bluuebunny/crossref_metadata_2025 huggingface dataset:
A randomized sequential trial of creatine in amyotrophic lateral sclerosis
Authors: Jan Groeneveld Geert , Veldink Jan H. , van der Tweel Ingeborg , Kalmijn Sandra , Beijer Cornelis , de Visser Marianne , Wokke John H. J. , Franssen Hessel , Berg Leonard H. van den
Published: March 2003

Amyotrophic lateral sclerosis (ALS) is a fatal disease with no cure. In a transgenic mouse model of ALS, creatine monohydrate showed a promising increase in survival. We performed a double‐blind, placebo‐controlled, sequential clinical trial to assess the effect of creatine monohydrate on survival and disease progression in patients with ALS. Between June 2000 and December 2001, 175 patients with probable, probable‐laboratory supported, or definite ALS were randomly assigned to receive either creatine monohydrate or placebo 10gm daily. A sequential trial design was used with death, persistent assisted ventilation, or tracheostomy as primary end points. Secondary outcome measurements were rate of decline of isometric arm muscle strength, forced vital capacity, functional status, and quality of life. The trial was stopped when the null hypothesis of indifference was accepted. Creatine did not affect survival (cumulative survival probability of 0.70 in the creatine group vs 0.68 in the placebo group at 12 months, and 0.52 in the creatine group vs 0.47 in the placebo group at 16 months), or the rate of decline of functional measurements. Creatine intake did not cause important adverse reactions. This placebo‐controlled trial did not find evidence of a beneficial effect of creatine monohydrate on survival or disease progression in patients with ALS. Ann Neurol 2003;53:437–445
Maternal neuronal antibodies associated with autism and a language disorder
Authors: Dalton Paola , Deacon Robert , Blamire Andy , Pike Michael , McKinlay Ian , Stein John , Styles Peter , Vincent Angela
Published: March 2003

Neurodevelopmental disorders could be caused by maternal antibodies or other serum factors. We detected serum antibodies binding to rodent Purkinje cells and other neurons in a mother of three children: the first normal, the second with autism, and the third with a severe specific language disorder. We injected the serum (0.5–1.0ml/day) into pregnant mice during gestation and found altered exploration and motor coordination and changes in cerebellar magnetic resonance spectroscopy in the mouse offspring, comparing with offspring of mice injected with sera from mothers of healthy children. This evidence supports a role for maternal antibodies in some forms of neurodevelopmental disorder. Ann Neurol 2003;53:533–537
Cyclohex‐1‐ene Carboxylic Acids: Synthesis and Biological Evaluation of Novel Inhibitors of Human 5α Reductase
Authors: Baston Eckhard , Salem Ola I. A. , Hartmann Rolf W.
Published: March 2003

In search of novel nonsteroidal mimics of steroidal inhibitors of 5α reductase, 4‐(2‐phenylethyl)cyclohex‐1‐ene carboxylic acids 1—5 were synthesized with different substituents in para position of the phenyl ring (1: N, N‐diisopropylcarbamoyl, 2: phenyl, 3: phenoxy, 4: benzoyl, and 5: benzyl). The principal synthetic approach for the desired compounds consisted of a Wittig olefination between 1, 4‐dioxaspiro [4.5]‐decane‐8‐carbaldehyde (4g and the appropriate phosphonium salts. The compounds were tested for inhibition of human 5α reductase isozymes 1 and 2 using DU 145 cells and preparations from prostatic tissue, respectively. They turned out to be good inhibitors of the prostatic isozyme 2 with compound 1 being the most potent one (IC50 = 760 nM). Isozyme 1 was only slightly inhibited. It is concluded that the novel structures are appropriate for being further optimized, aiming at the development of a novel drug for the treatment of benign prostatic hyperplasia.
Unique reactivity of α,β‐unsaturated carboxylic acid imidazolides: Catalytic asymmetric synthesis of α,β‐epoxy esters and α,β‐epoxy carboxylic acid derivatives
Authors: Nemoto Tetsuhiro , Tosaki Shin‐Ya , Ohshima Takashi , Shibasaki Masakatsu
Published: March 2003

Catalytic asymmetric synthesis of α,β‐epoxy esters and α,β‐epoxy carboxylic acid derivatives is described. Catalytic asymmetric epoxidation of α,β‐unsaturated carboxylic acid imidazolides using La–BINOL–Ph3As=O complex gave the corresponding α,β‐epoxy peroxy tert‐butyl esters, which were directly converted to the α,β‐epoxy methyl esters by adding methanol to the reaction. This catalytic system had broad generality for epoxidation of various substrates. With the use of 5–10 mol% of the catalyst, both β‐aryl and β‐alkyl‐substituted‐α,β‐epoxy methyl esters were obtained in up to 91% yield and in up to 93% enantiomeric excess. In addition, efficient transformations of α,β‐epoxy peroxy tert‐butyl esters into the α,β‐epoxy amides, α,β‐epoxy aldehydes, and γ,δ‐epoxy β‐keto esters are also reported. Chirality 15:306–311, 2003. © 2003 Wiley‐Liss, Inc.
Enantioresolution and absolute configurations of chiral meta‐substituted diphenylmethanols as determined by x‐ray crystallographic and 1H NMR anisotropy methods
Authors: Kosaka Masashi , Sugito Takeo , Kasai Yusuke , Kuwahara Shunsuke , Watanabe Masataka , Harada Nobuyuki , Job Gabriel E. , Shvet Alex , Pirkle William H.
Published: March 2003

meta‐Substituted diphenylmethanols were enantioresolved by the method of chiral phthalic acid yielding enantiopure alcohols. Their absolute configurations were unambiguously determined by X‐ray crystallography of chiral phthalate esters and/or by the 1H NMR anisotropy method using 2‐methoxy‐2‐(1‐naphthyl)propionic acid. Chirality 15:324–328, 2003. © 2003 Wiley‐Liss, Inc.
Stereoselectivity in the oxidation of bufuralol, a chiral substrate, by human cytochrome P450s
Authors: Narimatsu Shizuo , Takemi Chie , Kuramoto Shino , Tsuzuki Daisuke , Hichiya Hiroyuki , Tamagake Keietsu , Yamamoto Shigeo
Published: March 2003

Bufuralol (BF), a nonselective β‐adrenoceptor blocking agent, has a chiral center in its molecule, yielding the enantiomers 1′R‐BF and 1′S‐BF. β‐Adrenoceptor blocking potency is much higher in 1′S‐BF than in 1′R‐BF. One of the metabolic pathways of BF is 1″‐hydroxylation of an ethyl group attached at the aromatic 7‐position forming a carbinol metabolite (1″‐hydroxybufuralol, 1″‐OH‐BF), and further oxidation (or dehydrogenation) produces a ketone metabolite (1‐oxobufuralol, 1″‐Oxo‐BF). Both 1″‐OH‐BF and 1″‐Oxo‐BF are known to have β‐adrenoceptor blocking activities comparable to or higher than those of the parent drug. The 1″‐hydroxylation introduces another chiral center into the BF molecule and four 1″‐OH‐BF diastereomers are formed from BF racemate in mammals, including humans, making elucidation of the metabolic profiles complicated. HPLC methods employing derivatization, reversed phase, or chiral columns have been developed to efficiently separate the four 1″‐OH‐BF diastereomers formed from BF enantiomers or racemate. Accumulated in vitro experimental results revealed that 1′R‐BF is a much more preferential substrate than 1′S‐BR for BF 1″‐hydroxylation in human liver microsomes. Kinetic studies using recombinant human cytochrome P450 (CYP) enzymes indicate that CYP2D6 serves as a major BF 1″‐hydroxylase and that CYP1A2 and CYP2C19 also contribute to BF 1″‐hydroxylation in human livers. This mini‐review summarizes the knowledge reported so far on the pharmacology of BF and its metabolites and the profiles of BF metabolism, especially focusing on the stereoselectivity in the oxidation of BF mainly in human livers and recombinant CYP enzymes. Chirality 15:333–339, 2003. © 2003 Wiley‐Liss, Inc.
Cover Picture: A Facile Synthesis of a Push‐Pull Mixed‐Ligand Pd‐Dithiolene Complex Containing the Et2timdt Ligand (Et2timdt = Monoreduced Diethylimidazolidine‐2,4,5‐trithione) (Eur. J. Inorg. Chem. 7/2003)
Authors: Aragoni M. Carla , Arca Massimiliano , Denotti Carla , Devillanova Francesco A. , Grigiotti Emanuela , Isaia Francesco , Laschi Franco , Lippolis Vito , Pala Luca , Slawin Alexandra M. Z. , Zanello Piero , Woollins J. Derek
Published: March 2003

The cover picture shows the X‐ray structure of [Pd(Et2timdt)Br2] (left; Et2timdt = diethylimidazolidine‐2,4,5‐trithione), obtained by treating the symmetrically substituted dithiolene [Pd(Et2timdt)2] with Br2 or IBr. This complex has been exploited as a starting material for the synthesis of the new mixed‐ligand, push‐pull dithiolene [Pd(Et2timdt)(mnt)] (mnt = maleonitriledithiolate), whose X‐ray molecular structure is depicted on the right. Details are discussed in the Short Communication by M. Arca et al. on p. 1291 ff.
Synthesis and Structure of Two New High Nuclearity Ru/Pt Mixed‐Metal Clusters
Authors: Johnson Brian F. G. , Hermans Sophie , Khimyak Tetyana
Published: March 2003

The reaction of the dianion [Ru5C(CO)14]2− with [PtCl2(MeCN)2] in the presence of silica yields [Ru5PtC(CO)16] (1) and the new compound [PPN]2[Ru10Pt2C2(CO)28] (2), while, in a related reaction, [Ru6C(CO)16]2− undergoes addition of [PtCl2(MeCN)2] to yield the cluster [Ru12PtC2(CO)32(MeCN)2] (3). The high nuclearity compounds 2 and 3 have been fully characterized and their structures determined by single crystal X‐ray analysis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Hydrothermal Synthesis and Characterization of Novel Lanthanide 2,2′‐Diphenyldicarboxylate Complexes
Authors: Wang Yi‐Bo , Zheng Xiang‐Jun , Zhuang Wen‐Juan , Jin Lin‐Pei
Published: March 2003

Lanthanide complexes with a one‐dimensional chain, [Ln2(dpdc)3(H2O)2]n [Ln = La (1), Pr (2), Eu (3), Tb (4); dpdc = 2,2′‐diphenyldicarboxylate] were obtained by hydrothermal reaction of lanthanide(III) chlorides and 2,2′‐diphenyldicarboxylic acid, and characterized by X‐ray diffraction. The crystal structure data reveal that they are isostructural. In the asymmetric unit, the two Ln3+ ions are both eight‐coordinate but they have different coordination environments. Lanthanide ions arranged in a zigzag manner are bridged by the dpdc ligands into a 1‐D chain, while the structure appears like a pinwheel viewed along the c axis. In these complexes, 2,2′‐diphenyldicarboxylate anions exhibit tetradentate and pentadentate coordination modes. A laser‐induced highresolution spectrum (resolution: 0.2 cm−1) of 3 was obtained, which shows two Eu3+ sites in 3. This is in agreement with the results of single‐crystal X‐ray diffraction studies of 3. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Low‐Valent Organobismuth Compounds with Intramolecular Coordination: cyclo‐R3Bi3, cyclo‐R4Bi4, RBi[W(CO)5]2, and R4Bi2 [R = 2‐(Me2NCH2)C6H4]
Authors: Balazs Lucia , Breunig Hans J. , Lork Enno , Silvestru Cristian
Published: March 2003

The cyclobismuthanes RnBin, [R = 2‐(Me2NCH2)C6H4; n = 3 (1a), 4 (1b)] have been synthesised by reduction of RBiCl2 with Na in liquid NH3 or by reaction of R2BiCl with LiAlH4 in Et2O. The reaction of 1a/b with W(CO)5·THF afforded the bismuthinidene complex RBi[W(CO)5]2 (2). R2BiCl reacts with Mg in THF to give the dibismuthane R4Bi2 (3). Single‐crystal X‐ray structure analyses of 1b, 2, and 3 reveal intramolecular coordination of the pendant CH2NMe2 groups to the bismuth atom. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Polypeptide Adsorption on a Synthetic Montmorillonite: A Combined Solid‐State NMR Spectroscopy, X‐ray Diffraction, Thermal Analysis and N2 Adsorption Study
Authors: Gougeon Régis D. , Soulard Michel , Reinholdt Marc , Miehé‐Brendlé Jocelyne , Chézeau Jean‐Michel , Dred Ronan Le , Marchal Richard , Jeandet Philippe
Published: March 2003

Two homopolypeptides, polylysine and polyglutamic acid, were adsorbed on a synthetic montmorillonite clay, in acidic medium. These organic‐inorganic complexes can be heated up to 110 °C without any degradation of the polypeptide. 1H‐13C CP‐MAS NMR spectra show that these polypeptides, which exhibit a mixture of α‐helical and random coil conformations in the bulk, tend to unfold and adopt a more extended random coil structure on adsorption on the phyllosilicate. The values of the basal spacing measured by X‐ray diffraction on dehydrated samples clearly indicate that in the presence of adsorbed polypeptide, the silicate layers do not collapse. The incorporation of polypeptide fragments within the interlayer space is also revealed by the decrease in the specific surface areas measured by N2‐adsorption BET experiments. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Assembly of Hydrogen‐Bonded Organic Layers with Macrocyclic Complexes Acting as Pillars
Authors: Suh Myunghyun Paik , Min Kil Sik , Ko Jung Woo , Choi Hye Jin
Published: March 2003

Novel supramolecular networks of 2D {[Ni(cyclam)][C6H9(COOH)2(COO)]2}n(1) and 3D {[Ni(cyclam)][C6H3(OH)2(COO)]2}n(2) have been constructed by the self‐assembly of [Ni(cyclam)](ClO4)2withcis,cis‐1,3,5‐cyclohexanetricarboxylic acid (H3CTC) and 3,5‐dihydroxybenzoic acid (HDHB), respectively, in py/MeCN/H2O. In the crystal structure of1, each nickel(II) macrocyclic complex binds two H2CTC−ions at the axial sites. The coordinated H2CTC−ions form hydrogen bonds with one another, which results in organic bilayers having macrocyclic complexes as pillars. In the crystal structure of2, each nickel(II) macrocyclic complex binds two DHB−ions in thetransposition. Two free hydroxyl groups and one carbonyl oxygen atom of the coordinated DHB−ion are extensively hydrogen‐bonded with the DHB−ligand of the neighboring complexes, which results in a 3D network where 2D organic layers are linked by the macrocyclic complexes acting as pillars. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Five‐ and Six‐Membered Cobaltocycles with C,P‐Chelating Ligands through Regiospecific Cyclometalation of Mono(2‐Substituted) Triphenylphosphane
Authors: Klein Hans‐Friedrich , Beck Robert , Flörke Ulrich , Haupt Hans‐Jürgen
Published: March 2003

Cyclometalation in the aliphatic ring occurs in the reaction between [CoCH3(PMe3)4] and 5‐(diphenylphosphanyl)‐1,2,3,4‐tetrahydronaphthalene to give [{8‐(diphenylphosphanyl)‐1,2,3,4‐tetrahydronaphthyl‐(C1,P)}tris(trimethylphosphane)cobalt] (1), containing a five‐membered metallacycle as shown in the molecular structure. While 1‐(diphenylphosphanyl)naphthalene reacts accordingly, affording [{8‐(diphenylphosphanyl)naphthyl‐(C1,P)}tris(trimethylphosphane)cobalt] (2), 2‐(diphenylphosphanyl)biphenyl yields ortho‐metalated [{2‐(diphenylphosphanyl)‐3‐phenylphenyl‐(C1,P)}tris(trimethylphosphane)cobalt] (3), containing a four‐membered metallacycle. 1‐(Diphenylphosphanyl)‐8‐methylnaphthalene is metalated in the aliphatic substituent to form [{[8‐(diphenylphosphanyl)naphth‐1‐yl]methyl‐(C,P)}tris(trimethylphosphane)cobalt] (4). The molecular structure shows a trigonal‐bipyramidal configuration of the cobalt atom accommodating a six‐membered metallacycle. 2‐(Diphenylphosphanyl)styrene replaces two trimethylphosphane ligands to give [{2‐(diphenylphosphanyl)styrene‐(C,C‐η2,P)}methylbis(trimethylphosphane)cobalt] (5), avoiding metalation. Replacement of equatorial trimethylphosphane in compounds 1−3 by ethene gives π‐ethene complexes 6−8. In the molecular structure of 7 the C−C vector of the π‐ethene ligand is arranged in the equatorial plane of a trigonal bipyramid. Under 1 bar of CO, compound 2 forms a monocarbonyl complex 9, in which an equatorial carbonyl ligand is found in the molecular structure. Iodomethane transforms 2 into pentacoordinate [{2‐(diphenylphosphanyl)naphthyl‐(C1,P)}iodobis(trimethylphosphane)cobalt] (10) with retention of the metallacycle. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003
Towards an ontology for electronic transaction services
Authors: Adams Nick , Fraser John , Macintosh Ann , McKay‐Hubbard Andy
Published: March 2003

In this paper we present an ontology for transaction services built upon an established ontology for corporate knowledge called the Enterprise Ontology. We introduce the SmartGov platform for the ‘Smart’ deployment of online services for Public Authorities (PAs) whose requirement of a model of PAs has motivated the ontology, and describe our approach to constructing it. After presenting the ontology we then relate it to the pilot application areas in which the SmartGov platform will be trialed and evaluated. Copyright © 2003 John Wiley & Sons, Ltd.
Energies, structures, and electronic properties of molecules in solution with the C‐PCM solvation model
Authors: Cossi Maurizio , Rega Nadia , Scalmani Giovanni , Barone Vincenzo
Published: March 2003

The conductor‐like solvation model, as developed in the framework of the polarizable continuum model (PCM), has been reformulated and newly implemented in order to compute energies, geometric structures, harmonic frequencies, and electronic properties in solution for any chemical system that can be studied in vacuo. Particular attention is devoted to large systems requiring suitable iterative algorithms to compute the solvation charges: the fast multipole method (FMM) has been extensively used to ensure a linear scaling of the computational times with the size of the solute. A number of test applications are presented to evaluate the performances of the method. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 669–681, 2003
Dependence of the rate constants on the treatment of internal rotation modes: The reaction OH + CH3SH → CH3S + H2O as an example
Authors: Masgrau Laura , González–Lafont Àngels , Lluch José M.
Published: March 2003

The title reaction has been used as an example to test the importance of using a hindered rotor treatment instead of a harmonic oscillator model for calculating vibrational partition functions corresponding to low‐frequency internal rotation modes. First, a normal‐mode analysis according to the Ayala and Schlegel's algorithm has been used to identify the internal rotation modes of methanethiol and the transition state structure. Then, after calculation of the energy barrier for each internal rotation, the corresponding hindered rotor partition functions have been calculated following the CW scheme of Chuang and Truhlar. The results show that the anharmonic treatment produces a rather modest improvement of the rate constants at room temperature or below. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 701–706, 2003
Implementation of a general multireference configuration interaction procedure with analytic gradients in a semiempirical context using the graphical unitary group approach
Authors: Koslowski Axel , Beck Michael E. , Thiel Walter
Published: March 2003

The graphical unitary group approach has been applied in an efficient implementation of a general multireference configuration interaction (MRCI) method for use with small active molecular orbital spaces in a semiempirical framework. Gradients can be computed analytically for molecular orbitals from a closed‐shell or a half‐electron open‐shell Hartree‐Fock calculation. CPU times for single point energy and gradient calculations are reported. The code allows MRCI geometry optimizations of large molecules, as illustrated for the singlet ground state and the four lowest triplet states of fullerene C76. © 2003 Wiley Periodicals, Inc. J Comput Chem 6: 714–726, 2003
Prediction of protein secondary structure content by artificial neural network
Authors: Cai Yu‐Dong , Liu Xiao‐Jun , Chou Kuo‐Chen
Published: March 2003

The neural network method was applied to the prediction of the content of protein secondary structure elements, including α‐helix, β‐strand, β‐bridge, 310‐helix, π‐helix, H‐bonded turn, bend, and random coil. The “pair‐coupled amino acid composition” originally proposed by K. C. Chou [J Protein Chem 1999, 18, 473] was adopted as the input. Self‐consistency and independent‐dataset tests were used to appraise the performance of the neural network. Results of both tests indicated high performance of the method. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 727–731, 2003
The single‐vehicle routing problem with unrestricted backhauls
Authors: Süral Haldun , Bookbinder James H.
Published: March 2003

Suppose that a private carrier delivers to a set of customers and also has a number of (optional) backhaul opportunities. It wants to choose the best of these, depending on the revenue generated, and insert them in a revised tour. This will be at an expense of deviation from the original tour, because, here, deliveries need not precede backhauls. The problem is to find the mixed tour whose net cost is the lowest, selecting the most profitable backhauls subject to the overall capacity. We thus generalize several other vehicle routing problems with backhauls. A mixed‐integer model is developed for the problem. It is based on Miller–Tucker–Zemlin subtour elimination constraints. We address several improvement techniques aimed at increasing computational tractability of the formulation. Computational results show that medium‐sized problems can be solved optimally in a reasonable time by using a general‐purpose commercial solver. © 2003 Wiley Periodicals, Inc.
Network flow models for designing diameter‐constrained minimum‐spanning and Steiner trees
Authors: Gouveia Luis , Magnanti Thomas L.
Published: March 2003

We formulate and computationally test several models for the Diameter‐Constrained Minimum Spanning and Steiner Tree Problems, which seek a least‐cost spanning or Steiner tree subject to a (diameter) bound imposed on the number of edges in the tree between any node pair. A traditional multicommodity flow model with a commodity for every pair of nodes was unable to solve a 20‐node and 100‐edge spanning tree problem after 1 week of computation. In contrast, the new models were able to optimality solve this problem in less than 1 second and larger problem instances with up to 100 nodes and 1000 edges. The largest model contains more than 250,000 integer variables and more than 125,000 constraints. The new models simultaneously find a directed tree with a central node or a central edge that serve as a source for the commodities in a multicommodity flow model with hop constraints. Our results demonstrate the power of using single‐sourcing combined with other reformulation techniques: directing the model and using hop‐indexed formulations. Enhancements improve the models when the diameter bound is odd (these situations are more difficult to solve). The linear programming relaxation of the best formulations discussed in this paper always give an optimal integer solution for two special, polynomially solvable cases of the problem. © 2003 Wiley Periodicals, Inc.
Voronoi cell finite difference method for the diffusion operator on arbitrary unstructured grids
Authors: Sukumar N.
Published: March 2003

Voronoi cells and the notion of natural neighbours are used to develop a finite difference method for the diffusion operator on arbitrary unstructured grids. Natural neighbours are based on the Voronoi diagram, which partitions space into closest‐point regions. The Sibson and the Laplace (non‐Sibsonian) interpolants which are based on natural neighbours have shown promise within a Galerkin framework for the solution of partial differential equations. In this paper, we focus on the Laplace interpolant with a two‐fold objective: first, to unify the previous developments related to the Laplace interpolant and to indicate its ties to some well‐known numerical methods; and secondly to propose a Voronoi cell finite difference scheme for the diffusion operator on arbitrary unstructured grids. A conservation law in integral form is discretized on Voronoi cells to derive a finite difference scheme for the diffusion operator on irregular grids. The proposed scheme can also be viewed as a point collocation technique. A detailed study on consistency is conducted, and the satisfaction of the discrete maximum principle (stability) is established. Owing to symmetry of the Laplace weight, a symmetric positive‐definite stiffness matrix is realized which permits the use of efficient linear solvers. On a regular (rectangular or hexagonal) grid, the difference scheme reduces to the classical finite difference method. Numerical examples for the Poisson equation with Dirichlet boundary conditions are presented to demonstrate the accuracy and convergence of the finite difference scheme. Copyright © 2003 John Wiley & Sons, Ltd.
Crack identification of a planar frame structure based on a synthetic artificial intelligence technique
Authors: Shim Mun‐Bo , Suh Myung‐Won
Published: March 2003

It has been established that a crack has an important effect on the dynamic behaviour of a structure. This effect depends mainly on the location and depth of the crack. To identify the location and depth of a crack in a planar frame structure, a method is presented in this paper which uses a synthetic artificial intelligence technique, i.e. adaptive‐network‐based fuzzy inference system (ANFIS) solved via a hybrid learning algorithm (the backpropagation gradient descent and the least‐squares method) and continuous evolutionary algorithms (CEAs) solving single objective optimization problems with a continuous function and continuous search space efficiently are unified. With ANFIS and CEAs it is possible to formulate the inverse problem. ANFIS is used to obtain the input (the location and depth of a crack)–output (the structural eigenfrequencies) relation of the structural system. CEAs are used to identify the crack location and depth by minimizing the difference from the measured frequencies. We have tried this idea on 2D beam structures and the results are promising. Copyright © 2003 John Wiley & Sons, Ltd.
A new fixed‐point algorithm for hardening plasticity based on non‐linear mixed variational inequalities
Authors: Venini P. , Nascimbene R.
Published: March 2003

Moving from the seminal papers of Han and Reddy, we propose a fixed‐point algorithm for the solution of hardening plasticity two‐dimensional problems. The continuous problem may be classified as a mixed non‐linear non‐differentiable variational inequality of the second type and is discretized by means of a truly mixed finite‐element scheme. One of the main peculiarities of our approach is the use of the composite triangular element of Johnson and Mercier for the approximation of the stress field. The non‐differentiability is coped with via regularization whereas the non‐linearity is approached with a fixed‐point iterative strategy. Numerical results are proposed that investigate the sensitivity of the approach with respect to the mesh size and the regularization parameter ε. The simplicity of the proposed fixed‐point scheme with respect to more classical return mapping approaches seems to represent one of the key features of our algorithm. Copyright © 2003 John Wiley & Sons, Ltd.
An arbitrary Lagrangian Eulerian finite‐element approach for fluid–structure interaction phenomena
Authors: Kuhl E. , Hulshoff S. , de Borst R.
Published: March 2003

The present contribution is concerned with the design of a family of consistent fluid–structure interaction algorithms based on a unique temporal and spatial discretization of the governing equations. The characterization of the moving fluid–structure interface is realized by means of the arbitrary Lagrangian Eulerian technique. The spatial discretization is performed with the finite‐element method, whereby either a first‐order upwind scheme or the classical second‐order upwind Petrov–Galerkin technique are used to discretize the linearized fluid equations while the standard Bubnov–Galerkin method is applied to the structural equations. In order to streamline coupling, the structure is discretized in a velocity‐based fashion. The temporal discretization of both the fluid and the structural equations is embedded in the generalized‐α framework by making use of classical Newmark approximations in time. To quantify the sources of error of the proposed algorithms, systematic studies in terms of the one‐dimensional piston model problem are presented. Copyright © 2003 John Wiley & Sons, Ltd.
Race and gender differences in philanthropy: Indiana as a test case
Authors: Mesch Debra J. , Rooney Patrick Michael , Chin William , Steinberg Kathryn S.
Published: March 2003

Rigorous economic research provides clear indications regarding the likelihood of volunteering and giving among demographic groups.
Building learning‐centered communities through public engagement
Authors: Tagle Richard
Published: March 2003

Local education funds can effectively engage their communities to align resources, policies, and public will to provide children and youth with supportive learning environments.
High school after school: Creating pathways to the future for adolescents
Authors: Wynn Joan R.
Published: March 2003

This article proposes a strategy for the use of out‐of‐school time for adolescents, illustrates this strategy in action in Chicago, and discusses the challenges it faces.
Learning with excitement: Bridging school and after‐school worlds and project‐based learning
Authors: Noam Gil G.
Published: March 2003

A bridging typology captures a range of ways that after‐school programs connect children's diverse worlds and support project‐based learning.
A moving horizon technique for the simulation of automobile test‐drives
Authors: Gerdts M.
Published: March 2003

The test‐drive of an automobile along a given test‐course can be modeled by formulation of a suitable optimal control problem. For the numerical solution the optimal control problem is discretized by a direct shooting method and transformed into a finite dimensional nonlinear optimization problem. With increasing length of the test‐course, the dimension of the nonlinear optimization problem increases as well and its numerical solution becomes very difficult due to stability reasons. Therefore a moving horizon technique with reduced range of vision for the test‐driver is introduced. Instead of treating the complete test‐course, a comparatively short local sector is considered on which a corresponding local optimal control problem can be solved comfortably. The local solutions are then combined by suitable transient conditions. A numerical example with a realistic car model is given.
Hypoelasticity‐based analytical stress solutions in the simple shearing process
Authors: Lin R.
Published: March 2003

In the present work a set of hypoelasticity‐based analytical stress solutions of simple shearing is formulated. The rate constitutive equations based on the Jaumann, Green‐Naghdi, Oldroyd, Truesdell, Cotter‐Rivlin, logarithmic and OE‐ and OL‐based stress rates are exploited. From a representation principle of the material spins, a concise formula of the spin tensors for simple shearing is derived. Based on the derived spin equation a novel analytical stress solution related to the OL‐based stress rates is formulated. For completeness the issued stress solutions in conjunction with the other stress rates are also reformulated. All analytical stress solutions are illustrated and compared.
Effects of viscosity on linear gravity waves due to surface disturbances in water of finite depth
Authors: Bandyopadhyay A.
Published: March 2003

The three‐dimensional problem of waves due to an arbitrary initial time‐dependent surface pressure together with an elevation of the surface in a viscous fluid of constant finite depth h is examined. It is shown that the multiple‐integral expression for the surface displacement ζ is reducible to one which is correct to terms of order O(ν'), ν' = ν/(4gh3)1/2, for small coefficient of viscosity ν, under certain conditions. When the Laplace inversion is completed in ζ we arrive at new results which differ significantly from those obtained in an earlier analysis of the problem by Nikitin and Potetyunko [1].
Response of a diffusion‐wave system subjected to deterministic and stochastic fields
Authors: Agrawal O.P.
Published: March 2003

This paper presents a general analytical technique for a Fractional Diffusion‐Wave (FDW) system subjected to a non‐homogeneous field, which can be deterministic or stochastic. In this formulation, the response of the system is written as a linear combination of the eigenfunctions which are identified using the method of separation of variables. The properties of the eigenfunctions are used to reduce the FDW equation defined in space‐time domain into a set of infinite Fractional Differential Equations (FDEs) defined in the time domain only. A Laplace transform technique is used to obtain the fractional Green's function and a Duhamel integral type expression for the system's response. For a stochastic analysis, the input field is treated as a random process with specified mean and correlation functions. An expectation operator is applied on a set of expressions to obtain the stochastic characteristics of the system. Several special cases are discussed and numerical results are presented to show the deterministic and stochastic response of FDW systems. When the order of the fractional derivative of the equation is <1, 1, >1, and 2 the equation represents a model of a sub‐diffusion, a diffusion, a diffusion‐wave propagation, and a wave propagation system, respectively. Thus the formulation provides a unified approach for stochastic analysis of all these systems. The approach can be equally applied to all those systems for which the existence of eigenmodes is guaranteed.
Detection of Intestinal Ischemia Using a Microdialysis Technique in an Animal Model
Authors: Sommer Thorbjorn , Larsen Jens Fromholt
Published: March 2003

Abstract

The purpose of this study was to use a microdialysis technique to demonstrate the metabolic changes that occur in the intestinal wall during ischemia in vivo. Continuous monitoring of glucose, lactate, and glycerol using a microdialysis technique was performed in the jejunal wall of 10 pigs during steady‐state and occlusive ischemia. The microdialysis catheters were introduced 50, 80, and 110 cm from the ligament of Treitz. Occlusive ischemia was established to two segments after steady state was reached. Microdialysate samples were collected from ischemic/nonischemic intestinal segments simultaneously every 20 minutes. For comparison with the microdialysis measurements, systemic blood samples were drawn from the cannulated femoral artery and analyzed consecutively. A significant increase of microdialysate lactate and a significant decrease of microdialysate glucose were found during occlusive ischemia as compared to the preischemic samples and samples from the nonischemic control catheters. The microdialysate glycerol increased during ischemia, but later than the lactate. No changes were observed in systemic serum lactate, serum glucose, pH, pco2, and po2, but serum potassium increased by 1.1 mmole (median) during ischemia. Microdialysis measured in the intestinal wall identifies local ischemia and may be a new method for the monitoring of intestinal perfusion.
Reconstruction after Distal Gastrectomy by Interposition of a Double‐jejunal Pouch Using a Triangulating Stapling Technique
Authors: Ikeda Masami , Ueda Tetsuro , Yamagata Kuniyoshi , Takatsuka Jun , Yamaguchi Muneyuki , Shiba Tadaaki
Published: March 2003

Abstract

Sustaining good nutrition and preventing postgastrectomy syndrome are important for increasing the quality of life after distal gastrectomy. Many surgeons have proposed surgical methods designed to enhance long‐term patient quality of life. An immediate, safe method based on current physiologic reconstructive principles shown to reduce postoperative patient complaints is presented. A reconstructive method using a modified interpositioned double‐jejunal pouch after distal gastrectomy in 18 cancer patients was reviewed. This method uses a triangulating stapling technique with wide end‐to‐side anastomosis between the residual stomach and the pouch. In all patients, the anastomosis site was without leakage or stenosis, and there were no episodes of severe reflux esophagitis, residual gastritis, or dumping syndrome. The mean pooling rate was 44.2%, and emptying half‐time was 73.0 minutes. After 2 years the body weight was 91.3% of the preoperative weight, the food volume was 89.2% of normal intake, and meal frequency was 3.0 per day. This method of reconstruction is useful for immediate and safe creation of a wide anastomosis between the residual stomach and the double‐jejunal pouch after distal gastrectomy and in the prevention of esophagitis and residual gastritis.
Novel insights into cadherin processing by subtilisin‐like convertases
Authors: Posthaus Horst , Dubois Claire M , Müller Eliane
Published: March 2003

Proprotein convertases (PCs) are known to activate many important molecules and their overexpression plays a significant role in tumor progression. Only little is known about the involvement of PCs in the processing of cadherin adhesion molecules, which are potent tumor suppressors. Here we show in a baculovirus overexpression system that the desmosomal cadherins Dsg1 and Dsg3 are substrates for the PC furin. Accordingly, inhibition of PCs in differentiating mouse keratinocytes by α1‐anti‐trypsin Portland (α1‐PDX) negatively interfered with pro‐epithelial (proE)‐cadherin processing, but unexpectedly also resulted in a dramatic reduction of E‐cadherin, Dsg1 and Dsg3 protein and Dsg1 mRNA. Because loss of intercellular adhesion is a rate‐limiting step in the transition from benign to malignant tumors, these results have significant implications for the use of PC inhibitors as possible therapeutic tools.
Cyclin B1 transcription is enhanced by the p300 coactivator and regulated during the cell cycle by a CHR‐dependent repression mechanism
Authors: Wasner Mark , Tschöp Katrin , Spiesbach Katja , Haugwitz Ulrike , Johne Cindy , Mössner Joachim , Mantovani Roberto , Engeland Kurt
Published: March 2003

Cyclin B is a central regulator of transition from the G2 phase of the cell cycle to mitosis. In mammalian cells two B‐type cyclins have been characterised, cyclin B1 and B2. Both are expressed with a maximum in G2 and their synthesis is mainly regulated on the transcriptional level. We show that a single cell cycle genes homology region, lacking a functional cell cycle‐dependent element in tandem with it, contributes most of the cell cycle‐dependent transcription from the cyclin B1 promoter. The coactivator p300 binds to the cyclin B1 promoter and synergises with the transcription factor NF‐Y in activating transcription of cyclin B1.
Identification of a mitochondrial glycerol‐3‐phosphate dehydrogenase from Arabidopsis thaliana: evidence for a mitochondrial glycerol‐3‐phosphate shuttle in plants
Authors: Shen Wenyun , Wei Yangdou , Dauk Melanie , Zheng Zhifu , Zou Jitao
Published: March 2003

We report molecular characterization of an Arabidopsis gene encoding a mitochondrial FAD‐dependent glycerol‐3‐phosphate dehydrogenase (FAD‐GPDH) that oxidizes glycerol‐3‐phosphate (G‐3‐P) to dihydroxyacetone phosphate. We demonstrate through in vitro targeting assays that the encoded gene product can be imported into mitochondrial membrane systems. Enzyme activity of the protein was confirmed through heterologous expression in Escherichia coli. The Arabidopsis gene is expressed throughout plant development, but at the highest level during seed germination. We also show that expression of the Arabidopsis FAD‐GPDH gene is coupled to oxygen consumption and affected by ABA and stress conditions. Together with an NAD+‐dependent GPDH, this enzyme could form a G‐3‐P shuttle, as previously established in other eukaryotic organisms, and links cytosolic G‐3‐P metabolism to carbon source utilization and energy metabolism in plants.
Involvement of NF‐Y and Sp1 binding sequences in basal transcription of the human telomerase RNA gene
Authors: Zhao Jiangqin , Bilsland Alan , Hoare Stacey F. , Keith W.Nicol
Published: March 2003

The proximal promoter of the telomerase RNA gene, hTR, contains four Sp1 sites and one CCAAT box. We have carried out a functional analysis of the role of these sequence elements. Two Sp1 sites downstream of the CCAAT box mediated negative regulation, while the other two Sp1 sites were positive regulators with the strongest effect mediated by the negative regulatory Sp1 site closely flanking the CCAAT box. Basal transcriptional activity is maintained via the CCAAT box even when all four Sp1 sites are mutated, suggesting nuclear factor‐Y (NF‐Y) is a fundamental regulator of hTR promoter function. Chromatin immunoprecipitation revealed binding of NF‐Y, Sp1 and TFIIB to the promoter in vivo. Thus the interaction of NF‐Y at the CCAAT box is pivotal to hTR gene transcription and surrounding sequence elements may provide an environment for the regulation of activity through recruitment of additional protein complexes.
The kinetics of V–J joining throughout 3.5 megabases of the mouse Igκ locus fit a constrained diffusion model of nuclear organization
Authors: Li Shuyu , Garrard William T
Published: March 2003

To gain insight into the nuclear organization of the mouse Igκ locus and how it may relate to the formation of synapses during recombination, we have studied the kinetics of rearrangement of different Vκ gene families to Jκ gene segments in the pre‐B cell line, 103bcl2. Remarkably, Vκ gene families separated by more than 3.5 Mb from Jκ gene segments rearranged with nearly identical kinetics to those as close as 18 kb to Jκ gene segments. These results fit a model of nuclear organization in which the entire VκJκ region resides within a single nuclear subcompartment and is capable of exhibiting multiple reversible contacts through diffusion and Brownian motion.
Detection of bound and free IGF‐1 and IGF‐2 in human plasma via biomolecular interaction analysis mass spectrometry
Authors: Nedelkov Dobrin , Nelson Randall W. , Kiernan Urban A. , Niederkofler Eric E. , Tubbs Kemmons A.
Published: March 2003

Insulin like growth factor (IGF)‐1 and IGF‐2 were assayed from human plasma via biomolecular interaction analysis mass spectrometry, utilizing antibodies as ligands for affinity retrieval. Detection of both targeted and non‐targeted IGFs in the mass spectra indicated possible protein complex retrieval by the individual antibodies. A series of control experiments eliminated the possibility of analyte cross‐walking between flow cells, significant antibodies cross‐reactivity, and direct IGF interactions. To disrupt the putative protein complex and release its constituent proteins, plasma samples were treated with detergents. An SDS‐treated plasma yielded IGF signals in a different ratio than the one observed in the mass spectra from the non‐treated plasma, suggesting disruption of the protein complex, and its retrieval from non‐treated plasma. Novel truncated IGF‐2 variant, missing its N‐terminal Alanine, was detected in all mass spectra.
NHERF‐1 uniquely transduces the cAMP signals that inhibit sodium–hydrogen exchange in mouse renal apical membranes
Authors: Weinman Edward J , Steplock Deborah , Shenolikar Shirish
Published: March 2003

Sodium–hydrogen exchanger regulatory factor isoform‐1 (NHERF‐1) and NHERF‐2 are two structurally related PDZ‐domain‐containing protein adapters that effectively transduce cyclic AMP (cAMP) signals that inhibit NHE3, the sodium–hydrogen exchanger isoform present at the apical surface of kidney and gut epithelia. The mouse renal proximal tubule expresses both NHERF isoforms, suggesting their redundant functions as regulators of renal electrolyte metabolism. To define the role of NHERF‐1 in the physiological control of NHE3, we analyzed NHE3 activity in isolated brush border membrane (BBM) preparations from renal proximal tubules of wild‐type (WT) and NHERF‐1 (−/−) mice. Basal Na+–H+ exchange was indistinguishable in BBMs from WT and NHERF‐1 (−/−) mice (0.96±0.08 and 0.95±0.10 nmol/mg protein/10 s, respectively). Activation of membrane bound cAMP‐dependent protein kinase (PKA) by cAMP inhibited NHE3 activity in WT BBMs (0.55±0.07 nmol/mg protein/10 s or 40±9%, P<0.01) but had no discernible effect on Na+–H+ exchange in the NHERF‐1 (−/−) BBM (0.97±0.07 nmol/mg protein/10 s; P=not significant). This was associated with a significant decrease in cAMP‐stimulated phosphorylation of NHE3 immunoprecipitated from solubilized NHERF‐1 (−/−) BBMs. As the protein levels for NHE3, NHERF‐2, PKA and ezrin were not changed in the NHERF‐1 (−/−) BBMs, the data suggest a unique role for NHERF‐1 in cAMP‐mediated inhibition of NHE3 activity in the renal proximal tubule of the mouse.
The hypolipidemic drug metabolites nafenopin‐CoA and ciprofibroyl‐CoA are competitive P2Y1 receptor antagonists
Authors: Coddou Claudio , Loyola Gloria , Boyer José Luis , Bronfman Miguel , Huidobro-Toro J.Pablo
Published: March 2003

Coenzyme A (CoA‐SH), endogenous and drug‐derived CoA‐derivatives were tested as putative antagonists of P2Y receptors expressed in Xenopus laevis oocytes, a method used to determine calcium‐activated chloride current, an indicator of the activation of these receptors. CoA‐SH antagonized reversibly and in a concentration‐dependent manner the ATP‐gated currents evoked by the human P2Y1 but not the P2Y2 receptor. Palmitoyl‐CoA was four‐fold more potent than CoA‐SH as an antagonist while palmitoyl‐carnitine was inactive, highlighting the role of the CoA‐SH moiety in the antagonism. The CoA derivatives of nafenopin and ciprofibrate, two clinically relevant hypolipidemic drugs, increased 13 and three‐fold the potency of CoA‐SH, respectively. The K
Bs of nafenopin‐CoA and ciprofibroyl‐CoA were 58 and 148 nM, respectively; the slopes of the Schild plots were unitary. Neither 100 μM nafenopin nor ciprofibrate alone altered the P2Y1 receptor activity. Neither CoA‐SH nor ciprofibroyl‐CoA antagonized the rat P2X2 or the P2X4 nucleotide receptors nor interacted with the 5‐HT2A/C receptors. The bulky drug CoA‐SH derivatives identify a hydrophobic pocket, which may serve as a potential target for novel selective P2Y1 antagonists.
Essential role of protein kinase Cζ in the impairment of insulin‐induced glucose transport in IRS‐2‐deficient brown adipocytes
Authors: Arribas Mónica , Valverde Angela M , Burks Deborah , Klein Johannes , Farese Robert V , White Morris F , Benito Manuel
Published: March 2003

Insulin receptor substrate‐2‐deficient (IRS‐2−/−) mice develop type 2 diabetes. We have investigated the molecular mechanisms by which IRS‐2−/− immortalized brown adipocytes showed an impaired response to insulin in inducing GLUT4 translocation and glucose uptake. IRS‐2‐associated phosphatidylinositol 3‐kinase (PI 3‐kinase) activity was blunted in IRS‐2−/− cells, total PI 3‐kinase activity being reduced by 30%. Downstream, activation of protein kinase C (PKC) ζ was abolished in IRS‐2−/− cells. Reconstitution with retroviral IRS‐2 restores IRS‐2/PI 3‐kinase/PKCζ signalling, as well as glucose uptake. Wild‐type cells expressing a kinase‐inactive mutant of PKCζ lack GLUT4 translocation and glucose uptake. Our results support the essential role played by PKCζ in the insulin resistance and impaired glucose uptake observed in IRS‐2‐deficient brown adipocytes.
Synthetic and structural studies on Pyrularia pubera thionin: a single‐residue mutation enhances activity against Gram‐negative bacteria
Authors: Vila-Perelló Miquel , Sánchez-Vallet Andrea , Garcı́a-Olmedo Francisco , Molina Antonio , Andreu David
Published: March 2003

The thionin from Pyrularia pubera (Pp‐TH), a 47‐residue peptide with four internal disulfide bonds, was efficiently produced by chemical synthesis. Its antimicrobial activity in vitro against several representative pathogens (EC50=0.3–3.0 μM) was identical to that of natural Pp‐TH. This peptide has a unique Asp32 instead of the consensus Arg found in other thionins of the same family. In order to evaluate the effect of this mutation, the Arg32 analogue (Pp‐TH(D32R)) was also synthesized and showed a significant increase in antibiotic activity against several Gram‐negative bacteria, whereas it retained the same activity against other pathogens. The overall structure of Pp‐TH(D32R) was maintained, though a slight decrease in the helical content of the peptide was observed.