bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapid determination method of caffeine and application to monitoring of caffeine‐assisted chemotherapy
Authors: Kawahara Masami , Kagiyama Hiromi , Kanazawa Yoshimitsu , Tsuchiya Hiroyuki , Tomita Katsuro , Yokogawa Koichi , Miyamoto Ken‐ichi
Published: February 2004

Caffeine‐assisted chemotherapy for bone and soft tissue tumours is very effective. However, high serum caffeine concentrations cause severe side effects, so monitoring of the serum level during therapy is important. For this purpose, a rapid determination method was established by high‐performance liquid chromatography after solid‐phase extraction. This method can measure caffeine and its three major metabolites in serum samples within 8 min. The mean serum caffeine concentrations of patients were 34.6±7.8, 54.5±11.9 and 73.0±12.8 μg/ml at 24, 48 and 72 h, respectively, after the start of a 1500 mg/m2/day continuous infusion for 72 h. The distribution volume of caffeine was 0.65±0.23 l/kg, and the total body clearance was 0.025±0.011 l/h/kg, which was one‐third of the reported low dose clearance. The appropriate infusion rate was calculated to avoid severe side effects in the final phase of the infusion by using a one‐compartment constant infusion model based on the serum levels measured at 24 and 48 h. Caffeine clearance did not correlate with the metabolite/caffeine ratio in serum at any time. It is concluded that individual monitoring with this method for the purpose of dose adjustment is useful for avoiding the side effects of caffeine‐assisted chemotherapy. Copyright © 2004 John Wiley & Sons, Ltd.
Evaluation of pharmacokinetics, brain levels and protein binding of centpropazine in rats
Authors: Bhattaram Venkatesh Atul , Paliwal Jyoti K. , Gupta Ram C.
Published: February 2004

The pharmacokinetics of centpropazine (CNPZ), an antidepressant, was studied in rats. CNPZ was administered to groups of rats (n=3 to 5) via oral (40 mg/kg), intravenous (5 mg/kg), intraperitoneal (5 mg/kg) and intraduodenal (4 and 8 mg/kg) routes. The AUCs of CNPZ were estimated and the bioavailabilities were calculated. CNPZ was characterized by a short elimination half‐life (39.5 min), a high clearance (118 ml/min/kg) and a relatively large volume of distribution (1945 ml/kg) after intravenous administration. After oral administration CNPZ exhibited a very low oral bioavailability (∼0.2%). The total first pass effect (Egit+liver) was calculated as 98.7%. The bioavailability of CNPZ was similar when administered by intraduodenal and oral routes. CNPZ readily penetrated into the brain and reached Cmax by 30 min post oral dosing. About 92.0%±0.8% of the drug was bound to serum proteins. Low oral bioavailability of CNPZ following oral administration is likely due to its metabolism by intestinal mucosa and liver. Copyright © 2004 John Wiley & Sons, Ltd.
Pharmacokinetics of HEPP, a new anticonvulsant, in healthy subjects and rabbits after multiple doses
Authors: González‐Esquivel Dinora F. , Pérez M Rodolfo , Cook Helgi Jung
Published: February 2004

In the present study the pharmacokinetics of D,L‐3hydroxy‐3‐phenylpropionamide (HEPP) a new anticonvulsant compound was studied after multiple dose administration in healthy male volunteers and in rabbits. The study in humans involved the oral administration of 375mg of HEPP b.i.d. for 7 consecutive days. The study in rabbits explored doses of 30mg/kg intraperitoneal (i.p.) given once daily for 6 days. In both studies pharmacokinetic (PK) profiles were characterized after the first dose and after the last multiple dose. Plasma HEPP concentrations were measured by HPLC. Pharmacokinetic parameters were calculated by noncompartmental methods. The results in humans as well as in rabbits showed that after multiple doses the AUC values decreased and CL/F values were significantly increased, which could be due to an induction process in the metabolic disposition of the drug. Copyright © 2004 John Wiley & Sons, Ltd.
In vitro dissolution and in vivo oral absorption of methylphenidate from a bimodal release formulation in healthy volunteers
Authors: Wang Yanfeng , Lee Lucy , Somma Russell , Thompson Glenn , Bakhtiar Ray , Lee James , Rekhi Gurvinder Singh , Lau Henry , Sedek Greg , Hossain Mohammad
Published: February 2004

Purpose—The objective of this study was to evaluate the in vitro dissolution and in vivo absorption of D,L‐threo‐methylphenidate (MPH) from a novel bimodal release formulation (Ritalin® LA capsule) compared with an immediate‐release formulation (Ritalin IR tablet) in healthy volunteers.

Methods—The bimodal release formulation contains 50% of the dose in the immediate‐release (IR) beads and 50% in polymethacrylate‐coated, delayed‐release (DR) beads. To better understand the impact of dissolution from the DR beads on oral absorption of MPH, three Ritalin LA formulations with different dissolution profiles for the DR beads (referred to as slow‐, medium and fast‐release formulations) were prepared, and tested together with the immediate‐release formulation in 18 healthy male and female volunteers after a single oral dose under fasted conditions. The rate and extent of oral absorption of MPH were evaluated based on the overall Cmax, tmax and AUC values, as well as the Cmax, tmax and AUC values for each individual peak of the bimodal plasma concentration‐time profile. The in vivo absorption‐time profile was also examined by deconvolution.

Results—All three Ritalin LA formulations demonstrated similar bimodal plasma concentration–time profiles with two peak concentrations observed at ∼2 and ∼6 h post dose, mimicking that of Ritalin IR tablets given 4 h apart. Deconvolution results showed that the absorption of MPH was biphasic, with a rapid absorption phase between 0 to ∼2 h, and a somewhat slower second absorption between ∼3–6 h, consistent with the in vitro bimodal release characteristics of Ritalin LA formulation. The three Ritalin LA formulations were bioequivalent to one another based on the overall Cmax and AUC values and the corresponding values describing the first and second peaks, although their in vitro dissolution profiles for the DR beads were different. Compared with Ritalin IR, the Ritalin LA formulation demonstrated a similar rate of absorption for the first peak, a lower second Cmax and a higher trough concentration between peaks, as well as similar overall plasma AUC.

Conclusions—Following a single oral drug administration, Ritalin LA demonstrated a two‐peak plasma concentration–time profile, similar to that of the IR formulation given 4 h apart, but with less fluctuation in the plasma concentration–time profile. The in vivo biphasic absorption of MPH appeared to be well correlated with the bimodal dissolution characteristics of this new Ritalin LA formulation, and some changes in the dissolution profiles for the DR beads appeared not to affect the overall bioavailability of MPH in humans. Copyright © 2004 John Wiley & Sons, Ltd.
Photoinduced Interactions Between Oxidized and Reduced Lipoic Acid and Riboflavin (Vitamin B2)
Authors: Lu Changyuan , Bucher Götz , Sander Wolfram
Published: February 2004

As a powerful natural antioxidant, lipoic acid (LipSS) and its reduced form dihydrolipoic acid (DHLA) exert significant antioxidant activities in vivo and in vitro by deactivation of reactive oxygen and nitrogen species (ROS and RNS). In this study the riboflavin (RF, vitamin B2) sensitized UVA and visible‐light irradiation of LipSS and DHLA was studied employing continuous irradiation, fluorescence spectroscopy, and laser flash photolysis (LFP). Our results indicate that LipSS and DHLA quench both the singlet state (1RF*) and the triplet state (3RF*) of RF by electron transfer to produce the riboflavin semiquinone radical (RFH.) and the radical cation of LipSS and DHLA, respectively. The radical cation of DHLA is rapidly deprotonated twice to yield a reducing species; the radical anion of LipSS (LipSS.−). When D2O was used as solvent, it was confirmed that the reaction of LipSS with 3RF* consists of a simple electron‐transfer step, while loss of hydrogen occurs in the case of DHLA oxidation. Due to the strong absorption of RFH. and the riboflavin ground state, the absorption of the radical cation and the radical anion of LipSS can not be observed directly by LFP. N,N,N′,N′‐tetramethyl‐p‐phenylenediamine (TMPD) and N,N,N′,N′‐tetramethyl benzidine (TMB) were added as probes to the system. In the case of LipSS, the addition resulted in the formation of the radical cation of TMPD or TMB by quenching of the LipSS radical cation. If DHLA is the reducing substrate, no formation of probe radical cation is observed. This confirms that LipSS.+ is produced by riboflavin photosensitization, and that there is no oxidizing species produced after DHLA oxidization.
Synthesis of Silver and Gold Nanoparticles by a Novel Electrochemical Method
Authors: Ma Houyi , Yin Bingsheng , Wang Shuyun , Jiao Yongli , Pan Wei , Huang Shaoxin , Chen Shenhao , Meng Fanjun
Published: February 2004

Spherical silver and gold nanoparticles with narrow size distributions were conveniently synthesized in aqueous solution by a novel electrochemical method. The technological keys to the electrochemical synthesis of monodispersed metallic nanoparticles lie in the choice of an ideal stabilizer for the metallic nanoclusters and the use of a rotating platinum cathode. Poly(N‐vinylpyrrolidone) (PVP) was chosen as the stabilizer for the silver and gold clusters. PVP not only protects metallic particles from agglomeration, but also promotes metal nucleation, which tends to produce small metal particles. Using a rotating platinum cathode effectively solves the technological difficulty of rapidly transferring the (electrochemically synthesized) metallic nanoparticles from the cathode vicinity to the bulk solution, avoiding the occurrence of flocculates in the vicinity of the cathode, and ensuring the monodispersity of the particles. The particle size and particle size distribution of the silver and gold nanoparticles were improved by adding sodium dodecyl benzene sulfonate (SDBS) to the electrolyte. The electrochemically synthesized nanoparticles were characterized by TEM and UV/Vis spectroscopy.
Cover Picture: In Situ Spectroscopic Analysis of Nanocluster Formation (ChemPhysChem 1/2004)
Authors: Wang Jia , Boelens Hans F. M. , Thathagar Mehul B. , Rothenberg Gadi
Published: February 2004

The cover picture shows an artist's impression of the formation of a metal nanocluster in a solution containing ions and atoms of two different metals. Nanoclusters are UV/Vis active, and in theory it should be possible to follow the exact kinetics of their formation by UV/Vis spectroscopy. In practice, however, the decomposition of the spectra presents a formidable problem. To read how Rothenberg et al. managed to solve this problem, turn to p. 93.
Performance evaluation of TCP session considering long‐range dependence of RTT
Authors: Hagiwara Tatsuya , Matsuda Takahiro , Yamamoto Miki
Published: February 2004

Recent research has shown that long‐range dependence is found not only in network traffic volume, but also in the propagation delay time of packets. The round‐trip propagation time of packets, which is known as the round‐trip time (RTT), is one of the most important parameters for determining TCP performance. The ability to understand its characteristics can contribute to an improvement in TCP performance. Therefore, in this paper, to determine the impact of the long‐range dependence of the RTT on TCP performance, the authors looked at the two congestion control phases known as congestion avoidance and slow start in TCP window control and used computer simulations to evaluate performance. First, the evaluation related to the impact on the congestion avoidance phase showed that higher long‐range dependence and larger transfer files caused greater variability in the file transfer completion time. Next, the evaluation related to the impact on the slow start phase, which evaluated the impact of the long‐range dependence of the RTT on the TCP retransmission timeout (RTO), showed that higher long‐range dependence causes unnecessary timeouts, which end up causing the resending of packets that have not actually been lost, to occur more frequently. The authors also performed investigations for mitigating the impact of the long‐range dependence of the RTT and made a number of modifications to the existing RTO estimation algorithm to show that TCP performance can be improved. © 2004 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 87(6): 52–60, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.10073
Synchronous CSMA/CD on PTMP access networks
Authors: Kobayashi Hiroshi , Ozawa Kazuyoshi , Kamura Koichirou , Moriya Osamu
Published: February 2004

In order to realize high‐speed Internet access on PTMP access networks such as bidirectional CATV, the Synchronous CSMA/CD method has been developed. The main points are that, when multiple packets collide, the collision state always starts from the head of the colliding packets by synchronizing the arrival of the packets at the hub device with the predetermined timing, and that the hub device always monitors the access status of the uplink and broadcasts the status through the downlink. As a result, the CSMA/CD method can be applied to PTMP networks, and the maximum network length can be arbitrarily set without dependence on the minimum packet length. © 2004 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 87(6): 43–51, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.10074
Beat interference suppression techniques by means of transmission diversity and adaptive equalization
Authors: Kubo Hiroshi , Okazaki Akihiro , Tanada Kazuo , Murakami Keishi
Published: February 2004

In this paper, we discuss techniques for transmitting signals over the same frequency by synchronizing multiple base stations in order to achieve both high communication quality and excellent spectral efficiency in broadcast (P‐MP: Point to Multipoint) communication (single‐frequency, multistation simultaneous transmission). Specifically, in this paper, we propose a communication technique that uses the concept of transmission diversity and converts beat interference to intersymbol interference to suppress beat interference, which becomes a problem in single‐frequency, multistation simultaneous transmission. The proposed technique features (1) controlling the transmit timing or waveform of the signal transmitted from each base station, and (2) using an adaptive equalizer to compensate for intersymbol interference produced during transmission. Finally, we assume a high‐speed Rayleigh fading environment in addition to a beat interference environment in computer simulations and demonstrate the effectiveness of the proposed technique when maximum likelihood sequence estimation based on per‐survivor processing is adopted. © 2004 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 87(6): 12–21, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.10167
Production of a Laccase and Decrease of the Phenolic Content in Canola Meal during the Growth of the Fungus Pleurotus ostreatus in Solid State Fermentation Processes
Authors: Hu J. , Duvnjak Z.
Published: February 2004

Solid state fermentation of canola meal was carried out with the fungus Pleurotus ostreatus DAOM 197961, which is a producer of laccase. The aim of this study was to examine the effects of moisture content, inoculum size, homogenisation of inoculum and particle size of canola meal on the growth of the fungus, the production of a laccase and the decrease of the content of sinapic acid esters (SAE) in a solid state process. The results showed that the optimum moisture content, which was varied in the media between 50% and 75%, for the growth and enzyme production was 60%. The initial rate of SAE content decrease was faster in the media with 70% and 75% moisture than in those with lower moisture levels. In the study of the effects of inoculum concentration in the range of 1.1 mg to 5.5 mg/g of the medium, it was found that larger amounts of biomass and enzyme were produced in the media with inoculum concentrations from 1.1 mg to 3.3 mg/g of the medium than in the media with a higher inoculum concentration. The final and approximately the same concentrations of SAE were reached at the same time regardless of the inoculum concentration. Considering that the fungus formed pellets under the conditions at which it was grown during the inoculum preparation, it was necessary to break them by homogenisation prior to their utilisation as an inoculum. The homogenisation was carried out during a period between 15s and 200s. Although higher biomass concentrations and enzyme activities were obtained in the media which were inoculated with the inoculum homogenised for 15s and 30s, the maximum enzyme activities and biomass concentrations were reached in the media inoculated with the inoculum, which was homogenised for 120s and 200s. The time of inoculum homogenisation did not influence the kinetics of the SAE decrease. When the effects of the particle size of canola meal on the process were studied, it was found that larger particles of the meal in the solid media were more favourable for the production of the biomass and enzyme, and for a faster decrease of the SAE content than those of smaller sizes. From the obtained results it can be concluded that the tested variables have a significant influence on the growth of the fungus Pleurotus ostreatus DAOM 197961, the production of laccase and the decrease of the SAE content in canola meal. The data could be useful for the development of a solid state process for the production of laccase and for the decrease of the phenolics content in canola meal.
Carbon Dioxide Emission in Relation to the Growth of Geotrichum candidum in Solid Cultures
Authors: Couzon S. , Couriol C. , Amrane A. , Prigent Y.
Published: February 2004

Geotrichum candidum plays an important role in the ripening of Camembert‐type cheeses. However, the direct measurement of the biomass concentration is rather tedious and, therefore, the development of alternative methods for monitoring the growth on solid media would be very useful. For this purpose, a non‐structured model was previously developed to describe the CO2 emission during the growth of G. candidum in liquid cultures. The CO2 production was assumed to be partially associated with growth: a part resulted from growth and the remaining from cellular maintenance. This model has also been validated in solid cultures on peptone‐lactate based medium. The coefficients for growth‐associated and non‐growth‐associated production were found to be 0.301 and 0.123 per day, respectively. Therefore, the CO2 production may be a non‐destructive and useful tool to monitor fungal growth in solid cultures. In the case of mixed cultures of both fungi (Geotrichum candidum and Penicillium camembertii) involved in the ripening of Camembert cheeses, CO2 emission can be related to the total viable biomass, while ammonia and volatile sulphur compounds can be linked to G. candidum biomass. Indeed, it was previously shown that Penicillium camembertii released only very low amounts of both compounds.
New Developments in Chemical Engineering for the Production of Drug Substances
Authors: Behr A. , Brehme V.A. , Ewers Ch.L.J. , Grön H. , Kimmel T. , Küppers S. , Symietz I.
Published: February 2004

The pharmaceutical industry is moving towards a profitability gap between increasing costs and decreasing prices. Finally, management has understood that mergers and acquisitions, high throughput screening, and biotechnology alone will not save the companies' earnings. Therefore, classical approaches like the optimization of production technologies for drug substances, that might help to increase profitability, are receiving increasing attention. This paper shows how the combination of innovative components will guide the way to very efficient and cost‐effective production. The first component is the design and manufacturing of production facilities. The second component is a process streamlining of the production process. The key technologies discussed here are process control and miniplant technology. For these technologies a brief outlook on future trends is given.
Test of Porous Ceramic Material for the Immobilisation of Predominant Nitrifying Bacteria and for the Improvement of the AAO Process
Authors: Lee J.M. , Choi I.S. , Wiesmann U.
Published: February 2004

The efficiency of nitrification in a fixed bed reactor was compared to that found in an activated sludge reactor to determine their sensitivity to changing loads and lower temperatures. Two structurally identical lab‐scale systems, using the anaerobic/anoxic/aerobic (AAO) process to remove nitrogen and phosphorus simultaneously, were operated in parallel with secondary clarifiers and sludge return. The first aerobic system was operated as an activated sludge reactor, the second system as a fixed bed reactor. The aerobic fixed bed reactor was filled with porous ceramic materials for the immobilisation of predominantly nitrifying bacteria. The removal efficiencies of 99 % NH4+‐N, 90 % DOC, and 98 % PO43–‐P for normal loads of 0.11 g/L d DOC, 0.06 g/L d NH4+‐N, and 0.0054 g/L d PO43–‐P were achieved for both systems. However, the system with an aerobic fixed bed reactor was characterised by the following advantages over the system with an activated sludge reactor: a shorter time to reach almost complete nitrification, a higher nitrification rate at higher loads of NH4+‐N and a lower sensitivity of nitrification at lower temperatures down to 12 °C.
Visualization of Differential Gene Expression – Using Fluorescence‐Based cDNA‐AFLP
Authors: Gigliotti S. , Hausman J.‐F. , Evers D.
Published: February 2004

cDNA‐AFLP is one of the techniques developed to study differentially expressed genes. This recent technique is advantageous because it does not need prior sequence knowledge and is reliable due to highly stringent PCR conditions.

The traditional cDNA‐AFLP method uses radioactively labelled products and is characterised by high sensitivity and resolution. Here, the use of Cy5‐labelled primers to detect products on polyacrylamide gels is reported. This non‐radioactive method, based on fluorescence, is shown to be faster and the recovery of interesting bands is easier.

The study of the differential gene expression of the interaction between potato and Phytophthora infestans was used for the valuation of this method.

Different gene expression profiles – such as up‐regulation, down‐regulation or point expression – were obtained. Moreover, this technique was shown to be highly reproducible.
Improving the Production of Ectomycorrhizal Fungus Mycelium in a Bioreactor by Measuring the Ergosterol Content
Authors: Carrillo C. , Díaz G. , Honrubia M.
Published: February 2004

The cultivation of some ectomycorrhizal fungi growing in bioreactors under submerged aerobic conditions was modified by regulating the cultivation parameters and determining the optimum duration of the process. For this goal, the active mycelium was determined by quantifying its ergosterol content.Lactarius deliciosus(strain LDF5) andSuillus mediterraneensis(strain 35 AM) were cultivated in a BRAUN Biostat®B bioreactor under the following fermentation conditions: 23 °C, pH 5.5, 60’% dissolved oxygen, 100 rpm stirring, and 1.2‐‐2 L/min air flow. In addition, several cultivation conditions were assayed forL. deliciosus. During the fermentation cycle, samples were taken at different times. Ergosterol was extracted and quantified using high‐performance liquid chromatography (HPLC). The quantity of ergosterol inL. deliciosusincreased with the age of the culture up to 4.7 μg/mg (17‐day‐old culture). In the case ofS. mediterraneensis, this quantity increased up to day 11 of the cultivation, and then it decreased. Three days after the addition of fresh medium, a maximum of 8.9 μg/mg was reached. On the other hand, the highest ergosterol content inL. deliciosus(6.3 μg/mg) was obtained using MMN medium with the addition of agar.
On modelling nonlinear microwave power amplifiers in multi‐carrier transmission systems
Authors: Ermolova Natalia , Vainikainen Pertti
Published: February 2004

A nonlinear model of the power amplifier in a multi‐carrier transmission system is discussed. It is emphasized that when the amplifier is driven by a signal with a large dynamic range, the third‐order model of its nonlinearity may be invalid. Taking into account high order components of the nonlinear model is especially important if the power amplifier produces phase distortions. A technique for an accurate prediction of the output spectrum of a nonlinear power amplifier in a multi‐carrier transmission system is presented. It is based on the fifth‐order Taylor series expansion of the complex gain of the power amplifier. The obtained formulas are simple and convenient to use. They can be employed as a basis for both design and analysis of microwave amplifiers. Copyright © 2004 AEI
A low‐complexity speech‐pause detection algorithm for communication in noisy environments
Authors: Beritelli Francesco , Casale Salvatore , Serrano Salvatore
Published: February 2004

The paper presents a new low‐complexity algorithm for silence suppression in adverse acoustic environments. The algorithm uses a single time‐domain input parameter (signal power) given to a simple matching block. The decision module adapts a series of thresholds depending on the current estimated signal‐to‐noise‐ratio (SNR) of the signal. A series of tests carried out using a large speech database confirm a 10% improvement in pause detection performance as compared with the AMR VAD option 1 recently adopted by ETSI for 3rd‐generation mobile systems. Copyright © 2004 AEI
Electrophysiological properties of retinal Müller glial cells from myelin mutant rat
Authors: Chávez Andrés E. , Pannicke Thomas , Roncagliolo Manuel , Reichenbach Andreas , Palacios Adrián G.
Published: February 2004

The structural and functional similarities between Müller cells and oligodendrocytes prompted the present study of the electrophysiological properties of Müller (glia) cells obtained from the retinae of control and myelin mutant taiep rats during the postnatal developmental period (P12–P180). The whole‐cell configuration of the patch‐clamp technique was used to characterize the general properties and the K+ currents from dissociated Müller cells. During the first 3 weeks of life, a decrease of the membrane resistance and an increase of the membrane potential were observed in Müller cells from both control and taiep rats. However, Müller cells from taiep rats never achieved the very negative membrane potential (−50 mV vs −80 mV) and the low membrane resistance characteristic for control cells. Furthermore, Müller cells displayed increased inward and outward K+ currents during postnatal development up to P30/60 in controls; however, in taiep rats, this increase ceased at P20/30, and low‐amplitude currents persisted into adulthood. These results provide first evidence of physiological changes in retinal Müller cells as a consequence of a myelin mutation causing a progressive deterioration of the central nervous system (CNS) due to a disturbance of the microtubule network of oligodendrocytes. We hypothesize that the progressive dysmyelination process of the optic nerve, accompanied by functional deficits of retinal neurons (e.g., ganglion cells), induces physiological alterations of Müller cells. © 2003 Wiley‐Liss, Inc.
The 36K protein of zebrafish CNS myelin is a short‐chain dehydrogenase
Authors: Morris Jacqueline K. , Willard Belinda B. , Yin Xinghua , Jeserich Gunnar , Kinter Michael , Trapp Bruce D.
Published: February 2004

Previous studies identified homologues to mammalian myelin genes expressed in the teleost central nervous system (CNS), including myelin basic protein (MBP), protein zero (P0), and a member of the proteolipid protein family, DM20. In addition, an uncharacterized 36‐kDa (36K) protein is a major component of teleost myelin, but is not a major component of myelin in other species. In the present study, we sought to better understand myelin proteins and myelination in one teleost, zebrafish, by molecular characterization of the zebrafish 36K protein. Purified zebrafish CNS myelin was isolated and the amino acid sequences of peptides present in the 36‐kDa band were determined by mass spectrometry. These sequences matched a previously uncharacterized EST in The Institute for Genome Research (TIGR) zebrafish database that is related to the short‐chain dehydrogenase/reductase (SDR) protein family. In vitro expression of the zebrafish 36K cDNA in Neuro 2a cells resulted in a protein product that was recognized by a 36K polyclonal antibody. The zebrafish 36K mRNA and protein expression patterns were determined and correlated to other known myelin gene expression profiles. In addition, we determined by in situ hybridization that a human 36K homologue (FLJ13639) is expressed in oligodendrocytes and neurons in the adult human cortex. This study identified a major myelin protein in zebrafish, 36K, as a member of the SDR superfamily; an expression pattern similar to other myelin genes was demonstrated. © 2003 Wiley‐Liss, Inc.
High‐Throughput Experimentation in Organic Coating and Thin Film Research: State‐of‐the‐Art and Future Perspectives
Authors: Schmatloch Stefan , Bach Hermann , van Benthem Rolf A. T. M. , Schubert Ulrich S.
Published: February 2004

Summary: The success of automated and parallel drug‐discovery workflows in pharmaceutical research has sparked similar developments in materials science. This contribution provides an overview of published high‐throughput experimentation work in the area of polymeric coatings and thin films. Methodological aspects, experimental examples, and remaining challenges are discussed.

Robotic system (GE) for crosshatch application.

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Robotic system (GE) for crosshatch application.
Instability and Dewetting of Conducting‐Insulating Polymer Thin‐Film Bilayers
Authors: Chattopadhyay Santanu , Meredith J. Carson
Published: February 2004

Communication: Combinatorial thickness‐gradient libraries are used to explore stability and dewetting in thin bilayers of polystyrene (PS) on poly(3‐octylthiophene) (P3OT) on Si. At low P3OT thicknesses (90–175 nm), P3OT screens the unfavorable van der Waals (VDW) interactions between PS and Si, and the instability onset thickness of PS is depressed from 56 to 23 nm. A dramatic and unexpected transition to a VDW‐unstable interface is discovered at P3OT thicknesses above 175 nm.

A digital image of a representative bilayer library.

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A digital image of a representative bilayer library.
Rapid Synthesis of Polyanhydrides by Microwave Polymerization
Authors: Vogel Brandon M. , Mallapragada Surya K. , Narasimhan Balaji
Published: February 2004

Summary: Polyanhydrides were synthesized from aliphatic and aromatic diacids using microwave radiation without vacuum at significantly reduced reaction times when compared to conventional melt polycondensation. Reaction conditions, such as duration of polymerization, equivalents of acetic anhydride, and choice of starting species, were studied. In addition, copolymers were synthesized and monomer sequence lengths were calculated using dyad conditional probabilities. The results are in good agreement with monomer sequence lengths from conventional copolymerization.

Comparison of the monomer sequence lengths in poly(CPH‐co‐SA) synthesized both conventionally and by microwave heating.

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Comparison of the monomer sequence lengths in poly(CPH‐co‐SA) synthesized both conventionally and by microwave heating.
Parallel Dynamic Thermomechanical Measurements of Polymer Libraries
Authors: Kossuth Mary Beth , Hajduk Damian A. , Freitag Christopher , Varni John
Published: February 2004

Summary: A common bottleneck in combinatorial materials science occurs at the characterization stage. Here we discuss an instrument for the rapid measurement of mechanical properties of polymer libraries, which allows for 96 simultaneous measurements to be taken under a variety of conditions. For example, plateau moduli and glass transition temperatures can be measured by ramping temperature while applying a deformation at a constant amplitude and frequency, much like a conventional DMTA.

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Techniques and Instrumentation for Combinatorial and High‐Throughput Polymer Research: Recent Developments
Authors: Schmatloch Stefan , Schubert Ulrich S.
Published: February 2004

Summary: Emerging from the field of biochemistry and pharmaceutical research, combinatorial and high‐throughput synthesis and screening methodologies are rapidly being adopted in polymer and materials research. Alternative solutions to cost intensive custom‐made synthetic robot systems have become commercially available and further accelerate this field of research not just in industry, but also in an academic environment. High‐throughput analysis, materials characterization, and testing (surface energy, hardness, wettability, crystallinity etc.) are key techniques and require suitable instrumentation. Here we present a short overview of recent developments of robotic synthesizers and analytical equipment extending the review from January 2003.

A picture of the Accelerator™PXT100 which allows up to forty individual reactions to be performed in parallel in various modes.

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A picture of the Accelerator™PXT100 which allows up to forty individual reactions to be performed in parallel in various modes.
Combinatorial Approach to Characterizing Epoxy Curing
Authors: Eidelman Naomi , Raghavan Dharmaraj , Forster Aaron M. , Amis Eric J. , Karim Alamgir
Published: February 2004

Summary: Three complementary techniques that probe different characteristics of curing: FTIR microspectroscopy, confocal microscopy and axisymmetric adhesion testing were used to study discrete epoxy samples cured at different temperatures and to follow curing across a continuous gradient combinatorial library. Together, these techniques provide a comprehensive picture of chemical and physical changes.

FTIR microspectroscopy map of epoxy film cured on a temperature gradient. Red represents the highest and blue the lowest curing.

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FTIR microspectroscopy map of epoxy film cured on a temperature gradient. Red represents the highest and blue the lowest curing.
Combinatorial Physical Vapor Deposition of π‐Conjugated Organic Thin Film Libraries
Authors: Fukumoto Hiroki , Muramatsu Yukiko , Yamamoto Takakazu , Yamaguchi Jun , Itaka Kenji , Koinuma Hideomi
Published: February 2004

Summary: Thin film technology has been attracting much interest as a tool for making combinatorial libraries of solid state materials including organic compounds and polymers as well as their devices. Especially, physical vapor deposition is very frequently used in research and development of semiconductors, metals, and advanced ceramics and its coupling with combinatorial chemical concepts has been making remarkable progress and success in recent years. Here we provide a short overview of recent studies on combinatorial fabrication of organic thin film libraries by physical vapor deposition for optimization of their structure and properties for device application.

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Combinatorial Exploration of Polymeric Transport Agents for Targeted Delivery of Bioactives to Human Tissues
Authors: Petro Miroslav , Nguyen Son Hoai , Liu Mingjun , Kolosov Oleg
Published: February 2004

Summary: Recently, in material science domain, combinatorial approaches in design, construction and screening of novel compounds and formulations have led to a significant acceleration of discovery and development. The versatility of polymeric materials offers a great opportunity to dial‐in a desired set of performance features via a proper combination of various building blocks such as monomer units or polymer chain segments. Further enhancement comes from the formulation of the polymer into its final environment in a combinatorial way. Within the last few years, a variety of parallel polymerization, purification and formulation techniques, supported by rapid automated analyses in combination with a suite of high‐throughput protocols for application‐related benefit screening, were developed and successfully applied in different fields of industry. At Symyx Technologies Inc., we have integrated a variety of synthesis, screening and information tools and procedures into robust workflows, targeting discovery and development of novel polymeric materials. In addition to the performance features of the polymeric materials, controlled by their chemical, physical and mechanical properties, we can monitor interactions of polymers with a variety of molecules and substrate surfaces. That allows us to extend the applicability of the combinatorial approach towards the macromolecular delivery agents with a wide range of use in personal care, biotech and pharma areas. The current paper reports on a generic workflow developed and applied for identification of selective transport agents for targeted delivery of bioactives to human tissues.

Hit selection using screening data on polymer substantivity to substrates representing the tissue‐1 as object of preferred delivery (left) and the competitive tissue‐2 (right).

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Hit selection using screening data on polymer substantivity to substrates representing the tissue‐1 as object of preferred delivery (left) and the competitive tissue‐2 (right).
High‐Throughput Automated Parallel Evaluation of Zinc‐Based Catalysts for the Copolymerization of CHO and CO2 to Polycarbonates
Authors: van Meerendonk Wouter J. , Duchateau Robbert , Koning Cor E. , Gruter Gert‐Jan M.
Published: February 2004

Summary: Copolymerization of CO2 and oxiranes using high‐pressure autoclaves typically allows one experiment per reactor per day. As a high‐throughput approach for this chemistry would be extremely valuable, a parallel setup has been validated for the copolymerization of CO2 and cyclohexene oxide (CHO) with two β‐diiminato zinc complexes. Molecular weights, polydispersities and activities were found to be comparable with literature values.

Polycarbonate from cyclohexene oxide (CHO) and CO2.

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Polycarbonate from cyclohexene oxide (CHO) and CO2.
Natural orbital functional approach: Calculation of dielectric properties in molecules
Authors: Piris Mario , Martinez Alberto , Otto Peter
Published: February 2004

Recently, we proposed a new natural orbital functional for taking into account the electronic correlation in molecular systems. Calculation of dipole moments and polarizabilities of eight selected molecules are presented. By comparison with other correlated methods, it is shown that the method has predictive capabilities for these properties. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Evaluation of two‐center, three‐ and four‐electron integrals over Slater‐type orbitals in elliptical coordinates
Authors: Budziński Jan
Published: February 2004

An algorithm for evaluation of two‐center, three‐electron integrals with the correlation factors of the type rr and rrr as well as four‐electron integrals with the correlation factors rrr and rrr in the Slater basis is presented. This problem has been solved here in elliptical coordinates, using the generalized and modified form of the Neumann expansion of the interelectronic distance function r for k ≥ −1. Some numerical results are also included. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Critical evaluation of a high‐throughput analytical method for polychlorinated biphenyls in human serum: which detector for the establishment of the reference values?
Authors: Turci Roberta , Mariani Giulio , Marinaccio Alessandro , Balducci Claudio , Bettinelli Maurizio , Fanelli Roberto , Nichetti Simona , Minoia Claudio
Published: February 2004

A rapid screening method, previously developed and validated for the determination of 60 PCB congeners in human serum by using high‐resolution gas chromatography coupled with low‐resolution mass spectrometry, was applied to the establishment of the reference values in the general population. The reliability of this method was further confirmed by analyzing ten serum samples, obtained from the same population group involved in the original study, by electron impact ionization with either low‐ or high‐resolution mass spectrometry. Analyses in electron capture negative ionization mode were also performed for the determination of ‘dioxin‐like’ isomers. The data were found to be in good accordance with one another, especially for the congeners of highest environmental significance. Then, 162 real serum samples were analyzed for the presence of PCBs. Comparison with the results from other studies reported in the literature showed that a similar profile was observed; the most abundant congeners were #153, #180, #138 and #170. A statistical analysis was performed to determine whether there were significant correlations between PCB concentrations and specific variables such as age, gender, and dietary habits. Copyright © 2004 John Wiley & Sons, Ltd.
Alpha‐ and beta‐ cleavages of the amino‐terminus of the cellular prion protein
Authors: Mangé Alain , Béranger Florence , Peoc’h Katell , Onodera Takashi , Frobert Yveline , Lehmann Sylvain
Published: February 2004

Abstract It is commonly assumed that the physiological isoform of prion protein, PrPC, is cleaved during its normal processing between residues 111/112, whereas the pathogenic isoform, PrPSc, is cleaved at an alternate site in the octapeptide repeat region around position 90. Here we demonstrated both in cultured cells and in vivo, that PrPC is subject to a complex set of post‐translational processing with the molecule being cleaved upstream of position 111/112, in the octapeptide repeat region or at position 96. PrP has therefore two main cleavage sites that we decided to name α and β. Cleavage of PrPC at these sites leads us to re‐evaluate the function of both N‐ and C‐terminus fragments thus generated.
Neurotrophins and extracellular matrix molecules modulate sensory axon outgrowth
Authors: Hari Ashwinii , Djohar Baharak , Skutella Thomas , Montazeri Sonia
Published: February 2004

Neurotrophins have been known to play a pivotal role in axonal guidance. Recent research has implicated the role of extracelluar matrix molecules in co‐ordinating axonal movement. In this study, we examined the influence of neurotrophins (nerve growth factor (NGF) and neurotrophin‐3 (NT‐3)) and extracellular matrix molecules (laminin, fibronectin, and poly‐l‐lysin) on sensory neurite outgrowth in thoracic dorsal root ganglia (DRG) dissected from rats at embryonic day 13. Adjacent DRG were embedded in a collagen gel matrix and supplemented with NGF or NT‐3. Under NT‐3 conditions, DRG axons extended towards each other and intermingled, while neurites from NGF‐treated DRG demonstrated a strong repellent effect, resulting in turning responses and growth cone collapse. This effect was not observed on a collagen culture surface. Interestingly, the composition of the extracellular matrix strongly influenced the observed repellent effect. Sensory neurites from NGF‐stimulated DRG again demonstrated a repellent effect when plated on a laminin surface, but showed intermingling behavior when plated on poly‐l‐lysin or fibronectin. This observation suggests that a factor secreted by NGF‐treated DRG axons interacts with laminin, enabling repulsion. This factor and its interaction with the extracellular matrix play an important role in the mechanism of sensory axonal pathfinding.
Thrust sequences in the central part of the External Hellenides
Authors: SOTIROPOULOS SPILIOS , KAMBERIS EVANGELOS , TRIANTAPHYLLOU MARIA V. , DOUTSOS THEODOR
Published: February 2004

The model of a foreland propagating sequence already presented for the External Hellenides is significantly modified in this paper. New data are used, including structural maps, cross-sections, stratigraphic determinations and seismic profiles. In general, thrusts formed a foreland propagating sequence but they acted simultaneously for a long period of time. Thus, during the Middle Eocene the Pindos thrust resulted in the formation of the Ionian–Gavrovo foreland and acted in tandem with the newly formed Gavrovo thrust within the basin until the Late Oligocene. The Gavrovo thrust consists of segments, showing that out-of-sequence thrusting was important. Thrust nucleation and propagation history is strongly influenced by normal faults formed in the forebulge region of the Ionian–Gavrovo foreland basin. Shortening rates within the Gavrovo–Ionian foreland are low, about 1 mm/year. Although thrust load played an important role in the formation of this basin, the additional load of 3500 m thick clastics in the basin enhanced subsidence and underthrusting.
Schumann's Manfred in the mental theatre
Authors: TUNBRIDGE LAURA
Published: February 2004

Byron was determined from the start that Manfred should not be performed on stage. Writing from Venice in spring 1817 he told his publisher, John Murray, that: The thing I have sent you will see at a glimpse - could never be attempted or thought of for the stage . . . I composed it actually with a horror of the stage - with a view to render even the thought of it impracticable, knowing the zeal of my friends, that I should try that for which I have an invincible repugnance - viz. - a representation.
Handel the postmodernist
Authors: EMSLIE BARRY
Published: February 2004

I have a picture by Mondrian in front of me. It is made of up of a wide range of different, discrete rectangular shapes. The paint has been applied precisely. The colors are varied and striking and contribute to the overall impression of exactness in the detail and variety in the general. There are no people in the picture. It reminds me of a Handel opera. More or less any Handel opera.
THE CATASTROPHIZING WORRY PROCESS IN GENERALIZED ANXIETY DISORDER: A PRELIMINARY INVESTIGATION OF AN ANALOG POPULATION
Authors: Hazlett-Stevens Holly , Craske Michelle G.
Published: February 2004

Effects of structured worry interviews were examined among analog-GAD and nonanxious college students. Thirty-four analog-GAD and 29 nonanxious control participants generated sequences of possible catastrophic outcomes for each of six worry topics using the Catastrophizing Interview Technique (Vasey and Borkovec, 1992). Threat ratings for each topic were collected, and ratings of subjective distress, likelihood of the feared outcome, and perceived control over the feared outcome were obtained immediately following each interview. Results indicated that the analog-GAD group rated the worry topics of achievement, social relations, and economics as more threatening than their nonanxious counterparts. The analog-GAD group also generated more catastrophizing steps and reported higher levels of negative mood following the worry interviews. In addition, the eventual fear underlying each worry was determined by coding the content of the final outcome step from each interview. Results from the coded interview responses indicated that fears of negative emotion and of failure were the most frequently coded categories in each of the six topical domains for the analog-GAD group. Although there was no difference in the proportion of negative emotion codes between analog-GAD and nonanxious groups, the analog-GAD group did receive a greater proportion of failure codes than the nonanxious control group. Results largely replicated the findings of Vasey and Borkovec in an analog-GAD sample. In addition, results suggest that fear of negative emotion underlies worry in general, regardless of diagnostic status, while fears of failure or ineffectiveness are more specific to GAD.