bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic chemical shift markers for loop conformation and substrate and cofactor binding in dihydrofolate reductase complexes
Authors: Osborne Michael J. , Venkitakrishnan Rani P. , Dyson H. Jane , Wright Peter E. 
Published: September 2003

AbstractHeteronuclear NMR methods have been used to probe the conformation of four complexes of Escherichia coli dihydrofolate reductase (DHFR) in solution. 1HN, 15N, and 13Cα resonance assignments have been made for the ternary complex with folate and oxidized NADP+ cofactor and the ternary complex with folate and a reduced cofactor analog, 5,6‐dihydroNADPH. The backbone chemical shifts have been compared with those of the binary complex of DHFR with the substrate analog folate and the binary complex with NADPH (the holoenzyme). Analysis of 1HN and 15N chemical shifts has led to the identification of marker resonances that report on the active site conformation of the enzyme. Other backbone amide resonances report on the presence of ligands in the pterin binding pocket and in the adenosine and nicotinamide–ribose binding sites of the NADPH cofactor. The chemical shift data indicate that the enzyme populates two dominant structural states in solution, with the active site loops in either the closed or occluded conformations defined by X‐ray crystallography; there is no evidence that the open conformation observed in some X‐ray structures of E. coli DHFR are populated in solution.
β Edge strands in protein structure prediction and aggregation
Authors: Siepen Jennifer A. , Radford Sheena E. , Westhead David R. 
Published: September 2003

AbstractIt is well established that recognition between exposed edges of β‐sheets is an important mode of protein–protein interaction and can have pathological consequences; for instance, it has been linked to the aggregation of proteins into a fibrillar structure, which is associated with a number of predominantly neurodegenerative disorders. A number of protective mechanisms have evolved in the edge strands of β‐sheets, preventing the aggregation and insolubility of most natural β‐sheet proteins. Such mechanisms are unfavorable in the interior of a β‐sheet. The problem of distinguishing edge strands from central strands based on sequence information alone is important in predicting residues and mutations likely to be involved in aggregation, and is also a first step in predicting folding topology. Here we report support vector machine (SVM) and decision tree methods developed to classify edge strands from central strands in a representative set of protein domains. Interestingly, rules generated by the decision tree method are in close agreement with our knowledge of protein structure and are potentially useful in a number of different biological applications. When trained on strands from proteins of known structure, using structure‐based (Dictionary of Secondary Structure in Proteins) strand assignments, both methods achieved mean cross‐validated, prediction accuracies of ∼78%. These accuracies were reduced when strand assignments from secondary structure prediction were used. Further investigation of this effect revealed that it could be explained by a significant reduction in the accuracy of standard secondary structure prediction methods for edge strands, in comparison with central strands.
Detection of four oxidation sites in viral prolyl‐4‐hydroxylase by top‐down mass spectrometry
Authors: Ge Ying , Lawhorn Brian G. , ElNaggar Mariam , Sze Siu Kwan , Begley Tadhg P. , McLafferty Fred W. 
Published: September 2003

AbstractOxidative inactivation is a common problem for enzymatic reactions that proceed via iron oxo intermediates. In an investigation of the inactivation of a viral prolyl‐4‐hydroxylase (26 kD), electrospray mass spectrometry (MS) directly shows the degree of oxidation under varying experimental conditions, but indicates the addition at most of three oxygen atoms per molecule. Thus, molecular ion masses (M + nO) of one sample indicate the oxygen atom adducts n = 0, 1, 2, 3, and 4 of 35, 41, 19, 5 ± 3, and <2%, respectively; “top‐down” MS/MS of these ions show oxidation at the sites R28–V31, E95–F107, and K216 of 22%, 28%, and 34%, respectively, but with a possible (∼4%) fourth site at V125–D150. However, for the doubly oxidized molecular ions (increasing the precursor oxygen content from 0.94 to 2), MS/MS showed an easily observable ∼13% oxygen at the V125–D150 site. For the “bottom‐up” approach, detection of the ∼4% oxidation at the V125–D150 site by MS analysis of a proteolysis mixture would have been very difficult. The unmodified peptide containing this site would represent a few percent of the proteolysis mixture; the oxidized peptide not only would be just ∼4% of this, but the uniqueness of its mass value (∼1–2 kD) would be far less than the 11,933 Dalton value used here. Using different molecular ion precursors for top‐down MS/MS also provides kinetic data from a single sample, that is, from molecular ions with 0.94 and 2 oxygens. Little oxidation occurs at V125–D150 until K216 is oxidized, suggesting that these are competitively catalyzed by the iron center; among several prolyl‐4‐hydroxylases the K216, H137, and D139 are conserved residues.
Staphostatins resemble lipocalins, not cystatins in fold
Authors: Rzychon Malgorzata , Filipek Renata , Sabat Artur , Kosowska Klaudia , Dubin Adam , Potempa Jan , Bochtler Matthias 
Published: September 2003

AbstractStaphostatins are the endogenous inhibitors of the major secreted cysteine proteases of Staphylococcus aureus, the staphopains. Here, we present the 1.4 Å crystal structure of staphostatin B and show that the fold can be described as a fully closed, highly sheared eight‐stranded β‐barrel. Thus, staphostatin B is related to β‐barrel domains that are involved in the inhibition or regulation of proteases of various catalytic types and to the superfamily of lipocalins/cytosolic fatty acid binding proteins. Unexpectedly for a cysteine protease inhibitor, staphostatin B is not significantly similar to cystatins.
Dynamics of Ca2+‐saturated calmodulin D129N mutant studied by multiple molecular dynamics simulations
Authors: Likić Vladimir A. , Strehler Emanuel E. , Gooley Paul R. 
Published: September 2003

AbstractFifteen independent 1‐nsec MD simulations of fully solvated Ca2+ saturated calmodulin (CaM) mutant D129N were performed from different initial conditions to provide a sufficient statistical basis to gauge the significance of observed dynamical properties. In all MD simulations the four Ca2+ ions remained in their binding sites, and retained a single water ligand as observed in the crystal structure. The coordination of Ca2+ ions in EF‐hands I, II, and III was sevenfold. In EF‐hand IV, which was perturbed by the mutation of a highly conserved Asp129, an anomalous eightfold Ca2+ coordination was observed. The Ca2+ binding loop in EF‐hand II was observed to dynamically sample conformations related to the Ca2+‐free form. Repeated MD simulations implicate two well‐defined conformations of Ca2+ binding loop II, whereas similar effect was not observed for loops I, III, and IV. In 8 out of 15 MD simulations Ca2+ binding loop II adopted an alternative conformation in which the Thr62 〉C=O group was displaced from the Ca2+ coordination by a water molecule, resulting in the Ca2+ ion ligated by two water molecules. The alternative conformation of the Ca2+ binding loop II appears related to the “closed” state involved in conformational exchange previously detected by NMR in the N‐terminal domain fragment of CaM and the C‐terminal domain fragment of the mutant E140Q. MD simulations suggest that conformations involved in microsecond exchange exist partially preformed on the nanosecond time scale.
Finding evolutionary relations beyond superfamilies: Fold‐based superfamilies
Authors: Matsuda Keiko , Nishioka Takaaki , Kinoshita Kengo , Kawabata Takeshi , Go Nobuhiro 
Published: September 2003

AbstractSuperfamily classifications are based variably on similarity of sequences, global folds, local structures, or functions. We have examined the possibility of defining superfamilies purely from the viewpoint of the global fold/function relationship. For this purpose, we first classified protein domains according to the β‐sheet topology. We then introduced the concept of kinship relations among the classified β‐sheet topology by assuming that the major elementary event leading to creation of a new β‐sheet topology is either an addition or deletion of one β‐strand at the edge of an existing β‐sheet during the molecular evolution. Based on this kinship relation, a network of protein domains was constructed so that the distance between a pair of domains represents the number of evolutionary events that lead one from the other domain. We then mapped on it all known domains with a specific core chemical function (here taken, as an example, that involving ATP or its analogs). Careful analyses revealed that the domains are found distributed on the network as >20 mutually disjointed clusters. The proteins in each cluster are defined to form a fold‐based superfamily. The results indicate that >20 ATP‐binding protein superfamilies have been invented independently in the process of molecular evolution, and the conservative evolutionary diffusion of global folds and functions is the origin of the relationship between them.
Directed evolution of a bacterial α‐amylase: Toward enhanced pH‐performance and higher specific activity
Authors: Bessler Cornelius , Schmitt Jutta , Maurer Karl‐Heinz , Schmid Rolf D. 
Published: September 2003

Abstractα‐Amylases, in particular, microbial α‐amylases, are widely used in industrial processes such as starch liquefaction and pulp processes, and more recently in detergency. Due to the need for α‐amylases with high specific activity and activity at alkaline pH, which are critical parameters, for example, for the use in detergents, we have enhanced the α‐amylase from Bacillus amyloliquefaciens (BAA). The genes coding for the wild‐type BAA and the mutants BAA S201N and BAA N297D were subjected to error‐prone PCR and gene shuffling. For the screening of mutants we developed a novel, reliable assay suitable for high throughput screening based on the Phadebas assay. One mutant (BAA 42) has an optimal activity at pH 7, corresponding to a shift of one pH unit compared to the wild type. BAA 42 is active over a broader pH range than the wild type, resulting in a 5‐fold higher activity at pH 10. In addition, the activity in periplasmic extracts and the specific activity increased 4‐ and 1.5‐fold, respectively. Another mutant (BAA 29) possesses a wild‐type‐like pH profile but possesses a 40‐fold higher activity in periplasmic extracts and a 9‐fold higher specific activity. The comparison of the amino acid sequences of these two mutants with other homologous microbial α‐amylases revealed the mutation of the highly conserved residues W194R, S197P, and A230V. In addition, three further mutations were found K406R, N414S, and E356D, the latter being present in other bacterial α‐amylases.
The Value Relevance of Foreign Income: an Australian, Canadian, and British Comparison
Authors: Bodnar Gordon M. , Hwang Lee‐Seok , Weintrop Joseph 
Published: September 2003

AbstractIn this paper we examine the value relevance of geographical earnings disclosures for firms listed and domiciled in Australia, Canada and the United Kingdom. We find that foreign earnings in all three countries are valued differently than domestic earnings. The estimate of the association coefficient for foreign earnings changes with returns is positive in all three countries and statistically larger than the association coefficient for domestic earnings changes in Canada and the United Kingdom. Further tests show that this difference is related to relative growth opportunities of overseas operations to domestic operations. These findings are similar to results for foreign earnings association coefficients for American‐based multinationals found in Bodnar and Weintrop (1997). These results indicate that across countries the market perceives the results of foreign operations as value relevant and suggests that greater emphasis should be placed on the required disclosure of segmental data rather than on the concern that all countries prepare the segmental information using a common GAAP.
Firm‐level Disclosures and the Relative Roles of Culture and Legal Origin
Authors: Hope Ole‐Kristian 
Published: September 2003

AbstractIn this paper, I investigate the relative roles of legal origin and national culture in explaining firm‐level disclosure levels internationally. Using a significantly larger and more representative sample than prior research, I document, using univariate and multivariate analyses, that both legal origin and culture (as operationalized by Hofstede and Schwartz) are important in explaining firm disclosure. Neither legal origin nor culture dominates with respect to overall explanatory power for variations in disclosure levels. Consequently, it is premature to write off culture as an important factor in the financial reporting environment. Furthermore, I find that legal origin is an important conditioning variable for the role of culture. Finally, although legal origin is a key determinant of disclosure levels, I hypothesize and find that its importance decreases with the richness of a firm's information environment.
Corporate Nonfinancial Disclosure Practices and Financial Analyst Forecast Ability Across Three European Countries
Authors: Vanstraelen Ann , Zarzeski Marilyn T. , Robb Sean W. G. 
Published: September 2003

AbstractThis paper presents evidence that companies across three continental European countries (Belgium, Germany and the Netherlands) provide varying degrees of analyst recommended nonfinancial disclosures to the marketplace. This study is the first to examine the relationship of Jenkins Committee nonfinancial disclosure levels with the accuracy and dispersion of financial analysts' earnings forecasts. Seemingly unrelated regression tests show that larger companies and companies with a global focus voluntarily provide higher levels of both forward looking and historical nonfinancial disclosures. Additionally, higher levels of forward looking nonfinancial disclosures are associated with lower dispersion and higher accuracy in financial analysts' earnings forecasts.
Rational Speculative Bubbles: An Empirical Investigation of the London Stock Exchange
Authors: Brooks Chris , Katsaris Apostolos 
Published: September 2003

AbstractIn recent years, a sharp divergence of London Stock Exchange equity prices from dividends has been noted. In this paper, we examine whether this divergence can be explained by reference to the existence of a speculative bubble. Three different empirical methodologies are used: variance bounds tests, bubble specification tests, and cointegration tests based on both ex post and ex ante data. We find that, stock prices diverged significantly from their fundamental values during the late 1990's, and that this divergence has all the characteristics of a bubble.
Partial Delegation in a Model of Currency Crisis
Authors: Boinet Virginie 
Published: September 2003

AbstractThis paper shows that, in a fixed exchange‐rate system with an escape clause, delegating the decision on the magnitude of realignment to an inflation‐averse central banker reduces the range of realignment costs for which the policy‐maker necessarily devalues. Stressing the influence of devaluation expectations on currency crises, it is also shown that this strategy of delegation reduces the width of the multiple equilibria zone within which self‐fulfilling crises occur, thus promoting further the exchange‐rate system's stability. The higher the central banker's degree of inflation aversion, the greater is this reduction.
Utility Functions whose Parameters depend on Initial Wealth
Authors: Pedersen Christian S. , Satchell S. E. 
Published: September 2003

AbstractConventional one‐period utility functions in Economics assume that initial wealth only enters preferences through the definition of final wealth. Consequently, those utility functions most utilized (i.e., exponential and quadratic) have implausible risk characteristics. The authors characterize a new class of utility function whose risk parameters depend upon initial wealth and obtain several desirable results. In particular, investors with quadratic and exponential utility functions can have decreasing risk aversion, and risky assets in a quadratic utility multi‐asset environment do not have to be inferior as implied by the traditional framework.
Testing for Temporal Asymmetry in the Price‐Volume Relationship
Authors: Moosa Imad A. , Silvapulle Param , Silvapulle Mervyn 
Published: September 2003

AbstractThis paper presents some evidence for the presence of temporal asymmetry in the price‐volume relationship in the crude oil futures market. By using threshold models we show that there is bidirectional causality between volume and prices, whereas the conventional model that assumes symmetry can only detect unidirectional causality. The results also show that the price‐volume relationship is asymmetric, in the sense that negative price and volume changes have stronger effects (on each other) than positive changes. Some explanations for asymmetry in the price‐volume relationship are suggested.
Luenberger and Malmquist Productivity Indices: Theoretical Comparisons and Empirical Illustration
Authors: Boussemart Jean‐Philippe , Briec Walter , Kerstens Kristiaan , Poutineau Jean‐Christophe 
Published: September 2003

AbstractThis contribution establishes, from a theoretical viewpoint, the relations between the Malmquist productivity indices, that measure in either input or output orientations, and the Luenberger productivity indices, that can simultaneously contract inputs and expand outputs, but that can also measure in either input or output orientations. The main result is that a Malmquist productivity index overestimates productivity changes, since it provides productivity measures that are nearly twice those given by the Luenberger productivity index looking for simultaneous contractions of inputs and expansions of outputs. This relationship is empirically illustrated using data from 20 OECD countries over the 1974–97 period.
A Note on the Most‐Favoured‐Customer Pricing Policy
Authors: Ohnishi Kazuhiro 
Published: September 2003

AbstractThis paper extends the retroactive most‐favoured‐customer pricing policy examined by Cooper (1986). He showed that the policy enabled both firms in a duopoly to offer higher prices and to enjoy higher profits. This paper introduces a variable into the most‐favoured‐customer pricing policy. Then, it shows that there is an equilibrium in which the duopolists can further increase their profits.
Infantile Autism and Associated Autosomal Chromosome Abnormalities: A Register‐based Study and a Literature Survey
Authors: Lauritsen M. , Mors O. , Mortensen P. B. , Ewald H. 
Published: September 2003

Infantile autism is a heterogenous disorder with unknown aetiology. Evidence from the relatively few family and twin studies suggests a genetic component. Co‐occurrence or cosegregation between infantile autism and chromosomal abnormalities may identify candidate regions, which could be tested in linkage or association studies.The purpose of this study was to use the Danish Cytogenetic Central Register in order to detect autosomal chromosome abnormalities associated with infantile autism, and to review the literature for cases of autism associated with autosomal chromosome abnormalities to identify candidate chromosomal regions.The register‐based study identified possible candidate regions on chromosome 7q21 and 10q21.2, which have not previously been reported.A few interesting candidate regions, 15q11–13, 16q23, and 17p11.2 were found in the literature survey.
The Psychological Impact of War and the Refugee Situation on South Sudanese Children in Refugee Camps in Northern Uganda: An Exploratory Study
Authors: Paardekooper B. , De Jong J. T. V. M. , Hermanns J. M. A. 
Published: September 2003

This paper presents the results of an exploratory study on the psychosocial effects of the war situation and subsequent fight on South Sudanese children who were compared to a group of Ugandan children who did not have these experiences of war and fight. In addition to the independent variables such as sociodemographic variables and traumatic events and dailylife stress, the dependent variable psychological consequences—according to parents and children themselves—as well as the influence of the mediating factors of social support and coping behaviour are presented.Results showed that Sudanese refugee children had experienced significantly more traumatic events and suffered more daily hassles than the Ugandese comparison group. They were less satisfied with the social support they received. At the same time, they used more coping modes. Compared to Ugandan children, the Sudanese reported significantly more PTSD‐like complaints, behavioural problems, and depressive symptoms.
Prospective Childhood Predictors of Deviant Peer Affiliations in Adolescence
Authors: Fergusson David M. , Horwood L. John 
Published: September 2003

Data gathered over the course of a longitudinal study of a birth cohort of over 900 New Zealand children were used to examine factors associated with the formation of affiliations with delinquent or substance using peers in adolescence (15 years). The findings of this study include:(1) Adolescent peer affiliations were associated with a wide range of prospectively measured social, family, parental, and individual factors. This analysis indicated that those children most at risk of forming deviant peer affiliations were those from socially disadvantaged backgrounds, dysfunctional families, who showed early onset conduct problems and other difficulties.(2) Regression analysis suggested that specific factors that were associated with increased risks of later deviant peer affiliations included family socioeconomic status, parental conflict, mother/hild interaction, childhood sexual abuse, parental alcoholism, parental criminal offending, parental illicit drug use, parental smoking, early conduct problems, early anxiety/withdrawal, and early smoking experimentation.It is concluded that peer affiliations in adolescence are shaped by a complex social, family, and individual process that includes social stratification, family functioning, and individual behavioural predispositions.
Behavioural Treatment for Sleep Problems in Children with Severe Learning Disabilities and Challenging Daytime Behaviour: Effect on Daytime Behaviour
Authors: Wiggs Luci , Stores Gregory 
Published: September 2003

The study aimed to investigate a group of children with severe learning disabilities, challenging daytime behaviour, and severe sleep problems to see if successful behavioural treatment of the children's sleep problems resulted in reduced daytime challenging behaviour as reported by mothers and teachers.A randomised controlled trial of behavioural interventions for the children's sleep problems was conducted (N = 30). The intervention group received an individually tailored behavioural programme and were supported by telephone calls from the therapist. Baseline assessments of the children's behaviour were made using the Aberrant Behavior Checklist and were repeated 1 month and 3 months after the start of intervention.There were no behavioural changes that were specific to children in the treatment group. However, improvements in some behaviours were seen in both the intervention and the control group at the 1‐month and 3‐month assessments and there was agreement between mothers' and teachers' reports for many of these changes.The results suggest that nonspecific effects of participating in the study (including an increased sleep duration, which was seen in both groups), rather than resolution of sleep problem per se, may have a beneficial effect on child behaviour and these factors need to be identified for therapeutic use.