gene or region, for example, as defined by haplotype blocks. Third, missing genotypes in the data set and other data quality issues can pose challenges when comparisons across platforms and replications are planned. Finally, depending on the type of univariate analysis, computational burden can arise as the number of markers continues to grow into the millions. One way to deal with these and related challenges is to consider higher units for the analysis, such as genes or regions. This article summarizes analytical methods and strategies that have been proposed and applied by Group 16 to two genome‐wide association data sets made available through the Genetic Analysis Workshop 16. Genet. Epidemiol. 33 (Suppl. 1):S105–S110, 2009. © 2009 Wiley‐Liss, Inc.
Expression of the HGF receptor c‐met by macrophages in experimental autoimmune encephalomyelitis
Authors: Moransard Martijn , Sawitzky Mandy , Fontana Adriano , Suter Tobias
Published: November 2009

Hepatocyte growth factor (HGF) is a pleiotropic cytokine able to evoke a wide array of cellular responses including proliferation, migration, and survival through activation of its receptor c‐met. Various types of leukocytes have been described to express c‐met suggesting that HGF/c‐met signaling may directly influence leukocyte responses in inflammation. We have investigated the HGF/c‐met pathway in experimental autoimmune encephalomyelitis (EAE), a common mouse model of multiple sclerosis (MS), in which macrophages play a dual role, contributing directly to CNS damage at disease onset but promoting recovery during remission by removing myelin debris. Here we show that during EAE both HGF and c‐met are expressed in the CNS and that c‐met is activated. We subsequently demonstrate that c‐met is primarily expressed in inflammatory lesions by macrophages and a small number of dendritic cells (DCs) and oligodendrocyte progenitor cells (OPCs) but not by microglia or T cells. Complementary in vitro experiments show that only LPS and TNFα, but not IL‐6, IL‐10, or IL‐13, are able to induce c‐met expression in macrophages. In addition, using TNF signaling deficient macrophages we demonstrate that LPS and TNFα induce c‐met through distinct pathways. Furthermore, TNFα‐ and LPS‐induced c‐met is functional because treatment of macrophages with recombinant HGF results in rapid phosphorylation of c‐met. Interestingly, HGF/c‐met signaling does not modulate cytokine expression, phagocytosis, or antigen presentation but promotes proliferation of activated macrophages. Taken together, our data indicate a pro‐inflammatory role for the HGF/c‐met pathway in EAE rather than a role in the initiation of repair mechanisms. © 2009 Wiley‐Liss, Inc.
A novel type of glial cell in the retina is stimulated by insulin‐like growth factor 1 and may exacerbate damage to neurons and Müller glia
Authors: Fischer Andy J. , Scott Melissa A. , Zelinka Christopher , Sherwood Patrick
Published: November 2009

Recent studies have demonstrated that insulin can have profound affects on the survival of neurons within the retina. The purpose of this study was to determine how insulin‐like growth factor 1 (IGF1) influences retinal cells; in particular, the glial cells. We identify a novel type of glial cell in the avian retina and provide evidence that these cells can respond to acute damage and IGF1. In normal retinas, we found a distinct cell‐type, scattered across the ganglion cell and inner plexiform layers that express Sox2, Sox9, Nkx2.2, vimentin, and transitin, the avian homologue of mammalian nestin. These glial cells have a unique immunohistochemical profile, morphology, and distribution that are distinct among other known types of retinal glia, including microglia, oligodendrocytes, astrocytes, and Muller glia. We termed these cells nonastrocytic inner retinal glia‐like (NIRG) cells. We found that the NIRG cells may express the IGF1 receptor and respond to IGF1 by proliferating, migrating distally into the retina, and upregulating transitin. In addition, IGF1 stimulated microglia to become reactive and upregulate lysosomal membrane glycoprotein and CD45. With microglia and NIRG cells stimulated by IGF1 there were elevated levels of cell death and numerous focal detachments across the retina in response to excitotoxic damage. Cell death was prominent within the areas of detachment coinciding with a stark loss of Müller glia and accumulation of NIRG cells. We conclude that NIRG cells are a novel type of retinal glia that is sensitive to IGF1 and whose activity may impact the survival of neurons and Müller glia. © 2009 Wiley‐Liss, Inc.
Flexible and stable optical parametric oscillator based laser system for coherent anti‐Stokes Raman scattering microscopy
Authors: Zhang Wei , Parsons Maddy , McConnell Gail
Published: November 2009

The characteristics of a stable and flexible laser system based on a synchronously pumped optical parametric oscillator (OPO) is presented. This OPO can offer very stable operation with both ∼1 ps and ∼300 fs outputs over a broad wavelength range, i.e., 920–1200 nm. Combining the pump tuning with the OPO tuning, a total Raman range of 1900–5500 cm−1 is accessible. For maximum spectral sensitivity, the CARS microsope based on the ps laser system is presented in detail. The lateral resolution of the microscope is diffraction limited to be about 390 nm. Fast wavelength switching (sub‐second) between two Raman vibrational frequencies, i.e., 2848 cm−1 for CH aliphatic vibrations and 3035 cm−1 for CH aromatic vibrations is presented as an example, although this also extends to other Raman frequencies. The possibility of obtaining a multimodal imaging system based on the fs laser system is also discussed. Microsc. Res. Tech., 2010. © 2009 Wiley‐Liss, Inc.
Transient detection of E1‐containing adenovirus in saliva after the delivery of a first‐generation adenoviral vector to human parotid gland
Authors: Zheng Changyu , Nikolov Nikolay P. , Alevizos Ilias , Cotrim Ana P. , Liu Shuying , McCullagh Linda , Chiorini John A. , Illei Gabor G. , Baum Bruce J.
Published: November 2009

Background

Radiation‐induced salivary hypofunction is a common side‐effect of treatment for head and neck cancers. Patients suffer significant morbidity and there is no suitable conventional therapy. We are conducting a Phase I clinical trial, using a first‐generation serotype 5 adenoviral (Ad5) vector encoding human aquaporin‐1 (AdhAQP1) to treat such patients. One week after the administration of AdhAQP1 to an enrolled, generally healthy patient, E1‐containing adenovirus was detected in parotid saliva.

Methods

The real‐time quantitative polymerase chain reactuion (PCR) was used to measure the Ad5 E1 gene and AdhAQP1 in saliva and serum. PCR and sequencing were used to characterize viral/vector DNA extracted from saliva. The presence of infectious adenovirus was assessed by the inoculation of A549 cells with aliquots of saliva. Serum Ad5 neutralizing antibodies were measured by the inhibition of 293‐cell transduction with an Ad5 vector encoding luciferase. Multiple clinical evaluations were performed.

Results

On day 7 after AdhAQP1 delivery, low levels of the Ad5 E1 gene were detected in parotid saliva (82 copies/µl). In addition, significant levels of AdhAQP1 were also detected (1.5 × 103 copies/µl). The patient was asymptomatic and subsequent analysis of parotid saliva samples prior to day 7 and after day 7 until day 42 was negative for both virus and vector. No virus or vector was detected in serum at any time. Detailed PCR analyses of DNA extracted from the day 7 parotid saliva sample suggested the absence of a recombination event, and no infectious virus was found.

Conclusions

The patient most likely had a latent Ad5 infection in the targeted parotid gland that was activated after gene transfer and was without clinical consequence. Published in 2009 by John Wiley & Sons, Ltd.
Use of perfluoro groups in nucleophilic 18F‐fluorination
Authors: Blom Elisabeth , Karimi Farhad , Långström Bengt
Published: November 2009

Substrates with leaving groups that contained perfluoro moieties were investigated in labelling chemistry in order to exploit their properties to improve reactivity and purification. [18F](Fluoromethyl)benzene was used as the model target compound. Precursors containing perfluoroalkyl and perfluoroaryl sulfonate moieties were subjected to nucleophilic 18F‐fluorination, and the impact of perfluoro groups on the substitution reaction and product purification was investigated. [18F]Fluoride interacted with perfluoroalkyl chains, precluding nucleophilic substitution. When perfluoroaryl groups were used, the substitution proceeded, and the separation of product was explored. The radiolabelled product was obtained in 32% analytical yield and the radiochemical purity was increased to approximately 77% using fluorous solid phase extraction purification. Copyright © 2009 John Wiley & Sons, Ltd.
Influence of [2H]‐labelled acetic acid as solvent in the synthesis of [2H]‐labelled perhexiline
Authors: Schou Søren Christian
Published: November 2009

Preparation of deuterium‐labelled perhexiline from an unsaturated analogue was performed via reduction with deuterium gas and PtO2 in acetic acid. Low incorporation was observed when using acetic acid as solvent (most abundant mass peak was M), but when changing the solvent to deuterium‐labelled acetic acid, e.g. acetic acid‐OD or acetic acid‐d4, a higher incorporation was observed (most abundant mass peak was M). Using hydrogen gas instead of deuterium gas with deuterium‐labelled acetic acid, high levels of deuterium incorporation were observed (most abundant mass peak was M). An attempt to reduce a precursor with a fully deuterated pyridine to obtain perhexiline with a higher content of deuterium failed. Copyright © 2009 John Wiley & Sons, Ltd.
Preparation and biodistribution of [125I]Melphalan: a potential radioligand for diagnostic and therapeutic applications
Authors: Amin A. M. , Soliman S. E. , El‐Aziz H. A.
Published: November 2009

This paper addresses the development of a new radiopharmaceutical for cancer imaging and therapy. The optimization of the labeling conditions of thymidine analogue, melphalan, with125I is described. High radiochemical yield 96.8% was obtained by reacting 0.2 mg melphalan with 125I in the presence of choloramin‐T as oxidizing agent in 0.5 M phosphate buffer, pH 7, at 70°C for 15 min. Preliminary in vivo study was done in non‐tumor bearing mice. The results revealed that this new tracer,125I‐melphalan, has a high affinity to be localized in the tumor site for a long period, which indicates the specificity of this tracer to the tumor cells. The labeled compound was cleared quickly from most of the body organs. These findings suggest that 125I‐melphalan allows imaging and treatment of cancer. 125I‐melphalan meets most of the requirements necessary to be used as a successful diagnostic and therapeutic agent: it is a low‐molecular‐weight molecule that diffuses readily in the tissues, and dose not induce an antibody response. Copyright © 2009 John Wiley & Sons, Ltd.
Lindlar catalyst mediated tritiation of a triazole substituted isoxazoline insecticide
Authors: Rauh James J. , Lahm George P. , Pahutski Thomas F. , Ullas Giliyar V. , Filer Crist N.
Published: November 2009

The radiolabelling of isoxazoline insecticide 1a employing a Lindlar catalyst tritium dehalogenation of a bromo precursor is described. Copyright © 2009 John Wiley & Sons, Ltd.
Molecular recognition of RNA: challenges for modelling interactions and plasticity
Authors: Fulle Simone , Gohlke Holger
Published: November 2009

There is growing interest in molecular recognition processes of RNA because of RNA's widespread involvement in biological processes. Computational approaches are increasingly used for analysing and predicting binding to RNA, fuelled by encouraging progress in developing simulation, free energy and docking methods for nucleic acids. These developments take into account challenges regarding the energetics of RNA–ligand binding, RNA plasticity, and the presence of water molecules and ions in the binding interface. Accordingly, we will detail advances in force field and scoring function development for molecular dynamics (MD) simulations, free energy computations and docking calculations of nucleic acid complexes. Furthermore, we present methods that can detect moving parts within RNA structures based on graph‐theoretical approaches or normal mode analysis (NMA). As an example of the successful use of these developments, we will discuss recent structure‐based drug design approaches that focus on the bacterial ribosomal A‐site RNA as a drug target. Copyright © 2009 John Wiley & Sons, Ltd.
Thermodynamic and structural analysis of interactions between peptide ligands and SEB
Authors: Dudak Fahriye Ceyda , Soykut Esra Acar , Oğuz Murat Erman , Yaşar Fatih , Boyacı İsmail Hakkı
Published: November 2009

Staphylococcal enterotoxin B (SEB) is an exotoxin produced by Staphylococcus aureus and commonly associated with food poisoning. In this study, SEB‐binding peptides were identified by screening a phage displayed peptide library. The binding of peptides to SEB was tested with isothermal titration calorimetry (ITC) and of the five selected peptides, three showed affinity to SEB, with one measured to have the highest affinity constant (105 M−1). ITC revealed that the interaction of peptide ligands with SEB was driven entropically and the binding was dominated by hydrophobic interactions. Circular dichroism (CD) measurements and molecular dynamics (MD) simulations, together, give a structural insight into the interaction of peptides with SEB. While SEB binding peptides showed random coil structure before binding, after complex formation they had more ordered structures. The peptide with highest affinity to SEB showed stable conformation during MD simulation. Taken together, our approach about thermodynamic and structural characterization of peptide ligands can be used to develop aptamers, with high affinity and selectivity, for biosensor applications. Copyright © 2009 John Wiley & Sons, Ltd.
What can isothermal titration microcalorimetry experiments tell us about the self‐organization of surfactants into micelles?
Authors: Bouchemal Kawthar , Agnely Florence , Koffi Armand , Djabourov Madeleine , Ponchel Gilles
Published: November 2009

The aim of the present review is to give a concise analysis of the thermodynamic parameters obtained from isothermal titration microcalorimetry (ITC) experiments for the characterization of the self‐organization of surfactants into micelles. This review is also focused on works describing some methods allowing to overcome ITC limitation and to extract accurate thermodynamic values from ITC data. Copyright © 2009 John Wiley & Sons, Ltd.
A test of CoupModel for assessing the nitrogen leaching in grassland systems with two different fertilization levels
Authors: Conrad Yvonne , Fohrer Nicola
Published: November 2009

Land‐use and crop‐biomass development influence water and nutrient dynamics in soils. Nitrate‐N leaching rises with increasing mineral‐N input during seepage periods in sandy soils. Leaching of N was simulated for two grassland treatments (N0: unfertilized; N300: highly fertilized: 300 kg mineral N ha–1 y–1) using CoupModel. Parameter uncertainty was considered by an automated calibration based on the General Likelihood Uncertainty Estimation (GLUE) approach. The results of this optimization approach showed a realistic reproduction of abiotic and biotic patterns of the system. Modeled abiotic parameters, i.e., soil temperatures and water contents in different soil depths, led to plausible results with minor differences between fertilization levels and some respect for discrepancies due to heterogeneous soil conditions. Groundwater levels were slightly underestimated by CoupModel with a smoother dynamic than measured in both treatments. CoupModel provided plausible results for nitrate‐N concentrations below the rooting zone at 60 cm depth with higher uncertainty ranges than standard deviations of the measurements. Simulated nitrate‐N concentrations of the unfertilized grassland confirmed the measurements, and no potential environmental risk for water bodies existed according to the standards of the European Drinking Water Directive. The model reproduced satisfactorily the observations for the N300 system with a slightly overestimation in 40% of the simulated seepage periods. Higher uncertainties were found for the simulated N300 than for the N0 plot. Modeled N flows below the rooting zone of 11 kg nitrate‐N ha–1 per seepage period were comparable to calculations of the model “Büchter” with a mean of 10 kg nitrate‐N ha–1. For the N300 plot, a more than twice as high N‐leaching amount of 74 kg nitrate‐N ha–1 was modeled compared to a calculated average of 30 kg nitrate‐N ha–1. Finally, small‐scale modeling can provide plausible results for nitrate‐N leaching on plot‐scale when uncertainties in soil water, N flows, and biomass growth are considered.
An assessment of the impact of climate change on evapotranspiration, groundwater recharge, and low‐flow conditions in a mesoscale catchment in Northeast Germany
Authors: Wegehenkel Martin , Kersebaum Kurt‐Christian
Published: November 2009

Future climate changes might have some impacts on the discharge regime of rivers in Germany regarding, e.g., longer low‐flow periods in summer months due to a decreased precipitation and increased evapotranspiration. During such low‐flow periods, water temperature increases leading to a reduced oxygen concentration and a decrease in water quality. An assessment of such impacts is required to derive adaptation strategies for future water‐resources management. The main objective of our study was to obtain an estimation of the impact of projected future climate change on evapotranspiration, groundwater recharge, and low‐flow conditions. For that purpose, we applied a hydrological catchment model in the Ucker catchment with an area of 2415 km2 located in the lowlands of NE Germany using meteorological time series from 1951 to 2055. These time series were generated by the Potsdam Institute of Climate Impact Research based on the A1B‐Scenario with an increase of 1.4°C of the mean annual temperature and a mean decrease of 8% in annual rates of precipitation. After model calibration, the comparison of simulated and observed daily discharge rates from 1989 to 2003 led to a Nash‐Sutcliffe‐Index NS = 0.63. The results of this simulation study indicated that the amount of days with low‐flow conditions in the Ucker river will increase and groundwater recharge especially at forested areas will decrease in an order of magnitude of 1%–94%.
Do reactive oxygen species (ROS) induced by NaCl contribute to ammonium accumulation in Spartina alterniflora?
Authors: Hessini Kamel , Cruz Cristina , Gandour Mhemmed , Soltani Abdelaziz , Abdelly Chedly
Published: November 2009

Growth, activity of antioxidant enzymes viz. glutathione reductase (GR), superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX) and guaiacol peroxidase (GPX), and some metabolic processes related to ammonium metabolism were investigated in a salt‐tolerant Spatina alterniflora. In comparison to 0 mM–NaCl treatment, growth of S. alterniflora plant increased significantly at 200 mM NaCl, but was highly inhibited at 500 mM NaCl. Ammonium concentration in the leaves and roots increased 2.1–3.4 times when plants were treated with 500 mM NaCl. Under 200 mM NaCl, antioxidant‐enzyme activities increased, however, at 500 mM the antioxidant system was unable to compensate reactive oxygen species induced by NaCl. At this high level of salinity, ammonium production through nitrate reductase (NR) was inhibited, but no significant changes in the activities of glutamine synthetase (GS) or glutamate dehydrogenase (GDH) were found. We conclude that the accumulation of ammonium under high salt stress was not due to inhibition of the assimilatory activities of GS or GDH. Ammonia accumulation under high salinity may result from amino acid and protein catabolism activated by reactive oxygen species (ROS) and/or a lack of carbon skeletons to incorporate ammonium into organic molecules due to a decrease in photosynthetic activity in salt‐stressed plants.
Comparison of the response of ion distribution in the tissues and cells of the succulent plants Aloe vera and Salicornia europaea to saline stress
Authors: Zheng Qingsong , Liu Ling , Liu Zhaopu , Chen Jianmiao , Zhao Gengmao
Published: November 2009

There exists a great variability among plant species regarding their sensitivity and resistance to high salinity in soil, and most often this variability is related with the ability of a particular plant species to regulate ion homeostasis and transport. In this study, we have investigated the effects of NaCl on growth rate, water status, and ion distribution in different cells and tissues of two succulent plants, Aloe vera and Salicornia europaea. Our results showed that the growth of A. vera seedlings was significantly decreased in response to salinity. However, the growth of S. europaea seedlings was greatly stimulated by high concentrations of NaCl. Under saline conditions, S. europaea seedlings maintained K+ and Ca2+ uptake in roots and showed a higher root‐to‐shoot flux of Na+ and Cl– as compared to A. vera. Despite great accumulation of Na+ and Cl– in photosynthetically active shoot cells in S. europaea, its growth was enhanced, indicating S. europaea is capable of compartmentalizing salt ions in the vacuoles of shoot cells. Aloe vera seedlings, however, showed a low transport rate of Na+ and Cl– to leaves and suppressed uptake of K+ and Ca2+ in roots during NaCl treatment. Our results also implicate that A. vera may be able to accumulate Na+ and Cl– in the metabolically inactive aqueous cells in leaves and, as a result, the plant can survive and can maintain growth under saline conditions.
Superior semicircular canal dehiscence associated with external, middle, and inner ear abnormalities
Authors: Wang Jenny R. , Parnes Lorne S.
Published: November 2009

We report a case of bilateral superior semicircular canal dehiscence (SSCD) in a 38‐year‐old man who presented with congenital hearing loss without vestibular symptoms. This case is unusual due to the association of SSCD with multiple congenital anomalies of the external, middle, and inner ears, but without any other craniofacial or systemic developmental anomalies. Findings of multiple malformations of temporal bone structures in this case lend support to the theory that SSCD may have an underlying developmental or congenital etiology. Laryngoscope, 2010
Severe obstructive sleep apnea: Sleepy versus nonsleepy patients
Authors: Oksenberg Arie , Arons Elena , Nasser Khitam , Shneor Ophir , Radwan Henryk , Silverberg Donald S.
Published: November 2009

Objectives/Hypothesis:

To compare demographic and polysomnographic data of sleepy versus nonsleepy severe obstructive sleep apnea (OSA) patients according to the Epworth Sleepiness Scale (ESS).

Study Design:

Retrospective cohort.

Methods:

Six hundred forty‐four consecutive severe (apnea‐hypopnea index [AHI] ≥ 30) adult OSA patients who underwent a polysomnographic evaluation in our sleep disorders unit. ESS data were available in 569 (88.3%). Three hundred twenty‐seven (57.5%) patients had ESS > 10.

Results:

Sleepy severe OSA patients are slightly younger and more obese than nonsleepy patients. These sleepy patients have shorter sleep latency and lower percentage of slow wave sleep. They consistently show a higher AHI, both supine and lateral AHI, have a higher number of short arousals, and a higher arousal index. They also have higher snoring loudness in the supine and both lateral positions and a lower minimal SaO2 in rapid eye movement and non‐rapid eye movement sleep. After adjusting for confounders, a logistic regression model points to apnea index as a significant prognostic factor for excessive daytime sleepiness.

Conclusions:

Severe OSA sleepy patients have a syndrome that is significantly more severe than nonsleepy patients. Sleepy patients have worse sleep‐related breathing parameters, and their sleep patterns are lighter and more fragmented than nonsleepy patients. Apnea index appears as an important prognostic factor for excessive daytime sleepiness. Laryngoscope, 2010
Large‐scale assessment of soil erosion using a neuro‐fuzzy model combined with GIS: A case study of Hubei Province, China
Authors: Zhu D. , Wang T. W. , Cai C. F. , Li L. , Shi Z. H.
Published: November 2009

Reliable and cost‐effective soil erosion assessment is an important precondition for soil conservation measures, which remains a major challenge at large scale. Considering that the neuro‐fuzzy model has the special advantage in multi‐index comprehensive assessment and GIS technology is adept at geo‐spatial information processing, through the combination of them, it is possible to provide an effective approach for this difficult problem. Taking Hubei Province as a case study area, five evaluating indicators were selected for the large‐scale assessment, in which the GIS technology was used to construct the classification maps of evaluating indicators and to divide basic assessment units, and the neuro‐fuzzy model was adopted to extract fuzzy rules for individual units assessment from available ground truth data. According to the optimized assessment criteria generated by the neuro‐fuzzy model, the soil erosion state of the entire study area was then assessed. To represent the spatial distribution of soil erosion, a detailed map was produced by statistical mapping, which was represented with six erosion levels (from slight to severe) at a map scale of 1:250 000. The resulting map showed that about 30.1% of the total land area in Hubei was affected by different levels of soil erosion problem. Western high mountains and eastern low mountains suffered from the most serious erosion damage, a strong level of soil erosion was widely observed in these mountains. Large areas of moderate level erosion occurred in the northern hills. In contrast, most of the central plains were characterized as slight level erosion effect. The validation indicated that an overall accuracy of 88% and a κ of 0.89 were achieved, proving that the resulting map was in conformity with actual conditions, which indicates this assessment approach was reasonable and applicable. Copyright © 2009 John Wiley & Sons, Ltd.
Survey evidence on price‐setting patterns of Romanian firms
Authors: Copaciu Mihai , Neagu Florian , Braun‐Erdei Horia
Published: November 2009

This paper presents for Romanian firms the results of the first survey on price‐setting patterns among the New Member States of the EU. Diverging from Inflation Persistence Network (IPN) findings, generally small firms perceive higher competitive pressure and adopt the market price, using a state‐dependent rule, while lower perceived competition is consistent with medium and large firms using mark‐up pricing. Prices are reviewed and changed more often than for EMU firms and are more flexible than wages. Similar to IPN evidence, contracts are the main sources of price stickiness. The survey suggests full price transmission of large unanticipated financial shocks. Copyright © 2009 John Wiley & Sons, Ltd.
Difluorobenzenes revisited: an experimental and theoretical study of spin–spin coupling constants for 1,2‐, 1,3‐, and 1,4‐difluorobenzene
Authors: Alkorta Ibon , Blanco Fernando , Del Bene Janet E. , Elguero José , Hernández‐Folgado Laura , Jimeno María‐Luisa
Published: November 2009

The experimental spin–spin coupling constants (SSCCs) for 1,3‐ and 1,4‐difluorobenzene have been determined anew, and found to be consistent with previously determined values. SSCCs for 1,2‐, 1,3‐, and 1,4‐difluorobenzene have been analyzed by comparing them with the coupling constants computed using the second‐order polarization propagator approximation (SOPPA) and the equation‐of‐motion coupled cluster singles and doubles method (EOM‐CCSD). Eighty experimental values have been analyzed using SOPPA calculations, and a subset of 40 values using both SOPPA and EOM‐CCSD approaches. One‐bond coupling constants 1J(CC) and 1J(CF) are better described by EOM‐CCSD, whereas one‐bond 1J(CH) values are better described by SOPPA. An empirical equation is presented which allows for the prediction of unknown coupling constants from computed SOPPA values. A similar approach may prove useful for predicting coupling constants in larger systems. Copyright © 2009 John Wiley & Sons, Ltd.
Insights of the effects of polyethylene glycol 400 on mammalian and avian nerve terminals
Authors: Oshima Mário , Leite Gildo Bernardo , Rostelato‐Ferreira Sandro , Da Cruz‐Höfling Maria Alice , Rodrigues‐Simioni Léa , Oshima‐Franco Yoko
Published: November 2009

Polyethylene glycol (PEG) has been widely used as a solvent among other applications. An ideal solvent is one that does not interfere with an in vitro biological system, unless it is a bioactive agent. Herein, a facilitatory neurotransmission effect was exhibited by PEG (20 μM) in mammalian (67 ± 12.5%,n= 4) and avian (74 ± 6.8%,n= 6) neuromuscular preparations. In curarized preparations, PEG did not reverse the neurotransmission blockade induced by D‐tubocurarine (D‐Tc, 5.8 μM,n= 6) as promoted by neostigmine (12 μM,n= 4). A possible presynaptic action of PEG was ruled out, because quantal acetylcholine (ACh) content was similar to the control Tyrode‐incubated mammalian preparation. PEG showed improved sarcolemmal sensitivity, both under direct (sarcolemma) and indirect stimulation (motor axon), because it was able to release calcium from the sarcoplasmic reticulum, even when 30 μM dantrolene (n= 5) was previously applied. Neurotransmission decreased at a higher PEG concentration (100 μM,n= −6) in the depolarized membrane, but it did not alter normal muscle fiber morphology. In addition, it partially recovered twitch tension amplitude (55 ± 5.7%) after washing the preparations. More than a simple solvent, we suggest that PEG 400 is able to act on the sarcolemmal membrane, probably at the triad level, which is in line with its well‐known ability as drug carrier. Muscle Nerve, 2010
Short‐term training adaptations in maximal motor unit firing rates and afterhyperpolarization duration
Authors: Christie Anita , Kamen Gary
Published: November 2009

In this study we investigated age‐ and training‐related adaptations in maximal motor unit firing rates and the duration of the motoneuron afterhyperpolarization (AHP) in the dorsiflexor muscles of the foot. Subjects included 30 young (21.9 ± 3.1 years) and 30 older (72.9 ± 4.6 years) individuals, who were randomly assigned to a control or training group. Maximal voluntary force (MVC), maximal motor unit firing rate, and motoneuron AHP duration were measured on two occasions. The training group participated in six dorsiflexor exercise training sessions between test and retest. At baseline, young subjects had higher MVC force and maximal motor unit firing rate, and shorter AHP duration, compared with older subjects. Young and older subjects in the trained group demonstrated a respective 17.4% and 19.8% increase in MVC force, a 6.8% and 24.3% increase in maximal MUFR, and a 7.4% and 14.2% decrease in AHP duration. These results indicate that age‐related changes in neuromuscular function are not a necessary consequence of aging. Muscle Nerve, 2010
Correlation between the combined sensory index and clinical outcome after carpal tunnel decompression: A retrospective review
Authors: Malladi Niriksha , Micklesen Paula J. , Hou Juliet , Robinson Lawrence R.
Published: November 2009

The combined sensory index (CSI) is a useful electrodiagnostic tool, but it was not known if the CSI can be correlated with clinical outcome following carpal tunnel decompression. The objective of this study was to examine the association between the CSI and symptom relief from pain and parasthesiae following surgical intervention. Retrospective chart review was performed on 272 patients, diagnosed with carpal tunnel syndrome by electrodiagnostic criteria, who proceeded to undergo open or endoscopic carpal tunnel release with postoperative follow‐up at an academic medical center between 1996 and 2006. The CSI demonstrated statistical significance (P = 0.03) for correlation with resolution of pain and parasthesiae following carpal tunnel decompression. Patients with a CSI of 2.5–4.6 had the best prognosis for resolution of pain and parasthesiae following surgical intervention. Median compound muscle action potential (CMAP) amplitude and median motor latency were also associated with resolution of parasthesiae, but not pain. The CSI effectively establishes correlation with clinical outcomes following surgical intervention for carpal tunnel syndrome, and thus a range of optimal outcomes (CSI between 2.5 and 4.6) can also be established. Muscle Nerve, 2010