bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteome analysis of human colon cancer by two‐dimensional difference gel electrophoresis and mass spectrometry
Authors: Friedman David B. , Hill Salisha , Keller Jeffrey W. , Merchant Nipun B. , Levy Shawn E. , Coffey Robert J. , Caprioli Richard M.
Published: February 2004

Two‐dimensional difference gel electrophoresis (2‐D DIGE) coupled with mass spectrometry (MS) was used to investigate tumor‐specific changes in the proteome of human colorectal cancers and adjacent normal mucosa. For each of six patients with different stages of colon cancer, Cy5‐labeled proteins isolated from tumor tissue were combined with Cy3‐labeled proteins isolated from neighboring normal mucosa and separated on the same 2‐D gel along with a Cy2‐labeled mixture of all 12 normal/tumor samples as an internal standard. Over 1500 protein spot‐features were analyzed in each paired normal/tumor comparison, and using DIGE technology with the mixed‐sample internal standard, statistically significant quantitative comparisons of each protein abundance change could be made across multiple samples simultaneously without interference due to gel‐to‐gel variation. Matrix‐assisted laser desorption/ionization‐time of flight (MALDI‐TOF) and tandem (TOF/TOF) MS provided sensitive and accurate mass spectral data for database interrogation, resulting in the identification of 52 unique proteins (including redundancies due to proteolysis and post‐translationally modified isoforms) that were changing in abundance across the cohort. Without the benefit of the Cy2‐labeled 12 sample mixture internal standard, 42 of these proteins would have been overlooked due to the large degree of variation inherent between normal and tumor samples.
Extensive analysis of the human platelet proteome by two‐dimensional gel electrophoresis and mass spectrometry
Authors: García Angel , Prabhakar Sripadi , Brock Chris J. , Pearce Andrew C. , Dwek Raymond A. , Watson Steve P. , Hebestreit Holger F. , Zitzmann Nicole
Published: February 2004

Platelets play a key role in the control of bleeding and wound healing, contributing to the formation of vascular plugs. Under pathologic circumstances, they are involved in thrombotic disorders, including heart disease. Since platelets do not have a nucleus, proteomics offers a powerful alternative approach to provide data on protein expression in these cells, helping to address their biology. In this publication we extend the previously reported analysis of the pI 4–5 region of the human platelet proteome to the pI 5–11 region. By using narrow pI range two‐dimensional electrophoresis (2‐DE) for protein separation followed by high‐throughput tandem mass spectrometry (MS/MS) for protein identification, we were able to identify 760 protein features, corresponding to 311 different genes, resulting in the annotation of 54% of the pI 5–11 range 2‐DE proteome map. We evaluated the physicochemical properties and functions of the identified platelet proteome. Importantly, the main group of proteins identified is involved in intracellular signalling and regulation of the cytoskeleton. In addition, 11 hypothetical proteins are reported. In conclusion, this study provides a unique inventory of the platelet proteome, contributing to our understanding of platelet function and building the basis for the identification of new drug targets.
Chemical Kinetics of the Thermal Decomposition of NTO
Authors: Kondrikov Boris N. , Smirnov S. P. , Minakin A. V. , Doherty Ruth M.
Published: February 2004

The kinetics of thermal decomposition of 3‐nitro‐2,4‐dihydro‐3H‐1,2,4‐triazol‐5‐one (NTO) in the temperature interval from 200 °C to 260 °C was investigated using a glass Bourdon gauge. The overall decomposition reaction includes two distinct stages: the fast first‐order decomposition and the subsequent autocatalytic reaction. The importance of the first stage increases with increasing decomposition temperature and decreasing loading density of the Bourdon gauge (m/V). A period of preliminary heating, at a lower temperature, strongly influences the autocatalytic stage when the decomposition is carried out at a higher temperature. In the temperature domain 200–220 °C, the Arrhenius constants of the decomposition reaction are found to be close to the values usually observed for nitrocompounds: E=173 kJ/mol and log10 k≈12.5 (s−1). It is shown that a simple model of NTO decomposition based on an autocatalytic reaction of the m‐th order can describe the course of the decomposition at high temperature but the m number appears to be excessively high, up to 4. A new model of the decomposition is developed, including an initial monomolecular reaction, decomposition of the crystalline substance, and an autocatalytic reaction of NTO dissolved in liquid decomposition products. This model gives the common order of autocatalysis, m=1.
Antitumor activity of irofulven monotherapy and in combination with mitoxantrone or docetaxel against human prostate cancer models
Authors: Van Laar Emily S. , Weitman Steven , MacDonald John R. , Waters Stephen J.
Published: February 2004

BACKGROUND

Irofulven (6‐hydroxymethylacylfulvene, HMAF, MGI 114) is a novel antitumor agent currently undergoing clinical trials in hormone‐refractory prostate cancer. This report examines the efficacy of irofulven alone or in combination with mitoxantrone or docetaxel against androgen‐independent prostate cancer cell lines.

METHODS

To elucidate the activity of irofulven monotherapy and in combination, PC‐3 and DU‐145 cell lines were utilized in cellular viability assessments and tumor growth inhibition studies.

RESULTS

Viability assays with irofulven and mitoxantrone show additive to synergistic activity. Furthermore, irofulven and mitoxantrone in combination exhibit enhanced antitumor activity against PC‐3 and DU‐145 xenografts. Additive combination effects are also observed when irofulven and docetaxel were tested against PC‐3 xenografts and curative activity (8/10 CR) is observed in DU‐145 xenografts.

CONCLUSIONS

These studies demonstrate that irofulven displays strong activity as monotherapy and in combination with mitoxantrone or docetaxel against androgen‐independent prostate cancer in vitro and in vivo; thus, supporting the clinical investigation of irofulven against hormone‐refractory prostate cancer. © 2003 Wiley‐Liss, Inc.
Phenylephrine‐induced neurogenic prostatitis facilitates the promotion of PIN‐like lesions in rats
Authors: Rosenzweig N. , Horodniceanu J. , Abramovici A.
Published: February 2004

BACKGROUND

Atypical prostate hyperplasia, resembling PIN lesions in men, together with chronic inflammatory exudates, have been reported after chronic administration of phenylephrine (PE). The present study aims to characterize the evolution of the expression of typical leukocyte markers immunohistochemically as correlated to the promotion of PIN lesions.

METHODS

Adolescent rats received injections of PE (subcutaneously) (10 mg/kg BW/per day) and were euthanized 3, 8 hr, 1, 3, 7, 14 days thereafter. The dissected prostates were fixed in formalin, and paraffin embedded sections were cut and immunoreacted.

RESULTS

PE exerted a time related bi‐phasic effect on the rat prostate. A first inflammatory reaction phase took place at 3–8 hr post injection characterized by vascular dilatation, congestion, edema, and massive leukocytic infiltrate, mainly of ED1+ cells. At 24 hr, the amount of ED1+ cells decreased approaching the equivalent values of ED2+, CD8+ cells, and mastocytes. Their values remained relatively high for the rest of the experimental period. A second phase of proliferative changes, consisting of healing fibrosis as well as dysplastic epithelial lesions, similar to human PIN lesions, appeared on the 7th day.

CONCLUSIONS

Neuro‐immune interactions promote prostatic fibrosis and dysplastic changes; these being preceded by an acute and transient inflammatory reaction. © 2003 Wiley‐Liss, Inc.
Gain of androgen receptor gene copies in primary prostate cancer due to X chromosome polysomy
Authors: Röpke Albrecht , Erbersdobler Andreas , Hammerer Peter , Palisaar Jüri , John Kerstin , Stumm Markus , Wieacker Peter
Published: February 2004

BACKGROUND

Prostate cancer is an androgen dependent tumor. In advanced prostate cancers androgen deprivation has proved to be an effective therapy, but 25% show no response. In this study prostatectomy specimens from patients without preoperative therapy were analyzed to determine the possible mechanism of primary antiandrogen resistance.

METHODS

The number of androgen receptor (AR) gene copies and X‐centromeres were investigated from 80 prostate cancer specimens by FISH analysis.

RESULTS

In 9 out of 80 prostate cancers additional X‐chromosomes with the corresponding AR gene could be detected. Polysomy of the X‐chromosome correlates with pathological classification and tumor volume.

CONCLUSIONS

Additional AR genes due to polysomy of the X‐chromosome are present in a subgroup of primary prostate cancers prior to antiandrogen therapy. Because the growth of prostate cancers is androgen dependent, these specimens may have an advantage in low concentrations of androgens. This may be a factor for initial antiandrogen resistance. © 2003 Wiley‐Liss, Inc.
Association of prostate cancer risk and aggressiveness to androgen pathway genes: SRD5A2, CYP17, and the AR
Authors: Cicek Mine S. , Conti David V. , Curran Anthony , Neville Phillippa J. , Paris Pamela L. , Casey Graham , Witte John S.
Published: February 2004

BACKGROUND

The prostate is an androgen‐regulated organ and polymorphisms in genes involved in testosterone synthesis, in particular, SRD5A2 (A49T and V89L variants), CYP17 (MspAI variant), and the AR (CAG, GGC repeats), represent candidate risk factors for prostate cancer incidence and aggressiveness.

METHODS

We evaluated the relationship between these five polymorphisms and prostate cancer risk in a family‐based case‐control study (N = 920). Cases were diagnosed at major medical institutions in Cleveland Ohio, and Detroit Michigan, and their unaffected brothers were used as controls. Associations were investigated with regard to prostate cancer risk, and clinical characteristics at diagnosis (i.e., tumor stage/grade, age, family history).

RESULTS

The SRD5A2 V89L variant was associated with an increased risk of prostate cancer (OR = 1.56, P = 0.02). This association was driven primarily by men diagnosed at an earlier age (OR = 2.35, P = 0.001), or with more aggressive disease (OR = 1.63, P = 0.06). None of the other variants exhibited noteworthy associations with disease.

CONCLUSIONS

These findings suggest that the SRD5A2 V89L variant may influence risk of developing prostate cancer, especially among men with a younger age of diagnosis or more aggressive disease. © 2003 Wiley‐Liss, Inc.
Molecular modeling study of the editing active site of Escherichia coli leucyl‐tRNA synthetase: Two amino acid binding sites in the editing domain
Authors: Lee Keun Woo , Briggs James M.
Published: February 2004

Aminoacyl‐tRNA synthetases (aaRSs) strictly discriminate their cognate amino acids. Some aaRSs accomplish this via proofreading and editing mechanisms. Mursinna and coworkers recently reported that substituting a highly conserved threonine (T252) with an alanine within the editing domain of Escherichia coli leucyl‐tRNA synthetase (LeuRS) caused LeuRS to cleave its cognate aminoacylated leucine from tRNALeu (Mursinna et al., Biochemistry 2001;40:5376–5381). To achieve atomic level insight into the role of T252 in LeuRS and the editing reaction of aaRSs, a series of molecular modeling studies including homology modeling and automated docking simulations were carried out. A 3D structure of E. coli LeuRS was constructed via homology modeling using the X‐ray structure of Thermus thermophilus LeuRS as a template because the E. coli LeuRS structure is not available from X‐ray or NMR studies. However, both the X‐ray T. thermophilus and homology‐modeled E. coli structures were used in our studies. Amino acid binding sites in the proposed editing domain, which is also called the connective polypeptide 1 (CP1) domain, were investigated by automated docking studies. The root mean square deviation (RMSD) for backbone atoms between the X‐ray and homology‐modeled structures was 1.18 Å overall and 0.60 Å for the editing (CP1) domain. Automated docking studies of a leucine ligand into the editing domain were performed for both structures: homology structure of E. coli LeuRS and X‐ray structure of T. thermophilus LeuRS for comparison. The results of the docking studies suggested that there are two possible amino acid binding sites in the CP1 domain for both proteins. The first site lies near a threonine‐rich region that includes the highly conserved T252 residue, which is important for amino acid discrimination. The second site is located in a flexible loop region surrounded by residues E292, A293, M295, A296, and M298. The important T252 residue is at the bottom of the first binding pocket. Proteins 2004;54:000–000. © 2004 Wiley‐Liss, Inc.
Computer modeling of the rhamnogalacturonase–“hairy” pectin complex
Authors: Choi Jong Keun , Lee Beom Hyoung , Chae Chong Hak , Shin Whanchul
Published: February 2004

The structure of a pectin‐bound complex of rhamnogalacturonase was modeled to identify the amino acid residues involved in catalysis and substrate binding. The “hairy” region of pectin, represented by six repeating stretches of (1→4)‐D‐galacturonate‐(1→2)‐L‐rhamnose dimer, was flexibly docked into the putative binding site of rhamnogalacturonase from Aspergillus aculeatus whose X‐ray structure is known. A search of the complex configurational space was performed using AutoDock for the dimeric and tetrameric sugar units in which the −1 galacturonate residue has various ring conformations. Then the plausible AutoDock solutions were manually extended to the dodecameric pectin models. Subsequently, the resulting complex models were subjected to solvated molecular dynamics using AMBER. In the best model, the substrate has an extended pseudo‐threefold helix with the −1 ring in a 4H3 half‐chair that approaches the transition state conformation. The catalytic machinery is clearly defined: Asp197 is a general acid and the activated water bound between Asp177 and Glu198 is a nucleophile. The active site is similar, with a small yet significant difference, to that of polygalacturonase that degrades the pectic “smooth” region of linear homopolymer of D‐(1→4)‐linked galacturonic acid. Rhamnogalacturonase has ten binding subsites ranging from −3 to +7, while polygalacturonase has eight subsites from −5 to +3. The model suggests that the eight amino acids including three arginine and three lysine residues, all of which are invariantly conserved in the rhamnogalacturonase family of proteins, are important in substrate binding. The present study may aid in designing mutational studies to characterize rhamnogalacturonase. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Roles of physical interactions in determining protein‐folding mechanisms: Molecular simulation of protein G and α spectrin SH3
Authors: Yup Lee Seung , Fujitsuka Yoshimi , Kim Do Hyun , Takada Shoji
Published: February 2004

Protein‐folding mechanisms of two small globular proteins, IgG binding domain of protein G and α spectrin SH3 domain are investigated via Brownian dynamics simulations with a model made of coarse‐grained physical energy functions responsible for sequence‐specific interactions and weak Gō‐like energies. The folding pathways of α spectrin SH3 are known to be mainly controlled by the native topology, while protein G folding is anticipated to be more sensitive to the sequence‐specific effects than native topology. We found in the folding of protein G that the C terminal β hairpin is formed earlier and is rigid, once ordered, in the presence of an intact C terminal turn. The α helix is found to exhibit repeated partial formations/deformations during folding and to be stabilized via the tertiary contact with preformed β sheets. This predicted scenario is fully consistent with experimental ϕ value data. Moreover, we found that the folding route is critically affected when the hydrophobic interaction is excluded from physical energy terms, suggesting that the hydrophobicity critically contributes to the folding propensity of protein G. For the folding of α spectrin SH3, we found that the distal β hairpin and diverging turn are parts formed early, fully in harmony with previous results of simple Gō‐like and experimental analysis, supporting that the folding route of SH3 domain is robust and coded by the native topology. The hybrid method provides useful tools for analyzing roles of physical interactions in determining folding mechanisms. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Missense mutations in transmembrane domains of proteins: Phenotypic propensity of polar residues for human disease
Authors: Partridge Anthony W. , Therien Alex G. , Deber Charles M.
Published: February 2004

Previous experiments on the cystic fibrosis transmembrane conductance regulator suggested that non‐native polar residues within membrane domains can compromise protein structure/function. However, depending on context, replacement of a native residue by a non‐native residue can result either in genetic disease or in benign effects (e.g., polymorphisms). Knowledge of missense mutations that frequently cause protein malfunction and subsequent disease can accordingly reveal information as to the impact of these residues in local protein environments. We exploited this concept by performing a statistical comparison of disease‐causing mutations in protein membrane‐spanning domains versus soluble domains. Using the Human Gene Mutation Database of 240 proteins (including 80 membrane proteins) associated with human disease, we compared the relative phenotypic propensity to cause disease of the 20 naturally occurring amino acids when removed from—or inserted into—native protein sequences. We found that in transmembrane domains (TMDs), mutations involving polar residues, and ionizable residues in particular (notably arginine), are more often associated with protein malfunction than soluble proteins. To further test the hypothesis that interhelical cross‐links formed by membrane‐embedded polar residues stabilize TMDs, we compared the occurrence of such residues in the TMDs of mesophilic and thermophilic prokaryotes. Results showed a significantly higher proportion of ionizable residues in thermophilic organisms, reinforcing the notion that membrane‐embedded electrostatic interactions play critical roles in TMD stability. Proteins 2004;54:000.000. © 2004 Wiley‐Liss, Inc.
Novel approaches for modeling of the A1 adenosine receptor and its agonist binding site
Authors: Gutiérrez‐de‐Terán Hugo , Centeno Nuria B. , Pastor Manuel , Sanz Ferran
Published: February 2004

The present work describes the building of a human A1 adenosine receptor (hA1AR) model, based on the X‐ray crystal structure of bovine rhodopsin, and its use as a basis for the investigation of some important structural characteristics of the receptor. One of the issues investigated was the protonation position of two histidine residues known to influence ligand binding, with protonation of His251 (6.52) in epsilon position and His278 (7.43) in delta position showing the best agreement with experimental evidence. The model was also used to study the position and structural role of water molecules present in the helical bundle. Finally, the binding site location and the ligand docking were investigated using an objective strategy. A suitable site for the binding of the ribose moiety of adenosine was first postulated and further confirmed by means of a novel chemometric strategy based on GRIND descriptors. Using this position as an anchor point, the binding of adenosine was studied by docking and molecular dynamics simulations obtaining two putative binding positions in good agreement with experimental data. Proteins 2004;54:000–000. © 2004 Wiley‐Liss, Inc.
Flexibility of β‐sheets: Principal component analysis of database protein structures
Authors: Emberly Eldon G. , Mukhopadhyay Ranjan , Tang Chao , Wingreen Ned S.
Published: February 2004

Protein folds are built primarily from the packing together of two types of structures: α‐helices and β‐sheets. Neither structure is rigid, and the flexibility of helices and sheets is often important in determining the final fold (e.g., coiled coils and β‐barrels). Recent work has quantified the flexibility of α‐helices using a principal component analysis (PCA) of database helical structures (J. Mol. Bio. 2003, 327, pp. 229–237). Here, we extend the analysis to β‐sheet flexibility using PCA on a database of β‐sheet structures. For sheets of varying dimension and geometry, we find two dominant modes of flexibility: twist and bend. The distributions of amplitudes for these modes are found to be Gaussian and independent, suggesting that the PCA twist and bend modes can be identified as the soft elastic normal modes of sheets. We consider the scaling of mode eigenvalues with sheet size and find that parallel β‐sheets are more rigid than antiparallel sheets over the entire range studied. Finally, we discuss the application of our PCA results to modeling and design of β‐sheet proteins. Proteins 2004. © 2004 Wiley‐Liss, Inc.
A novel approach to predict active sites of enzyme molecules
Authors: Chou Kuo‐Chen , Cai Yu‐dong
Published: February 2004

Enzymes are critical in many cellular signaling cascades. With many enzyme structures being solved, there is an increasing need to develop an automated method for identifying their active sites. However, given the atomic coordinates of an enzyme molecule, how can we predict its active site? This is a vitally important problem because the core of an enzyme molecule is its active site from the viewpoints of both pure scientific research and industrial application. In this article, a topological entity was introduced to characterize the enzymatic active site. Based on such a concept, the covariant discriminant algorithm was formulated for identifying the active site. As a paradigm, the serine hydrolase family was demonstrated. The overall success rate by jackknife test for a data set of 88 enzyme molecules was 99.92%, and that for a data set of 50 independent enzyme molecules was 99.91%. Meanwhile, it was shown through an example that the prediction algorithm can also be used to find any typographic error of a PDB file in annotating the constituent amino acids of catalytic triad and to suggest a possible correction. The very high success rates are due to the introduction of a covariance matrix in the prediction algorithm that makes allowance for taking into account the coupling effects among the key constituent atoms of active site. It is anticipated that the novel approach is quite promising and may become a useful high throughput tool in enzymology, proteomics, and structural bioinformatics. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Protein simple sequence conservation
Authors: Sim Kim Lan , Creamer Trevor P.
Published: February 2004

Protein simple sequences, a subset of low‐complexity sequences, are regions of sequence highly enriched in one or a few residue types. Simple sequences are exceedingly common, the average being more than one per protein sequence. Despite being so common, such sequences are not well‐studied. The simple sequences that have been subjected to detailed study are often found to possess important functions. Here we present a survey of protein simple sequences, generally enriched in a single residue type, with the aim of studying their conservation. We find that the majority of such simple sequences are not conserved. However, conserved protein simple sequences are relatively common, with ∼11% of the surveyed protein families possessing a conserved simple sequence. The data obtained in this study support the idea that simple sequences are conserved for functional reasons. Such functions can range from substrate binding, to mediating protein‐protein interactions, to structural integrity. A perhaps surprising finding is that the residue enriching a conserved simple sequence is itself not necessarily conserved. Neither is the length of many of the highly conserved simple sequences. In the few cases where structural and functional data is available it is found that the conserved simple sequences are consistent with both local structure and function. The data presented support the idea that protein simple sequences can be conserved and have important roles in protein structure and function. Proteins 2004;54:000–000. © 2004 Wiley‐Liss, Inc.
What is the protein design alphabet?
Authors: Dokholyan Nikolay V.
Published: February 2004

Selecting a protein sequence that corresponds to a specific three‐dimensional protein structure is known as the protein design problem. One principal bottleneck in solving this problem is our lack of knowledge of precise atomic interactions. Using a simple model of amino acid interactions, we determine three crucial factors that are important for solving the protein design problem. Among these factors is the protein alphabet—a set of sequence elements that encodes protein structure. Our model predicts that alphabet size is independent of protein length, suggesting the possibility of designing a protein of arbitrary length with the natural protein alphabet. We also find that protein alphabet size is governed by protein structural properties and the energetic properties of the protein alphabet units. We discover that the usage of average types of amino acid in proteins is less than expected if amino acids were chosen randomly with naturally occurring frequencies. We propose three possible scenarios that account for amino acid underusage in proteins. These scenarios suggest the possibility that amino acids themselves might not constitute the alphabet of natural proteins. Proteins 2004;54:000–000. © 2004 Wiley‐Liss, Inc.
A novel method for protein secondary structure prediction using dual‐layer SVM and profiles
Authors: Guo Jian , Chen Hu , Sun Zhirong , Lin Yuanlie
Published: February 2004

A high‐performance method was developed for protein secondary structure prediction based on the dual‐layer support vector machine (SVM) and position‐specific scoring matrices (PSSMs). SVM is a new machine learning technology that has been successfully applied in solving problems in the field of bioinformatics. The SVM's performance is usually better than that of traditional machine learning approaches. The performance was further improved by combining PSSM profiles with the SVM analysis. The PSSMs were generated from PSI‐BLAST profiles, which contain important evolution information. The final prediction results were generated from the second SVM layer output. On the CB513 data set, the three‐state overall per‐residue accuracy, Q3, reached 75.2%, while segment overlap (SOV) accuracy increased to 80.0%. On the CB396 data set, the Q3 of our method reached 74.0% and the SOV reached 78.1%. A web server utilizing the method has been constructed and is available athttp://www.bioinfo.tsinghua.edu.cn/pmsvm. Proteins 2004;00:000–000. © 2004 Wiley‐Liss, Inc.
The role of pH on instability and aggregation of sickle hemoglobin solutions
Authors: Manno M. , San Biagio P. L. , Palma M. U.
Published: February 2004

Understanding the physical basis of protein aggregation covers strong physical and biomedical interests. Sickle hemoglobin (HbS) is a point‐mutant form of normal human adult hemoglobin (HbA). It is responsible for the first identified “molecular disease,” as its propensity to aggregation is responsible for sickle cell disease. At moderately higher than physiological pH value, this propensity is inhibited: The rate of aggregate nucleation becomes exceedingly small and solubility after polymerization increases. These order‐of‐magnitude effects on polymer nucleation rates and concurrent relatively modest changes of solubility after polymerization are here shown to be related to both pH‐induced changes of location and shape of the liquid–liquid demixing (LLD) region. This allows establishment of a self‐consistent contact between the thermodynamics of the solution as such (i.e., the LLD region), the kinetics of fiber nucleation, the theory of percolation, and the thermodynamics of gelation. The observed pH‐induced changes are largely attributable to strong perturbations of hydrophobic hydration configurations and related free energy by electric charges. Similar mechanisms of effective control of aggregate nucleation rates by means of agents such as cosolutes, pH, salts, and additives, shifting the LLD and associated regions of anomalous fluctuations, promise to be relevant to the whole field of protein aggregation pathologies. Proteins 2004;00:000–000. © 2004 Wiley‐Liss, Inc.
Conformational subspace in simulation of early‐stage protein folding
Authors: Jurkowski Wiktor , Brylinski Michał , Konieczny Leszek , Wiíniowski Zdzisław , Roterman Irena
Published: February 2004

A probability calculus was used to simulate the early stages of protein folding in ab initio structure prediction. The probabilities of particular ϕ and ψ angles for each of 20 amino acids as they occur in crystal forms of proteins were used to calculate the amount of information necessary for the occurrence of given ϕ and ψ angles to be predicted. It was found that the amount of information needed to predict ϕ and ψ angles with 5° precision is much higher than the amount of information actually carried by individual amino acids in the polypeptide chain. To handle this problem, a limited conformational space for the preliminary search for optimal polypeptide structure is proposed based on a simplified geometrical model of the polypeptide chain and on the probability calculus. These two models, geometric and probabilistic, based on different sources, yield a common conclusion concerning how a limited conformational space can represent an early stage of polypeptide chain‐folding simulation. The ribonuclease molecule was used to test the limited conformational space as a tool for modeling early‐stage folding. Proteins 2004. © 2004 Wiley‐Liss, Inc.
Evaluation of the Quality of a Car Braking System by a Dynamic Simulator
Authors: Celentano G. , Iervolino R. , Fontana V. , Porreca S.
Published: February 2004

Quality has become one of the more important factors in the purchasing decisions of the consumer. At the moment, the tools available for variability analysis in the production process, which is the main cause of quality degradation, are mostly based on statistical approaches that neglect the physical relationships that exist in a man‐made system. In this paper a new general methodology is proposed, which gives evidence of how the development of a mathematical model could be more suitable if set by a relatively limited amount of data and a number of experimental tests. The implementation of the model in a dynamic simulator allows one to evaluate the effects of the variability of the most critical elements on the quality of the whole system numerically. The effectiveness of the procedure is demonstrated by the evaluation of some quality indexes of a car braking system. Copyright © 2004 John Wiley & Sons, Ltd.
Experimental ‘Reliability Growth’ or ‘Reliability Verification’ Related with the Amount of Innovation in a New Car Model
Authors: Parigi P. , Vianello M.
Published: February 2004

Reliability growth testing, i.e. the ‘growth’ of reliability, is a consolidated systematic method used by Fiat Auto to increase and ‘demonstrate’ reliability while testing vehicles. If a new car model is not very different from the previous one (being used as reference), a single ‘verification’ experimental phase on the vehicles which is consistent with the end product may be sufficient for a reliability statistical demonstration. In this case, the resultant confidence interval may be very large, especially when we want to predict the in field failure frequency after applying corrective actions. Conversely, if the new product shows too many problems, we could obviously define, at any moment, a specific (and more demanding) reliability growth plan and restart the experiments. This paper suggests the cases in which we should choose a reliability growth test or a reliability verification test, whilst considering the total amount of design variations with respect to the reference model: completely new model, restyling, face lifting, etc. Copyright © 2004 John Wiley & Sons, Ltd.
Rules of electron correlation energies of van der Waals' complexes RgX (Rg = Ar, Kr, X = F, Cl, Br)
Authors: Wei Jichong , Zhuo Shuping , Ju Guanzhi
Published: February 2004

First, the intrapair and interpair correlation energies of the Rg atom, X atom, and the optimized RgX (Rg = Ar, Kr, X = F, Cl, Br) complexes are calculated by the MELD program at the 6‐311++g(d), 6‐311++g(3df, 3pd), and cc‐pvqz basis sets (denoted by basis sets a, b, and c, respectively). It is found that the relationship Ecorr(RgX) ≈ Ecorr(Rg) + Ecorr(X) is correct for all the above systems but introducing an unsound absolute error for some RgX systems. Second, the same calculations are selectively carried out for ArF (the smallest system) and KrBr (the largest system) at their increasing interatomic distance. It was found that both the correlation energies of ArF and those of KrBr will decrease whenever the interatomic distance of them become larger. On the basis of our results, we provided an approach to quickly estimate the correlation energies of RgX complexes by which not only the absolute error becomes smaller but more computation work is saved than the direct calculation. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Model for phase coexistence in phase transitions
Authors: Wang Y. , Ahuja R. , Johansson B.
Published: February 2004

We propose a general model for describing the phenomena of phase coexistence in relation to pressure induced phase transformations by means of the T–P distribution in statistical thermodynamics. Using the well‐known B1–B2 transition in NaCl as a prototype, we demonstrate how phase coexistence gives rise to the changes in the bulk modulus and the equation‐of‐state across the transition. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Application of physical habitat simulation (PHABSIM) modelling to modified urban river channels
Authors: Booker D. J. , Dunbar M. J.
Published: February 2004

Prediction of changes to in‐stream ecology are highly desirable if decisions on river management, such as those relating to water abstractions, effluent discharges or modifications to the river channel, are to be justified to stakeholders. The physical habitat simulation (PHABSIM) system is a well‐established hydro‐ecological model that provides a suite of tools for the numerical modelling of hydraulic habitat suitability for fish and invertebrate species. In the UK, the most high‐profile PHABSIM studies have focused on rural, groundwater‐dominated rivers and have related to low flow issues. Conversely, there have been few studies of urban rivers. This paper focuses on the application of PHABSIM to urban rivers and demonstrates how sensitivity analyses can be used to assess uncertainty in PHABSIM applications. Results show that physical habitat predictions are sensitive to changes in habitat suitability indices, hydraulic model calibration and the temporal resolution of flow time‐series. Results show that there is greater suitable physical habitat over a wider range of flows in a less engineered river channel when compared to a more engineered channel. The work emphasizes the need for accurate information relating to the response of fish and other organisms to high velocities. Copyright © 2004 John Wiley & Sons, Ltd.
Simulating effects of hydro‐dam alteration on thermal regime and wild steelhead recruitment in a stable‐flow Lake Michigan tributary
Authors: Horne Brad D. , Rutherford Edward. S. , Wehrly Kevin E.
Published: February 2004

Hydroelectric dams may affect anadromous fish survival and recruitment by limiting access to upstream habitats and adversely affecting quality of downstream habitats. In the Manistee River, a tributary to Lake Michigan, two hydroelectric dams potentially limit recruitment of anadromous rainbow trout (steelhead) by increasing tailrace water temperatures to levels that significantly reduce survival of young‐of‐year (YOY) fish. The objectives of this study were to determine whether proposed restoration scenarios (dam removals or a bottom withdrawal retrofit) would alter the Manistee River thermal regime and, consequently, improve wild steelhead survival and recruitment. Physical process models were used to predict Manistee River thermal regimes following each dam alteration scenario. Empirical relationships were derived from historical field surveys to quantify the effect of temperature on YOY production and potential recruitment of Manistee River steelhead. Both dam alteration scenarios lowered summer temperatures and increased steelhead recruitment by between 59% and 129%, but total recruitments were still low compared to other Great Lakes tributaries. Considering only temperature effects, bottom withdrawal provides the greatest promise for increasing natural steelhead recruitment by decreasing the likelihood of year‐class failures in the warmest summers. Results of this study may allow managers to evaluate mitigation alternatives for Manistee River dams during future relicensing negotiations, and illustrate the utility of physical process temperature models in groundwater‐fed rivers. Copyright © 2004 John Wiley & Sons, Ltd.
Application of a 2D hydrodynamic model to design of reach‐scale spawning gravel replenishment on the Mokelumne River, California
Authors: Pasternack Gregory B. , Wang C. Lau , Merz Joseph E.
Published: February 2004

In‐stream chinook salmon (Oncorhynchus tschawytscha) spawning habitat in California's Central Valley has been degraded by minimal gravel recruitment due to river impoundment and historic gravel extraction. In a recent project marking a new direction for spawning habitat rehabilitation, 2450 m3 of gravel and several boulders were used to craft bars and chutes. To improve the design of future projects, a test was carried out in which a commercial modelling package was used to design and evaluate alternative gravel configurations in relation to the actual pre‐ and post‐project configurations. Tested scenarios included alternate bars, central braid, a combination of alternate bars and a braid, and a flat riffle with uniformly spaced boulders. All runs were compared for their spawning habitat value and for susceptibility to erosion. The flat riffle scenario produced the most total, high, and medium quality habitat, but would yield little habitat under flows deviating from the design discharge. Bar and braid scenarios were highly gravel efficient, with nearly 1 m2 of habitat per 1 m3 of gravel added, and yielded large contiguous high quality habitat patches that were superior to the actual design. At near bankfull flow, negligible sediment entrainment was predicted for any scenario. Copyright © 2004 John Wiley & Sons, Ltd.
Lend me your wallets: the effect of charismatic leadership on external support for an organization
Authors: Flynn Francis J. , Staw Barry M.
Published: February 2004

We argue that charismatic leadership can influence external support for the organization, particularly in making the company more attractive to outside investors. Two studies were conducted to test this general hypothesis. First, an archival study demonstrated that the stock of companies headed by charismatic leaders appreciated more than the stock of comparable companies, even after differences in corporate performance were controlled. It was also found that the effect of charismatic leadership was heightened under more difficult economic conditions. Second, an experiment was conducted in which the salience of charismatic leadership was manipulated, along with information about the prospects for an organization's turnaround. Results showed that appeals from a charismatic leader led to increased investment in the firm, and the leader's influence was greater when the prospects for an organizational turnaround were more difficult. It was also found that an endowment of stock enhanced the influence of charismatic appeals and that charismatic leadership may have affected the general risk propensities of followers. These findings were interpreted in terms of an external perspective on leadership, illustrating how leaders can manage the firm's economic and social environment. Copyright © 2004 John Wiley & Sons, Ltd.
Corruption and change: the impact of foreign direct investment
Authors: Robertson Christopher J. , Watson Andrew
Published: February 2004

This study examines influences on the level of corruption in countries from a strategic perspective. Corruption is one of the country‐level influences on market entry, investment, and other decisions fundamental to strategic management at the international level. The study examines the impact on corruption of change in levels of foreign direct investment (FDI). It uses the Corruption Perceptions Index (CPI) scores computed by Transparency International for 1999 and 2000. Results indicate that the more rapid the rate of change in FDI, the higher the level of corruption. Higher levels of perceived corruption are associated with each of two dimensions of national culture: uncertainty avoidance and masculinity. Research and managerial implications are also discussed. Copyright © 2004 John Wiley & Sons, Ltd.
Fast, accurate call graph profiling
Authors: Spivey J. M.
Published: February 2004

Existing methods for call graph profiling, such as that used by gprof, deal badly with programs that have shared subroutines, mutual recursion, higher‐order functions, or dynamic method binding. This article discusses a way of improving the accuracy of a call graph profile by collecting more information during execution, without significantly increasing the overhead of profiling. The method is based on keeping track of a context, consisting of the set of subroutines that are active at a particular moment during execution, together with the calling arcs between these subroutines. The profiler records the time spent in each context during execution of the program, and thus obtains an accurate measurement of the total time during which each subroutine was active. By recording arc information for only the most recent activation of each subroutine, it is possible to arrange that even recursive programs give rise to a finite number of these contexts, and in typical real programs, the number of distinct contexts remains manageably small. The data can be collected efficiently during execution by constructing a finite‐state machine whose states correspond to contexts, so that when a context is entered for a second or subsequent time, only a single access of a hash table is needed to update the state of the profiling monitor. Copyright © 2003 John Wiley & Sons, Ltd.
A ReScUE XML/EDI model
Authors: Lu Eric Jui‐Lin , Wu Chang‐Chuan
Published: February 2004

Since electronic data interchange (EDI) is one of the most important components in electronic commerce and since Extensible Markup Language (XML) provides Internet developers with a powerful vehicle for exchanging messages, XML/EDI has received much attention from almost all well‐known international enterprises and is believed to be the next generation EDI. However, since XML allows developers to design their own elements and attributes, it is almost certain businesses will receive XML documents with unknown elements. Generally, human intervention is required to solve the problem. Therefore, it is indispensable to design an efficient scheme to resolve the unknown elements. In this paper, we propose a ReScUE XML/EDI model such that transformation templates will be generated automatically for documents with unknown elements, and the documents will be converted into expected format. This model increases the flexibility of XML/EDI systems and reduces human intervention. Copyright © 2003 John Wiley & Sons, Ltd.
Silica‐supported biomimetic membranes
Authors: Ariga Katsuhiko
Published: February 2004

The hybridization of lipid membranes with inorganic silica‐based framework results in mechanically stable biomembrane mimics. This account describes three types of silica‐based biomimetic membranes. As the first example, a Langmuir monolayer of dialkylalkoxysilane was polymerized and immobilized onto a porous glass plate. Permeability through the monolayer‐immobilized glass was regulated by phase transition of the immobilized monolayer. In the second example, spherical vesicles covalently attached to a silica cover layer (Cerasome) were prepared. The Cerasome was stable enough to be assembled into layer‐by‐layer films without destruction of its vesicular structure. This material could be an example of the multicellular assembly. Mesoporous silica films densely filling peptide assemblies (Proteosilica) are introduced as the third example. The Proteosilica was synthesized as a transparent film through template sol‐gel reaction using amphiphilic peptides. © 2004 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 3: 297–307; 2004: Published online in Wiley InterScience (www.interscience.wiley.com) DOI 10.1002/tcr.10071
Synthesis of tumor‐associated glycopeptide antigens for the development of tumor‐selective vaccines
Authors: Dziadek Sebastian , Kunz Horst
Published: February 2004

In contrast to normal cells, the glycoprotein profile on epithelial tumor cells is distinctly altered. Due to an incomplete
formation of the glycan side‐chains resulting from a premature sialylation, additional peptide epitopes become accessible
to the immune system in mucin‐type glycoproteins on tumor cells. These tumor‐associated structure alterations
constitute the basis for a selective immunological attack on cancer cells. For the construction of immunostimulating antigens,
glycopeptide partial structures from the mucins MUC1 and MUC4 carrying the tumor‐associated sialyl‐TN,
α2,6‐sialyl‐T and α2,3‐sialyl‐T antigens have been synthesized. Employing different
linkers such as the allylic HYCRON or the fluoride‐sensitive PTMSEL anchor, the antigenic glycopeptide structures
were constructed on the solid phase utilizing pre‐assembled glycosyl amino acid building blocks prepared in
solution by convergent chemical or chemoenzymatic strategies. The proliferation of cytotoxic T cells has been induced
applying a construct composed of a sialyl‐TN MUC1‐glycopeptide conjugated with a tetanus toxin
T cell peptide epitope. © 2004 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 3: 308–321,
2004: Published online in Wiley InterScience (www.interscience.wiley.com)
DOI 10.1002/tcr10074