bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specification and correctness proof of a WAM extension with abstract type constraints
Authors: Beierle Christoph , Börger Egon 
Published: February 2005

Abstract
We provide a mathematical specification of an extension of Warren's Abstract Machine (WAM) for executing Prolog to type-constraint logic programming and prove its correctness. Our aim is to provide a full specification and correctness proof of a concrete system, the PROTOS Abstract Machine (PAM), an extension of the WAM by polymorphic order-sorted unification as required by the logic programming language PROTOS-L.
In this paper, while leaving the details of the PAM's type constraint representation and solving facilities to a sequel to this work, we keep the notion of types and dynamic type constraints abstract to allow applications to different constraint formalisms like Prolog III or CLP(R). This generality permits us to introduce modular extensions of Börger's and Rosenzweig's formal derivation of the WAM. Since the type constraint handling is orthogonal to the compilation of predicates and clauses, we start from type-constraint Prolog algebras with compiled AND/OR structure that are derived from Börger's and Rosenzweig's corresponding compiled standard Prolog algebras. The specification of the type-constraint WAM extension is then given by a sequence of evolving algebras, each representing a refinement level, and for each refinement step a correctness proof is given. Thus, we obtain the theorem that for every such abstract type-constraint logic programming system L, every compiler to the WAM extension with an abstract notion of types which satisfies the specified conditions, is correct.
A tactic calculus — abridged version
Authors: Martin A. P. , Gardiner P. H. B. , Woodcock J. C. P. 
Published: February 2005

Abstract

We present a very general language for expressing tactic programs. The paper describes some essential tactic combinators (tacticals), and gives them a formal semantics. Those definitions are used to produce a complete calculus for reasoning about tactics written in this language. The language is extended to cover
structural combinators
which enable the tactics to be precisely targeted upon particular sub-expressions.
A New Historian?
Authors: FINK CAROLE 
Published: February 2005

-Your mother is a judge. It's her job to put a line through the past by passing sentence. I'm a historian. For me the past is a gold mine of surprises and possibilities.-A gold mine?…A dunghill is more like it.-Dunghills have their surprises too.President Ion Iliescu [of Romania] has just announced the formation of an international expert commission charged with studying the history of the Holocaust in Romania between 1937 and 1951.Historians are not judges. A historical commission is not a court of law.
Sodium–lithium countertransport and the Gly460→Trp α-adducin polymorphism in essential hypertension
Authors: MEAD Paul A. , HARVEY John N. , RUTHERFORD Peter A. , LEITCH Helen , THOMAS Trevor H. 
Published: February 2005

A polymorphism of the α-subunit of adducin, Gly460→Trp, may affect membrane ion transport and be associated with human EH (essential hypertension). The α-adducin Gly460→Trp polymorphism was determined in 242 NC (normal controls) and 73 patients with EH and was related to the membrane ion transport marker in EH, erythrocyte Na/LiCT (sodium–lithium countertransport), in a subgroup of these subjects. The Km for external sodium was lower in patients with EH than NC. The Km of the Trp allele was lower than with the Gly/Gly genotype [NC, 105±6 compared with 88±5 mmol Na/l respectively (P=0.05); patients with EH, 76±5 compared with 64±4 mmol Na/l respectively (P=0.06)]. The Km was lower in patients with EH than NC for any adducin genotype. Thiol alkylation with NEM (N-ethylmaleimide) caused a decrease in Km in NC, but not in patients with EH. With a Trp allele, NEM lowered Km less in NC (−20 compared with −35) and increased it in patients with EH (+24 compared with +3; P=0.007 for genotype effect). Thiol alkylation with NEM caused an increase in Vmax in patients with EH but not in NC. With a Trp allele, NEM increased Vmax substantially in patients with EH (+0.12 compared with +0.03) but did not cause a decrease in NC (+0.02 compared with −0.06; P=0.007 for genotype effect). In conclusion, the Gly460→Trp polymorphism of α-adducin modifies the kinetics of Na/LiCT. The effect of this genotype is different in patients with EH compared with NC and it does not explain the abnormal kinetics in patients with EH. The Trp allele was not associated with disease in the population studied. Several cytoskeletal proteins may interact with adducin in the overall phenotype of EH.
Preparation of new organotin polymers via exchange reactions
Authors: Azab M.M. , El‐Dougdoug W.I.A. 
Published: February 2005

PurposePreparation of new organotin polymers via a new synthetic route based on the exchange reactions of pentachlorophenyl acrylate or methacrylate with amino‐tri‐phenyltin benzoates or hydroxyl‐tri‐phenyltin benzoates.Design/methodology/approachThe pentachlorophenyl acrylate or methacrylate was prepared by polymerisation in solution with azobisisobutyrontrile as a free radical initiator. The polymers obtained were allowed to undergo exchange reactions with amino‐tri‐phenyltin benzoates or hydroxyl‐tri‐phenyltin benzoates. The structure of the polymers prepared was confirmed by IR spectroscopy. Films were prepared from purified organotin polymers solution on glass, PVC and tin plates. The release of tin compound from the films, when immersed in aqueous media, was assessed. The concentration of the released tin (ppm) was measured by atomic adsorption spectrophotometer.FindingsThe new synthetic route was effective, the organotin polymers prepared had good film properties and the release of tin compounds increased with the content of tin in the organotin polymers.Research limitations/implicationsThe alkaline resistance of the polymeric films prepared needs improvement.Practical implicationsThe polymers prepared provide a family of effective polymeric fungicide useful for a number of applications including water sterilisation.Originality/valueThe polymers prepared contained pendent triphenyltin moieties which slowly hydrolysed to give fungicidal and antifouling effects.
Structural and mechanistic studies of chloride induced activation of human pancreatic α‐amylase
Authors: Maurus Robert , Begum Anjuman , Kuo Hsin‐Hen , Racaza Andrew , Numao Shin , Andersen Carsten , Tams Jeppe W. , Vind Jesper , Overall Christopher M. , Withers Stephen G. , Brayer Gary D. 
Published: February 2005

AbstractThe mechanism of allosteric activation of α‐amylase by chloride has been studied through structural and kinetic experiments focusing on the chloride‐dependent N298S variant of human pancreatic α‐amylase (HPA) and a chloride‐independent TAKA‐amylase. Kinetic analysis of the HPA variant clearly demonstrates the pronounced activating effect of chloride ion binding on reaction rates and its effect on the pH‐dependence of catalysis. Structural alterations observed in the N298S variant upon chloride ion binding suggest that the chloride ion plays a variety of roles that serve to promote catalysis. One of these is having a strong influence on the positioning of the acid/base catalyst residue E233. Absence of chloride ion results in multiple conformations for this residue and unexpected enzymatic products. Chloride ion and N298 also appear to stabilize a helical region of polypeptide chain from which projects the flexible substrate binding loop unique to chloride‐dependent α‐amylases. This structural feature also serves to properly orient the catalytically essential residue D300. Comparative analyses show that the chloride‐independent α‐amylases compensate for the absence of bound chloride by substituting a hydrophobic core, altering the manner in which substrate interactions are made and shifting the placement of N298. These evolutionary differences presumably arise in response to alternative operating environments or the advantage gained in a particular product profile. Attempts to engineer chloride‐dependence into the chloride‐independent TAKA‐amylase point out the complexity of this system, and the fact that a multitude of factors play a role in binding chloride ion in the chloride‐dependent α‐amylases.
Impact of remote mutations on metallo‐β‐lactamase substrate specificity: Implications for the evolution of antibiotic resistance
Authors: Oelschlaeger Peter , Mayo Stephen L. , Pleiss Juergen 
Published: February 2005

AbstractMetallo‐β‐lactamases have raised concerns due to their ability to hydrolyze a broad spectrum of β‐lactam antibiotics. The G262S point mutation distinguishing the metallo‐β‐lactamase IMP‐1 from IMP‐6 has no effect on the hydrolysis of the drugs cephalothin and cefotaxime, but significantly improves catalytic efficiency toward cephaloridine, ceftazidime, benzylpenicillin, ampicillin, and imipenem. This change in specificity occurs even though residue 262 is remote from the active site. We investigated the substrate specificities of five other point mutants resulting from single‐nucleotide substitutions at positions near residue 262: G262A, G262V, S121G, F218Y, and F218I. The results suggest two types of substrates: type I (nitrocefin, cephalothin, and cefotaxime), which are converted equally well by IMP‐6, IMP‐1, and G262A, but even more efficiently by the other mutants, and type II (ceftazidime, benzylpenicillin, ampicillin, and imipenem), which are hydrolyzed much less efficiently by all the mutants. G262V, S121G, F218Y, and F218I improve conversion of type I substrates, whereas G262A and IMP‐1 improve conversion of type II substrates, indicating two distinct evolutionary adaptations from IMP‐6. Substrate structure may explain the catalytic efficiencies observed. Type I substrates have R2 electron donors, which may stabilize the substrate intermediate in the binding pocket. In contrast, the absence of these stabilizing interactions with type II substrates may result in poor conversion. This observation may assist future drug design. As the G262A and F218Y mutants confer effective resistance to Escherichia coli BL21(DE3) cells (high minimal inhibitory concentrations), they are likely to evolve naturally.
Contributions of hydrophobic domain interface interactions to the folding and stability of human γD‐crystallin
Authors: Flaugh Shannon L. , Kosinski‐Collins Melissa S. , King Jonathan 
Published: February 2005

AbstractHuman γD‐crystallin (HγD‐Crys) is a monomeric eye lens protein composed of two highly homologous β‐sheet domains. The domains interact through interdomain side chain contacts forming two structurally distinct regions, a central hydrophobic cluster and peripheral residues. The hydrophobic cluster contains Met43, Phe56, and Ile81 from the N‐terminal domain (N‐td) and Val132, Leu145, and Val170 from the C‐terminal domain (C‐td). Equilibrium unfolding/refolding of wild‐type HγD‐Crys in guanidine hydrochloride (GuHCl) was best fit to a three‐state model with transition midpoints of 2.2 and 2.8 M GuHCl. The two transitions likely corresponded to sequential unfolding/refolding of the N‐td and the C‐td. Previous kinetic experiments revealed that the C‐td refolds more rapidly than the N‐td. We constructed alanine substitutions of the hydrophobic interface residues to analyze their roles in folding and stability. After purification from E. coli, all mutant proteins adopted a native‐like structure similar to wild type. The mutants F56A, I81A, V132A, and L145A had a destabilized N‐td, causing greater population of the single folded domain intermediate. Compared to wild type, these mutants also had reduced rates for productive refolding of the N‐td but not the C‐td. These data suggest a refolding pathway where the domain interface residues of the refolded C‐td act as a nucleating center for refolding of the N‐td. Specificity of domain interface interactions is likely important for preventing incorrect associations in the high protein concentrations of the lens nucleus.
Dynamics of the gp130 cytokine complex: A model for assembly on the cellular membrane
Authors: Schroers Andreas , Hecht Oliver , Kallen Karl‐Josef , Pachta Michael , Rose‐John Stefan , Grötzinger Joachim 
Published: February 2005

AbstractCytokines of the interleukin‐6 (IL‐6)‐type family all bind to the glycoprotein gp130 on the cell surface and require interaction with two gp130 or one gp130 and another related signal transducing receptor subunit. In addition, some cytokines of this family, such as IL‐6, interleukin‐11, ciliary neurotrophic factor, neuropoietin, cardiotrophin‐1, and cardiotrophin‐1‐like‐cytokine, interact with specific ligand binding receptor proteins. High‐ and low‐affinity binding sites have been determined for these cytokines. So far, however, the stoichiometry of the signaling receptor complexes has remained unclear, because the formation of the cytokine/cytokine‐receptor complexes has been analyzed with soluble receptor components in solution, which do not necessarily reflect the situation on the cellular membrane. Consequently, the binding affinities measured in solution have been orders of magnitude below the values obtained with whole cells. We have expressed two gp130 extracellular domains in the context of a Fc‐fusion protein, which fixes the receptors within one dimension and thereby restricts the flexibility of the proteins in a fashion similar to that within the plasma membrane. We measured binding of IL‐6 and interleukin‐b receptor (IL‐6R) by means of fluorescence‐correlation spectroscopy. For the first time we have succeeded in recapitulating in a cell‐free condition the binding affinities and dynamics of IL‐6 and IL‐6R to the gp130 receptor proteins, which have been determined on whole cells. Our results demonstrate that a dimer of gp130 first binds one IL‐6/IL‐6R complex and only at higher ligand concentrations does it bind a second IL‐6/IL‐6R complex. This view contrasts with the current perception of IL‐6 receptor activation and reveals an alternative receptor activation mechanism.
Test of the Binding Threshold Hypothesis for olfactory receptors: Explanation of the differential binding of ketones to the mouse and human orthologs of olfactory receptor 912‐93
Authors: Hummel Patrick , Vaidehi Nagarajan , Floriano Wely B. , Hall Spencer E. , Goddard William A. 
Published: February 2005

AbstractWe tested the Binding Threshold Hypothesis (BTH) for activation of olfactory receptors (ORs): To activate an OR, the odorant must bind to the OR with binding energy above some threshold value. The olfactory receptor (OR) 912‐93 is known experimentally to be activated by ketones in mouse, but is inactive to ketones in human, despite an amino acid sequence identity of ∼66%. To investigate the origins of this difference, we used the MembStruk first‐principles method to predict the tertiary structure of the mouse OR 912‐93 (mOR912‐93), and the HierDock first‐principles method to predict the binding site for ketones to this receptor. We found that the strong binding of ketones to mOR912‐93 is dominated by a hydrogen bond of the ketone carbonyl group to Ser105. All ketones predicted to have a binding energy stronger than EBindThresh = 26 kcal/mol were observed experimentally to activate this OR, while the two ketones predicted to bind more weakly do not. In addition, we predict that 2‐undecanone and 2‐dodecanone both bind sufficiently strongly to activate mOR912‐93. A similar binding site for ketones was predicted in hOR912‐93, but the binding is much weaker because the human ortholog has a Gly at the position of Ser105. We predict that mutating this Gly to Ser in human should lead to activation of hOR912‐93 by these ketones. Experimental substantiations of the above predictions would provide further tests of the validity of the BTH, our predicted 3D structures, and our predicted binding sites for these ORs.
Structure and mechanism of ADP‐ribose‐1″‐monophosphatase (Appr‐1″‐pase), a ubiquitous cellular processing enzyme
Authors: Kumaran Desigan , Eswaramoorthy Subramaniam , Studier F. William , Swaminathan Subramanyam 
Published: February 2005

AbstractAppr‐1″‐pase, an important and ubiquitous cellular processing enzyme involved in the tRNA splicing pathway, catalyzes the conversion of ADP‐ribose‐1″monophosphate (Appr‐1″‐p) to ADP‐ribose. The structures of the native enzyme from the yeast and its complex with ADP‐ribose were determined to 1.9 Å and 2.05 Å, respectively. Analysis of the three‐dimensional structure of this protein, selected as a target in a structural genomics project, reveals its putative function and provides clues to the catalytic mechanism. The structure of the 284‐amino acid protein shows a two‐domain architecture consisting of a three‐layer αβα sandwich N‐terminal domain connected to a small C‐terminal helical domain. The structure of Appr‐1″‐pase in complex with the product, ADP‐ribose, reveals an active‐site water molecule poised for nucleophilic attack on the terminal phosphate group. Loop‐region residues Asn 80, Asp 90, and His 145 may form a catalytic triad.
Microsecond timescale backbone conformational dynamics in ubiquitin studied with NMR R1ρ relaxation experiments
Authors: Massi Francesca , Grey Michael J. , Palmer Arthur G. 
Published: February 2005

AbstractNMR spin relaxation experiments are used to characterize the dynamics of the backbone of ubiquitin. Chemical exchange processes affecting residues Ile 23, Asn 25, Thr 55, and Val 70 are characterized using on‐ and off‐resonance rotating‐frame 15N R1ρ relaxation experiments to have a kinetic exchange rate constant of 25,000 sec−1 at 280 K. The exchange process affecting residues 23, 25, and 55 appears to result from disruption of N‐cap hydrogen bonds of the α‐helix and possibly from repacking of the side chain of Ile 23. Chemical exchange processes affecting other residues on the surface of ubiquitin are identified using 1H‐15N multiple quantum relaxation experiments. These residues are located near or at the regions known to interact with various enzymes of the ubiquitin‐dependent protein degradation pathway.
Binding of the anti‐tubercular drug isoniazid to the arylamine N‐acetyltransferase protein from Mycobacterium smegmatis
Authors: Sandy James , Holton Simon , Fullam Elizabeth , Sim Edith , Noble Martin 
Published: February 2005

AbstractIsoniazid is a frontline drug used in the treatment of tuberculosis (TB). Isoniazid is a prodrug, requiring activation in the mycobacterial cell by the catalase/peroxidase activity of the katG gene product. TB kills two million people every year and the situation is getting worse due to the increase in prevalence of HIV/AIDS and emergence of multidrug‐resistant strains of TB. Arylamine N‐acetyltransferase (NAT) is a drug‐metabolizing enzyme (E.C. 2.1.3.5). NAT can acetylate isoniazid, transferring an acetyl group from acetyl coenzyme A onto the terminal nitrogen of the drug, which in its N‐acetylated form is therapeutically inactive. The bacterium responsible for TB, Mycobacterium tuberculosis, contains and expresses the gene encoding the NAT protein. Isoniazid binds to the NAT protein from Salmonella typhimurium and we report here the mode of binding of isoniazid in the NAT enzyme from Mycobacterium smegmatis, closely related to the M. tuberculosis and S. typhimurium NAT enzymes. The mode of binding of isoniazid to M. smegmatis NAT has been determined using data collected from two distinct crystal forms. We can say with confidence that the observed mode of binding of isoniazid is not an artifact of the crystallization conditions used. The NAT enzyme is active in mycobacterial cells and we propose that isoniazid binds to the NAT enzyme in these cells. NAT activity in M. tuberculosis is likely therefore to modulate the degree of activation of isoniazid by other enzymes within the mycobacterial cell. The structure of NAT with isoniazid bound will facilitate rational drug design for anti‐tubercular therapy.
Damages Caps, Insurability, and the Performance of Medical Malpractice Insurance
Authors: Viscusi W. Kip , Born Patricia H. 
Published: February 2005

AbstractThis article uses the complete property‐casualty insurance files of the National Association of Insurance Commissioners from 1984 to 1991 to assess the effect of medical malpractice reforms pertaining to damages levels and the degree to which these damages are insurable. Limits on noneconomic damages were most influential in affecting insurance market outcomes. Several punitive damages variables specifically affected the medical malpractice insurance market, including limits on punitive damage levels, prohibitions of the insurability of punitive damages, and prohibition of punitive damages awards. Estimates for insurance losses, premiums, and loss ratios indicate effects of reform in the expected directions, where the greatest constraining effects were for losses. The quantile regression analysis of losses indicates that punitive damages reforms and limits were most consequential for firms at the high end of the loss spectrum. Tort reforms also enhanced insurer profitability during this time period.
Differential usage of photoreceptors for chalcone synthase gene expression during plant development
Authors: Frohnmeyer Hanns , Ehmann Bruno , Kretsch Thomas , Rocholl Martin , Harter Klaus , Nagatani Akira , Furuya Masaki , Batschauer Alfred , Hahlbrock Klaus , Schäfer Eberhard 
Published: February 2005

SummaryPhotoregulation of chalcone synthase (CHS) mRNA accumulation was analysed in parsley (Petroselinum crispum) and mustard (Sinapis alba) plants at different developmental stages. In both species, CHS mRNA accumulation in young etiolated seedlings was primarily under phytochrome control. In leaves of adult re‐etiolated plants, a UV‐B photoreceptor was predominantly involved in photocontrol. The reduced red light control in mature leaves was not due to the absence of immunoreactive phytochrome. The apparent dependence of photoreceptor usage on the developmental state of the cell or organism was in accordance with observations on the photoregulation of fusion constructs between CHS promoters from parsley or mustard and the β‐glucuronidase reporter gene (GUS). When tested in the parsley protoplast transient expression system, both constructs yielded the same type of photoregulation as observed for the endogenous CHS gene.
Differential gene expression during somatic embryogenesis in Digitalis Ianata analyzed by in vivo and in vitro protein synthesis
Authors: Reinbothe Christiane , Tewes Annegret , Luckner Martin , Reinbothe Steffen 
Published: February 2005

SummaryDuring somatic embryogenesis in Digitalis Ianata, proembryogenic masses (PEMs) develop into globular‐, heart‐ and torpedo‐shaped embryos. The morphogenesis is correlated with drastic alterations in the composition of cellular and extracellular polypeptides. By comparing the spectra of in vivo translated polypeptides after two‐dimensional gel electrophoresis, three main classes of polypeptides were distinguished: (i) decreasing proteins; (ii) increasing proteins; (iii) constitutive polypeptides. Distinct subclasses of PEM‐ and embryo‐specific proteins could be discerned. The embryo‐specific polypeptides reached the highest relative prevalence in either the globular‐, heart‐ or torpedo‐shaped embryos and were not expressed in a non‐embryogenic cell line of D. Ianata, strain 119, indicating their temporally defined and embryogenesis‐related pattern of expression.The alterations of protein synthesis did not correlate with corresponding changes in the spectrum of abundant in vitro ‐translatable mRNAs. Relatively few PEM‐and embryo‐specific mRNAs could be discerned from constitutive messengers suggesting a posttranscriptional mode of control for the majority of protein genes during embryogenesis. However, for those in vitro synthesized (homologous) polypeptides which had a counterpart of identical isoelectric point and relative molecular mass among the in vivo translated polypeptides, a transcriptional type of gene expression was implied, since the mRNA content and the in vivo rate of protein synthesis changed similarly.