bluuebunny/crossref_metadata_2025_split huggingface dataset:
Skeletal muscle energetics with PNMR: personal views and historic perspectives
Authors: Chance Britton , Im Joohee , Nioka Shoko , Kushmerick Martin 
Published: October 2006

AbstractThis article reviews historical and current NMR approaches to describing in vivo bioenergetics of skeletal muscles in normal and diseased populations. It draws upon the first author's more than 70 years of personal experience in enzyme kinetics and the last author's physiological approaches. The development of in vivo PNMR jointly with researchers around the world is described. It is explained how non‐invasive PNMR has advanced human exercise biochemistry, physiology and pathology. Further, after a brief explanation of bioenergetics with PNMR on creatine kinase, anerobic glycolysis and mitochondrial oxidative phosphorylation, some basic and controversial subjects are focused upon, and the authors' view of the subjects are offered, with questions and answers. Some of the research has been introduced in exercise physiology. Future directions of NMR on bioenergetics, as a part of system biological approaches, are indicated. Copyright © 2006 John Wiley & Sons, Ltd.
Interval finite element method for dynamic response of closed‐loop system with uncertain parameters
Authors: Zhang Xiao Ming , Ding Han , Chen Su Huan 
Published: October 2006

AbstractIn practical engineering, it is difficult to obtain all possible solutions of dynamic responses with sharp bounds even if an optimum scheme is adopted where there are many uncertain parameters. In this paper, using the interval finite element (IFE) method and precise time integration (PTI) method, we discuss the dynamic response of vibration control problem of structures with interval parameters. With matrix perturbation theory and interval arithmetic, the algorithm for estimating upper and lower bounds of dynamic response of the closed‐loop system is developed directly from the interval parameters. Two numerical examples are given to illustrate the application of the present method. The example 1 is used to show the applicability of the present method. The example 2 is used to show the validity of the present method by comparing the results with those obtained by the classical random perturbation method. Copyright © 2006 John Wiley & Sons, Ltd.
Photo‐ and electroluminescent properties of a π‐conjugated copolymer containing 2,2′‐bipyridyl units
Authors: Deichmann Vitor Angelo Fonseca , Cirpan Ali , Karasz Frank E , Akcelrud Leni 
Published: October 2006

AbstractThe synthesis, structural characteristics, and photo‐ and electroluminescent properties of a soluble light‐emitting copolymer built up of regularly alternating segments of 1,4‐dihexyloxybenzene and 2,2′‐bipyridyl (PBPyDHB) are described and discussed. Optical properties of the polymer were investigated in solution and solid‐state conditions, demonstrating that in film form the predominant emission centers are inter‐macromolecular aggregates, either in photo‐ or electroluminescence. Thermogravimetric analysis indicates that PBPyDHB has very high thermal stability, with a maximum decomposition rate around 400 °C and onset with 10% mass loss at 342 °C. The polymer is a blue emitter, and the good solubility, thermal behavior, and electroluminescence properties make it a promising material for electro‐optical applications. Copyright © 2006 Society of Chemical Industry
Towards in silico lead optimization: Scores from ensembles of protein/ligand conformations reliably correlate with biological activity
Authors: Popov Veljko M. , Yee W. Atom , Anderson Amy C. 
Published: October 2006

AbstractAccurately ranking protein/ligand interactions and distinguishing subtle differences between homologous compounds in a virtual focused library in silico is essential in a structure‐based drug discovery program. In order to establish a predictive model to design novel inhibitors of dihydrofolate reductase (DHFR) from the parasitic protozoa, Cryptosporidium hominis, we docked a series of 30 DHFR inhibitors with measured inhibition constants against the crystal structure of the protein. By including protein flexibility and averaging the energies of the 25 lowest protein/ligand conformers we obtained more accurate total nonbonded energies from which we calculated a predicted biological activity. The calculated and measured biological activities showed reliable correlations of 72.9%. Additionally, visual analysis of the ensemble of protein/ligand conformations revealed alternative ligand binding pockets in the active site. Using the same principles we then created a homology model of DHFR from Toxoplasma gondii and docked 11 inhibitors. A correlation of 50.2% between docking score and activity validates both the method and the model. The correlations presented here are particularly compelling considering the high structural similarity of the ligands and the fact that we have used structures derived from crystallographic data and homology modeling. These docking principles may be useful in any lead optimization study where accurate ranking of similar compounds is desired. Proteins 2007. © 2006 Wiley‐Liss, Inc.
Validation of a real‐time PCR for the quantitative estimation of a G143A mutation in the cytochrome bc1 gene of Pyrenophora teres
Authors: Kianianmomeni Arash , Schwarz Gerhard , Felsenstein Friedrich G , Wenzel Gerhard 
Published: October 2006

AbstractA single nucleotide polymorphism (SNP) in the cytochrome b gene confers resistance to strobilurin fungicides for several fungal pathogens. Therefore, on the basis of a change at amino acid position 143 from glycine to alanine, a real‐time PCR assay was established for the quantitative detection of the analogous SNP in the cytochrome b sequence of Pyrenophora teres Drechsler, which causes barley net blotch. Allelic discrimination was achieved by using allele specific primers with artificially mismatched nucleic acid bases and minor groove binding probes. Validation parameters for the lower limits of the working range, namely limits of detection (LOD) and limits of quantification (LOQ), were statistically determined by the variance of calibration data, as well as by the variance of the 100% non‐strobilurin‐resistant allele DNA sample (blank values). It was found that the detection was limited by the variance of blank values (five in 801 458 copies; 0.0006%), whereas the quantification was limited by the variance of calibration data (37 in 801 458 copies; 0.0046%). The real‐time PCR assay was finally used to monitor strobilurin‐resistant cytochrome b alleles in barley net blotch field samples, which were already classified in in vivo biotests to be fully sensitive to strobilurins. All signals for strobilurin‐resistant cytochrome b alleles were below the LOD, and therefore the results are in total agreement with the phenotypes revealed by biotests. Copyright © 2006 Society of Chemical Industry
Development of a pheromone trap monitoring system for orange wheat blossom midge, Sitodiplosis mosellana, in the UK
Authors: Bruce Toby JA , Hooper Antony M , Ireland Lynda , Jones Owen T , Martin Janet L , Smart Lesley E , Oakley Jon , Wadhams Lester J 
Published: October 2006

AbstractField‐trapping experiments with synthetic 2,7‐nonadiyl dibutyrate, the female‐produced sex pheromone of the orange wheat blossom midge, Sitodiplosis mosellana (Géhin), demonstrated that pheromone traps were highly attractive to males and caught very few non‐target organisms. Different formulations of pheromone were tested to identify the optimum release rate and dispenser type for use in pheromone traps in the UK. Key findings were that racemic pheromone was as effective as enantiomerically pure (2S,7R)‐2,7‐nonadiyl dibutyrate, that release rates higher than 0.5 µg day−1 were not necessary and that the optimal formulation was a 1 mg pheromone loading in a rubber septum. Pheromone traps gave a reliable indication of peak midge emergence, onset of flight and abundance of midges throughout the season. A strong correlation between maximum trap catch and crop infestation levels was obtained. Copyright © 2006 Society of Chemical Industry
First principle study of the structure of conjugated amides and thioamides
Authors: Velkov Zhivko , Velkov Yasen , Balabanova Elena , Tadjer Alia 
Published: October 2006

AbstractOn the basis of ab initio and density functional theory (DFT) calculations of the o‐coumaric amide and thioamide, the latter is found to have better delocalization. It is demonstrated that the thioamide function features stronger attraction for electron density from the conjugated residue. Therefore, the electronic distribution in the thioamide favors stable phenoxyl radical formation. This is a reason to expect better antioxidant activity of the thioamide. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007
Theoretical study of the structure and electronic spectra of fully protonated emeraldine oligomers
Authors: Zhekova H. , Tadjer A. , Ivanova A. , Petrova J. , Gospodinova N. 
Published: October 2006

AbstractPolyaniline (PANI) is one of the most studied conducting polymers. Obtained in its conducting form (known as “emeraldine salt”) by chemical or electrochemical oxidation of aniline in aqueous acidic medium, this polymer manifests an array of attractive properties. Nevertheless, these properties still need to be described at the molecular level. Intense theoretical investigations during the past few years aim at explaining the chain organization, conductivity mechanism, and other structural and spectral characteristics. Most studies adopt simplified models in which hydration effect is underestimated, since all simulations are performed either in vacuum or in the presence of a limited number of water molecules. The present computational study sheds light on the molecular organization of a number of model PANI hydrated clusters with different alignment and multiplicity, which can explain the experimentally recorded UV/VIS spectra. The influence of hydration and interaction with adjacent oligomers is estimated. Short‐chain doubly protonated emeraldine oligomers are used as model systems. The calculations are performed at the semi‐empirical (AM1) and/or molecular mechanics (AMBER96) level. Proper configurations of the clusters are selected using Monte Carlo simulations. Electron correlation (CIS) is accounted for upon evaluation of the absorption spectra of the clusters. The relative strength of the interchain coupling is estimated by simulation of PANI clusters consisting of two PANI tetramers in water. Comparison to experimental results is made. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2007
Vesuvius before the 1631 eruption
Authors: Guidoboni Emanuela , Boschi Enzo 
Published: October 2006

of which a printed transcription will shortly be published [Guidoboni, 2006], provided new data concerning the activity of Vesuvius 60 years prior to its last great eruption, on 16 December 1631. This activity, which had until now been unknown to modern science, calls for a re‐evaluation of the current conditions of the volcano and of possible precursors to the next major eruption.Vesuvius is one of the most dangerous volcanoes in the world: Its activity can affect an area comprising 18 municipalities that are inhabited by more than 700,000 people in an area less than eight kilometers away from the volcano vent. The volcano has been dormant since 1944, but the history of Vesuvius has been punctuated by violent and destructive, albeit infrequent, Plinian‐type explosive eruptions, during which material is continuously ejected at a high velocity and at a great height (up to a few tens of kilometers) from the vent, forming a typical eruptive column with an umbrella cloud. In the past 3500 years, in between one Plinian eruption and the following one, several minor eruptive events have taken place, ranging from subplinian eruptions to more or less violent Strombolian activity and lava flow emissions.
Quantitative assessment of regional emphysema distribution in patients with chronic obstructive pulmonary disease (COPD)
Authors: Stavngaard T. , Shaker S. B. , Bach K. S. , Stoel B. C. , Dirksen A. 
Published: October 2006

Purpose: To compare objective and subjective assessment of the distribution of emphysema in unselected patients with chronic obstructive pulmonary disease (COPD). Material and Methods: 167 patients were computed tomography (CT) scanned, and the relative area (RA-910) of emphysema in each CT slice was plotted against table position. The craniocaudal distribution was calculated as the slope of the regression line, and grouped as upper-lung-zone predominance (ULP), lower-lung-zone predominance (LLP), or mild/homogeneous distribution (MHE). CT scans were also classified as ULP, LLP, and MHE based on visual assessment of three high-resolution CT (HRCT) slices, and the leading pattern of emphysema was classified as centrilobular (CLE), paraseptal (PSE), panlobular (PLE), or no emphysema (NE). Results: By objective classification, scans were divided into almost equal numbers of ULP, LLP, and MHE, whereas visual evaluation classified more scans as ULP ( P<0.001) and very few as LLP ( P<0.0001). In patients with CLE, 49% had ULP by objective classification, whereas LLP was the commonest leading pattern in PSE, PLE, and NE. Conclusion: We found significant discrepancies between the objective and subjective distributions of emphysema in various morphological patterns, which may be of clinical importance in, for instance, lung-volume-reduction surgery.
Phage display selection of efficient glutamine‐donor substrate peptides for transglutaminase 2
Authors: Keresztessy Zsolt , Csősz Éva , Hársfalvi Jolán , Csomós Krisztián , Gray Joe , Lightowlers Robert N. , Lakey Jeremy H. , Balajthy Zoltán , Fésüs László 
Published: October 2006

AbstractUnderstanding substrate specificity and identification of natural targets of transglutaminase 2 (TG2), the ubiquitous multifunctional cross‐linking enzyme, which forms isopeptide bonds between protein‐linked glutamine and lysine residues, is crucial in the elucidation of its physiological role. As a novel means of specificity analysis, we adapted the phage display technique to select glutamine‐donor substrates from a random heptapeptide library via binding to recombinant TG2 and elution with a synthetic amine‐donor substrate. Twenty‐six Gln‐containing sequences from the second and third biopanning rounds were susceptible for TG2‐mediated incorporation of 5‐(biotinamido)penthylamine, and the peptides GQQQTPY, GLQQASV, and WQTPMNS were modified most efficiently. A consensus around glutamines was established as pQX(P,T,S)l, which is consistent with identified substrates listed in the TRANSDAB database. Database searches showed that several proteins contain peptides similar to the phage‐selected sequences, and the N‐terminal glutamine‐rich domain of SWI1/SNF1‐related chromatin remodeling proteins was chosen for detailed analysis. MALDI/TOF and tandem mass spectrometry‐based studies of a representative part of the domain, SGYGQQGQTPYYNQQSPHPQQQQPPYS (SnQ1), revealed that Q6, Q8, and Q22 are modified by TG2. Kinetic parameters of SnQ1 transamidation (KMapp = 250 μM, kcat = 18.3 sec−1, and kcat/KMapp = 73,200) classify it as an efficient TG2 substrate. Circular dichroism spectra indicated that SnQ1 has a random coil conformation, supporting its accessibility in the full‐length parental protein. Added together, here we report a novel use of the phage display technology with great potential in transglutaminase research.
Catalytic mechanism of cyclophilin as observed in molecular dynamics simulations: Pathway prediction and reconciliation of X‐ray crystallographic and NMR solution data
Authors: Trzesniak Daniel , van Gunsteren Wilfred F. 
Published: October 2006

AbstractCyclophilins are proteins that catalyze X‐proline cis–trans interconversion, where X represents any amino acid. Its mechanism of action has been investigated over the past years but still generates discussion, especially because until recently structures of the ligand in the cis and trans conformations for the same system were lacking. X‐ray crystallographic structures for the complex cyclophilin A and HIV‐1 capsid mutants with ligands in the cis and trans conformations suggest a mechanism where the N‐terminal portion of the ligand rotates during the cis–trans isomerization. However, a few years before, a C‐terminal rotating ligand was proposed to explain NMR solution data. In the present study we use molecular dynamics (MD) simulations to generate a trans structure starting from the cis structure. From simulations starting from the cis and trans structures obtained through the rotational pathways, the seeming contradiction between the two sets of experimental data could be resolved. The simulated N‐terminal rotated trans structure shows good agreement with the equivalent crystal structure and, moreover, is consistent with the NMR data. These results illustrate the use of MD simulation at atomic resolution to model structural transitions and to interpret experimental data.
Characterization of two potentially universal turn motifs that shape the repeated five‐residues fold—Crystal structure of a lumenal pentapeptide repeat protein from Cyanothece 51142
Authors: Buchko Garry W. , Ni Shuisong , Robinson Howard , Welsh Eric A. , Pakrasi Himadri B. , Kennedy Michael A. 
Published: October 2006

AbstractThe genome of the diurnal cyanobacterium Cyanothece sp. PCC 51142 has recently been sequenced and observed to contain 35 pentapeptide repeat proteins (PRPs). These proteins, while present throughout the prokaryotic and eukaryotic kingdoms, are most abundant in cyanobacteria. The sheer number of PRPs in cyanobacteria coupled with their predicted location in every cellular compartment argues for important, yet unknown, physiological and biochemical functions. To gain biochemical insights, the crystal structure for Rfr32, a 167‐residue PRP with an N‐terminal 29‐residue signal peptide, was determined at 2.1 Å resolution. The structure is dominated by 21 tandem pentapeptide repeats that fold into a right‐handed quadrilateral β‐helix, or Rfr‐fold, as observed for the tandem pentapeptide repeats in the only other PRP structure, the mycobacterial fluoroquinoline resistance protein MfpA from Mycobacterium tuberculosis. Sitting on top of the Rfr‐fold are two short, antiparallel α‐helices, bridged with a disulfide bond, that perhaps prevent edge‐to‐edge aggregation at the C terminus. Analysis of the main‐chain (Φ,Ψ) dihedral orientations for the pentapeptide repeats in Rfr32 and MfpA makes it possible to recognize the structural details for the two distinct types of four‐residue turns adopted by the pentapeptide repeats in the Rfr‐fold. These turns, labeled type II and type IV β‐turns, may be universal motifs that shape the Rfr‐fold in all PRPs.
Statistical potential for assessment and prediction of protein structures
Authors: Shen Min‐yi , Sali Andrej 
Published: October 2006

AbstractProtein structures in the Protein Data Bank provide a wealth of data about the interactions that determine the native states of proteins. Using the probability theory, we derive an atomic distance‐dependent statistical potential from a sample of native structures that does not depend on any adjustable parameters (Discrete Optimized Protein Energy, or DOPE). DOPE is based on an improved reference state that corresponds to noninteracting atoms in a homogeneous sphere with the radius dependent on a sample native structure; it thus accounts for the finite and spherical shape of the native structures. The DOPE potential was extracted from a nonredundant set of 1472 crystallographic structures. We tested DOPE and five other scoring functions by the detection of the native state among six multiple target decoy sets, the correlation between the score and model error, and the identification of the most accurate non‐native structure in the decoy set. For all decoy sets, DOPE is the best performing function in terms of all criteria, except for a tie in one criterion for one decoy set. To facilitate its use in various applications, such as model assessment, loop modeling, and fitting into cryo‐electron microscopy mass density maps combined with comparative protein structure modeling, DOPE was incorporated into the modeling package MODELLER‐8.
Pharmacokinetics and safety assessments of high‐dose and 4‐week treatment with S‐3304, a novel matrix metalloproteinase inhibitor, in healthy volunteers
Authors: Mant Timothy G. K. , Bradford Daniel , Amin Dipti M. , Pisupati Jaya , Kambayashi Yoshikazu , Yano Yoshitaka , Tanaka Kazushige , Yamada‐Sawada Takuko 
Published: October 2006

AimsTo investigate the tolerability, safety and pharmacokinetics of S‐3304 in healthy volunteers treated with high doses of S‐3304 for 28 days.MethodsThirty‐two healthy volunteers were recruited. Four male and four female subjects were allocated to one of four doses (800 mg, 1600 mg, 2400 mg and 3200 mg). At each dose six volunteers took active medication and two volunteers took placebo in a double‐blind fashion. Volunteers took a single dose on days 1 and 28 for pharmacokinetic purposes, and took twice daily doses from day 3–27. The pharmacokinetics of S‐3304 and its hydroxy metabolites were evaluated. Tolerance was based on subjective adverse events, clinical examination, vital signs, ECG and laboratory tests including haematology and biochemistry profiles using CTC grading.ResultsDoses up to 2400 mg twice daily were generally well tolerated. At 3200 mg twice daily, five volunteers including one randomized to placebo were withdrawn from treatment mainly due to alanine aminotransferase (ALT) elevation. Cmax of S‐3304 on day 1, whose geometric mean and 95% confidence interval were 66.3 µg ml−1 (48.8, 90.0) for 800 mg, 82.6 µg ml−1 (69.3, 98.6) for 1600 mg, 89.5 µg ml−1 (79.5, 100.7) for 2400 mg, and 110.5 µg ml−1 (88.9, 137.7) for 3200 mg, respectively, was correlated with the log‐transformed peak ALT (P < 0.0001 for male and P = 0.048 for female volunteers).ConclusionsIn healthy volunteers the maximum tolerated dose of S‐3304 was 2400 mg twice daily. ALT elevation was the most frequent dose‐limiting factor and was correlated with Cmax on day 1.
Current management of follicular lymphomas
Authors: Hiddemann Wolfgang , Buske Christian , Dreyling Martin , Weigert Oliver , Lenz Georg , Unterhalt Michael 
Published: October 2006

SummaryAfter decades of stagnation, the prognosis of patients with follicular lymphomas (FL) has changed substantially within the last few years due to new and effective therapeutic modalities. These include myeloablative therapy followed by autologous stem cell transplantation (ASCT) in younger patients in first remission, which showed a significant prolongation of remission duration in three prospective randomised trials while the impact on overall survival still needs to be determined. Adding the anti‐CD 20 antibody Rituximab to conventional chemotherapy resulted in a significant increase in remission rate, remission duration and, in two of four currently available prospective randomised studies, even in a longer overall survival. A prolongation of remission duration was also seen when Rituximab was given as maintenance after cytoreductive therapy including Rituximab. Radio‐immunotherapy (RIT) with radioisotopes coupled to monoclonal antibodies produced encouraging data in several phase II studies. New therapeutic perspectives have also emerged from increasing insights into the biology of the disease that unravel molecular targets for novel agents, some of which have entered clinical evaluation already.