bluuebunny/crossref_metadata_2025 huggingface dataset:
Recent changes in rainfall and rainy days in Ethiopia
Authors: Seleshi Yilma , Zanke Ulrich
Published: June 2004

Changes in annual, June–September and March–May rainfall and rainy days herein (defined as a day with rainfall greater than 1 mm) have been analysed based on 11 key stations located in different climatic zones of Ethiopia over the common period 1965–2002. The progressive Mann–Kendall trend test shows that there is no trend in the annual rainfall total, the seasonal rainfall total or rainy days over central, northern and northwestern Ethiopia in the period 1965–2002. In contrast, the annual and the June–September total rainfalls for the eastern (Jijiga, 137 mm/decade), southern (Negele, 119 mm/decade) and southwestern (Gore 257 mm/decade) stations show a significant decline since about 1982. Correlation analysis shows that the decline of rainfall in eastern, south and southwestern Ethiopia is caused by the corresponding persistent warming of the South Atlantic Ocean over the period approximately from 1986 to 2002. The sea‐surface temperature (SST) over the tropical eastern Pacific Ocean is not significantly correlated with the main rainfall of the semi‐arid lowland areas of eastern, southern, and southwestern Ethiopia, except at marginal zones in transition to the Ethiopian Highlands.

June–September rainfall over the Ethiopian Highlands is positively correlated to the equatorial east Pacific sea‐level pressure and the southern oscillation index, and negatively correlated to SST over the tropical eastern Pacific Ocean as expected, confirming again that warm El Niño–southern oscillation episodes are associated with below‐average June–September rainfall over the Ethiopian Highlands. Copyright © 2004 Royal Meteorological Society
Smothering dystonia in a patient with oromandibular dystonia
Authors: Grill Stephen
Published: June 2004

A case report is presented of a patient with pathologically confirmed striatonigral degeneration who experienced episodic syncope as a result of oromandibular dystonia obstructing inhalation through her mouth and nose. © 2004 Movement Disorder Society
Health‐related quality of life in Huntington's disease: A comparison of two generic instruments, SF‐36 and SIP
Authors: Ho Aileen K. , Robbins Anna O.G. , Walters Stephen J. , Kaptoge Stephen , Sahakian Barbara J. , Barker Roger A.
Published: June 2004

Whereas several clinical endpoints in monitoring the response to treatment in patients with Huntington's disease (HD) have been explored, there has been a paucity of research in the quality of life in such patients. The aim of this study was to validate the use of two generic health‐related quality of life instruments (the Short Form 36 health survey questionnaire [SF‐36] and the Sickness Impact Profile [SIP]) and to evaluate their psychometric properties. We found that both instruments demonstrated acceptable convergent validity and reliability for patients and carers. However, there was an advantage in using the SF‐36 because of its more robust construct validity and test–retest reliability; furthermore, motor symptoms appeared to influence some strictly nonmotor dimensions of the SIP. On a pragmatic level, the SF‐36 is shorter and quicker to administer and, therefore, easier for patients at various stages of the disease to complete. Thus, the SF‐36 would appear to be the recommended instrument of choice for patients with HD and their carers, although further work needs to be done to investigate the sensitivity of this instrument longitudinally. © 2004 Movement Disorder Society
Size effect on fracture energy induced by non‐locality
Authors: Jirásek M. , Rolshoven S. , Grassl P.
Published: June 2004

Experimental results available in the literature indicate that the nominal fracture energy of concrete (defined as total work of fracture divided by the ligament area) depends on the size of the specimen. Theoretical modelling of the size effect on nominal fracture energy based on a non‐local constitutive model is attempted in this paper. The influence of various details of the integral‐type non‐local formulation, e.g. of the specific form of non‐local averaging in the vicinity of a physical boundary, is studied and a physical explanation is provided. The numerical results are compared to experimental data for notched compact tension specimens, and conclusions are drawn for individual formulations. It is shown that the best agreement with experimentally observed trends is achieved if the notch is modelled as a layer of completely damaged material. Fitting of the size effects on both strength and fracture energy permits a unique identification of the model parameters. Copyright © 2004 John Wiley & Sons, Ltd.
A micromechanical approach to the strength criterion of Drucker‐Prager materials reinforced by rigid inclusions
Authors: Barthélémy Jean‐François , Dormieux Luc
Published: June 2004

At the microscopic scale, concrete can be considered as a frictional matrix (cement paste) surrounding rigid inclusions (aggregate or sand inclusions). The present paper proposes a theoretical approach to the strength criterion of such a composite material. It is shown that the macroscopic stress states on the yield surface can be obtained from the solution to non‐linear viscous problems defined on a representative volume element. The practical determination of the yield surface implements a non‐linear homogenization scheme based on the modified secant method. The role of the interface between the matrix and the inclusions is also investigated. Two extreme modellings are considered: perfect bonding and non‐frictional interfaces. In both cases, the method yields a macroscopic strength criterion of the Drucker–Prager type. The macroscopic friction angle is a function of that of the matrix and of the volume fraction of the inclusions. In the case of perfect bonding, the inclusions have a reinforcing effect. In contrast, this may not be true for a non‐frictional interface. Copyright © 2004 John Wiley & Sons, Ltd.
Double brittle‐to‐ductile transition in bending of fibre reinforced concrete beams with rebars
Authors: Carpinteri Alberto , Ferro Giuseppe , Ventura Giulio
Published: June 2004

The bridged crack model has been demonstrated to be an efficient numerical tool for investigating the behaviour of structural elements in bending. In the model, Linear Elastic Fracture Mechanics concepts are used to determine the equilibrium and the compatibility equations of a beam segment subjected to bending in presence of a mode I crack. Recently, the model has been extended to include the presence of closing stresses as a function of the crack opening in addition to steel reinforcement closing traction. This allows the characterization of the mechanical behaviour of fibre reinforced structural elements. Some new techniques, recently introduced for reducing significantly the computing time in presence of cohesive stresses, are presented in the paper and the model is extended by a criterion for detecting concrete crushing in compression. Some experimental results are commented in this light. Copyright © 2004 John Wiley & Sons, Ltd.
Boundary layer in shape optimization of convective fins using a meshfree approach
Authors: Bobaru Florin , Rachakonda Srinivas
Published: June 2004

We show how shape optimization of fin arrays for increased heat flux through the base under area constraint leads to non‐existence of optimal solutions. An additional constraint in terms of the boundary layer eliminates the apparent paradox. We consider a variable heat transfer coefficient and we use a fixed‐point iteration scheme to solve the resulting non‐linear boundary value problem for the steady‐state heat operator with temperature, flux, and convection boundary conditions. We propose a simple yet effective algorithm for evaluating the boundary layer constraint and eliminating the constraint violation. There are large shape changes between the initial and final design but no remeshing is required because we use a meshfree method that is not sensitive to shape distortion of integration cells as long as they remain convex. The resulting optimal unit cell is repeated by periodicity to produce the optimal fin array. The obtained shapes display similarities to shapes seen in natural systems governed by diffusion/convection and conduction processes. A length‐scale for the unit cell is naturally introduced by the non‐overlap condition imposed on the thermal boundary layer in the cooling ambient fluid. Copyright © 2004 John Wiley & Sons, Ltd.
Algebraic grid generation on trimmed parametric surface using non‐self‐overlapping planar Coons patch
Authors: Wang Charlie C. L. , Tang Kai
Published: June 2004

Using a Coons patch mapping to generate a structured grid in the parametric region of a trimmed surface can avoid the singularity of elliptic PDE methods when only C1 continuous boundary is given; the error of converting generic parametric C1 boundary curves into a specified representation form is also avoided. However, overlap may happen on some portions of the algebraically generated grid when a linear or naïve cubic blending function is used in the mapping; this severely limits its usage in most of engineering and scientific applications where a grid system of non‐self‐overlapping is strictly required. To solve the problem, non‐trivial blending functions in a Coons patch mapping should be determined adaptively by the given boundary so that self‐overlapping can be averted. We address the adaptive determination problem by a functional optimization method. The governing equation of the optimization is derived by adding a virtual dimension in the parametric space of the given trimmed surface. Both one‐ and two‐parameter blending functions are studied. To resolve the difficulty of guessing good initial blending functions for the conjugate gradient method used, a progressive optimization algorithm is then proposed which has been shown to be very effective in a variety of practical examples. Also, an extension is added to the objective function to control the element shape. Finally, experiment results are shown to illustrate the usefulness and effectiveness of the presented method. Copyright © 2004 John Wiley & Sons, Ltd.
Mesh‐free simulation of ductile fracture
Authors: Simonsen Bo Cerup , Li Shaofan
Published: June 2004

This paper is concerned with mesh‐free simulations of crack growth in ductile materials, which is a major technical difficulty in computational mechanics. The so‐called reproducing kernel particle method, which is a member of the mesh‐free method family, is used together with the Gurson–Tvergaard–Needleman constitutive model for simulation of ductile fracture. A study has been carried out to compare the proposed mesh‐free simulation with the available experimental results and previous finite element simulations for crack propagation in a three‐point‐bending steel specimen. The results show that the mesh‐free simulation agrees well with experimental results, and it is confirmed that the proposed method provides a convenient and yet accurate means for simulation of ductile fracture. Copyright © 2004 John Wiley & Sons, Ltd.
A novel technique for determination of histories of SIF distributions along 3D crack fronts of a body subjected to thermal shock
Authors: Lu Yan‐Lin , Huang Xian‐Ping , Lu Cong‐Da , Weng Xiao‐Hong
Published: June 2004

The thermal weight function (TWF) is dependent only on the crack configuration and body geometry, and is independent of temperature fields. TWF is independent of time during thermal shock, so the whole variation of transient stress intensity factors (SIFs) can be directly calculated through integration of products of TWF and transient temperatures and temperature gradients. The basic equation for the 3D TWF method for Mode I is derived. Then a novel technique, referred to as the multiple virtual crack extension (MVCE) technique, is proposed to solve the basic equations in the 3D TWF method. The specially selected linearly independent VCE modes are directly used as shape functions for the interpolation of unknown SIFs. The coefficient matrix of the final system of equations is a triple‐diagonal matrix and the values of the coefficients on the main diagonal are usually large. The system of equations has good numerical properties. The number of linearly independent VCE modes which can be introduced in a problem is unlimited. The complex situations that the SIFs vary dramatically along the crack fronts can be numerically well simulated by the MVCE technique. Examples show that the scheme is of very high efficiency and of good accuracy. The results show that the histories of SIF distributions along 3D crack fronts are very complex. In order to understand the behaviour of 3D cracks correctly it should be calculated in detail. Copyright © 2004 John Wiley & Sons, Ltd.
Faunal Exploitation during the Middle Palaeolithic in south‐eastern France and north‐western Italy
Authors: Valensi Patricia , Psathi Eleni
Published: June 2004

Six Middle Palaeolithic sites (Lazaret, Madonna dell'Arma, Caverna delle Fate, Arma delle Manie, Santa Lucia Superiore and San Francesco), dated from Oxygen Isotopic Stages 6 to 3 (OIS 6 to 3), have been studied from a zooarchaeological and palaeoecological point of view. The sites have yielded faunal assemblages rich in cervids, generally dominated by Cervus elaphus. The frequency of other ungulate taxa is inextricably linked to the topography of each site, as well as to climatic and environmental conditions. Taphonomic analysis indicates that humans were the main agents of accumulation of the large mammal remains. Mortality and seasonality data show various patterns of age distribution of the ungulate species, and suggest that there is no relation between the occupation season of these sites and the hunting of a particular species. The dominance of red deer can be explained by their natural abundance and by their high rendering in terms of hunting transport, meat quantity, and other useful materials like skins, tendons, and soon. Neanderthal subsistence strategies do not show any evolution in the studied area during the period of Oxygen Isotopic Stages 6 to 3. Copyright © 2004 John Wiley & Sons, Ltd.
Ecology and subsistence strategies in the eastern Italian Alps during the Middle Palaeolithic
Authors: Fiore Ivana , Gala Monica , Tagliacozzo Antonio
Published: June 2004

Italy is very rich in Middle Palaeolithic sites, and the Veneto region ranges among those with the best archaeozoological information. Most of the Middle Palaeolithic sites are located in caves and rock shelters situated at the mouths of the Alpine valleys, in the piedmont slopes. The two sites that offer the best archaeozoological data are Grotta di Fumane and Grotta S. Bernardino. Grotta S. Bernardino was occupied alternately by humans and carnivores, in particular bear. The fauna is largely dominated by ungulate remains, with red and roe deer prevalent over chamois and ibex; elk and giant deer are also present. Among the carnivores, the most frequent species is cave bear followed by lynx and leopard. Furthermore, hare, beaver and marmot are present together with remains of both fish and birds. It is possible that bears or birds of prey introduced the rare fish remains. In the Mousterian levels, hunting of the most common species was mainly directed towards young adult and adult individuals, suggesting the possibility of selective hunting. Marmot, beaver and probably bear, together with some species of birds (ducks, geese and Galliformes) were also hunted. At Grotta Fumane, Mousterian and Aurignacian levels reveal evidence of human activity related to carcass processing and bone exploitation. The most frequent ungulates are red deer, followed by roe deer and ibex; less frequent are chamois, bovids and giant deer (Megaloceros giganteus). Among the carnivores, bears (both Ursus arctos and Ursus spelaeus) are present, as are wolf, red fox and hyena (Crocuta crocuta). Hare and marmot are also present together with abundant bird remains. The most common species of bird are: Tetrao tetrix, Crex crex and Pyrrhocorax graculus. Mortality data for ungulates suggest that young adults and adults were preferentially selected. The faunal assemblage indicates that economic, ecological and climatic changes took place between the Mousterian and the Aurignacian levels. Copyright © 2004 John Wiley & Sons, Ltd.
Gasoline prices and motor vehicle fatalities
Authors: Grabowski David C. , Morrisey Michael A.
Published: June 2004

Fatal motor vehicle crashes per capita remained relatively stable over the 1990s, in spite of new traffic safety laws and vehicle innovations. One explanation for this stability is that the price of gasoline declined, which resulted in more vehicle miles traveled and potentially more fatalities. By using 1983–2000 monthly gasoline price and fatality panel data and fixed effects specifications, this study exploits within‐state variation over time in gasoline prices and found that a 10‐cent decrease in gasoline prices increased motor vehicle fatalities by 2.3 percent over a 2‐year period. The effect on higher‐risk younger adults is more than twice as large. The secular decline in real gasoline prices over the 1990s may partially explain why motor vehicle fatalities per capita have not decreased even with the adoption of more stringent state policies. © 2004 by the Association for Public Policy Analysis and Management.
Proneness to, perceptions of, and responses to teasing: the influence of both intrapersonal and interpersonal factors
Authors: Kowalski Robin M.
Published: June 2004

In spite of the frequency with which people tease and are teased by others, until recently surprisingly little research attention has been devoted to the phenomenon of teasing, and existing research has been plagued by conceptual disparities and relatively atheoretical formulations of teasing. To address these problems, a social interactionist model of teasing is presented as a framework for examining intrapersonal and interpersonal variables that influence a perpetrator's willingness to tease and the target's susceptibility to victimization and reactions to being teased. Representative variables include personality characteristics, past history with teasing, affect, the nature of the relationship between the target and the perpetrator, and the presence of an audience. Copyright © 2004 John Wiley & Sons, Ltd.
Atomic force microscopy revelation of molecular complexes in the multiprotein cytochrome P450 2B4‐containing system
Authors: Kuznetsov Vadim Yu. , Ivanov Yuri D. , Archakov Alexander I.
Published: June 2004

The application of atomic force microscopy (AFM) to the identification and visualization of individual molecules and their complexes in a reconstituted monooxygenase P450 2B4 system without the phospholipid was demonstrated. The method employed in this study distinguishes the monomeric proteins from their binary complexes and, also, the binary from the ternary complexes. The AFM images of the full‐length P450 2B4 system's constituent components – cytochrome P450 2B4 (2B4), NADPH‐cytochrome P450 reductase and cytochrome b5 (b5), were obtained on highly‐oriented pyrolitic graphite. The typical heights of the d‐2B4, d‐flavoprotein (Fp) and d‐b5 molecules were measured and found to be 2.2 ± 0.2, 2.3 ± 0.2 and 1.8 ± 0.1 nm, respectively. The measured heights of the binary d‐Fp/d‐2B4 and d‐2B4/d‐b5 complexes were estimated to be 3.4 ± 0.2 and 2.8 ± 0.2 nm, respectively. No formation of d‐Fp/d‐b5 complexes was registered. The ternary d‐Fp/d‐2B4/d‐b5 complexes were visualized and their heights were found to be roughly equal to 4.3 ± 0.3 nm and 6.2 ± 0.3 nm.
Identification of proteins in activated human neutrophils susceptible to tyrosyl radical attack. A proteomic study using a tyrosylating fluorophore
Authors: Avram Diana , Romijn Edwin P. , Pap Everard H. W. , Heck Albert J. R. , Wirtz Karel W. A.
Published: June 2004

Tyrosyl radicals cross‐linked to protein tyrosine residues (tyrosylated proteins) represent hallmarks of neutrophil‐mediated injury at the inflammatory locus. Yet the proteins targeted by tyrosyl radicals in an intact cellular system remain to be elucidated. Here, we show that tyrosyl radicals generated by human neutrophils after activation by phorbol 12‐myristate 13‐acetate (PMA), interferon‐γ (IFN‐γ) or TNF‐α could act in an autocrine manner by cross‐linking to endogenous proteins. We have identified the tyrosylated proteins by using a membrane‐impermeable tyrosine analogue, tyramine coupled to fluorescein (TyrFluo), in combination with proteomics techniques. Confocal microscopy images indicated that initially the tyrosylated proteins were localized in patches at the cell surface to become internalized subsequently. In the neutrophil membrane‐associated proteome, lactoferrin was the prime target of tyrosylation. Out of three isoforms identified, an 80 kDa neutral isoform was tyrosylated more extensively than the 85 kD basic isoform, particularly after PMA activation. Although all three stimuli induced tyrosylation of the filamentous component vimentin, additional tyrosylated vimentin fragments were detected after IFN‐γ‐ and TNF‐α‐stimulation. Moreover, upon activation the bulk of vimentin behaved as a dimer (Mr 120 kDa) being slightly tyrosylated, yet phosphorylated at Thr‐425 possibly as a requirement for its externalization. Unexpectedly, bovine catalase added to end tyrosyl radicals formation was detected as a highly tyrosylated neutrophil‐associated protein. A moderate stimulus‐dependent tyrosylation of ATP synthase‐β, α‐enolase, glyceraldehyde 3‐phosphate dehydrogenase, cytokeratin‐10, filamin‐A, and annexin‐I was also observed. When the membrane‐permeable probe (acetylTyrFluo) was used, protein tyrosylation was not observed indicating that the intracellular proteins were well protected against oxidative attack. This study shows that human neutrophils can modulate their proteome via a tyrosine oxidation pathway induced by pro‐inflammatory mediators.
Heterochain model for simultaneous long‐chain branching and crosslinking. I. Matrix formula for the weight‐average molecular weights
Authors: Tobita Hidetaka
Published: June 2004

The hetrochain model was applied to develop a matrix formula describing the weight‐average molecular weights for a reaction system that involves simultaneous long‐chain branching and crosslinking. The heterochain model describes the molecular architecture formed through the primary chain connection that follows the Markovian statistics; therefore, this matrix formula is valid regardless of the chemical and reactor systems used, as long as the Markovian nature is preserved for the chain‐connection statistics. Application to free‐radical (co)polymerization systems is described in subsequent research. The gel point is simply described as a point at which the largest eigenvalue of the matrix M, which defines the chain‐connection statistics, reaches unity. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 2780–2790, 2004
Evaluation of the relative stability of liganded versus ligand‐free protein conformations using Simplicial Neighborhood Analysis of Protein Packing (SNAPP) method
Authors: Sherman Douglas B. , Zhang Shuxing , Pitner J. Bruce , Tropsha Alexander
Published: June 2004

Many proteins change their conformation upon ligand binding. For instance, bacterial periplasmic binding proteins (bPBPs), which transport nutrients into the cytoplasm, generally consist of two globular domains connected by strands, forming a hinge. During ligand binding, hinge motion changes the conformation from the open to the closed form. Both forms can be crystallized without a ligand, suggesting that the energy difference between them is small. We applied Simplicial Neighborhood Analysis of Protein Packing (SNAPP) as a method to evaluate the relative stability of open and closed forms in bPBPs. Using united residue representation of amino acids, SNAPP performs Delaunay tessellation of the protein, producing an aggregate of space‐filling, irregular tetrahedra with nearest neighbor residues at the vertices. The SNAPP statistical scoring function is derived from log‐likelihood scores for all possible quadruplet compositions of amino acids found in a representative subset of the Protein Data Bank, and the sum of the scores for a given protein provides the total SNAPP score. Results of scoring for bPBPs suggest that in most cases, the unliganded form is more stable than the liganded form, and this conclusion is corroborated by similar observations of other proteins undergoing conformation changes upon binding their ligands. The results of these studies suggest that the SNAPP method can be used to predict the relative stability of accessible protein conformations. Furthermore, the SNAPP method allows delineation of the role of individual residues in protein stabilization, thereby providing new testable hypotheses for rational site‐directed mutagenesis in the context of protein engineering. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Combining evolutionary and structural information for local protein structure prediction
Authors: Pei Jimin , Grishin Nick V.
Published: June 2004

We study the effects of various factors in representing and combining evolutionary and structural information for local protein structural prediction based on fragment selection. We prepare databases of fragments from a set of non‐redundant protein domains. For each fragment, evolutionary information is derived from homologous sequences and represented as estimated effective counts and frequencies of amino acids (evolutionary frequencies) at each position. Position‐specific amino acid preferences called structural frequencies are derived from statistical analysis of discrete local structural environments in database structures. Our method for local structure prediction is based on ranking and selecting database fragments that are most similar to a target fragment. Using secondary structure type as a local structural property, we test our method in a number of settings. The major findings are: (1) the COMPASS‐type scoring function for fragment similarity comparison gives better prediction accuracy than three other tested scoring functions for profile–profile comparison. We show that the COMPASS‐type scoring function can be derived both in the probabilistic framework and in the framework of statistical potentials. (2) Using the evolutionary frequencies of database fragments gives better prediction accuracy than using structural frequencies. (3) Finer definition of local environments, such as including more side‐chain solvent accessibility classes and considering the backbone conformations of neighboring residues, gives increasingly better prediction accuracy using structural frequencies. (4) Combining evolutionary and structural frequencies of database fragments, either in a linear fashion or using a pseudocount mixture formula, results in improvement of prediction accuracy. Combination at the log‐odds score level is not as effective as combination at the frequency level. This suggests that there might be better ways of combining sequence and structural information than the commonly used linear combination of log‐odds scores. Our method of fragment selection and frequency combination gives reasonable results of secondary structure prediction tested on 56 CASP5 targets (average SOV score 0.77), suggesting that it is a valid method for local protein structure prediction. Mixture of predicted structural frequencies and evolutionary frequencies improve the quality of local profile‐to‐profile alignment by COMPASS. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Structural components of SCAN‐domain dimerizations
Authors: Nam Kiyean , Honer Christian , Schumacher Christoph
Published: June 2004

The SCAN or leucine‐rich domain has been characterized as a highly conserved sequence in zinc finger transcription factors that mediates selective dimer formation between SCAN‐domain‐containing proteins. In order to accommodate various SCAN‐domain sequence features, a minimal functional folding unit was defined on the premise of proper structural folding and biochemical binding. The 58‐amino acid minimal functional units derived from each of four SCAN‐domain protein families were subjected to a three‐dimensional position‐specific scoring matrix (3D‐PSSM) and ungapped threading analysis. The resulting fold prediction represented the SCAN‐domain's minimal functional unit as a bundle of three alpha helices folded to a core structure. In addition, the minimal functional folding unit biochemically retained the selective dimerization properties of the native proteins. In order to elucidate the structural components within the SCAN‐domain that engage in binding interactions, we attempted to correlate the physicochemical helix properties, as represented by a hydropathy profile, with the experimental dimerization selectivities. The amino‐terminal helix revealed the highest diversity measure among the three helices of the minimal functional unit and is therefore likely to offer critical surface‐exposed binding residues. Indeed, by interchanging the amino‐terminal helix between SCAN‐domains without alteration of their structural frames consisting of conserved hydrophobic residues, a modulation of binding preferences was demonstrated. The minimal functional folding unit of SCAN‐domains may therefore contain within the amino‐terminal alpha helix structural components that determine selective dimerization patterns and combinatorial control of transcription factors. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Transition states for folding of circular‐permuted proteins
Authors: Chen Jie , Wang Jun , Wang Wei
Published: June 2004

To explore the role of entropy and chain connectivity in protein folding, a particularly interesting scheme, namely, the circular permutation, has been used. Recently, experimental observations showed that there are large differences in the folding mechanisms between the wild‐type proteins and their circular permutants. These differences are strongly related to the change in the intrachain connectivity. Some results obtained by molecular dynamics simulations also showed a good agreement with the experimental findings. Here, we use a topology‐based free‐energy functional method to study the role of the chain connectivity in folding by comparing features of transition states of the wild‐type proteins with those of their circular permutants. We concentrate our study on 3 small globular proteins, namely, the α‐spectrin SH3 domain (SH3), the chymotrypsin inhibitor 2 (CI2), and the ribosomal protein S6, and obtain exciting results that are consistent with the available experimental and simulation results. A heterogeneity of the interaction energies between contacts for protein CI2 and for protein S6 is also introduced, which characterizes the strong interactions between contacts with long loops, as speculated from experiments for protein S6. The comparison between the folding nucleus of the wild‐type proteins and those of their circular permutants indicates that chain connectivity affects remarkably the shapes of the energy profiles and thus the folding mechanism. Further comparisons between our theoretical calculated ϕth values and the experimental observed ϕexp values for the 3 proteins and their permutants show that our results are in good agreement with experimental ones and that correlations between them are high. These indicate that the free‐energy functional method really provides a way to analyze the folding behavior of the circular‐permuted proteins and therefore the folding mechanism of the wild‐type proteins. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Fast and accurate computation of the 13C chemical shifts for an alanine‐rich peptide
Authors: Vila Jorge A. , Baldoni Héctor A. , Ripoll Daniel R. , Scheraga Harold A.
Published: June 2004

The purpose of this work is, first, to present a fast and accurate technique to compute Boltzmann‐averaged values of the quantum‐chemical 13C chemical shifts for each amino acid in oligopeptides, demonstrated here by an application to the peptide Ac‐XXAAAAAAAOO‐NH2 (where X denotes diaminobutyric acid, A is alanine, and O is ornithine) [XAO] and, second, to discuss the capability of the 13Cα and 13Cβ chemical shifts to distinguish the PPII conformation from the α‐helix and statistical‐coil conformations. Use is made of a combination of approaches, summarized as follows: (1) derivation of an ensemble of conformations by using a molecular mechanics technique; (2) use of a clustering procedure to form families and build a reduced set of conformations consisting of the lowest‐energy conformations of each family, and (3) computation of the 13C chemical shifts for the lowest‐energy conformations of each family, using a quantum‐chemical approach that treats a selected residue, or group of residues, with a 6‐311+G(2d,p) locally‐dense basis set, while the remaining residues in the sequence are treated with a 3‐21G basis set. The whole procedure is quite accurate and speeds up the computation of the Boltzmann‐averaged values of the 13C‐chemical shifts by several orders of magnitude. The present application sheds some light on the conformational preference for alanine and non‐alanine residues to occupy the PPII helical region of the Ramachandran map. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Gibbs adsorption isotherm combined with Monte Carlo sampling to see action of cosolutes on protein folding
Authors: Harries Daniel , Parsegian V. Adrian
Published: June 2004

Driven by conditions set by smaller solutes, proteins fold and unfold. Experimentally, these conditions are stated as intensive variables ‐ pH and other chemical potentials ‐ as though small solutes were infinite resources that come at an externally varied free energy cost. Computationally, the finite spaces of simulation allow only fixed numbers of these solutes. By combining the analytic Gibbs adsorption isotherm with the computational Monte Carlo sampling of polymer configurations, we have been able to overcome an inherent limitation of computer simulation. The idea is to compute analytically the free energy changes wrought by solutes on each particular configuration. Then numerical computation is needed only to sample the set of configurations as efficiently as when no bathing solute is present. For illustration, the procedure is applied to an idealized two‐dimensional heteropolymer to yield lessons about the effect of cosolutes on protein stability. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Efficiency of a second‐generation HIV‐1 protease inhibitor studied by molecular dynamics and absolute binding free energy calculations
Authors: Lepšík M. , Kříž Z. , Havlas Z.
Published: June 2004

A subnanomolar inhibitor of human immunodeficiency virus type 1 (HIV‐1) protease, designated QF34, potently inhibits the wild‐type and drug‐resistant enzyme. To explain its broad activity, the binding of QF34 to the wild‐type HIV‐1 protease is investigated by molecular dynamics simulations and compared to the binding of two inhibitors that are used clinically, saquinavir (SQV) and indinavir (IDV). Analysis of the flexibility of protease residues and inhibitor segments in the complex reveals that segments of QF34 were more mobile during the dynamics studies than the segments of SQV and IDV. The dynamics of hydrogen bonding show that QF34 forms a larger number of stable hydrogen bonds than the two inhibitors that are used clinically. Absolute binding free energies were calculated with molecular mechanics–generalized Born surface area (MM–GBSA) methodology using three protocols. The most consistent results were obtained using the single‐trajectory approach, due to cancellation of errors and inadequate sampling in the separate‐trajectory protocols. For all three inhibitors, energy components in favor of binding include van der Waals and electrostatic terms, whereas polar solvation and entropy terms oppose binding. Decomposition of binding energies reveals that more protease residues contribute significantly to the binding of QF34 than to the binding of SQV and IDV. Moreover, contributions from protease main chains and side chains are balanced in the case of QF34 (52:48 ratio, respectively), whereas side chain contributions prevail in both SQV and IDV (main‐chain:side‐chain ratios of 41:59 and 45:55, respectively). The presented results help explain the ability of QF34 to inhibit multiple resistant mutants and should be considered in the design of broad‐specificity second‐generation HIV‐1 protease inhibitors. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Domain swapping of CD4 upon dimerization
Authors: Sanejouand Yves‐Henri
Published: June 2004

It has recently been shown that disulfide bond Cys130—Cys159 in domain 2 of monomeric CD4 is involved in the formation of CD4 disulfide‐bonded dimers on cell surfaces and that it can influence the permissiveness of cells to HIV infection. Because this disulfide bond is buried in the monomer, a large conformational change must take place in order to allow for such disulfide exchange. Using standard optimization techniques, whose efficiency was first checked in the well‐documented CD2 case, we have shown that 3D domain swapping is a likely candidate for the conformational change, the hinge loop, or linker, being loop E—F. Indeed, as a consequence of domain swapping, because Cys130 and Cys159 belong to β‐strands C and F, respectively, two disulfide bonds become established between Cys130 in one monomer and Cys159 in the other one. Such a disulfide exchange has already been observed when the nuclear magnetic resonance (NMR) structure of the prion protein was compared to the crystallographic, dimeric one. In both cases, domain swapping implies disulfide exchange because the linker is located in the sequence between two disulfide‐bonded cysteines. As in the CD2 case, the proposed configuration of the CD4 dimer is found as a pair of neighboring monomers in the crystallographic unit cell. Moreover, because in this configuration the epitope of monoclonal antibody MT151, which does not compete with Gp120 for CD4 binding, is in the cleft between the pair of CD4 monomers, it is suggested that MT151 achieves its HIV‐blocking activity by interfering with the formation of CD4 domain‐swapped dimers on cell surface. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Toward an atomistic model for predicting transcription‐factor binding sites
Authors: Endres Robert G. , Schulthess Thomas C. , Wingreen Ned S.
Published: June 2004

Identifying the specific DNA‐binding sites of transcription‐factor proteins is essential to understanding the regulation of gene expression in the cell. Bioinformatics approaches are fast compared to experiments, but require prior knowledge of multiple binding sites for each protein. Here, we present an atomistic force‐field method to predict binding sites based only on the X‐ray structure of a related bound complex. Specific flexible contacts between the protein and DNA are modeled by a library of amino acid side‐chain rotamers. Using the example of the mouse transcription factor, Zif268, a well‐studied zinc‐finger protein, we show that the protein sequence alone, without the detailed experimental structure, gives a strong bias toward the consensus binding site. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Backbone–backbone geometry of tertiary contacts between α‐helices
Authors: Källblad Per , Dean Philip M.
Published: June 2004

Knowledge about how secondary‐structure elements combine together to form the tertiary structure is crucial for understanding protein folding. We have examined packing solutions for α‐helices by performing a crystal survey of the underlying backbone–backbone inter‐geometry of tertiary contacts. The information content is different from, and complementary to, the results of side‐chain to side‐chain crystal surveys and studies of helix–helix‐crossing angles. Six geometry descriptors were recorded from each tertiary contact in nonredundant data sets of globular and transmembrane proteins. The descriptors included distances, angles, and dihedral angles that together describe completely the underlying geometry of each contact. From the results it is possible to identify differences in the geometry requirements of tertiary contacts between α‐helices in general and transmembrane α‐helices. The differences become more apparent when the correlation between the different geometry descriptors is analyzed. The results are compared with those of other types of secondary structure. Finally, an investigation of how the geometry of tertiary contacts changes with the amino‐acid types involved in the contact is performed using multivariate techniques. The results of this study provide a well‐defined overview of the underlying structural framework of tertiary contacts between α‐helices, in both globular and TM environments, that will have valuable implications for predicting protein tertiary structure. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Conventional and unconventional techniques in quantum chemistry
Authors: Quiney Harry M. , Grant Ian P.
Published: June 2004

The computational cost of ab initio molecular electronic structure calculations is dominated by the generation of electron–electron repulsion integrals, of which there are O(N4), where N is the dimension of the basis set. Even if allowance is made for integral economization schemes, the rapidity with which the computational cost grows as N increases is a problem for all ab initio calculations, particularly the intrinsically more laborious relativistic approaches. There is therefore a strong motive to search for accurate but inexpensive algorithms without having to simplify the equations. We report a preliminary assessment of a promising new scheme that scales much more slowly with N. The key idea is the equivalence of the conventional expression for the energy of an atom or molecule with the integral of the energy density of the related electromagnetic fields over all space. The electrostatic energy density can be constructed cheaply as the sum of scalar products of O(N2) pairs of electric fields Eij(r) generated by the overlap charge densities ρij(r). The integration of the total energy density over the whole molecule can be done by adapting a numerical integration scheme used in contemporary density functional (DFT) algorithms requiring only a relatively small number of cubature points. We explore the implications of this approach for calculations in quantum chemistry. In relativistic quantum theory the total energy can be expressed as the sum of scalar products of both electric Eij(r) fields and magnetic Bij(r) fields generated by the overlap charge and current densities. In the long‐wavelength approximation, in which retardation is neglected, this leads to a new interpretation of the Breit interaction energy as the energy of the associated magnetic fields. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Closed formulae for (1s|1s), Slater two‐center integrals, using the three‐center nuclear attraction integral program in spherical coordinates
Authors: Jain J. L. , Jones H. W. , Weatherford C. A. , Hoggan P. E.
Published: June 2004

The strategy of using expansions in spherical harmonics of displaced Slater‐type (exp(−αx)) orbitals to evaluate multicenter molecular integrals is applied to three‐centered nuclear attraction integrals (potential due to the product of separated Slater‐type orbitals). Closed formulae are produced for nine terms of an infinite series for interior region, (inside − ipot) r2 < a, and 14 terms for Exterior Region, (outside − epot) r2 > a. The value a = 2 is chosen for the interior region and r = 14 for the exterior region. Our focus is to obtain a closed formula for the Slater formula. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Produktmodelle zur Optimierung der Projektabwicklung
Authors: Haller Hans‐Walter , Hörenbaum Christoph , Osterrieder Peter , Saal Helmut
Published: June 2004

Ein Produktmodell ist ein ganzheitlicher EDV‐Standard, durch den sämtliche Anwendungssoftware in Bauprojekten verlustfrei gekoppelt werden kann. In diesem Beitrag werden die Entstehung und die Anwendung zweier verwandter Produktmodelle beschrieben: die “Produktschnittstelle Stahlbau”, die für die Projektabwicklung und die Fertigung im Stahlbau entwickelt wurde und vom Deutschen Stahlbau‐Verband zur Anwendung empfohlen wird, sowie deren Übertragung auf den Holzbau, das Produktmodell “Datentransfer im Holzbau (DtH)“.
A numerical method for choice of weighting matrices in active controlled structures
Authors: AGRANOVICH G. , RIBAKOV Y. , BLOSTOTSKY B.
Published: June 2004

A feedback control system usually implements active and semi‐active control of seismically excited structures. The objective of the control system is described by a performance index, including weighting matrix norms. The choice of weighting matrices is usually based on engineering experience. A new procedure for weighting matrix components choice based on the parametric optimization method is developed in this study. It represents a two‐step optimization process. In the first step a discrete‐time control system is synthesized according to a quadratic performance index. In the second step the weighting coefficients are obtained using the results of the first step. Numerical simulation of a typical structure subjected to earthquakes is carried out in order to demonstrate the effectiveness of the proposed method. It shows that applying the proposed technique provides a choice of the weighting matrices and results in enhanced structural behaviour under different earthquakes. Copyright © 2003 John Wiley & Sons, Ltd.
Role of the 14–3–3 protein in carbon metabolism of the pathogenic yeast Candida albicans
Authors: Wang Ying‐Kai , Das Biswadip , Huber David H. , Wellington Melanie , Kabir M. Anaul , Sherman Fred , Rustchenko Elena
Published: June 2004

We previously demonstrated that the pathogenic yeast Candida albicans effectively adapts to utilize L‐sorbose (Sou+) by a novel mechanism based on the loss of one copy of chromosome 5, probably due to the reduction of copy number of a negative regulator located on this chromosome. We report here another negative regulator of L‐sorbose utilization, an orthologue of the Saccharomyces cerevisiae BMH1 gene, which encodes the evolutionarily conserved protein 14–3–3. This essential gene is located on chromosome 1, does not have paralogues, and is supposedly a component of the regulatory network. Experiments involving disruption of one allele of BMH1 and overexpression of BMH1 revealed that BMH1 represses the transcription of SOU1, which is responsible for the utilization of L‐sorbose. Although the exact mechanism of the interaction between BMH1 and SOU1 is not known, it is clear that the control is based on the ratio of gene copy number, and that BMH1 does not control the loss of chromosome 5, the major mechanism producing Sou+ mutants. We propose that function of BMH1 as a negative regulator of SOU1 contributes to a general cellular homeostasis. This is a first report on the role of the C. albicans essential gene BMH1 as a negative regulator of the utilization of secondary carbon source in yeast, which further substantiates the involvement of 14–3–3 proteins in diverse functions. Copyright © 2004 John Wiley & Sons, Ltd.
A simple and efficient procedure for transformation of Schizosaccharomyces pombe
Authors: Morita Tomotake , Takegawa Kaoru
Published: June 2004

We describe a simple and efficient procedure for transformation of Schizosaccharomyces pombe. Sz. pombe colonies grown on minimal (SD) plates were directly removed and suspended in a 100 µl reaction mixture containing 70 µl PLATE solution (50% polyethylene glycol‐4000, 100 mM lithium acetate, 10 mM Tris–HCl, pH 4.9, and 1 mM EDTA), 10 µl plasmid DNA (1 µg), 10 µl carrier DNA (100 µg) and 10 µl sterile distilled water. After incubation at 30 °C for 1 h followed by heat shock treatment at 42 °C for 15 min, the reaction mixture was spread on a selection plate. The transformation efficiency obtained using the procedure was approximately 8000 transformants/µg DNA. The method is simple and time‐saving, making it especially useful for a large number of samples and when a high transformation efficiency is not required. Copyright © 2004 John Wiley & Sons, Ltd.