bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of claspin as a proliferation marker in human cancer and normal tissues
Authors: Tsimaratou K , Kletsas D , Kastrinakis NG , Tsantoulis PK , Evangelou K , Sideridou M , Liontos M , Poulias I , Venere M , Salmas M , Kittas C , Halazonetis TD , Gorgoulis VG
Published: December 2006

Claspin is a nuclear protein involved in DNA replication and the DNA damage response. Its structural and functional properties suggest that it may represent a potentially useful proliferation marker. To this end, a monoclonal antibody was generated and the expression of claspin was investigated in normal fibroblasts and various cancer cell lines, as well as in tumour and normal tissues from patients with primary epithelial carcinomas. Immunoblotting analysis confirmed the specificity of the antibody, while immunohistochemistry demonstrated its applicability in archival material. In normal cells and tissues, claspin expression was weak, whereas increased levels were observed in cancer cell lines and tumour specimens. Claspin staining correlated strongly with Ki67 staining in both normal (p < 0.001) and tumour tissues (p < 0.001). However, the labelling index (LI) of claspin was consistently lower than that of Ki67, suggesting that claspin expression may be limited to a narrower part of the cell cycle. Co‐localization assays with cyclin A and cell synchronization experiments indicated that claspin expression coincides with the S phase. Interestingly, the relative increase of the claspin LI in tumour samples compared with normal tissues was significantly higher (14‐fold) than that of the Ki67 LI (five‐fold), suggesting that claspin may be a more sensitive marker of aberrant proliferation. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Transcriptional profiling suggests that secondary and primary large B‐cell lymphomas of the gastrointestinal (GI) tract are blastic variants of GI marginal zone lymphoma
Authors: Barth TFE , Barth CA , Kestler HA , Michl P , Weniger MA , Buchholz M , Möller P , Gress T
Published: December 2006

The pathogenetic relationship of marginal zone B‐cell lymphoma (MALT lymphoma) of the gastrointestinal (GI) tract and eventually co‐existing aggressive B‐cell lymphoma and primary aggressive B‐cell lymphoma remains to be elucidated. The RNA of laser‐microdissected cells was isolated and amplified from small and/or large cell compartments of eight MALT lymphomas (small cell lymphoma, SCL), 14 GI diffuse large B‐cell lymphomas (large cell lymphoma, LCL), and ten GI B‐cell lymphomas with composite small and large cell compartments (ComL) and expression analyses were performed using cDNA arrays. Hierarchical cluster analysis clearly separated SCL and LCL and the small and large cell compartments of ComL. Likewise, cluster analysis with all samples of SCL, LCL, and ComL yielded two main ‘small cell’ and ‘large cell’ branches. Furthermore, 60 genes were differentially expressed between SCL and LCL, and 82 genes between the small and large cell components of ComL; 26 genes were discriminators in both settings. Use of the profiles of ComL as training sets for class prediction resulted in 95% accuracy for the classification of SCL and LCL. Collectively, the data strongly suggest that both secondary and primary aggressive B‐cell lymphomas of the GI tract are blastic marginal zone lymphomas. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Collagen loss and impaired wound healing is associated with c‐Myb deficiency
Authors: Kopecki Z , Luchetti MM , Adams DH , Strudwick X , Mantamadiotis T , Stoppacciaro A , Gabrielli A , Ramsay RG , Cowin AJ
Published: December 2006

Collagen type I serves as an abundant structural and signalling component of skin. It is also an established target gene of the transcription factor, c‐Myb. When c‐myb−/− embryos were examined it was observed that their skin was markedly thinner than normal. Importantly, immunohistochemical investigation showed complete absence of collagen type I. Although these homozygous knock‐out embryos fail to develop beyond day 15, fibroblasts established from these embryos (mouse embryonic fibroblasts [MEFs]) show defective proliferative responses. Furthermore, in vitro scratch wound assays demonstrated that these c‐myb−/− MEFs also exhibit slower closure than their wild‐type counterparts. Embryonic lethality has meant that examination of the role of c‐Myb in adult mouse skin has not been reported to date. However, in view of the abundance of collagen type I in normal skin, its role in skin integrity and the in vitro data showing proliferative and migration defects in c‐myb−/− MEFs, we investigated the consequences of heterozygous c‐myb loss in adult mice on the complex process of skin repair in response to injury. Our studies clearly demonstrate that heterozygous c‐myb deficiency has a functional effect on wound repair, collagen type I levels and, in response to wounding, transforming growth factor‐β1 (an important collagen stimulating factor) induction expression is aberrantly high. Manipulation of c‐Myb may therefore provide new therapeutic opportunities for improving wound repair while uncontrolled expression may underpin some fibrotic disorders. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Feature‐based reappraisal of the Bacillus subtilis exoproteome
Authors: Tjalsma Harold
Published: December 2006

Proteomics‐based verification of computer‐assisted predictions on bacterial protein export have indicated that problems occur with the distinction between (Sec‐type) signal peptides that govern protein secretion, and lipoprotein signal peptides or amino‐terminal membrane anchors that cause protein retention in the membrane. Therefore, the main aim of this study was to investigate whether feature‐based predictions by the SecretomeP (SecP) algorithm will aid the proteomics‐based analysis of protein export in Bacillus subtilis. The SecP algorithm is trained to recognize features such as secondary structure and disordered regions, which are generally present in secreted proteins. The results showed that membrane‐retained proteins receive, in general, high SecP scores, similar to the scores of secretory proteins. Importantly, the SecP algorithm aided in the re‐evaluation of a class of previously identified proteins that remain attached to the membrane despite the presence of an apparent Sec‐type signal peptide. These so‐called ‘Sec‐attached’ proteins receive on average a lower SecP score, and several of these proteins could be unmasked as transmembrane proteins by combined SecP and signal peptide analyses. Finally, the present study suggests that feature‐based outlier analysis may provide leads towards the discovery of novel special‐purpose pathways for bacterial protein export.
Banana (Musa spp.) as a model to study the meristem proteome: Acclimation to osmotic stress
Authors: Carpentier Sebastien C. , Witters Erwin , Laukens Kris , Van Onckelen Harry , Swennen Rony , Panis Bart
Published: December 2006

Banana (Musa spp.) multiple shoot meristems are an excellent model to study the meristem proteome. Using a 2‐DE protocol developed for small amounts of tissue and MS‐based cross species polypeptide identification, we have revealed the meristem proteome and investigated the influence of sucrose‐mediated osmotic stress in a dehydration‐tolerant variety. Proteins that were significantly up‐ or down‐regulated due to the high‐sucrose treatment were classified using non‐parametric univariate statistics. Our results suggest that the maintenance of an osmoprotective intracellular sucrose concentration, the enhanced expression of particular genes of the energy‐conserving glycolysis and the conservation of the cell wall integrity are essential to maintain homeostasis, to acclimate and to survive dehydration. By comparing the dehydration‐tolerant variety with a dehydration‐sensitive variety, we were able to distinguish several genotype‐specific proteins (isoforms), and could associate the dehydration‐tolerant variety with proteins involved in energy metabolism (e.g., phosphoglycerate kinase, phosphoglucomutase, UDP‐glucose pyrophosphorylase) and proteins that are associated with stress adaptation (e.g., OSR40‐like protein, abscisic stress ripening protein‐like protein). This work shows that proteome analysis can be used successfully to perform quantitative difference analysis and to characterize genetic variations in a recalcitrant crop.
Synthesis, characterization and properties of novel highly oxygen permeable amphiphilic membranes
Authors: Karunakaran Radhakrishnan , Kennedy Joseph P.
Published: December 2006

The objective of this research was to develop new strategies for the synthesis of novel optically clear highly oxygen permeable membranes exhibiting appropriate water uptake and mechanical properties for possible ophthalmic applications. Thus a series of bicontinuous amphiphilic conetworks containing well‐defined poly‐ (ethylene glycol) and polydimethylsiloxane segments crosslinked by three novel crosslinking/modifying agents were synthesized, characterized, and evaluated. This paper concerns the design and synthesis of the crosslinking/modifying agents (see Fig. 2), and their use for the synthesis of clear, highly oxygen permeable amphiphilic membranes. Select membranes exhibit outstanding oxygen permeabilities (>200 barrers) far superior to contemporary commercial soft contact lenses, together with mechanical properties and water uptake appropriate for extended wear soft contact lens application. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 308–316, 2007
Deactivation reactions in the modeled 2,2,6,6‐tetramethyl‐1‐piperidinyloxy‐mediated free‐radical polymerization of styrene: A comparative study with the 2,2,6,6‐tetramethyl‐1‐piperidinyloxy/acrylonitrile system
Authors: Kaim Andrzej
Published: December 2006

The competitiveness of the combination and disproportionation reactions between a 1‐phenylpropyl radical, standing for a growing polystyryl macroradical, and a 2,2,6,6‐tetramethyl‐1‐piperidinyloxy (TEMPO) radical in the nitroxide‐mediated free‐radical polymerization of styrene was quantitatively evaluated by the study of the transition geometry and the potential energy profiles for the competing reactions with the use of quantum‐mechanical calculations at the density functional theory (DFT) UB3‐LYP/6‐311+G(3df, 2p)//(unrestricted) Austin Model 1 level of theory. The search for transition geometries resulted in six and two transition structures for the radical combination and disproportionation reactions, respectively. The former transition structures, mainly differing in the out‐of‐plane angle of the NO bond in the transition structure TEMPO molecule, were correlated with the activation energy, which was determined to be in the range of 8.4–19.4 kcal mol−1 from a single‐point calculation at the DFT UB3‐LYP/6‐311+G(3df, 2p)//unrestricted Austin Model 1 level. The calculated activation energy for the disproportionation reaction was less favorable by a value of more than 30 kcal mol−1 in comparison with that for the combination reaction. The approximate barrier difference for the TEMPO addition and disproportionation reaction was slightly smaller for the styrene polymerization system than for the acrylonitrile polymerization system, thus indicating that a β‐proton abstraction through a TEMPO radical from the polymer backbone could diminish control over the radical polymerization of styrene with the nitroxide even more than in the latter system. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 232–241, 2007
Synthesis and properties of novel sulfonated polyimides containing binaphthyl groups as proton‐exchange membranes for fuel cells
Authors: Li Yuhan , Jin Rizhe , Wang Zhen , Cui Zhiming , Xing Wei , Gao Lianxun
Published: December 2006

A novel sulfonated diamine monomer, 2,2′‐bis(p‐aminophenoxy)‐1,1′‐binaphthyl‐6,6′‐disulfonic acid (BNDADS), was synthesized. A series of sulfonated polyimide copolymers containing 30–80 mol % BNDADS as a hydrophilic component were prepared. The copolymers showed excellent solubility and good film‐forming capability. Atomic force microscopy phase images clearly showed hydrophilic/hydrophobic microphase separation. The relationship between the proton conductivity and degree of sulfonation was examined. The sulfonated polyimide copolymer with 60 mol % BNDADS showed higher proton conductivity (0.0945–0.161 S/cm) at 20–80 °C in liquid water. The membranes exhibited methanol permeability from 9 × 10−8 to 5 × 10−7 cm2/s at 20 °C, which was much lower than that of Nafion (2 × 10−6cm2/s). The copolymers were thermally stable up to 300 °C. The sulfonated polyimide copolymers with 30–60 mol % BNDADS showed reasonable mechanical strength; for example, the maximum tensile strength at break of the sulfonated polyimide copolymer with 40 mol % BNDADS was 80.6 MPa under high moisture conditions. The optimum concentration of BNDADS was found to be 60 mol % from the viewpoint of proton conductivity, methanol permeability, and membrane stability. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 222–231, 2007
Developing an outcome measurement for meaning‐making intervention with Chinese cancer patients
Authors: Chan Timothy H. Y. , Ho Rainbow T. H. , Chan Cecilia L. W.
Published: December 2006

Psychosocial programs designed for cancer patients often facilitate the search for meaning as one of the therapeutic components. This study aimed to develop a self‐report instrument, namely Chinese Cancer Coherence Scale (CCCS), which measures the patients' meaning‐making process with reference to the concept of coherence. A panel of eight veteran social workers and psychologists generated statements pertaining to the cancer experience. Results from a two‐phase study involving 390 breast cancer patients revealed a two‐factor structure of the CCCS, namely incoherent‐embittered and coherent‐enlightened. The use of the CCCS by practitioners and researchers is recommended in order to understand how Chinese cancer patients make sense of their cancer experience. Copyright © 2006 John Wiley & Sons, Ltd.
Does tetracycline bind helix 2 of prion? An integrated spectroscopical and computational study of the interaction between the antibiotic and α helix 2 human prion protein fragments
Authors: Ronga Luisa , Langella Emma , Palladino Pasquale , Marasco Daniela , Tizzano Barbara , Saviano Michele , Pedone Carlo , Improta Roberto , Ruvo Menotti
Published: December 2006

We demonstrate here that tetracycline (TC) can strongly interact (KD′ = 189 ± 7 nM) with model peptides derived from the C‐terminal globular domain of the prion protein, hPrP [173‐195], and that interaction concerns residues within the C‐terminal half of the helix 2, a short region previously indicated as endowed with ambivalent conformational behavior and implicated in PrP conversion to the β‐sheet‐rich, infective scrapie variant. Data have been confirmed by binding studies with the N‐terminal truncated 180‐195 variant that displays a dissociation constant of 483 ± 30 nM. Remarkably, TC does not influence the structure of the N‐terminally fluoresceinated peptides that both show α‐helical conformations. Docking calculations and molecular dynamics simulations suggest a direct, strong interaction of the antibiotic with exposed side chain functional groups of threonines 190‐193 on the solvent‐exposed surface of helix 2. Proteins 2007 © 2006 Wiley‐Liss, Inc.
Probabilistic alignment detects remote homology in a pair of protein sequences without homologous sequence information
Authors: Koike Ryotaro , Kinoshita Kengo , Kidera Akinori
Published: December 2006

Dynamic programming (DP) and its heuristic algorithms are the most fundamental methods for similarity searches of amino acid sequences. Their detection power has been improved by including supplemental information, such as homologous sequences in the profile method. Here, we describe a method, probabilistic alignment (PA), that gives improved detection power, but similarly to the original DP, uses only a pair of amino acid sequences. Receiver operating characteristic (ROC) analysis demonstrated that the PA method is far superior to BLAST, and that its sensitivity and selectivity approach to those of PSI‐BLAST. Particularly for orphan proteins having few homologues in the database, PA exhibits much better performance than PSI‐BLAST. On the basis of this observation, we applied the PA method to a homology search of two orphan proteins, Latexin and Resuscitation‐promoting factor domain. Their molecular functions have been described based on structural similarities, but sequence homologues have not been identified by PSI‐BLAST. PA successfully detected sequence homologues for the two proteins and confirmed that the observed structural similarities are the result of an evolutional relationship. Proteins 2007. © 2006 Wiley‐Liss, Inc.
Prediction‐based fingerprints of protein–protein interactions
Authors: Porollo Aleksey , Meller Jarosław
Published: December 2006

The recognition of protein interaction sites is an important intermediate step toward identification of functionally relevant residues and understanding protein function, facilitating experimental efforts in that regard. Toward that goal, the authors propose a novel representation for the recognition of protein–protein interaction sites that integrates enhanced relative solvent accessibility (RSA) predictions with high resolution structural data. An observation that RSA predictions are biased toward the level of surface exposure consistent with protein complexes led the authors to investigate the difference between the predicted and actual (i.e., observed in an unbound structure) RSA of an amino acid residue as a fingerprint of interaction sites. The authors demonstrate that RSA prediction‐based fingerprints of protein interactions significantly improve the discrimination between interacting and noninteracting sites, compared with evolutionary conservation, physicochemical characteristics, structure‐derived and other features considered before. On the basis of these observations, the authors developed a new method for the prediction of protein–protein interaction sites, using machine learning approaches to combine the most informative features into the final predictor. For training and validation, the authors used several large sets of protein complexes and derived from them nonredundant representative chains, with interaction sites mapped from multiple complexes. Alternative machine learning techniques are used, including Support Vector Machines and Neural Networks, so as to evaluate the relative effects of the choice of a representation and a specific learning algorithm. The effects of induced fit and uncertainty of the negative (noninteracting) class assignment are also evaluated. Several representative methods from the literature are reimplemented to enable direct comparison of the results. Using rigorous validation protocols, the authors estimated that the new method yields the overall classification accuracy of about 74% and Matthews correlation coefficients of 0.42, as opposed to up to 70% classification accuracy and up to 0.3 Matthews correlation coefficient for methods that do not utilize RSA prediction‐based fingerprints. The new method is available at http://sppider.cchmc.org. Proteins 2007. © 2006 Wiley‐Liss, Inc.
Data Pipelines and Virtual Screening: Automating the Process
Authors: Brown Robert D. , Varma‐O'Brien Shikha , Rogers David
Published: December 2006

The application of virtual screens to sets of ligands can involve several complex modeling and database packages and a considerable amount of manual intervention to transfer and reformat data between computational steps. This is time‐consuming and error‐prone for a computational chemist, and can put the process beyond the capabilities of a project scientist. In this paper, we discuss the application of a workflow methodology known as data pipelining to automate the process of virtual screening. We show that this can allow computational chemists to automate the application of virtual screens, encapsulate their expertise in the form of computational protocols (workflows), and deploy these protocols to bench scientists to allow them to apply virtual screening methods in a simple, automated fashion.
Estimation of Compartmental Half‐lives of Organic Compounds – Structural Similarity versus EPI‐Suite
Authors: Kühne Ralph , Ebert Ralf‐Uwe , Schüürmann Gerrit
Published: December 2006

A k Nearest Neighbors (KNN) approach is developed to extrapolate from existing semiquantitative compartmental half‐lives of organic compounds to respective data for untested substances. It is based on the evaluation of structural similarity through atom‐centered fragments (ACFs). For the model development and leave‐one‐out cross‐validation, a set of 293 compounds with reference half‐lives for the four compartments air, water, soil, and sediment was taken from literature. Comparative analysis of the model performance with results based on EPI‐Suite predictions of degradation rates due to indirect photolysis, biodegradation, and hydrolysis demonstrates the superiority of the new approach to predict compartmental half‐lives. The latter are needed as input information for modeling the multimedia fate and life‐time of organic compounds. The discussion includes an analysis of the problems associated with converting process‐specific loss rates into compartmental half‐lives.
Atom‐Based 2D Quadratic Indices in Drug Discovery of Novel Tyrosinase Inhibitors: Results of In Silico Studies Supported by Experimental Results
Authors: Ponce Yovani Marrero , Khan Mahmud Tareq Hassan , Martín Gerardo M. Casañola , Ather Arjumand , Sultankhodzhaev Mukhlis N. , Torrens Francisco , Rotondo Richard , Alvarado Ysaias J.
Published: December 2006

Herein we present results of QSAR studies of tyrosinase inhibitors employing one of the atom‐based TOMOCOMD‐CARDD (acronym of TOpological MOlecular COMputer Design‐Computer Aided “Rational” Drug Design) descriptors, molecular quadratic indices, and Linear Discriminant Analysis (LDA) as pattern recognition method. In this way, a database of 246 organic chemicals, reported as tyrosinase inhibitors having great structural variability, was analyzed and presented as a helpful tool, not only for theoretical chemists but also for other researchers in this area. In total, 12 LDA‐based QSAR models were obtained, the first six with the non‐stochastic total and local quadratic indices and the six remaining models with the stochastic molecular descriptors. The best two models for the non‐stochastic and stochastic molecular descriptors, showed an appropriate overall accuracy (92.68 and 89.10%, respectively) and a high Matthews correlation coefficient (C of 0.85 and of 0.84, correspondingly) when applied to the training set. External validation series were also used to validate the obtained models; the 91.67% (C=0.82) and 90.00% (C=0.78), were correctly classified, respectively. In order to show the possibilities of the present approach for the ligand‐based virtual screening of tyrosinase inhibitors, the developed models were used afterwards in a simulation of a virtual search for tyrosinase inhibitors. For instance, more than 93% (93.33%) and 96% (96.66%) of the screened chemicals were correctly classified by the two best LDA‐based QSAR models developed with non‐stochastic and stochastic quadratic indices, respectively. Finally, the combination of the obtained models permitted the selection/identification of new diterpenoidal alkaloid leads as tyrosinase inhibitors. The found activity is supported by observed inhibitory effects on mushroom tyrosinase enzyme, even comparable with some reference tyrosinase inhibitors. These results support a role for TOMOCOMD‐CARDD descriptors in the biosilico discovery of novel tyrosinase inhibitors from large databases of chemical structures (virtual or “in silico”), which may be used to prevent or treat pigmentation disorders.
Principal Component Analysis of Catalytic Functions in the Composition Space of Heterogeneous Catalysts
Authors: Sieg Simone C. , Suh Changwon , Schmidt Timm , Stukowski Michael , Rajan Krishna , Maier Wilhelm F.
Published: December 2006

The objective of this paper is to identify which combinations of constituents of heterogeneous catalysts are related to which final products from a large combinatorially generated dataset. To this end, data on the composition of catalysts are combined with a set of four catalytic activities, and analyzed using a Principle Component Analysis (PCA). From the first attempt of PCA, a dataset of pentanary‐mixed metal oxides, CraMobNicCodMneOx, is visualized on the planes of principal components (PCs) in a way of linking the composition spread with the activities toward each product. It has been possible to identify three key elements (Mo, Co, and Cr) out of five by PCA. Having these key elements identified from PCA, a ternary system of mixed metal oxide catalysts, MoaCobCrcOx, was analyzed again in the PC space for further relationships between composition of catalysts and activities of final products. These two case studies demonstrate how large multidimensional datasets can be analyzed to identify relevant key parameters for catalyst discovery and optimization.
Quantitative Cationic Activity Relationships for Predicting Toxicity of Metal Ions from Physicochemical Properties and Natural Occurrence Levels
Authors: Walker John D. , Enache Monica , Dearden John C.
Published: December 2006

Quantitative Cationic Activity Relationships (QCARs) were developed to predict the toxicity of metal ions from physicochemical properties and natural occurrence levels. In vivo toxicity data for different concentrations of nitrate salts of 17 metal ions were developed based on germination of sunflower seeds (F.1. Helianthus annuus ‘Sunspot’) in distilled water. The EC50 data were reported as the concentration giving 50% inhibition of radicle growth 1 day after emergence. Stepwise regression of the toxicity data produced correlations with some physicochemical properties and natural occurrence levels. For physicochemical properties, good results were obtained with the density of the elements, enthalpy of formation of metal sulphides and the stability constants of metal ions with sulphate ($\rm{ r_{{\rm{adj}}.}^2 }$=0.72−0.81). For natural occurrence levels, good results were obtained with metal concentrations in soil, the median elemental composition of soils and the calculated mean of the elemental content in land plants ($\rm{ r_{{\rm{adj}}.}^2 }$=0.69−0.83).
3‐D‐QSAR Analysis of 2‐(Oxalylamino) benzoic acid Class of Protein Tyrosine Phosphatase 1B Inhibitors by CoMFA and Cerius2.GA
Authors: Ramar Subbiah , Bag Seema , Tawari Nilesh R. , Degani Mariam S.
Published: December 2006

Three‐Dimensional Quantitative Structure–Activity Relationship (3‐D‐QSAR) studies for 2‐(oxalylamino) benzoic acids as Protein Tyrosine Phosphatase 1B (PTP1B) inhibitors were performed using the genetic function approximation algorithm (Cerius2.GA) and Comparative Molecular Field Analysis (CoMFA). A five‐term equation was developed with crossvalidated $\rm{ r_{}^{\rm{2}} }$ ($\rm{ r_{{\rm{CV}}}^{\rm{2}} }$) and conventional correlation coefficient (r2) of 0.642 and 0.748, respectively, using Cerius2.GA. The CoMFA model from multifit alignment produced good statistical significance with $\rm{ r_{{\rm{CV}}}^{\rm{2}} }$ and r2 of 0.671 and 0.900, respectively. The predictive abilities of Cerius2.GA and CoMFA were determined using a test set of ten molecules giving predictive correlation coefficients of 0.666 and 0.643, respectively, indicating good predictive power. Furthermore, the robustness of the models was verified by bootstrapping analysis. Based on the information derived from Cerius2.GA and CoMFA, we have identified some key features that may be used to design new derivatives and predict their PTP affinities prior to synthesis.
Determination of bond dissociation energies using mass spectrometry
Authors: El‐Nakat John Hanna , Ghanem Noha , Yammine Paolo , Willett Gary , Fisher Keith
Published: December 2006

Fourier transform ion cyclotron resonance mass spectrometry (FT‐ICR/MS) offers the opportunity for gas phase cluster formation reactions at very low pressures and at temperatures that are different from room temperature. Reactions take place with single positive‐charge metal ions that are normally +2, +3, +4, etc., charged in solution. The ions formed are detected by measuring the current induced by their cyclotron rotation, but they cannot be physically separated and collected. Collision‐induced dissociation (CID) is widely used for ion‐structure determination via the fragmentation of the excited ions. CID study aims to determine the relationship between the Vpp [peak‐to‐peak voltage of the radiofrequency (rf) pulse] and the mass‐to‐charge (m/z) ratio, which will be used for the calculation of the center‐of‐mass translational kinetic energy (Ekcm) of the excited ion under investigation. CID studies are restricted to stable ions with relatively high abundance. Nevertheless, with the evolution of computational chemistry, such problems can be overcome whereby CID calculations will be used to provide the substantial parameters for computer software, such as the Gaussian 03 program, for the structure determination of the less stable NixS anions. The latter constitutes the core for our current research. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007
Sample size determination for logistic regression revisited
Authors: Demidenko Eugene
Published: December 2006

There is no consensus on the approach to compute the power and sample size with logistic regression. Some authors use the likelihood ratio test; some use the test on proportions; some suggest various approximations to handle the multivariate case. We advocate the use of the Wald test since the Z‐score is routinely used for statistical significance testing of regression coefficients. The null‐variance formula became popular from early studies, which contradicts modern software, which utilizes the method of maximum likelihood estimation (MLE), when the variance of the MLE is estimated at the MLE, not at the null. We derive general Wald‐based power and sample size formulas for logistic regression and then apply them to binary exposure and confounder to obtain a closed‐form expression. These formulas are applied to minimize the total sample size in a case–control study to achieve a given power by optimizing the ratio of controls to cases. Approximately, the optimal number of controls to cases is equal to the square root of the alternative odds ratio. Our sample size and power calculations can be carried out online at www.dartmouth.edu/∼eugened. Copyright © 2006 John Wiley & Sons, Ltd.
Methods for the statistical analysis of binary data in split‐mouth designs with baseline measurements
Authors: Donner A. , Zou G. Y.
Published: December 2006

Many split‐mouth trials are characterized by the pairing of site‐specific outcome and baseline data within each segment of a subject's mouth. However when the response variable of interest is binary, methods of statistical analysis for this design are not well developed. In this paper we present several analytic approaches that may be taken to the resulting data, showing how the efficiency of statistical inferences can be improved by appropriately incorporating the baseline information. The advantages and disadvantages of the different approaches are discussed in the context of an example from the published literature. The results from a limited simulation study are also presented. Copyright © 2006 John Wiley & Sons, Ltd.
Intervention on occupational stress among teachers in the middle schools in China
Authors: Wu Siying , Li Jian , Wang Mianzhen , Wang Zhiming , Li Huangyuan
Published: December 2006

The purpose of this study was to evaluate the effectiveness of the interventions on occupational stress among teachers in middle schools. The study group consists of 459 teachers (247 men and 212 women) from four middle schools. The control group consists of 502 teachers (271 men and 231 women). The three dimensions of occupational adjustment (including occupational stress, psychological strain, and coping resources) were measured with the Occupational Stress Inventory‐Revised Edition (OSI‐R) and the work ability was assessed with the Work Ability Index (WAI) among teachers. The integrated interventions (involving organizational and individual level intervention) were taken to the teachers in the study group. The main results were as follows. The scores of some scales of occupational role questionnaire and personal strain questionnaire decreased significantly and the scores of some scales of personal resources questionnaire and WAI increased significantly after intervening. This study suggested that interventions were efficient in reducing the teachers' occupational stressors, increased their coping resources and improved their work ability. Copyright © 2006 John Wiley & Sons, Ltd.
Post‐traumatic reactions among rescue personnel before and after exposure to trauma: a brief report
Authors: Ben‐Ezra Menachem , Essar Nir , Saar Ronen
Published: December 2006

There are only a few studies that check rescue personnel before and after exposure to trauma. Peritraumatic dissociation and post‐traumatic reactions were examined among rescue personnel in a rescue course and 36–48h after exposure to a gas pipe explosion in Tel Aviv. The entire rescue personnel were examined for peritraumatic dissociation and post‐traumatic reactions. Only those with prior measurements of peritraumatic dissociation and post‐traumatic reactions were eligible for analysis. The results showed that the only significant increase among rescue personnel was in peritraumatic dissociation between before in comparison to after exposure to trauma. No significant change was found in avoidance, intrusion, and post‐traumatic symptoms. These results correspond with previous studies that found increased peritraumatic dissociation among rescue personnel as a function of exposure severity. Explanations for these results are discussed. Copyright © 2006 John Wiley & Sons, Ltd.
PTSD and ADHD: underlying factors in many cases of burnout
Authors: Brattberg Gunilla
Published: December 2006

Objective: To analyse the extent to which traumatic life events, post‐traumatic stress disorder (PTSD) and the neuropsychiatric disorder attention deficit hyperactivity disorder (ADHD) can be contributors associated with burnout and the long‐term sick leave that results from it.

Subjects: Sixty‐two individuals on long‐term sick leave due to stress‐related poor health and burnout, and 83 working individuals were screened for the presence of traumatic life events, PTSD and ADHD. Potential background factors involved in burnout were analysed using a multiple logistic regression.

Results: Fifty‐two per cent of those on long‐term sick leave were judged to have PTSD and 24 per cent to have ADHD. The number of suspected/possible cases was even higher—71 per cent and 56 per cent, respectively. Nineteen per cent were judged to have both PTSD and ADHD; 56 per cent were judged to have PTSD and/or ADHD. PTSD, ADHD and traumatic life events in the form of sexual assault and severe human suffering were all strongly associated with both burnout and long‐term sick leave.

Conclusions: Since ADHD is almost never discussed and PTSD rarely so in the occupational rehabilitation of individuals with burnout, these results should act as a warning signal. Further studies are needed, however, including clinical examinations in order to establish with certainty if PTSD and ADHD can predict burnout followed by long‐term sick leave. Copyright © 2006 John Wiley & Sons, Ltd.
Application of a ray theory model to the prediction of noise emissions from isolated wind turbines and wind parks
Authors: Prospathopoulos John M. , Voutsinas Spyros G.
Published: December 2006

Various propagation models have been developed to estimate the level of noise near residential areas. Predictions and measurements have proven that proper modelling of the propagation medium is of particular importance. In the present work, calculations are performed using a ray theory methodology. The ray trajectory and transport equations are derived from the linear acoustics equations for a moving medium in three dimensions. Ground and atmospheric absorption, wave refraction and diffraction and atmospheric turbulence are taken into account by introducing appropriate coefficients in the equations. In the case of a wind turbine (W/T) it is assumed that noise is produced by a point source located at the rotor centre. Given the sound power spectrum, the noise spectrum at the receiver is obtained by solving the axisymmetric propagation problem. The procedure consists of (a) finding the eigenrays, (b) calculating the energy losses along the eigenrays and (c) synthesizing the sound pressure level (SPL) by superposing the contributions of the eigenrays. In the case of a wind park the total SPL is calculated by superposing the contributions of all W/Ts. Application is made to five cases of isolated W/Ts in terrains of varying complexity. In flat or even smooth terrain the predictions agree well with the measurements. In complex terrain the predictions can be considered satisfactory, taking into account the assumption of constant wind velocity profile. Application to a wind park shows clearly the influence of the terrain on the wind velocity and consequently on the SPL. Copyright © 2006 John Wiley &Sons, Ltd.
Nerve Transfers for Adult Traumatic Brachial Plexus Palsy (Brachial Plexus Nerve Transfer)
Authors: Rohde Rachel S. , Wolfe Scott W.
Published: December 2006

Adult traumatic brachial plexus injuries can have devastating effects on upper extremity function. Although neurolysis, nerve repair, and nerve grafting have been used to treat injuries to the plexus, nerve transfer makes use of an undamaged nerve to supply motor input over a relatively short distance to reinnervate a denervated muscle. A review of several recent innovations in nerve transfer surgery for brachial plexus injuries is illustrated with surgical cases performed at this institution.
Ulnar Nerve Compression in the Cubital Tunnel by an Epineural Ganglion: A Case Report
Authors: Boursinos Loukas A. , Dimitriou Christos G.
Published: December 2006

Epineural ganglia are considered to be a usual cause of peripheral nerve compression. In this report, we present a rare case of ulnar nerve compression by an epineural ganglion in the cubital tunnel. A 28-year-old right-handed female secretary developed progressive pain, numbness, and weakness in her right elbow, forearm, and hand for 6 months. Atrophy of the adductor pollicis and the first dorsal interosseous muscles was apparent. Clinical examination revealed a cystic mass at the posterior side of the elbow. Magnetic resonance imaging identified a ganglion while electrophysiologic studies revealed a severe conduction block of the ulnar nerve at the elbow. During surgery a 2-cm diameter epineural ganglion was identified compressing the ulnar nerve and was excised using microsurgery techniques. Two months postoperatively, the clinical recovery of the patient was very satisfactory, although the postoperative electrophysiologic studies demonstrated a less dramatic improvement.
The potential role for arachidonic and docosahexaenoic acids in protection against some central nervous system injuries in preterm infants
Authors: Crawford M. A. , Golfetto I. , Ghebremeskel K. , Min Y. , Moodley T. , Poston L. , Phylactos A. , Cunnane S. , Schmidt W.
Published: December 2006

The risk of central nervous, visual, and auditory damage increases from 2/1000 live births in the normal birthweight to >200/1000 as birthweight falls below 1500 g. Such babies are most likely to be born preterm. Advances in infant care have led to increasing numbers of very‐low‐birthweight, preterm infants surviving to school age with moderate to severe brain damage. Steroids are one of the current treatments, but they cause significant, long‐term problems. The evidence reported here suggests an additional approach to protecting the very preterm infant by supporting neurovascular membrane integrity. The complications of preterm, very‐low‐birthweight babies include bronchopulmonary dysplasia, retinopathy of prematurity, intraventricular hemorrhage, periventricular leukomalacia, and necrotizing enterocolitis, all of which have a vascular component. Arachidonic acid (AA) and DHA are essential, structural, and functional constituents of cell membranes. They are especially required for the growth and function of the brain and vascular systems, which are the primary biofocus of human fetal growth. Molecular dynamics and experimental evidence suggest that DHA could be the ligand for the retinoid X receptor (RXR) in neural tissue. RXR activation is an obligatory step in signaling to the nucleus and in the regulation of gene expression. Very preterm babies are born with minimal fat stores and suboptimal circulating levels of these nutrients. Postanatally, they lose the biomagnification of the proportions of AA and DHA by the placenta for the fetus. No current nutritional management repairs these deficits. The placental biomagnification profile highlights AA rather than DHA. The resultant fetal FA profile closely resembles that of the vascular endothelium and not the brain. Without this nourishment, cell membrane abnormalities would be predicted. We present a scientific rationale for a common pathogenic process in the complications of prematurity.
Diets could prevent many diseases
Authors: Lands William E. M.
Published: December 2006

The 2002 ISSFAL Meeting arranged a special evening discussion with professional dietitians about diet‐tissue‐disease relationships involving essential fatty acids and eicosanoids. The balance of eicosanoid precursors in human tissues differs widely, reflecting voluntary dietary choices among different groups worldwide. An empirical quantitative diet‐tissue relationship fits these diverse values as well as other research reports on essential fatty acid metabolism. Information for dietitians and nutritionists about essential fatty acids and eicosanoids is also given in two distance learning web sites, http://ods.od.nih.gov/eicosanoids/ and http:// efaeducation.nih.gov/, which facilitate dietitian education and diet counseling. These sites also have an innovative, interactive diet planning software program with the empirical equation embedded in it to help evaluate personal food choices in the context of the diet‐tissue‐disease relationship and other widely recommended dietary advice.
Fatty acids, the immune response, and autoimmunity: A question of n−6 essentiality and the balance between n−6 and n−3
Authors: Harbige Laurence S.
Published: December 2006

The essentiality of n−6 polyunsaturated fatty acids (PUFA) is described in relation to a thymus/thymocyte accretion of arachidonic acid (20∶4n−6, AA) in early development, and the high requirement of lymphoid and other cells of the immune system for AA and linoleic acid (18∶2n−6, LA) for membrane phospholipids. Low n−6 PUFA intakes enhance whereas high intakes decrease certain immune functions. Evidence from in vitro and in vivo studies for a role of AA metabolites in immune cell development and functions shows that they can limit or regulate cellular immune reactions and can induce deviation toward a T helper (Th)2‐like immune response. In contrast to the effects of the oxidative metabolites of AA, the longer‐chain n−6 PUFA produced by γ‐linolenic acid (18∶3n−6, GLA) feeding decreases the Th2 cytokine and immunoglobulin (Ig)G1 antibody response. The n−6 PUFA, GLA, dihomo‐γ‐linolenic acid (20∶3n−6, DHLA) and AA, and certain oxidative metabolites of AA can also induce T‐regulatory cell activity, e.g., transforming growth factor (IGF)‐β‐producing T cells; GLA feeding studies also demonstrate reduced proinflammatory interleukin (IL)‐1 and tumor necrosis factor (TNF)‐α production. Low intakes of long‐chain n−3 fatty acids (fish oils) enhance certain immune functions, whereas high intakes are inhibitory on a wide range of functions, e.g., antigen presentation, adhesion molecule expression, Th1 and th2 responses, proinflammatory cytokine and eicosanoid production, and they induce lymphocyte apoptosis. Vitamin E has a demonstrable critical role in long‐chain n−3 PUFA interactions with immune functions, often reversing the effects of fish oil. The effect of dietary fatty acids on animal autoimmune disease models depends on both the autoimmune model and the amount and type of fatty acids fed. Diets low in fat, essential fatty acid deficient (EFAD), or high in long‐chain n−3 PUFA from fish oils increase survival and reduce disease severity in spontaneous autoantibody‐mediated disease, whereas high‐fat LA‐rich diets increase disease severity. In experimentally induced T cell‐mediated autoimmune disease, EFAD diets or diets supplemented with long‐chain n−3 PUFA augment disease, whereas n−6 PUFA prevent or reduce the severity. In contrast, in both T cell‐ and antibody‐mediated autoimmune disease, the desaturated/elongated metabolites of LA are protective. PUFA of both the n−6 and n−3 families are clinically useful in human autoimmune‐inflammatory disorders, but the precise mechanisms by which these fatty acids exert their clinical effects are not well understood. Finally, the view that all n−6 PUFA are proinflammatory requires revision, in part, and their essential regulatory and developmental role in the immune system warrants appreciation.
Fish consumption and blood lipids in three ethinic groups of Québec (canada)
Authors: Dewailly Éric , Blanchet Carole , Gingras Suzanne , Lemieux Simone , Holub Bruce John
Published: December 2006

The purpose of this study was to compare fish intake and plasma phospholipid concentrations of n−3 fatty acids, in particular of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), among representative population samples of Québecers, James Bay Cree, and Inuit of Nunavik (Canada). The relationships between these concentrations and cardiovascular disease (CVD) risk factors were also investigated and compared in the three populations. In 1990–1992, the study subjects had participated in the extensive Santé Québec health surveys conducted in southern Québec, James Bay, and Nunavik. Significant differences in levels of CVD risk factors were found among these three populations. Globally, Inuit showed the lowest risk status for CVD compared with Cree and Québecers, despite the high prevalence of cigarette smoking and obesity. Daily fish intakes varied significantly among the three groups, averaging 13, 60, and 131 g for Québecers, Cree, and Inuit, respectively. Concentrations of EPA+DHA in plasma phospholipids were highest among Inuit (8.0%), second‐highest among Cree (3.9%), and lowest among Québecers (1.8%). When the three populations were grouped together, there was a positive association between concentrations of EPA+DHA stratified into quartiles and HDL cholesterol, with a significant relation in quartile 4 (EPA+DHA ≥4.04%). An inverse relation was also found betwen EPA+DHA and triacylglycerols in quartile 4. Our results indicate that increased consumption of fish as a source of n−3 fatty acids is beneficially associated with levels of HDL cholesterol and triacylglycerols.