bluuebunny/crossref_metadata_2025_split huggingface dataset:
When, in the context of drug design, can a fluorine atom successfully substitute a hydroxyl group?
Authors: Hoffmann Marcin , Rychlewski Jacek 
Published: October 2002

AbstractIn this article, we deal with the question of whether a fluorine atom can substitute a hydroxyl group in such a way that will lead to a compound showing a desired biologic activity, that is, a potential new drug. It is obvious that a fluorine atom differs from a hydroxyl group, as it cannot donate hydrogen bonds. However, it can accept them. Moreover, both fluorine and oxygen are of similar size and are the most electronegative elements. Therefore, a fluorine atom is thought to be a good substitute for a hydroxyl group. However, it was shown that for conformationally labile aliphatic compounds a replacement of a hydroxyl by a fluorine increases conformational diversity, so the fluorine‐containing aliphatic molecules are present in equilibrium at room temperature as a mixture of several different conformers. In contrast, for cyclic compounds the substitution of an OH group by an F atom does not much change shape and electrostatic potential around corresponding conformers. Moreover, these compounds are present in equilibrium at room temperature in aqueous solution as a mixture of the same most favored structures. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002
Study of phenothiazine and N‐methyl phenothiazine by infrared, raman, 1H‐, and 13C‐NMR spectroscopies
Authors: Alcolea Palafox M. , Gil M. , Núñez J. L. , Tardajos G. 
Published: October 2002

AbstractA complete vibrational analysis of the Fourier transform (FT) infrared (IR) and FT‐Raman spectra of both molecules was carried out using quantum chemical calculations. The structure of phenothiazine (PTZ) and N‐methylphenothiazine (N‐MePTZ) were studied by semiempirical, and ab initio methods. Different basis sets and two new procedures for scaling the frequencies of the ring modes were used. Vibrational data of the methyl group in N‐MePTZ were interpreted in terms of the different molecular conformations in the solid state. The 1H‐ and 13C–nuclear magnetic resonance (NMR) data were interpreted in terms of the electron densities on the atoms and the stacking solute–solute association in dimethyl sulfoxide solution. Chemical shifts were related to the Merz‐Kollman atomic charges. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002
On‐line high‐performance liquid chromatography/mass spectrometric characterization of native oligosaccharides from glycoproteins
Authors: Barroso Begona , Dijkstra Rene , Geerts Marlieke , Lagerwerf Fija , Veelen Peter van , Ru Arnoud de 
Published: October 2002

AbstractAn on‐line high‐performance liquid chromatography/mass spectrometry (HPLC/MS) method is described for the rapid characterization of any type of oligosaccharide released from glycoproteins. The procedure can be applied without further manipulation to fractions collected from a high‐performance anion‐exchange chromatography‐pulse amperometric detection (HPAEC‐PAD) system commonly used for glycosylation mapping of glycoproteins, or to a pool of oligosaccharides directly released from glycoproteins. The system consists of a porous graphitized high‐performance chromatography column (Hypercarb) coupled to a quadrupole time‐of‐flight (TOF) mass spectrometer. Oligosaccharides are eluted from the column with a gradient of ammonium acetate/acetonitrile and directly identified following in‐source fragmentation. Some applications of the method are presented, as well as information about the spectra and fragmentation behavior observed for N‐ and O‐linked oligosaccharides released from some recombinant glycoproteins. Low femtomole limits of detection are achieved using proper miniaturization. Copyright © 2002 John Wiley & Sons, Ltd.
Identification of 1‐hydroxypyrene glucuronide in tissue of marine polychaete Nereis diversicolor by liquid chromatography/ion trap multiple mass spectrometry
Authors: Giessing Anders M. B. , Lund Torben 
Published: October 2002

Abstract1‐Hydroxypyrene glucuronide is identified as the single major aqueous metabolite of the tetracyclic aromatic hydrocarbon pyrene, in tissue from a deposit‐feeding marine polychaete, Nereis diversicolor. Identification was performed using an ion trap mass spectrometer fitted with an atmospheric pressure chemical ionization (APCI) probe and connected to a high‐performance liquid chromatography/diode array detector (HPLC/DAD) system. Besides 1‐hydroxypyrene, the 339‐nm UV trace of tissue samples from pyrene‐exposed worms showed only one dominant peak that could be related to pyrene metabolism. Negative APCI‐MS of this supposed 1‐ hydroxypyrene conjugate gave a characteristic signal at m/z 429 corresponding to the molecular ion of 1‐hydroxypyrene glucuronide plus eluent adducts ([M − H + 2H2O]−). Fragmentation pathways were studied by isolating the abundant ion at m/z 429 in the ion trap and performing multiple mass spectrometric experiments (MSn). The fragmentations observed were consistent with the proposed identification. Two low intensity LC peaks that could be related to pyrene metabolism by their DAD absorption spectra were also present in the 339‐nm UV chromatogram of tissue samples. However, these peaks could not be identified by their mass spectra in negative ion mode due to ion suppression by very abundant co‐eluting impurities. The present method shows that LC/MSn is a fast and useful analytical tool for identification of aqueous polycyclic aromatic hydrocarbon biotransformation products in samples from relatively small marine invertebrates with limited sample preparation. Copyright © 2002 John Wiley & Sons, Ltd.
Identification of the main by‐products of the developing agent N‐hydroxyethyl‐N‐ethyl‐3‐methyl‐p‐phenylenediamine in photographic effluents by liquid chromatography/mass spectrometry
Authors: Lunar Loreto , Rubio Soledad , Pérez‐Bendito Dolores , Jiménez César 
Published: October 2002

AbstractN‐Hydroxyethyl‐N‐ethyl‐3‐methyl‐p‐phenylenediamine (CD4) is commonly used as a developing agent in color photographic processes. The main by‐products formed in developer baths used in the process were separated and identified by liquid chromatography/electron ionization mass spectrometry (LC/EI‐MS) and liquid chromatography/atmospheric pressure ionization mass spectrometry (LC/API‐MS). A number of side reactions, in addition to the main reactions involved in the developing process, were found to occur. Such side reactions involved in the formation of CD4 by‐products included oxidation, hydroxylation, sulfonation and the formation of coupling products. A reaction pathway for the degradation of CD4 based on the nature of the by‐products identified is proposed and discussed. Copyright © 2002 John Wiley & Sons, Ltd.
SITE Demonstration of Enhanced In‐Situ Bioremediation of Chlorinated and Nonchlorinated Organic Compounds in Fractured Bedrock
Authors: Gallardo Vicente J. , Beckman Scott W. , Tillman Joseph W. 
Published: October 2002

AbstractA field demonstration of an enhanced in‐situ bioremediation technology was conducted between March 1998
and August 1999 at the ITT Industries Night Vision (ITTNV) Division plant in Roanoke, Virginia. The
bioremediation process was evaluated for its effectiveness in treating both chlorinated and nonchlorinated
volatile organic compounds (VOCs) in groundwater located in fractured bedrock. Chlorinated compounds,
such as trichloroethene (TCE), in fractured bedrock pose a challenging remediation problem. Not only are
chlorinated compounds resistant to normal biological degradation, but the fractured bedrock presents difficulties
to traditional techniques used for recovery of contaminants and for delivery of amendments or reagents for
in‐situ remediation.The demonstration was conducted under the U.S. Environmental Protection Agency's Superfund Innovative
Technology Evaluation (SITE) program. The SITE program was established to promote the development,
demonstration, and use of innovative treatment technologies for the cleanup of Superfund and other hazardous waste
sites. This article presents selected results of the demonstration and focuses on understanding the data in light
of the fractured bedrock formation. © 2002 Wiley Periodicals, Inc.
Changes in fish communities of the Shoalhaven River 20 years after construction of Tallowa Dam, Australia
Authors: Gehrke P. C. , Gilligan D. M. , Barwick M. 
Published: October 2002

AbstractThis study was undertaken as part of a long‐term investigation of the ability of high‐level fishways to rehabilitate fish communities upstream of high dams. Effects of Tallowa Dam on fish of the Shoalhaven River system were studied by comparing species abundances, population size‐structures and the structure of fish communities above and below the dam. Fish were sampled twice yearly for two years at 12 sites throughout the catchment. Species richness was greater downstream of the dam, with 21 species, compared to 16 species upstream of the dam. Ten diadromous species are believed to be extinct above the dam because of obstructed fish passage. Another four migratory species capable of climbing the wall have reduced abundances upstream. Accumulations of fish, particularly juveniles, directly below the dam were evident for nine species. Fish communities upstream and downstream of the dam differed significantly, identifying the dam as a significant discontinuity in the available fish habitats within the system. Historical evidence suggests that before the dam was built, fish communities from the tidal limit to at least 130 m elevation were largely continuous. This study has demonstrated that Tallowa Dam is a major barrier to fish migration and has had adverse effects on the biodiversity of the system. The creation of Lake Yarrunga by Tallowa Dam has resulted in distinctive fish communities in riverine and lacustrine habitats. Populations of five species that occur both upstream and downstream of the dam have developed differences in their size structures. The fish community downstream of the dam also differs from its historical condition because of the virtual disappearance of Australian grayling (Prototroctes maraena) and the establishment of non‐native species.A high‐level fishway is now being designed for the dam to restore fish passage. Data from this study will serve as a baseline against which to assess the effectiveness of the fishway in rehabilitating fish communities of the river system. Copyright © 2002 John Wiley & Sons, Ltd.
Meaningful learning: The essential factor for conceptual change in limited or inappropriate propositional hierarchies leading to empowerment of learners
Authors: Novak Joseph D. 
Published: October 2002

AbstractThe construction and reconstruction of meanings by learners requires that they actively seek to integrate new knowledge with knowledge already in their cognitive structure. Ausubel's assimilation theory of cognitive learning has been shown to be effective in guiding research and instructional design to facilitate meaningful learning (Ausubel, The psychology of meaningful verbal learning, New York: Grune and Stratton, 1963; Educational psychology: A cognitive view, New York: Holt, Rinehart and Winston, 1968; The acquisition and retention of knowledge, Dordrecht: Kluwer, 2000). Gowin's Vee heuristic has been employed effectively to aid teachers and students in understanding the constructed nature of knowledge (Gowin, Educating, Ithaca, NY: Cornell University Press, 1981). “Situated learning” occurs when learning is by rote or at a lower level of meaningful learning. Concept mapping has been used effectively to aid meaningful learning with resulting modification of student's knowledge structures. When these knowledge structures are limited or faulty in some way, they may be referred to as Limited or Inappropriate Propositional Hierarchies (LIPH's). Conceptual change, or more accurately conceptual reconstrution, requires meaningful learning to modify LIPH's. Collaborative group learning facilitates meaningful learning and new knowledge construction. World‐wide economic changes are forcing major changes in business and industry placing a premium on the power and value of knowledge and new knowledge production. These changes require changes in school and university education that centers on the nature and power of meaningful learning. New computer tools are available to facilitate teaching activities targeted at modifying LIPH's, and aiding meaningful learning in general. © 2002 Wiley Periodicals, Inc. Sci Ed 86:548–571, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/sce.10032
Diagnostics for conformity of paired quantitative measurements
Authors: Hawkins Douglas M. 
Published: October 2002

AbstractMatched pairs data arise in many contexts – in case‐control clinical trials, for example, and from cross‐over designs. They also arise in experiments to verify the equivalence of quantitative assays. This latter use (which is the main focus of this paper) raises difficulties not always seen in other matched pairs applications. Since the designs deliberately vary the analyte levels over a wide range, issues of variance dependent on mean, calibrations of differing slopes, and curvature all need to be added to the usual model assumptions such as normality. Violations in any of these assumptions invalidate the conventional matched pairs analysis. A graphical method, due to Bland and Altman, of looking at the relationship between the average and the difference of the members of the pairs is shown to correspond to a formal testable regression model. Using standard regression diagnostics, one may detect and diagnose departures from the model assumptions and remedy them – for example using variable transformations. Examples of different common scenarios and possible approaches to handling them are shown. Copyright © 2002 John Wiley & Sons, Ltd.
A solution to the problem of separation in logistic regression
Authors: Heinze Georg , Schemper Michael 
Published: October 2002

AbstractThe phenomenon of separation or monotone likelihood is observed in the fitting process of a logistic model if the likelihood converges while at least one parameter estimate diverges to ± infinity. Separation primarily occurs in small samples with several unbalanced and highly predictive risk factors. A procedure by Firth originally developed to reduce the bias of maximum likelihood estimates is shown to provide an ideal solution to separation. It produces finite parameter estimates by means of penalized maximum likelihood estimation. Corresponding Wald tests and confidence intervals are available but it is shown that penalized likelihood ratio tests and profile penalized likelihood confidence intervals are often preferable. The clear advantage of the procedure over previous options of analysis is impressively demonstrated by the statistical analysis of two cancer studies. Copyright © 2002 John Wiley & Sons, Ltd.
Estimating the causal effect of zidovudine on CD4 count with a marginal structural model for repeated measures
Authors: Hernán Miguel A. , Brumback Babette A. , Robins James M. 
Published: October 2002

AbstractEven in the absence of unmeasured confounding factors or model misspecification, standard methods for estimating the causal effect of a time‐varying treatment on the mean of a repeated measures outcome (for example, GEE regression) may be biased when there are time‐dependent variables that are simultaneously confounders of the effect of interest and are predicted by previous treatment. In contrast, the recently developed marginal structural models (MSMs) can provide consistent estimates of causal effects when unmeasured confounding and model misspecification are absent. We describe an MSM for repeated measures that parameterizes the marginal means of counterfactual outcomes corresponding to prespecified treatment regimes. The parameters of MSMs are estimated using a new class of estimators – inverse‐probability of treatment weighted estimators. We used an MSM to estimate the effect of zidovudine therapy on mean CD4 count among HIV‐infected men in the Multicenter AIDS Cohort Study. We estimated a potential expected increase of 5.4 (95 per cent confidence interval ‐1.8,12.7) CD4 lymphocytes/l per additional study visit while on zidovudine therapy. We also explain the theory and implementation of MSMs for repeated measures data and draw upon a simple example to illustrate the basic ideas. Copyright © 2002 John Wiley & Sons, Ltd.
Analysis of mutational spectra: locating hotspots and clusters of mutations using recursive segmentation
Authors: Fijal Bonnie A. , Idury Ramana M. , Witte John S. 
Published: October 2002

AbstractMutations within different regions of disease‐causing genes can vary in their impact on disease initiation and progression. Determining how individual mutations within such genes affect disease risk and progression can improve the accuracy of prognoses and help guide treatment selection. Estimates of mutation‐specific risks can be poor, however, when genes have a large number of distinct mutations, and data for any given mutation is sparse. To address this problem, we present here a method of analysing the spectrum of mutations observed across a gene that pools together mutations that appear to have similar effects on disease. One of the assumptions underlying the analysis of mutational spectra created in this manner is that the frequency of the mutation in the sample reflects the degree of its effect on disease development. Additionally, mutations that disrupt the same functionally important region of the gene are expected to have a similar impact on disease development. These mutations tend to form a cluster within the spectrum. Therefore, we developed an algorithm that segments a spectrum into regions containing sites with similar mutational frequencies, and have derived by simulation equations that allow one to evaluate whether segmentation is needed. We used this approach to investigate the spectrum of mutations observed in the p53 tumour suppressor gene in colorectal cancer tumours. Here, recursive segmentation identified the boundaries of apparent clusters better than did other methods, and this approach could identify clusters of mutations which corresponded to biologically important regions of the p53 protein. Copyright © 2002 John Wiley & Sons, Ltd.
Meta‐analysis combining parallel and cross‐over clinical trials. I: Continuous outcomes
Authors: Curtin François , Altman Douglas G. , Elbourne Diana 
Published: October 2002

AbstractAmong clinical trials assessing a given treatment, often parallel and cross‐over designs are used together. In the first paper of a series of three, we explore two methods to pool continuous outcomes in a meta‐analysis combining parallel and cross‐over trial designs: the weighted mean difference (WMD) and the standardized weighted mean difference (SWMD). The combined design meta‐analytic formulae are based on a weighted average of the two design treatment estimates. A random effects model can be implemented. Both WMD and SWMD can be used, the choice of the method is determined by the type of outcomes obtained in the trials. Compared to the number of included subjects, the relative weight of the cross‐over design is large in combined‐design meta‐analysis. Differences in the weight estimation between WMD and SWMD can also accentuate the relative weight of cross‐over trials, which must be considered a case of design‐specific bias. Copyright © 2002 John Wiley & Sons, Ltd.
Edith Penrose's contribution to the resource‐based view of strategic management
Authors: Rugman Alan M. , Verbeke Alain 
Published: October 2002

AbstractEdith Penrose's (1959) book,The Theory of the Growth of the Firm, is considered by many scholars in the strategy field to be the seminal work that provided the intellectual foundations for the modern, resource‐based theory of the firm. However, the present paper suggests that Penrose's direct or intended contribution to resource‐based thinking has been misinterpreted. Penrose never aimed to provide useful strategy prescriptions for managers to create a sustainable stream of rents; rather, she tried to rigorously describe the processes through which firms grow. In her theory, rents were generally assumed not to occur. If they arose this reflected an inefficient macro‐level outcome of an otherwise efficient micro‐level growth process. Nevertheless, her ideas have undoubtedly stimulated ‘good conversation’ within the strategy field in the spirit of Mahoney and Pandian (1992); their emerging use by some scholars as building blocks in models that show how sustainable competitive advantage and rents can be achieved is undeniable, although such use was never intended by Edith Penrose herself. Copyright © 2002 John Wiley & Sons, Ltd.
Competitive advantages exist: a critique of Powell
Authors: Durand Rodolphe 
Published: October 2002

AbstractThis response is a plea for considering cautiously the use of formal logic and philosophy in strategic management. In a recent article, logical and philosophical considerations on the relationship between competitive advantage and superior returns led to a pragmatic view of competitive advantage. First, we propose a different logical analysis of the links between competitive advantage and superior performance. Using the same premises, this analysis leads to different conclusions. Second, our commentaries suggest that philosophy should be employed for opening discussions and perspectives rather than as an instrument for conviction. Copyright © 2002 John Wiley & Sons, Ltd.
Region‐specific targeting of dopamine D2‐receptors and somatodendritic vesicular monoamine transporter 2 (VMAT2) within ventral tegmental area subdivisions
Authors: Pickel Virginia M. , Chan June , Nirenberg Melissa J. 
Published: October 2002

AbstractThroughout the ventral tegmental area (VTA), dopamine is packaged within subcellular organelles by the vesicular monoamine transporter‐2 (VMAT2). Somatodendritically released dopamine in this region binds to the D2 receptor (D2R) to modulate ongoing neurotransmission. Although autoregulation of mesocortical dopaminergic neurons in the parabrachial VTA (PB‐VTA) is known to be less efficacious than that of mesolimbic dopaminergic neurons in the paranigral (PN‐VTA), the cellular basis for this regional heterogeneity is not known. For this reason, we used electron microscopic immunocytochemistry to determine the subcellular localization of the dopamine storage vesicles (identified by the presence of VMAT2) in relation to the D2R in these VTA subdivisions. In both regions, D2R immunoreactivity was principally located on extrasynaptic dendritic plasma membranes near excitatory‐type synapses. Equivalent percentages (72 and 74%) of the D2R‐labeled dendrites in each region contained VMAT2‐immunoreactive tubulovesicles. Of the total VMAT2‐labeled dendrites, however, a significantly lower percentage in the PB‐VTA (26%) than in the PN‐VTA (38%) contained D2R labeling. In contrast, a significantly higher number of VMAT2 immunogold‐silver deposits was seen within individual dendrites in the PB‐VTA than in PN‐VTA. In both regions, D2R immunoreactivity was also detected in VMAT2‐negative axon terminals that formed synapses on dendrites containing VMAT2. Our results are the first to demonstrate that within VTA neurons and their afferents the D2R is strategically positioned for activation by dopamine released from dendritic storage vesicles. These findings also suggest that the potential for D2R activation may affect the expression levels of VMAT2 in VTA dendrites. Synapse 45:113–124, 2002. © 2002 Wiley‐Liss, Inc.