bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk factors for early death due to recurrence after liver resection for hepatocellular carcinoma: Results of a multicenter study
Authors: Regimbeau Jean Marc , Abdalla Eddie K. , Vauthey Jean Nicolas , Lauwers Gregory Y. , Durand François , Nagorney David M. , Ikai Iwao , Yamaoka Yoshio , Belghiti Jacques
Published: December 2003

Background and Objectives

Recurrence after partial liver resection for hepatocellular carcinoma (HCC) is a major cause of death from this disease. To identify risk factors for early death from recurrence after liver resection for HCC.

Methods

All 547 patients in this study had greater than 1 year of follow‐up after complete resection of HCC (1980–1999) at one of the four hepatobiliary centers in Japan, France, and the United States. Patients who died of recurrence ≤1 year post‐resection and all of those alive at least 1 year were compared. Survival and clinicopathological factors associated with death from recurrence within 1 year of resection were analyzed.

Results

Overall postoperative mortality rate was 5%. In the first postoperative year, 123 (22%) patients died. Of these, 53 (43%) died of recurrence, 30 (24%) of postoperative complications, and 40 (33%) of liver failure/hemorrhage. On multivariate analysis, tumor size greater than 5 cm (P < 0.02; odds ratio, 3.0), multiple tumors (P < 0.01; odds ratio, 3.3), and greater than 5 mitoses per 10 high‐power fields (P < 0.03; odds ratio, 3) were associated with increased risk of early death due to recurrence.

Conclusions

These findings enable identification of patients with HCC who are at high risk for early death due to recurrence following potentially curative resection who might be candidates for adjuvant therapy trials. J. Surg. Oncol. 2004;85:36–41. © 2003 Wiley‐Liss, Inc.
Breast‐conserving therapy (BCT) for early‐stage breast cancer
Authors: Benda Rashmi K. , Mendenhall Nancy Price , Lind D. Scott , Cendan Juan C. , Shea Barbara F. , Richardson Lisa C. , Copeland Edward M.
Published: December 2003

Several patient and tumor factors go into the decision process to determine whether a breast cancer patient is a good candidate for breast‐conserving therapy. The patient must be seen by all disciplines before any therapeutic intervention. When used appropriately, breast‐conserving therapy produces maximal disease control and improves quality of life in patients with early‐stage breast cancer. J. Surg. Oncol. 2004;85:14–27. © 2003 Wiley‐Liss, Inc.
Strategies for cancer gene therapy
Authors: Hughes Rhiannon M.
Published: December 2003

Gene therapy offers new opportunities for cancer treatment and prevention through the use of targeted, relatively nontoxic treatments that can identify, disable, and destroy malignant cells. This article reviews the principles behind oncogene inactivation, tumor suppressor gene replacement, inhibition of angiogenesis, immunopotentiation, molecular chemotherapy, and addition of drug resistance genes. The adcantages and limitations of viral and nonviral vectors for delivery of the therapeutic genes are presented. J. Surg. Oncol. 2004;85:28–35. © 2003 Wiley‐Liss, Inc.
The Savanna Principle
Authors: Kanazawa Satoshi
Published: December 2003

Why do microeconomic theories (such as decision theory and game theory) often fail to predict human behavior despite their mathematical elegance and deductive rigor? I suggest that such empirical failures stem from the theory's misconception of how the human brain functions. Drawing on evolutionary psychology, I propose theSavanna Principle, which posits that a hypothesis about human behavior fails to the extent that its scope conditions and assumptions are inconsistent with the ancestral environment, and its experimental corollary, that the Savanna Principle holds (and the hypothesis fails) to the extent that the conditions of the experiment resemble the ancestral environment. I suggest that the Savanna Principle and its corollary might together explain the relative empirical failure of noncooperative game theory and public choice theory, and the relative success of network exchange theory and competitive price theory tested in double auction markets in experimental economics. Copyright © 2003 John Wiley & Sons, Ltd.
Behavioral uncertainty and investments in cooperative relationships
Authors: Vetschera Rudolf
Published: December 2003

We study a cooperative relationship between two economic agents, in which one agent can make investments in the relationship to reduce the probability that the other agent defects. The probability of defection is derived from an incomplete information decision model of the transaction partner. We show that the relationship between investment and probability of defection depends on the type of uncertainty considered and analyze the effects of parameter changes on the optimal level of investment. Copyright © 2004 John Wiley & Sons, Ltd.
Coupons and price discrimination in vertically‐correlated markets
Authors: Hu Jin‐Li , Chiou Yu‐Hsiu , Hwang Hong
Published: December 2003

This research analyzes the non‐cooperative and cooperative strategies with respect to manufacturer and retailer coupons. In a model with one manufacturer selling its product to one retailer, it is found that the retailer can achieve third‐degree price discrimination equilibrium in retail markets by issuing coupons to demanders with higher elasticity. Although facing only one retailer, the manufacturer can also achieve the same third‐degree price discrimination equilibrium by issuing coupons directly to demanders of higher elasticity. However, when only one firm issues the coupon, both manufacturer and retailer coupons can help alleviate the channel profit loss due to double marginalization. If the manufacturer and the retailer non‐cooperatively issue coupons, then the subgame‐perfect Nash equilibrium outcomes are equivalent to those under the successive third‐degree price discrimination. Moreover, cooperative strategies between the manufacturer and the retailer can eliminate double marginalization, achieve the vertical integration effect, and lead to higher profits, consumer surpluses, and social surpluses than non‐cooperative coupon strategies. Copyright © 2004 John Wiley & Sons, Ltd.
Financial health and airline safety
Authors: Noronha Gregory , Singal Vijay
Published: December 2003

Agency‐cost models suggest that firms may pursue riskier strategies in times of financial distress. For example, stockholders of financially weak firms in industries where quality cannot be observed ex‐ante have an incentive to compromise safety and quality to maximize current period profit. However, there exists only a modest amount of empirical evidence that relates financial health to the risk‐taking behavior of firms.

We explore this relationship for the airline industry. Using bond ratings to proxy for financial health and airline mishaps to measure safety, we find a significant correlation: airlines with higher quality bond ratings are less likely to experience mishaps than airlines with lower quality ratings. On average, a whole letter grade better bond rating is associated with a 10% lower probability of a mishap. Copyright © 2004 John Wiley & Sons, Ltd.
Mechanical properties and morphology of nylon‐6 hybrid composites
Authors: Unal H , Mimaroglu A , Alkan M
Published: December 2003

In this investigation, the influence of filler type and filler content on the mechanical properties of nylon‐6 is investigated. The mineral fillers were selected on the basis of their shape and size: flake‐like kaolin and talc, spherical glass beads or fibrous wollastonite. These fillers were added to nylon‐6 individually or in mixed combinations. They were added at different percentages varying between 10 and 30% w/w. Samples of the composites were prepared by the injection moulding process. Uniaxial tensile, Izod impact and flexural tests were carried out. Tensile strength, elongation at break, modulus of elasticity and impact energy were obtained and compared. In case of single fillers the results showed that the tensile strength, modulus of elasticity and their flexural values for nylon‐6 composite improve with the increase in filler content while mixed compounds showed no significant changes above 15% + 15% w/w filler. However, for single and mixed filler up to 10% w/w, the impact strength and maximum elongation at break showed significant decrease. In general, the maximum improvement in mechanical the addition of 10–15% w/w filler. Copyright © 2003 Society of Chemical Industry
Surface modification of ePTFE vascular grafts with O‐carboxymethylchitosan
Authors: Zhu Aiping , Zhang Ming , Zhang Zheng
Published: December 2003

O‐Carboxymethylchitosan (OCMCS) was covalently immobilized onto expanded poly(tetrafluoroethylene) (ePTFE) vascular graft using a photosensitive hetero‐bifunctional crosslinking reagent, 4‐azidobenzoic acid. 4‐Azidobenzoic‐bonded OCMCS (Az‐OCMCS) was prepared by reaction between an acid group of the crosslinking reagent and a free amino group of OCMCS. Immobilization was accomplished by irridiating the A3‐OCMCS coating on the substrate surface with ultraviolet light. Electron spectroscopy and water contact angle were used to characterize that OCMCS had been bonded on the ePTFE vascular graft surface. The hydrophilicity of ePTFE was enhanced greatly by surface bonding with OCMCS. Platelet adhesion assay showed that the ePTFE vascular surface bonded with OCMCS demonstrated good blood‐compatibility. Copyright © 2003 Society of Chemical Industry
Copolymers of aniline with o‐ and m‐toluidine: synthesis and characterization
Authors: Savitha P , Sathyanarayana DN
Published: December 2003

Copolymers of aniline and toluidine were synthesized by oxidative chemical polymerization using different ratios of the monomers in the feed, and characterized by a number of techniques including UV–visible, IR, Raman, 1H NMR and EPR spectroscopies, as well as by thermogravimetric analysis and conductivity measurements. The properties of the copolymers are influenced by the amount of toluidine in the copolymer. Poly(o‐toluidine) and poly(m‐toluidine) are noticeably different in their solubility and conductivity. The copolymers show better solubilities than polyaniline but have lower conductivities. Differences in the properties of the salt and base forms of the copolymers are pointed out. Copyright © 2003 Society of Chemical Industry
Toughening of an epoxy anhydride resin system using an epoxidized hyperbranched polymer
Authors: Varley Russell J , Tian Wendy
Published: December 2003

This paper reports on the use of an epoxidized hyperbranched polymer (HBP) as an additive to an epoxy anhydride resin system. The hyperbranched polymer used was an aliphatic polyester with a molecular weight of around 10 500 g mol−1. The epoxy resin mixture used was a combination of a difunctional diglycidyl ether of bisphenol A (DGEBA) epoxy and an epoxy novolac, and was cured with a catalysed anhydride curing agent. It has been shown that, at a concentration range of 0 to 20 wt% addition, the HBP is able to almost double the fracture toughness, with little evidence of any deleterious effects upon processing and the durability of the cured resin system. The flexural modulus and stress, however, were found to both decrease by about 30% as a result of HBP addition while the Tg was found to decrease by about 10%. The processability of the uncured resin systems has been investigated by using rheological and calorimetric techniques and it was found that the processability window, as determined by the gel time and viscosity changes, was relatively unaffected by HBP addition. The fracture surfaces were evaluated by using scanning electron microscopy which showed that the unique structure of the HBP facilitates an enhanced interaction with the polymer matrix to achieve excellent toughness enhancement of the polymer matrix. The durability of the epoxy network has been investigated via thermogravimetric analysis (TGA) and solvent uptake, and the HBP has been shown to have little systematic deleterious effect upon the degradation temperatures and the total amount of solvent absorbed. Copyright © 2003 Society of Chemical Industry
Photoinitiated radical polymerization of some substituted tetrahydrophthalimido and maleimidophenyl methacrylates
Authors: Gryshchuk LYu , Vretik LO , Syromyatnikov VG , Novikova OO , Paskal LP , Voytekunas VYu , Abadie MJM
Published: December 2003

The photopolymerization of some substituted tetrahydrophthalimido and 4‐(maleimido)phenyl methacrylates in N,N‐dimethylformamide solutions was investigated by photo‐differential scanning calorimetry at ambient temperature. Auto‐acceleration of photopolymerization and the formation of cross‐linked products were observed as a result of temperature increases up to 60–80 °C. Substituted 4‐(maleimido)phenyl methacrylates demonstrated higher cross‐linking abilities at elevated temperatures than tetrahydrophthalimidophenyl methacrylates. Copyright © 2003 Society of Chemical Industry
Reactions of cellulose and wood superficial hydroxy groups with organometallic compounds
Authors: Fabbri Paola , Champon Géraldine , Castellano Maila , Belgacem Mohamed Naceur , Gandini Alessandro
Published: December 2003

Various lignocellulosic substrates, including microcrystalline cellulose, pinewood and hemp fibres, were treated with triethylaluminium and triethylboron in suspensions, in non‐swelling media. Chemical and spectroscopic analyses show that coupling surface reactions took place between one or two metal‐to‐carbon (Mt–C) bonds and the OH groups of the natural polymers. The remaining unreacted Mt–C bonds were exploited to graft numerous molecular structures derived from alcohols and amines. The occurrence of the second reaction was proved by Fourier‐transform infrared spectroscopy, elemental analyses, X‐ray photoelectron spectroscopy and contact angle measurements. Copyright © 2004 Society of Chemical Industry
The use of master curves to describe the simultaneous effect of cooling rate and pressure on polymer crystallization
Authors: La Carrubba Vincenzo , Brucato Valerio , Piccarolo Stefano
Published: December 2003

In a previous work a master‐curve approach was applied to experimental density data to explain isotactic polypropylene (iPP) behaviour under pressure and high cooling rates. Suitable samples were prepared by solidification from the melt under various cooling rate and pressure conditions with the help of a special apparatus based on a modified injection moulding machine. The approach here reported is more general than the case study previously shown, and is suitable to be applied to several materials and for different measures related to crystalline content. The proposed simple model is able to predict successfully the final polymer properties (density, micro‐hardness, crystallinity) by superposition of the effect of cooling rate and the effect of pressure in a wide range of experimental conditions. For this purpose three semi‐crystalline polymers were studied [iPP, polyamide‐6 (PA6) and poly(ethyleneterephthalate) (PET)], which exhibited remarkably different behaviour when crystallized under pressure and high cooling rates Copyright © 2003 Society of Chemical Industry
Formulation design, optimization, characterization and swelling behaviour of a cationic superabsorbent based on a copolymer of [3‐(methacryloylamino)propyl]trimethylammonium chloride and acrylamide
Authors: Saeidi Ardeshir , Katbab AA , Vasheghani‐Farahani E , Afshar F
Published: December 2003

A series of crosslinked copolymers with cationic nature have been prepared based on acrylamide (AAm) and [3‐(methacryloylamino)propyl]trimethyl ammonium chloride (MAPTAC) using N,N′ methylene‐bis‐acrylamide (MBA) as crosslinking agent. Taguchi's method has been employed for the purpose of formulation design and optimization as well as investigating the effects of various compositional parameters, such as total monomer concentration, cationic monomer and crosslinking agent concentration. The swelling behaviour of the synthesized gels in electrolyte solutions composed of ions with different valency has been studied and compared with an anionic‐based superabsorbent. The swelling capacity and absorbency were found to be enhanced with increase of the MAPTAC moieties of the copolymer chains, and therefore increase of their cationic character. All the cationic hydrogels prepared had greater swelling capacity, with less change in their swelling behaviour, when immersed into aqueous solutions containing multivalent cations. The anionic‐based hydrogels collapsed in similar ionic solutions with moderate‐to‐high ionic strength and did not show any tendency to re‐swell. The complex modulus (G*) of the crosslinked copolymers in the equilibrium swollen state was measured by rheomechanical spectroscopy and was correlated with the chemical composition of the network. Thermogravimetric analysis of the dry cationic superabsorbent showed more bound water but similar thermal behaviour to crosslinked polyacrylamide Copyright © 2003 Society of Chemical Industry
The effect of morphology on the optical properties of transparent epoxy/montmorillonite composites
Authors: Deng Yuming , Gu Aijuan , Fang Zhengping
Published: December 2003

Three kinds of epoxy‐based transparent nanocomposites were prepared by the reaction of alkylammonium‐exchanged montmorillonite (AMT) with diglycidyl ether of bisphenol A (DGEBA) and triethylamine as the curing agent. The morphology of these composites was characterized by X‐ray diffraction, scanning electron microscopy and transmission electron microscopy. The effect of morphology on the optical transparency of epoxy/AMT composites (Ep/AMT) was investigated. The light transmittance of Ep/AMT depended greatly on the exfoliation degree (ED) of AMT in the epoxy matrix, and the transmittance of the composites with higher ED was notably higher than that with lower ED under the same AMT content. The light transmittance of composites prepared with different amounts of curing agent was also studied. Results suggested that the composites prepared with insufficient curing agent were more transparent than those prepared with stoichiometric and higher contents of curing agent because insufficient curing agent was benefitial to the exfoliation of AMT. An equation describes the relationship of the light transmittance of nanocomposites with the concentration, particle size and basal spacing of AMT as well as the wavelength. Theoretical analysis suggested that the effect of morphology on the transparence mainly comes from the changes of the particle size and basal spacing of AMT, and that the effect of the former is more significant than that of the latter Copyright © 2003 Society of Chemical Industry
Class‐specific correlations between protein folding rate, structure‐derived, and sequence‐derived descriptors
Authors: Kuznetsov Igor B. , Rackovsky Shalom
Published: December 2003

Small single‐domain proteins that fold by simple two‐state kinetics have been shown to exhibit a wide variation in their folding rates. It has been proposed that folding mechanisms in these proteins are largely determined by the native‐state topology, and a significant correlation between folding rate and measures of the average topological complexity, such as relative contact order (RCO), has been reported. We perform a statistical analysis of folding rate and RCO in all three major structural classes (α, β, and α/β) of small two‐state proteins and of RCO in groups of analogous and homologous small single‐domain proteins with the same topology. We also study correlation between folding rate and the average physicochemical properties of amino acid sequences in two‐state proteins. Our results indicate that 1) helical proteins have statistically distinguishable, class‐specific folding rates; 2) RCO accounts for essentially all the variation of folding rate in helical proteins, but for only a part of the variation in β‐sheet‐containing proteins; and 3) only a small fraction of the protein topologies studied show a topology‐specific RCO. We also report a highly significant correlation between the folding rate and average intrinsic structural propensities of protein sequences. These results suggest that intrinsic structural propensities may be an important determinant of the rate of folding in small two‐state proteins. Proteins 2003. © 2003 Wiley‐Liss, Inc.
A new pairwise folding potential based on improved decoy generation and side‐chain packing
Authors: Loose C. , Klepeis J. L. , Floudas C. A.
Published: December 2003

A new force field for pairwise residue interactions as a function of Cα to Cα distances is presented. The force field was developed through the solution of a linear programming formulation with large sets of constraints. The constraints are based on the construction of >80,000 low‐energy decoys for a set of proteins and requiring the decoy energies for each protein system to be higher than the native conformation of that particular protein. The generation of a robust force field was facilitated by the use of a novel decoy generation process, which involved the rational selection of proteins to add to the training set and included a significant energy minimization of the decoys. The force field was tested on a large set of decoys for various proteins not included in the training set and shown to perform well compared with a leading force field in identifying the native conformation for these proteins. Proteins 2003. © 2003 Wiley‐Liss, Inc.
ProVal: A protein‐scoring function for the selection of native and near‐native folds
Authors: Berglund Anders , Head Richard D. , Welsh Eric A. , Marshall Garland R.
Published: December 2003

A low‐resolution scoring function for the selection of native and near‐native structures from a set of predicted structures for a given protein sequence has been developed. The scoring function, ProVal (Protein Validate), used several variables that describe an aspect of protein structure for which the proximity to the native structure can be assessed quantitatively. Among the parameters included are a packing estimate, surface areas, and the contact order. A partial least squares for latent variables (PLS) model was built for each candidate set of the 28 decoy sets of structures generated for 22 different proteins using the described parameters as independent variables. The Cα RMS of the candidate structures versus the experimental structure was used as the dependent variable. The final generalized scoring function was an average of all models derived, ensuring that the function was not optimized for specific fold classes or method of structure generation of the candidate folds. The results show that the crystal structure was scored best in 64% of the 28 test sets and was clearly separated from the decoys in many examples. In all the other cases in which the crystal structure did not rank first, it ranked within the top 10%. Thus, although ProVal could not distinguish between predicted structures that were similar overall in fold quality due to its inherently low resolution, it can clearly be used as a primary filter to eliminate ∼90% of fold candidates generated by current prediction methods from all‐atom modeling and further evaluation. The correlation between the predicted and actual Cα RMS values varies considerably between the candidate fold sets. Proteins 2003;53:000–000. © 2003 Wiley‐Liss, Inc.
Type I collagen N‐Telopeptides adopt an ordered structure when docked to their helix receptor during fibrillogenesis*
Authors: Malone James P. , George Anne , Veis Arthur
Published: December 2003

The in vitro rate and specificity of fibrillogenesis in type I collagen depends on the integrity of the amino (N)‐telopeptide domain. In vivo an intact N‐telopeptide domain is also required for normal fibril assembly. Although Chou–Fasman predictions and NMR studies suggested that a type I β‐turn could be induced in α1(I) N‐telopeptide chains, computer modeling did not identify ordered structures. Nevertheless, X‐ray analysis and electron tomography studies have shown that the N‐telopeptide is in one of the most highly ordered fibril domains. This study was undertaken to determine if the docking of the N‐telopeptide to its helix receptor domain could induce the telopeptides to take up a specific conformation. With use of molecular modeling suite of programs, a (Gly‐Pro‐Pro)n triple‐helical structure was built on the basis of high‐resolution X‐ray crystallographic coordinates and then replaced with the actual bovine collagen residues 924–938, the triple‐helical α1(I)‐N‐telopeptide‐receptor sequences. Energy minimization produced a modified triple‐helical conformation. The bovine α1(I) N‐telopeptide sequence was similarly minimized and docked to this receptor. The docking induced an ordered conformation with a stabilizing hydrogen bond in the N‐telopeptide and, importantly, a reciprocal reordering of the triple‐helical conformation in the binding domain. This docked structure placed Lys residues in both telopeptide and helix in the correct locations for cross‐link formation. The modeling has been extended to the three‐chain N‐telopeptide domain and finally to the construction of the Hulmes–Miller quasi‐hexagonal packing structure. Each N‐telopeptide domain can form linkages with two adjacent, aligned helix receptor domains. The telopeptides and the order of staggering of the three chains in the helix play crucial roles in the packing and intrafibrillar cross‐linking patterns and the relative azimuthal orientations of adjacent molecules in the fibril. The models confirm the high order in the N‐telopeptide 4D overlap zone. Proteins 2003;9999:000–000. © 2003 Wiley‐Liss, Inc.
Evaluation of protein fold comparison servers
Authors: Novotny Marian , Madsen Dennis , Kleywegt Gerard J.
Published: December 2003

When a new protein structure has been determined, comparison with the database of known structures enables classification of its fold as new or belonging to a known class of proteins. This in turn may provide clues about the function of the protein. A large number of fold comparison programs have been developed, but they have never been subjected to a comprehensive and critical comparative analysis. Here we describe an evaluation of 11 publicly available, Web‐based servers for automatic fold comparison. Both their functionality (e.g., user interface, presentation, and annotation of results) and their performance (i.e., how well established structural similarities are recognized) were assessed. The servers were subjected to a battery of performance tests covering a broad spectrum of folds as well as special cases, such as multidomain proteins, Cα‐only models, new folds, and NMR‐based models. The CATH structural classification system was used as a reference. These tests revealed the strong and weak sides of each server. On the whole, CE, DALI, MATRAS, and VAST showed the best performance, but none of the servers achieved a 100% success rate. Where no structurally similar proteins are found by any individual server, it is recommended to try one or two other servers before any conclusions concerning the novelty of a fold are put on paper. Proteins 2004. © 2003 Wiley‐Liss, Inc.
Effective scoring function for protein sequence design
Authors: Liang Shide , Grishin Nick V.
Published: December 2003

We have developed an effective scoring function for protein design. The atomic solvation parameters, together with the weights of energy terms, were optimized so that residues corresponding to the native sequence were predicted with low energy in the training set of 28 protein structures. The solvation energy of non‐hydrogen‐bonded hydrophilic atoms was considered separately and expressed in a nonlinear way. As a result, our scoring function predicted native residues as the most favorable in 59% of the total positions in 28 proteins. We then tested the scoring function by comparing the predicted stability changes for 103 T4 lysozyme mutants with the experimental values. The correlation coefficients were 0.77 for surface mutations and 0.71 for all mutations. Finally, the scoring function combined with Monte Carlo simulation was used to predict favorable sequences on a fixed backbone. The designed sequences were similar to the natural sequences of the family to which the template structure belonged. The profile of the designed sequences was helpful for identification of remote homologues of the native sequence. Proteins 2004;54:000–000. © 2003 Wiley‐Liss, Inc.
A Shannon entropy‐based filter detects high‐ quality profile–profile alignments in searches for remote homologues
Authors: Capriotti Emidio , Fariselli Piero , Rossi Ivan , Casadio Rita
Published: December 2003

Detection of homologous proteins with low‐sequence identity to a given target (remote homologues) is routinely performed with alignment algorithms that take advantage of sequence profile. In this article, we investigate the efficacy of different alignment procedures for the task at hand on a set of 185 protein pairs with similar structures but low‐sequence similarity. Criteria based on the SCOP label detection and MaxSub scores are adopted to score the results. We investigate the efficacy of alignments based on sequence–sequence, sequence–profile, and profile–profile information. We confirm that with profile–profile alignments the results are better than with other procedures. In addition, we report, and this is novel, that the selection of the results of the profile–profile alignments can be improved by using Shannon entropy, indicating that this parameter is important to recognize good profile–profile alignments among a plethora of meaningless pairs. By this, we enhance the global search accuracy without losing sensitivity and filter out most of the erroneous alignments. We also show that when the entropy filtering is adopted, the quality of the resulting alignments is comparable to that computed for the target and template structures with CE, a structural alignment program. Proteins 2004. © 2003 Wiley‐Liss, Inc.
Crystal structure of the C67A mutant of isopentenyl diphosphate isomerase complexed with a mechanism‐based irreversible inhibitor
Authors: Wouters J. , Oudjama Y. , Stalon V. , Droogmans L. , Poulter C.D.
Published: December 2003

Isopentenyl diphosphate:dimethylallyl diphosphate (IPP:DMAPP) isomerase is a key enzyme in the biosynthesis of isoprenoids. The mechanism of the isomerization reaction involves protonation of the unactivated carbon‐carbon double bond in the substrate. Analysis of the 1.97 Å crystal structure of the inactive C67A mutant of E. coli isopentenyl diphosphate:dimethylallyl diphosphate isomerase complexed with the mechanism‐based inactivator 3,4‐epoxy‐3‐methyl‐1‐butyl diphosphate is in agreement with an isomerization mechanism involving Glu 116, Tyr 104, and Cys 67. In particular, the results are consistent with a mechanism where Glu116 is involved in the protonation step and Cys67 in the elimination step. Proteins 2003;53:000–000. © 2003 Wiley‐Liss, Inc.
Picosecond dynamics of the glutamate receptor in response to agonist‐induced vibrational excitation
Authors: Kubo Minoru , Shiomitsu Eiji , Odai Kei , Sugimoto Tohru , Suzuki Hideo , Ito Etsuro
Published: December 2003

Conformational changes of proteins are dominated by the excitation and relaxation processes of their vibrational states. To elucidate the mechanism of receptor activation, the conformation dynamics of receptors must be analyzed in response to agonist‐induced vibrational excitation. In this study, we chose the bending vibrational mode of the guanidinium group of Arg485 of the glutamate receptor subunit GluR2 based on our previous studies, and we investigated picosecond dynamics of the glutamate receptor caused by the vibrational excitation of Arg485 via molecular dynamics simulations. The vibrational excitation energy in Arg485 in the ligand‐binding site initially flowed into Lys730, and then into the J‐helix at the subunit interface of the ligand‐binding domain. Consequently, the atomic displacement in the subunit interface around an intersubunit hydrogen bond was evoked in about 3 ps. This atomic displacement may perturb the subunit packing of the receptor, triggering receptor activation. Proteins 2004;54:000–000. © 2003 Wiley‐Liss, Inc.
Quantifying the effect of burial of amino acid residues on protein stability
Authors: Zhou Hongyi , Zhou Yaoqi
Published: December 2003

The average contribution of individual residue to folding stability and its dependence on buried accessible surface area (ASA) are obtained by two different approaches. One is based on experimental mutation data, and the other uses a new knowledge‐based atom–atom potential of mean force. We show that the contribution of a residue has a significant correlation with buried ASA and the regression slopes of 20 amino acid residues (called the buriability) are all positive (pro‐burial). The buriability parameter provides a quantitative measure of the driving force for the burial of a residue. The large buriability gap observed between hydrophobic and hydrophilic residues is responsible for the burial of hydrophobic residues in soluble proteins. Possible factors that contribute to the buriability gap are discussed. Proteins 2004;54:000–000. © 2003 Wiley‐Liss, Inc.
Evolutionary trace analysis of scorpion toxins specific for K‐channels
Authors: Zhu Shunyi , Huys Isabelle , Dyason Karin , Verdonck Fons , Tytgat Jan
Published: December 2003

Scorpion α‐K+ channel toxins are a large family of polypeptides with a similar structure but diverse pharmacological activities. Despite many structural and functional data available at present, little progress has been made in understanding the toxin′s molecular basis responsible for the functional diversification. In this paper, we report the first complete cDNA sequences of toxins belonging to subfamily 6 and identify five new members, called α‐KTx 6.6‐6.10. By analyzing the rates of mutations that occurred in the corresponding cDNAs, we suggest that accelerated evolution in toxin‐coding regions may be associated with the functional diversification of this subfamily. To pinpoint sites probably involved in the functional diversity of α‐KTx family, we analyzed this family of sequences using the evolutionary trace method. This analysis highlighted one channel‐binding surface common for all the members. This surface is composed of one conserved lysine residue at position 29 assisted by other residues at positions 10, 26, 27, 32, 34, and 36. Of them, the positions 29, 32, and 34 have been reported to be the most major determinants of channel specificity. Interestingly, another contrary surface was also observed at a higher evolutionary time cut‐off value, which may be involved in the binding of ERG (ether‐a‐go‐go‐related gene) channel‐specific toxins. The good match between the trace residues and the functional epitopes of the toxins suggested that the evolutionary trace results reported here can be applied to predict channel‐binding sites of the toxins. Because, the side‐chain variation in the trace positions is strongly linked with the functional alteration and channel‐binding surface transfer of α‐KTx family, we conclude that our findings should also be important for the rational design of new toxins targeting a given potassium channel with high selectivity. Proteins 2004;54:000–000. © 2003 Wiley‐Liss, Inc.
Strand‐loop‐strand motifs: Prediction of hairpins and diverging turns in proteins
Authors: Kuhn Michael , Meiler Jens , Baker David
Published: December 2003

β‐sheet proteins have been particularly challenging for de novo structure prediction methods, which tend to pair adjacent β‐strands into β‐hairpins and produce overly local topologies. To remedy this problem and facilitate de novo prediction of β‐sheet protein structures, we have developed a neural network that classifies strand‐loop‐strand motifs by local hairpins and nonlocal diverging turns by using the amino acid sequence as input. The neural network is trained with a representative subset of the Protein Data Bank and achieves a prediction accuracy of 75.9 ± 4.4% compared to a baseline prediction rate of 59.1%. Hairpins are predicted with an accuracy of 77.3 ± 6.1%, diverging turns with an accuracy of 73.9 ± 6.0%. Incorporation of the β‐hairpin/diverging turn classification into the ROSETTA de novo structure prediction method led to higher contact order models and somewhat improved tertiary structure predictions for a test set of 11 all‐β‐proteins and 3 αβ‐proteins. The β‐hairpin/diverging turn classification from amino acid sequences is available online for academic use (Meiler and Kuhn, 2003; www.jens‐meiler.de/turnpred.html). Proteins 2004;54:000–000. © 2003 Wiley‐Liss, Inc.
A Semantics for Distributed Execution of Statemate
Authors: Fränzle Martin , Niehaus Jürgen , Metzner Alexander , Damm Werner
Published: December 2003

We present a semantics for the statechart variant implemented in the Statemate product of i-Logix. Our semantics enables distributed code generation for Statemate models in the context of rapid prototyping for embedded control applications. We argue that it seems impossible to efficiently generate distributed code using the original Statemate semantics. The new, distributed semantics has the advantages that, first, it enables the generation of efficient distributed code, second, it preserves many aspects of the original semantics for those parts of a model that are not distributed, and third, the changes made regarding the interaction of distributed model parts are similar to the interaction between the model and its environment in the original semantics, thus giving designers a familiar execution model. The semantics has been implemented in Grace, a framework for rapid prototyping code generation for embedded control applications.
Redesign of a Systems Engineering Language: Formalisation of χ
Authors: Bos Victor , Kleijn Jeroen
Published: December 2003

This paper describes the redesign of a systems engineering language called χ. This is an engineering language designed to specify and analyse industrial systems. The main objective of this redesign was to enable mathematical reasoning about χ specifications. We discuss the original χ language, the requirements and design decisions, and the resulting syntax and semantics of the new version of χ, called χ. In particular, we elaborate on semantical aspects of χ’s time model.
Intensional and Extensional Semantics of Dataflow Programs
Authors: Gay Simon , Nagarajan Rajagopal
Published: December 2003

We compare two semantic models of dataflow programs: a synchronous version of the classical Kahn semantics, and a new semantics in a category of synchronous processes. We consider the Kahn semantics to be extensional, as it describes the functions computed by dataflow nodes, and the categorical semantics to be intensional, as it describes the step-by-step production of output tokens from input tokens. Assuming that programs satisfy Wadge’s cycle sum condition and are therefore deadlock-free, we prove that the two semantics are equivalent. This equivalence result amounts to a proof that function composition in the extensional semantics is faithfully modelled by the detailed interactions of the intensional semantics, and provides further insight into the nature of dataflow computation.
Paleoecology and high-resolution paleohydrology of a kettle peatland in upper Michigan
Authors: Booth Robert K. , Jackson Stephen T. , Gray Catherine E.D.
Published: December 2003

We investigated the developmental and hydrological history of a Sphagnum-dominated, kettle peatland in Upper Michigan using testate amoebae, plant macrofossils, and pollen. Our primary objective was to determine if the paleohydrological record of the peatland represents a record of past climate variability at subcentennial to millennial time scales. To assess the role of millennial-scale climate variability on peatland paleohydrology, we compared the timing of peatland and upland vegetation changes. To investigate the role of higher-frequency climate variability on peatland paleohydrology, we used testate amoebae to reconstruct a high-resolution, hydrologic history of the peatland for the past 5100 years, and compared this record to other regional records of paleoclimate and vegetation. Comparisons revealed coherent patterns of hydrological, vegetational, and climatic changes, suggesting that peatland paleohydrology responded to climate variability at millennial to sub-centennial time scales. Although ombrotrophic peatlands have been the focus of most high-resolution peatland paleoclimate research, paleohydrological records from Sphagnum-dominated, closed-basin peatlands record high-frequency and low-magnitude climatic changes and thus represent a significant source of unexplored paleoclimate data.
MIRACLES AND THE COUNTER-REFORMATION MISSION TO ENGLAND
Authors: WALSHAM ALEXANDRA
Published: December 2003

This article explores the way in which the Counter Reformation priests sent to England after 1574 cultivated and harnessed the culture of the miraculous in their efforts to reform and evangelize the populace and to defend doctrines and practices assaulted by Protestant polemicists. Drawing on the insights emerging from recent research on Catholic renewal on the Continent, it shows how the seminary clergy and especially the Jesuits fostered traditional beliefs and practices associated with saints, relics, and sacramentals and exploited the potential of exorcisms and visions for didactic and proselytizing purposes. Close examination of these strategies serves to question some existing assumptions about the nature, objectives, and impact of the English Catholic mission and to illuminate the particular challenges that persecution presented to a movement determined to purge popular piety of its ‘superstitious’ accretions. It underlines the tensions between ecclesiastical direction and lay initiative which characterized a context in which Catholicism was a minority Church and highlights the frictions and divisions which these attempts to utilize supernatural power stimulated within the ranks of the Counter Reformation priesthood itself.
THE CAREER OF SIR JOHN HYNDE COTTON (1686–1752)
Authors: GLICKMAN GABRIEL
Published: December 2003

This article examines the character of John Hynde Cotton, a leading tory opponent of Sir Robert Walpole, who played a particularly puzzling role in the conspiracies behind the Jacobite rebellion of 1745, and the parliaments of George II. Entering a coalition ministry in 1744, he was immersed at the same time in intrigue with the exiled Stuart court, and at one stage pledged to use resignation from government as the signal for rebellion. The article explores the background to his career, tracing the intellectual, professional and kinship networks into which he was pressed, and their impact on his political commitments. Cotton's views on government and society were the product of a man caught up in a conflict between image and reality, torn between a set of different identities: robust doyen of rural squiredom, political and commercial ‘insider’, scholar, and ideologue shaped profoundly by the politico-religious crises of the previous century. The article aims to stimulate a new analysis of the facts of a tory-Jacobite career, and so enhance a debate that is in danger of appearing stale. It aspires to reach a deeper understanding of the meaning and principles of eighteenth-century toryism, beyond the mere counting of ‘Jacobite’ or ‘Hanoverian’ heads.
RACE, EMPIRE, AND THE LIMITS OF NINETEENTH-CENTURY SCOTTISH NATIONHOOD
Authors: KIDD COLIN
Published: December 2003

Scotland's Unionist culture has already become a world we have lost, investigation of which is hampered by the misleading notion of a ‘Celtic fringe’. Nineteenth-century Lowland Scots were not classified as Celts; indeed they vociferously projected a Teutonic racial identity. Several Scots went so far as to claim not only that the Saxon Scots of the Lowlands were superior to the Celts of the Highlands, but that the people of the Lowlands came from a more purely Anglian stock than the population of southern England. For some Scots the glory of Scottish identity resided in the boast that Lowlanders were more authentically ‘English’ than the English themselves. Moreover, Scottish historians reinterpreted the nation's medieval War of Independence – otherwise a cynosure of patriotism – as an unfortunate civil war within the Saxon race. Curiously, racialism – which was far from monolithic – worked at times both to support and to subvert Scottish involvement in empire. The late nineteenth century also saw the formulation of Scottish proposals for an Anglo-Saxon racial empire including the United States; while Teutonic racialism inflected the nascent Scottish home rule movement as well as the Udal League in Orkney and Shetland.
THE GREAT WAR AND THE CRISIS OF LIBERALISM IN SPAIN, 1916–1917
Authors: SALVADÓ FRANCISCO J. ROMERO
Published: December 2003

Based largely on primary sources, this article concentrates on the Liberal administration led by Count Romanones between December 1915 and April 1917. This is regarded as a crucial moment in the country's transition from elite to mass politics. The social and economic impact of the First World war brought about massive economic dislocation and social distress that in turn generated unprecedented levels of popular mobilization against the regime. Intertwined with domestic uproar, the country was polarized by the question of neutrality. Alienated from the ruling classes by his pro-Allied stance, Romanones was not only the target of a fierce campaign to oust him but also presided over the acceleration of existing movements of social and political protest. At his fall in April 1917, he left behind a storm of discontent and turmoil that threatened to bring down the entire political order.
THE STRANGE DEATH OF CHRISTIAN BRITAIN: ANOTHER LOOK AT THE SECULARIZATION DEBATE
Authors: MORRIS JEREMY
Published: December 2003

This article reviews the recent historiography of religion in modern Britain, concentrating on the debate about secularization and the work of Callum Brown in particular, but also with reference to Sarah Williams and Simon Green. It endorses, broadly, the criticisms made by these and other historians of older assumptions of a one-way, ‘inevitable’ link between modernization and religious decline, but in turn accuses them of attenuating the concept of ‘religion’ in the modern period to the point where it has lost internal sophistication. It suggests, instead, the compatibility of indices of institutional church decline with the persistence of religious identity and limited church affiliation.
THE ORIGINS OF SOE IN FRANCE
Authors: MURPHY CHRISTOPHER J.
Published: December 2003

This article explores the official motivation behind the authorization in 1960 of research into the activities of the Special Operations Executive (SOE) during the Second World War by M. R. D. Foot, leading to the publication of SOE in France in 1966. The work has traditionally been viewed as the official response to critical investigative works on SOE published during the 1950s, combined with the vocal campaign of Dame Irene Ward, who made several calls in the House of Commons for an official account of SOE to be published. Material now available at the Public Record Office reveals that these were not the sole considerations in official minds, nor the most significant, concerning the possibility of publishing such a work. The foreign office was particularly concerned that Britain's contribution to wartime resistance in Europe, exemplified by SOE, was being overshadowed by both soviet propoganda, emphasizing the communist contribution to resistance, and the publicity being given to SOE's American counterpart, the Office of Strategic Services (OSS). The ‘campaign’ of Dame Irene Ward, supported by the negative slant given to SOE in the books of Jean Overton Fuller and Elizabeth Nicholas, unknowingly gave support to a frame of mind that was already in existence in favour of an unofficial account of SOE activity, albeit for different reasons.