bluuebunny/crossref_metadata_2025_split huggingface dataset:
Total Enantioselective Synthesis and In Vivo Biological Evaluation of a Novel Fluorescent BODIPY α‐Galactosylceramide
Authors: Vo‐Hoang Yen , Micouin Laurent , Ronet Catherine , Gachelin Gabriel , Bonin Martine 
Published: January 2003

AbstractNatural killer T (NKT) cells are a distinct subset of mature lymphocytes endowed with features of activated and regulatory T cells. α‐Galactosylceramides (α‐GalCers), the synthetic prototype of which is KRN7000, are the only natural reagents recognised by the T‐cell receptor of NKT cells. The α‐GalCer‐activated NKT cells promptly release IFNγ and IL‐4 (IFN=interferon; IL=interleukin) and undergo apoptotic death within hours. In mice, activated NKT cells are responsible for antitumour activity and protection against autoimmune diseases. KRN7000 can thus be considered as the root of a family of novel immunoregulatory drugs. To get insights into the in vivo behaviour of α‐galactosylceramides, an original fluorescent derivative has been prepared by following a convergent synthetic scheme. This strategy allows the introduction of different acyl chains, carbohydrate residues and various labels in the final steps of the synthesis. The fluorescent BODIPY probe derived from a versatile glycolipid precursor is as active as KRN7000 for inducing apoptosis of liver NKT cells. Fluorescence was detected in peritoneal macrophages and splenic antigen‐presenting cells, in Kupffer‐like cells in the liver, but not in lymphocytes.
Assembly of Designed Oligonucleotides as an Efficient Method for Gene Recombination: A New Tool in Directed Evolution
Authors: Zha Dongxing , Eipper Andreas , Reetz Manfred T. 
Published: January 2003

AbstractA new and practical method for gene recombination with formation of libraries of mutant genes is presented. The method is based on the assembly of appropriately prepared oligonucleotides whose design is guided by sequence information. High recombination frequency with formation of full‐length products is achieved by controlled overlapping of the designed oligomers. This process (ADO) minimizes self‐hybridization of parental genes, which constitutes a significant advantage over conventional family shuffling as used in the directed evolution of functional enzymes. ADO was applied to the recombination of two lipase family genes from Bacillus subtilis (LipA and LipB). In a library of 3000 lipase variants created by this method, several were found that display increased enantioselectivity in a model reaction involving the hydrolysis of a meso‐diacetate.
Solution Structure and Stability of Tryptophan‐Containing Nucleopeptide Duplexes
Authors: Gómez‐Pinto Irene , Marchán Vicente , Gago Federico , Grandas Anna , González Carlos 
Published: January 2003

AbstractCovalently linked peptide–oligonucleotide hybrids were used as models for studying tryptophan–DNA interactions. The structure and stability of several hybrids in which peptides and oligonucleotides are linked through a phosphodiester bond between the hydroxy group of a homoserine (Hse) side chain and the 3′‐end of the oligonucleotide, have been studied by both NMR and CD spectroscopy and by restrained molecular dynamics methods. The three‐dimensional solution structure of the complex between Ac‐Lys‐Trp‐Lys‐Hse(p3′dGCATCG)‐Ala‐OH (p=phosphate, Ac=acetyl) and its complementary strand 5′dCGTAGC has been determined from a set of 276 experimental NOE distances and 33 dihedral angle constraints. The oligonucleotide structure is a well‐defined duplex that belongs to the B‐form family of DNA structures. The covalently linked peptide adopts a folded structure in which the tryptophan side chain stacks against the 3′‐terminal guanine moiety, which forms a cap at the end of the duplex. This stacking interaction, which resembles other tryptophan–nucleobase interactions observed in some protein–DNA complexes, is not observed in the single‐stranded form of Ac‐Lys‐Trp‐Lys‐Hse(p3′dGCATCG)‐Ala‐OH, where the peptide chain is completely disordered. A comparison with the pure DNA duplex, d(5′GCTACG3′)–(5′CGTAGC3′), indicates that the interaction between the peptide and the DNA contributes to the stability of the nucleopeptide duplex. The different contributions that stabilize this complex have been evaluated by studying other nucleopeptide compounds with related sequences.
Design of a Composite Ethidium–Netropsin–Anilinoacridine Molecule for DNA Recognition
Authors: Carrasco Carolina , Helissey Philippe , Haroun Michelyne , Baldeyrou Brigitte , Lansiaux Amélie , Colson Pierre , Houssier Claude , Giorgi‐Renault Sylviane , Bailly Christian 
Published: January 2003

AbstractControl of gene expression is a cherished goal of cancer chemotherapy. Small ligand molecules able to bind tightly to DNA in a well‐defined configuration are being actively searched for. With this goal in mind, we have designed and synthesized the trifunctional molecule R‐132, which combines a bispyrrole skeleton for minor groove DNA recognition and two different chromophores, anilinoacridine and ethidium. The affinity and mode of binding of R‐132 to DNA were studied by a combination of complementary biochemical and biophysical techniques, which included absorption and fluorescence spectroscopy and circular and linear dichroism. A surface plasmon resonance biosensor analysis was also performed to quantify the kinetic parameters of the drug–DNA interaction process. Altogether, the results demonstrate that the three moieties of the hybrid molecule are engaged in the interaction process, thus validating the rational design strategy. At the biological level, R‐132 stabilizes topoisomerase‐II–DNA covalent complexes and displays potent cytotoxic activities, which are attributable to its DNA‐binding properties. R‐132 easily enters and accumulates in cell nuclei, as evidenced by confocal microscopy. R‐132 therefore provides a novel lead compound for the design of gene‐targeted anticancer agents.
Synthesis and Biological Activity of a Platinum(II) 6‐Phenyl‐2,2′‐bipyridine Complex and Its Dimeric Analogue
Authors: Chan Hing‐Leung , Ma Dik‐Lung , Yang Mengsu , Che Chi‐Ming 
Published: January 2003

AbstractWe have synthesized (pyridyl)‐(6‐phenyl‐2,2′‐bipyridine)platinum(II) hexafluorophosphate (1) and its corresponding dimer, μ‐N,N′‐bis(isonicotinyl)‐1,6‐hexanediamino bis‐[6‐phenyl‐2,2′‐bipyridine‐platinum(II)] dichloride (2). The DNA binding constants of 1 and 2 at 20 °C were determined by absorption titration to be 2.25×104 M−1 and 3.07×106 M−1, respectively. Compound 1 showed an AT preference, while 2 had no base preference. The binding site sizes of 2 for [poly(dA‐dT)]2, calf thymus DNA (ctDNA), and [poly(dG‐dC)]2, as determined by fluorescence titration, were 6.6, 4.0, and 2.8 bp, respectively. Compound 2 probably bound to [poly(dA‐dT)]2 through bisintercalation, and to [poly(dG‐dC)]2 by monointercalation. Binding of DNA by both complexes is favorable, since the binding free energies of 1 and 2 were estimated to be −5.8 and −8.7 kcal mol−1, respectively. The results of viscosity measurements and gel mobility shift assay demonstrated that binding of 1 and 2 caused DNA lengthening. The cytotoxicities of the complexes in various human cancer cell lines were determined by MTT assay. Complex 2 exhibited cytotoxicity comparable to that of cisplatin, and was more toxic than 1 by an order of magnitude.
Synthesis and Biological Evaluation of Pyrazolylnaphthoquinones as New Potential Antiprotozoal and Cytotoxic Agents
Authors: Sperandeo Norma R. , Brun Reto 
Published: January 2003

AbstractThe importance of American trypanosomiasis (Chagas' disease) in human pathology is widely known. The prognosis of this disease is poor and the choice of effective medicines limited, thus study of new drugs is absolutely necessary. In this work, the activities of three new pyrazolylnaphthoquinones, heterocyclic naphthoquinones bearing 3‐aminopyrazole rings, were evaluated on Trypanosoma cruzi, the etiological agent of Chagas' disease. These activities were compared with those of three 5‐aminoisoxazole analogues. In addition, since these compounds belong to a family of antiprotozoal and cytotoxic/antitumor agents, the activities of all six against Plasmodium falciparum, Trypanosoma brucei rhodesiense, and murine L‐6 cells were also investigated. In the biological tests, five of the compounds showed significant in vitro trypanocidal activities against T. cruzi, with activities similar to that of benznidazole. Two of the 5‐aminoisoxazole analogues also showed good activities, in one case highly selective, against the K1 and NF54 strains of P. falciparum (IC50<0.12 μg mL−1). Three of the compounds were cytotoxic to murine L‐6 cells (IC50=0.21–0.50 μg mL−1). The results suggested that the three pyrazolylnaphthoquinones and one of the 5‐aminoisoxazole analogues could be starting points for lead optimization programs against T. cruzi and P. falciparum, respectively.
Conformational Features of Human Melanin‐Concentrating Hormone: An NMR and Computational Analysis
Authors: Vitale Rosa Maria , Zaccaro Laura , Di Blasio Benedetto , Fattorusso Roberto , Isernia Carla , Amodeo Pietro , Pedone Carlo , Saviano Michele 
Published: January 2003

AbstractThe conformational features of human melanin‐concentrating hormone (hMCH) [Asp1‐Phe2‐Asp3‐Met4‐Leu5‐Arg6‐cyclo(SS)(Cys7‐Met8‐Leu9‐Gly10‐Arg11‐Val12‐Tyr13‐Arg14‐Pro15‐Cys16)‐Trp17‐Gln18‐Val19], in water and in a CD3CN/H2O (1:1 v/v) mixture at 298 K, have been determined by NMR spectroscopy followed by simulated annealing and molecular dynamics analyses to identify conformer populations. Backbone clustering analysis of NMR‐spectroscopy‐derived structures in the 7–16 peptide region led to the identification of a single representative structure in each solvent. Both root mean square deviation clustering and secondary structure analysis of the final conformers in both solvents show substantial convergence of most conformers into a single fold in the 4–17 region, with a limited variability around Gly10 and Tyr13 on going from CD3CN/H2O to pure water. The main feature deduced from the analysis of secondary structures is the occurrence of an N‐terminalαhelix of variable length, which spans an overall residue range of 2–9. A comparative analysis in the two solvents highlights that these structures are substantially different from that reported in the literature for the cyclic MCH(5–14) subunit of salmon MCH, which was used to perform a molecular characterization of the MCH/receptor complex. Our conformational data call for a critical revision of the proposed MCH/receptor complex model.
Optimization of Electrochemical and Peroxide‐Driven Oxidation of Styrene with Ultrathin Polyion Films Containing Cytochrome P450cam and Myoglobin
Authors: Munge Bernard , Estavillo Carmelita , Schenkman John B. , Rusling James F. 
Published: January 2003

AbstractThe catalytic and electrochemical properties of myoglobin and cytochrome P450cam in films constructed with alternate polyion layers were optimized with respect to film thickness, polyion type, and pH. Electrochemical and hydrogen peroxide driven epoxidation of styrene catalyzed by the proteins was used as the test reaction. Ionic synthetic organic polymers such as poly(styrene sulfonate), as opposed to SiO2 nanoparticles or DNA, supported the best catalytic and electrochemical performance. Charge transport involving the iron heme proteins was achieved over 40–320 nm depending on the polyion material and is likely to involve electron hopping facilitated by extensive interlayer mixing. However, very thin films (ca. 12–25 nm) gave the largest turnover rates for the catalytic epoxidation of styrene, and thicker films were subject to reactant transport limitations. Classical bell‐shaped activity/pH profiles and turnover rates similar to those obtained in solution suggest that films grown layer‐by‐layer are applicable to turnover rate studies of enzymes for organic oxidations. Major advantages include enhanced enzyme stability and the tiny amount of protein required.
Novel Trifluoromethyl Ketones as Potent Gastric Lipase Inhibitors
Authors: Kokotos George , Kotsovolou Stavroula , Verger Robert 
Published: January 2003

AbstractNovel inhibitors of human digestive lipases, lipophilic trifluoromethyl ketones, were developed. These analogues of the natural triacylglycerol substrates of lipases were designed to contain the carbonyl group of the trifluoromethyl ketone functionality in place of the carbonyl group of the scissile ester bond at the sn‐1 position. The ester bond at the sn‐3 position was replaced by an ether bond, while the secondary hydroxy group was either esterified or etherified. The inhibitors were prepared starting from solketal. The inhibition of human pancreatic and gastric lipases by the trifluoromethyl ketones was studied by the monolayer technique. 5,5,5‐Trifluoro‐1‐(dodecyloxymethyl)‐4‐oxopentyl decanoate is the best synthetic inhibitor of human gastric lipase ever reported (inhibition constant α50=0.003).
Evaluation of Lipopolysaccharide Aggregation by Light Scattering Spectroscopy
Authors: Santos Nuno C. , Silva Ana C. , Castanho Miguel A. R. B. , Martins‐Silva J. , Saldanha Carlota 
Published: January 2003

AbstractLipopolysaccharides (LPS) are cell wall components of Gram‐negative bacteria. These molecules behave as bacterial endotoxins and their release into the bloodstream is a determinant of the development of a wide range of pathologies. These amphipathic molecules can self‐aggregate into supramolecular structures with different shapes and sizes. The formation of these structures occurs when the LPS concentration is higher than the apparent critical micelle concentration (CMCa). Light scattering spectroscopy (both static and dynamic) was used to directly characterize the aggregation process of LPS from Escherichia coli serotype 026:B6. The results point to a CMCa value of 14 μg mL−1 and the existence of premicelle LPS oligomers below this concentration. Both structures were characterized in terms of molecular weight (5.5×106 and 16×106 g mol−1 below and above the CMCa, respectively), interaction with the aqueous environment, gyration radius (56 and 105 nm), hydrodynamic radius, (60 and 95 nm) and geometry of the supramolecular structures (nearly spherical). Our data indicates that future in vitro experiments should be carried out both below and above the CMCa. The search for drugs that interact with the aggregates, and thus change the CMCa and condition LPS interactions in the bloodstream, could be a new way to prevent certain bacterial‐endotoxin‐related pathologies.
Features of the Java Commodity Grid Kit
Authors: von Laszewski Gregor , Gawor Jarek , Lane Peter , Rehn Nell , Russell Mike 
Published: January 2003

AbstractIn this paper we report on the features of the Java Commodity Grid Kit (Java CoG Kit). The Java CoG Kit provides middleware for accessing Grid functionality from the Java framework. Java CoG Kit middleware is general enough to design a variety of advanced Grid applications with quite different user requirements. Access to the Grid is established via Globus Toolkit protocols, allowing the Java CoG Kit to also communicate with the services distributed as part of the C Globus Toolkit reference implementation. Thus, the Java CoG Kit provides Grid developers with the ability to utilize the Grid, as well as numerous additional libraries and frameworks developed by the Java community to enable network, Internet, enterprise and peer‐to‐peer computing. A variety of projects have successfully used the client libraries of the Java CoG Kit to access Grids driven by the C Globus Toolkit software. In this paper we also report on the efforts to develop serverside Java CoG Kit components. As part of this research we have implemented a prototype pure Java resource management system that enables one to run Grid jobs on platforms on which a Java virtual machine is supported, including Windows NT machines. Copyright © 2002 John Wiley & Sons, Ltd.
A CORBA Commodity Grid Kit
Authors: Parashar Manish , von Laszewski Gregor , Verma Snigdha , Gawor Jarek , Keahey Kate , Rehn Nell 
Published: January 2003

AbstractThis paper reports on an ongoing research project aimed at designing and deploying a Common Object Resource Broker Architecture (CORBA) (ww.omg.org) Commodity Grid (CoG) Kit. The overall goal of this project is to enable the development of advanced Grid applications while adhering to state‐of‐the‐art software engineering practices and reusing the existing Grid infrastructure. As part of this activity, we are investigating how CORBA can be used to support the development of Grid applications. In this paper, we outline the design of a CORBA CoG Kit that will provide a software development framework for building a CORBA ‘Grid domain’. We also present our experiences in developing a prototype CORBA CoG Kit that supports the development and deployment of CORBA applications on the Grid by providing them access to the Grid services provided by the Globus Toolkit. Copyright © 2002 John Wiley & Sons, Ltd.
MPI‐CHECK: a tool for checking Fortran 90 MPI programs
Authors: Luecke Glenn , Chen Hua , Coyle James , Hoekstra Jim , Kraeva Marina , Zou Yan 
Published: January 2003

AbstractMPI is commonly used to write parallel programs for distributed memory parallel computers. MPI‐CHECK is a tool developed to aid in the debugging of MPI programs that are written in free or fixed format Fortran 90 and Fortran 77. MPI‐CHECK provides automatic compile‐time and run‐time checking of MPI programs. MPI‐CHECK automatically detects the following problems in the use of MPI routines: (i) mismatch in argument type, kind, rank or number; (ii) messages which exceed the bounds of the source/destination array; (iii) negative message lengths; (iv) illegal MPI calls before MPI_INIT or after MPI_FINALIZE; (v) inconsistencies between the declared type of a message and its associated DATATYPE argument; and (vi) actual arguments which violate the INTENT attribute. Copyright © 2003 John Wiley & Sons, Ltd.
GridSim: a toolkit for the modeling and simulation of distributed resource management and scheduling for Grid computing
Authors: Buyya Rajkumar , Murshed Manzur 
Published: January 2003

AbstractClusters, Grids, and peer‐to‐peer (P2P) networks have emerged as popular paradigms for next generation parallel and distributed computing. They enable aggregation of distributed resources for solving large‐scale problems in science, engineering, and commerce. In Grid and P2P computing environments, the resources are usually geographically distributed in multiple administrative domains, managed and owned by different organizations with different policies, and interconnected by wide‐area networks or the Internet. This introduces a number of resource management and application scheduling challenges in the domain of security, resource and policy heterogeneity, fault tolerance, continuously changing resource conditions, and politics. The resource management and scheduling systems for Grid computing need to manage resources and application execution depending on either resource consumers' or owners' requirements, and continuously adapt to changes in resource availability.The management of resources and scheduling of applications in such large‐scale distributed systems is a complex undertaking. In order to prove the effectiveness of resource brokers and associated scheduling algorithms, their performance needs to be evaluated under different scenarios such as varying number of resources and users with different requirements. In a Grid environment, it is hard and even impossible to perform scheduler performance evaluation in a repeatable and controllable manner as resources and users are distributed across multiple organizations with their own policies. To overcome this limitation, we have developed a Java‐based discrete‐event Grid simulation toolkit called GridSim. The toolkit supports modeling and simulation of heterogeneous Grid resources (both time‐ and space‐shared), users and application models. It provides primitives for creation of application tasks, mapping of tasks to resources, and their management. To demonstrate suitability of the GridSim toolkit, we have simulated a Nimrod‐G like Grid resource broker and evaluated the performance of deadline and budget constrained cost‐ and time‐minimization scheduling algorithms. Copyright © 2002 John Wiley & Sons, Ltd.
Polyurethane/clay and polyurethane/POSS nanocomposites as flame retarded coating for polyester and cotton fabrics
Authors: Devaux Eric , Rochery Maryline , Bourbigot Serge 
Published: January 2003

AbstractPolyurethane resins (PU) are widely used as coatings for textile fabrics in order to improve some properties (for example mechanical behaviour, water repellency and air impermeability). Two kinds of additives have been added to the polyurethane in order to provide flame retardancy to the coated textile structure: montmorillonite clay and polyhedral oligomeric silsesquioxanes (POSS) have been used to process PU nanocomposites. The paper presents some results obtained with PU/clay and PU/POSS coated polyester or cotton fabrics, using cone calorimetry and thermogravimetric analysis. The efficiency of the additive chosen is clearly demonstrated and discussed. In particular, the great potential of using POSS for fire retardant applications is highlighted. Copyright © 2002 John Wiley & Sons, Ltd.
PIPD, a new high‐modulus and high‐strength polymer fibre with exceptional fire protection properties
Authors: Northolt M.G. , Sikkema D.J. , Zegers H.C. , Klop E.A. 
Published: January 2003

AbstractThe development of the new high‐modulus and high‐strength fibre M5, made of poly{2,6‐diimidazo[4,5‐b:4′,5′‐e]‐pyridinylene‐1,4(2,5‐dihydroxy)phenylene} or PIPD, has resulted in an organic polymer fibre with exceptional fire protection properties when compared with PBO, Twaron, Kevlar and Nomex fibres. The PIPD as‐spun fibre with a modulus of 150 GPa and a tensile strength of 2.5 GPa is a crystal hydrate containing 21 wt% water. Cone calorimeter measurements yielded a fire performance index (FPI) 20 times higher than Nomex, with extremely low value for the specific extinction area (SEA) characterizing the smoke formation. The PIPD‐HT fibre (recrystallized in an after treatment into the anhydrous crystalline structure) with a modulus >300 GPa and a strength >5 GPa has a FPI value similar to PBO but shows much less smoke formation than this fibre. Copyright © 2002 John Wiley & Sons, Ltd.
Enhancing polymer flame retardancy by reaction with phosphorylated polyols. Part 2. Cellulose treated with a phosphonium salt urea condensate (proban CC®) flame retardant
Authors: Horrocks A. Richard , Zhang Sheng 
Published: January 2003

AbstractPhosphorylation of cellulose flame retarded with an ammonia‐cured, polycondensed tetrakis(hydroxymethyl) phosphonium‐urea derivative (as Proban CC, Rhodia) with a polyol diphosphoryl chloride or phosphorochloridate like spirocyclic pentaerythritol di(phosphoryl chloride) or diphosphorochloridate, SPDPC can yield phosphorus levels in excess of 10% (w/w). Such high levels suggest up to 82% yields of reaction if phosphorylation of the free secondary amine groups present in the cross‐linked flame retardant is the assumed site.The presence of substituted pentaerythritol phosphate moieties significantly increases char formation above 400°C and scanning electron microscopy indicates that the char has an intumescent structure. The char‐forming characteristic is not influenced by subjecting the phosphorylated flame retardant cellulose to boiling in a 1% detergent solution in water thereby suggesting that the product is durable. The potential of this reaction to create a durable, intumescent flame retardant for cellulose is discussed. Copyright © 2002 John Wiley & Sons, Ltd.