bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generalized correlation for biomolecular dynamics
Authors: Lange Oliver F. , Grubmüller Helmut 
Published: December 2005

AbstractCorrelated motions in biomolecules are often essential for their function, e.g., allosteric signal transduction or mechanical/thermodynamic energy transport. Because correlated motions in biomolecules remain difficult to access experimentally, molecular dynamics (MD) simulations are particular useful for their analysis. The established method to quantify correlations from MD simulations via calculation of the covariance matrix, however, is restricted to linear correlations and therefore misses part of the correlations in the atomic fluctuations. Herein, we propose a general statistical mechanics approach to detect and quantify any correlated motion from MD trajectories. This generalized correlation measure is contrasted with correlations obtained from covariance matrices for the B1 domain of protein G and T4 lysozyme. The new method successfully quantifies correlations and provides a valuable global overview over the functionally relevant collective motions of lysozyme. In particular, correlated motions of helix 1 together with the two main lobes of lysozyme are detected, which are not seen by the conventional covariance matrix. Overall, the established method misses more than 50% of the correlation. This failure is attributed to both, an interfering and unnecessary dependence on mutual orientations of the atomic fluctuations and, to a lesser extent, attributed to nonlinear correlations. Our generalized correlation measure overcomes these problems and, moreover, allows for an improved understanding of the conformational dynamics by separating linear and nonlinear contributions of the correlation. Proteins 2006. © 2005 Wiley‐Liss, Inc.
Magnetic studies of the carbothermal effect on LiFePO4
Authors: Ait‐Salah A. , Zaghib K. , Mauger A. , Gendron F. , Julien C. M. 
Published: December 2005

AbstractThe effect of carbon coating on the properties of LiFePO4 particles is studied from magnetic measurements. Magnetization experiments are an excellent tool to detect very low concentrations of iron‐based impurities (<1 ppm) which are poisoning the phospho‐olivine used as positive electrode material in rechargeable Li‐ion batteries. The results indicate that addition of 5% carbon withdraws traces of the Fe(III) phase such as Fe2P and/or Fe2O3. This carbothermal effect appears to be beneficial for long‐term application of LiFePO4 materials in Li‐ion batteries. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
On Selection of Training and Test Sets for the Development of Predictive QSAR models
Authors: Leonard J. Thomas , Roy Kunal 
Published: December 2005

AbstractThe development of predictive QSAR models depends not only on the statistical method but also on the algorithm used for the selection of training and test sets. Here, we describe the validation of QSAR models for three data sets with different sizes (n=35, 56 and 87) based on random division, sorted biological activity data andK‐means clusters for the factor scores of the original variable matrix along with/without biological activity values. When the training and test sets were generated by random division or by the activity‐range algorithm, predictive models were not obtained in most of the cases. In case of random division of the data sets into training and test sets, there is no correlation between internal and external validation statistics. However, good external validation statistics were obtained when training and test sets were selected based onK‐means clusters of factor scores of the descriptor space along with/without the biological activity values. So, the selection of training and test sets should be based on the proximity of the representative points of the test set to representative points of the training set in the multidimensional descriptor space. The concept of closeness is based on the general assumption underlying all QSAR theories: similar compounds have similar activities. Thus, if one wishes to validate a QSAR model, the points of the test set must be close to the points of the training set in the multidimensional descriptor space. Based on the results of several methods for the division of the training and test sets, we propose thatK‐means‐cluster‐based division of training and prediction sets can be used as a reliable method of division of data set into training and test sets for developing predictive QSAR models.
On the design and development of hybrid journal bearings: a review
Authors: Garg H.C. , Sharda H.B. , Kumar V. 
Published: December 2005

AbstractThis paper presents a comprehensive review of developments in the design and application of hydrostatic and hybrid journal bearing systems during the last few decades. Revolutionary changes have taken place in the applications of hydrostatic and hybrid journal bearings, from very low‐speed radar to very high‐speed turbo‐machinery and ultra‐precision machine tools requiring high stiffness to improve accuracy. Hydrostatic and hybrid bearings are of interest because of their potential at very high operating speed and heavy load‐carrying capacity. This paper also outlines the analyses done of these types of journal bearings in practical application, which has led to improved bearing design. This review critically discusses the parameters that significantly affect the static and dynamic performance of a journal bearing. This review includes coverage of recent publications in the literature pertaining to hydrostatic and hybrid journal bearings focusing on the influence of parameters such as bearing geometry, supply pressure, flow control devices, fluid compressibility, fluid inertia, journal misalignment, bearing flexibility, surface roughness, and thermal effects. Copyright © 2006 John Wiley & Sons, Ltd.
Effect of wear on EHD film thickness in sliding contacts
Authors: Michalczewski R. , Szczerek M. , Wiśniewski M. 
Published: December 2005

AbstractA theoretical solution to the elastohydrodynamic (EHD) lubrication problem in sliding contacts, which takes into consideration the effect of the change in shape of the gap due to wear on the load‐carrying capacity, is presented. The model of such a contact is based on assumptions of Grubin and Ertel (von Mohrenstein). The resultant dimensionless Reynolds and film profile equations have been solved numerically for a number of cases with several values of thickness of the worn layer. Iteration of the EHD film thickness is performed by means of the secant method.Values of the calculated dimensionless film thickness are presented as a function of dimensionless wear. The conclusions concern the influence of the linear wear on the film thickness in heavily loaded sliding contacts. Copyright © 2006 John Wiley & Sons, Ltd.
Studies of lubricating oil base stock: characterisation and composition
Authors: Khan H.U. , Nautiyal S.P. , Anwar M. , Agrawal K.M. 
Published: December 2005

AbstractA lubricating oil base stock, Inter Neutral type, boiling range 282–562°C, was fractionated into three boiling ranges of 282–456, 456–492, and 492–562°C. The waxes were isolated from the parent base stock and its fractions by solvent dewaxing. Hydrocarbon‐type constituents, i.e., saturates, naphthenic aromatics, and polar aromatics, were separated by elution chromatography and were characterised for their physical properties. The viscosity–temperature behaviour of the base stock sample and its various fractions and components, i.e., dewaxed oil, extracted waxes, saturates, naphthenic aromatics, and polar aromatics, was determined and correlated with the composition. It was found that the concentration, nature, and type of hydrocarbon components present greatly influenced the physical properties as well as the viscosity–temperature behaviour. The average chain lengths of the waxes obtained by 1H NMR match well with those determined by gas chromatography. Copyright © 2006 John Wiley & Sons, Ltd.
Dynamic characteristics of spiral groove bearing spindles: comparison between rotating‐shaft and fixed‐shaft designs
Authors: Zou Q. , Tian Y. , Wen S. , Konno D. 
Published: December 2005

AbstractIn this paper, two types of spiral groove bearing (SGB) spindles, a rotating‐shaft spindle and a fixed‐shaft spindle, are analysed, and the dynamic characteristics of these two types of spindles are tested and compared. The effects of lubricants on the dynamic characteristics and power consumption of the spindles are considered. It is found that the dynamic characteristics of the fixed‐shaft spindle are much better in terms of non‐repeatable run out than those of the rotating‐shaft spindle. The lubricants are found to have significant effects on both the dynamic characteristics and power consumption of the spindles. Copyright © 2006 John Wiley & Sons, Ltd.
Reconstruction of the tensor tympani tendon
Authors: Bauer M , Vóna I , Gerlinger I 
Published: December 2005

We describe a case in which reconstruction of the tendon of the tensor tympani muscle was necessary for the successful restoration of sound conduction.The right ear of a nine-year-old boy was treated for cholesteatoma with staged surgery. During the first operation, the tendon was cut to ensure good visibility in the tympanic cavity. Post-operatively, maintenance of aeration of the middle ear required ventilation tubes at first and Valsalva manoeuvres later on. The position of the reconstructed tympanic membrane varied a great deal, moving between the medial wall of the tympanic cavity and extreme bulging. This made exact measurement of a columella for ossicular reconstruction impossible.The preserved handle of the malleus was bound to the cochleariform process with ionomer cement, using a piece of surgical suture material as a substitute for the tendon. This arrangement prevented the tympanic membrane from undergoing excessive lateral movement after inflation and the ossicular chain was replaced with a successful ossiculoplasty with an autogenous bone ‘drum to footplate’ columella. The pre-operative 55.0 dB air–bone gap decreased immediately to 3.3 dB, widening after three years to 15.0 dB.
SMAD 8 binding to mice Msx1 basal promoter is required for transcriptional activation
Authors: Binato Renata , Alvarez Martinez Cristina E. , Pizzatti Luciana , Robert Benoit , Abdelhay Eliana 
Published: December 2005

The Msx1 gene in mice has been proven to be induced by BMP (bone morphogenetic protein) proteins, and three binding sites for SMAD, an intracellular BMP signalling transducer, have already been identified in its promoter. Gel shift analyses were performed and they demonstrated that the consensus found very near the transcription start site, a region designed BP (basal promoter), is functional for binding nuclear proteins from 10.5, 11.5 and 13.5 dpc (days post-coitum) embryos. Notably, this binding occurs only when the SMAD-binding consensus sequence is maintained, suggesting that it is required for the formation of a protein complex over BP. Binding of purified SMAD 1 and SMAD 4 as well as supershift assay with SMAD 1/SMAD 5/SMAD 8 antibody proved that a SMAD protein is present in this complex. Transfection assays in cell cultures with fragments from BP driving the expression of luciferase confirmed that only in the presence of the SMAD consensus site is Msx1 expression activated. A proteomic analysis of the complex components after immunoprecipitation identified several proteins necessary to activate transcription including SMAD 8. Our results suggest that BMP2/BMP4 signalling through SMAD 8 is required for transcriptional activation of the mouse Msx1 gene.
The hnRNPs F and H2 bind to similar sequences to influence gene expression
Authors: Alkan Serkan A. , Martincic Kathleen , Milcarek Christine 
Published: December 2005

The hnRNPs (heterogeneous nuclear ribonucleoproteins) F and H2 share a similar protein structure. Both have been implicated as regulating polyadenylation, but hnRNP H2 had a positive effect, whereas hnRNP F acted negatively. We therefore carried out side-by-side comparisons of their RNA-binding and in vivo actions. The binding of the CstF2 (64 kDa cleavage stimulatory factor) to SV40 (simian virus 40) late pre-mRNA substrates containing a downstream GRS (guanine-rich sequence) was reduced by hnRNP F, but not by hnRNP H2, in a UV-cross-linking assay. Point mutations of the 14-nt GRS influenced the binding of purified hnRNP F or H2 in parallel. Co-operative binding of the individual proteins to RNA was lost with mutations of the GRS in the G1−5 or G12−14 regions; both regions seem to be necessary for optimal interactions. Using a reporter green fluorescent protein assay with the GRS inserted downstream of the poly(A) (polyadenine) signal, expression in vivo was diminished by a mutant G1−5 sequence which decreased binding of both hnRNPs (SAA20) and was enhanced by a 12–14-nt mutant that showed enhanced hnRNP F or H2 binding (SAA10). Using small interfering RNA, down-regulation of hnRNP H2 levels diminished reporter expression, confirming that hnRNP H2 confers a positive influence; in contrast, decreasing hnRNP F levels had a negligible influence on reporter expression with the intact GRS. A pronounced diminution in reporter expression was seen with the SAA20 mutant for both. Thus the relative levels of hnRNP F and H2 in cells, as well as the target sequences in the downstream GRS on pre-mRNA, influence gene expression.
Archaeal Pyrococcus furiosus thymidylate synthase 1 is an RNA-binding protein
Authors: Kanai Akio , Sato Asako , Imoto Jun , Tomita Masaru 
Published: December 2005

Using a stem–loop RNA oligonucleotide (19-mer) containing an AUG sequence in the loop region as a probe, we screened the protein library from a hyperthermophilic archaeon, Pyrococcus furiosus, and found that a flavin-dependent thymidylate synthase, Pf-Thy1 (Pyrococcus furiosus thymidylate synthase 1), possessed RNA-binding activity. Recombinant Pf-Thy1 was able to bind to the stem–loop structure at a high temperature (75 °C) with an apparent dissociation constant of 0.6 μM. A similar stem–loop RNA structure was located around the translation start AUG codon of Pf-Thy1 RNA, and gel-shift analysis revealed that Pf-Thy1 could also bind to this stem–loop structure. In vitro translation analysis using chimaeric constructs containing the stem–loop sequence in their Pf-Thy1 RNA and a luciferase reporter gene indicated that the stem–loop structure acted as an inhibitory regulator of translation by preventing the binding of its Shine–Dalgarno-like sequence by positioning it in the stem region. Addition of Pf-Thy1 into the in vitro translation system also inhibited translation. These results suggested that this class of thymidylate synthases may autoregulate their own translation in a manner analogous to that of the well characterized thymidylate synthase A proteins, although there is no significant amino acid sequence similarity between them.
Probing the substrate binding site of Candida tenuis xylose reductase (AKR2B5) with site-directed mutagenesis
Authors: Kratzer Regina , Leitgeb Stefan , Wilson David K. , Nidetzky Bernd 
Published: December 2005

Little is known about how substrates bind to CtXR (Candida tenuis xylose reductase; AKR2B5) and other members of the AKR (aldo–keto reductase) protein superfamily. Modelling of xylose into the active site of CtXR suggested that Trp23, Asp50 and Asn309 are the main components of pentose-specific substrate-binding recognition. Kinetic consequences of site-directed substitutions of these residues are reported. The mutants W23F and W23Y catalysed NADH-dependent reduction of xylose with only 4 and 1% of the wild-type efficiency (kcat/Km) respectively, but improved the wild-type selectivity for utilization of ketones, relative to xylose, by factors of 156 and 471 respectively. Comparison of multiple sequence alignment with reported specificities of AKR members emphasizes a conserved role of Trp23 in determining aldehyde-versus-ketone substrate selectivity. D50A showed 31 and 18% of the wild-type catalytic-centre activities for xylose reduction and xylitol oxidation respectively, consistent with a decrease in the rates of the chemical steps caused by the mutation, but no change in the apparent substrate binding constants and the pattern of substrate specificities. The 30-fold preference of the wild-type for D-galactose compared with 2-deoxy-D-galactose was lost completely in N309A and N309D mutants. Comparison of the 2.4 Å (1 Å=0.1 nm) X-ray crystal structure of mutant N309D bound to NAD+ with the previous structure of the wild-type holoenzyme reveals no major structural perturbations. The results suggest that replacement of Asn309 with alanine or aspartic acid disrupts the function of the original side chain in donating a hydrogen atom for bonding with the substrate C-2(R) hydroxy group, thus causing a loss of transition-state stabilization energy of 8–9 kJ/mol.
Biotinylation of glycan chains in β2 glycoprotein I induces dimerization of the molecule and its detection by the human autoimmune anti-cardiolipin antibody EY2C9
Authors: Dupuy d'Angeac Arnaud , Stefas Ilias , Graafland Hubert , de Lamotte Frédéric , Rucheton Marcel , Palais Caroline , Eriksson Anna-Karin , Bosc Priscille , Rosé Caroline , Chicheportiche Robert 
Published: December 2005

Binding of β2GPI (β2 glycoprotein I), a human plasma protein, to AnPLs (anionic phospholipids) plays a key role in the formation of antiphospholipid antibodies involved in autoimmune diseases like antiphospholipid syndrome or systemic lupus erythematosus. We recently showed that binding of β2GPI to AnPLs was enhanced by biotinylation of its glycan chains with biotin-hydrazide. In the present study, we investigated why this chemical modification of β2GPI increased both its affinity for AnPLs and its recognition by anti-cardiolipin antibodies. Electrophoretic analysis showed that: (i) high molecular mass β2GPI (dimers and other oligomers) covalently coupled by imine bonds, were present in variable amounts in oxidized β2GPI and in β2GPI-bh (β2GPI-biotin-hydrazide), but were absent in native β2GPI; (ii) binding of β2GPI-bh to phosphatidylserine-coated microtitre plates generated high molecular mass polymers in a time-dependent manner. Native β2GPI did not polymerize in these conditions. These polymers did not bind more strongly to AnPLs than the monomer β2GPI. However, in solution at 1 μM β2GPI-bh essentially appeared as a dimer as revealed by light-scattering analysis. SPR (surface plasmon resonance) analysis showed that the increased affinity of β2GPI-bh for AnPL monolayers was due to a lower dissociation rate constant compared with native β2GPI. Finally, the monoclonal human aCL (auto-immune anti-cardiolipin antibody) EY2C9 bound to β2GPI-bh but did not bind to monomeric native and oxidized β2GPI. It is likely that the dimeric quaternary structure of β2GPI-bh is in fact responsible for the appearance of the epitopes targeted by the EY2C9 antibody.
Nkx3.1 binds and negatively regulates the transcriptional activity of Sp-family members in prostate-derived cells
Authors: Simmons Steven O. , Horowitz Jonathan M. 
Published: December 2005

Nkx3.1 is a homeodomain-containing transcription factor that is expressed early in the development of the prostate gland and is believed to play an important role in the differentiation of prostatic epithelia. Loss of Nkx3.1 protein expression is often an early event in prostate tumorigenesis, and the abundance of Nkx3.1-negative epithelial cells increases with disease progression. In a number of systems, homeodomain proteins collaborate with zinc-finger-containing transcription factors to bind and regulate target genes. In the present paper, we report that Nkx3.1 collaborates with Sp-family members in the regulation of PSA (prostate-specific antigen) in prostate-derived cells. Nkx3.1 forms protein complexes with Sp proteins that are dependent on their respective DNA-binding domains and an N-terminal segment of Nkx3.1, and Nkx3.1 negatively regulates Sp-mediated transcription via Trichostatin A-sensitive and -insensitive mechanisms. A distal 1000 bp portion of the PSA promoter is required for transrepression by Nkx3.1, although Nkx3.1 DNA-binding activity is itself not required. We conclude that Nkx3.1 negatively regulates Sp-mediated transcription via the tethering of histone deacetylases and/or by inhibiting the association of Sp proteins with co-activators.
Stronger control of ATP/ADP by proton leak in pancreatic β-cells than skeletal muscle mitochondria
Authors: Affourtit Charles , Brand Martin D. 
Published: December 2005

Pancreatic beta cells respond to rising blood glucose concentrations by increasing their oxidative metabolism, which leads to an increased ATP/ADP ratio, closure of KATP channels, depolarization of the plasma membrane potential, influx of calcium and the eventual secretion of insulin. Such a signalling mechanism implies that the ATP/ADP ratio is flexible in beta cells (β-cells), which is in contrast with other cell types (e.g. muscle and liver) that maintain a stable ATP/ADP poise while respiring at widely varying rates. To determine whether this difference in flexibility is accounted for by mitochondrial peculiarities, we performed a top-down metabolic control analysis to quantitatively assess how ATP/ADP is controlled in mitochondria isolated from rat skeletal muscle and cultured beta cells. We show that the ATP/ADP ratio is more strongly controlled (approx. 7.5-fold) by proton leak in beta cells than in muscle. The comparatively high importance of proton leak in beta cell mitochondria (relative to phosphorylation) is evidenced furthermore by its relatively high level of control over membrane potential and overall respiratory activity. Modular-kinetic analysis of oxidative phosphorylation reveals that these control differences can be fully explained by a higher relative leak activity in beta cell mitochondria, which results in a comparatively high contribution of proton leak to the overall respiratory activity in this system.