bluuebunny/crossref_metadata_2025 huggingface dataset:
Promoting social initiation in children with autism using video modeling
Authors: Nikopoulos Christos K. , Keenan Michael
Published: March 2003

A large number of studies have shown that children and youths with autism can improve their social skills when provided with appropriate and well planned treatment strategies. Here, a video modeling procedure was implemented with seven developmentally delayed children, using a multiple‐treatment design. Each child watched a videotape showing a model and the experimenter engaged in a simple social interactive play in an adapted play setting. Afterwards each child's behavior was assessed in this setting, while the experimenter's behavior remained the same as that shown in the videotape. The video modeling training enhanced the social initiation skills of four children. It also facilitated appropriate play engagement, which generalized across settings, peers, and toys. These changes maintained after a 1‐ and 2‐month follow‐up period. The intervention was evaluated as a time‐efficient teaching tool as well as a means of enhancing appropriate play skills. Copyright © 2003 John Wiley & Sons, Ltd.
Combination of extinction and protective measures in the treatment of severely self‐injurious behavior
Authors: Yang Lizen J.
Published: March 2003

Two female adolescents with profound mental retardation and physical disabilities residing in a state facility exhibited self‐injurious behavior (SIB). They had been wearing restrictive mechanical restraints for more than two years to prevent injuries from occurring. By using an indirect method of functional analysis, social attention was found to be the factor reinforcing and maintaining their behaviors. Extinction in combination with non‐intrusive protective measures was selected as the intervention strategy to reduce SIB. The outcomes of the treatment were evaluated with an AB probe design. Incidents of SIB decreased quickly and sharply after the treatment began. Once the incidents had reached a level of zero for three consecutive sessions, a six‐month follow‐up was started. No SIB was observed or reported during the follow‐up. The advantages of using extinction, especially in conjunction with the non‐intrusive protective measures to treat SIB, are discussed. Copyright © 2003 John Wiley & Sons, Ltd.
Additive concentration effects on enantioselective separations in supercritical fluid chromatography
Authors: Phinney Karen W. , Sander Lane C.
Published: March 2003

Polar additive concentration effects in supercritical fluid chromatography were studied on chiral stationary phases having either a macrocyclic glycopeptide or a derivatized polysaccharide as the chiral selector. Two basic additives, isopropylamine and triethylamine, were incorporated into the methanol modifier at various concentrations and the effects on retention, selectivity, and resolution were monitored. Many of the analytes failed to elute from the macrocyclic glycopeptide stationary phase in the absence of an additive and the most noticeable effect of increasing additive concentration was a significant decrease in retention. On the derivatized polysaccharide stationary phase the additives had little effect on retention, but they did foster significant improvements in peak shape and resolution. Chirality 15:287–294, 2003. Published 2003 Wiley‐Liss, Inc.
Enantiospecific disposition of pranoprofen in beagle dogs and rats
Authors: Imai Teruko , Nomura Tadayuki , Aso Mayumi , Otagiri Masaki
Published: March 2003

The pharmacokinetic characteristics of pranoprofen enantiomer were examined and compared with the disposition of the corresponding isomer after the administration of racemic pranoprofen to beagle dogs and rats. The plasma levels of (+)‐(S)‐isomer were significantly higher than those of (–)‐(R)‐isomer in dogs and rats by either intravenous or oral administration. Although the oral bioavailability and absorption rate constant between the (–)‐(R)‐ and (+)‐(S)‐form was the same, the elimination rate constant of the (+)‐(S)‐form was significantly lower than that of the (–)‐(R)‐form in both dogs and rats. This discrepancy can be explained on the basis of differences in protein binding and the metabolism of the two enantiomers. The (–)‐(R)‐isomer was predominantly conjugated depending on its higher free plasma level and its faster metabolic rate than the (+)‐(S)‐form, and thus was excreted more rapidly in the urine and bile in the form of pranoprofen glucuronide. Furthermore, a (–)‐(R)‐ to (+)‐(S)‐inversion occurred to the extent of 14% in beagle dogs, but not in rats. This chiral inversion might be an important factor in the slow elimination of the (+)‐(S)‐form in dogs. The most efficient organ for chiral inversion was the liver, followed by kidney and intestine. Chirality 15:312–317, 2003. © 2003 Wiley‐Liss, Inc.
Convenient method for determining the absolute configuration of chiral alcohols with racemic 1H NMR anisotropy reagent, MαNP acid: Use of HPLC‐CD detector
Authors: Kasai Yusuke , Watanabe Masataka , Harada Nobuyuki
Published: March 2003

A convenient method for determining the absolute configuration of chiral secondary alcohols using the racemic NMR anisotropy reagent, (±)‐2‐methoxy‐2‐(1‐naphthyl)propionic acid [(±)‐MαNP acid], and an HPLC‐CD detector was developed. The method was successfully applied to some chiral alcohols derived from (–)‐α‐santonin. Chirality 15:295–299, 2003. © 2003 Wiley‐Liss, Inc.
Chiral inversion of the second generation IMiD™ CC‐4047 (ACTIMID™) in human plasma and phosphate‐buffered saline
Authors: Teo Steve K. , Chen Yong , Muller George W. , Chen Roger S. , D. Thomas Steve , Stirling David I. , Chandula Reddy S.
Published: March 2003

CC‐4047 is a racemic second‐generation immunomodulatory drug currently in clinical development for various oncologic indications. It has potent effects on key cytokines including tumor necrosis factor‐α, interleukin (IL‐10), and interferon (IFN‐γ). The S‐isomer of CC‐4047 has been reported to be the more potent enantiomer of the racemate. In this article we report on the rapid racemization of the S‐isomer of CC‐4047 in human plasma and phosphate‐buffered saline. These results support the further development of the racemate instead of the S‐isomer. Chirality 15:348–351, 2003. © 2003 Wiley‐Liss, Inc.
A DFT Study of Tin‐ and Crown‐Ether‐Based Host Molecules Capable of Binding Anions and Cations Simultaneously
Authors: Vivas‐Reyes Ricardo , De Proft Frank , Biesemans Monique , Willem Rudolph , Geerlings Paul
Published: March 2003

DFT calculations are reported for a series of tin‐ and crown‐ether‐based host compounds {i.e., the trimethyl derivatives [18]‐crown‐6‐C6H3COOSn(CH3)3and [15]‐crown‐5‐C6H3COOSn(CH3)3} capable of binding cations and anions simultaneously. The B3LYP functional together with the 6‐31G* basis set was used for the atoms C, H, N, O, S, Na and K and the 3‐21G* basis set for Sn in order to obtain insights into the factors determining the nature of the interactions of these compounds with the neutral molecules acetone and H2O, the SCN−anion, and the Na+and K+cations. The interaction strength pattern with these molecules was explained by the use of a series of reactivity descriptors such as the Fukui function, hardness, local softness, and the MEP (molecular electrostatic potential). In all cases studied in this paper, the complexes with Na+were more stable than those with K+, correlating with the size of the cation and the volume available in the crown ether. Moreover, this finding is also in accordance with the greater hardness of Na+relative to K+, in combination with the hard environment of the crown ether moiety. This region was also analysed by computation of electrostatic potentials, which showed that highly negative values are associated with the inside region of the cavity of the crown, this region thus being amenable to electrophilic attack. The HSAB principle, characterising the reactive sites on the basis of local softness and the Fukui function, provided a firm explanation of the reactivity of the tin atom of the crown ether benzocarboxylate towards SCN−, acetone and water. The HSAB concept was also successfully used to explain the preference of the tin atoms in both crown ethers to bind with the nitrogen atom rather than the sulfur atom of SCN−. This result is a confirmation that the tin atoms in the compounds under consideration behave as hard atoms. Overall, these results fit remarkably well with previous experimentally measured NMR spectroscopy data and demonstrate that the interactions of this kind of molecules can be predicted and interpreted by the use of DFT calculations and DFT‐based reactivity descriptors, as well as MEP calculations. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Direct Synthesis of (PhSe)4Ge and (PhTe)4Ge from Activated Hydrogenated Germanium − Crystal Structure and Twinning of (PhTe)4Ge
Authors: Schlecht Sabine , Friese Karen
Published: March 2003

The germanium chalcogenolates (PhSe)4Ge and (PhTe)4Ge were synthesized from activated hydrogenated germanium (Ge*) and diphenyldiselenide or diphenylditelluride, respectively. (PhTe)4Ge is the first homoleptic organotellurolate of germanium. It was characterized spectroscopically and by X‐ray crystal structure analysis. (PhTe)4Ge crystallizes in the monoclinic space group P21/c with a = 12.8018(14), b = 9.1842(9), c = 23.690(3) Å and β = 105.458(8)°. The molecules show a tetrahedral GeTe4 core. Weak Te‐Te interactions connect neighbouring tetrahedra to infinite helices along [010]. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
Web usage mining approaches to page recommendation and restructuring
Authors: Ishikawa Hiroshi , Ohta Manabu , Yokoyama Shohei , Nakayama Junya , Katayama Kaoru
Published: March 2003

As an increasing number of Web sites such as e‐businesses consist of an increasing number of pages, users find it more difficult to rapidly reach their own target pages. Ill‐structured design of Web sites also prevents the users from rapidly accessing the target pages. In this paper, we describe two complementary approaches to Web usage mining as a key solution to these issues. First, we describe an adaptable recommendation system called the L‐R system, which constructs user models by classifying the Web access logs and by extracting access patterns based on the transition probability of page accesses and recommends the relevant pages to the users based on both the user models and the Web structures. We have evaluated the prototype system and have obtained the positive effects. Second, we describe another approach to constructing user models, which clusters Web access logs based on access patterns. The user models also help to discover unexpected access paths corresponding to ill‐formed Web site design. Copyright © 2003 John Wiley & Sons, Ltd.
Mechanistic insights into oxidosqualene cyclizations through homology modeling
Authors: Schulz–Gasch Tanja , Stahl Martin
Published: March 2003

2,3‐Oxidosqualene cyclases (OSC) are key enzymes in sterol biosynthesis. They catalyze the stereoselective cyclization and skeletal rearrangement of (3S)‐2,3‐oxidosqualene to lanosterol in mammals and fungi and to cycloartenol in algae and higher plants. Sequence information and proposed mechanism of 2,3‐oxidosqualene cyclases are closely related to those of squalene‐hopene cyclases (SHC), which represent functional analogs of OSCs in bacteria. SHCs catalyze the cationic cyclization cascade converting the linear triterpene squalene to fused ring compounds called hopanoids. High stereoselectivity and precision of the skeletal rearrangements has aroused the interest of researchers for nearly half a century, and valuable data on studying mechanistic details in the complex enzyme‐catalyzed cyclization cascade has been collected. Today, interest in cyclases is still unbroken, because OSCs became targets for the development of antifungal and hypocholesterolemic drugs. However, due to the large size and membrane‐bound nature of OSCs, three‐dimensional structural information is still not available, thus preventing a complete understanding of the atomic details of the catalytic mechanism. In this work, we discuss results gained from homology modeling of human OSC based on structural information of SHC from Alicyclobacillus acidocaldarius and propose a structural model of human OSC. The model is in accordance with previously performed experimental studies with mechanism‐based suicide inhibitors and mutagenesis experiments with altered activity and product specificity. Structural insight should strongly stimulate structure‐based design of antifungal or cholesterol‐lowering drugs. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 741–753, 2003
Free energy perturbation and molecular dynamics calculations of copper binding to azurin
Authors: Pappalardo Matteo , Milardi Danilo , Grasso Domenico M. , La Rosa Carmelo
Published: March 2003

Free energy perturbation/molecular dynamics simulations have been carried out on copper/azurin systems calculating the binding affinities of copper (II) ion to azurin either in the native or in the unfolded state. In order to test the validity of the strategy adopted for the calculations and to establish what force field is suitable for these kinds of calculations, three different force fields, AMBER, CVFF, and CFF, have been alternatively used for the calculations and the results have been compared with experimental data obtained by spectroscopic titrations of copper (II)/azurin solutions and denaturation experiments. Our findings have pointed out that only CFF gives satisfactory results, thus providing a reliable tool for copper binding simulations in copper protein. © 2003 Wiley Periodicals, Inc. J Comput Chem 6: 779–785, 2003
Balanced network flows. VIII. A revised theory of phase‐ordered algorithms and the O( $\bf\it\sqrt{n}m$ log(n2/m)/log n) bound for the nonbipartite cardinality matching problem
Authors: Fremuth‐Paeger Christian , Jungnickel Dieter
Published: March 2003

This paper closes some gaps in the discussion of nonweighted balanced network flow problems. These gaps all concern the phase‐ordered augmentation algorithm, which can be viewed as the matching counterpart of the Dinic max‐flow algorithm. We show that this algorithm runs in O(n2m) time compared to the bound of O(nm2) derived in Part III of this series and that the bipartiteness requirement can be omitted. The result which deserves attention is the complexity bound for the cardinality matching problem which was shown for the bipartite case by Feder and Motwani. This bound was previously claimed for the general case in a preprint of Goldberg and Karzanov but omitted in later versions of this paper. © 2003 Wiley Periodicals, Inc.
The potential impact of proposed government funding for faith‐based philanthropy
Authors: Guellich Margaret
Published: March 2003

Key factors need to be considered when discussing the capacity of faith‐based organizations to manage government funding.
Wheat Starch Gelatinization — the Effects of Sucrose, Emulsifier and the Physical State of the Emulsifier
Authors: Richardson Gisela , Langton Maud , Bark Axel , Hermansson Anne‐Marie
Published: March 2003

The effect of emulsifier and/or sucrose on the swelling of an 8% wheat starch dispersion was evaluated by microscopy. Visual observations of smeared starch pastes under the light microscope, image analysis of the starch granule sizes and viscosity measurements of the starch paste during heating were combined to explain the effects of the added ingredients.

Sucrose (12 or 24%, w/w) was shown to delay the swelling of the granules at least up to 50 °C. Above this temperature, the leakage of amylose and granule fragmentation were delayed, but the swelling itself seemed to be accelerated. The polyglycerol ester emulsifier (PGE/MG) at concentrations of 0.5 and 4.0% hindered amylose leakage completely up to 90 °C, followed by a sudden granule rupture. The size of the granules increased up to about 70 °C, but not above this temperature. The monoglyceride (MG) emulsifier in α‐form already had a restrictive effect on the swelling at low temperatures, while the same emulsifier in β‐form did not restrict the swelling until higher temperatures were reached. The emulsifier itself converted into the lamellar state at between 55 and 70 °C, irrespective of the initial form, but the final viscosity was higher in the paste with MG in β‐form. Thus, the initial physical state of the emulsifier was shown to have an influence on the final properties of the gel.
A semi‐smooth Newton method for constrained linear‐quadratic control problems
Authors: Hintermüller M. , Stadler G.
Published: March 2003

Es wird ein verallgemeinertes Newton‐Verfahren für die numerische Lösung von linear‐quadratischen Optimalsteuerprozessen mit zweiseitigen Restriktionen an die Steuerung eingeführt und analysiert. Bedingungen werden hergeleitet, unter denen der Algorithmus global konvergiert. Unter Verwendung von Glättungseigenschaften des Lösungsoperators der Zustandsgleichung und einem verallgemeinerten Ableitungsbegriff lassen sich lokal superlineare Konvergenzeigenschaften nachweisen. Umfassende numerische Tests unterstützen die theoretischen Ergebnisse, beweisen die Effizienz des neuen Verfahrens und liefern einen numerischen Nachweis für die Gitterunabhängigkeit des Algorithmus.

A semi‐smooth Newton method for the numerical solution of linear‐quadratic optimal control problems with bilateral control constraints is introduced and analyzed. Conditional global convergence results are proved. Based on the smoothing property of the control‐to‐state operator and on generalized derivatives locally superlinear convergence is established. A report on comprehensive numerical tests supports the theoretical results, proves the efficiency of the new algorithm, and allows to argue mesh‐independence.
The Courant‐Herrmann conjecture
Authors: Gladwell G.M.L. , Zhu H.
Published: March 2003

The Courant‐Herrmann Conjecture (CHC) concerns the sign properties of combinations of the Dirichlet eigenfunctions of elliptic pde's, the most important of which is the Helmholtz equation $\Delta u + \lambda \rho u = 0$ for \documentclass{article}\usepackage{amssymb}\pagestyle{empty}\begin{document}$D \in \mathbb{R}^N$\end{document}. If the eigenvalues are ordered increasingly, CHC states that the nodal set of a combination $v = \sum_{i=1}^nc_iu_i$ of the first $n$ eigenfunctions, divides $D$ into no more than $n$ sign domains in which $v$ has one sign. The conjecture is classically known to hold for $N=1$, we conjecture that it is true for rectangular boxes in \documentclass{article}\usepackage{amssymb}\pagestyle{empty}\begin{document}$\mathbb{R}^N (N\geq2)$\end{document}, but show that it is false in general.
Impact of Perioperative Treatment of Recombinant Human Growth Hormone on Cell Immune Function and Intestinal Barrier Function: Randomized, Double‐blind, Controlled Trial
Authors: Liu Wei , Jiang Zhu , Wang Xiu , Shu Hong , Cui Wei , Wilmore Douglas W.
Published: March 2003

Abstract

The objective of this study was to evaluate the effects of recombinant human growth hormone (GH) on cell immune function, intestinal barrier function, and outcome. A placebo‐controlled randomized double‐blind trial was performed, with 20 patients undergoing abdominal surgery enrolled in the study. The patients in the study group received GH (0.3 IU/kg/day) subcutaneously from day 3 before operation until day 7 after operation. The patients in the control group received placebo injections. All the patients were given isonitrogenic (0.15 g N/kg/day) and isocaloric (20 kcal/kg/day) parenteral nutrition from preoperative day 1 through postoperative day (POD) 6. The serum GH and insulin‐like growth factor‐1 (IGF‐1) levels, intestinal permeability, peripheral CD4+/CD8+ lymphocyte subsets, and routine blood and biochemistry analyses were evaluated before and after GH treatment. In the study group a significant increase in serum levels of GH and IGF‐1 was observed on PODs 3 and 7. A significant decrease in the CD4+ subset population and the CD4+/CD8+ ratio was observed in the control group on POD 7 compared with preoperative studies, whereas no change was observed in the study group. The lactulose/mannitol excretion (L/M) ratio in the control group was elevated significantly on POD 7 compared with that before operation (p = 0.01), whereas the L/M ratio in the study group did not change compared to preoperative values (p = 0.08). No adverse reactions were related to the administration. There were no differences observed in operation‐related complications or postoperative hospital stays between the two groups. This small pilot study suggests that GH attenuated the depression in cellular immunity following surgical stress and possibly reduced the increase in intestinal permeability that occurs following operation. Further studies of a large group of patients are needed to determine if these changes can be translated into improved outcome in surgical patients.
Peptides derived from the heptad repeat region near the C‐terminal of Sendai virus F protein bind the hemagglutinin‐neuraminidase ectodomain
Authors: Tomasi Maurizio , Pasti Claudia , Manfrinato Cristina , Dallocchio Franco , Bellini Tiziana
Published: March 2003

Previously, we showed that Sendai virus fusion protein (F) acts as an inhibitor of neuraminidase activity of hemagglutinin‐neuraminidase (HN) protein. Here we report that synthetic peptides derived from the heptad repeat region proximal to the transmembrane domain (HR2) of Sendai virus F inhibit fusion and enhance the enzymatic activity of the HN. This occurs on the virus‐bound HN and on its soluble globular head. The enhancing effect on virus‐bound HN is reversible and depends on the presence of F. The data indicate that, by binding to the HN ectodomain, the HR2 peptides abolish the F inhibition of HN and disrupt the communication between the F and HN essential to promote virus–cell fusion.
Prion‐like protein Doppel expression is not modified in scrapie‐infected cells and in the brains of patients with Creutzfeldt–Jakob disease
Authors: Peoc'h K , Volland H , De Gassart A , Beaudry P , Sazdovitch V , Sorgato M.C , Creminon C , Laplanche J.-L , Lehmann S
Published: March 2003

Doppel protein has been discovered in prnp knock‐out mouse lines, with overproduction of this protein in the brain causing ataxia and neurodegeneration. We investigated whether Doppel expression (i) affected or was affected by the course of prion propagation in neuroblastoma cells, or (ii) modulated Creutzfeldt–Jakob disease pathogenesis. No change in Doppel production was detected in N2a cells, before or after infection. Transient murine Doppel gene expression had no effect on N2a viability or PrPSc production. A sensitive immunometric assay revealed low levels of Doppel in human brain, reflecting weak transcription of the corresponding gene. No difference in brain Doppel levels was observed between Creutzfeldt–Jakob disease patients and controls, adding further evidence that Doppel is unlikely to be involved in prion disease pathogenesis.
BML‐190 and AM251 act as inverse agonists at the human cannabinoid CB2 receptor: signalling via cAMP and inositol phosphates
Authors: New David C , Wong Yung H
Published: March 2003

The aminoalkylindole BML‐190 and diarylpyrazole AM251 ligands have previously been shown to bind to cannabinoid CB2 and CB1 receptors, respectively. In HEK‐293 cells stably expressing the human CB2 receptor, BML‐190 and AM251 potentiated the forskolin‐stimulated accumulation of cAMP. Moreover, the CB2 receptor can interact productively with 16z44, a promiscuous Gα16/z chimera. BML‐190 and AM251 reduce the basal levels of inositol phosphate production in cells expressing the CB2 receptor and 16z44. These results demonstrate that BML‐190 and AM251 act as inverse agonists at the human CB2 receptor acting via Gαi/o and Gαq family‐coupled pathways.
Nitric oxide inhibition of IGF‐1 stimulated proteoglycan synthesis: Role of cGMP
Authors: Studer R. K. , Decker K. , Melhem S. , Georgescu H.
Published: March 2003

Insulin‐like growth factor (IGF‐1) is critical for normal development and maintenance of cartilage, however arthritic cartilage responds poorly to IGF‐1; part of this insensitivity is mediated by nitric oxide (NO). These studies test if cGMP is responsible for NO dependent insensitivity to IGF‐1 in chondrocytes in situ in organ culture and in monolayer culture. Lapine cartilage and chondrocytes in monolayer culture and cartilage from osteoarthritic human knees were used. Tissues were exposed to NO from iNOS induced by IL‐1, and proteoglycan synthesis in response to IGF‐1 was evaluated in the presence and absence of cGMP dependent protein kinase (PKG) inhibitors. PKG activators inhibited IGF‐1 responses in cartilage but not chondrocytes in monolayer. IL‐1 stimulated cGMP synthesis in both monolayer and organ cultures. However, PKG inhibitors in cartilage slices but not in monolayer cultures restored response to IGF‐1. PKG activity was detected in both fresh and monolayer chondrocytes, confirming this part of the cGMP signal cascade is intact in both of the preparations evaluated. Arthritic cartilage response to IGF‐1 was restored by both N‐monomethyl‐L‐arginine inhibition of NO synthesis and PKG inhibitors. The data suggests that cGMP mediated effects are critical to NO actions on chondrocytes in situ in the cartilage matrix and supports a role for cGMP in the pathophysiologic effects of NO in osteoarthritis. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Connexin 40 expression in bovine and rat retinas
Authors: Matesic Diane , Tillen Terri , Sitaramayya Ari
Published: March 2003

Retinal neurons are extensively coupled through gap junction intercellular channels, but few connexin subtypes have been identified in mammalian retinal neurons. Based on previous findings that retinal gap junctional coupling is modulated by both dopamine and nitric oxide, presumably through connexin phosphorylation, we examined whether the connexin phosphoprotein subtype, connexin 40 (Cx40), was expressed in mammalian retinas. Immunostaining of rat and bovine retinas using Cx40‐specific antibodies from two independent sources showed punctate staining between cells in the outer nuclear layer (ONL) and a sublayer of cells within the inner nuclear layer (INL). In addition, sparse punctate staining was detected in the ganglion cell/axon fiber layers (GCL/AFL). No punctate staining was observed in the outer (OS) or inner segment (IS) layers, and rarely in the outer plexiform layer (OPL) or inner plexiform layer (IPL). Double immunostaining of bovine retinas with antibodies to Go, which stains bipolar cells, and to Cx40, showed little overlap, suggesting these bipolar cells do not express Cx40. Western blot analysis of alkaline‐extracted bovine retinal membranes revealed Cx40 immunopositive bands of about 40 kD (monomer) and 80 kD (dimer). In both locations (monomer and dimer), the bands appeared as doublets, and their immunoreactivity was abolished when the antibody was pre‐adsorbed with immunogenic Cx40 peptide. The doublet at 40 kD co‐migrated with an immunopositive doublet present in heart membranes. Treatment with alkaline phosphatase altered the banding pattern of Cx40. The results suggest that the connexin phosphoprotein subtype, Cx40, is expressed within the neural layers of the mammalian retina.
Chronobiology of the proliferative events related to angiogenesis in mice liver regeneration after partial hepatectomy
Authors: Furnus C.C. , Inda A.M. , Andrini L.B. , García M.N. , García A.L. , Badrán A.F. , Errecalde A.L.
Published: March 2003

In liver regeneration the formation of new capillary blood vessels is a fundamental requirement for cellular proliferation. Vascular endothelial growth factor (VEGF) is involved in the events of angiogenesis, the mRNA of which is expressed in both hepatocytes and non‐parenchymal cells. In this experimental design we try to establish if during liver regeneration in mouse, the expression of VEGF is produced before or after the hepatocytes proliferation. C3H/S adult male mice were divided in three groups in order to study: VEGF expression; S‐phase index (SI); and mitotic activity (MA) of hepatocytes. The results that were analyzed by ANOVA, show that VEGF expression starts to increase 26 h after PH with a peak at 28 h. Furthermore, the DNA synthesis (DNAs) reaches maximal level 42 h after pH, meanwhile the MA of the hepatocytes shows an increase 8 h after the DNAs peak. In conclusion, it could be argued that the chronobiology of the events related to liver regeneration in mice started with a release of VEGF by the hepatocytes, followed by its DNAs and mitosis.
E‐NTPase/E‐NTPDase: a potential regulatory role in E‐kinase/PKA‐mediated CD36 activation
Authors: Kannan Subburaj
Published: March 2003

CD36 is a platelet surface receptor protein that plays a major role in platelet aggregation and accumulation that is mediated by parasitic attachment. The CD36 receptor is constitutively phosphorylated by E‐kinase/PKA, resulting in increased affinity for collagen, but preventing spontaneous platelet aggregation. Dephosphorylation of CD36 by protein phosphatase 2A (PP2A) leads to increased affinity for thrombospondin at a different rate than that of collagen‐mediated platelet aggregation. Depletion of the E‐kinase/PKA substrate [ATP]0by E‐NTPase‐mediated hydrolysis, in conjunction with inhibition of PP2A by okadaic acid, could prove to be a valuable tool in inhibiting CD36 activation, thus preventing platelet aggregation and thrombus formation.
Accuracy of doppler echocardiography in the assessment of pulmonary hypertension in liver transplant candidates
Authors: Kim Ray W. , Krowka Michael J. , Plevak David J. , Lee Jaeho , Rettke Steven R. , Frantz Robert P. , Wiesner Russell H.
Published: March 2003

Pulmonary hypertension has been associated with poor outcome after liver transplantation. We assessed the diagnostic accuracy of Doppler echocardiography in detecting significant pulmonary hypertension. Seventy-four potential liver transplant candidates underwent Doppler echocardiography in which the systolic right ventricular pressure (RVsys) was used to estimate the systolic pulmonary artery pressure (PAsys). Group 1 included 39 consecutive patients with RVsys ≥50 mm Hg who underwent elective right heart catheterization. Group 2 consisted of 35 patients with RVsys <50 mm Hg in whom pulmonary artery pressures were measured at the beginning of the transplantation procedure. The accuracy of the estimates by Doppler echocardiography was assessed against measurements made by direct catheterization. Patients in groups 1 and 2 were comparable in their demographic and liver disease characteristics. There was a strong correlation between RVsys by Doppler echocardiography and PAsys by right heart catheterization (r = .78, P < .01). Of the 39 patients in group 1, 29 (72%) had at least moderate pulmonary hypertension (mean pulmonary artery pressure [MPAP] ≥35 mm Hg), including 12 (30%) with severe pulmonary hypertension (MPAP ≥50 mm Hg). Only 1 of the group 2 patients had MPAP ≥35 mm Hg. Thus, in the diagnosis of moderate to severe pulmonary hypertension, the sensitivity of echocardiography was 97% and specificity was 77%. Doppler echocardiography is an accurate screening test to detect moderate to severe pulmonary hypertension. We advise that liver transplant candidates with RVsys ≥50 mm Hg undergo right heart catheterization to fully characterize pulmonary hemodynamics.
Decentralisation and Poverty Alleviation in Indonesia
Authors: Booth Anne
Published: March 2003

Indonesia has embarked on an ambitious decentralisation programme which is aimed at empowering regional parliaments and giving them far more autonomy in formulating budgets and implementing expenditures. Beginning in the calendar (and fiscal) year 2001, the central government replaced many of the existing grants from the centre to the regions with a ‘general allocation grant’; in addition, those regions with substantial mining and forestry sectors received a share of the revenues accruing from exploitation of these resources. The author explores the background to these reforms by examining the regional grants system which developed through the Soeharto era, and the criticisms which this system attracted. The impact of the new system on both rich and poor regions is also discussed.
Educational Restructuring from a Community Viewpoint: A Case Study of School Closure from Invercargill, New Zealand
Authors: Witten Karen , Kearns Robin , Lewis Nick , Coster Heather , McCreanor Tim
Published: March 2003

Beyond their educational function, schools are frequently a focal point for community life. We argue that this latter role was compromised in New Zealand by a decade of neoliberal realignments within education policy. During the 1990s the abolition of school zones, the commodification of education, and the drive for efficiency in the allocation of educational resources undermined the place of school in community life. In this paper we explore the impacts of a school closure on an urban neighbourhood in Invercargill, New Zealand. We present and interpret narratives gathered during an interview-based study of the closure of Surrey Park Primary School. Our analysis highlights parents' perspectives on the role of the educational bureaucracy in the closure debate, the ambiguous role assigned to ‘community’ within the restructured system, the impact of the closure for low-income families, and the place of schools in contributing to the neighbourhood social cohesion. Our analysis concurs with international research suggesting that breaking links between schools and communities has potentially significant educational impacts on children.
RHAMM Is a Centrosomal Protein That Interacts with Dynein and Maintains Spindle Pole Stability
Authors: Maxwell Christopher A. , Keats Jonathan J. , Crainie Mary , Sun Xuejun , Yen Tim , Shibuya Ellen , Hendzel Michael , Chan Gordon , Pilarski Linda M.
Published: March 2003

The receptor for hyaluronan-mediated motility (RHAMM), an acidic coiled coil protein, has previously been characterized as a cell surface receptor for hyaluronan, and a microtubule-associated intracellular hyaluronan binding protein. In this study, we demonstrate that a subset of cellular RHAMM localizes to the centrosome and functions in the maintenance of spindle integrity. We confirm a previous study showing that the amino terminus of RHAMM interacts with microtubules and further demonstrate that a separate carboxy-terminal domain is required for centrosomal targeting. This motif overlaps the defined hyaluronan binding domain and bears 72% identity to the dynein interaction domain of Xklp2. RHAMM antibodies coimmunprecipitate dynein IC from Xenopus and HeLa extracts. Deregulation of RHAMM expression inhibits mitotic progression and affects spindle architecture. Structure, localization, and function, along with phylogenetic analysis, suggests that RHAMM may be a new member of the TACC family. Thus, we demonstrate a novel centrosomal localization and mitotic spindle-stabilizing function for RHAMM. Moreover, we provide a potential mechanism for this function in that RHAMM may cross-link centrosomal microtubules, through a direct interaction with microtubules and an association with dynein.
Binding Partners for the COOH-Terminal Appendage Domains of the GGAs and γ-Adaptin
Authors: Lui Winnie W.Y. , Collins Brett M. , Hirst Jennifer , Motley Alison , Millar Caroline , Schu Peter , Owen David J. , Robinson Margaret S.
Published: March 2003

The adaptor appendage domains are believed to act as binding platforms for coated vesicle accessory proteins. Using glutathione S-transferase pulldowns from pig brain cytosol, we find three proteins that can bind to the appendage domains of both the AP-1 γ subunit and the GGAs: γ-synergin and two novel proteins, p56 and p200. p56 elicited better antibodies than p200 and was generally more tractable. Although p56 and γ-synergin bind to both GGA and γ appendages in vitro, immunofluorescence labeling of nocodazole-treated cells shows that p56 colocalizes with GGAs on TGN46-positive membranes, whereas γ-synergin colocalizes with AP-1 primarily on a different membrane compartment. Furthermore, in AP-1–deficient cells, p56 remains membrane-associated whereas γ-synergin becomes cytosolic. Thus, p56 and γ-synergin show very strong preferences for GGAs and AP-1, respectively, in vivo. However, the GGA and γ appendages share the same fold as determined by x-ray crystallography, and mutagenesis reveals that the same amino acids contribute to their binding sites. By overexpressing wild-type GGA and γ appendage domains in cells, we can drive p56 and γ-synergin, respectively, into the cytosol, suggesting a possible mechanism for selectively disrupting the two pathways.
Identifying Phase-specific Genes in the Fungal PathogenHistoplasma capsulatumUsing a Genomic Shotgun Microarray
Authors: Hwang Lena , Hocking-Murray Davina , Bahrami Adam K. , Andersson Margareta , Rine Jasper , Sil Anita
Published: March 2003

A fundamental feature of the fungal pathogen Histoplasma capsulatum is its ability to shift from a mycelial phase in the soil to a yeast phase in its human host. Each form plays a critical role in infection and disease, but little is understood about how these two morphologic phases are established and maintained. To identify phase-regulated genes of H. capsulatum, we carried out expression analyses by using a genomic shotgun microarray representing approximately one-third of the genome, and identified 500 clones that were differentially expressed. Genes induced in the mycelial phase included several involved in conidiation, cell polarity, and melanin production in other organisms. Genes induced in the yeast phase included several involved in sulfur metabolism, extending previous observations that sulfur metabolism influences morphology in H. capsulatum. Other genes with increased expression in the yeast phase were implicated in nutrient acquisition and cell cycle regulation. Unexpectedly, differential regulation of the site of transcript initiation was also observed in the two phases. These findings identify genes that may determine some of the major characteristics of the mycelial and yeast phases.
Interactions between the Evolutionarily Conserved, Actin-related Protein, Arp11, Actin, and Arp1
Authors: Eckley D. Mark , Schroer Trina A.
Published: March 2003

The dynein activator dynactin is a multiprotein complex with distinct microtubule- and cargo-binding domains. The cargo-binding domain contains a short, actin-like filament of the actin-related protein Arp1, a second actin-related protein, Arp11, and conventional actin. The length of this filament is invariant in dynactin isolated from multiple species and tissues, suggesting that activities that regulate Arp1 polymerization are important for dynactin assembly. Arp11 is present in a protein complex localized at the pointed end of the Arp1 minifilament, whereas actin capping protein (CapZ) is present at the barbed end. Either might cooperate with conventional actin to cap Arp1. We tested the ability of Arp11 to interact with conventional actin and found it could coassemble. Like Arp1, cytosolic Arp11 is found only in dynactin, suggesting that Arp11 and free cytosolic actin do not interact significantly. Recombinant Arp11 and Arp1 were demonstrated to interact by coprecipitation. We developed an in vivo assay for Arp11–Arp1 interaction based on previous observations that Arp1 forms filamentous assemblies when overexpressed in cultured cells. Arp11 significantly decreases the formation of these organized Arp1 assemblies. Finally, this assay was used to confirm the identity of a putative Arp11 homolog in Drosophila melanogaster.
(3 + 1)-Dimensional structure refinement of the fresnoite framework-structure type compound Ba2TiGe2O8
Authors: Höche Thomas , Esmaeilzadeh Saeid , Uecker Reinhard , Lidin Sven , Neumann Wolfgang
Published: March 2003

The incommensurately modulated structure of the fresnoite framework-structure type compound Ba2TiGe2O8 has been solved using a (3 + 1)-dimensional superspace approach. The structure is orthorhombic and adopts the superspace group Cmm2(0,β,1/2)s00 with β ≃ 0.635 at room temperature. The refinement was based on neutron powder diffraction data obtained from a powdered single crystal grown by Czochralski pulling. The modulation parameters that were obtained support the idea that frozen-in rigid-unit modes cause the modulation. The modulation is mainly manifested by positional displacements of O atoms. Barium ions are either eightfold, ninefold or tenfold coordinated in the one-dimensional modulated structure. A significant improvement of the bond-valence sum for both barium positions is achieved by the introduction of the positional modulation. This finding strongly suggests that underbonded barium positions are critically involved in provoking the incommensurate modulation in Ba2TiGe2O8.
Developments in electronic publishing in the biomedical sciences
Authors: Lambert Jill
Published: March 2003

This paper reports on developments in biomedical electronic publishing since the mid‐1990s. These cover the HighWire, PubMed Central, BioOne, the Public Library of Science, E‐BioSci and BioMed Central services. The issues raised by these developments are outlined and include the need to attract good quality papers, the ownership of copyright, how developments are funded, the question of whether a distributed or centralised system is adopted, and preservation of content.
Information operations in the Kuwaiti corporate sector: an analysis
Authors: ur Rehman Sajjad , Marouf Laila
Published: March 2003

The purpose of the study was to investigate the conduct of information operations in Kuwait. One of the top executives or managers from each of the 39 companies, which volunteered to participate in the study, was interviewed. Participant input was sought on a carefully designed questionnaire, containing 19 questions, covering the scatter of information operations. It was noted that most of these companies were engaged in a number of activities for determining user needs and collecting, organising, servicing, packaging, searching and retrieving information from formal and structured information sources. Against this backdrop, the absence of any information unit or professional was quite significant. Little activity was also noted in the use of Web technology and Internet utilities. Another finding, worthy of the attention of the policy makers, was related to little activity in the organisation, control and use of the internal information sources of these companies.
Use of ICT in Thai libraries: an overview
Authors: Siriwongworawat Suwakhon
Published: March 2003

Since the 1980s many libraries in Thailand have used computers and particularly the Unesco‐developed CDS/ISIS for their library operations and many databases have been created in higher educational institutions. In 1987, Chiang Mai University library was the first to introduce a commercial integrated library management system when the URICA software was used for the processes of cataloguing and providing online public access. By 1992 the National Library of Thailand had installed the Dynix Library Automated System software. Nowadays a range of library management software is used including ALICE, Dynix, INNOPAC, TINlib and VTLS, in the libraries of higher educational institutions and some private agencies. The trend for library operations now is for electronic information resources, electronic books and the virtual library. The future goal of the library is how to provide users with access to more and better information with a quicker and easier approach. An overview of these ICT developments in Thai libraries is provided in this paper.
Synthesis of N4-Alkyl-5-azacytidines and Their Base-Pairing with Carbamoylguanidines - A Contribution to Explanation of the Mutagenicity of 2'-Deoxy-5-azacytidine
Authors: Pískala Alois , Hanna Naeem B. , Masojídková Milena , Otmar Miroslav , Fiedler Pavel , Ubik Karel
Published: March 2003

A series of N4-alkyl-5-azacytidines 3a-3h were prepared by treatment of the 4-methoxy analogue 4 with the respective amines. In the case of propyl-, butyl-, sec-butyl-, benzyl- or furfurylamine, aggregates of azacytidines 3a-3e with their hydrolytic products 5a-5e were isolated. Similar aggregates were obtained with 1-methyl-5-azacytosine (6) and 2-(methylcarbamoyl)guanidine (7). Compound 7 was prepared by the reaction of guanidine with methyl isocyanate; the reaction of 2 or 3 equivalents gave the di- or tricarbamoyl derivatives 11 and 12, respectively. Cyclization of 7 and 11 with DMF dimethyl acetal afforded azacytosines 6 and 13, respectively. Aggregates of guanosine with 5-azacytosine nucleosides 1, 2 and 15 or of 5-aza-5,6-dihydrocytosine nucleosides 16 and 17 with 5-azacytidine (1) and its 2'-deoxy congener 2 have been prepared by co-crystallization of the respective pairs of nucleosides. The anomers of (deoxyribosylcarbamoyl)guanidine 20a and 20b have been prepared by hydrolysis of the deoxy nucleoside 2. An aggregate of the picrate (8a) of (ribosylcarbamoyl)guanidine 8 with cytidine (9) has been obtained by co-crystallization of both components. Reaction of the methoxy nucleoside 4 with tert-butylamine gave, by contrast to the above mentioned amines, the α-anomer of O-methylribosylisobiuret 22, which was cyclized by DMF dimethyl acetal to the α-anomer of N4,N4-dimethyl-5-azacytidine 24. The connection of the base-pairing ability of carbamoylguanidines with the mutagenicity of 2'-deoxy-5-azacytidine (2) as well as the mechanism of inhibition of DNA methyltransferase by this nucleoside analogue is discussed. In contrast to the unsubstituted 5-azacytidine (1) or its N4-methyl derivatives, none of the N4-alkyl derivatives exhibited any antibacterial or antitumor activity at 100 μg/ml or 10 μmol/l concentrations, respectively.
MODELING THE CONTROL OF ISOMETRIC FORCE PRODUCTION WITH PIECE-WISE LINEAR, STOCHASTIC MAPS OF MULTIPLE TIME-SCALES
Authors: MAYER-KRESS GOTTFRIED , DEUTSCH KATHERINE M. , NEWELL KARL M.
Published: March 2003

In human movement, the large number of system degrees of freedom at different levels of analysis of the system, joints, muscles, motor units, cells etc, naturally affords complexity and adaptability in action. It also leads to variability in movement and its outcome, even in intentional efforts to reproduce the same movement or action goal. An example is continuous isometric force output to a constant force level where the amount and structure of force variability changes with information available, force level and individual differences. In this paper we model the control of isometric force production with piece-wise linear stochastic maps of multiple time scales. At the core of our model is a piecewise linear function, depending on three parameters that can be estimated from the observed data that is perturbed by additive Gaussian noise at a given level. The result of the stochastic forcing is that outside of a threshold interval the system behaves like a discrete Ornstein-Uhlenbeck process and inside it performs a Brownian motion. The model is shown to simulate the basic findings of the structure of human force variability that decreasing variability is correlated with increased dynamical complexity as measured with the "Approximate Entropy (ApEn)" statistic.
Covalent Trapping of Protein-DNA Complexes
Authors: Verdine Gregory L. , Norman Derek P.G.
Published: March 2003

▪ Abstract  High-resolution structural studies of protein-DNA complexes have proven to be an invaluable means of understanding the diverse functions of proteins that manage the genome. Most of the structures determined to date represent proteins bound noncovalently to various DNA sequences or structures. Although noncovalent complexation is often adequate to study the structures of proteins that have robust, specific interactions with DNA, it is poorly suited to the study of transient intermediates in enzyme-catalyzed DNA processing reactions or of complexes that exist in multiple equilibrating forms. In recent years, strategies developed for the covalent trapping of protein-DNA complexes have begun to show promise as a window into an otherwise inaccessible world of structure.