bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing the efficacy of cyclooxygenase 2–specific inhibitors in treating osteoarthritis: Appropriate trial design considerations and results of a randomized, placebo‐controlled trial
Authors: Gibofsky Allan , Williams Gary W. , McKenna Frank , Fort John G. 
Published: November 2003

AbstractObjectiveTo compare the efficacy of the cyclooxygenase 2 (COX‐2)–specific inhibitors celecoxib and rofecoxib in treating the signs and symptoms of osteoarthritis (OA).MethodsIn this randomized, placebo‐controlled, double‐blind, multicenter study, 475 patients with OA of the knee received either celecoxib 200 mg/day (n = 189), rofecoxib 25 mg/day (n = 190), or placebo (n = 96) for 6 weeks. Arthritis assessments were performed at baseline, week 3, and week 6 (or at the time of early termination).ResultsIn primary measures of efficacy (OA pain score on a 100‐mm visual analog scale [VAS] and total domain score on the Western Ontario and McMaster Universities Osteoarthritis Index), celecoxib 200 mg/day and rofecoxib 25 mg/day demonstrated similar efficacy. At week 6, celecoxib was associated with a 34‐mm mean improvement on the VAS for OA pain, compared with 31.6 mm for rofecoxib and 21.2 mm for placebo. The difference between celecoxib and rofecoxib was −2.5 mm, with an upper limit of the 95% confidence interval of 2.7 mm and within the prespecified definition of noninferiority. Secondary measures of efficacy showed similar results. All differences in primary and secondary measures of efficacy between the 2 active treatments and placebo were statistically significant (P < 0.02), whereas all of the comparisons of efficacy between celecoxib and rofecoxib met the predefined criteria for noninferiority. All treatments were well tolerated throughout the study, with similar proportions of patients withdrawing due to adverse events.ConclusionCelecoxib 200 mg/day and rofecoxib 25 mg/day are equally efficacious in treating the signs and symptoms of OA.
The emancipatory character of action research, its history and the present state of the art
Authors: Boog Ben W. M. 
Published: November 2003

AbstractRight from the start, action research was intended to be emancipatory research, and it still is. This article will underpin this by outlining its history and the present state of the art. Though a variety of action research approaches have developed along divergent theoretical pathways, it will be stressed that these approaches share the most important characteristics of action research and are basically different applications of different action theories. They are all supported by a participatory worldview and are meant to be a double‐sided process of research, self research and education directed at individual empowerment and collective empowerment and/or emancipation. Since the relationship between the researcher and the subjects being researched is crucial for the success of action research as an emancipatory or empowering activity, this article will maintain that the most important task of action researchers is to develop refined heuristics concerning this communication. The article will end by making some recommendations for the improvement of action research as an emancipatory practice. Copyright © 2003 John Wiley & Sons, Ltd.
’︁No limits‚: doing participatory action research with young people in Northumberland
Authors: Bostock Jan , Freeman Jane 
Published: November 2003

AbstractPeople's health needs tend to be responded to by professionally led, individualistic and reactive services, rather than preventive interventions, or by drawing on lay expertise. In this project, we used a participatory approach to involve young people in researching their needs and views of how sources of support can be improved and developed. We present the background to the work undertaken; the participatory methods used; results and recommendations. The young people emphasized their preferences for informal support rather than counselling services; and changes in the attitudes of professionals towards young people, rather than major new service developments. We discuss the implications of a participatory approach to the research and to the individuals involved. Copyright © 2003 John Wiley & Sons, Ltd.
From participative research to participative practice—a study in youth care
Authors: Roose Rudi , De Bie Maria 
Published: November 2003

AbstractIn this contribution the development in action research of a participative care practice in youth care is discussed. The study was prompted by the intention of the Flemish government to reform youth care. The initial research‐question was how youth care can be organized in such a way that it (also) represents an added value for the client(s). The aim was to find out to what extent the reorganization of youth care could contribute to a social service that enhances a dignified existence for their clients and contributes to a participative care. Hence, the aim of the research was not just to reorganize youth care, but also to develop a participative care practice. The research findings highlight the tension between a reorganization that takes as its starting point an expert way of thinking, and the realization of participative care in which the clients' perspective is taken as central point of departure. Against the background of this tension, the question to what extent care workers actually have room to realize a participative care practice turned out to be one of the most important issues within the research. Copyright © 2003 John Wiley & Sons, Ltd.
4‐Fluorophenylglycine as a Label for 19F NMR Structure Analysis of Membrane‐Associated Peptides
Authors: Afonin Sergii , Glaser Ralf W. , Berditchevskaia Marina , Wadhwani Parvesh , Gührs Karl‐Heinz , Möllmann Ute , Perner Andrea , Ulrich Anne S. 
Published: November 2003

AbstractThe non‐natural amino acid 4‐fluorophenylglycine (4F‐Phg) was incorporated into several representative membrane‐associated peptides for dual purpose. The 19F‐substituted ring is directly attached to the peptide backbone, so it not only provides a well‐defined label for highly sensitive 19F NMR studies but, in addition, the D and L enantiomers of the stiff side chain may serve as reporter groups on the transient peptide conformation during the biological function. Besides peptide synthesis, which is accompanied by racemisation of 4F‐Phg, we also describe separation of the epimers by HPLC and removal of trifluoroacetic acid. As a first example, 18 different analogues of the fusogenic peptide “B18” were prepared and tested for induction of vesicle fusion; the results confirmed that hydrophobic sites tolerated 4F‐Phg labelling. Similar fusion activities within each pair of epimers suggest that the peptide is less structured in the fusogenic transition state than in the helical ground state. In a second example, five doubly labelled analogues of the antimicrobial peptide gramicidin S were compared by using bacterial growth inhibition assays. This cyclic β‐sheet peptide could accommodate both L and D substituents on its hydrophobic face. As a third example, we tested six analogues of the antimicrobial peptide PGLa. The presence of d‐4F‐Phg reduced the biological activity of the peptide by interfering with its amphiphilic α‐helical fold. Finally, to illustrate the numerous uses of l‐4F‐Phg in 19F NMR spectroscopy, we characterised the interaction of labelled PGLa with uncharged and negatively charged membranes. Observing the signal of the free peptide in an aqueous suspension of unilamellar vesicles, we found a linear saturation behaviour that was dominated by electrostatic attraction of the cationic PGLa. Once the peptide is bound to the membrane, however, solid‐state 19F NMR spectroscopy of macroscopically oriented samples revealed that the charge density has virtually no further influence on the structure, alignment or mobility of the peptide.
Mutagenic Stabilization of the Photocycle Intermediate of Green Fluorescent Protein (GFP)
Authors: Wiehler Jens , Jung Gregor , Seebacher Christian , Zumbusch Andreas , Steipe Boris 
Published: November 2003

AbstractThe optical spectra of the Aequorea victoria green fluorescent protein (GFP) are governed by an equilibrium between three different chromophore states. Mutants that predominantly show either the protonated (A) or the deprotonated (B) form of the chromophore have previously been described. In contrast, the I form, which is formed by rapid excited‐state deprotonation of the A form of the chromophore, has only been described as an obligatory photochemical intermediate. We report the design of a new GFP mutant with a stabilized I form. For this purpose, we introduced two isosteric point mutations, Thr203Val and Glu222Gln, that selectively raise the potential energy of both the A and the B form. Knowledge of the absorption spectrum of the I form at room temperature allows the detailed analysis of concentration dependent changes in bulk wild‐type(wt)‐GFP spectra, as well as the determination of the dimerization constant of GFP. This information expands the use of GFP to that of a spectral probe for protein concentration. We determined energy differences between the chromophore ground states in the monomer and the dimer and reconstructed part of the potential energy surface.
Gene Expression within Cell‐Sized Lipid Vesicles
Authors: Nomura Shin‐ichiro M. , Tsumoto Kanta , Hamada Tsutomu , Akiyoshi Kazunari , Nakatani Yoichi , Yoshikawa Kenichi 
Published: November 2003

AbstractFunctional protein synthesis was observed in cell‐sized lipid vesicles following encapsulation of a gene‐expression system. Expression of rsGFP (red‐shifted green fluorescent protein) within individual vesicles was observed by fluorescence microscopy. Interestingly, at the early stage of the reaction, the expression efficiency inside the vesicle was remarkably higher than that in the solution outside. The synthesized rsGFP in individual vesicles is safe from attack by proteinase K added to the external aqueous solution. Studies on cell‐sized vesicles expressing protein should contribute to a fundamental understanding of certain aspects of living systems and will be useful for practical applications, such as the construction of microreactors.
Chemical and Enzymatic Synthesis of Fluorinated‐Dehydroalanine‐Containing Peptides
Authors: Zhou Hao , Schmidt Dawn M. Z. , Gerlt John A. , van der Donk Wilfred A. 
Published: November 2003

AbstractMichael acceptors have long been recognized as reactive functionalities that may link a biologically active molecule to its cellular target. 1,2‐Dehydro amino acids are potential Michael acceptors present in a large number of natural products, but their reactivity is modulated by the deactivating nature of the α‐amino group engaged in an amide bond. We describe here the preparation of 3‐fluoro‐1,2‐dehydroalanine moieties within peptides that significantly enhance the reactivity of the Michael acceptor. Two different routes were designed to access these compounds, one relying on chemical means to introduce the desired functionality and the second taking advantage of a peptide epimerase. In the chemical approach, the fluoro‐Pummerer reaction of cysteine derivatives afforded 3‐fluorocysteine residues that were oxidized to the corresponding sulfoxides, followed by thermolytic elimination to provide the desired 3‐fluorodehydroalanines. The mechanism of the fluoro‐Pummerer reaction was investigated and several possible pathways were ruled out. The enzymatic approach utilized the dipeptide epimerase YcjG from Escherichia coli. Difluorinated alanine was incorporated at the C terminus of a dipeptide by chemical means. The resulting peptide proved to be a substrate for YcjG, which catalyzed fluoride elimination to provide the 3‐fluorodehydroalanine‐containing peptide. Mechanistic investigations showed that fluoride elimination occurred faster than epimerization and at a rate close to that of epimerization of Ala‐Ala.
Real‐Time Polymerase Chain Reaction
Authors: Wilhelm Jochen , Pingoud Alfred 
Published: November 2003

AbstractReal‐time PCR is the state‐of‐the‐art technique to quantify nucleic acids for mutation detection, genotyping and chimerism analysis. Since its development in the 1990s, many different assay formats have been developed and the number of real‐time PCR machines of different design is continuously increasing. This review provides a survey of the instruments and assay formats available and discusses the pros and cons of each. The principles of quantitative real‐time PCR and melting curve analysis are explained. The quantification algorithms with internal and external standardization are derived mathematically, and potential pitfalls for the data analysis are discussed. Finally, examples of applications of this extremely versatile technique are given that demonstrate the enormous impact of real‐time PCR on life sciences and molecular medicine.
On the Mechanism of the Laccase–Mediator System in the Oxidation of Lignin
Authors: Crestini Claudia , Jurasek Lubo , Argyropoulos Dimitris S. 
Published: November 2003

AbstractIn an effort to elucidate the role of phenolic and non‐phenolic lignin subunits in a laccase mediator (LM) system, vanillyl alcohol was oxidized with laccase in the presence and absence of the mediator 1‐hydroxybenzotriazol (HBT). Furthermore, the role of phenolic, aliphatic hydroxyl, and carboxylic acid moieties in lignin degradation was elucidated by selectively blocking them. The modified samples were then subjected to laccase and laccase–HBT treatments. On the basis of this data it was possible to establish the role of this mediator. HBT mediates the oxidation of lignin by inducing side‐chain oxidation and oxygen‐addition products rather than oxidative coupling reactions.
Gas‐Phase Activation and Reaction Dynamics of Chiral Ion–Dipole Complexes
Authors: Filippi Antonello , Speranza Maurizio 
Published: November 2003

AbstractA family of enantiomerically pure oxonium ions, that is O‐protonated 1‐aryl‐1‐methoxyethanes, has been generated in the gas phase by the (CH3)2Cl+ methylation of the corresponding 1‐arylethanols. Some information on their reaction dynamics was obtained from a detailed kinetic study of their inversion of configuration and dissociation. The activation parameters of the inversion reaction are found to obey two different isokinetic relationships depending upon the nature and the position of the substituents in the oxonium ions. In contrast, the activation parameters of the dissociation reaction obey a single isokinetic relationship. The inversion and dissociation rate constants do not follow simple linear free‐energy relationships. This complicated kinetic picture has been rationalized in terms of different activation dynamics in gaseous CH3Cl, which, in turn, determine the reaction dynamics of the oxonium ion. When the predominant activation of the oxonium ion involves resonant energy exchange from the 1015 cm−1 CH3 rocking mode of unperturbed CH3Cl, the inversion reaction proceeds through the dynamically most favored TS, characterized by the unassisted CαO bond elongation. When, instead, the activation of the oxonium ions requires the formation of an intimate encounter complex with CH3Cl, the inversion reaction takes place via the energetically most favored TS, characterized by multiple coordination of the CH3OH moiety with the Hα and Hortho atoms of the benzylic residue. The activation dynamics operating in the intimate encounter complex with CH3Cl is also responsible for the dissociation of most selected oxonium ions.
Facial Selectivity of the (R)‐1,3‐Dimethyl‐1‐Cyclohexyl Cation in the Gas Phase
Authors: Filippi Antonello 
Published: November 2003

AbstractThe model reaction between the (R)‐1,3‐dimethyl‐1‐cyclohexyl cation (I) and methanol has been investigated under gas‐phase radiolytic conditions (750 Torr; 25–120 °C) with the aim of evaluating the intrinsic factors that govern the facial selectivity of biased carbocations. The peculiarity of the experimental approach allows the formation of different CH318OH⋅I ionic adducts. Subsequent conversion of these adducts to give the corresponding E/Z covalent products follows different reaction coordinates, which are characterized by their own activation parameters. On the grounds of density functional theory (DFT) results, several [CH3OH⋅I] structures have been located on the relevant potential‐energy surface (PES). The experimental results point to a gas‐phase facial selectivity, which is mainly governed by entropic factors that arise as a result of the occurrence of different noncovalent ion–molecule “facial adducts” (FA). The formation of FAs may also play an important role in both the reaction dynamics and the positional selectivity. The present results cannot be interpreted by any of the models based on solution‐phase experiments.
Structural Study of the Thermal and Photochemical Spin States in the Spin Crossover Complex [Fe(phen)2(NCSe)2]
Authors: MacLean Elizabeth J. , McGrath Catherine M. , O'Connor Charles J. , Sangregorio Claudio , Seddon Jon M. W. , Sinn Ekk , Sowrey Frank E. , Teat Simon J. , Terry Ann E. , Vaughan Gavin B. M. , Young Nigel A. 
Published: November 2003

AbstractThe first structural data for [Fe(phen)2(NCSe)2] (obtained using the extraction method of sample preparation) in its high‐spin, low‐spin and LIESST induced metastable high‐spin states have been recorded using synchrotron radiation single crystal diffraction. The space group for all of the spin states was found to be Pbcn. On cooling from the high‐spin state (HS‐1) at 292 K through the spin crossover at about 235 K to the low‐spin state at 100 K (LS‐1) the iron coordination environment changed to a more regular octahedral geometry and the FeN bond lengths decreased by 0.216 and 0.196 Å (FeN(phen)) and 0.147 Å (FeN(CSe)). When the low‐spin state was illuminated with visible light at about 26 K, the structure of this LIESST induced metastable high‐spin state (HS‐2) was very similar to that of HS‐1 with regards to the Fephen bond lengths, but there were some differences in the bond lengths in the Fe–NCSe unit between HS‐1 and HS‐2. When HS‐2 was warmed in the dark to 50 K, the resultant low‐spin state (LS‐2) had an essentially identical structure to LS‐1. In all spin states, all of the shortest intermolecular contacts (in terms of van der Waals radii) involved the NCSe ligand, which may be important in describing the cooperativity in the solid state. The quality of the samples was confirmed by magnetic susceptibility and IR measurements.
Aromaticity of Benzene in the Facial Coordination Mode: A Structural and Theoretical Study
Authors: Wadepohl Hubert , Entrialgo Castaño Maria 
Published: November 2003

AbstractThe effects of facial coordination of benzene to a trinuclear transition‐metal cluster have been studied by structure correlation and DFT calculational methods. Data taken from the X‐ray crystal structures of twelve complexes [{(η‐C5H4R″)Co}3(μ3‐η2:η2:η2‐C6H4RR′)]1 b–1 mwere analyzed by using standard statistical methods. The prototypal facial arene ligand is considerably expanded with respect to free benzene and shows a small but highly significant Kekulè distortion (dCC=1.42, 1.45 Å). DFT MO calculations were carried out on the model complexes [{(η‐C5H5)M}3(μ‐η2:η2:η2‐C6H6)]1 a(M=Co),2(M=Rh), and3(M=Ir). Ring currents in the facial benzene and apical cyclopentadienyl ligands have been assessed by nucleus independent chemical shift (NICS) calculations. Compared to the free ligand (with the optimizedD6hstructure as well as withD3hand aC3vgeometries similar to that in the prototypal facial arene), facial benzene exhibits somewhat reduced but still substantial cyclic electron delocalization (CED). The calculated order of CED is benzene ∼[(CO)3Cr(η‐C6H6)]4 > 1 > 2 > 3.
Nanomorphology of Polymer Frameworks and their Role as Templates for Generating Size‐Controlled Metal Nanoclusters
Authors: Artuso Frederica , D'Archivio Angelo A. , Lora Silvano , Jerabek Karel , Králik Milan , Corain Benedetto 
Published: November 2003

AbstractThe microporous (gel‐type) functional resin co‐poly‐N,N‐dimethylacrylamide (DMAA) (88 % mol)/methacrylic acid (MAA) (8 % mol)/N,N′‐methylenebisacrylamide (MBAA) (4 % mol) (MPIF(H)) is employed as the hosting framework for the production of resin‐supported Pd0 nanoclusters. The obtained composite MPIF−Na+/Pd0 is prepared upon reducing, in ethanol, MPIF−Pd2+0.5, obtained upon previous homogeneous dispersion of “Pd2+” inside the resin particles (XRMA control) through ion‐exchange. Metal nanoclusters appear to be size‐controlled (2.0±0.2 nm) and are seen to reasonably fit the predominant resin “nanopores” diameter, determined in ethanol (3.2 nm) by means of inverse steric exclusion chromatography (ISEC).
Controlling Multivalent Interactions in Triply‐Threaded Two‐Component Superbundles
Authors: Balzani Vincenzo , Clemente‐León Miguel , Credi Alberto , Lowe James N. , Badjić Jovica D. , Stoddart J. Fraser , Williams David J. 
Published: November 2003

AbstractWe have investigated the 1H NMR spectra, the absorption spectra, the fluorescence spectra and decays, and the electrochemical properties of i) a tritopic receptor in which three benzo[24]crown‐8 macrorings are fused onto a triphenylene core, ii) a trifurcated trication wherein three dibenzylammonium ions are linked 1,3,5 to a central benzenoid core, and iii) their 1:1 adduct which constitutes a triply‐threaded, two‐component supramolecular bundle. X‐Ray crystallography has established the precise geometry of this paucivalent recognition motif in the solid state. In addition to [N+‐H⋅⋅⋅O] hydrogen bonding and [C‐H⋅⋅⋅O] interactions between the NH2+ centers on the three dibenzylammonium ion containing arms of the trication and the three crown ether rings in the tritopic receptor, there is a stabilizing [π⋅⋅⋅π] stacking interaction between the two aromatic cores. Mass spectrometry and 1H NMR spectroscopy have confirmed the integrity of the 1:1 adduct beyond the solid state, provided the solvents are relatively apolar (e.g., chloroform and acetonitrile). The intense fluorescence emissions of the two recognition components are quenched upon association with the concomitant appearance of a lower energy, broad fluorescence band originating from the π–π stacking in the 1:1 adduct of the aromatic cores in the two matching components. Titration experiments, including Job plots, establish the 1:1 stoichiometry of the adduct, an observation which is also confirmed by electrochemical experiments. The electrochemical results show that, both in the tritopic receptor and in the superbundle itself, the first oxidation process is associated with the hexaalkoxytriphenylene core. The successive oxidation processes of the peripheral dioxybenzene units are affected by charge‐transfer interactions in the tritopic receptor, whereas, in the superbundle, such units are not interacting. In acetonitrile solution, dethreading/rethreading of the 1:1 adduct can be controlled quantitatively by addition of base and acid. Dethreading and rethreading is also observed by 1H NMR spectroscopy when dimethylsulfoxide is added to a solution of the 1:1 adduct in equal volumes of acetonitrile and chloroform. A trifurcated trication where methyl groups are located on the para positions of the three dibenzylammonium ions, which are linked 1,3,5 to the neutral benzenoid core, has been employed to demonstrate that dethreading of the 1:1 adduct involves doubly‐threaded and singly‐threaded species, that is, the paucivalent site is dismembered in a sequence of logical steps involving stable intermediates. This molecular recognition system is a rare example of a supramolecular entity based on a cooperative binding motif that can be switched on and off by chemical means.