bluuebunny/crossref_metadata_2025 huggingface dataset:
Improving the modal strain energy method for damped structures using a dyadic matrix perturbation approach
Authors: Landi F P , Scarpa F , Rongong J A , Tomlinson G
Published: January 2003

A dyadic matrix based perturbation method has been developed to evaluate the natural frequencies and modal loss factors of viscoelastically damped structures. This approach improves the accuracy of the prediction given by the modal strain energy (MSE) method by making use of the modal basis of the undamped system. Examples involving lumped parameter systems and a constrained layer viscoelastic sandwich beam are presented. In each case, the solutions given by exact numerical methods, MSE and the perturbation approach are compared. Results are also correlated with performance indices to assess the damping level and type in the system. A solution involving a reduced modal basis of the original structure using the perturbation approach is also presented. This approach also gives a significant improvement over the original MSE prediction.
Design evaluation of two-roller conveyors for semi-self-flowing transportation
Authors: Kosse V
Published: January 2003

In conveyors utilizing the principle of semi-self-flowing transportation, parts are put on a surface moving in the lateral direction by means of vibration or on two rollers rotating in opposite directions. Advantages of the latter one are that parts can be supplied on demand and a very small angle of inclination is required (less than 3°). Formulae found in scientific literature for the velocity of transportation as a function of the roller velocity give large discrepancies with experimental results. Extensive experimental modelling allows the dependence of the frictional coefficient on the shape of parts and the contact angle to be established. A new mathematical model of the conveyor has been developed and a new formula for the velocity of transportation has been derived, which is in good agreement with experimental data.
Stability analysis of the rolling process and regenerative chatter on 2030 tandem mills
Authors: Chen Y , Liu S , Shi T , Yang S , Liao G
Published: January 2003

Chatter in the rolling stack of high-velocity tandem mills and temper mills is a widespread problem and affects the quality of the finished product and the productivity of the rolling mill. One factor that clearly plays an important role in causing mill vibration is the inherent gap between the roll chocks and mill housings. In order to control chatter in cold rolling operations, a much deeper understanding of the basic mechanics of the problem is required. Therefore, this paper proposes a rolled piece vibration model for comprehending instability of the strip due to the variation of the friction coefficient in the roll bite. Subsequently, owing to the time delay effect of the chatter marks between the immediate stands, a regenerative chatter model is developed and stability analysis of the regenerative chatter model due to negative damping is presented. Finally, for a more detailed understanding of the regenerative chatter phenomena, a simulator is developed and industrial investigations are carried out in practice. It follows from the numerical simulations and industrial investigations that regenerative chatter is a more serious vibration phenomenon than simple chatter.
Penetration of tubulars into horizontal oil wells
Authors: McCourt I , Truslove T , Kubie J
Published: January 2003

Penetration of tubulars into horizontal oil wells is investigated in this work. Locking of the tubulars by frictional forces alone is modelled by inserting small diameter rubber rods into horizontal acrylic tubes. Three different regions of the penetrating rod are described: the initial straight section, followed by sinusoidal deformations with gradually decreasing lengths and increasing amplitudes, which finally develop into helical deformations with subsequent lock-up. The effect of the insertion velocity is also investigated. A simplified model is developed, which is in reasonable agreement with experimental data.
Optimal trajectory planning for a hexapod machine tool during contour machining
Authors: Pugazhenthi S , Nagarajan T , Singaperumal M
Published: January 2003

This paper addresses the problem of optimal trajectory planning for Stewart platform based machine tools. The objectives are to maximize the stiffness of the structure and to minimize the force requirement of the actuators while satisfying the constraints of workspace and singularity. A computational algorithm for searching the optimum location of machining trajectory is developed. The algorithm is applied to two contour machining examples involving end milling. The simulation results of contour machining along the optimal trajectory are discussed.
On the quasi-rigid body motion of the head actuator assembly in hard disk drives
Authors: Zeng S
Published: January 2003

A quasi-rigid (QR) vibration mode between 3 and 5 kHz is common in current hard disk drives (HDDs), which hinders servo bandwidth improvement and thus limits growth in the areal density (numbers of bits that can be stored per unit area) of HDDs. In this paper, a finite element (FE) model of a head actuator assembly (HAA) is developed and an experimental set-up is established to study the quasi-rigid body mode. The FE model result is compared with the experimental data. It is found that the quasi-rigid body mode is in fact a butterfly-like mode, which integrates the flexibility of the pivot assembly as well as the flexibility and the mass of the whole head actuator body.
The Effect of Nano-sized SEI Film Formed by Vinyl Acetate Additive for Li-ion Batteries
Authors: Yoshitake H , Abe K , Kitakura T , Gong J B , Lee Y S , Nakamura H , Yoshio M
Published: January 2003

The electrochemical performance of Li/graphite and LiCoO2/graphite cells were investigated in 1 M LiPF6 dissolved in propylene carbonate (PC) + dimethyl carbonate (DMC) (Vol. 1:2) alone and with 1 wt.% vinyl acetate (VA) additive in this study. Decomposition of solvents at graphite electrode could be remarkably suppressed by addition of the VA additive in the electrolyte, leading to the improvement of electrochemical performances of the cells. We found that the VA additive should give a solid electrolyte interphase (SEI) on the surface of graphite electrode, which effectively suppressed the PC decomposition in the electrolyte.
Amperometric Detection of Oxidized and Reduced Glutathione at Anodically Pretreated Diamond Electrodes
Authors: Terashima Chiaki , Rao Tata N , Sarada Bulusu V , Fujishima Akira
Published: January 2003

Anodically oxidized diamond electrodes have enabled direct oxidation of not only thiols but also disulfides such as oxidized glutathione. Coupled with LC separation after sample pretreatment, simultaneous determination of oxidized and reduced glutathione in rat whole blood was achieved at 1.50 V vs Ag/AgCl. The present method was comparable with enzymatic assay in real sample analysis.
Electrocatalytic Activation of Organosulfur Redox Reactions by Metal Nanoparticles
Authors: Park Jong-Eun , Hatozaki Osamu , Oyama Noboru
Published: January 2003

The effect of Ag nanoparticles on the redox reactions of organosulfur compounds was investigated. Adding the nanoparticles to 2,5-dimercapto-1,3,4-thiadiazole (DMcT)-polyaniline composites, redox activity of the composites was enhanced due to electrocatalytic activation of DMcT by the nanoparticles. It was expected that adsorption of DMcT to the nanoparticles would make a positive contribution to the electrocatalysis.
Theoretical Evaluation of the Reaction Intermediate Complex for an Asymmetric Reaction Using a Chiral Lithium Amide by the Molecular Mechanics (MM3) Calculations
Authors: Yoshida Takashi , Sakakibara Kazuhisa , Asami Masatoshi
Published: January 2003

The structures and conformational energies of the reaction intermediate complex for an asymmetric reaction, in which cyclohexene oxide is transformed to chiral (S)-2-cyclohexen-1-ol with high enantioselectivity by various chiral lithium amide in tetrahydrofuran (THF), were evaluated well by the extended Allinger’s MM3 force field calculations.
Rhodium-Catalyzed Intramolecular Aminocarbonylation of Aryl Halides Using Aldehydes as a Source of Carbon Monoxide
Authors: Morimoto Tsumoru , Fujioka Masahiko , Fuji Koji , Tsutsumi Ken , Kakiuchi Kiyomi
Published: January 2003

The reaction of N-Ts-(2-bromophenyl)alkylamines with aldehydes in the presence of a catalytic amount of a rhodium complex results in the intramolecular aminocarbonylation of the aryl halides to give five-, six-, and seven-membered benzolactams.
Iodide-induced Oscillations in BrO3−–Tyrosine–H2SO4 System
Authors: Li Hexing , Zhu Jian , Dai Yeping , Wang Qin
Published: January 2003

The KBO3–tyrosine(Tyr)–H2SO4 system gave rise to sustained uncatalyzed oscillations in a suitable concentration range. Under the case that the reactants’ concentrations were out of the oscillating range, initially adding iodide into the above system induced another kind of oscillations with much higher frequency and more oscillation cycles in comparison with the original uncatalyzed oscillations in the absence of iodide.
Significance of crustaceans in dwarfed faunas
Authors: Scott Harold William
Published: January 2003

A survey of literature on fossil anti living crustacea fails to uncover a single reported case of unquestioned dwarfing. The molt stages of crustacea introduce a factor that is not ordinarily involved in the study of other invertebrates. Ostracodes pass through 7-9 molt stages. lt is conceivable that a group of molts could be misinterpreted as "dwarfing." An investigation concerning dwarfing in trilobites failed to uncover any evidence which would indicate the existence of such a fauna. The crustaceans are normal in dwarfed faunas because they were free swimming forms and lived in that portion of the water which had a normal pH. Whereas, the dwarfed forms were bottom dwellers that lived in an environment where the pH was low and the H 2 S high.
Beeinflusst die Strukturgüte von Fließgewässern das Vorkommen von Makrophyten?
Authors: Passauer Barbara , Meilinger Petra , Melzer Arnulf , Schneider Susanne
Published: January 2003

Eine wichtige Rolle bei der integrierenden Bewertung von Fließgewässern spielt neben der Nährstoffsituation, die über die Makrophytenvegetation indiziert werden kann, die Gewässerstruktur. Die Frage nach möglicherweise bestehenden Zusammenhängen zwischen der Strukturgüte und der Makrophytenvegetation steht im Mittelpunkt der Arbeit. Im Sommer 2000 wurden in 135 Kartierabschnitten an Fließgewässern in Süddeutschland die Gewässerstruktur nach LAWA, die Makrophytenvegetation sowie ausgewählte Standortparameter kartiert. Da in Gewässern mit hoher struktureller Diversität höhere Artenzahlen zu erwarten sind als in solchen mit geringer Standortvielfalt, wurden die Artenzahlen der Makrophyten in den einzelnen Strukturgüteklassen verglichen. Bei Betrachtung aller Arten ließ sich kein statistisch signifikanter Unterschied in der Artenzahl mit sich verschlechternder Strukturgüte nachweisen. Während die Bryophyta eine signifikante Abnahme in der Artenzahl mit sich verringernder Strukturqualität zeigten, war eine leichte Zunahme bei den übrigen Lebensformgruppen erkennbar. Mit Hilfe einer Kanonischen Korrespondenzanalyse wurde die Beziehung des Parameters Gewässerstruktur zu den anderen Umweltfaktoren untersucht. Die strukturell hochwertigen Gewässer wiesen dabei eine meist hohe Fließgeschwindigkeit auf und waren stark beschattet. Diese Umweltbedingungen, die charakteristisch für die Gewässertypen höherer Lagen sind, wurden vorwiegend von den Bryophyta toleriert. Von den übrigen Lebensformgruppen bevorzugte Gewässertypen waren strukturell mehr oder weniger stark beeinträchtigt.

Ein Zusammenhang zwischen der Artenzahl von Makrophyten und der Gewässerstrukturklasse ließ sich damit bei Betrachtung aller Gewässertypen nicht nachweisen, da typspezifische ökomorphologische Parameter die Unterschiede in den Artenzahlen maskieren. Diese Einflussfaktoren werden diskutiert. Für Gefäßpflanzen und Characeen können auch beeinträchtigte Gewässer gute Lebensbedingungen bieten. Von der Strukturgüteklasse kann daher nur bei einer Differenzierung nach Gewässertyp auf die Besiedlungsbedingungen für Makrophyten geschlossen werden.
Development of an interactive multimedia teaching package for a course on metalworking
Authors: Ong S. K. , Mannan M. A.
Published: January 2003

In this paper, the development of a comprehensive interactive and multimedia courseware for supplementing the teaching of the concepts and principles in the metallurgy of metalworking is presented. The objective was to create teaching materials that would be interactive, interesting, and useful for students to easily learn the concepts in this topic, so that the students would learn more effectively and enthusiastically. The course material developed involved a substantial amount of animations to illustrate the various metalworking principles, so as to effectively improve the learning of key concepts. In addition, quizzes were implemented to test the students understanding of the concepts. A few development tools were tested, and the final decision was to use mainly Macromedia Flash and Microsoft Front Page. © 2003 Wiley Periodicals, Inc. Comput Appl Eng Educ 10: 215–228, 2002; Published online in Wiley InterScience (www.interscience.wiley.com.); DOI 10.1002/cae.10021
Interactive web‐based training tool for CAD in a virtual environment
Authors: Ou Shih‐Ching , Sung Wen‐Tsai , Hsiao Sung‐Jung , Fan Kuo‐Chin
Published: January 2003

Innovative products and reduced time‐to‐market are essential for competitiveness in the modern market. Consequently, it is very important for industry to apply new information technologies and training tools to support product development, production planning, and other product processes. Virtual reality is one of these enabling technologies. This investigation proposes a novel approach to enhance CAD training and design in a web‐based environment such as a Web browser or VR browser. Previous investigations successfully developed a CAD curriculum analysis and design, and also proposed the use of virtual reality modeling to improve training techniques. For this reason, this study designs a simple interactive web‐based training tool for CAD in a virtual environment, along with an integrated graphics real‐time system. Using OpenGL, the proposed system can run on different operating systems, such as Windows 2000, Windows 98, Windows 95, Windows NT, Linux and Macintosh. Owing to the increasing need for design and training CAD in network environments, drawing real‐time complex curves and surfaces in a network browser is an emerging technological trend. © 2003 Wiley Periodicals, Inc. Comput Appl Eng Educ 10: 182–193, 2002; Published online in Wiley InterScience (www.interscience.wiley.com); DOI 10.1002/cae.10024
Low cost vision system for an educational platform in artificial intelligence and robotics
Authors: Martin Juan F. , Chiang Luciano
Published: January 2003

This paper presents a web‐cam based vision system for performing image processing in real time. It was implemented as part of an AI and Robotics educational platform designed to study collaborative moving robots in a dynamic environment. A color based image segmentation algorithm was developed with careful attention to algorithm efficiency, due to hardware limitations for the maximum frame rate. This led to a simple and cost‐effective vision system that is able to detect and identify several mobile robots through successive frames. © 2003 Wiley Periodicals, Inc. Comput Appl Eng Educ 10: 238–248, 2002; Published online in Wiley InterScience (www.interscience.wiley.com); DOI 10.1002/cae.10026
Stock exchange game model as an example for graduate level distance studies
Authors: Mockus Jonas
Published: January 2003

This paper deals with the development of a Web‐based integrated system for distance graduate studies of theories of optimization, games, and markets, which is aimed to support core curriculum and to provide students with hands‐on experience on effective use of software tools. The main objective is to stimulate and develop creative abilities to work as independent researchers. This can be explained by detailed description of a typical example: the Stock Exchange Game Model (SEGM). That is the purpose of this paper. The web‐site http://mockus.org/optimum includes SEGM and accompanying models. © 2003 Wiley Periodicals, Inc. Comput Appl Eng Educ 10: 229–237, 2002; Published online in Wiley InterScience (www.interscience.wiley.com); DOI 10.1002/cae.10027
Dynamic strategy for teaching structural analysis
Authors: El‐Rimawi Jamal , El‐Hamalawi Ashraf
Published: January 2003

Improving students' understanding of structural analysis within a limited time represents a challenge for both students and lecturers. As a result, emphasis is usually placed on either the analytical or conceptual aspect of the subject. This paper argues that, within the same time frame, the simultaneous development of both aspects could lead to a better understanding of the subject. The development and implementation of a computer program suitable for this purpose is described, and its application to the compatibility method is illustrated. © 2003 Wiley Periodicals, Inc. Comput Appl Eng Educ 10: 194–203, 2002; Published online in Wiley InterScience (www.interscience.wiley.com); DOI 10.1002/cae.10028
A Process in Need Is a Process Indeed: Scalable Enantioselective Synthesis of Chiral Compounds for the Pharmaceutical Industry
Authors: Ikunaka Masaya
Published: January 2003

This report deals with enantioselective synthesis of viracept1(nelfinavir mesylate, AG 1343), a potent HIV protease inhibitor, and 3‐hydroxytetradecanoic acid3, a component of lipid A comprising lipopolysaccharide embedded in the cell surface of Gram‐negative bacteria, from both strategic and practical perspectives. As regards the synthesis of1, the synthetic approaches to its central intermediate2possessing the common structural motif of 1,4‐differentially substituted‐2‐amino‐3‐hydroxylbutane are mainly discussed with emphasis on the molecular symmetry that has helped streamline the synthetic strategy. In the discussion of the synthetic strategies to access a single enantiomer of3, the chiral methodologies that have been applied so far are assessed for industrial viability; the synthetic alternatives explored include resolution via diastereomeric salt formation, lipase‐catalyzed kinetic resolution, asymmetric synthesis, and chiral pool approaches.
Total Synthesis of the Antitumor Acetogenin Mosin B: Desymmetrization Approach to the Stereodivergent Synthesis of threo/trans/erythro‐Type Acetogenins
Authors: Maezaki Naoyoshi , Kojima Naoto , Sakamoto Atsunobu , Tominaga Hiroaki , Iwata Chuzo , Tanaka Tetsuaki , Monden Morito , Damdinsuren Bazarragchaa , Nakamori Shoji
Published: January 2003

A total synthesis of the threo/trans/erythro‐type acetogenin mosin B and one of its diastereomers has been achieved. The carbon skeleton is assembled in a convergent fashion from two segments (a THF ring segment and a γ‐lactone segment) through the Nozaki–Hiyama–Kishi reaction. The THF ring segment was stereoselectively constructed by a stereodivergent synthesis starting from a common intermediate (4‐cyclohexene‐1,2‐diol) based on a desymmetrization strategy. The γ‐lactone segment was synthesized by coupling a triflate and a chiral α‐sulfenyl γ‐lactone. By virtue of these synthetic results, we suggest that the absolute configuration of natural mosin B is 1 a. Antiproliferative effects of 1 a and 1 b were also investigated.
Metal‐Free, Noncovalent Catalysis of Diels–Alder Reactions byNeutralHydrogen Bond Donors in Organic Solvents and in Water
Authors: Wittkopp Alexander , Schreiner Peter R.
Published: January 2003

We examined the catalytic activity of substituted thioureas in a series of Diels–Alder reactions and 1,3‐dipolar cycloadditions. The kinetic data reveal that the observed accelerations in the relative rates are more dependent on the thiourea substituents than on the reactants or solvent. Although the catalytic effectiveness is the strongest in noncoordinating, nonpolar solvents, such as cyclohexane, it is also present in highly coordinating polar solvents, such as water. In 1,3‐dipolar cycloadditions, the thiourea catalysts demonstrate only very moderate selectivity for reactions with inverse electron demand. Our experiments emphasize that both hydrophobic and polar interactions can co‐exist, making these catalysts active, even in highly coordinating solvents. This class of catalysts increases the reaction rates andendo‐selectivities of Diels–Alder reactions, in a similar manner to weak Lewis acids, without concomitant product inhibition.
Flexible but with a Defined Turn—Influence of the Template on the Binding Properties of Two‐Armed Receptors
Authors: Wennemers Helma , Nold Matthias C. , Conza Matteo M. , Kulicke Klaus J. , Neuburger Markus
Published: January 2003

Combinatorial binding studies revealed that the di(trans‐4‐aminoproline)diketopiperazine is an ideal template for two‐armed receptors with highly selective binding properties towards peptides. It is not only superior to structurally very different diamines but also to the diastereomeric di(cis‐4‐aminoproline)diketopiperazine. These empiric results are rationalized by the analysis of the conformation of the diastereomeric diketopiperazines in the solid state, by X‐ray crystal structure analysis, as well as by NMR studies in solution: to observe highly selective binding, the template needs to be not only conformationally rigid but it must have a specific turn geometry. The combination of combinatorial binding studies, X‐ray crystal structure analysis, and NMR spectroscopy gave insight into why thetrans,trans‐diketopiperazine is a superior template compared to other diamines. Additionally, the results provide a guide for the rational design of two‐armed receptors with good binding properties towards peptidic guests.
Nitrogen Photofixation on Nanostructured Iron Titanate Films
Authors: Rusina Olga , Linnik Oksana , Eremenko Anna , Kisch Horst
Published: January 2003

A nanostructured iron titanate thin film has been prepared by a sol–gel method from iron(III) chloride and titanium tetraisopropylate. Energy‐dispersive X‐ray analysis and Mößbauer spectroscopy suggest the presence of a Fe2Ti2O7 phase, which was previously obtained as an intermediary phase upon heating ilmenite. In the presence of ethanol or humic acids and traces of oxygen, the novel film photocatalyzes the fixation of dinitrogen to ammonia (17 μM) and nitrate (45 μM). In the first observable reaction step, hydrazine is produced and then undergoes further photoreduction to ammonia. Oxidation of the latter by oxygen affords nitrate as the final product. Since the reaction occurs also in air and with visible light (λ>455 nm), and since the iron titanate phase may be formed by the weathering of ilmenite minerals, it may be a model for mutual nonenzymatic nitrogen fixation in nature.
A unique mushroom body substructure common to basal cockroaches and to termites
Authors: Farris Sarah M. , Strausfeld Nicholas J.
Published: January 2003

The mushroom bodies of the cockroach Periplaneta americana are made up of intrinsic neurons (class I and class II Kenyon cells) with dendrites in a dorsal calyx and axons that bifurcate into medial and vertical lobes. Here, we describe a substructure of the cockroach mushroom bodies composed of a previously unrecognized class of Kenyon cells with distinct morphologies. The embryonically produced class III Kenyon cells form a separate accessory calyx below the calyx proper. The medial branches of class III Kenyon cell axons form the previously described “γ bulb,” whereas the vertical branches leave the vertical lobe to form a toroidal “lobelet” around the posterior surface. Taking advantage of the morphologically and immunochemically distinct nature of the lobelet, we have attempted to determine the distribution of this unique structure in other insects of the taxon Dictyoptera (cockroaches, mantises, and termites). Our data indicate that the lobelet is present only in basal cockroaches and in termites, supporting existing theories of a close phylogenetic relationship between these groups. Higher termites possess a duplicated lobe structure due to immense elaboration of the processes of class III Kenyon cells. The degree of complexity in the mushroom body lobes of termites agrees with current taxonomic arrangements of the Isoptera based on non‐neural morphological and DNA sequence analyses. It thus appears that the evolution of the Dictyoptera has been accompanied by increasing complexity of the mushroom bodies, achieved in part through the further specialization and elaboration of a subset of Kenyon cells. J. Comp. Neurol. 456:305–320, 2003. © 2003 Wiley‐Liss, Inc.
Increased density of hippocampal kainate receptors but normal density of NMDA and AMPA receptors in a rat model of prenatal protein malnutrition
Authors: Fiacco Todd A. , Rosene Douglas L. , Galler Janina R. , Blatt Gene J.
Published: January 2003

The postnatal development of excitatory amino acid receptor types including kainate, N‐methyl‐D‐aspartate (NMDA), and α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA) was assessed in the hippocampus, entorhinal cortex, and adjacent neocortex in normal and prenatally protein malnourished rats ages 15, 30, 90, and 220 postnatal days by quantitative autoradiography. Tritiated ligands used to measure binding site density were 3[H]kainate, 3[H]MK‐801, and 3[H]AMPA, respectively. Kainate receptors showed statistically significant increases in binding density in stratum lucidum of CA3 (hippocampal mossy fiber zone) in 90‐ and 220‐day‐old malnourished rats compared with age‐ and sex‐matched controls but not in 15‐ or 30‐day‐old malnourished rats. Compared with previous anatomic studies, these results are mostly in agreement with a significantly decreased hippocampal mossy fiber plexus in 15‐, 90‐, and 220‐day‐old rats but not in 30‐day‐old rats. These results suggested that the increased density of postsynaptic kainate receptors located mainly on proximal apical dendrites of CA3 pyramidal cells may be compensatory to decreased glutamate release due to the reduction in mossy fiber plexus. In contrast, the density of putative NMDA and AMPA receptors quantified in prenatally malnourished rats was comparable to the density quantified in age‐ and sex‐matched control rats, as were all three receptor types in entorhinal cortex and adjacent neocortex. Thus, the selectivity of the compensation of 3[H]kainate‐labeled mossy fiber plexus in adult but not in early postnatal developing malnourished rats may help ensure continued breeding and survival of the species under otherwise adverse environmental conditions. J. Comp. Neurol. 456:350–360, 2003. © 2003 Wiley‐Liss, Inc.
Distribution of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate‐type glutamate receptor subunits (GluR2/3) along the ventral visual pathway in the monkey
Authors: Xu Lihua , Tanigawa Hisashi , Fujita Ichiro
Published: January 2003

By using immunohistochemical methods, we examined the distribution of cells expressing subunits of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA)‐selective glutamate receptors (GluR2/3) in the cortical areas of the occipitotemporal pathway in monkeys. GluR2/3‐immunoreactive (‐ir) cells were primarily pyramidal cells; this category, however, also included large stellate cells in layer IVB of the striate cortex (V1) and fusiform cells in layer VI of all the areas examined. GluR2/3 immunoreactivity differed among the areas in laminar distribution and intensity. In V1, GluR2/3‐ir cells were identified mainly in layers II, III, IVB, and VI. The prestriate areas V2 and V4 and the inferior temporal areas TEO and TE contained GluR2/3‐ir cells in layers II, III, and VI. In the TE, GluR2/3‐ir cells were also abundant in layer V. In area 36 of the perirhinal cortex, neurons in layers II, III, V, and VI were labeled in a similar manner to the TE labeling, but with greater staining intensity and numbers, especially in layer V. Thus, GluR2/3 immunoreactivity increased rostrally along the pathway. Within V1 and V2, cells strongly stained for GluR2/3 formed clusters that colocalized with cytochrome oxidase (CO)‐rich regions. These distinct laminar and regional distribution patterns of GluR2/3 expression may contribute to the specific physiological properties of neurons within various visual areas and compartments. J. Comp. Neurol. 456:396–407, 2003. © 2003 Wiley‐Liss, Inc.
Drug induced nightmares—an etiology based review
Authors: Pagel J. F. , Helfter P.
Published: January 2003

Objective

Recent clinical trials have included patient complaints of nightmares as a category of reportable medication side effects. This study integrates that data into current experimental and theoretical research of drug effects that may alter dreaming and nightmares. The objective is to provide a clinical and theoretical framework useful in categorizing the potential and reported drug effects on nightmares.

Methodology

This study reviews case reports and clinical trials that have reported nightmares or alterations in dreaming occurring secondary to medication usage. These data are analysed as to the probability of the drug/nightmare association, and integrated into current electrophysiological and neurochemical theories of dreaming and nightmares.

Results

Pharmacological agents affecting the neurotransmitters norepinephrine, serotonin and dopamine are clearly associated with patient reports of nightmares. Agents affecting immunological response to infectious disease are likely to induce nightmares in some patients. A possible association exists between reports of nightmares and agents affecting the neurotransmitters acetylcholine, GABA and histamine, as well as for some anesthetics, antipsychotics and antiepileptic agents.

Conclusion

By utilizing our current experimental and theoretical knowledge base, the potential etiology of a majority of reported drug effects on nightmares can be classified. These data support current neurochemical theories of dreaming, as well as suggesting that the biochemical basis for dreaming and nightmare induction may be more complex than generally suggested. Copyright © 2003 John Wiley & Sons, Ltd.
Actigraphy in human psychopharmacology: a review
Authors: Stanley Neil
Published: January 2003

Over the last 25 years wrist actigraphy has predominantly been used in sleep research and chronobiology where the technique has proved useful in the measurement of sleep and the characterisation of the sleep/wake cycle. Whilst there are a large number of studies published that have used actigraphy, there have only been relatively few studies that have shown that the technique is capable of measuring drug‐induced changes in nocturnal and/or diurnal behaviour. Thus the use of actigraphy to measure drug effects in clinical trials has up till now remained on the periphery of psychopharmacology. However this may be because of the disparate nature of the studies published rather than lack of usefulness. This paper reviews the relevant literature and in doing so concludes that there is a convincing body of evidence for the utility of actigraphy as a technique in human psychopharmacology. Copyright © 2003 John Wiley & Sons, Ltd.
Spontaneous activation and signaling by overexpressed epidermal growth factor receptors in glioblastoma cells
Authors: Thomas Christopher Y. , Chouinard Michael , Cox Michael , Parsons Sarah , Stallings‐Mann Melody , Garcia Roy , Jove Richard , Wharen Robert
Published: January 2003

Overexpressed epidermal growth receptor factor receptors (EGFRs) are thought to contribute to the malignant phenotype of human glioblastomas (GBMs), but the mechanism is not well understood. We found that SKMG‐3 cells, a rare GBM cell line that maintains EGFR gene amplification in vitro, produced high levels of EGFR protein. The cells also expressed the related receptors HER2/neu and HER4, but not HER3. Immunoblots and tryptic phosphopeptide maps showed that the SKMG‐3 EGFRs were intact and functional and that a subset of these receptors were spontaneously autophosphorylated. EGF treatment stimulated phosphorylation of the EGFRs as well as the downstream effectors Erk, AKT1, stat3 and c‐Cbl. Under minimal growth conditions, the unstimulated SKMG‐3 cells contained constitutively phosphorylated Erk and AKTI but no detectable stat3 DNA‐binding complexes. The EGFR kinase inhibitor PD158780 reduced the constitutive phosphorylation of the receptor and Erk but not that of AKT1. In contrast, inhibition of phosphatidylinositol‐3‐kinase (PI3K) blocked the constitutive phosphorylation of Erk and AKT‐1 but not the EGFR. We conclude that the SKMG‐3 cells represent the subset of GBMs with amplified EGFR genes that overexpress intact receptors. The results also suggest that in some GBMs, signals from overexpressed EGFRs contribute to the constitutive phosphorylation of Erk, but these signals may not required for the constitutive activation of PI3K or AKT1. © 2002 Wiley‐Liss, Inc.
Serologic analysis of ovarian tumor antigens reveals a bias toward antigens encoded on 17q
Authors: Stone Brad , Schummer Michèl , Paley Pamela J. , Thompson Lucas , Stewart Julie , Ford Molly , Crawford Meghan , Urban Nicole , O'Briant Kathy , Nelson Brad H.
Published: January 2003

We utilized SEREX immunoscreening to identify a set of novel tumor antigens that are associated with human serous ovarian cancer and may prove useful for the early detection and treatment of this disease. Extensive screening with a panel of sera from 25 late‐stage ovarian cancer patients against 3 independent cDNA libraries identified a set of 9 antigens that were immunogenic in more than 1 patient and not in a panel of 20–45 normal female serum donors. These antigens include p53, NY‐ESO‐1, UBQLN1, HOXB6, TOP2A, putative helicase‐RUVBL (RUVBL), HMBA‐inducible (HEXIM1), DDX5 and HDCMA. Ten of 25 ovarian cancer patients (40%) expressed serum IgG to at least 1 of these antigens, while 14% (4/25) had antibodies to 2 or more antigens. Unexpectedly, 4 antigens identified in this screen, DDX5, HEXIM1, TOP2A and HOXB6, are encoded within a region of 17q that also includes the genes for HER2/neu, Homeobox‐B7 and BRCA1. Real‐time RT‐PCR analysis showed that mRNA for HER2/neu and 3 SEREX‐defined antigens, TOP2A, HOXB6 and DDX5, was more abundant in ovarian tumors than most normal tissues, including normal and benign ovarian tissues, suggesting that elevated expression of genes encoded within this region of chromosome 17 is a common event in ovarian tumors. Thus, these abnormal expression patterns combined with the endogenous immune response suggests that these antigens represent potential targets for immunotherapy. © 2002 Wiley‐Liss, Inc.
Clinical course of bladder neoplasms and single nucleotide polymorphisms in the CDKN2A gene
Authors: Sakano Shigeru , Berggren Petra , Kumar Rajiv , Steineck Gunnar , Adolfsson Jan , Onelöv Erik , Hemminki Kari , Larsson Per
Published: January 2003

Point mutations and single nucleotide polymorphisms (SNPs) in the CDKN2A gene in bladder cancer patients have been resolved only to a limited extent. The exact frequency of mutations remains uncertain and reports on SNPs are lacking. In this population‐based study we investigated mutations and polymorphisms in the CDKN2A gene in bladder cancer patients from all hospitals within the Stockholm County. Mutations were determined in 4 exons of the CDKN2A gene in tumor‐tissues from 172 bladder cancer patients and 2 single nucleotide polymorphisms in the 3′ UTR of the CDKN2A gene were studied in 309 cases. Missense mutations were identified in only 4 of 172 (2.3%) cases, including 1 in the germ‐line. Frequencies of the 500 C→G and 540 C→T polymorphisms in the 3′ UTR of the CDKN2A in bladder cancer cases were not statistically significantly different compared to an ethnically matched control population. The tumor‐specific survival was significantly shorter in patients with either the 500 C→G or 540 C→T polymorphism than those with wild‐type CDKN2A gene (P = 0.02). Our results corroborate the earlier findings that single base mutation is not the prime mode of inactivation of the CDKN2A gene in bladder cancer. Further, the results indicate, a role for the 3′ UTR polymorphisms in the CDKN2A gene in tumor invasiveness. © 2002 Wiley‐Liss, Inc.
The E2F‐1 transcription factor is negatively regulated by its interaction with the MDMX protein
Authors: Strachan Gordon D. , Jordan‐Sciutto Kelly L. , Rallapalli Ravikumar , Tuan Rocky S. , Hall David J.
Published: January 2003

Several proteins with important roles in oncogenesis have been shown to regulate the function of the E2F‐1 transcription factor, which is known to activate the expression of genes required for proliferation and apoptosis. Here we identify the MDMX oncoprotein as an E2F‐1‐binding factor, from a yeast‐two hybrid screen using a portion of the E2F‐1 protein as “bait.” We demonstrate that the region within MDMX needed for the E2F‐1:MDMX interaction is located in the central part of the protein, C‐terminal of the p53‐binding domain. The region within E2F‐1 needed for this association is adjacent to the DNA binding domain. Further, when expressed in vivo or in vitro the MDMX protein migrates as two isoforms on SDS‐PAGE, the faster migrating isoform having the stronger affinity for the E2F‐1 proteins. It appears that this interaction reduces the ability of E2F‐1 to bind DNA. Expression of MDMX along with E2F‐1 and Dp‐1 in Saos2 cells reduces the ability of E2F‐1 to bind to its consensus DNA sequence, without altering E2F‐1 protein levels. These data indicate that the MDMX protein is capable of associating with E2F‐1 and negatively regulating its DNA binding ability. © 2002 Wiley‐Liss, Inc.
Gene therapy and tissue engineering in repair of the musculoskeletal system
Authors: Wu Daniel , Razzano Pasquale , Grande Daniel A.
Published: January 2003

Historically, surgeons have sought and used different procedures in order to augment the repair of various skeletal tissues. Now, with the completion of the Human Genome Project, many researchers have turned to gene therapy as a means to aid various ailments. In the orthopedic field, many strides have been made toward using gene therapy and tissue engineering in a clinical setting. In this review, several studies are outlined in different areas that gene therapy has or will influence orthopedic surgery. Gene therapy and tissue engineering can aid in fracture healing and spinal fusions by inducing bone formation, ligamentous repairs by increasing the production of connective tissue fibers, intervertebral disc disease by creating potential replacements, and articular cartilage repairs by providing means to improve cartilage. As we continue to see great contributions, such as the few mentioned here, this field will continue to mature and develop. © 2002 Wiley‐Liss, Inc.
Differential regulation of cellular adhesion and migration by recombinant laminin‐5 forms with partial deletion or mutation within the G3 domain of α3 chain
Authors: Kariya Yoshinobu , Tsubota Yoshiaki , Hirosaki Tomomi , Mizushima Hiroto , Puzon‐McLaughlin Wilma , Takada Yoshikazu , Miyazaki Kaoru
Published: January 2003

The basement membrane protein laminin‐5 promotes cell adhesion and migration. The carboxyl‐terminal G3 domain in the α3 chain is essential for the unique activity of laminin‐5. To investigate the function of the G3 domain, we prepared various recombinant laminin‐5 forms with a partially deleted or mutated G3 domain. The deletion of the carboxyl‐terminal 28 amino acids (region III) markedly decreased the cell adhesion activity with a slight loss of the cell motility activity toward BRL and EJ‐1 cells. This change was attributed to the loss of Lys‐Arg‐Asp sequence. Further deletion of 83 amino acids (region II) led to almost complete loss of the cell motility activity. All charged amino acid residues tested in this region were not responsible for the activity loss. These results suggest that the G3 domain contains two distinct regions that differently regulate cell adhesion and migration. Analysis of laminin‐5 receptors showed that integrins α3β1, α6β1, and α6β4 had different but synergistic effects on cell adhesion and migration on laminin‐5. However, the structural change of the G3 domain appeared not to change integrin specificity. The present study demonstrates that the G3 domain in laminin‐5 plays a central role to produce different biological effects on cells. © 2002 Wiley‐Liss, Inc.
Phosphorylation of proteins in neuron terminals: Specificity depends on coincidental signaling
Authors: Zhang Lixing , Tinette Sylvette , Robichon Alain
Published: January 2003

We investigate the role of neuronal coincidental signaling mediated by the second messengers, on phosphorylation of three major proteins of neurosecretory vesicles. Our data show that different combinations of coincidental signaling generate specific pattern of phosphoproteins and not strictly additional effects. This suggests that an added phosphate on a site might ‘mask’ or ‘unmask’ the next sites for specific kinases and phosphatases action by inducing conformation change or protein association. We show that a function of vesicles such as the uptake of glutamate is highly regulated by coincidental signaling. © 2002 Wiley‐Liss, Inc.
Mutation analysis of the non‐muscle myosin light chain kinase (MLCK) deletion constructs on CV1 fibroblast contractile activity and proliferation
Authors: Wadgaonkar Raj , Nurmukhambetova Saule , Zaiman Ari L. , Garcia Joe G.N.
Published: January 2003

Smooth muscle myosin light chain kinase (MLCK) is a multifunctional molecule composed of an N‐terminal actin binding domain, a central kinase domain, and C‐terminal calmodulin‐ and myosin‐binding domains. We previously cloned and characterized a novel MLCK isoform from endothelial cells (EC MLCK) consisting of 1,914 amino acids displaying a higher molecular weight (210 kDa) and a novel‐amino‐terminal stretch of 922 amino acids not shared by the smooth muscle isoform (smMLCK, 150 kDa). To further define the role of specific EC MLCK motifs in endothelial and non‐muscle cells, we constructed two epitope‐tagged EC MLCK deletion mutants in mammalian expression vectors lacking either the C‐terminal auto‐inhibitory and calmodulin‐binding domain (EC MLCK1745) or the ATP‐binding site (EC MLCKATPdel). Expression of EC MLCK1745 in CV1 fibroblasts showed increased basal actin stress fiber formation, which was markedly enhanced after tumor necrosis factor (TNF‐α) or thrombin treatment. Distribution of EC MLCK1745 was largely confined to stress fibers, cortical actin filaments, and focal adhesion contacts, and co‐localized with myosin light chains (MLCs) diphosphorylated on Ser19 and Thr18. In contrast, immunofluorescence staining demonstrated that EC MLCKATPdel abolished thrombin‐ and TNFα‐induced stress fiber formation and MLC phosphorylation, suggesting this kinase‐dead mutant functions as a dominant‐negative MLCK construct, thereby confirming the role of EC MLCK in stress fiber formation. Finally, we compared the serum‐stimulated growth rate of mutant MLCK‐transfected fibroblasts to sham controls, and found EC MLCK1745 to augment thymidine incorporation whereas EC MLCKATPdel reduced CV1 growth rates. These data demonstrate the necessary role for MLCK in driving the contractile apparatus via MLC phosphorylation, which can alter fibroblast growth and contractility. © 2002 Wiley‐Liss, Inc.
IRES‐dependent translational control of Cbfa1/Runx2 expression
Authors: Xiao Zhou‐Sheng , Simpson Leigh G. , Quarles L. Darryl
Published: January 2003

The P1 and P2 promoters of the Cbfa1/Runx2 gene produce Type I and II mRNAs with distinct complex 5′‐untranslated regions, respectively designated UTR1 and UTR2. To evaluate whether the 5′‐UTRs impart different translational efficiencies to the two isoforms, we created SV40 promoter‐UTR–luciferase reporter (luc) constructs in which the translational potential of the 5′‐UTR regions was assessed indirectly by measurement of luciferase activity in transfected cell lines in vitro. In MC3T3‐E1 pre‐osteoblasts, UTR2 was translated approximately twice as efficiently as the splice variants of UTR1, whereas translation of unspliced UTR1 was repressed. To determine if the UTRs conferred internal ribosome entry site (IRES)‐dependent translation, we tested bicistronic SV40 promoter‐Rluc‐UTR‐Fluc constructs in which Fluc is expressed only if the intercistronic UTR permits IRES‐mediated translation. Transfection of bicistronic constructs into MC3T3‐E1 osteoblasts demonstrated that both UTR2 and the spliced forms of UTR1 possess IRES activity. Similar to other cellular IRESs, activity increased with genotoxic stress induced by mitomycin C. In addition, we observed an osteoblastic maturation‐dependent increase in IRES‐mediated translation of both UTR2 and the spliced forms of UTR1. These findings suggest that Cbfa1 UTRs have IRES‐dependent translational activities that may permit continued Cbfa1 expression under conditions that are not optimal for cap‐dependent translation. © 2003 Wiley‐Liss, Inc.
Raf‐independent and MEKK1‐dependent activation of NF‐κB by hydrogen peroxide in 70Z/3 pre‐B lymphocyte tumor cells
Authors: Lee Michael , Koh Woo Suk
Published: January 2003

We have previously demonstrated that hydrogen peroxide (H2O2) treatment of murine 70Z/3 pre‐B lymphocytes inhibits the immune response to lipopolysaccharide by attenuating signaling through c‐Jun N‐terminal kinase (JNK) activation. In the present study, we further examined the signaling intermediates responsible for immunosuppression by H2O2, focusing on NF‐κB, a dimeric transcription factor whose activation is implicated in a number of immune response. Treatment of 70Z/3 pre‐B cells with H2O2 caused activation of NF‐κB in the nuclei by detection of NF‐κB specific DNA binding, concomitant with phosphorylation of IκBα. H2O2 stimulation of NF‐κB occurred within 20 min of treatment, reached maximum level at 60 min, and sustained for 2 h or more. Especially, MEK1 may contribute to H2O2‐induced NF‐κB activation as shown in the inhibition of NF‐κB binding activity by the MEK1 inhibitor, PD 98059, and H2O2‐induced MEK1 activation. However, H2O2 exhibited no effect on the activity of Raf‐1 kinase, which was an upstream activator of MEK1. Furthermore, B‐58l and α‐hydroxyfarnesylphosphonic acid, two inhibitors of Ras, did not block NF‐κB activation. In addition, the transient transfection of a dominant negative Ras (RasN17) construct showed a negligible inhibitory effect on the activation of NF‐κB by H2O2. Instead, treatment of 70Z/3 cells with H2O2 resulted in the activation of MAPK kinase kinase 1 (MEKK1) as well as JNK. Therefore, our data suggest that H2O2 regulates the activity of NF‐κB by MEK1 activation through MEKK1‐dependent but Ras/Raf‐independent mechanism. © 2002 Wiley‐Liss, Inc.
Simulated microgravity suppresses osteoblast phenotype, Runx2 levels and AP‐1 transactivation
Authors: Ontiveros C. , McCabe Laura R.
Published: January 2003

Conditions of disuse such as bed rest, space flight, and immobilization result in decreased mechanical loading of bone, which is associated with reduced bone mineral density and increased fracture risk. Mechanisms involved in this process are not well understood but involve the suppression of osteoblast function. To elucidate the influence of mechanical unloading on osteoblasts, a rotating wall vessel (RWV) was employed as a ground based model of simulated microgravity. Mouse MC3T3‐E1 osteoblasts were grown on microcarrier beads for 14 days and then placed in the RWV for 24 h. Consistent with decreased bone formation during actual spaceflight conditions, alkaline phosphatase and osteocalcin expression were decreased by 80 and 50%, respectively. In addition, runx2 expression and AP‐1 transactivation, key regulators of osteoblast differentiation and bone formation, were reduced by more than 60%. This finding suggests that simulated microgravity could promote dedifferentiation and/or transdifferentiation to alternative cell types; however, markers of adipocyte, chondrocyte, and myocyte lineages were not induced by RWV exposure. Taken together, our results indicate that simulated microgravity may suppress osteoblast differentiation through decreased runx2 and AP‐1 activities. © 2002 Wiley‐Liss, Inc.