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Selected AbstractsBig Consequences of Small Changes (Non-locality and non-linearity of Hartree-Fock equations)CONTRIBUTIONS TO PLASMA PHYSICS, Issue 7-8 2009M.Ya. Amusia Abstract It is demonstrated that non-locality and non-linearity of Hartree-Fock equations dramatically affect the properties of their solutions that essentially differ from solutions of Schrödinger equation with a local potential. Namely, it acquires extra zeroes, has different coordinate asymptotic, violates so-called gauge-invariance, has different scattering phases at zero energy, has in some cases several solutions with the same set of quantum numbers, usually equivalent expressions of current and Green's functions became non-equivalent. These features result in a number of consequences for probabilities of some physical processes, leading e. g. to extra width of atomic Giant resonances and enhance considerably the ionization probability of inner atomic electrons by a strong field (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Optimal Board Monitoring in Family-owned Companies: Evidence from AsiaCORPORATE GOVERNANCE, Issue 1 2010En-Te Chen ABSTRACT Manuscript Type: Empirical Research Question/Issue: We propose that high levels of monitoring are not always in the best interests of minority shareholders. In family-owned companies the optimal level of board monitoring required by minority shareholders is expected to be lower than that of other companies. This is because the relative benefits and costs of monitoring are different in family-owned companies. Research Findings/Insights: At moderate levels of board monitoring, we find concave relationships between board monitoring variables and firm performance for family-owned companies but not for other companies. The optimal level of board monitoring for our sample of Asian family-owned companies equates to board independence of 38 per cent, separation of the chairman and CEO positions, and establishment of audit and remuneration committees. Additional testing shows that the optimal level of board monitoring is sensitive to the magnitude of the agency conflict between the family group and minority shareholders and the presence of substitute monitoring. Theoretical/Academic Implications: This study shows that the effect of additional monitoring on agency costs and firm performance differs across firms with different ownership structures. Practitioner/Policy Implications: For policymakers, the results show that more monitoring is not always in the best interests of minority shareholders. Therefore, it may be inappropriate for regulators to advise all companies to follow the same set of corporate governance guidelines. However, our results also indicate that the board governance practices of family-owned companies are still well below the identified optimal levels. [source] Head regeneration in HydraDEVELOPMENTAL DYNAMICS, Issue 2 2003Hans R. Bode Abstract Hydra, a primitive metazoan, has a simple structure consisting of a head, body column, and foot aligned along a single oral,aboral axis. The body column has a high capacity for regeneration of both the head and foot. Because of the tissue dynamics that take place in adult Hydra, the processes governing axial patterning are continuously active to maintain the form of the animal. Regeneration in hydra is morphallactic and closely related to these axial patterning processes. As might be expected, analysis at the molecular level indicates that the same set of genes are involved in head regeneration and the maintenance of the head in the context of the tissue dynamics of the adult. The genes analyzed so far play roles in axial patterning processes in bilaterians. Developmental Dynamics 226:225,236, 2003. © 2003 Wiley-Liss, Inc. [source] The origins and evolution of links between word learning and conceptual organization: new evidence from 11-month-oldsDEVELOPMENTAL SCIENCE, Issue 2 2003Sandra Waxman How do infants map words to their meaning? How do they discover that different types of words (e.g. noun, adjective) refer to different aspects of the same objects (e.g. category, property)? We have proposed that (1) infants begin with a broad expectation that novel open-class words (both nouns and adjectives) highlight commonalities (both category- and property-based) among objects, and that (2) this initial expectation is subsequently fine-tuned through linguistic experience. We examine the first part of this proposal, asking whether 11-month-old infants can construe the very same set of objects (e.g. four purple animals) either as members of an object category (e.g. animals) or as embodying a salient object property (e.g. four purple things), and whether naming (with count nouns vs. adjectives) differentially influences their construals. Results support the proposal. Infants treated novel nouns and adjectives identically, mapping both types of words to both category- and property-based commonalities among objects. [source] The Use of Generalizability (G) Theory in the Testing of Linguistic MinoritiesEDUCATIONAL MEASUREMENT: ISSUES AND PRACTICE, Issue 1 2006Flores, Guillermo Solano We contend that generalizability (G) theory allows the design of psychometric approaches to testing English-language learners (ELLs) that are consistent with current thinking in linguistics. We used G theory to estimate the amount of measurement error due to code (language or dialect). Fourth- and fifth-grade ELLs, native speakers of Haitian-Creole from two speech communities, were given the same set of mathematics items in the standard English and standard Haitian-Creole dialects (Sample 1) or in the standard and local dialects of Haitian-Creole (Samples 2 and 3). The largest measurement error observed was produced by the interaction of student, item, and code. Our results indicate that the reliability and dependability of ELL achievement measures is affected by two facts that operate in combination: Each test item poses a unique set of linguistic challenges and each student has a unique set of linguistic strengths and weaknesses. This sensitivity to language appears to take place at the level of dialect. Also, students from different speech communities within the same broad linguistic group may differ considerably in the number of items needed to obtain dependable measures of their academic achievement. Whether students are tested in English or in their first language, dialect variation needs to be considered if language as a source of measurement error is to be effectively addressed. [source] Prediction of biodegradation from the atom-type electrotopological state indicesENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 10 2001Jarmo Huuskonen Abstract A group contribution method based on atom-type electrotopological state indices for predicting the biodegradation of a diverse set of 241 organic chemicals is presented. Multiple linear regression and artificial neural networks were used to build the models using a training set of 172 compounds, for which the approximate time for ultimate biodegradation was estimated from the results of a survey of an expert panel. Derived models were validated by using a leave-25%-out method and against two test sets of 12 and 57 chemicals not included in the training set. The squared correlation coefficient (r2) for a linear model with 15 structural parameters was 0.76 for the training set and 0.68 for the test set of 12 molecules. The model predicted correctly the biodegradation of 48 chemicals in the test set of 57 molecules, for which biodegradability was presented as rapid or slow. The use of artificial neural networks gave better prediction for both test sets when the same set of parameters was tested as inputs in neural network simulations. The predictions of rapidly biodegradable chemicals were more accurate than the predictions of slowly bio-degradable chemicals for both the regression and neural network models. [source] Epstein,Barr virus reactivation and multiple sclerosisEUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2008Ø. Torkildsen Infection with Epstein,Barr virus (EBV) is considered one of the possible key environmental factors in the aetiology of multiple sclerosis (MS). Whether EBV plays an underlying role as an activator of MS remains, however, controversial. Sixty-one patients with definite relapsing,remitting multiple sclerosis (RRMS) according to the Poser criteria were followed for 1 year. Blood samples were drawn at baseline, months 3, 6 and 12, and in case of any clinical exacerbation. Twenty-three baseline,paired exacerbation samples in the same set were quantitatively analysed to examine whether exacerbations in MS were associated with a change in anti-diffuse component of the EBV-early antigen (EA-D) IgG ratio. All the 61 patients (100%) were anti-viral capsid antigen (VCA) IgG positive, one (2%) was anti-VCA IgM positive and 60 (98%) were anti-EBV nuclear antigen IgG positive. Mean anti-EA-D IgG at baseline was 0.57 (range 0.12,2.70) and at the time of exacerbations 0.61 (range 0.11,2.70). Wilcoxon signed rank test revealed no differences between the 23 baseline and paired exacerbation samples (P = 0.58). Our findings suggest that reactivation of latent EBV infection does not play a significant role for exacerbations in RRMS. [source] Context-specific modulation of cocaine-induced locomotor sensitization and ERK and CREB phosphorylation in the rat nucleus accumbensEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2009Marcelo T. Marin Abstract Learned associations are hypothesized to develop between drug effects and contextual stimuli during repeated drug administration to produce context-specific sensitization that is expressed only in the drug-associated environment and not in a non-drug-paired environment. The neuroadaptations that mediate such context-specific behavior are largely unknown. We investigated context-specific modulation of cAMP-response element-binding protein (CREB) phosphorylation and that of four upstream kinases in the nucleus accumbens that phosphorylate CREB, including extracellular signal-regulated kinase (ERK), cAMP-dependent protein kinase, calcium/calmodulin-dependent kinase (CaMK) II and CaMKIV. Rats received seven once-daily injections of cocaine or saline in one of two distinct environments outside their home cages. Seven days later, test injections of cocaine or saline were administered in either the paired or the non-paired environment. CREB and ERK phosphorylation were assessed with immunohistochemistry, and phosphorylation of the remaining kinases, as well as of CREB and ERK, was assessed by western blotting. Repeated cocaine administration produced context-specific sensitized locomotor responses accompanied by context-specific enhancement of the number of cocaine-induced phosphoCREB-immunoreactive and phosphoERK-immunoreactive nuclei in a minority of neurons. In contrast, CREB and CaMKIV phosphorylation in nucleus accumbens homogenates were decreased by cocaine test injections. We have recently shown that a small number of cocaine-activated accumbens neurons mediate the learned association between cocaine effects and the drug administration environment to produce context-specific sensitization. Context-specific phosphorylation of ERK and CREB in the present study suggests that this signal transduction pathway is selectively activated in the same set of cocaine-activated accumbens neurons that mediate this learned association. [source] Dissociation of function between the dorsal and the ventral hippocampus in spatial learning abilities of the rat: a within-subject, within-task comparison of reference and working spatial memoryEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2004Helen H. J. Pothuizen Abstract Lesions restricted to the dorsal, but not the ventral, hippocampus severely impair the formation of spatial memory. This dissociation was first demonstrated using the water maze task. The present study investigated whether the dorsal and the ventral hippocampus are involved differentially in spatial reference and spatial working memory using a four-baited/four-unbaited version of the eight-arm radial maze task. This test allows the concurrent evaluation of reference and working memory with respect to the same set of spatial cues, and thereby enables a within-subjects within-task comparison between the two forms of memory functions. Rats with N -methyl- d -aspartic acid-induced excitotoxic lesions of the dorsal hippocampus, ventral hippocampus or both were compared with sham and unoperated controls. We showed that dorsal lesions were as effective as complete lesions in severely disrupting both reference and working spatial memory, whereas rats with ventral lesions performed at a level comparable with controls. These results lend further support to the existence of a functional dissociation between the dorsal and the ventral hippocampus, with the former being preferentially involved in spatial learning. [source] IS INBREEDING DEPRESSION LOWER IN MALADAPTED POPULATIONS?EVOLUTION, Issue 7 2009A QUANTITATIVE GENETICS MODEL Despite abundant empirical evidence that inbreeding depression varies with both the environment and the genotypic context, theoretical predictions about such effects are still rare. Using a quantitative genetics model, we predict amounts of inbreeding depression for fitness emerging from Gaussian stabilizing selection on some phenotypic trait, on which, for simplicity, genetic effects are strictly additive. Given the strength of stabilizing selection, inbreeding depression then varies simply with the genetic variance for the trait under selection and the distance between the mean breeding value and the optimal phenotype. This allows us to relate the expected inbreeding depression to the degree of maladaptation of the population to its environment. We confront analytical predictions with simulations, in well-adapted populations at equilibrium, as well as in maladapted populations undergoing either a transient environmental shift, or gene swamping in heterogeneous habitats. We predict minimal inbreeding depression in situations of extreme maladaptation. Our model provides a new basis for interpreting experiments that measure inbreeding depression for the same set of genotypes in different environments, by demonstrating that the history of adaptation, in addition to environmental harshness per se, may account for differences in inbreeding depression. [source] CONVERGENCE AND THE MULTIDIMENSIONAL NICHEEVOLUTION, Issue 2 2005Luke J. Harmon Abstract Convergent evolution has played an important role in the development of the ecological niche concept. We investigated patterns of convergent and divergent evolution of Caribbean Anolis lizards. These lizards diversified independently on each of the islands of the Greater Antilles, producing the same set of habitat specialists on each island. Using a phylogenetic comparative framework, we examined patterns of morphological convergence in five functionally distinct sets of morphological characters: body size, body shape, head shape, lamella number, and sexual size dimorphism. We find evidence for convergence among members of the habitat specialist types for each of these five datasets. Furthermore, the patterns of convergence differ among at least four of the five datasets; habitat specialists that are similar for one set of characters are often greatly different for another. This suggests that the habitat specialist niches into which these anoles have evolved are multidimensional, involving several distinct and independent aspects of morphology. [source] Adjusting life for quality or disability: stylistic difference or substantial dispute?,HEALTH ECONOMICS, Issue 11 2009Mara Airoldi Abstract This paper focuses on the contrast between describing the benefit of a healthcare intervention as gain in health (QALY-type ideas) or a disability reduction (DALY-type ideas). The background is an apparent convergence in practice of the work conducted under both traditions. In the light of these methodological developments, we contrast a health planner who wants to maximise health and one who wants to minimise disability. To isolate the effect of framing the problem from a health or a disability perspective, we do not use age-weighting in calculating DALY and employ a common discounting methodology and the same set of quality of life weights. We find that interventions will be ranked in a systematically different way. The difference, however, is not determined by the use of a health or a disability perspective but by the use of life expectancy tables to determine the years of life lost. We show that this feature of the DALY method is problematic and we suggest its dismissal in favour of a fixed reference age rendering the use of a health or a disability perspective merely stylistic. Copyright © 2008 John Wiley & Sons, Ltd. [source] Downscaling of global climate models for flood frequency analysis: where are we now?HYDROLOGICAL PROCESSES, Issue 6 2002Christel Prudhomme Abstract The issues of downscaling the results from global climate models (GCMs) to a scale relevant for hydrological impact studies are examined. GCM outputs, typically at a spatial resolution of around 3° latitude and 4° longitude, are currently not considered reliable at time scales shorter than 1 month. Continuous rainfall-runoff modelling for flood regime assessment requires input at the daily or even hourly time-step. A review of the different methodologies suggested in the literature to downscale GCM results at smaller spatial and temporal resolutions is presented. The methods, from simple interpolation to more sophisticated dynamical modelling, through multiple regression and weather generators, are, however, mostly based directly on GCM outputs, sometimes at daily time-step. The approach adopted is a simple, empirical methodology based on modelled monthly changes from the HadCM2 greenhouse gases experiment for the time horizon 2050s. Three daily rainfall scenarios are derived from the same set of monthly changes, representing different possible changes in the rainfall regime. The first scenario represents an increase of the occurrence of frontal systems, corresponding to a decrease in the rainfall intensity; the second corresponds to an increase in convective storm-type rainfall, characterized by extreme events with higher intensity; the third one assumes an increase in the monthly rainfall without any change in rainfall variability. A continuous daily rainfall-runoff model, calibrated for the Severn catchment, was used to generate daily flow series for the 1961,90 baseline period and the 2050s, and a peaks-over-threshold analysis was undertaken to produce flood frequency distributions for the two time horizons. Though the three scenarios lead to an increase in the magnitude and the frequency of the extreme flood events, the impact is strongly influenced by the type of daily rainfall scenario applied. We conclude that if the next generation of GCMs produce more reliable rainfall variance estimates, then more appropriate ways of deriving rainfall scenarios could be developed using weather generators rather than empirical methods. Copyright © 2002 John Wiley & Sons, Ltd. [source] Facial identity and facial expression matching in 5,12-year-old children and adultsINFANT AND CHILD DEVELOPMENT, Issue 5 2009Frini Karayanidis Abstract Facial identity and facial expression matching tasks were completed by 5,12-year-old children and adults using stimuli extracted from the same set of normalized faces. Configural and feature processing were examined using speed and accuracy of responding and facial feature selection, respectively. Facial identity matching was slower than face expression matching for all age groups. Large age effects were found on both speed and accuracy of responding and feature use in both identity and expression matching tasks. Eye region preference was found on the facial identity task and mouth region preference on the facial expression task. Use of mouth region information for facial expression matching increased with age, whereas use of eye region information for facial identity matching peaked early. The feature use information suggests that the specific use of primary facial features to arrive at identity and emotion matching judgments matures across middle childhood. Copyright © 2009 John Wiley & Sons, Ltd. [source] A unified bounding surface plasticity model for unsaturated soilsINTERNATIONAL JOURNAL FOR NUMERICAL AND ANALYTICAL METHODS IN GEOMECHANICS, Issue 3 2006A.R. Russell Abstract A unified constitutive model for unsaturated soils is presented in a critical state framework using the concepts of effective stress and bounding surface plasticity theory. Consideration is given to the effects of unsaturation and particle crushing in the definition of the critical state. A simple isotropic elastic rule is adopted. A loading surface and a bounding surface of the same shape are defined using simple and versatile functions. The bounding surface and elastic rules lead to the existence of a limiting isotropic compression line, towards which the stress trajectories of all isotropic compression load paths approach. A non-associated flow rule of the same general form is assumed for all soil types. Isotropic hardening/softening occurs due to changes in plastic volumetric strains as well as suction for some unsaturated soils, enabling the phenomenon of volumetric collapse upon wetting to be accounted for. The model is used to simulate the stress,strain behaviour observed in unsaturated speswhite kaolin subjected to three triaxial test load paths. The fit between simulation and experiment is improved compared to that of other constitutive models developed using conventional Cam-Clay-based plasticity theory and calibrated using the same set of data. Also, the model is used to simulate to a high degree of accuracy the stress,strain behaviour observed in unsaturated Kurnell sand subjected to two triaxial test load paths and the oedometric compression load path. For oedometric compression theoretical simulations indicate that the suction was not sufficiently large to cause samples to separate from the confining ring. Copyright © 2005 John Wiley & Sons, Ltd. [source] FETI-DP, BDDC, and block Cholesky methodsINTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN ENGINEERING, Issue 2 2006Jing Li Abstract The FETI-DP and BDDC algorithms are reformulated using Block Cholesky factorizations, an approach which can provide a useful framework for the design of domain decomposition algorithms for solving symmetric positive definite linear system of equations. Instead of introducing Lagrange multipliers to enforce the coarse level, primal continuity constraints in these algorithms, a change of variables is used such that each primal constraint corresponds to an explicit degree of freedom. With the new formulation of these algorithms, a simplified proof is provided that the spectra of a pair of FETI-DP and BDDC algorithms, with the same set of primal constraints, are essentially the same. Numerical experiments for a two-dimensional Laplace's equation also confirm this result. Copyright © 2005 John Wiley & Sons, Ltd. [source] A batch-type time-true ATM-network simulator,design for parallel processingINTERNATIONAL JOURNAL OF COMMUNICATION SYSTEMS, Issue 8 2002Michael Logothetis Abstract This paper presents a new type of network simulator for simulating the call-level operations of telecom networks and especially ATM networks. The simulator is a pure time-true type as opposed to a call-by-call type simulator. It is also characterized as a batch-type simulator. The entire simulation duration is divided into short time intervals of equal duration, t. During t, a batch processing of call origination or termination events is executed and the time-points of these events are sorted. The number of sorting executions is drastically reduced compared to a call-by-call simulator, resulting in considerable timesaving. The proposed data structures of the simulator can be implemented by a general-purpose programming language and are well fitted to parallel processing techniques for implementation on parallel computers, for further savings of execution time. We have first implemented the simulator in a sequential computer and then we have applied parallelization techniques to achieve its implementation on a parallel computer. In order to simplify the parallelization procedure, we dissociate the core simulation from the built-in call-level functions (e.g. bandwidth control or dynamic routing) of the network. The key point for a parallel implementation is to organize data by virtual paths (VPs) and distribute them among processors, which all execute the same set of instructions on this data. The performance of the proposed batch-type, time-true, ATM-network simulator is compared with that of a call-by-call simulator to reveal its superiority in terms of sequential execution time (when both simulators run on conventional computers). Finally, a measure of the accuracy of the simulation results is given. Copyright © 2002 John Wiley & Sons, Ltd. [source] Accurate closed-form model for computation of conductor loss of coplanar waveguideINTERNATIONAL JOURNAL OF RF AND MICROWAVE COMPUTER-AIDED ENGINEERING, Issue 1 2010Payal Majumdar Abstract This study estimates the accuracy of HFSS and Sonnet and other models against the experimental results from three sources. A closed-form model for experiment based stopping distance is developed to calculate accurately conductor loss of CPW. The present improved Holloway and Kuester (IHK) model has an average accuracy of 3.7% against the experimental results from different sources in the frequency range 1,120 GHz with conductor thickness of 0.25,1.58 ,m. The original Holloway and Kuester model has an average accuracy of 13.7% and model of Ponchak et al. 17.1 % against same set of experimental results. HFSS and Sonnet have average accuracy of 7.86% and 10.33% against same set of experimental data. The accuracy of IHK model is also examined against HFSS and Sonnet for the conductor thickness up to 9 ,m and substrate relative permittivity in the range of 3.8,20. © 2009 Wiley Periodicals, Inc. Int J RF and Microwave CAE, 2010. [source] Adaptive sampling applied to multivariate, multiple output rational interpolation models with application to microwave circuitsINTERNATIONAL JOURNAL OF RF AND MICROWAVE COMPUTER-AIDED ENGINEERING, Issue 4 2002Robert Lehmensiek Abstract A fast and efficient adaptive sampling algorithm for multivariate, multiple output rational interpolation models is presented, which is based on convergents of Thiele type branched continued fractions. The multiple output interpolation model consists of a set of rational interpolants, and each interpolant models one of the output parameters. A single global error function is defined that incorporates all the output parameters, and it is used for the selection of the same set of support points for all the interpolants. The technique is evaluated on several passive microwave structures and compared to previously published results. © 2002 Wiley Periodicals, Inc. Int J RF and Microwave CAE 12: 332,340, 2002. Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mmce10032 [source] Confidence and Investors' Reliance on Disciplined Trading StrategiesJOURNAL OF ACCOUNTING RESEARCH, Issue 3 2003Mark W. Nelson abstract Researchers and practitioners in accounting and finance often investigate or advocate particular disciplined trading strategies, but little work investigates the determinants of individual investors' trading-strategy reliance. We report two experiments, which provide evidence that the dual-source model of overconfidence (Sniezek and Buckley [1991]) predicts the circumstances in which investors are more likely to rely on disciplined trading strategies. Our results indicate that reliance is more likely when investors trade portfolios of securities rather than trading on a case-by-case basis, particularly when investors have received feedback that their previous (unaided) trading decisions have been unprofitable. These results are driven by the number of shares that investors transact rather than by investors' directional agreement with the recommendations of the trading strategy, suggesting that the effects of a portfolio approach and trading experience occur by mitigating investors' overconfidence. The effects violate an aspect of economic rationality because our experiments ensure that investors in all conditions trade the same set of securities based on the same set of information. [source] Comparative Pharmacology of Guinea Pig Cardiac Myocyte and Cloned hERG (IKr) ChannelJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 11 2004CHRISTINA DAVIE Ph.D. Introduction: This study used whole-cell, patch clamp techniques on isolated guinea pig ventricular myocytes and HEK293 cells expressing cloned human ether-a-go-go-related gene (hERG) to examine the action of drugs causing QT interval prolongation and torsades de pointes (TdP) in man. Similarities and important differences in drug actions on cardiac myocytes and cloned hERG IKr channels were established. Qualitative actions of the drugs on cardiac myocytes corresponded with results obtained from Purkinje fibers and measurement of QT interval prolongation in animal and human telemetry studies. Methods and Results: Adult guinea pig ventricular myocytes were isolated by enzymatic digestion. Cells were continuously perfused with Tyrode's solution at 33,35°C. Recordings were made using the whole-cell, patch clamp technique. Action potentials (APs) were elicited under current clamp. Voltage clamp was used to study the effect of drugs on IKr (rapidly activating delayed rectifier potassium current), INa (sodium current), and ICa (L-type calcium current). Dofetilide increased the myocyte action potential duration (APD) in a concentration-dependent manner, with a pIC50 of 7.3. Dofetilide 1 ,M elicited early afterdepolarizations (EADs) but had little affect on ICa or INa. E-4031 increased APD in a concentration-dependent manner, with a pIC50 of 7.2. In contrast, 10 ,M loratadine, desloratadine, and cetirizine had little effect on APD or IKr. Interestingly, cisapride displayed a biphasic effect on myocyte APD and inhibited ICa at 1 ,M. Even at this high concentration, cisapride did not elicit EADs. A number of AstraZeneca compounds were tested on cardiac myocytes, revealing a mixture of drug actions that were not observed in hERG currents in HEK293 cells. One compound, particularly AR-C0X, was a potent blocker of myocyte AP (pIC50 of 8.4). AR-C0X also elicited EADs in cardiac myocytes. The potencies of the same set of drugs on the cloned hERG channel also were assessed. The pIC50 values for dofetilide, E-4031, terfenadine, loratadine, desloratadine, and cetirizine were 6.8, 7.1, 7.3, 5.1, 5.2, and <4, respectively. Elevation of temperature from 22 to 35°C significantly enhanced the current kinetics and amplitudes of hERG currents and resulted in approximately fivefold increase in E-4031 potency. Conclusion: Our study demonstrates the advantages of cardiac myocytes over heterologously expressed hERG channels in predicting QT interval prolongation and TdP in man. The potencies of some drugs in cardiac myocytes were similar to hERG, but only myocytes were able to detect important changes in APD characteristics and display EADs predictive of arrhythmia development. We observed similar qualitative drug profiles in cardiac myocytes, dog Purkinje fibers, and animal and human telemetry studies. Therefore, isolated native cardiac myocytes are a better predictor of drug-induced QT prolongation and TdP than heterologously expressed hERG channels. Isolated cardiac myocytes, when used with high-throughput patch clamp instruments, may have an important role in screening potential cardiotoxic compounds in the early phase of drug discovery. This would significantly reduce the attrition rate of drugs entering preclinical and/or clinical development. The current kinetics and amplitudes of the cloned hERG channel were profoundly affected by temperature, significantly altering the potency of one drug (E-4031). This finding cautions against routine drug testing at room temperature compared to physiologic temperature when using the cloned hERG channel. [source] Complete graph conjecture for inner-core electrons: Homogeneous index caseJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 9 2003Lionello Pogliani Abstract The complete graph conjecture that encodes the inner-core electrons of atoms with principal quantum number n , 2 with complete graphs, and especially with odd complete graphs, is discussed. This conjecture is used to derive new values for the molecular connectivity and pseudoconnectivity basis indices of hydrogen-suppressed chemical pseudographs. For atoms with n = 2 the new values derived with this conjecture are coincident with the old ones. The modeling ability of the new homogeneous basis indices, and of the higher-order terms, is tested and compared with previous modeling studies, which are centered on basis indices that are either based on quantum concepts or partially based on this new conjecture for the inner-core electrons. Two similar algorithms have been proposed with this conjecture, and they parallel the two "quantum" algorithms put forward by molecular connectivity for atoms with n > 2. Nine properties of five classes of compounds have been tested: the molecular polarizabilities of a class of organic compounds, the dipole moment, molar refraction, boiling points, ionization energies, and parachor of a series of halomethanes, the lattice enthalpy of metal halides, the rates of hydrogen abstraction of chlorofluorocarbons, and the pED50 of phenylalkylamines. The two tested algorithms based on the odd complete graph conjecture give rise to a highly interesting model of the nine properties, and three of them can even be modeled by the same set of basis indices. Interesting is the role of some basis indices all along the model. © 2003 Wiley Periodicals, Inc. J Comput Chem 9: 1097,1109, 2003 [source] Computational alanine scanning of the 1:1 human growth hormone,receptor complexJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 1 2002Shuanghong Huo Abstract The MM-PBSA (Molecular Mechanics,Poisson,Boltzmann surface area) method was applied to the human Growth Hormone (hGH) complexed with its receptor to assess both the validity and the limitations of the computational alanine scanning approach. A 400-ps dynamical trajectory of the fully solvated complex was simulated at 300 K in a 101 Å×81 Å×107 Å water box using periodic boundary conditions. Long-range electrostatic interactions were treated with the particle mesh Ewald (PME) summation method. Equally spaced snapshots along the trajectory were chosen to compute the binding free energy using a continuum solvation model to calculate the electrostatic desolvation free energy and a solvent-accessible surface area approach to treat the nonpolar solvation free energy. Computational alanine scanning was performed on the same set of snapshots by mutating the residues in the structural epitope of the hormone and the receptor to alanine and recomputing the ,Gbinding. To further investigate a particular structure, a 200-ps dynamical trajectory of an R43A hormone,receptor complex was simulated. By postprocessing a single trajectory of the wild-type complex, the average unsigned error of our calculated ,,Gbinding is ,1 kcal/mol for the alanine mutations of hydrophobic residues and polar/charged residues without buried salt bridges. When residues involved in buried salt bridges are mutated to alanine, it is demonstrated that a separate trajectory of the alanine mutant complex can lead to reasonable agreement with experimental results. Our approach can be extended to rapid screening of a variety of possible modifications to binding sites. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 15,27, 2002 [source] Molecular mechanics (MM4) calculations on carbonyl compounds part I: aldehydesJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 13 2001Charles H. Langley Abstract Aliphatic aldehydes have been studied with the aid of the MM4 force field. The structures, moments of inertia, vibrational spectra, conformational energies, barriers to internal rotation, and dipole moments have been examined for six compounds (nine conformations). MM4 parameters have been developed to fit the indicated quantities to the wide variety of experimental data. Ab initio (MP2) and density functional theory (B3LYP) calculations have been used to augment and/or replace experimental data, as appropriate. Because more, and to some extent, better, data have become available since MM3 was developed, it was anticipated that the overall accuracy of the information calculated with MM4 would be better than with MM3. The best single measure of the overall accuracy of a force field is the accuracy to which the moments of inertia of a set of compounds (from microwave spectroscopy) can be reproduced. For all of the 20 moments (seven conformations) experimentally known for the aldehyde compounds, the MM4 rms error is 0.30%, while with MM3, the most accurate force field presently available, the rms error over the same set is 1.01%. The calculation of the vibrational spectra was also improved overall. For the four aldehydes that were fully analyzed (over a total of 78 frequencies), the rms errors with MM4 and MM3 are 18 and 38 cm,1, respectively. These improvements came from several sources, but the major ones were separate parameters involving the carbonyl carbon for formaldehyde, the alkyl aldehydes and the ketones, and new crossterms featured in the MM4 force field that are not present in the MM3 version. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1396,1425, 2001 [source] Incremental Organizational Change in a Transforming Society: Managing Turbulence in Hungary in the 1990sJOURNAL OF MANAGEMENT STUDIES, Issue 3 2000Laszlo Czaban The rapid liberalization of the former state socialist economies of Eastern Europe coupled with privatization were thought by many in the early 1990s likely to generate effective capitalist firms quite quickly. However, the radical institutional transformation and collapse of Soviet markets resulted in considerable uncertainty for most companies which, together with high sunk costs and lack of resources, inhibited organizational restructuring and strategic change. Despite high levels of foreign ownership and control by the mid-1990s, many Hungarian companies continued to produce much the same kinds of products for mostly the same customers with inputs from mostly the same suppliers as in 1990. While most had reduced employment substantially, and many had disposed of ancillary organizational units, the bulk of the companies considered here had not greatly altered their work systems and overall organizational structures. In the few enterprises where the production process had been extensively reorganized by 1996, this was funded and directed by foreign firms who had taken them over. These foreign firm-controlled companies also tended to have new top managers from outside the enterprise. They additionally introduced new products more often than Hungarian firms, albeit within rather narrow product lines that usually dominated the domestic market. Overall, most of the enterprises studied were still doing much the same set of activities in the mid-1990s, though with fewer staff, as at the start of the decade, and privatization per se had not led to major shifts in enterprise structure and strategy, nor did it seem likely to do so in the foreseeable future. [source] Reduced expression of MAb6B4 epitopes on chondroitin sulfate proteoglycan aggrecan in perineuronal nets from cerebral cortices of SAMP10 mice: A model for age-dependent neurodegenerationJOURNAL OF NEUROSCIENCE RESEARCH, Issue 6 2008Yuko Saitoh Abstract The accelerated senescence-prone SAMP10 mouse strain is a model for age-dependent neurodegeneration and is characterized by brain atrophy and deficits in learning and memory. Because perineuronal nets play an important role in the synaptic plasticity of adult brains, we examined the distributions of molecules that constitute perineuronal nets in SAMP10 mouse brain samples and compared them with those in control SAMR1 mouse samples. Proteoglycan-related monoclonal antibody 6B4 (MAb6B4) clearly immunostained perineuronal nets in SAMR1 mice cortices, but the corresponding immunostaining in SAMP10 mice was very faint. MAb6B4 recognizes phosphacan/PTP, in immature brains. However, this antibody recognized several protein bands, including a 400-kDa core glycoprotein from chondroitin sulfate proteoglycan in homogenates of mature cortices from SAMR1 mice. The 400-kDa band was also recognized by antiaggrecan antibodies. The aggrecan core glycoprotein band was also detectable in samples from SAMP10 mice, but this glycoprotein was faintly immunostained by MAb6B4. Because MAb6B4 recognized the same set of protein bands that the monoclonal antibody Cat-315 recognized in mature cerebral cortices of SAMR1 mice, the MAb6B4 epitope appears to be closely related to that of Cat-315 and presumably represents a novel type of oligosaccharide that attaches to aggrecans. The Cat-315 epitope colocalized with aggrecan in perineuronal nets from SAMR1 mouse brain samples, whereas its expression was prominently reduced in SAMP10 mouse brain samples. The biological significance of the MAb6B4/Cat-315 epitope in brain function and its relationship to the neurodegeneration and learning disabilities observed in SAMP10 mice remain to be elucidated. © 2007 Wiley-Liss, Inc. [source] Strategy-Proofness and the Tops-Only PropertyJOURNAL OF PUBLIC ECONOMIC THEORY, Issue 1 2008JOHN A. WEYMARK A social choice function satisfies the tops-only property if the chosen alternative only depends on each person's report of his most-preferred alternatives on the range of this function. On many domains, strategy-proofness implies the tops-only property provided that the range of the social choice function satisfies some regularity condition. The existing proofs of this result are model specific. In this paper, a general proof strategy is proposed for showing that a strategy-proof social choice function satisfies the tops-only property when everyone has the same set of admissible preferences. [source] Promoting Physical Activity in GirlsJOURNAL OF SCHOOL HEALTH, Issue 2 2005A Case Study of One School's Success ABSTRACT: This case study profiles one of 24 high schools that participated in a school-based, NIH-funded study to increase physical activity among high school girls. The case study school was one of 12 randomly assigned to the intervention group. The study intervention was based on the premise that a successful intervention is developed and tailored by teachers and staff to fit the context of their school. Intervention guidelines (Essential Elements) and the Coordinated School Health Program (CSHP) model were used to direct intervention activities for physical education, health education, school environment, school health services, faculty/staff health promotion, and family/community involvement. All girls at the case study school received the intervention. A team of school employees provided leadership to develop and implement the intervention in collaboration with a university project staff. Data collected over a two-year period were used to describe changes that occurred in each CSHP area. Key changes were made in the school environment, curricula, policies, and practices. Qualitative measures showed girls more involved in physical activity. Quantitative measures taken in eighth grade, and repeated with the same set of girls in ninth grade, showed increases in both moderate-to-vigorous physical activity (p = < .01) and vigorous physical activity (p = .04). Other schools can use this case to modify components of the CSHP model to increase physical activity among high school girls. [source] ANALYZING CORRELATIONS BETWEEN STREAM AND WATERSHED ATTRIBUTES,JOURNAL OF THE AMERICAN WATER RESOURCES ASSOCIATION, Issue 3 2003John Van Sickle ABSTRACT: Bivariate correlation analysis has been widely used to explore relationships between stream and watershed attributes that have all been measured on the same set of watersheds or sampling locations. Researchers routinely test H0: ,= 0 for each correlation in a large table and then go on to discuss only those that are declared "significant." Such test results are inaccurate because no allowance is made for multiple testing, and also because the tests are not mutually independent. This paper reviews the Bonferroni approach to controlling the overall error rate in multiple testing and shows how the approach becomes impractical for large correlation tables. The Hotelling/Williams test is introduced for comparing two dependent correlations that share a variable, and numerical constraints for two such correlations are illustrated. References are also given for testing other hypothesized patterns among dependent correlations, and links to dependent correlation software are provided. The methods are illustrated for watershed and stream variables sampled in 23 small agricultural watersheds of the Willamette Valley, Oregon. [source] Evaluation of statistical protocols for quality control of ecosystem carbon dioxide fluxesJOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES A (STATISTICS IN SOCIETY), Issue 1 2007Jorge F. Perez-Quezada Summary., The process of quality control of micrometeorological and carbon dioxide (CO2) flux data can be subjective and may lack repeatability, which would undermine the results of many studies. Multivariate statistical methods and time series analysis were used together and independently to detect and replace outliers in CO2 flux data derived from a Bowen ratio energy balance system. The results were compared with those produced by five experts who applied the current and potentially subjective protocol. All protocols were tested on the same set of three 5-day periods, when measurements were conducted in an abandoned agricultural field. The concordance of the protocols was evaluated by using the experts' opinion (mean ± 1.96 standard deviations) as a reference interval (the Bland,Altman method). Analysing the 15 days together, the statistical protocol that combined multivariate distance, multiple linear regression and time series analysis showed a concordance of 93% on a 20-min flux basis and 87% on a daily basis (only 2 days fell outside the reference interval), and the overall flux differed only by 1.7% (3.2 g CO2 m,2). An automated version of this or a similar statistical protocol could be used as a standard way of filling gaps and processing data from Bowen ratio energy balance and other techniques (e.g. eddy covariance). This would enforce objectivity in comparisons of CO2 flux data that are generated by different research groups and streamline the protocols for quality control. [source] | |||||||||||||||||||||||||||||||||||||||||||