bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced co‐solubilities of Ca and Si in YAG (Y3Al5O12)
Authors: Kuru Yener , Onur Savasir Erdem , Zeynep Nergiz Saide , Oncel Cinar , Ali Gulgun Mehmet
Published: June 2008

General garnet structure (Ia3d) is a forgiving host and can accommodate cations of varying sizes and valence states. Studies on highly yttrium doped alumina ceramics with Ca and Si contamination indicated that YAG precipitates in the ceramic had a propensity to allow simultaneous incorporation of small amounts of Ca and Si impurities in their structure. In this study, using chemical synthesis techniques it was shown that YAG can accommodate up to approximately 8 cation% Ca+2 and Si+4 (i.e. Ca+2/Y+3 and Si+4/Y+3) if they are incorporated together. Equilibrium conditions are established by calcining samples at 900 °C for 2 hours and cooling the samples to room temperature in the furnace. Disappearing‐phase method and energy dispersive X‐ray spectroscopy were used to determine solubility and co‐solubility limits. Beyond the solubility limit phase separation occurred and three crystalline yttrium aluminate phases (YAG, YAP (yttrium aluminate perovskite, YAlO3), YAM (yttrium aluminate monoclinic, Y4Al2O9)) were observed. It is believed that the excess Ca and Si above co‐solubility limit precipitate out in the form of an x‐ray amorphous anorthite‐like glass in the system. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Post annealing effects on the properties of sputtered nano‐crystallite indium tin oxide thin films on flexible polyimide substrate
Authors: Mohammadi Gheidari A. , Hadad Dabaghi H. , Kalhor D. , Iraj M. , Kazemzad M. , Behafarid F.
Published: June 2008

Indium tin oxide (ITO) thin films were deposited onto flexible polyimide substrates using RF sputtering system at room temperature. The deposited films were then heat treated at different temperatures in air and vacuum atmospheres. The structural variations and as consequence the electro‐optical characteristic variations of the films were systematically investigated as a function of post annealing temperature and atmosphere. The structure of the films was studied by means of XRD and SEM techniques and the electro‐optical characteristics were measured by four point probe and spectrophotometer, respectively. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Effect of strain and alloy composition inhomogeneity on the electronic and optical properties of III‐nitride semiconductors
Authors: Skoulidis Nikos , Polatoglou Hariton
Published: June 2008

Using the empirical tight binding method with a sp3s* basis for the first neighbour interactions and only p–p interactions for the second neighbours, we calculated the optical properties near the fundamental gap of cubic GaxAl1–xN alloys for x<0.33 grown on a substrate whose lattice constant varies from the lattice constant of cubic AlN to GaN. We found that the spectra of the fully relaxed alloy have a tail with onset energy at the indirect gap of AlN and an edge at the direct gap of the alloy which follows the Vegard's law within 0.1 eV. The maximum of band gap for each alloy composition is found for a substrate with the lattice constant of the fully relaxed alloy. When the substrate composition is such that induces negative tetragonal strain on the alloy (εxx<0) the energy band gap is mainly affected by the alloy composition while for εxx>0 the alloy composition has a limited effect. The total effect of substrate and alloy composition in the calculated range on the band gap can be as much as 0.4 eV and is mainly due to the valence band shift as the conduction band is only slightly affected by the substrate or the alloy composition. This band gap change is adequate to explain the experimentally observed double photoluminescence peak of open quantum dots. The energy separation of the double peak is 0.1 eV and one peak can be attributed to the tetragonically strained wetting layer and the other to the fully relaxed quantum dots. Furthermore the present results can be used to estimate any possible stoichiometric inhomogeneity and help design structures with specific energies for the pair of peaks. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Influence of different phosphorus precursors on the electrical properties of the SiO2‐P2O5 films obtained by sol‐gel
Authors: Vasiliu Cristina , Vancea Cosmin , Latia Adina , Anastasescu Mihai , Todan Ligia , Predoana Luminita , Zaharescu Maria , Pavelescu Gabriela , Grigorescu Cristiana
Published: June 2008

This work aims at establishing the influence of different phosphor‐precursors on the electrical properties of 90%SiO2‐10%P2O5 (%mol) thin films prepared by sol‐gel method from triethylphosphate, triethylphosphite and phosphoric acid precursors. Glass and respectively ITO‐coated glass were used as substrates. The films were annealed at 200 °C and respectively 500 °C. For all selected precursors the results show that the conduction in the phosphate glass films decreases with increasing annealing temperature, giving thus evidence of a reduced release‐ and transfer‐activity of protons within the films. The activation energy of the conduction process takes values in the range 0.033‐0.04 eV. The correlation between the electrical properties and optical and structural data is also discussed. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Optical isolator with TiO2/magnetic garnet waveguide employing nonreciprocal phase shift
Authors: Yokoi Hideki , Kono Hideki , Sekine Kenichi , Shoji Yuya , Mizumoto Tetsuya
Published: June 2008

An interferometric optical isolator, with a TiO2/magnetic garnet waveguide, employing a nonreciprocal phase shift was studied. The nonreciprocal phase shift in the magneto‐optic waveguide was calculated at a wavelength of 1.55 μm. The large nonreciprocal phase shift was obtained when the magneto‐optic waveguide had a TiO2/magnetic garnet guiding layer. An optical isolator which could be operated in a unidirectional magnetic field was also discussed. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The contact characteristics of Al p‐GaSe Schottky diode
Authors: Huang Wen‐Chang , Horng Chia‐Tsung , Chen Yu‐Min , Hsu Yu‐Kuei , Chang Chen‐Shiung
Published: June 2008

The Schottky barrier characteristics of Al on a Bridgman grown p‐GaSe layered semiconductor have been investigated using current‐voltage‐temperature (I‐V‐T) characteristics over a temperature range of 198 K∼373 K. The forward I‐V‐T data reveals a decrease at the barrier height, but an increase at the ideality factor with decreasing in measurement temperature. For the 300 °C‐annealed diode, the barrier height decreased from 1.04 eV to 0.6 eV and the ideality increased from 1.4 to 2.4, as the temperature decreased from 373 K to 198 K. The Richardson plot showed activation energy of 0.26 eV at high temperature region, while showed a lower energy of 0.07eV at low temperature region. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Oxygen permeation in PET bottles with passive and active walls
Authors: Di Felice Renzo , Cazzola Daniela , Cobror Sandro , Oriani Luis
Published: June 2008

The aim of this paper is to provide a framework, whereby gas permeation rates through plastic packaging walls, and hence, food shelf life may be estimated. Although the approach is quite general, specific attention is given to the case of liquid‐filled polyethylene terephthalate (PET) bottles with oxygen as the permeating gas.

Two situations are considered: when the walls simply provide a passive resistance to the flux (as is the case for standard PET or PET blended with some other low permeability material) and when an active gas scavenger is incorporated within the boundary material.

For the passive wall, permeability data relative to oxygen have been collected from literature sources and also measured using specific oxygen transmission rate experiments. For the active walls, scavenger kinetic constants were estimated from data obtained using test bottles prepared with varying scavenger concentrations. Numerical predictions in both cases have been verified by comparison with data on gas concentration in water‐filled bottles maintained under controlled conditions for periods of up to 6 months. Copyright © 2008 John Wiley & Sons, Ltd.
Photoelastic stress and thermographic measurements of automotive windscreen defects generated by projectile impact
Authors: Donne Kelvin E. , Thomas Richard D. , Davies Christopher , Calvert Geoffrey
Published: June 2008

This paper describes an experimental technique to evaluate the stress distribution around an automotive windscreen ‘chip’, which is created by projectile impact. This stress distribution is measured before and after a typical resin injection repair procedure, and the results indicate a significant reduction in the residual shear stress. Concurrent thermographic measurements of the impact region during the repair procedure also suggest that the quality of the repair is dependent on the temperature profile at the time of repair. Preliminary computational modelling of a representative windscreen defect illustrates the predisposition of ‘star‐shaped’ chips to crack‐off to a windscreen edge under typical vehicle usage. Copyright © 2008 John Wiley & Sons, Ltd.
Principles of evaluating quality investments
Authors: Freiesleben Johannes
Published: June 2008

Quality departments often experience difficulties selling the idea that first priority should be given to quality improvement. Most approaches to project budgeting favour traditional investments such as new product development, which are perceived as potential profit boosters. To compete with such investments, a clear economic logic is needed, which stresses the long‐term benefits of better quality. The aim of this paper, therefore, is to provide a concise framework of how to think about quality investments in economic terms. By focusing on the principles of an economic evaluation, it highlights the major aspects of an improvement assessment and derives a simple measure for helping practitioners to determine the advantageousness of a quality initiative. Copyright © 2008 John Wiley & Sons, Ltd.
Quantitative Structure–Activity Relationship Study on Fish Toxicity of Substituted Benzenes
Authors: Gong Zhiguo , Xia Binbin , Zhang Ruisheng , Zhang Xiaoyun , Fan Botao
Published: June 2008

Many chemicals cause latent harm, such as erratic diseases and change of climate, and therefore it is necessary to evaluate environmentally safe levels of dangerous chemicals. Quantitative Structure–Toxicity Relationship (QSTR) analysis has become an indispensable tool in ecotoxicological risk assessments. Our paper used QSTR to deal with the modeling of the acute toxicity of 92 substituted benzenes. The molecular descriptors representing the structural features of the compounds were calculated by CODESSA program. Heuristic Method (HM) and Radial Basis Function Neural Networks (RBFNNs) were utilized to construct the linear and the nonlinear QSTR models, respectively. The predictive results were in agreement with the experimental values. The optimal QSTR model which was established based on RBFNNs gave a correlation coefficient (R2) of 0.893, 0.876, 0.889 and Root‐Mean‐Square Error (RMSE) of 0.220, 0.205, 0.218 for the training set, the test set, and the whole set, respectively. RBFNNs proved to be a very good method to assess acute aquatic toxicity of these compounds, and more importantly, the RBFNNs model established in this paper has fewer descriptors and better results than other models reported in previous literatures. The current model allows a more transparent chemical interpretation of the acute toxicity in terms of intermolecular interactions.
3D‐QSAR and Docking Studies of Quinazoline Derivatives with the Inhibitory Activity Toward NF‐κB
Authors: Qian Li , Shen Yong , Chen Jin‐Can , Wang Ya‐Xue , Wu Xiao‐Tian , Chen Tao‐Ju , Zheng Kang‐Cheng
Published: June 2008

Nuclear Factor‐κB (NF‐κB) is an important transcription factor for regulation expression of many cytokines that are involved in the pathogenesis of inflammatory diseases such as Adult Respiratory Distress Syndrome (ARDS), sepsis syndrome, and HIV. It is recently proposed that quinazoline derivatives are capable of inhibiting the activation of NF‐κB. To study the inhibiting mechanism and obtain some helpful information for designing functional inhibitor against the protein, 3‐D Quantitative Structure–Activity Relationship (3D‐QSAR) studies such as Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) and docking analysis on 29 inhibitors, quinazoline derivatives, have been carried out. The CoMFA and CoMSIA models give a cross‐validated coefficient q2 of 0.822 and 0.801, respectively. The binding pockets around the DNA binding sites in p50 and p65 have been tested for docking. The docking results at site 1 of p50 show a significant correlation between the energy scores and the corresponding experimental values with the correlation coefficient R=0.817. The contour maps of 3D‐QSAR model are shown in a good agreement with the structural characteristics of the corresponding binding site. These results indicate a NF‐κB‐DNA binding inhibiting mechanism for these compounds, which prevent free NF‐κB from binding to DNA. Therefore, the final 3D‐QSAR models and the information of the binding site would be useful in developing new quinazoline derivatives with favorable activity.
The Quantitative Structure–Retention Relationship (QSRR) Analysis of Some Centrally Acting Antihypertensives and Diuretics
Authors: Filipic Slavica , Nikolic Katarina , Krizman Mitja , Agbaba Danica
Published: June 2008

The complete separation of 15 guanidine/imidazoline derivatives, acting as antihypertensive drugs, was achieved by capillary electrophoresis employing 30 mM phosphate background electrolyte (pH 1.5) containing 15 mM β‐Cyclodextrin (BCD). Here the Quantitative Structure–Retention Relationship (QSRR) models of the inclusion complexes between the analyzed compounds (ligands) and BCD were performed to investigate the correlations between electrophoresis migration order and the constitutional, geometrical, physico‐chemical, and electronical properties of the molecular models. The ChemPro, Marvin 4.0.5 ChemAxon, and CS Gaussian 98 [B3LYP/6–31G+(d,p) and HF/3–21G(d) basis sets] programs were applied for molecular parameters computation of the optimized ligands and ligand–BCD complexes. Total charge of the analyzed compounds at experimental pH 1.5, HOMO (BCD–ligand) energy, and Solvent‐Accessible Surface (SAS) (BCD–ligand) area account for the electrophoresis retention parameter log(t). The multiple linear regression models with three variables, log(t)=f [Total Charge (ligand), SAS (BCD–ligand), HOMO (BCD–ligand)], were obtained with R2=0.914 and crossvalidation parameter of prediction $\rm{ q_{{\rm{pre}}}^{\rm{2}} }$=0.778. The developed QSRR approach can help in understanding the structural features that contribute to the electrophoresis retention parameter [log(t)] of the investigated antihypertensives. Therefore, the theoretical method presented could be used as a fast, easy, and reliable tool for electrophoretic migration parameters prediction of other related antihypertensives.
Synchronization of uncertain complex dynamical networks via adaptive control
Authors: Wang Lei , Dai Huaping , Kong Xiangjie , Sun Youxian
Published: June 2008

In this paper, synchronization of an uncertain dynamical network with time‐varying delay is investigated by means of adaptive control schemes. Time delays and uncertainties exist universally in real‐world complex networks. Especially, parameters of nodes in these complex networks are usually partially or completely uncertain. Considering the networks with unknown or partially known nodes, we design adaptive controllers for the corresponding complex dynamical networks, respectively. Several criteria guaranteeing synchronization of such systems are established by employing the Lyapunov stability theorem. Analytical and numerical results show that the proposed controllers have high robustness against parameter variations including network topologies, coupling structures, and strength. Copyright © 2008 John Wiley & Sons, Ltd.
On the use of mixed‐integer linear programming for predictive control with avoidance constraints
Authors: Maia Marcelo H. , Galvão Roberto K. H.
Published: June 2008

This technical note concerns the predictive control of discrete‐time linear models subject to state, input and avoidance polyhedral constraints. Owing to the presence of avoidance constraints, the optimization associated with the predictive control law is non‐convex, even though the constraints themselves are convex. The inclusion of the avoidance constraints in the predictive control law is achieved by the use of a modified version of a mixed‐integer programming approach previously derived in the literature. The proposed modification consists of adding constraints to ensure that linear segments of the system trajectories between consecutive sampling times do not cross existing obstacles. This avoids the significant extra computation that would be incurred if the sampling time was reduced to prevent these crossings. Simulation results show that the inclusion of these additional constraints successfully prevents obstacle collisions that would otherwise occur. Copyright © 2008 John Wiley & Sons, Ltd.
Passivity‐based control of a magnetically levitated flexible beam
Authors: Shimizu T. , Kobayashi Y. , Sasaki M. , Okada T.
Published: June 2008

This paper solves the asymptotic stabilization problem for a magnetically levitated flexible beam using a nested‐loop passivity‐based controller design. Passivity analyses reveal that the system can be decomposed into two passive subsystems: a mechanical subsystem that consists of a flexible beam with both ends free and that defines a passive map from external forces to the velocity of the points on the flexible beam at which the external forces act; and an electrical subsystem that consists of a pair of electromagnets and that defines a strictly output‐passive map from voltages applied across the electromagnets to magnetic fluxes. The standard method for designing passivity‐based controllers leads to a nonlinear feed‐forward controller for the electrical subsystem, which enables the electrical subsystem to generate given desired magnetic forces, and an output feedback compensator for the mechanical subsystem, which computes the desired forces required to regulate the position and vibration of the beam. The asymptotic stability of each controller may be proven using Lyapunov's stability theory and LaSalle's invariant set theorem. Numerical simulations confirm the asymptotic stability of the equilibrium configuration of the closed‐loop system formed by the magnetically levitated flexible beam together with the proposed controllers. Copyright © 2008 John Wiley & Sons, Ltd.
Strongly absolute stability of Lur'e descriptor systems: Popov‐type criteria
Authors: Yang Chunyu , Zhang Qingling , Zhou Linna
Published: June 2008

In this paper, we consider the strongly absolute stability problem of Lur'e descriptor systems (LDSs). First, we define a generalized Lur'e Lyapunov function (GLLF) and show that the negative‐definite property of the derivative of the GLLF guarantees strongly absolute stability of LDSs. As a result, the existing Popov‐type criteria are reduced to sufficient conditions for the existence of the GLLF. Then, we propose a necessary and sufficient condition for the existence of the GLLF to guarantee the strongly absolute stability of LDSs. This criterion is shown to be less conservative than the existing ones. Finally, we discuss the computational issues and present two numerical examples to illustrate the effectiveness of the obtained results. Copyright © 2008 John Wiley & Sons, Ltd.
Adaptive observer design for a chaotic Duffing system
Authors: Bobtsov Alexey , Pyrkin Anton , Nikolaev Nikolay , Slita Olga
Published: June 2008

The problem of unknown encoded parameter reconstruction is solved by means of an adaptive observer design procedure for a chaotic Duffing system. Unlike the known analogues, the problem in question is solved by using only the output measurements of the chaotic system and in conditions of full parametrical uncertainty. Copyright © 2008 John Wiley & Sons, Ltd.
Beta‐binomial/Poisson regression models for repeated bivariate counts
Authors: Lora Mayra Ivanoff , Singer Julio M.
Published: June 2008

We analyze data obtained from a study designed to evaluate training effects on the performance of certain motor activities of Parkinson's disease patients. Maximum likelihood methods were used to fit beta‐binomial/Poisson regression models tailored to evaluate the effects of training on the numbers of attempted and successful specified manual movements in 1 min periods, controlling for disease stage and use of the preferred hand. We extend models previously considered by other authors in univariate settings to account for the repeated measures nature of the data. The results suggest that the expected number of attempts and successes increase with training, except for patients with advanced stages of the disease using the non‐preferred hand. Copyright © 2008 John Wiley & Sons, Ltd.
The determination of optimal software release times at different confidence levels with consideration of learning effects
Authors: Ho Jyh‐Wen , Fang Chih‐Chiang , Huang Yeu‐Shiang
Published: June 2008

As most software reliability models do not clearly explain the variance in the mean value function of cumulative software errors, they might not be effective in deducing the confidence interval regarding the mean value function. In such cases, software developers cannot estimate the possible risk variation in software reliability by using the randomness of the mean value function, thus reducing the decision‐making reliability when determining an optimal software release time. In this paper, the method of stochastic differential equations is used to build a software reliability model, which is validated based on practical data previously used in six published papers. Moreover, the estimation of the parameters of the proposed model, which can be defined as the autonomous error‐detected factor and the learning factor, is also illustrated, and the results of model validation empirically confirm that the proposed model is able to account for a fairly large portion of the variance of the mean value function. Additionally, the confidence intervals of the mean value function regarding software faults are employed to assist software developers in determining the optimal release times at different confidence levels. Finally, a numerical example is given to verify the effectiveness of the proposed model. Copyright © 2008 John Wiley & Sons, Ltd.
Evaluating product development systems using network analysis
Authors: Collins Shawn T. , Yassine Ali A. , Borgatti Stephen P.
Published: June 2008

This paper proposes the integration of two systems engineering analysis tools, the Design Structure Matrix (DSM) and Network Analysis (NA), to study task interactions in a Product Development Process (PDP). The DSM is a matrix‐based systems engineering tool that analyzes task sequences to improve PDP execution. Using NA metrics to measure properties of information flow helps to identify important product development tasks and interactions that constrain PDP execution. Project managers can use these data to structure team integration mechanisms or to identify coordinating mechanisms for groups of concurrently scheduled PDP tasks. Functional managers and process architects can use these data to identify important or overloaded tasks. They can also evaluate whether tasks like stage gates and design reviews are acting as effective information flow regulators in the PDP. This new Systems Engineering approach provides a rigorous decision support tool for managers who must alter ideal task sequences due to specific schedule, budget, and expertise constraints encountered on their projects. © 2008 Wiley Periodicals, Inc. Syst Eng
Diversity‐oriented synthesis
Authors: Spandl Richard J. , Díaz‐Gavilán Mónica , O'Connell Kieron M. G. , Thomas Gemma L. , Spring David R.
Published: June 2008

Diversity‐oriented synthesis (DOS), which describes the synthesis of structurally diverse collections of small molecules, was developed, in part, to address combinatorial chemistry's shortfalls. In this paper, we hope to give an indication of what can be achieved using the DOS approach to library generation. We describe some of the most successful strategies utilized in DOS, with special focus on our own area of interest; DOS from simple, pluripotent starting materials. © 2008 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 8: 129–142; 2008: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20144
Glutamate transporter blockers for elucidation of the function of excitatory neurotransmission systems
Authors: Shimamoto Keiko
Published: June 2008

L‐Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. Termination of glutamate receptor activation and maintenance of low extracellular glutamate concentrations are mainly achieved by glutamate transporters [excitatory amino acid transporters 1–5 (EAAT1–5)] located in nerve endings and surrounding glial cells. Selective and potent inhibitors have long been required to investigate the physiological significance of transporters in the regulation of synaptic transmission and the pathogenesis of neurological diseases. Non‐transportable blockers are desirable because, unlike competitive substrates, they do not cause ion flux and heteroexchange. After a series of possible candidate molecules, we synthesizedthreo‐β‐benzyloxyaspartate (TBOA), the first non‐transportable blocker for all subtypes of EAATs. In addition, TBOA analogs with a bulky substituent on their benzene ring showed enhanced inhibition of labeled glutamate uptake. Comparing the effects of substrates and non‐transportable blockers revealed the physiological roles of EAATs. We also developed a novel binding assay system using a tritium‐labeled TBOA analog. In this review, we describe the design and synthesis of these blockers and the functions of the EAATs elucidated with them. © 2008 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 8: 182–199; 2008: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20145
Catalytic enantioselective organozinc addition toward optically active tertiary alcohol synthesis
Authors: Hatano Manabu , Ishihara Kazuaki
Published: June 2008

A highly enantioselective organozinc (R2Zn) addition to a series of aldehydes and ketones was developed based on conjugate Lewis acid–Lewis base catalysis. Optically active secondary and tertiary alcohols were obtained in high yields with high enantioselectivities without Ti(IV) compounds. Bifunctional chiral 3,3′‐diphosphoryl‐BINOL ligands were designed and prepared through a phospho‐Fries rearrangement as a key step. On the other hand, bifunctional chiral phosphoramide ligands were designed and prepared from L‐valine. Mechanistic studies were performed by X‐ray analyses of Zn(II) cluster and chiral ligands, a 31P NMR experiment on Zn(II) complexes, and stoichiometric reactions with some chiral or achiral Zn(II) complexes to propose a transition state assembly that includes monomeric active intermediates. © 2008 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 8: 143–155; 2008: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20146
Cannabinoid CB1receptor antagonists in therapeutic and structural perspectives
Authors: Lange Jos H. M. , Kruse Chris G.
Published: June 2008

The observed antiobesity effect of rimonabant (1) in a pharmacological rodent model 10 years ago has led to a surge in the search for novel cannabinoid CB1antagonists as a new therapeutic target for the treatment of obesity. Rimonabant showed clinical efficacy in the treatment of obesity and also improved cardiovascular and metabolic risk factors. Cannabinoid CB1receptor antagonists have also good prospects in other therapeutic areas, including smoking and alcohol addiction as well as cognitive impairment. Solvay's research achievements in this fast‐moving field are reported in relation with the current state of the art. Several medicinal chemistry strategies have been pursued. The application of the concept of conformational constraint led to the discovery of more rigid analogs of the prototypic CB1receptor antagonist rimonabant. Replacement of the central heterocyclic pyrazole ring in rimonabant yielded imidazoles, triazoles, and thiazoles as selective CB1receptor antagonists. Dedicated medium‐throughput screening efforts delivered one 3,4‐diarylpyrazoline hit. Its poor pharmacokinetic properties were successfully optimized which led to the discovery of orally active and highly CB1/CB2receptor selective analogs in this series. Regioisomeric 1,5‐diarylpyrazolines, 1,2‐diarylimidazolines, and water‐soluble imidazoles have been designed as novel CB1receptor antagonist structure classes. © 2008 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 8: 156–168; 2008: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20147
Catalytic asymmetric Nozaki–Hiyama reactions with a tridentate bis(oxazolinyl)carbazole ligand
Authors: Inoue Masahiro , Suzuki Takahiro , Kinoshita Akihiro , Nakada Masahisa
Published: June 2008

Nozaki–Hiyama reactions are powerful CrII‐mediated CC bond‐forming reactions conducted under mild conditions that show excellent compatibility with various functional groups. Therefore, Nozaki–Hiyama reactions have been utilized for many total syntheses of complex natural products, but at least two equivalents of CrII salt are required to complete the reaction because CrII salt is a one‐electron donor. In 1996, however, the quantity of CrII salts required was successfully reduced by a catalytic redox system reported by Fürstner and Shi. Since the report by Fürstner, the catalytic asymmetric Nozaki–Hiyama reactions have attracted attention because they would allow control over enantioselectivity, thereby further enhancing the versatility of Nozaki–Hiyama reactions. In this review, we describe the development of a tridentate bis(oxazolinyl)carbazole ligand for the catalytic asymmetric Nozaki–Hiyama allylation, methallylation, propargylation, and allenylation. Also described are their successful applications to the highly stereoselective construction of the side chain of calcitriol lactone, as well as structure elucidation and the enantioselective first total synthesis of the potent 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors, FR901512 and FR901516. © 2008 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 8: 169–181; 2008: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.20148
Effects of ibuprofen on the viability and proliferation of rainbow trout liver cell lines and potential problems and interactions in effects assessment
Authors: Schnell Sabine , Kawano Atsushi , Porte Cinta , Lee Lucy E. J. , Bols Niels C.
Published: June 2008

Under some conditions ibuprofen was either cytotoxic or cytostatic to rainbow trout cell lines: RTL‐W1 (liver) and RTH‐149 (hepatoma). Ibuprofen at up to 15 μg/mL was not cytotoxic, regardless of dosing protocols, exposure conditions, viability endpoints, or cell lines. Responses to higher ibuprofen concentrations depended on the test methodology. No cytotoxicity was seen when stock ibuprofen solutions had been prepared in ethanol. For stock solutions in dimethylsulfoxide (DMSO), ibuprofen from 50 to 1500 μg/mL elicited little cytotoxicity in cultures in which the final DMSO concentration was 0.05% (v/v), but was consistently cytotoxic after 24 h for cultures with 0.5% DMSO (v/v). Cytotoxicity was evaluated with alamar Blue (AB) and carboxyfluoroscein diacetate acetoxymethyl ester (CFDA‐AM) as measures respectively of metabolic activity and membrane integrity. Effective concentrations (EC50s) for ibuprofen with AB and CFDA‐AM depended on whether the stock solution was dosed directly into a culture well or mixed in medium prior to being added to a well. For indirect dosing, ibuprofen was more cytotoxic in medium without fetal bovine serum (FBS), whereas for direct dosing ibuprofen was equally cytotoxic in medium with or without FBS. As judged by AB and CFDA‐AM EC50s, dosing ibuprofen was directly 10 to 30 times more cytotoxic. In FBS‐containing cultures, which was dosed with increasing ibuprofen and DMSO at 0.05% (v/v), cell proliferation was impaired at 50 and 150 μg/mL ibuprofen. Lipopolysaccharide (LPS) at 50 μg/mL had little influence on these cytotoxic and cytostatic effects of ibuprofen in medium with FBS. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009.
Effect of long‐term exposure to simazine on histopathology, hematological, and biochemical parameters in Cyprinus carpio
Authors: Oropesa A. L. , García‐Cambero J. P. , Gómez L. , Roncero V. , Soler F.
Published: June 2008

We investigated if residues of simazine in the natural waters would cause histological, hematological, and biochemical alterations in carps from contaminated areas in Badajoz (Spain). Some necrotic foci in kidney and liver, hepatitis, and hepatic steatosis were detected. No changes on measured hematological and biochemical parameters between fish from reference and contaminated ponds were observed. To assess if simazine exposure was the cause of these observations carps were exposed in the laboratory to simazine (45 μg/L) for 90 days. Some results obtained in the field were confirmed in laboratory, such as necrosis in kidney and liver and hepatic steatosis. Globular eosinophilic foci in kidney and a slight decrease of the hematocrit were also detected. These changes were moderate and indicative of an adaptation of the fish to the toxic stress caused by exposure to low simazine concentrations. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009.
Comparison of R‐metalaxyl and rac‐metalaxyl in acute, chronic, and sublethal effect on aquatic organisms: Daphnia magna, Scenedesmus quadricanda, and Danio rerio
Authors: Yao Kun , Zhu Lin , Duan Zhenghua , Chen Zhongzhi , Li Yan , Zhu Xiaoshan
Published: June 2008

Chiral pesticides are used widely in the world, and at present, older racemic products are being replaced by enantiopure products because of accelerated development of asymmetry synthesis techniques. Pesticides as xenobiotic released into environment impose a great stress on nontarget organisms. Although it is a necessary procedure for pesticides to have a registration based on toxicological data from nontarget organism, until now ecological risk assessment about metalaxyl only depend on racemic products. Hence, we investigated the acute, chronic, and sublethal toxicity of R‐metalaxy and rac‐metalaxyl on aquatic organisms such as D. magna (Daphnia magna), algae (Scenedesmus quadricanda), and adult zebrafish (Danio rerio). The results showed a significant difference in toxicity between R‐metalaxyl and rac‐metalaxyl. R‐Metalaxy was about 20‐fold more toxic to algae than rac‐metalaxyl with IC50 of 222.89 ± 1.18 mg/L and 19.95 ± 1.12 mg/L, respectively. Similarly, R‐metalaxyl was about fourfold toxic to D. magna than rac‐metalaxyl according to the individual 24‐h‐LC50 values, and sixfold toxic than rac‐metalaxyl based on 24‐h‐EC50 values. In the light of 48‐h‐LC50 and EC50, this difference in toxicity was more significant. As for adult zebrafish, there was no pronounced difference in acute toxicity, in addition, at sublethal level a different pattern in inducing Na+,K+‐ATPase activity between them was found. In general, R‐metalaxyl seemed more toxic to aquatic organisms than rac‐metalaxyl. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009.
Surgical Education and Postgraduate Training in Japan
Authors: Ito Yasuo
Published: June 2008

Japanese students must pass very competitive entrance examinations to enter medical school after graduating from high school at the relatively young age of 18. There are currently 80 medical schools in Japan, with approximately 7700 students graduating annually. Since 2004, after passing the National Medical Board Examination, all medical graduates are required to complete a 2‐year period of clinical training to become medical practitioners. Surgical residency starts only at the third postgraduate year. The Japan Surgical Society initiated a new surgical board certification system in 2002, defining minimum requirements to qualify for the specialty. Four subspecialties are recognized along with general surgery: gastroenterological surgery, cardiovascular surgery, thoracic surgery, and pediatric surgery. General surgery board certification is a prerequisite for subspecialty board certification. Notwithstanding these revisions, the number of surgery candidates is steadily declining because work conditions in the surgical profession are viewed as unfavorable. To regain some level of the previous attractiveness and glory of this specialty, surgeons need to receive significant incentives that counteract some of the downsides of the life of a surgeon.
Complications of Loop Ileostomy Closure: A Retrospective Cohort Analysis of 123 Patients
Authors: Mansfield S. D. , Jensen C. , Phair A. S. , Kelly O. T. , Kelly S. B.
Published: June 2008

Background

Loop ileostomies are often formed in order to defunction distal anastomoses. The aim of this study was to review the complications following closure of loop ileostomies.

Methods

This is a retrospective case note analysis of all loop ileostomy closures performed in the Northumbria Healthcare NHS Trust (population over 500,000) over a 5‐year period between 2001 and 2005.

Results

A total of 123 case records were reviewed. Complications occurred in 41 patients (33.3%), with 9 patients (7.3%) requiring further intervention. There were 4 (3.3%) postoperative deaths. Complications were more common in patients with increased comorbidity (p = 0.0007) and postoperative death was more frequent among the elderly (p = 0.0006). Postoperative death was more common in those patients who had their stomas created during surgery (elective or emergency) for diverticular disease (3 patients, p = 0.006). Patients with diverticular disease had significantly higher comorbidity and peritoneal contamination at the time of primary surgery. Ileostomy reversal after anterior resection for cancer was associated with a lower complication rate than the rest of the cohort (26%, p = 0.0003) but there was no significant difference in mortality. Neither the grade of the surgeon, the case volume, or the anastomotic technique affected postoperative morbidity. Reoperation was more common in patients whose closure procedure took less time (p = 0.002) and in those who had a shorter wait from creation to reversal of the stoma (p < 0.0001).

Conclusions

Reversal of loop ileostomy may be associated with significant morbidity and mortality. Increasing the delay from creation to closure may result in fewer complications.There is an increased risk in older patients with more comorbidity, particularly when the primary procedure is for diverticular disease with significant peritoneal contamination.
Diagnostic work‐up and management of patients with isolated methylmalonic acidurias in European metabolic centres
Authors: Zwickler T. , Lindner M. , Aydin H. I. , Baumgartner M. R. , Bodamer O. A. , Burlina A. B. , Das A. M. , de Klerk J. B. C. , Gökcay G. , Grünewald S. , Guffon N. , Maier E. M. , Morava E. , Geb S. , Schwahn B. , Walter J. H. , Wendel U. , Wijburg F. A. , Müller E. , Kölker S. , Hörster F.
Published: June 2008

The long‐term outcome of patients with methylmalonic aciduria (MMA) is still uncertain due to a high frequency of complications such as chronic renal failure and metabolic stroke. The understanding of this disease is hampered by a huge variation in the management of these patients. The major aim of this study was to evaluate the current practice in different European metabolic centres. A standardized questionnaire was sent to 20 metabolic centres asking for standard procedures for confirmation of diagnosis, testing cobalamin responsiveness, dietary treatment, pharmacotherapy, and biochemical and clinical monitoring. Sixteen of 20 metabolic centres (80%) returned questionnaires on 183 patients: 89 of the patients were classified as mut0, 36 as mut−, 13 as cblA, 7 as cblB, and 38 as cblA/B. (1) Confirmation of diagnosis: All centres investigate enzyme activity by propionate fixation in fibroblasts; six centres also perform mutation analysis. (2) Cobalamin response: Ten centres follow standardized protocols showing large variations. A reliable exclusion of nonspecific effects has not yet been achieved by these protocols. (3) Long‐term treatment: In cobalamin‐responsive patients, most centres use hydroxocobalamin (1–14 mg/week i.m. or 5–20 mg/week orally), while two centres use cyanocobalamin. All cobalamin‐nonresponsive patients and most cobalamin‐responsive patients are supplemented with l‐carnitine (50–100 mg/kg per day). Fourteen centres use intestinal decontamination by antibiotic therapy. Most centres follow D‐A‐CH (n = 6) or Dewey (n = 4) recommendations for protein requirements. Fourteen centres regularly use precursor‐free amino acid supplements. Standardized monitoring protocols are available in seven centres, again showing high variability.
Causes of and diagnostic approach to methylmalonic acidurias
Authors: Fowler B. , Leonard J. V. , Baumgartner M. R.
Published: June 2008

Several mutant genetic classes that cause isolated methylmalonic acidurias (MMAuria) are known based on biochemical, enzymatic and genetic complementation analysis. The mut0 and mut− defects result from deficiency of MMCoA mutase apoenzyme which requires adenosyl‐cobalamin (Ado‐Cbl) as coenzyme. The cblA, cblB and the variant 2 form of cblD complementation groups are linked to processes unique to Ado‐Cbl synthesis. The cblC, cblD and cblF complementation groups are associated with defective methyl‐cobalamin synthesis as well. Mutations in the genes associated with most of these defects have been described. Recently a few patients have been described with mild MMAuria associated with mutations of the MMCoA epimerase gene or with neurological symptoms due to SUCL mutations. A comprehensive diagnostic approach involves investigations at the level of metabolites, genetic complementation analysis and enzymatic studies, and finally mutation analysis. MMA levels in urine range from 10–20 mmol/mol creatinine in mild disturbances of MMA metabolism to over 20000 mmol/mol creatinine in severe MMCoA mutase deficiency, but show considerable overlap and are of limited value for differential diagnosis. The underlying defect in isolated MMAuria can be characterized in cultured skin fibroblasts using several assays, e.g. conversion of propionate to succinate, specific activity of MMCoA, cobalamin adenosyltransferase assay, cellular uptake of CN‐[57Co] cobalamin and its conversion to cobalamin coenzymes and complementation analysis. The reliable characterization of patients with isolated MMAuria pinpoints the correct gene for mutation analysis. Reliable classification of these patients is essential for ongoing and future prospective studies on treatment and outcome.
Movement disorders and inborn errors of metabolism in adults: A diagnostic approach
Authors: Sedel F. , Saudubray J.‐M. , Roze E. , Agid Y. , Vidailhet M.
Published: June 2008

Inborn errors of metabolism (IEMs) may present in adolescence or adulthood with various movement disorders including parkinsonism, dystonia, chorea, tics or myoclonus. Main diseases causing movement disorders are metal‐storage diseases, neurotransmitter synthesis defects, energy metabolism disorders and lysosomal storage diseases. IEMs should not be missed as many are treatable. Here we briefly review IEMs causing movement disorders in adolescence and adults and propose a simple diagnostic approach to guide metabolic investigations based on the clinical course of symptoms, the type of abnormal movements, and brain MRI abnormalities.
Newborn screening for methylmalonic acidurias—Optimization by statistical parameter combination
Authors: Lindner M. , Ho S. , Kölker S. , Abdoh G. , Hoffmann G. F. , Burgard P.
Published: June 2008

With the introduction of tandem mass spectrometry, newborn screening for disorders of propionate metabolism became widely available. However, there is controversy whether population screening for these disorders should be performed. The most widely used primary metabolite C3 itself has a poor specificity or lacks 100% sensitivity for milder forms and/or defects of cobalamin metabolism. Strategies to improve specificity have included the calculation of metabolite ratios (e.g. C3/C2) or second‐tier strategies with analysis of methylmalonic acid or 2‐methylcitric acid from the primary screening specimen. We report the results of a new statistical approach to identify parameter combinations that allow for 100% sensitivity as well as increased specificity. The promising results of this alternative approach will have to be substantiated on larger data sets.
Morphological differentiation of current‐year shoots of deciduous and evergreen lianas in temperate forests in Japan
Authors: Ichihashi Ryuji , Nagashima Hisae , Tateno Masaki
Published: June 2008

Morphological variation in current‐year shoots within plants was examined in five deciduous and four evergreen liana species from temperate forests in Japan to elucidate the role differentiation in shoots. All lianas had both shoots that twined or developed adventitious roots to gain support on host materials (searcher shoots) and self‐supporting shoots with no climbing structures (ordinary shoots). Searcher shoots were 20–295 times longer than ordinary shoots. The allometric relationships between stem length and leaf area differed between searcher and ordinary shoots, and the stem length for a given leaf area was greater in searcher shoots. Leaf area per shoot mass was 1.4–4.3 times higher in ordinary shoots because of the greater allocation to leaf biomass. Searcher shoots comprised only 1–6% of total shoots but 30–85% of total shoot length in deciduous lianas. Ordinary shoots accounted for 70–95% of the total leaf area in these liana species. These results suggest that the exploration of new space was primarily achieved by searcher shoots, whereas a large proportion of current photosynthetic production was achieved by ordinary shoots. The range of stem length and leaf mass ratio of ordinary shoots was similar to that in shoots of tree species. Specialization of shoots in lianas is discussed.
Dispersal, colored environmental noise, and spatial synchrony in population dynamics: analyzing a discrete host–parasitoid population model
Authors: Liu Zhiguang , Gao Meng , Li Zizhen , Liu Hua
Published: June 2008

Spatial synchrony is common, and its influences and causes have attracted the interest of ecologists. Spatially correlated environmental noise, dispersal, and trophic interactions have been considered as the causes of spatial synchrony. In this study, we developed a spatially structured population model, which is described by coupled‐map lattices. Our recent investigation showed that trophic correlation of environmental noise was another important factor that affects spatial synchrony. As a supplement, we considered the influence of the color of the environmental noise on the spatial synchrony in this study. The noise color refers to the temporal correlation in the time series data of the noise, and is expressed as the degree of (first‐order) autocorrelation for autoregressive noise. Patterns of spatial synchrony were considered for stable, periodic (quasi‐periodic), and chaotic population dynamics. Numerical simulations verified that the color of the environmental noise is another mechanism that causes spatial synchrony. Generally, the effect of the color of the noise on the synchrony is dependent on the type of dynamics (stable, cyclic, chaotic) present in the population. For cyclic dynamics, simulation results clearly demonstrate that reddened noise has higher synchrony than white noise. The importance of our research is that it enriches the theory of potential causes of spatial synchrony.