bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of a basic drug by on‐line solid‐phase extraction liquid chromatography/tandem mass spectrometry using a mixed mode sorbent
Authors: Mallet Claude R , Lu Ziling , Mazzeo Jeff , Neue Uwe
Published: August 2002

Two on‐line configurations using multiple 6‐ and 10‐port valves were investigated for high‐flow on‐line extraction of a basic drug in rat plasma and human urine using a reversed‐phase and a cation‐exchange SPE sorbent. The first configuration studied was a single reversed‐phase extraction cartridge (2.1 × 20 mm, 25µm) using an optimized washing protocol. The results showed that up to 1.5 mL of sample (urine or plasma diluted 1:1) can be injected with limits of quantification (LOQs) as low as 100 pg/mL. The second configuration studied was the combination of a cation exchanger and a reversed‐phase cartridge using at‐column dilution. The results showed better LOQs than those obtained with the single cartridge at 10 pg/mL with the same injection volume. The mass spectrometer was operated in the multiple reaction monitoring (MRM) mode. All calibration curves gave an average of 5% relative standard deviation (RSD). Copyright © 2002 John Wiley & Sons, Ltd.
The cellular receptor for measles virus—elusive no more
Authors: Yanagi Yusuke
Published: August 2002

The identity of the measles virus receptor has been controversial. Several years ago CD46 was identified as a cellular receptor for the Edmonston strain of measles virus, but most clinical isolates of measles virus, which are most efficiently isolated in the marmoset B cell line B95a, cannot grow in many CD46+ cell lines. Although some researchers attributed it to post‐entry block in viral replication, others believed that there is a receptor other than CD46 for wild‐type measles viruses. A new study showed that human signalling lymphocytic activation molecule (SLAM; also known as CDw150) is a cellular receptor for measles virus, including the Edmonston strain. SLAM is expressed on lymphocytes and dendritic cells, and plays an important role in lymphocyte activation. The identification of SLAM as a measles virus receptor nicely explains the pathogenesis of measles virus infection. Copyright © 2001 John Wiley & Sons, Ltd.
Zeno hybrid systems
Authors: Zhang Jun , Johansson Karl Henrik , Lygeros John , Sastry Shankar
Published: August 2002

The interacting continuous and discrete dynamics in hybrid systems may lead to Zeno executions, which are solutions of the system having infinitely many discrete transitions in finite time. Although physical systems do not show Zeno behaviour, models of real systems may be Zeno due to modelling abstraction. It is hard to analyse such models with the existing theory. Since abstraction is an important tool in the hierarchical design of hybrid systems, one would like to determine when it may lead to Zeno models. Zeno hybrid systems are studied in detail in the paper. Necessary and sufficient conditions for the existence of Zeno executions are given. The Zeno set is introduced as the ω limit set of a Zeno execution. Properties of the Zeno set are derived for a fairly large class of hybrid systems. Copyright 2001 © John Wiley & Sons, Ltd.
Randomized metarounding
Authors: Carr Robert , Vempala Santosh
Published: August 2002

Let P be a linear relaxation of an integer polytope Z such that the integrality gap of P with respect to Z is at most r, as verified by a polytime heuristic A, which on any positive cost function c returns an integer solution (an extreme point of Z) whose cost is at most r times the optimal cost over P. Then for any point x* in P (a fractional solution), rx* dominates some convex combination of extreme points of Z. A constructive version of this theorem is presented here, with applications to approximation algorithms, and can be viewed as a generalization of randomized rounding. © 2002 Wiley Periodicals, Inc. Random Struct. Alg., 20:343–352, 2002
Epistemologically authentic inquiry in schools: A theoretical framework for evaluating inquiry tasks
Authors: Chinn Clark A. , Malhotra Betina A.
Published: August 2002

A main goal of science education is to help students learn to reason scientifically. A main way to facilitate learning is to engage students in inquiry activities such as conducting experiments. This article presents a theoretical framework for evaluating inquiry tasks in terms of how similar they are to authentic science. The framework helps identify the respects in which these reasoning tasks are similar to and different from real scientific research. The framework is based on a recent theory of reasoning, models‐of‐data theory. We argue that inquiry tasks commonly used in schools evoke reasoning processes that are qualitatively different from the processes employed in real scientific inquiry. Moreover, school reasoning tasks appear to be based on an epistemology that differs from the epistemology of authentic science. Inquiry tasks developed by researchers have increasingly captured features of authentic science, but further improvement is still possible. We conclude with a discussion of the implications of our analysis for research, assessment, and instruction. © 2002 Wiley Periodicals, Inc. Sci Ed 86:175–218, 2002; DOI 10.1002/sce.10001
“Peripheral and subversive”: Women making connections and challenging the boundaries of the science community
Authors: Davis Kathleen S.
Published: August 2002

Researchers continue to report the underrepresentation of females in the science professions (AAUW, 1992; NSF, 1999; Vetter, 1992). Investigators have illuminated many factors that contribute to the insider status in the science community of some groups and the peripheral/outsider status of women and girls (Brickhouse, 1994; Delamont, 1989; Harding, 1991; Schiebinger, 1989). Some research has shown that supportive science networks have had a positive influence on women's participation and retention in science practices (AAUW, 1992; Keith & Keith, 1989; Kreinberg & Lewis, 1996; Varanka‐Martin, 1996). In order to provide a better understanding of the role social capital plays in women's legitimate participation in science, I draw upon the findings of a qualitative study that examines the valued capital, ways, and practices of a support group for women working in the sciences at an academic research institution. Findings from this study indicate how women 1) were given little access to powerful networks in science that would provide them with opportunities to acquire the knowledge, skills, and resources necessary to be legitimate in the traditional sense, and 2) encountered many obstacles in their attempts to develop networks and make such connections between themselves and other women. Findings also indicate that, despite these impediments, the support group provided a meaningful and resourceful network through which they developed a critical perspective of legitimacy as they sought to make explicit the “culture of science.” Participants not only employed the traditional methods of scientific inquiry, but also acknowledged and valued the voices and experiences of those from nondominant groups. They constructed a new discourse that was inclusive of diverse voices, created new career pathways, and developed a vision of mentoring that facilitated females' development of a critical view of the science community and their legitimate participation. © 2001 John Wiley & Sons, Inc. Sci Ed 85:368–409, 2001.
Measurement and control of business processes
Authors: Powell Stephen G. , Schwaninger Markus , Trimble Chris
Published: August 2002

It is widely accepted that any well‐designed organizational process includes a control mechanism through which management decides which aspects of the performance of the process are to be measured and how these measurements are to be used to change the level of resources utilized in the process. Little is known, however, about the best ways to design such a control mechanism for typical business processes. Our goal in this research is to identify control mechanisms for business processes that are effective in different types of environments. In this article we present a system dynamics model of a typical service‐sector business process, such as is used in processing administrative paperwork in insurance, banking, and so on. These processes are subject to random, time‐varying, and non‐postponable demands for service. They are also subject to randomness in processing times, as well as delays in the observation of system performance and in the execution of control actions. We assume management has the dual objectives of maximizing profits (revenues on completed work less the costs of labor employed) and keeping cycle times below a predetermined ceiling. In order to achieve these objectives it observes the state of the process and adjusts its labor force accordingly. Management must chose which of several aspects of process performance to measure (cycle time, backlog, or demand) and the parameters governing the control process. Our analysis highlights the interactions among the demand environment faced by the process (e.g., random or seasonal), the control signal chosen (e.g., cycle time or backlog), and the type of control used (e.g., proportional or differential). Our results suggest that, regardless of the demand environment, a control process based on system backlog is generally more robust than the alternatives in the sense that adequate performance is achieved over a broader range of control parameters. We also find that, in most cases, proportional control by itself is inadequate to provide effective performance and that differential control is a necessary adjunct. We conclude the article with a discussion of the managerial implications of this research. Copyright © 2001 John Wiley & Sons, Ltd.
Maps and models in system dynamics: a response to Coyle
Authors: Homer Jack , Oliva Rogelio
Published: August 2002

Geoff Coyle has recently posed the question as to whether or not there may be situations in which computer simulation adds no value beyond that gained from qualitative causal‐loop mapping. We argue that simulation nearly always adds value, even in the face of significant uncertainties about data and the formulation of soft variables. This value derives from the fact that simulation models are formally testable, making it possible to draw behavioral and policy inferences reliably through simulation in a way that is rarely possible with maps alone. Even in those cases in which the uncertainties are too great to reach firm conclusions from a model, simulation can provide value by indicating which pieces of information would be required in order to make firm conclusions possible. Though qualitative mapping is useful for describing a problem situation and its possible causes and solutions, the added value of simulation modeling suggests that it should be used for dynamic analysis whenever the stakes are significant and time and budget permit. Copyright © 2001 John Wiley & Sons, Ltd.
The role of boundaries during superplastic deformation
Authors: Mohamed Farghalli A.
Published: August 2002

Micrograin superplasticity refers to the ability of fine‐grained materials (d<10µm, where d is the grain size) to exhibit extensive neck‐free elongations during deformation at elevated temperatures (T>0.5Tm, where Tm is the melting point). Consideration of recent experimental data regarding the effects of impurities on the characteristics of micrograin superplasticity reveals an important role played by boundaries in superplastic alloys. This role pertains to the ability of boundaries to serve as favorable sites for the accumulation of impurities, i.e. boundary segregation. Evidence in support of boundary segregation during micrograin superplasticity is reviewed, with particular emphasis on creep behavior, cavitation, ductility, boundary sliding and the formation of cavity stringers. Copyright © 2001 John Wiley & Sons, Ltd.
Metal/ceramic interfaces: a microscopic analysis
Authors: Hosson Jeff Th. M. De , Kooi Bart J.
Published: August 2002

This contribution treats the fundamental and practical aspects of the analysis of interfaces between metals and ceramic materials. It is shown that, in principle at least, it is possible to assess the bond strength by investigating the atomic structure of the dislocation cores. We have chosen to exemplify our approach with the misfit‐dislocation structures at two, crystallographically different, systems, i.e. cube‐on‐cube and cube‐on‐non cube interfaces. It turns out that from high‐resolution transmission electron microscopy observations in combination with computer modelling studies a qualitative insight can be obtained about the bonding behaviour between these dissimilar materials. In general we may conclude that there is a fair correlation between the atomistic and linear elastic continuum description of interface dislocations. However, it is shown that the linear elastic continuum approach cannot account for the possible configurations at an interface with misfit, because it does not include the effects of different bonding strengths on the interface structure. This contribution directs also to some future experimental work. Segregation of other elements might affect the local bond strength which may become manifest in the experimental observations of atomic structure. Copyright © 2001 John Wiley & Sons, Ltd.
Light emission from surfaces, thin films and particles induced by high‐energy electron beam
Authors: Yamamoto N. , Araya K. , Toda A. , Sugiyama H.
Published: August 2002

Light emission generated by a high‐energy electron passing through surfaces, thin films and particles of several materials were studied using a light detection system combined with a transmission electron microscope with an accelerating voltage of 200 kV. A silver film with a rough surface gives rise to inhomogeneous intensity distribution in the photon maps, which is due to the coupling of light with the non‐radiative surface plasmon mode through the surface roughness. In the case of a rough surface of a silver film with a granular structure, light is strongly emitted from a localized region with high polarization. The emissions from silver particles with various diameters were observed. The emission spectra show multiple peaks corresponding to the multipole modes of the electromagnetic oscillation in the spherical particle. The results can be explained well by the theory involving the retardation effect. Copyright © 2001 John Wiley & Sons, Ltd.
Individual patient‐ versus group‐level data meta‐regressions for the investigation of treatment effect modifiers: ecological bias rears its ugly head
Authors: Berlin Jesse A. , Santanna Jill , Schmid Christopher H. , Szczech Lynda A. , Feldman Harold I.
Published: August 2002

When performing a meta‐analysis, interest often centres on finding explanations for heterogeneity in the data, rather than on producing a single summary estimate. Such exploratory analyses are frequently undertaken with published, study‐level data, using techniques of meta‐analytic regression. Our goal was to explore a real‐world example for which both published, group‐level and individual patient‐level data were available, and to compare the substantive conclusions reached by both methods. We studied the benefits of anti‐lymphocyte antibody induction therapy among renal transplant patients in five randomized trials, focusing on whether there are subgroups of patients in whom therapy might prove particularly beneficial. Allograft failure within 5 years was the endpoint studied. We used a variety of analytic approaches to the group‐level data, including weighted least‐squares regression (N=5 studies), logistic regression (N=628, the total number of subjects), and a hierarchical Bayesian approach. We fit logistic regression models to the patient‐level data. In the patient‐level analysis, we found that treatment was significantly more effective among patients with elevated (20 per cent or more) panel reactive antibodies (PRA) than among patients without elevated PRA. These patients comprise a small (about 15 per cent of patients) subgroup of patients that benefited from therapy. The group‐level analyses failed to detect this interaction. We recommend using individual patient data, when feasible, to study patient characteristics, in order to avoid the potential for ecological bias introduced by group‐level analyses. Copyright © 2002 John Wiley & Sons, Ltd.
Medical students' perspective on the teaching of medical statistics in the undergraduate medical curriculum
Authors: Astin Jeremy , Jenkins Tom , Moore Laurence
Published: August 2002

Two undergraduate medical students at the University of Bristol commented on their experiences of learning medical statistics. In general, medical students' focus is on acquiring skills needed to practice clinical medicine, and great care must be taken to explain why disciplines such as statistics and epidemiology are relevant to this. Use of real examples and an emphasis on the need for evidence has meant that medical students are increasingly aware of the pressure on clinicians to justify their treatment decisions, and the associated need to be able to understand and critically appraise medical research. It was felt that medical statistics courses should focus on critical appraisal skills rather than on the ability to analyse data, which can be acquired by particular students when they need to do this. Medical statistics should be taught early in the curriculum, but there is a need to reinforce such skills throughout the course. Teaching and assessment methods should recognize that what is being taught is a practical skill of clinical relevance. This means that problem based small groups, data interpretation exercises and objective structured clinical examinations will be more productive than traditional teaching and examination methods. Copyright © 2002 John Wiley & Sons, Ltd.
Accounting for correlation and compliance in cluster randomized trials
Authors: Loeys T. , Vansteelandt S. , Goetghebeur E.
Published: August 2002

This paper discusses causal inference with survival data from cluster randomized trials. It is argued that cluster randomization carries the potential for post‐randomization exposures which involve differentially selective compliance between treatment arms, even for an all or nothing exposure at the individual level. Structural models can be employed to account for post‐randomization exposures, but should not ignore clustering. We show how marginal modelling and random effects models allow to adapt structural estimators to account for clustering. Our findings are illustrated with data from a vitamin A trial for the prevention of infant mortality in the rural plains of Nepal. Copyright © 2001 John Wiley & Sons, Ltd.
Issues in the selection of a summary statistic for meta‐analysis of clinical trials with binary outcomes
Authors: Deeks Jonathan J.
Published: August 2002

Meta‐analysis of binary data involves the computation of a weighted average of summary statistics calculated for each trial. The selection of the appropriate summary statistic is a subject of debate due to conflicts in the relative importance of mathematical properties and the ability to intuitively interpret results. This paper explores the process of identifying a summary statistic most likely to be consistent across trials when there is variation in control group event rates. Four summary statistics are considered: odds ratios (OR); risk differences (RD) and risk ratios of beneficial (RR(B)); and harmful outcomes (RR(H)). Each summary statistic corresponds to a different pattern of predicted absolute benefit of treatment with variation in baseline risk, the greatest difference in patterns of prediction being between RR(B) and RR(H). Selection of a summary statistic solely based on identification of the best‐fitting model by comparing tests of heterogeneity is problematic, principally due to low numbers of trials. It is proposed that choice of a summary statistic should be guided by both empirical evidence and clinically informed debate as to which model is likely to be closest to the expected pattern of treatment benefit across baseline risks. Empirical investigations comparing the four summary statistics on a sample of 551 systematic reviews provide evidence that the RR and OR models are on average more consistent than RD, there being no difference on average between RR and OR. From a second sample of 114 meta‐analyses evidence indicates that for interventions aimed at preventing an undesirable event, greatest absolute benefits are observed in trials with the highest baseline event rates, corresponding to the model of constant RR(H). The appropriate selection for a particular meta‐analysis may depend on understanding reasons for variation in control group event rates; in some situations uncertainty about the choice of summary statistic will remain. Copyright © 2002 John Wiley & Sons, Ltd.
Estimating equations for kappa statistics
Authors: Thompson John R.
Published: August 2002

Kappa statistics are often used for measuring agreement or association. The original measure suggested by Cohen for use with nominal data has since been generalized in a number of ways, including the incorporation of weights, adaptation for use with more than one rater and the application to bivariate data. Each modification requires a new approximation to the standard error and these have usually been derived by the delta method. This paper illustrates the use of estimating equations for kappa which offer a unified approach to many previously considered situations and which is also applicable to more complex designs. Copyright © 2001 John Wiley & Sons, Ltd.
Probabilistic population estimation of the size and overlap of data sets based on date of birth
Authors: Banks Steven M. , Pandiani John A.
Published: August 2002

Probabilistic population estimation is a statistical procedure for deriving unduplicated counts of the number of people represented in data sets that do not include unique person identifiers and the number of people shared by data sets that do not share personal identifiers. Because the procedure relies on anonymous data sets, the personal privacy of individuals and the confidentiality of medical records is protected. This paper describes the mathematics of probabilistic population estimation, and applies the procedure to an important contemporary public policy issue. Copyright © 2001 John Wiley & Sons, Ltd.
A comparison of methods to detect publication bias in meta‐analysis
Authors: Macaskill Petra , Walter Stephen D. , Irwig Les
Published: August 2002

Meta‐analyses are subject to bias for many of reasons, including publication bias. Asymmetry in a funnel plot of study size against treatment effect is often used to identify such bias. We compare the performance of three simple methods of testing for bias: the rank correlation method; a simple linear regression of the standardized estimate of treatment effect on the precision of the estimate; and a regression of the treatment effect on sample size. The tests are applied to simulated meta‐analyses in the presence and absence of publication bias. Both one‐sided and two‐sided censoring of studies based on statistical significance was used. The results indicate that none of the tests performs consistently well. Test performance varied with the magnitude of the true treatment effect, distribution of study size and whether a one‐ or two‐tailed significance test was employed. Overall, the power of the tests was low when the number of studies per meta‐analysis was close to that often observed in practice. Tests that showed the highest power also had type I error rates higher than the nominal level. Based on the empirical type I error rates, a regression of treatment effect on sample size, weighted by the inverse of the variance of the logit of the pooled proportion (using the marginal total) is the preferred method. Copyright © 2001 John Wiley & Sons, Ltd.
Sample size tables for exact single‐stage phase II designs
Authors: A'Hern R. P.
Published: August 2002

Tables for single‐phase II trials based on the exact binomial distribution are presented. These are preferable to those generated using Fleming's design, which are based on the normal approximation and can give rise to anomalous results. For example, if the upper success rate is accepted, the lower success rate, which the trial is designed to reject, may be included in the final confidence interval for the proportion being estimated. Copyright © 2001 John Wiley & Sons, Ltd.
Estimating cohort health expectancies from cross‐sectional surveys of disability
Authors: Davis B. A. , Heathcote C. R. , O'Neill T. J.
Published: August 2002

A life history can be regarded as a random process that evolves with age through various states of health before terminating with absorption into the state of death. Health expectancies are the occupation times of the non‐absorbing states and their estimation is of interest. A continuing major problem has been the lack of satisfactory longitudinal data on which to base estimates and as a result standard inferential techniques may not be relevant. Supposing only cross‐sectional data available, we propose a method that is generally applicable and first estimates a logistic parametrization of the probabilities of the various states. A large sample approximation is obtained for the distribution of age specific log (odds). Parameters are estimated by weighted least squares, and this in turn leads to estimates of cohort health expectancies. A result of Liang and Zeger is used to find standard errors. The method is illustrated by application to Australian data from the health surveys of 1981, 1988 and 1993. Copyright © 2001 John Wiley & Sons, Ltd.
The continual reassessment method and its applications: a Bayesian methodology for phase I cancer clinical trials
Authors: Ishizuka Naoki , Ohashi Yasuo
Published: August 2002

We discuss the continual reassessment method (CRM) and its extension with practical applications in phase I and I/II cancer clinical trials. The CRM has been proposed as an alternative design of a traditional cohort design and its essential features are the sequential (continual) selection of a dose level for the next patients based on the dose–toxicity relationship and the updating of the relationship based on patients' response data using Bayesian calculation. The original CRM has been criticized because it often tends to allocate too toxic doses to many patients and our proposal for overcoming this practical problem is to monitor a posterior density function of the occurrence of the dose limiting toxicity (DLT) at each dose level. A simulation study shows that strategies based on our proposal allocate a smaller number of patients to doses higher than the maximum tolerated dose (MTD) compared with the original method while the mean squared error of the probability of the DLT occurrence at the MTD is not inflated. We present a couple of extensions of the CRM with real prospective applications: (i) monitoring efficacy and toxicity simultaneously in a combination phase I/II trial; (ii) combining the idea of pharmacokinetically guided dose escalation (PKGDE) and utilization of animal toxicity data in determining the prior distribution. A stopping rule based on the idea of separation among the DLT density functions is discussed in the first example and a strategy for determining the model parameter of the dose–toxicity relationship is suggested in the second example. Copyright © 2001 John Wiley & Sons, Ltd.
Bias reduction for risk ratio and vaccine effect estimators
Authors: Chick Stephen E. , Barth‐Jones Daniel C. , Koopman James S.
Published: August 2002

We examine the structural bias for established estimators of vaccine effects on susceptibility and for newer estimates of vaccine effects on infectiousness. We then propose and analyse new bias corrections for vaccine effect estimators of both susceptibility and infectiousness, as well as their combined effect on infection transmission. Each estimator is evaluated empirically with computer simulations. Of the estimators examined in this paper, those with the least bias and root mean squared error are computed by adding one to the positive count in the placebo population. We also identify a source of bias for a standard Bayesian estimator of risk ratios. Copyright © 2001 John Wiley & Sons, Ltd.
Asset divestiture following horizontal acquisitions: a dynamic view
Authors: Capron Laurence , Mitchell Will , Swaminathan Anand
Published: August 2002

Business acquisition, resource redeployment, and asset divestiture are elements of a dynamic process in which firms change their businesses by recombining internal and external resources. Analyzing 253 horizontal acquisitions, we show that post‐acquisition resource redeployment leads to asset divestiture from the business that receives the redeployed resources, but not from the business that contributes the new resources. Consistent with scale economies rationales, we find that strategic similarity also leads to greater asset divestiture from the target firms. Many theoretical perspectives are skeptical about the positive rationale for acquisitions and many of these believe that asset divestiture is evidence of acquisition failure. Our arguments and analysis help refine the accepted wisdom. In particular, the pattern of resource redeployment and asset divestiture in our analysis suggests that acquisitions provide a means of reconfiguring the structure of resources within firms and that asset divestiture is a logical consequence of this reconfiguration process. Copyright © 2001 John Wiley & Sons, Ltd.
An operationalization of Stevenson's conceptualization of entrepreneurship as opportunity‐based firm behavior
Authors: Brown Terrence E , Davidsson Per , Wiklund Johan
Published: August 2002

Stevenson (1983) holds that entrepreneurial management, defined as a set of opportunity‐based management practices, can help firms remain vital and contribute to firm and societal level value creation. While his conceptualization has received much attention, little progress has been made because of a lack of empirical tools to examine his propositions. This article seeks to resolve this by describing a new instrument that was developed specifically for operationalizing Stevenson's conceptualization. After two pre‐tests, the instrument was tested full scale on a very large (1200+ cases) stratified random sample of firms with different size, governance structure, and industry affiliation. The results show that both in the full sample and in various sub‐samples it was possible to identify six sub‐dimensions with high discriminant validity and moderate to high reliability, which represent dimensions of Stevenson's theoretical reasoning. We label these Strategic Orientation, Resource Orientation, Management Structure, Reward Philosophy, Growth Orientation and Entrepreneurial Culture. We were further able to show that these dimensions only partly overlap with ‘Entrepreneurial Orientation’, the hitherto best established empirical instrument for assessing a firm's degree of entrepreneurship. Our instrument should open up opportunities for researchers to further evaluate entrepreneurship in existing firms. Copyright © 2001 John Wiley & Sons, Ltd.
When do firms learn from their acquisition experience? Evidence from 1990 to 1995
Authors: Hayward Mathew L. A.
Published: August 2002

I use an organizational learning perspective to examine how the nature, performance and timing of a firm's acquisition experience helps it to learn how to select the right acquisition. I predict the performance of 214 acquisitions made by 120 firms in 6 industries between 1990 and 1995. Results show that a firm's focal acquisition performance positively relates to prior acquisitions that are a) not highly similar or dissimilar to the focal acquisition, b) associated with small losses and c) not too temporally close to or distant from the focal acquisition. Taken together, these results identify the broad conditions in which firms generate adaptive and timely inferences from acquisition experience. Copyright © 2002 John Wiley & Sons, Ltd.
Kainate‐induced currents in rat cortical neurons in culture are modulated by riluzole
Authors: Zona Cristina , Cavalcanti Silvio , De Sarro Giovanbattista , Siniscalchi Antonio , Marchetti Caterina , Gaetti Chiara , Costa Nicola , Mercuri Nicola , Bernardi Giorgio
Published: August 2002

The action of the neuroprotective and anticonvulsant agent riluzole on kainate‐induced currents was studied in rat cortical neurons in primary culture by using the whole‐cell configuration of the patch‐clamp technique. Kainate elicited macroscopic, 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX)‐sensitive inward currents in all the patched cells and the amplitude of the current was concentration‐dependent (EC50= 106 μM). Riluzole decreased the inward currents induced by 100 μM kainate at all holding potentials and the reduction was dose‐dependent (IC50= 101 μM). The maximal response to kainate decreased in the presence of 50 μM riluzole, without changing its EC50, indicating a noncompetitive mechanism of inhibition. The amplitude of the responses induced by kainate under control conditions and during riluzole was a linear function of the membrane potential and the reversal potential of the currents was not significantly different in the two experimental conditions. Instead, the total conductance of the cell membrane for the currents induced by 100 μM kainate was significantly reduced in the presence of 50 μM riluzole (P < 0.05). The analysis of the kainate membrane current noise performed under control conditions and during perfusion of 100 μM riluzole revealed that riluzole reduced the probability of kainate‐activated ionic channels to be in the open state. Conversely, the unitary conductance of channels, as well as their characteristic time constant, seemed to be unchanged. These results reveal an additional mechanism by which riluzole can interact with glutamatergic neurotransmission and provides further support for the idea that riluzole may prove beneficial in the treatment of central nervous system injuries involving the excitotoxic actions of glutamate. Synapse 43:244–251, 2002. © 2002 Wiley‐Liss, Inc.
Acute and chronic caffeine administration differentially alters striatal gene expression in wild‐type and adenosine A2A receptor‐deficient mice
Authors: Dassesse Donald , Ledent Catherine , Parmentier Marc , Schiffmann Serge N.
Published: August 2002

In order to assess for the respective involvement of adenosine A1 and A2A receptors (A2A‐R) in the consequences of short‐ and long‐term caffeine exposure on gene expression, the effects of acute caffeine administration on striatal, cortical, and hippocampal expression of immediate early genes (IEG), zif‐268 and arc, and the effects of long‐term caffeine or 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX) exposure (once daily for 15 days) on striatal gene expression of substance P, enkephalin, and glutamic acid decarboxylase isoforms, GAD65 and GAD67, were evaluated in wild‐type and A2A‐R‐deficient (A2A‐R−/−) mice. In situ hybridization histochemistry was performed using oligonucleotides followed by quantitative image analysis. Our results demonstrated that a biphasic response of IEG expression to acute caffeine observed in the wild‐type striatum was resumed in a monophasic response in the mutant striatum. In the cerebral cortex and hippocampus, the effect of caffeine was weak in wild‐type, whereas in mutant mice it induced a 2–3‐fold increase in the IEG expression to restore a level similar to the wild‐type basal expression. Chronic caffeine and DPCPX‐mediated regulation in neuropeptide and GADs striatal gene expression typically showed the mimicking of alterations resulting from the A2A‐R genetic deficiency in 25 mg/kg caffeine‐treated wild‐type mice as well as the dose‐dependent normalization of substance P and enkephalin expression in A2A‐R−/− mice. These results indicate that, depending on the dose, the blockade of A2A‐R or A1 receptors by caffeine is preferentially revealed leading to highly differential alterations in striatal gene expression and they also suggested the central role of these two receptors on the control of dopaminergic functions. Synapse 42:63–76, 2001. © 2001 Wiley‐Liss, Inc.
Expression of serotonin 5‐HT2A receptors in the human cerebellum and alterations in schizophrenia
Authors: Eastwood Sharon L. , Burnet Philip W.J. , Gittins Rebecca , Baker Kate , Harrison Paul J.
Published: August 2002

The occurrence of human cerebellar serotonin 5‐HT2A receptors (5‐HT2AR) is equivocal and their status in schizophrenia unknown. Using a range of techniques, we investigated cerebellar 5‐HT2AR expression in 16 healthy subjects and 16 subjects with schizophrenia. Immunocytochemistry with a monoclonal antibody showed labelling of Purkinje cell bodies and dendrites, as well as putative astrocytes. Western blots showed a major band at ∼45 kDa. Receptor autoradiography and homogenate binding with [3H]ketanserin revealed cerebellar 5‐HT2AR binding sites present at levels approximately a third of that in prefrontal cortex. 5‐HT2AR mRNA was detected by reverse transcriptase‐polymerase chain reaction, with higher relative levels in men than women. Several aspects of 5‐HT2AR expression were altered in schizophrenia. 5‐HT2AR immunoreactivity in Purkinje cells was partially redistributed from soma to dendrites and was increased in white matter. 5‐HT2AR mRNA was decreased in the male patients. 5‐HT2AR measured by dot blots and [3H]ketanserin binding (Bmax and Kd) were not significantly altered in schizophrenia. These data show that 5‐HT2AR gene products (mRNA, protein, binding sites) are expressed in the human cerebellum at nonnegligible levels; this bears upon 5‐HT2AR imaging studies which use the cerebellum as a reference region. 5‐HT2AR expression is altered in schizophrenia; the shift of 5‐HT2AR from soma to dendrites is noteworthy since atypical antipsychotics have the opposite effect. Finally, the results emphasise that expression of a receptor gene is a mutifaceted process. Measurement of multiple parameters is necessary to give a clear picture of the normal situation and to show the profile of alterations in a disease. Synapse 42:104–114, 2001. © 2001 Wiley‐Liss, Inc.
Effects of griseofulvin in medium‐term liver carcinogenesis assay and peripheral blood micronucleus test in rat
Authors: Labay Karine , Ould‐Elhkim Mostafa , Klés Virginie , Guffroy Magali , Poul Jean‐Michel , Sanders Pascal
Published: August 2002

Published data have suggested a possible link between the tumor promoting activity and the aneugenic properties of griseofulvin. The present study was conducted to explore this relationship. Griseofulvin was evaluated both for its potential promoting activity in liver carcinogenesis in partially hepatectomized F344 male rats initiated by diethylnitrosamine and for its genotoxic potential in the peripheral blood micronucleus assay. Rats were treated daily with 2,000 mg/kg body weight by oral gavage for 12 weeks in the medium‐term carcinogenesis bioassay. GST‐P‐positive foci (mean number and surface area) and altered cell foci were compared in the liver of rats treated with griseofulvin alone, diethylnitrosamine alone ,and griseofulvin in addition to diethylnitrosamine by using immunohistochemical and histopathological evaluation, respectively. This evaluation allowed the conclusion that griseofulvin did not initiate the carcinogenic process but rather had a potential in the liver for tumor promoting activity. Griseofulvin was found to be negative in the rat peripheral blood micronucleus test when given at a daily oral dose of 2,000 mg/kg body weight for at least 3 weeks. Teratogenesis Carcinog. Mutagen. 21:441–451, 2001. © 2001 Wiley‐Liss, Inc.
The chemistry and biological function of natural marine toxins
Authors: Yasumoto Takeshi
Published: August 2002

Studies on ciguatera fish poisoning led to clarification of the absolute stereochemistry of ciguatoxin, gambierol, gambieric acids, and maitotoxin. Anisotropic NMR reagents and fluorometric chiral HPLC reagents were effectively used together with synthesis of partial structures. Structures of 16 ciguatoxin congeners were successfully elucidated by FAB/MS/MS using samples of 5 μg or less. Stereochemical assignments were also achieved on dinophysistoxin‐1, pectenotoxins, yessotoxins, polycavernoside‐A, azaspiracid, and prymnesins. The toxins possessed poly‐cyclic‐ether structures and originated from unicellular algae. Biological functions are briefly described. © 2000 John Wiley & Sons, Inc. and The Japan Chemical Journal Forum Chem Rec 1:228–242, 2001
The development of lithium ion secondary batteries
Authors: Nishi Yoshio
Published: August 2002

Lithium ion secondary batteries (LIBs) were successfully developed as battery systems with high volumetric and gravimetric energy densities, which were inherited from lithium secondary batteries (LSBs) with metallic lithium anodes. LSBs have several drawbacks, however, including poor cyclability and quick‐charge rejection. The cell reaction in LIB is merely a topochemical one, namely the migration of lithium ions between positive and negative electroces. No chemical changes were observed in the two electrodes or in the electrolytes. This results in little chemical transformation of the active electrode materials and electrolytes, and thus, LIBs can overcome the weaknesses of LSBs; for example, LIBs show excellent cyclability and quick‐charge acceptance. Many difficulties, however, were encountered during the course of development, including capacity fade during cycling and safety issues. This article is the story of the development of LIBs and it describes how the difficulties were surmounted. © 2001 John Wiley & Sons, Inc. and The Japan Chemical Journal Forum Chem Rec 1:406–413, 2001
Emergent learning opportunities in an inner‐city youth gardening program
Authors: Rahm Jrene
Published: August 2002

An emphasis on doing science calls for rich descriptions of the kind of science that gets done in such informal educational contexts as science museums and science‐focused after‐school and summer programs. Described in this article is a study of an inner‐city youth gardening program and of the kinds of learning opportunities that it supported and that emerged from youth‐initiated actions and talk. In particular, there is an examination of the ways in which the garden environment and the experiential nature of the program gave support to the emergence of learning opportunities, while also making connections possible among science, community, and work. The description emphasizes the value of a science that emerges from participants' engagement in activities they deem valuable, meaningful, and authentic. In essence, the results of the study show that informal educational programs that do not have science as their primary goal may provide important insights into the development of learning communities in the classroom. The study highlights the educational value of a school science practice that is driven by its consumers, rather than being imposed on them, and that provides opportunities for the integration of science, work, and community. © 2002 John Wiley & Sons, Inc. J Res Sci Teach 39: 164‐184, 2002
Development and application of a two‐tier multiple choice diagnostic instrument to assess high school students' understanding of inorganic chemistry qualitative analysis*
Authors: Tan Kim Chwee Daniel , Goh Ngoh Khang , Chia Lian Sai , Treagust David F.
Published: August 2002

This article describes the development and application of a two‐tier multiple choice diagnostic instrument to assess high school students' understanding of inorganic chemistry qualitative analysis. The development of the diagnostic instrument was guided by the framework outlined by Treagust. The instrument was administered to 915 Grade 10 students (15 to 17 years old) from 11 schools after they had learned the theory involved in qualitative analysis and after a series of qualitative analysis practical sessions. The Cronbach alpha reliability of the instrument was .68, the facility indices ranged from .17 to .48, and the discrimination indices ranged from .20 to .53. The study showed that the Grade 10 students had difficulty understanding the reactions involved in the identification of cations and anions, for example, double decomposition reactions, the formation and reaction of complex salts, and thermal decomposition. The findings of the study and literature on practical work were used to develop a qualitative analysis teaching package. © 2002 Wiley Periodicals Inc. J Res Sci Teach 39: 283–301, 2002
Modeling science teaching on science practice? Painting a more accurate picture through an ethnographic lab study
Authors: Buxton Cory A.
Published: August 2002

This article reports an ethnographic study of a molecular biology research laboratory, “Sally's Lab.” By studying the daily practices of the lab members, and interpreting these observations through an anthropological lens grounded in practice theory, I portray the social and cultural construction of a scientific community. Findings include an examination of how good science practice was operationalized, status in the lab was constructed, members gained or lost interest in continuing on in careers in research science, and individual members conformed to and resisted localized norms of scientific practice. These issues have direct relevance to our work as science educators, in terms of how we present science practice to our students. For example, when K–16 science students engage in activities based on authentic science practice, upon whose experiences are these simulations based? The current study shows that there is not just one acceptable way to do science, nor one set of experiences that pertain to all members within a given community of science practice. Likewise, there should not be just one way that science is presented in school, nor one set of experiences we expect all our students to take from our classes. © 2001 John Wiley & Sons, Inc. J Res Sci Teach 38: 387–407, 2001
Depletion of Mab21l1 and Mab21l2 messages in mouse embryo arrests axial turning, and impairs notochord and neural tube differentiation
Authors: Wong Rebecca Lee Yean , Chow King Lau
Published: August 2002

Background

The nematode mab‐21 gene specifies sensory ray cell identity and was first isolated because of its mutant sensory ray defects. Vertebrate Mab21 orthologs have since been identified in mammals and amphibians. In this report, we characterized in detail two Mab21 orthologs in mouse, Mab21l1 and Mab21l2.

Methods

We examined the genomic organizations of Mab21 genes and used northern blot and in situ hybridizations to assay their temporal‐spatial expression pattern. Their embryonic functions were revealed by specific attenuation of Mab21 messages with antisense oligos in cultured embryos.

Results

Mab21l1 and Mab21l2 have very similar protein make‐up and gene structures. Both genes were expressed in overlapping domains of actively differentiating embryonic tissues. In addition, Mab21l1 had unique expression in the lens vesicles and genital tubercle whereas Mab21l2 was expressed in the retinal epithelium and umbilical cord. Mab21l1 and Mab21l2 depleted embryos had severe defects in notochord, neural tube, organogenesis, vasculogenesis, and axial turning.

Conclusions

The findings demonstrate that both Mab21 genes are required in developing embryos for embryonic turning, formation of the notochord, neural tube, and other organ tissues. Teratology 65:70–77, 2002. © 2002 Wiley‐Liss, Inc.
Encouraging Your Students to Give Feedback
Authors: Svinicki Marilla D.
Published: August 2002

Students can be encouraged to provide feedback that will help instructors improve the teaching and learning in their classes.
Cognitive Theory and the Design of Multimedia Instruction: An Example of the Two‐Way Street Between Cognition and Instruction
Authors: Mayer Richard E.
Published: August 2002

It is not possible to understand cognition fully without understanding how it works in realistic settings, and it is not possible to reform education appropriately without understanding how people learn and think.