bluuebunny/crossref_metadata_2025 huggingface dataset:
Interdiffusion at TiO2/Ti, TiO2/Ti3Al and TiO2/TiAl interfaces studied in bilayer structures
Authors: Zalar A. , van Lier J. , Mittemeijer E. J. , Kovač J.
Published: October 2002

Early‐stage interfacial reactions were studied in three different heat‐treated oxide/metal bilayers (the oxide is amorphous (a) TiO2 and the metal is crystalline (c) Ti, c‐Ti3Al or amorphous a‐TiAl) by means of Auger electron spectroscopy (AES) depth profiling. The oxide/metal bilayers were sputter deposited onto smooth silicon substrates, covered with a TiN or Al2O3 thin‐film diffusion barrier. In order to prevent the supply of oxygen from the external atmosphere, selected samples were covered with an additional protective Si3N4 thin film. Reactions at the oxide/metal interfaces were induced by heating the samples in an argon atmosphere at a linear heating rate of 40°C min−1 between room temperature and different final temperatures (350–700°C). The composition and microstructure of selected samples were investigated by XPS, x‐ray diffraction (XRD) and transmission electron microscopy (TEM).

Heating of the a‐TiO2/c‐Ti, a‐TiO2/c‐Ti3Al and a‐TiO2/a‐TiAl bilayers induced a decomposition of the a‐TiO2 layers, in association with diffusion and solid solution formation of oxygen in the corresponding metallic layers. In the early stage of the reactions, the presence of Al in the metallic layers resulted in a lower solubility of oxygen compared with a pure Ti layer. The beginning of interdiffusion at the a‐TiO2/c‐Ti interface was observed at ∼400°C and at the other two interfaces at ∼550°C. The temperature‐dependent effective diffusion coefficients were determined from the rate of increase of the interface width, as obtained in the oxygen depth profiles. The activation energies for oxygen diffusion from a‐TiO2 into the c‐Ti, c‐Ti3Al and a‐TiAl layers was found to be 1.5 eV (between 400 and 500°C) and 1.7 eV and 1.8 eV (between 550 and 650°C), respectively. Copyright © 2002 John Wiley & Sons, Ltd.
Organosilane self‐assembled monolayers formed at the vapour/solid interface
Authors: Sugimura Hiroyuki , Hozumi Atsushi , Kameyama Tetsuya , Takai Osamu
Published: October 2002

Self‐assembly of organosilane molecules at the vapour/solid interface under atmospheric pressure conditions was explored in order to form a monolayer on oxide‐covered silicon substrates. Three types of precursors were employed: n‐octadecyltrimethoxysilane (ODS: H3C(CH2)17Si(OCH3)3), n‐(6‐aminohexyl)aminopropyltrimethoxysilane (AHAPS: H2N(CH2)6NH(CH2)3Si(OCH3)3) and fluoroalkylsilane (FAS: heptadecafluoro‐1,1,2,2‐tetrahydro‐decyl‐1‐trimethoxysilane, F3C(CF2)7(CH2)2Si(OCH3)3). Characteristics of these self‐assembled monolayers (SAMs) formed at a temperature of 100–150°C were studied based on ellipsometry and x‐ray photoelectron spectroscopy. Chemical properties of the monolayers were characterized further by water contact angle and ζ‐potential measurements. The SAMs formed from ODS and FAS were hydrophobic so as to show water contact angles of >100°, whereas that of the SAM formed from AHAPS was ∼60°. ζ‐potentials and isoelectric points (IEPs) of SiO2 substrates covered with each of the SAMs were measured and compared with a naked SiO2 substrate. The IEPs of the SiO2 substrate covered with the ODS‐ or FAS‐SAM was pH 3.5–4.0, which was almost the same as those of polyethylene and polytetrafluoroethylene plates, whereas that of the naked SiO2 substrate was pH ∼2.0, as predicted from results on silica particles. In the case of the AHAPS‐SAM, its surface was positively charged under acidic conditions due to protonation of surface amino groups. Consequently, the AHAPS‐SAM‐covered substrate showed an IEP of pH 7.5–8.0. Copyright © 2002 John Wiley & Sons, Ltd.
MIES and UPS study of O‐predosed nickel surface reduction by H2 deposition
Authors: Fanjoux G. , Lescop B. , Le Nadan A.
Published: October 2002

The present study was aimed at investigating the reduction by hydrogen of an oxygen‐predosed nickel surface at high temperature (530 K) using metastable impact electron spectroscopy (MIES) and UPS (with He(I)) experimental techniques. Both techniques have allowed us to follow the evolution of the electronic structure of the valence band during H2 deposition. The work function variation seems to be related directly to the oxygen coverage of the surface and exhibits two stages: an induction period during which no reduction reaction occurs; a rapid reaction period corresponding to the reduction of oxygen. The reaction mechanism entails the formation of hydroxyl compounds but, owing to their thermal desorption at lower temperature in the form of water, no evident OH features have been observed in the MIES and UPS spectra.

The 3d band intensity, measured at 0.5 eV under the Fermi level using UPS, increased linearly during H2 deposition. This evolution could correspond to that of bare Ni atoms in the three or four surface layers. On the other hand, evolution of the MIES signal taken at 5.7 eV under the Fermi level provided us with more accurate information about the evolution of the outermost layer of the predosed nickel surface during H2 exposure. Copyright © 2002 John Wiley & Sons, Ltd.
Photoelectron signal simulation from textured samples with modified surface composition
Authors: Vutova K. , Mladenov G. , Tanaka T. , Kawabata K.
Published: October 2002

In this paper we propose a mathematical model for calculating XPS intensity distributions from multi‐component textured samples with a step‐like distribution approximating the depth compositional profiles. The surface roughness is approximated using triangular prisms. Analytical expressions for calculation of angular photoelectron intensity distributions are given. The results obtained concern textured samples where the height of the surface roughness structures are 3–5 times greater than the ejection depth. The values of the altered layer thickness and the values of the emitted photoelectron's ejection depth are of the same order. This model is appropriate when studying the changes of compositional depth profiles in the range of the photoelectron ejection depth. Copyright © 2002 John Wiley & Sons, Ltd.
Application of self‐organizing maps (SOMs) to chemical spectral analysis of elements in the Periodic Table
Authors: Tokutaka H. , Obu‐Cann K. , Fujimura K. , Ikeda Y. , Yoshihara K.
Published: October 2002

This paper reports on the application of self‐organizing maps (SOMs) to chemical spectral analysis. The SOM method that was developed by Kohonen was first applied to information processing. Currently, it has been applied to some problems of chemical spectral analysis using AES, XPS and x‐ray diffraction data. Using a two‐dimensional SOM, it became clear that the items that are described qualitatively by linguistic expressions could be explained more quantitatively by the position of the spectral data on the SOM, together with a grey‐level expression. Also, the composition of an unknown sample can be determined very precisely by the SOM that has been constructed using the spectra from samples of known composition. Furthermore, this paper addresses the attempts to develop a SOM of all the elements of the Periodic Table. Currently, only 77 elements have been mapped out. Copyright © 2002 John Wiley & Sons, Ltd.
Use of XPS to follow the evolution of a solution/solid interface: SiMo12O404− acidic solution/GaAs interface
Authors: Debiemme‐Chouvy Catherine , Quennoy Anne , Etcheberry Arnaud
Published: October 2002

In some cases, XPS analysis can be used to determine the reactions that take place at a solid/solution interface. In this study, the behaviour of GaAs in contact with an acidic aqueous solution containing a Keggin‐type heteropolyanion—SiMo12O404−—was investigated on the basis of the XPS data. During immersion in the solution, a film composed of elemental As and partially reduced heteropolyanion develops on the GaAs surface. The chemical composition of the surface film indicates that at the GaAs/solution interface the heteropolyanion is reduced whereas GaAs undergoes an anodic dissolution process. The GaAs dissolution rate is proportional to the heteropolyanion concentration. At a given immersion time, the nature of the GaAs surface film is independent of the heteropolyanion concentration, whereas the As0/heteropolyanion ratio and the film thickness depend on this concentration. Moreover, the chemical composition of the film changes by exposure to air, as some elemental As atoms volatilize. Copyright © 2002 John Wiley & Sons, Ltd.
In situ measurements of surface homogeneity of optical parameters of weakly absorbing thin films
Authors: Spousta J. , Urbánek M. , Chmelík R. , Jiruše J. , Zlámal J. , Navrátil K. , Nebojsa A. , Šikola T.
Published: October 2002

In this paper an instrument based on combining the principles of both spectral and multiple‐wavelength reflectivity, designed by our group for in situ monitoring of the surface homogeneity of the thickness of weakly absorbing thin films, was tested in a series of ex situ and in situ experiments. The tests confirmed that it is a convenient tool for the in situ quasi‐real‐time monitoring of the surface homogeneity of the thicknesses of small‐area thin films (up to 1 cm2) during their etching and growth. Using this method, homogeneous growth of an SiO2 film with an average growth rate of 103 nm h−1 in one pilot point during deposition by ion beam sputtering of a quartz target was monitored in situ. On the other hand, the ion beam etching rate of the thermal SiO2 film was <3.3 nm min−1 and an enhanced roughness of the etched film in comparison to the initial one was observed. Copyright © 2002 John Wiley & Sons, Ltd.
Micro‐XPS analysis of slide‐tested TiN films with/without Cl+ implantation
Authors: Yoshitake M. , Thananan A. , Aizawaki T. , Yoshihara K.
Published: October 2002

We analysed the surface of TiN films (∼2 µm thick) with/without Cl+ implantation by scanning XPS. Both TiN films were subjected to a sliding test by a stainless‐steel ball, resulting in round, 150 µm wide scratches on the surface. We examined the difference in chemical composition and chemical state between the worn and the unworn surfaces. On the TiN film without Cl+ implantation, the primary compounds found were TiO2 and TiN with carbon contamination. The friction coefficient was ∼0.8 on this surface. The chemical compound on the worn surface was mainly Fe2O3 with a small amount of TiO2. This suggests that TiN is hard but not lubricative and that elements from the stainless‐steel ball adhered to the surface of the TiN film during the sliding test. On the TiN film with Cl+ implantation, the main compound found was TiO2, although we also observed a small amount of TiN. Furthermore, we detected a small amount of Cl, whose chemical state indicated binding with a metal component. The friction coefficient was <0.2 on this surface. The chemical compounds on the worn surface were TiN and TiO2, and no Fe was detected. We could clearly detect TiO2 on the surface of the stainless‐steel ball, therefore we concluded that oxidation is enhanced on Cl+ implanted TiN and that titanium oxide functions as a lubricant. During the sliding test, oxidation of the TiN film seemed to continue and titanium oxide was supplied continuously. Copyright © 2002 John Wiley & Sons, Ltd.
Effect of reactive ion etching on amorphous carbon nitride films
Authors: Jiang Liudi , Fitzgerald A. G. , Rose M. J. , Gundlach A. M. , Cheung R.
Published: October 2002

Amorphous carbon nitride (a‐C : N) films have been deposited by reactive direct current magnetron sputtering of graphite using N2 as the sputtering gas. In order to study the effects of dry etching on the deposited films, post‐treatment of the films has been performed by reactive ion etching in an argon plasma and an oxygen plasma, respectively. Fourier transform infrared (FTIR) spectroscopy and x‐ray photoelectron spectroscopy (XPS) have been used to study the chemical bonding structures in the films. We have found that although the FTIR results are very similar in all the samples, by comparing the XPS results from all the samples the relative ratio of the β‐C3N4‐like phase over the graphite‐like carbon–nitrogen phase in the films increased significantly after oxygen bombardment. This indicates that an oxygen plasma works effectively as an etchant of the graphite‐like phase in a‐C : N films. This process is conducive to the production of CN films that have a higher concentration of the β‐C3N4‐like phase. Copyright © 2002 John Wiley & Sons, Ltd.
Determining the angular admittance of a cylindrical mirror analyser
Authors: Watts B. , Thomsen L. , Dastoor P. C.
Published: October 2002

Recent studies have demonstrated the need for the angular acceptance of a cylindrical mirror analyser (CMA) to be determined quantitatively. This acceptance probability function, with respect to the electron ejection angle, has not been reported previously. In this paper the angular acceptance function of a PHI‐550 double‐pass CMA has been determined quantitatively. A knowledge of this function makes it possible to extract some limited depth‐sensitive information from a standard CMA instrument without using a rotating aperture. Copyright © 2002 John Wiley & Sons, Ltd.
Characterization of the interface in rubber/silica composite materials
Authors: Salvi Anna Maria , Pucciariello Rachele , Guascito Maria Rachele , Villani Vincenzo , Intermite Luisa
Published: October 2002

In the rubber industry, especially tyre production, the most widely used elastomer is styrene–butadiene rubber (SBR) in which the styrene units generally are present at 25 wt.%. The unit repeats are random distributed along the macromolecular chains and the configuration of the butadiene units is mostly 1,4‐trans. The elastomer blends are mixed with fillers, acting as reinforcing agents, and the effect that silica particles have on their physical and mechanical properties is now well established. One of the most important parameters in determining the performance of such composite materials is the degree of adhesion at the rubber/silica interface. In this context, the interface characterization has been performed through a spectroscopic investigation (XPS/x‐ray‐induced Auger electron spectroscopy) in order to derive information from core‐level and Auger line chemical shifts. A series of composite rubbers have been examined by means of a detailed curve‐fitting procedure that allows the determination of intrinsic and extrinsic structures connected to each photopeak and the spectroscopic results compared with those of reference compounds. The changes in the C 1s lineshape and shake‐up region of the polymers and the reduced binding energies of silicon, oxygen and sulphur core lines have provided clear evidence of interfacial reactions. Moreover, the Auger parameters of silicon show systematic shifts that can be interpreted on a chemical state plot in terms of initial‐ and final‐state contributions and used for theoretical investigation of the local chemical environment. Copyright © 2002 John Wiley & Sons, Ltd.
Angle‐resolved XPS characterization of urea formaldehyde–epoxy systems
Authors: Perruchot Christian , Watts John F. , Lowe Chris , White Richard G. , Cumpson Peter J.
Published: October 2002

A series a coil coating primers, based on high‐molecular‐weight epoxy resins and a urea formaldehyde crosslinking agent, have been investigated by angle‐resolved XPS (ARXPS) analysis. The addition of a low amount of flow agent additive (<0.2 wt.%) in the formulations induced significant changes in the surface composition and the peak‐fitted carbon spectra compared with the reference formulation containing no additive. Characterization of the surface composition of the various coatings at different take‐off angles of analysis, combined with the use of a public domain forward transform routine (ARCtick 1.0 software, from the National Physical Laboratory, UK), allows the determination of the elemental depth profile for each formulation. In addition, changes of the relative intensities of specific components in the peak‐fitted carbon signals allow the determination of chemical depth profiles within the analysis depth of XPS (∼4–5 nm). Elemental and chemical compositions clearly demonstrate a preferential segregation of the flow agent additive towards the air/surface interface of the coating. The thickness of the additive outerlayer was evaluated in the range of 0.5–1.0 nm using the variations of the elemental and carbon chemistry depth profiles, which shows changes in the concentration of the additive. Copyright © 2002 John Wiley & Sons, Ltd.
Monitoring clinical trials: issues and controversies regarding confidentiality
Authors: Fleming Thomas R. , Ellenberg Susan , DeMets David L.
Published: October 2002

During phase III clinical trials in life‐threatening disease settings, it is important to ensure that the Data Monitoring Committee (DMC) has exclusive access to the interim efficacy and safety data generated by the data analysis centre, in order to minimize the risk of widespread prejudgement of unreliable trial results based on limited data. This prejudgement could adversely impact rates of patient accrual, continued adherence to trial regimens and ability to obtain unbiased and complete assessment of trial outcome measures. This also could result in publications of early results that might be very inconsistent with final study data on the benefit‐to‐risk profile of the study interventions. Circumstances arise only rarely in which unblinding of interim data beyond the DMC would enhance the ability of the trial to provide reliable results. However, to address the ethical imperative to protect the interests of study participants, the DMC itself should have access to unblinded efficacy and safety results. Copyright © 2002 John Wiley & Sons, Ltd.
The European regulatory experience
Authors: Lewis John A.
Published: October 2002

This paper discusses four methodological topics that have been a regular source of difficulty and debate in European regulatory work. (i) The increasing use of non‐inferiority trials in the development of medicinal products has highlighted several problems. These relate first to the choice of the non‐inferiority margin and secondly to the circumstances under which a non‐inferiority design is or is not appropriate. (ii) The use of meta‐analysis in regulatory applications is still controversial and acceptable uses need to be defined. (iii) Analysis of responders provides a useful insight into the size of treatment benefits but can be misleading, especially when it is impossible to be certain whether or not an individual patient has truly responded to treatment. (iv) The extent of the monitoring of clinical trial procedures and data still distinguishes industry‐sponsored trials from other trials: it is not clear that it should. These questions are all equally important for those involved in clinical trial work outside the arena of pharmaceutical development. Copyright © 2002 John Wiley & Sons, Ltd.
The occupational stress and health outcome profiles of clinical directors in child and adolescent psychiatry
Authors: Kirkcaldy B.D. , Siefen G.
Published: October 2002

Over 60 per cent of the Consultant Medical Directors of all 102 German Clinics for Child and Adolescent Psychiatry responded to a comprehensive questionnaire to assess specific facets of occupational stress and health outcome (psychological and physical well‐being), as well as individual difference variables (Type A behaviour, Locus of Control, and coping). Compared to other managers (n = 287), the medical professionals tended to exhibit greater job‐related stress, more specifically in terms of workload, managerial role and daily hassles. Conversely, they reported less stress associated with recognition and achievement. There were no differences in terms of Type A behaviour and coping, but medical directors displayed higher levels of internal locus of control. The majority expressed favourable evaluation of working climate. Overall, they were more satisfied with their work and this was most apparent with respect to intrinsic job satisfaction, organizational satisfaction and organizational security. Daily hassles (day to day irritants and aggravations in the workplace) emerged as the single stress determinant of physical and psychological well‐being for the physician group. Copyright © 2002 John Wiley & Sons, Ltd.
Hazing: Hidden campus crime
Authors: Hollmann Barbara B.
Published: October 2002

Initiation traditions and rites of passage are important for group and team membership, but the violent behavior and alcohol abuse involved in hazing constitute serious campus crime. This chapter helps campus administrators develop new strategies for attacking the hidden crime of hazing.
Integrating inquiry science and language development for English language learners
Authors: Stoddart Trish , Pinal America , Latzke Marcia , Canaday Dana
Published: October 2002

The traditional approach to the education of language minority students separates English language development from content instruction because it is assumed that English language proficiency is a prerequisite for subject matter learning. The authors of this article take the alternate view that the integration of inquiry science and language acquisition enhances learning in both domains. The report describes a conceptual framework for science–language integration and the development of a five‐level rubric to assess teachers' understanding of curricular integration. The science–language integration rubric describes the growth of teacher expertise as a continuum from a view of science and language as discreet unrelated domains to the recognition of the superordinate processes that create a synergistic relationship between inquiry science and language development. Examples from teacher interviews are used to illustrate teacher thinking at each level. © 2002 Wiley Periodicals, Inc. J Res Sci Teach 39: 664–687, 2002
Buthionine sulfoximine embryotoxicity is associated with prolonged AP‐1 activation
Authors: Ozolinš Terence R.S. , Harrouk Wafa , Doerksen Tonia , Trasler Jacquetta M. , Hales Barbara F.
Published: October 2002

Background

Many teratogens induce oxidative stress, altering redox status and redox signaling; this has led to the suggestion that developmental toxicants act by disturbing redox status. The goal of these studies was to determine the consequences of altering glutathione homeostasis during organogenesis on embryo development, total DNA methylation, and activator protein‐1 (AP‐1) DNA binding activity and gene expression.

Methods

Gestational day 10.5 rat embryos were cultured in vitro for up to 44 hour in the presence of L‐buthionine‐S,R‐sulfoximine (BSO), an irreversible inhibitor of γ‐glutamyl‐cysteine synthetase, the rate limiting step in glutathione biosynthesis. Effects of BSO on total, oxidized and reduced glutathione, embryo development, DNA methylation, AP‐1 DNA binding activity and gene expression were investigated.

Results

Significant depletion of glutathione by BSO was first noted at 6 hr in the embryo and at 3 hr in the yolk sac; total glutathione in the conceptus was depleted to the same extent after treatment with either 0.1 or 1.0 mM BSO. Exposure to 0.1 mM BSO did not cause a significant increase in embryotoxicity, although some impairment of growth and development was observed. In contrast, exposure to 1.0 mM BSO severely inhibited growth and development, significantly increasing the incidence of swollen hindbrains and of blebs in the forebrain, limb and maxillary regions. No significant treatment‐related differences in total DNA methylation were observed. Interestingly, AP‐1 DNA binding activity was similar in control and 0.1 mM BSO‐treated conceptuses; however, exposure to 1.0 mM BSO increased AP‐1 DNA binding at 6, 24, and 44 hr. The expression of several AP‐1 family genes and of γ‐glutamylcysteine synthetase was induced in embryos cultured with 1.0 mM BSO.

Conclusion

Exposure of embryos in vitro to BSO at a concentration that was embryotoxic induced prolonged AP‐1 DNA binding activity and altered gene expression. These data suggest that AP‐1 induction may serve as a biomarker of embryo stress. Teratology 66:192–200, 2002. © 2002 Wiley‐Liss, Inc.
Assessing e‐folios in the on‐line class
Authors: Canada Mark
Published: October 2002

Once they are aware of both the promises and pitfalls of e‐folios, professors can make effective use of these collections of student work to enhance their students' learning and facilitate their own process of responding to student work.
Assessing the on‐line degree program
Authors: Law Joe , Hawkes Lory , Murphy Christina
Published: October 2002

As on‐line degree programs are made available in greater numbers, the necessity of employing clearly articulated criteria for consistent evaluation across programs becomes increasingly evident. The best starting point for such assessment efforts is “Best Practices for Electronically Offered Degree and Certificate Programs,” developed by the Western Interstate Commission for Higher Education.
Mechanism and prediction for contamination of freshwater bivalves (Unionidae) with the cyanobacterial toxin microcystin in hypereutrophic Lake Suwa, Japan
Authors: Yokoyama Atsushi , Park Ho‐Dong
Published: October 2002

Seasonal changes of microcystin (MC) bioaccumulation in three freshwater Unionid bivalves, Anodonta woodiana, Cristaria plicata, and Unio douglasiae, were investigated in the hypereutrophic Lake Suwa. Total MC concentrations (MC‐RR and ‐LR) as determined by reverse‐phase high‐performance liquid chromatography were at high levels in the hepatopancreas of C. plicata and U. douglasiae, with maxima at 297 and 420 μg/g dry weight, respectively. The amounts and seasonal changes in the accumulated MC concentration differed in all species. The total MC concentration of A. woodiana was always less than that of other species (maximum concentration of 12.6 μg/g dry weight). The toxin concentration of C. plicata remained very low in summer, when the Microcystis bloom occurred, but increased rapidly in autumn, when the toxic bloom disappeared. For U. douglasiae, simple regression analyses were performed to clarify the relationship between MC bioaccumulation and environmental parameters such as water temperature, chlorophyll a, suspended solids (SS), intracellular MC per unit volume of lake water and per‐unit weight of SS and extracellular MC. The toxin concentration of U. douglasiae correlated more closely with qualitative factors, with intracellular toxin per SS (p < 0.001, R2 = 0.72) than with quantitative factors such as chlorophyll a and intracellular toxin per unit volume of lake water. No correlation could be found between MC in the tissues and extracellular MC. These results indicate that a long‐term survey is needed to assess the safety of bivalves. The study should take into consideration both interspecific differences in toxin content and what is the optimal monitoring parameter. © 2002 Wiley Periodicals, Inc. Environ Toxicol 17: 424–433, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/tox.10075
Chronic effects of p‐nonylphenol on survival and reproduction of Daphnia galeata: Multigenerational life table experiment
Authors: Tanaka Yoshinari , Nakanishi Junko
Published: October 2002

The chronic effect of p‐nonylphenol on survival and reproduction for two generations of the freshwater cladoceran Daphnia galeata was examined by life table experiments. The effects on survival and reproduction were used as the intrinsic rate of natural increase, r, with the Euler–Lotka equation and were analyzed with a simple mathematical model (a power function). The population‐level EC50, the concentration of a substance that reduces the intrinsic rate of natural increase by 50%, was estimated as 65.2 μg/L for the first generation and 81.5 μg/L for the second generation. No transgenerational effect that reinforces adverse responses in the offspring generation has been detected. From a 48‐h immobility test an acute LC50 was estimated to be 60.8 μg/L. The acute LC50 is a good indicator of the chronic population‐level effects of this chemical to this species. © 2002 Wiley Periodicals, Inc. Environ Toxicol 17: 487–492, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/tox.10083
Evaluation of the effects of diuron and its derivatives on Lemna gibba using a fluorescence toxicity index
Authors: Dewez David , Marchand Mathieu , Eullaffroy Philippe , Popovic Radovan
Published: October 2002

The herbicide diuron (DCMU) [3‐(3,4‐dichlorophenyl)‐1,1‐dimethylurea] is largely used in agricultural practices which contribute to water pollution in large areas. Its degradation induced by light or microbial activity is known to be a slow process, and may result in the accumulation of DCMU derivatives in the environment. In this report we used the yield of PSII variable fluorescence of Lemna gibba affected by the DCMU derivatives DCPMU [1‐(3,4‐dichlorophenyl)‐3‐methylurea], DCPU [1‐(3,4‐dichlorophenyl)urea], and DCA [3,4‐dichloroaniline] to calculate the fluorescence toxicity index. We found the fluorescence toxicity index to be a useful parameter to evaluate the inhibitory effect on PSII electron transport in L. gibba exposed to DCMU and its derivatives. The variations observed for the inhibitory effect between DCMU and its derivatives seem to be caused by the modification of the dimethylurea group within the DCMU molecule. The fluorescence toxicity index demonstrated a strong quantitative dependency between the inhibitory effect of PSII electron transport and pollutant concentrations. We propose the fluorescence toxicity index to be a useful tool for future bioassays in evaluating the quality of water polluted with herbicides that induce an inhibition to PSII photochemistry. © 2002 Wiley Periodicals, Inc. Environ Toxicol 17: 493–501, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/tox.10084
A language to model animation out of behaviour‐embedded graphical components
Authors: Pal Prabir K. , Sarkar Biswajit
Published: October 2002

Almost all entities—animate or inanimate—that we see around us change with time. The changes are brought about by changes in the values of their attributes. By using a set of parameters to represent the variable attributes of an entity, and by suitably manipulating their values at run time, the behaviour of an entity can be broadly mimicked in animation. The majority of entities, however, are all too complex to animate directly. They are better described in terms of nested layers of smaller and simpler entities, which we call components. Each component is structurally and behaviourally complete and can be described independent of its application. In the present paper, we propose a scheme for 3D animation that broadly follows this line. The keystone of this scheme is a language, nicknamed ‘V’, which defines the structural and visual attributes of each component of the scene and associates a parameterized behaviour with it, if necessary, in the form of a program script. Thereafter, wherever such a component appears, it does so with a built‐in behaviour, which can nevertheless be regulated by its higher‐level component through its parameters. The advantage is that an entire animation can be modelled in a declarative fashion in terms of nested components with embedded behaviour. Besides, each component is easy to write, alter and reuse. The effort for development, debugging and maintenance of animation modelled in this way is much less as the concerns are almost always local. Copyright © 2002 John Wiley & Sons, Ltd.
Indirect method for the determination of x‐ray tube primary spectra: application to x‐ray fluorescence analysis
Authors: Delgado Víctor
Published: October 2002

The spectral distribution of a fluorescence‐exciting x‐ray beam is related via a Volterra integral equation of the first kind to the fluorescence excited on a set of thick targets. The inversion of this equation is unstable, but the equation of the first kind can be transformed, by classical methods in integral equations, into a stable Volterra integral equation of the second kind for the cumulative spectral distribution. The x‐ray beam spectral distribution is the derivative of the cumulative spectral distribution. As the numerical differentiation of experimental data is also unstable, the intrinsic instability associated with a Volterra integral equation of the first kind appears again. Nevertheless, the cumulative spectral distribution of the x‐ray beam is, in itself, a complete functional description of the fluorescence exciting x‐ray. Further, it is convenient for use with the Sherman equations of x‐ray fluorescence production because these equations rely on the calculation of integrals of the spectral distribution weighted with functions which depend on the concrete composition of the sample used. When integration by parts is performed, the integrand becomes a product of the cumulative spectral distribution times the derivative of the weighting functions. Thus, instead of the unstable spectral distribution, the stable cumulative spectral distribution is used. Copyright © 2002 John Wiley & Sons, Ltd.
Reduction of monocrotaline‐induced hepatic injury by deleted variant of hepatocyte growth factor (dHGF) in rats
Authors: Yamashita Y , Fujise N , Imai E , Masunaga H. , Yamashita Yasushi , Fujise Nobuaki , Imai Eiichi , Masunaga Hiroaki
Published: October 2002

Abstract:  Background: Monocrotaline is a hepatotoxic agent which exerts predominant toxicity to central veins and centrilobular sinusoids. In this study, we investigated the effects of deleted variant of hepatocyte growth factor (dHGF) on monocrotaline‐induced hepatic injury in rats. Methods: 100 mg/kg monocrotaline was gavaged to male rats twice with a 4‐days' interval. Treatment of dHGF was started 4 days before the initial administration of monocrotaline and 500μg/kg was intravenously injected twice daily for 11 days. Results: Monocrotaline induced severe damage of central veins and destruction of central zone of hepatic lobules concurrent with derangement of blood levels of total protein, albumin, alanine‐aminotransferase, total bilirubin, direct bilirubin, and hepaplastin time. dHGF reduced the structural and blood‐chemical abnormalities induced by monocrotaline. Conclusions: These results suggest that dHGF prevented and repaired the monocrotaline‐induced hepatic injury, and could have therapeutic potency in hepatic failure with sever centrilobular destruction.
Inhibition of glucose production and stimulation of bile flow by R (+)‐α‐lipoic acid enantiomer in rat liver
Authors: Anderwald Christian , Koca Georg , Fürnsinn Clemens , Waldhäusl Werner , Roden Michael
Published: October 2002

Abstract:  Aims/Background: R (+)‐α‐lipoic acid (RLA) has been suggested for the treatment of liver diseases, but has also been shown to improve glucose utilization in diabetic patients. Because detailed information of RLA action on carbohydrate metabolism in intact liver is lacking, we examined concentration‐dependent effects of RLA on hepatic glucose production.

Methods: RLA (10−6−10−3 mol L−1) or buffer (control) was infused in isolated livers of fasted rats during recirculating perfusion for 90 min (n = 4–6/group). Hepatic glucose and lactate fluxes and bile secretion were continuously monitored.

Results: RLA reduced lactate (10 mmol L−1)‐dependent glucose production in concentration‐dependent fashion (R = − 0.780, P < 0.001) by up to 67% compared with control (0.36 ± 0.02 µmol min−1 g−1). In parallel, RLA dose dependently decreased lactate uptake (R = − 0.592, P < 0.001) also by up to 67% (control: 0.58 ± 0.08 µmol min−1 g−1). RLA (10−4 mol L−1 and 10−3 mol L−1) stimulated bile flow by ∼ 20 and ∼ 50%, respectively (P < 0.02 vs. control). After 10−3 mol L−1 RLA infusion, liver glycogen was ∼ 3 fold higher (5.2 ± 1.1 vs. control: 1.8 ± 0.2 µmol g−1, P < 0.002). Also at low lactate concentrations (1 mmol L−1), 10−3 mol L−1 RLA reduced glucose production by ∼ 53% and lactate uptake by ∼ 60%, but stimulated bile secretion by ∼ 50% (P < 0.05).

Conclusion: RLA reduces hepatic glucose release by inhibiting lactate‐dependent glucose production in a concentration‐dependent fashion.
Histone 2A stimulates glucose-6-phosphatase activity by permeabilization of liver microsomes
Authors: BENEDETTI Angelo , FULCERI Rosella , ALLAN Bernard B. , HOUSTON Pamela , SUKHODUB Andrey L. , MARCOLONGO Paola , ETHELL Brian , BURCHELL Brian , BURCHELL Ann
Published: October 2002

Histone 2A increases glucose-6-phosphatase activity in liver microsomes. The effect has been attributed either to the conformational change of the enzyme, or to the permeabilization of microsomal membrane that allows the free access of substrate to the intraluminal glucose-6-phosphatase catalytic site. The aim of the present study was the critical reinvestigation of the mechanism of action of histone 2A. It has been found that the dose-effect curve of histone 2A is different from that of detergents and resembles that of the pore-forming alamethicin. Inhibitory effects of EGTA on glucose-6-phosphatase activity previously reported in histone 2A-treated microsomes have been also found in alamethicin-permeabilized vesicles. The effect of EGTA cannot therefore simply be an antagonization of the effect of histone 2A. Histone 2A stimulates the activity of another latent microsomal enzyme, UDP-glucuronosyltransferase, which has an intraluminal catalytic site. Finally, histone 2A renders microsomal vesicles permeable to non-permeant compounds. Taken together, the results demonstrate that histone 2A stimulates glucose-6-phosphatase activity by permeabilizing the microsomal membrane.
Abundant expression of Dec1/stra13/sharp2 in colon carcinoma: its antagonizing role in serum deprivation-induced apoptosis and selective inhibition of procaspase activation
Authors: LI Yuxin , ZHANG He , XIE Mingxing , HU Maowen , GE Shujun , YANG Dongfang , WAN Yinsheng , YAN Bingfang
Published: October 2002

The basic helix—loop—helix (bHLH) proteins are intimately associated with developmental events such as cell differentiation and lineage commitment. The HLH domain in the bHLH motif is responsible for dimerization, whereas the basic region mediates DNA binding. Based on sequence alignment and domain analysis, differentially expressed in chondrocytes/stimulated with retinoic acid/split and hairy-related proteins (DEC/STRA/SHARPs) represent a new class of bHLH proteins. The present study describes the functional characterization of DEC1. Subtractive experiments and blotting analyses demonstrated that DEC1 was highly expressed in colon carcinomas, but not in the adjacent normal tissues. Several cell cycle blockers markedly induced DEC1 expression. Stable transfectants with a tetracycline-inducible construct demonstrated that DEC1 caused proliferation inhibition, antagonized serum deprivation-induced apoptosis and selectively inhibited the activation of procaspases. These activities were highly correlated with the abundance of tetracycline-induced DEC1. Stable transfectants expressing a mutant DEC1 (lacking the DNA-binding domain) exhibited neither proliferation inhibition nor apoptotic antagonism, which suggests that DNA binding is required for these actions. Enzymic assays and immunoblotting analyses demonstrated that induction of DEC1 by tetracycline significantly decreased the activation of procaspases 3, 7 and 9 but not procaspase 8. The selective suppression on the activation of procaspases 3, 7 and 9 over procaspase 8 suggests that DEC1-mediated anti-apoptosis is achieved by blocking apoptotic pathways initiated via the mitochondria. The results functionally distinguish DEC1 from other bHLH proteins and directly link this factor to oncogenesis.
Inhibition of telomerase by linear-chain fatty acids: a structural analysis
Authors: ODA Masako , UENO Takamasa , KASAI Nobuyuki , TAKAHASHI Hirotada , YOSHIDA Hiromi , SUGAWARA Fumio , SAKAGUCHI Kengo , HAYASHI Hideya , MIZUSHINA Yoshiyuki
Published: October 2002

In the present study, we have found that mono-unsaturated linear-chain fatty acids in the cis configuration with C18 hydrocarbon chains (i.e. oleic acid) strongly inhibited the activity of human telomerase in a cell-free enzymic assay, with an IC50 value of 8.6μM. Interestingly, fatty acids with hydrocarbon chain lengths below 16 or above 20 carbons substantially decreased the potency of inhibition of telomerase. Moreover, the cis-mono-unsaturated C18 linear-chain fatty acid oleic acid was the strongest inhibitor of all the fatty acids tested. A kinetic study revealed that oleic acid competitively inhibited the activity of telomerase (Ki = 3.06μM) with respect to the telomerase substrate primer. The energy-minimized three-dimensional structure of the linear-chain fatty acid was calculated and modelled. A molecule width of 11.53—14.26Å (where 1Å = 0.1nm) in the C16 to C20 fatty acid structure was suggested to be important for telomerase inhibition. The three-dimensional structure of the telomerase active site (i.e. the substrate primer-binding site) appears to have a pocket that could bind oleic acid, with the pocket being 8.50Å long and 12.80Å wide.
Transmission of Babesia microti in Minnesota through four blood donations from the same donor over a 6‐month period
Authors: Herwaldt Barbara L. , Neitzel David F. , Gorlin Jed B. , Jensen Kathryn A. , Perry Elizabeth H. , Peglow William R. , Slemenda Susan B. , Won Kimberly Y. , Nace Eva K. , Pieniazek Norman J. , Wilson Marianna
Published: October 2002

BACKGROUND
: Babesiosis is a tick‐borne zoonosis caused by intraerythrocytic protozoa. More than 40 US cases of
Babesia microti infection acquired by blood transfusion have been reported. This report describes the identification of a transfusion‐associated case of babesiosis and the subsequent identification of the infected blood donor and three other infected recipients of cellular blood components from three other donations by this donor.

STUDY DESIGN AND METHODS
: Serum specimens from the donors of blood that had been made into cellular components received by the index recipient and from other recipients of such components from the implicated donor were tested by the indirect fluorescent antibody (IFA) assay for antibodies to
B. microti.
Whole blood from IFA‐positive persons was tested by PCR for
B. microti DNA.

RESULTS : IFA testing of serum from 31 of 36 donors implicated a 45‐year‐old man (titer, 1 in 256), whose donation had been used for RBCs. He likely became infected when bitten by ticks while camping in Minnesota in June 1999 and had donated blood four times thereafter. As demonstrated by PCR, he remained parasitemic for at least 10 months. Of the five other surviving recipients of cellular blood components from the implicated donor, three recipients (one for each of the three other donations) had become infected through either RBC or platelet transfusions.

CONCLUSIONS : Babesiosis should be included in the differential diagnosis of posttransfusion febrile illness, and effective means for preventing transmission by blood transfusion are needed.
Unique CYP2D6 activity distribution and genotype‐phenotype discordance in black Americans
Authors: Gaedigk Andrea , Bradford L. DiAnne , Marcucci Kenda A. , Leeder J. Steven
Published: October 2002

Background

Although CYP2D6 has been studied extensively in differentpopulation groups, relatively little is known for black Americans.

Methods

CYP2D6 activity was assessed with dextromethorphan in 283 black American subjects and correlated with their genotype (2D6*2 to *12, 2D6*14, 2D6*15, 2D6*17, 2D6*18, and 2D6*29 and gene duplications). Volunteers provided information about ethnicity and concurrent medication, and they participated in either phenotyping (n = 225), genotyping (n = 251), or both (n = 193).

Results

The median urinary dextromethorphan/dextrorphan metabolic ratio (MR) indicated significantly lower CYP2D6 activity in the black American group (0.016) than in a white control population (0.0044; P = .0001) studied previously. The reduced function allele 2D6*17 was more common (frequency [f] = 0.395) among intermediate metabolizers (0.03 ≤ MR ≤ 0.3) than extensive metabolizers(MR ≤ 0.03; f = 0.148; P = .0001). Consistent with reduced function toward dextromethorphan of COS cell‐expressed 2D6.29 protein, 2D6*29 also was more frequent in intermediate metabolizers (f = 0.114) than in extensive metabolizers (f = 0.057; P = NS). Frequencies for 2D6*17 and 2D6*29 were f = 0.213 and 0.072, respectively. Of the 193 genotyped and phenotyped subjects, 14 were determined to be poor metabolizers, with dextromethorphan/dextrorphan ratios >0.3 (7.25%), but only 2 subjects(1.04%) carried 2 nonfunctional alleles (2D6*3/*4x2 and 2D6*4/*4). A new allelic variant, 2D6*40, was subsequently found in 2 discordant subjects (2D6*4/*40 and 2D6*6/*40), implying that the 18‐base pair (bp) insertion found in 2D6*40 renders it nonfunctional. The frequency of 2D6*40 was 0.006. For genotypes that contain 2D6*2, median MR values were consistently higherin black Americans than in white subjects, indicating that other unidentified factors also contribute to lower CYP2D6 activity in black Americans.

Conclusions

The lower CYP2D6 activity observed in a black American population is in part attributable to the presence of variant alleles that occur at a higher frequency in this population than in white subjects. Additional studies are required to ascertain the pharmacokinetic and pharmacodynamic consequences of these pharmacogenetic data in black Americans.

Clinical Pharmacology & Therapeutics (2002) 72, 76–89; doi: 10.1067/mcp.2002.125783
Pharmacokinetic modeling to predict morphine and morphine‐6‐glucuronide plasma concentrations in healthy young volunteers
Authors: Lötsch Jörn , Skarke Carsten , Schmidt Helmut , Liefhold Jürgen , Geisslinger Gerd
Published: October 2002

Objective

This investigation focused on the development of a predictive model of morphine, including morphine‐6‐glucuronide (M6G) for healthy young volunteers after morphine administration.

Methods

Population compartmental pharmacokinetic modeling with NONMEM was applied to the plasma concentration‐time data of morphine and M6G obtained from 8 healthy volunteers (4 men and 4 women; age range, 23 to 30 years) after intravenous bolus injection of 5.64 mg morphine base (7.5 mg morphine sulfate) and of 1 mg deuterium‐labeled M6G.

Results

Two models were identified that described the plasma concentration versus time courses of morphine and M6G after administration of morphine. The model consisted of a standard 3‐compartment model for morphine and a standard 2‐compartment model for M6G, with input into and output from the central compartments. The formation of M6G from morphine was modeled as a fraction of morphine clearance of about 14%, which accounted forthe formation of M6G, and a delay of the appearance of M6G in plasma modeled as afirst‐order process, with a mean metabolic transit time of 17.2 minutes. An alternative model assigned the formation of M6G among the first peripheral compartment of morphine andthe central compartment of M6G. Therefore the alternative 3‐compartment model of morphinehad the input into the central compartment and renal excretory elimination from the central compartment, but the metabolic clearance of morphine started from the first peripheralcompartment. M6G was again modeled with a standard 2‐compartment model. Both models predicted morphine and M6G plasma concentrations available from an independent study with acceptable accuracy and without bias.

Conclusions

Two models are provided that can predict plasma concentrations of morphine and M6G with acceptable accuracy in healthy young volunteers.

Clinical Pharmacology & Therapeutics (2002) 72, 151–162; doi: 10.1067/mcp.2002.126172