bluuebunny/crossref_metadata_2025 huggingface dataset:
Testing model fit in longitudinal data analysis against alternatives with omitted covariates
Authors: Wang Jin , Shao Jun , Palta Mari
Published: September 2002

Several types of common model misspecifications can be re‐formulated as problems of omitted covariates. These include situations with unmeasured confounders, measurement errors in observed covariates and informative censoring. Longitudinal data present special opportunities for detecting omitted covariates that are related to the observed ones differently across time than across individuals. This situation arises with period and cohort effects, as well as with usual formulations of classical measurement error in observed covariates. In this article we focus on testing for the existence of omitted covariates in longitudinal data analysis when models are fit by generalized estimation equations. When omitted covariates are present, specification of the correct link function conditionally on only observed covariates under the alternative usually involves complicated numerical integration. We propose a quasi‐score test statistic that avoids the need to fit such alternative models. The statistic is asymptotically chi‐square distributed under the null hypothesis of no omitted covariates with degrees of freedom determined by the assumed alternative structure. We study the significance level and the power of the quasi‐score test in linear and logistic regression models. The test is then applied to an analysis of excessive daytime sleepiness. Copyright © 2002 John Wiley & Sons, Ltd.
Individual bioequivalence testing under 2×3 designs
Authors: Chow Shein‐Chung , Shao Jun , Wang Hansheng
Published: September 2002

In recent years, as more generic drug products become available, it is a concern not only whether generic drug products that have been approved based on the regulation of average bioequivalence will have the same quality, safety and efficacy as that of the brand‐name drug product, but also whether the approved generic drug products can be used interchangeably. In its recent draft guidance, the U.S. Food and Drug Administration (FDA) recommends that individual bioequivalence (IBE) be assessed using the method proposed by Hyslop, Hsuan, and Holder to address drug switchability. The FDA suggests that a 2×4 cross‐over design be considered for assessment of IBE, while a 2×3 cross‐over design may be used as an alternative design to reduce the length and cost of the study. Little or no information regarding the statistical procedures under 2×3 cross‐over designs is discussed in the guidance. In this paper, a detailed statistical procedure for assessment of IBE under 2×3 cross‐over designs is derived. The main purpose of this paper, however, is to derive an IBE test under an alternative 2×3 design and show that the resulting IBE test is better than that under a 2×3 cross‐over design and is comparable to or even better than that under a 2×4 cross‐over design. Our conclusions are supported by theoretical considerations and empirical results. Furthermore, a method of determining the sample sizes required for IBE tests to reach a given level of power is proposed. Copyright © 2002 John Wiley & Sons, Ltd.
Meta‐analysis of method comparison studies
Authors: Williamson P. R. , Lancaster G. A. , Craig J. V. , Smyth R. L.
Published: September 2002

Methods for the meta‐analysis of results from randomized controlled trials are well established. However, there are currently no methods for the meta‐analysis of method comparison studies. Here the combination of results from studies comparing two methods of measurement on the same unit of observation is required. We compare standard methods for the pooling of k samples from the same Normal population to those for pooling parameter estimates, in order to estimate the pooled mean difference and 95 per cent limits of agreement. Methods for investigating heterogeneity across studies and for calculating random effects estimates are proposed. We postulate that for published studies either the estimated mean or variance of the difference between measurements will tend to be smaller than for unpublished studies and investigate the evidence for the existence of such publication bias. The methods are illustrated with an example evaluating the accuracy of temperature measured at the axilla compared to the rectum in children. Copyright © 2002 John Wiley & Sons, Ltd.
Bayesian two‐stage designs for phase II clinical trials
Authors: Tan Say‐Beng , Machin David
Published: September 2002

Many different statistical designs have been used in phase II clinical trials. The majority of these are based on frequentist statistical approaches. Bayesian methods provide a good alternative to frequentist approaches as they allow for the incorporation of relevant prior information and the presentation of the trial results in a manner which, some feel, is more intuitive and helpful. In this paper, we propose two new Bayesian designs for phase II clinical trials. These designs have been developed specifically to make them as user friendly and as familiar as possible to those who have had experience working with two‐stage frequentist phase II designs. Thus, unlike many of the Bayesian designs already proposed in the literature, our designs do not require a distribution for the response rate of the currently used drug or the explicit specification of utility or loss functions. We study the properties of our designs and compare them with the Simon two‐stage optimal and minimax designs. We also apply them to an example of two recently concluded phase II trials conducted at the National Cancer Centre in Singapore. Sample size tables for the designs are given. Copyright © 2002 John Wiley & Sons, Ltd.
Designing complex group sequential survival trials
Authors: Lakatos Edward
Published: September 2002

This paper presents methodology for designing complex group sequential survival trials when the survival curves will be compared using the logrank statistic. The method can be applied to any treatment and control survival curves as long as each hazard function can be approximated by a piecewise linear function. The approach allows arbitrary accrual patterns and permits adjustment for varying rates of non‐compliance, drop‐in and loss to follow‐up. The calendar‐time–information‐time transformation is derived under these complex assumptions. This permits the exploration of the operating characteristics of various interim analysis plans, including sample size and power. By using the calendar‐time–information‐time transformation, information fractions corresponding to desired calendar times can be determined. In this way, the interim analyses can be scheduled in information time, assuring the desired power and realization of the spending function, while the interim analyses will take place according to the desired calendar schedule. Copyright © 2002 John Wiley & Sons, Ltd.
Methods for estimating the AIDS incubation time distribution when date of seroconversion is censored
Authors: Geskus Ronald B.
Published: September 2002

In most cohort studies on HIV infection and AIDS, data on time from seroconversion to AIDS or death are doubly censored, both at the time origin and at the endpoint of interest. In epidemiological research, the most frequently adopted approach is to restrict the analysis to persons with narrow seroconversion intervals and to impute the midpoint of this interval as date of seroconversion. For many cohort studies, the consequence is that a substantial proportion of the data is not used. We consider four methods that are expected to be less biased when all cohort data are used: two imputation methods, conditional mean and multiple imputation, and two likelihood maximization methods. We derive the likelihood structure of the cohort data and clarify its dependence on study design. All methods are applied to data from the Amsterdam cohort study among injection drug users. In a simulation study the data generation process of this cohort study is imitated. The performance of midpoint, conditional mean and multiple imputation are compared. With midpoint imputation, both an analysis using the full data set, as well as one restricted to the cases with small seroconversion intervals, is performed. Conditional mean imputation comes out as the preferred method. It gives best results with respect to mean squared error. Moreover, when confidence intervals are computed through standard methods that ignore the uncertainty in the imputed date of seroconversion, coverage probabilities are almost correct. Copyright © 2001 John Wiley & Sons, Ltd.
Bayesian analyses of longitudinal binary data using Markov regression models of unknown order
Authors: Erkanli Alaattin , Soyer Refik , Angold Adrian
Published: September 2002

We present non‐homogenous Markov regression models of unknown order as a means to assess the duration of autoregressive dependence in longitudinal binary data. We describe a subject's transition probability evolving over time using logistic regression models for his or her past outcomes and covariates. When the initial values of the binary process are unknown, they are treated as latent variables. The unknown initial values, model parameters, and the order of transitions are then estimated using a Bayesian variable selection approach, via Gibbs sampling. As a comparison with our approach, we also implement the deviance information criterion (DIC) for the determination of the order of transitions. An example addresses the progression of substance use in a community sample ofn=242 American Indian children who were interviewed annually four times. An extension of the Markov model to account for subject‐to‐subject heterogeneity is also discussed. Copyright © 2001 John Wiley & Sons, Ltd.
Notes on interval estimation of the attributable risk in cross‐sectional sampling
Authors: Lui Kung‐Jong
Published: September 2002

The attributable risk (AR) is probably the most useful and commonly used epidemiologic index to measure the importance of a risk factor in public health issues. This paper focuses the discussion on interval estimation of the AR in cross‐sectional studies and compares the finite‐sample performance of five asymptotic interval estimators of the AR by calculating the coverage probability and the average length in a variety of situations. This paper notes that the coverage probability of the two interval estimators proposed by Leung and Kupper, including the one that combines the interval estimator on the basis of Wald's test statistic, can be substantially less than the desired confidence level when the underlying risk ratio equals 1. As long as the sample size is reasonably large (⩾100) and the probability of exposure is moderate (⩾0.20), the interval estimator suggested by Fleiss can consistently perform well with respect to the coverage probability in a variety of situations considered here. However, using this interval estimator tends to generally lose efficiency. This paper also finds that with respect to the coverage probability, the interval estimator using Fieller's theorem is generally preferable to the interval estimator on the basis of Wald's test statistic when the prevalence rate ratio (RR) between the exposure and the non‐exposure groups is ⩾2. Finally, this paper notes that if we know that the underlying parameter RR is large (⩾4) and the probability of exposure is not small (⩾0.05), the interval estimator suggested by Leung and Kupper will probably be preferable to all the other estimators considered here. Copyright © 2001 John Wiley & Sons, Ltd.
Testing for the presence of cured patients: a simulation study
Authors: Peng Yingwei , Dear Keith B. G. , Carriere K. C.
Published: September 2002

An important but difficult problem in clinical trials is to determine the presence of cured patients when long‐term survivors are observed. The likelihood ratio test has been studied for this purpose in the gamma mixture model. However, its asymptotic null distribution is not readily available due to a violation of boundary conditions in the standard asymptotic theory. In this paper, a simulation study is employed to examine a proposed asymptotic null distribution of the likelihood ratio test. We find that the distribution can also be used to approximate the asymptotic null distribution of the likelihood ratio test in the Weibull and log‐normal mixture models when the censoring rate is not too light. However, the simulation study also shows that null distribution of the likelihood ratio test deviates significantly from the suggested distribution under moderate sample sizes when the censoring rate is small or the hazard rate is large. Consequently caution is needed in this case to determine the presence of cured patients. Finally, the results are used to confirm the presence of cured patients in a leukaemia study. Copyright © 2001 John Wiley & Sons, Ltd.
Modelling bivariate ordinal responses smoothly with examples from ophthalmology and genetics
Authors: Bustami Rami , Lesaffre Emmanuel , Molenberghs Geert , Loos Ruth , Danckaerts Marina , Vlietinck Robert
Published: September 2002

A non‐parametric implementation of the bivariate Dale model (BDM) is presented as an extension of the generalized additive model (GAM) of Hastie and Tibshirani. The original BDM is an example of a bivariate generalized linear model. In this paper smoothing is introduced on the marginal as well as on the association level. Our non‐parametric procedure can be used as a diagnostic tool for identifying parametric transformations of the covariates in the linear BDM, hence it also provides a kind of goodness‐of‐fit test for a bivariate generalized linear model. Cubic smoothing spline functions for the covariates are estimated by maximizing a penalized version of the log‐likelihood. The method is applied to two studies. The first study is the classical Wisconsin Epidemiologic Study of Diabetic Retinopathy. The second study is a twin study, where the association between the elements of twin pairs is of primary interest. The results show that smoothing on the association level can give a significant improvement to the model fit. Copyright © 2001 John Wiley & Sons, Ltd.
Proportional hazards model for interval‐censored failure times and time‐dependent covariates: application to hazard of HIV infection of injecting drug users in prison
Authors: Seaman S. R. , Bird S. M.
Published: September 2002

Interval‐censored survival data are data in which the failure times are not known precisely, but are known to lie within an interval. Such data can be analysed using a proportional hazards model with piecewise‐exponential baseline hazard, a model which can be fitted by an EM algorithm easily programmed in standard statistical software. In this paper we extend the model to allow for time‐dependent covariates and left‐truncation, and demonstrate its use by assessing the effect of imprisonment on hazard of HIV infection in a cohort of injecting drug users from Edinburgh. No conclusive effect of incarceration on hazard of HIV infection was found, but there was a suggestion that imprisonment might have been a significant relative risk factor for infection in the later period, when risk behaviour among drug users in the community was reduced. Copyright © 2001 John Wiley & Sons, Ltd.
Covariate adjustment for non‐parametric tests for censored survival data
Authors: Li Zhengqing
Published: September 2002

We develop a method for covariate adjustment for a general class of non‐parametric tests for censored survival data which includes the widely used logrank and Wilcoxon tests. The covariate‐adjusted tests improve the power of the unadjusted counterparts and have advantages over the covariate‐adjusted Cox score test when there are outliers in the covariable space. We investigate the small sample properties of such test statistics through Monte Carlo simulations. Examples are given to illustrate the proposed procedures. Copyright © 2001 John Wiley & Sons, Ltd.
Bayesian cost‐effectiveness analysis from clinical trial data
Authors: O'Hagan Anthony , Stevens John W. , Montmartin Jacques
Published: September 2002

A key tool for assessing the relative cost‐effectiveness of two treatments in health economics is the incremental C/E acceptability curve. We present Bayesian computations for this curve in the case where data on both costs and efficacy are available from a clinical trial. Analysis is given under various formulations of prior information. A case study is analysed in which reasonable prior information is shown to strengthen substantially the posterior inference, leading to a more conclusive assessment of cost‐effectiveness. Calculations can be performed using readily available Bayesian software. Copyright © 2001 John Wiley & Sons, Ltd.
Maximum likelihood estimation of a survival function with a change point for truncated and interval‐censored data
Authors: Lim Heejeong , Sun Jianguo , Matthews David E.
Published: September 2002

This paper considers estimation of a survival function when there exists a change point and the survival time of interest is defined as elapsed time between two related events. Furthermore, there exists censoring on observations on the occurrences of both events and truncation on observations on the occurrence of the second event and thus the survival time of interest. To obtain the maximum likelihood estimator of a survival function, an EM algorithm is developed when the survival function is completely unknown before the change point and known up to a vector of unknown parameters after the change point. The idea is a generalization of that discussed in Moeschberger and Klein. Simulations and an example are used to evaluate and illustrate the algorithm. Copyright © 2002 John Wiley & Sons, Ltd.
An approach for extracting code fragments that implement functionality from source programs
Authors: Tan Hee Beng Kuan , Kow Juan Tiang
Published: September 2002

A data‐intensive program interacts with its environment through accepting and delivering information from and to its environment respectively. As such, the functionality in a program is achieved through its input/output statements. Based on this hypothesis, this paper proposes a novel approach for the extraction of code fragments for implementing functionality from program source code. This helps the software maintainer identify affected code fragments for making changes to program functionality. The code fragments extracted may also be suitable for reuse in other software projects. Copyright © 2001 John Wiley & Sons, Ltd.
Investigating the emotional roller‐coaster ride: a case study‐based assessment of the Future Search Conference design
Authors: Oels Angela
Published: September 2002

The aim of this paper is to make recommendations for the procedural optimization of the Future Search Conference design on the basis of empirical evidence from two case study conferences in Germany and the United Kingdom. The paper presents the major criticisms that have been raised against the step‐by‐step conference design in the theoretical literature and contrasts these with the empirical findings of two stakeholder‐based evaluations. The author draws attention to a number of weaknesses in the conference opening, the common ground phase and the action planning phase of the Future Search Conference design and makes proposals for design changes. The paper suggests that a systematic and stakeholder‐oriented evaluation should be part of interventions like Future Search Conferences. The paper concludes with a reminder that the political context and local power relations are a key variable in determining success or failure of a Future Search conference. Copyright © 2002 John Wiley & Sons, Ltd.
Communications security on the internet
Authors: Aura Tuomas , Gollmann Dieter
Published: September 2002

The Internet is an open network where all traffic is subject to interception by malicious outsiders. TUOMAS AURA and DIETER GOLLMANN overview the current major threats and security solutions for communication over the Internet. They note that the lack of satisfactory authentication infrastructures and guaranteed quality of service remain the main impediments for secure communication. Continuous evolution of the protection mechanisms, developer skills, and user culture are necessary to stay on track with the progress in communication technology. Copyright © 2001 John Wiley & Sons, Ltd.
An overview of program slicing
Authors: Harman Mark , Hierons Robert
Published: September 2002

MARK HARMANandROBERT HIERONSreview three semantic paradigms for slicing — static, dynamic and conditioned; and two syntactic paradigms — syntax‐preserving and amorphous. Slicing has been applied to many software development problems including testing, reuse, maintenance and evolution. This paper describes the main forms of program slice and some of the applications to which slicing has been put. Copyright © 2001 John Wiley & Sons, Ltd.
Plasmalemmal μ‐opioid receptor distribution mainly in nondopaminergic neurons in the rat ventral tegmental area
Authors: Garzón Miguel , Pickel Virginia M.
Published: September 2002

Opiate‐evoked reward and motivated behaviors reflect, in part, the enhanced release of dopamine produced by activation of the μ‐opioid receptor (μOR) in the ventral tegmental area (VTA). We examined the functional sites for μOR activation and potential interactions with dopaminergic neurons within the rat VTA by using electron microscopy for the immunocytochemical localization of antipeptide antisera raised against μOR and tyrosine hydroxylase (TH), the synthesizing enzyme for catecholamines. The cellular and subcellular distribution of μOR was remarkably similar in the two major VTA subdivisions, the paranigral (VTApn) and parabrachial (VTApb) nuclei. In each region, somatodendritic profiles comprised over 50% of the labeled structures. μOR immunolabeling was often seen at extrasynaptic/perisynaptic sites on dendritic plasma membranes, and 10% of these dendrites contained TH. μOR‐immunoreactivity was also localized to plasma membranes of axon terminals and small unmyelinated axons, none of which contained TH. The μOR‐immunoreactive axon terminals formed either symmetric or asymmetric synapses that are typically associated with inhibitory and excitatory amino acid transmitters. Their targets included unlabeled (30%), μOR‐labeled (25%), and TH‐labeled (45%) dendrites. Our results suggest that μOR agonists in the VTA affect dopaminergic transmission mainly indirectly through changes in the postsynaptic responsivity and/or presynaptic release from neurons containing other neurotransmitters. They also indicate, however, that μOR agonists directly affect a small population of dopaminergic neurons expressing μOR on their dendrites in VTA and/or terminals in target regions. Synapse 41:311–328, 2001. © 2001 Wiley‐Liss, Inc.
Regional distribution and cellular localization of 5‐HT2C receptor mRNA in monkey brain: Comparison with [3H]mesulergine binding sites and choline acetyltransferase mRNA
Authors: López‐Giménez Juan F. , Mengod Guadalupe , Palacios José M. , Vilaró M. Teresa
Published: September 2002

The distribution of serotonin 5‐HT2C receptor mRNA in monkey brain was studied by in situ hybridization and compared with the distribution of [3H]mesulergine binding sites as visualized by receptor autoradiography. 5‐HT2C receptor transcripts showed a widespread and heterogeneous distribution. The strongest hybridization signal was detected in choroid plexus. In neocortex, 5‐HT2C mRNA was detected in layer V of all cortical regions examined except in the calcarine sulcus, which was devoid of signal. Several structures within the striatum and basal forebrain were strongly labeled: nucleus accumbens, ventral aspects of anterior caudate and putamen, septal nuclei, diagonal band, ventral striatum, and extended amygdala. Several thalamic, midbrain, and brainstem nuclei also contained 5‐HT2C mRNA. Comparison of the distributions of 5‐HT2C mRNA and specific [3H]mesulergine binding sites showed a good agreement in the majority of brain regions, suggesting a predominant somatodendritic localization of 5‐HT2C receptors. A possible localization to axon terminals of 5‐HT2C receptors is suggested by the disagreement observed in some regions such as septal nuclei and horizontal limb of the diagonal band (presence of mRNA with apparent absence of binding sites) and interpeduncular nucleus (presence of binding sites with apparent absence of mRNA). Comparison of 5‐HT2C receptor and choline acetyltransferase mRNA distributions indicate that some regions where cholinergic cells are located are also enriched in cells containing 5‐HT2C mRNA. Although the present methodology does not allow strict colocalization of both mRNA species to the same cells, the codistribution observed in several regions provides a possible anatomical substrate for the described modulation of acetylcholine release by 5‐HT2C receptors. Synapse 42:12–26, 2001. © 2001 Wiley‐Liss, Inc.
Blockade of NMDA receptors by MK‐801 reverses the changes in striatal glutamate immunolabeling in 6‐OHDA‐lesioned rats
Authors: Robinson Siobhan , Krentz Lisa , Moore Cynthia , Meshul Charles K.
Published: September 2002

A lesion of the dopamine (DA)‐containing nigrostriatal pathway with 6‐hydroxydopamine (6‐OHDA) results in an increase in the density of nerve terminal glutamate immunolabeling and in the mean percentage of asymmetrical synapses containing a discontinuous postsynaptic density [Meshul et al. (1999) Neuroscience 88:1–16]. Similar alterations in striatal glutamate synapses have been reported following blockade of striatal DA D‐2 receptors with subchronic haloperidol treatment [Meshul et al. (1994) Brain Res 648:181–195]. The haloperidol‐induced change in glutamate synapses was blocked by coadministration of the N‐methyl‐D‐aspartate (NMDA) noncompetitive receptor antagonist MK‐801. In order to determine if blockade of NMDA receptors could alter the density of nerve terminal glutamate immunolabeling following a 6‐OHDA lesion of the nigrostriatal pathway, MK‐801 was administered to lesioned animals for 14 days. In addition, the number of apomorphine‐induced contralateral rotations was determined prior to and following the administration of MK‐801. MK‐801 administration reversed the increase in the density of nerve terminal glutamate immunolabeling due to a 6‐OHDA lesion. There was a small but significant decrease in the number of apomorphine‐induced contralateral rotations following administration of MK‐801 compared to the number of rotations prior to treatment with the NMDA antagonist. These results demonstrate that blockade of postsynaptic NMDA receptors affects the density of presynaptic glutamate immunolabeling and that this change in nerve terminal glutamate density is associated with a decreased behavioral response to direct DA receptor stimulation. Whether the effect of MK‐801 is directly on the striatum or acts through other excitatory pathways of the basal ganglia remains unclear. Synapse 42:54–61, 2001. Published 2001 Wiley‐Liss, Inc.
The establishing of performance level thresholds for steel moment‐resisting frame using an energy approach
Authors: Choi Byong J. , Shen Jay H.
Published: September 2002

In this study, an energy design approach is proposed within the framework of the performance‐based seismic design of steel frames. Accumulated plastic rotation is selected as a parameter to establish the performance level thresholds. The test results of steel connections are investigated to quantify the performance level thresholds. The hysteretic energy input is acquired from a previous statistical study of twelve six‐storey steel moment‐resisting frames. The seismic performance of three‐storey steel moment resisting frames using the energy approach is examined. The research concluded that the structure designed by the energy method performed better than the steel frame designed by the equivalent lateral force (ELF) of UBC‐97 in view of accumulated plastic rotation. Performance levels such as functional, life safety and collapse are discussed based on the ductility level and the performance characteristics. Copyright © 2001 John Wiley & Sons, Ltd.
Ethical dilemmas of relationship building in china
Authors: Stanley Snell Robin , Tseng Choo‐sin
Published: September 2002

We analyze and discuss some ethical dilemmas of doing business on the Chinese Mainland, referring to detailed accounts of the gift‐giving and contract‐getting experiences of two overseas Chinese managers in dealings with Mainland Chinese managers in the sporting and leisure industries. We compare these cases with accounts of transactions in worldwide ship repair, and with a newspaper report of a sport‐related case in Hong Kong. Using a version of Kohlberg's moral‐stages model, and identifying key differences between guanxi and rational‐legal ethics, we explain how guanxi can become entangled with corruption in China. We link our explanations to the absence of rational‐legal moral governance, and to the sociological phenomena of anomie and relative deprivation. We conclude with suggestions about the conduct of China business. � 2001 John Wiley & Sons, Inc.
Not just another financial derivatives book!
Authors: Lhabitant Fran�ois‐serge
Published: September 2002

Rubinstein M.: (1999) Derivatives: A PowerPlus Pic‐ture Book, In the Money, 381 pages plus CD‐ROM, distributed only through the Internet (http://www.in‐the‐money.com) Rubinstein M.: (2001) Rubinstein on Derivatives, Lon‐don: Risk Books, 471 pages, ISBN 1‐899332‐53‐7
An experimental approach to the determination of the surface ionization φ(0) in electron probe microanalysis
Authors: Bastin G. F. , Dijkstra J. M. , Heijligers H. J. M.
Published: September 2002

A compilation of experimentally determined surface ionization values for Al Kα and Pd Lα radiation on a wide variety of substrates, ranging from beryllium to bismuth, and measured between 4 and 30 kV, is presented. The values were extracted from our previously reported thin‐film measurements on aluminum and palladium films by electron probe microanalysis. The φ(0) values were determined by establishing the ratios of the intensities emitted from the supported and unsupported films for six film thicknesses and extrapolating towards a film thickness approaching zero. Some 180 φ(0) data each for Al Kα and Pd Lα x‐radiation were collected in this way. The purpose of this work was to provide systematic data on which the numerous existing expressions for φ(0) could be tested. In the final assessment procedure, in which we also included 108 data from the literature, we compared the performances of the various expressions from the literature for φ(0) and a newly developed expression of our own. Our final conclusion is that there is little to be chosen between the three to four of the highest ranking expressions. Copyright © 2001 John Wiley & Sons, Ltd.
Analysis of pine needles by XRF scanning techniques
Authors: Viksna A. , Selin Lindgren E. , Standzenieks P.
Published: September 2002

Concentrations of both essential and toxic elements in pine needles are known to be influenced by environmental factors, either directly from air pollutants or indirectly from acidification. In most previous work, mean concentrations for bulk samples of pine needles have been reported. In this investigation, elemental distributions along the length of pine needles without any visible morphological damage were studied for a number of important elements. The needles were sampled from locations with essentially sandy soils of different pH in different parts of Latvia. The variation of element concentrations along the needle length proved to be very large for some elements, e.g. Zn and Mn, whereas it was almost constant for others, e.g. Cu and Fe. For some elements, large differences between needles of different age class were observed, and also variations with soil pH and light conditions. Healthy needles of the same age class, growing under similar environmental conditions, have identical elemental concentration profiles. Scanning energy‐dispersive x‐ray fluorescence Spectrometry was used and the results were validated by independent analysis with graphite furnace atomic absorption spectrometry. Copyright © 2001 John Wiley & Sons, Ltd.
Synchrotron radiation‐induced TXRF of reactor steel samples
Authors: Pepponi G. , Wobrauschek P. , Streli C. , Zöger N. , Hegedüs F.
Published: September 2002

Synchrotron radiation‐induced total reflection x‐ray fluorescence (TXRF) analysis was used for the trace element analysis of steels exploited in the construction of core components of existing fission plants and future fusion power plants. Detection of traces of niobium in reactor pressure vessel steel allows a retrospective determination of the fast neutron flux. For the construction of future fusion reactors, low activation steels are being investigated. Traces of Nb, Pd, Ag, Eu, Gd, Tb, Dy, Ho, Er, Os and Bi cause a higher activity of the material than the steel itself. Synchrotron radiation allows the excitation of the heavier element K shells, avoiding the strong overlaps of their L lines. Moreover, the linear polarization of synchrotron radiation combined with side‐looking detection manages to reduce the scattering due to the matrix contained in the analysed samples. Experiments were carried out at Hasylab Beamline L (bending magnet). The experimental set‐up includes a double reflector collimator, a multilayer and a vacuum chamber. Chemical preparation of the sample included dissolution and separation by means of anion‐exchange chromatography. Minimum detectable concentrations of 37 ng g−1 for Nb and 400 ng g−1 for Tb in the steel were achieved. Copyright © 2001 John Wiley & Sons, Ltd.
Determination of dopants in ZnO‐based ceramic varistors by x‐ray fluorescence and inductively coupled plasma spectrometry
Authors: Caballero A. C. , Valle F. J. , Martín Rubí J. A.
Published: September 2002

A method is proposed for the x‐ray fluorescence (XRF) analysis of dopant concentrations in ZnO ceramic materials. The accuracy of the results is good for all the dopants analyzed except Bi2O3. The thermal behavior of this component was followed by thermogravimetry, showing that in an anhydrous Li2B4O7 medium, partial Bi2O3 volatilization occurs at the temperatures needed for glass bead formation (1100–1200 °C). For comparison, inductively coupled plasma atomic emission spectrometry (ICP‐AES) analysis of the materials was carried out following a wet procedure for sample solution preparation. The results were in agreement with those obtained by XRF except for Bi2O3. However, if Bi2O3 volatilization is avoided, the analysis is accurate. Copyright © 2001 John Wiley & Sons, Ltd.
Efficient calculation method for glancing angle x‐ray techniques
Authors: Pérez Roberto Daniel , Sánchez Hector Jorge , Rubio Marcelo
Published: September 2002

General depth profiling involves all kind of concentration profiles. The most complex samples present a wide variation of elemental composition with depth. In those cases, calculations of x‐ray propagation at grazing angles are done by representing the sample as a stratified structure in order to obtain an analytical solution of the problem. The density of each layer is an average of the real density inside the layer, and a large number of surface layers may be necessary for a correct representation of the sample. This involves a large number of mathematical operations and therefore an efficient calculation method of x‐ray propagation at glancing angles is required. In this paper, a mathematical algorithm for the calculation of x‐ray propagation at grazing angles is presented. It applies a new formalism introduced recently in the field. This formalism uses a matrix approach to take advantage of well‐known mathematical results, such as Hessenberg's matrix properties. The model allows one to reduce the number of mathematical operations for glancing angle x‐ray techniques. The method was used to study surface oxidation of copper and roughness of a glass surface by the grazing exit XRF technique. Data analysis in these samples shows the advantage of the present mathematical algorithm since both samples present a continuous depth profile. Copyright © 2002 John Wiley & Sons, Ltd.
L‐shell Coster–Kronig yields for Pb
Authors: Kumar Ajay , Puri Sanjiv , Mehta D. , Arora B. K. , Singh Nirmal
Published: September 2002

The f13 Coster–Kronig yield for Pb was determined as 0.60±0.03 using measured intensities of the Lα x‐rays emitted following selective ionization in the L3 sub‐shell by the Rb K x‐rays (B < Einc. < B) and of those emitted following ionization in the Li (i = 1, 2, 3) sub‐shells by 59.54 keV γ‐rays (B < Einc. < BK), BK and B being the K shell and Li sub‐shell ionization thresholds of Pb, respectively. The measurements were performed using a 241Am annular source in direct excitation mode and in secondary excitation mode along with an RbNO3 secondary exciter as photon sources and an Si(Li) detector. Measurements of the f12 and f23 Coster–Kronig yields using similar experimental set‐ups are also discussed. It is concluded that the f12 and f23 Coster–Kronig yields for 12 elements with 59 ≤ Z ≤ 90 measured by Oz et al. using a similar experimental set‐up are not reliable. Copyright © 2002 John Wiley & Sons, Ltd.
An algorithm combining neural networks with fundamental parameters
Authors: Luo Liqiang
Published: September 2002

An algorithm combining neural networks with the fundamental parameters equations (NNFP) is proposed for making corrections for non‐linear matrix effects in x‐ray fluorescence analysis. In the algorithm, neural networks were applied to relate the concentrations of components to both the measured intensities and the relative theoretical intensities calculated by the fundamental parameter equations. The NNFP algorithm is compared with the classical theoretical correction models, including the fundamental parameters approach, the Lachance–Traill model, a hyperbolic function model and the COLA algorithm. For an alloy system with 15 measured elements, in most cases, the prediction errors of the NNFP algorithm are lower than those of the fundamental parameters approach, the Lachance–Traill model, the hyperbolic function model and the COLA algorithm separately. If there are the serious matrix effects, such as matrix effects among Cr, Fe and Ni, the NNFP algorithm generally decreased predictive errors as compared with the classical models, except for the case of Cr by the fundamental parameters approach. The main reason why the NNFP algorithm has generally a better predictive ability than the classical theoretical correction models might be that neural networks can better calibrate the non‐linear matrix effects in a complex multivariate system. Copyright © 2002 John Wiley & Sons, Ltd.
Two non‐complementing genes encoding enzymatically active methylenetetrahydrofolate reductases control methionine requirement in fission yeast Schizosaccharomyces pombe
Authors: Naula Nicolas , Walther Claudia , Baumann Dominique , Ernst Schweingruber M.
Published: September 2002

By transforming two methionine auxotrophic mutants from fission yeast Schizosaccharomyces pombe with a wild‐type gene library, we defined two genes, met9 and met11, which both encode a methylenetetrahydrofolate reductase. The genes cannot complement each other. We detected single transcripts for both. In vitro measurements of enzymatic activities showed that the met11‐encoded enzyme was responsible for only 15–20% of the total methylenetetrahydrofolate reductase activity. A strain in which gene met9 was disrupted required significantly more methionine for full growth and efficient mating and sporulation than the strain disrupted for gene met11. The in vitro and in vivo data thus indicated that met9 was the major expressed gene. Our results are in accordance with the assumption that the two methylenetetrahydrofolate reductases generate the methyl groups necessary for methionine synthetase to convert homocysteine to methionine, and suggest that expression of the two genes is an important parameter in the control of methionine biosynthesis. Copyright © 2002 John Wiley & Sons, Ltd.
Dissection of the promoter of the HAP4 gene in S. cerevisiae unveils a complex regulatory framework of transcriptional regulation
Authors: Brons Janynke F. , de Jong Marian , Valens Michèle , Grivell Leslie A. , Bolotin‐Fukuhara Monique , Blom Jolanda
Published: September 2002

In S. cerevisiae, the heteromeric Hap2/3/4/5 complex is necessary for induced transcription of a large number of genes involved in oxidative metabolism on non‐fermentable carbon sources. The Hap4p subunit is the activator subunit and at the same time also the regulatory part of the complex, since it is the only one whose level is regulated by carbon source itself. HAP4 promoter analysis shows a 265 bp activating region at position −1006/−741 bp upstream of the ATG start codon. Specific and differential protein‐binding to a 30 nt CSRE‐like sequence within this region was observed with extracts from repressing and inducing carbon sources. Carbon source‐dependent activation mediated by the 265 bp fragment, as well as protein binding to the 30 nt CSRE‐like region, is dependent on the presence of CAT8 function, unveiling a complex framework by which the expression of the HAP4 gene is coordinated. Copyright © 2002 John Wiley & Sons, Ltd.
Molecular sex diagnosis in castoridae
Authors: Kühn Ralph , Schwab Gerhard , Schröder Wolfgang , Rottmann Oswald
Published: September 2002

Beavers do not exhibit any external sexual trait. Therefore, a simple method was established to differentiate between males and females by verifying the male‐specific SRY gene. Genomic DNA was prepared from hair root cells. Male samples displayed an electrophoretic 157‐bp band derived from the SRY gene after polymerase chain reaction (PCR) amplification. This band is missing in female samples. A 375‐bp fragment of the mitochondrial cytochrome b gene served as internal control and was visible in all samples. The technique can easily be used as a standard monitoring method, and is noninvasive, quick, and reliable. Zoo Biol 21:305–308, 2002. © 2002 Wiley‐Liss, Inc.
Low grip strength, impaired tongue force and hyperactivity induced by overexpression of neurotrophin‐3 in mouse skeletal muscle
Authors: Fowler S.C. , Zarcone T.J. , Chen R. , Taylor M.D. , Wright D.E.
Published: September 2002

Transgenic mice overexpressing neurotrophin‐3 (NT‐3) in skeletal muscle (mlc/NT‐3 mice) develop abnormal muscle spindles in skeletal muscle and display abnormal motor function in the form of gait and locomotive disturbances. The purpose of this work was to characterize the functional consequences of NT‐3 overexpression in skeletal muscle with further behavioral assessments that permitted inferences about muscle weakness in the tongue or forelimbs as well as potential central nervous system (CNS) abnormalities compared to wild‐type controls. Wild‐type (n=12) and mlc/NT‐3 (n=12) male mice were tested in five procedures (in chronological order): lick dynamics, locomotor activity, grid ataxia, go‐no‐go discrimination procedure, and grip strength. Relative to wild‐type mice, the mlc/NT‐3 mice exhibited lower tongue force, hyperactivity, slowed limb retrieval in the grid ataxia test, similar discrimination performance, and lower grip strength. Overall, the data suggest that chronically elevated levels of NT‐3 in mouse skeletal muscle cause muscle weakness in the mlc/NT‐3 mice. Surprisingly, mlc/NT‐3 mice also exhibited significant hyperactivity, suggesting that NT‐3 overexpression in the periphery may have caused abnormalities in the CNS that are related to the cortical processing of proprioceptive afferent information.
Compartmentalized NRG signaling and PDZ domain‐containing proteins in synapse structure and function
Authors: Huang Yang Z. , Wang Qiang , Won Sandra , Luo Zhen G. , Xiong Wen C. , Mei Lin
Published: September 2002

The synapse‐specific synthesis of the acetylcholine receptor (AChR) is mediated by multiple mechanisms including compartmentalized signaling induced by neuregulin (NRG). This paper presents evidence that NRG receptors—ErbB receptor tyrosine kinases interact with distinct PDZ domain‐containing proteins that are localized at the neuromuscular junction (NMJ). ErbB4 associates with the PSD‐95 (also known as SAP90)‐family members including PSD‐95, SAP97, and SAP102 whereas ErbB2 interacts with Erbin and PICK1. Although, ErbB kinases are concentrated at the NMJ, they are not colocalized with the AChR in cultured muscle cells even in the presence of agrin. Co‐expression of PSD‐95 causes ErbB4 to form clusters in COS cells. We propose that PDZ domain‐containing proteins play a role in anchoring ErbB proteins at the neuromuscular junction, and/or mediating downstream signaling pathways. Such mechanisms could be important for the maintenance and function of the synapse.
The Colorado mental retardation and developmental disabilities research center
Authors: Crnic Linda S.
Published: September 2002

The Colorado MRRC was one of the original MRRCs funded and has maintained its focus on genetic and nutritional causes of mental retardation and developmental disabilities. Significant discoveries of the center have included a number of metabolic disorders, including glutaric academia types I and II, electron transport flavoprotein (ETF) deficiency, ETF dehydrogenase deficiency, glycerol kinase deficiency, sphingolipidoses, genetic linkages in dyslexia, phonological deficits in dyslexia, and the importance of the trace mineral Zn in early development. Current research at the center is supported by program of projects grants on inborn errors of metabolism, Down syndrome (DS), autism, and dyslexia.
Phosphorylation of the recombinant ρ1 GABA receptor
Authors: Sedelnikova Anna , Weiss David S.
Published: September 2002

γ‐Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain. While a growing body of literature indicates that postsynaptic GABA receptors are regulated by phosphorylation, there is discrepancy as to the specific effects of phosphorylation on GABA receptor function. Here, we have identified phosphorylation sites on the human ρ1 GABA receptor for six protein kinases widely expressed in the brain: protein kinase C (PKC); cAMP‐dependent protein kinase (PKA); calmodulin‐dependent kinase (CaMKII); casein kinase (CKII); mitogen‐activated protein kinase (MAPK); and cGMP‐dependent protein kinase (PKG). We demonstrate that in nearly all cases, the consensus sites and actual phosphorylation sites do not agree supporting the risk of relying on a sequence analysis to identify potential phosphorylation sites. In addition, of the six kinases examined, only CKII phosphorylated the human ρ2 subunit. Site‐directed mutagenesis of the phosphorylation sites, or activation/inhibition of select kinase pathways, did not alter the receptor sensitivity or maximal GABA‐activated current of the ρ1 GABA receptor expressed in Xenopus laevis oocytes suggesting phosphorylation of ρ1 does not directly alter receptor properties. This study is a first and necessary step towards elucidating the regulation of ρ1 GABA receptors by phosphorylation.
Agent computing themes in biologically inspired models of learning and development
Authors: Reilly Kevin D.
Published: September 2002

After evaluating general features and attributes of the agent notion, the overlap of features in candidate (attribute) cores, and several less central features, the paper addresses agent and related theory in neuroscience, observing how agent notions have penetrated portions of this field and how the field itself emphasizes and further develops some agent themes via, e.g. schema theory, neural net‐artificial intelligence (AI) comparisons, and other research. In remaining sections, models for development of memory strategies in children are presented, illustrating cooperative and competitive neural modeling agents, an active role for a “human agent in the loop,” and integrating broadly‐based neural network (NN) modeling with other bio‐inspired models.