bluuebunny/crossref_metadata_2025_split huggingface dataset:
A study of ring‐substituent influence on pharmacological activity in a series of phenethylamine‐type psychedelics
Authors: King James W. , Molnar Stephen P. 
Published: September 2004

AbstractGeometry optimization for each member of a series of 15 substituted phenethylamines with reported psychotomimetic activity was performed using MM2 and MOPAC93 (AM1) methods. This was followed by calculation of previously developed, numerically unitary structure indices, viz., the molecular transform indices FTm, FTe, and FTc, indicating general, electronic, and charge properties respectively, and the analogous normalized molecular moment indices Mn, Me, and Mc. Each of the indices was used independently with the pharmacological data in a procedure to generate clusters containing three or more data points; linear correlations within each cluster were then determined. The Mn index performed best under the criteria, giving three clusters containing a total of 10 compounds; the other indices gave clusters accounting for totals of five to eight compounds for each index. Analysis of the clusters indicated that the 2‐ and 5‐positions on the phenyl ring should have substituents and that substitution at the 4‐position, preferably with a halogen, methyl, or thioether group, was critical for maximum pharmacological activity. The latter results suggest that ease of metabolic hydroxylation at the 4‐phenyl position (or the substituent group at that position, e.g., methyl, ethyl, etc.) is necessary for maximum activity. The performance of the Mn index appears to indicate more of a dependence on 3D spatial requirements for bioactivity, with molecular electronic and charge properties, respectively, being of secondary importance. Further, clustering and correlation regression of the biological data on the calculated logarithm of the octanol/water partition coefficient (CLogP) showed that the latter may be an important factor influencing pharmacological activity in this series. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
Are managers from Mars and academicians from venus? Toward an understanding of the relationship between academic quality and practical relevance
Authors: Baldridge David C. , Floyd Steven W. , Markóczy Lívia 
Published: September 2004

AbstractIn this paper, we propose a positive relationship between the academic quality and practical relevance of management research. The basis for this is the idea that academicians and practitioners both value research that is interesting and justified—meaning research that challenges and extends existing beliefs and research that offers compelling evidence for its conclusions. We acknowledge that there are likely to be many cases where academicians and practitioners disagree on what is interesting and justified. We argue, however, that there are also likely to be cases where the judgments of the two groups converge. Results from a stratified, random sample of 120 publications are consistent with this argument—showing a positive correlation between an objective measure of an article's academic quality and expert panel ratings of its practical relevance. The analysis also shows positive associations between panel members' global assessment of relevance and ratings of an article's interestingness and justification. These results lend support to the hypothesized overlap, but leave room for considerable difference in the way practitioners and academicians evaluate management research. Copyright © 2004 John Wiley & Sons, Ltd.
The formation of green strategies in Chinese firms: matching corporate environmental responses and individual principles
Authors: Branzei Oana , Ursacki‐Bryant Teri Jane , Vertinsky Ilan , Zhang Weijiong 
Published: September 2004

AbstractThis study examines how Chinese firms began responding to worsening environmental concerns in the late 1990s. Combining predictions from control theory, escalation of commitment, and goal theory, we seek to explain how leaders' cognitions shape the formation of novel responses to the value‐laden issue of corporate greening. We propose an iterative model that links leaders' principles with corporate actions and test it using survey data gathered from 360 firms. The model views strategy organically, as a set of adaptive goals and behaviors, and highlights the role of systemic and local feedback loops in strategy formation. We find that top executives who champion new strategic initiatives monitor early success or failure, and adjust their efforts to match early performance feedback. Perceptions of satisfactory performance strengthen leaders' efforts towards their initial target, while perceptions of unsatisfactory performance diminish them. This feedback relationship is invariant throughout favorable or unfavorable expectancies of success, contrary to the contingent prediction of control theory. The model also examines how top‐down and bottom‐up strategic initiatives combine to help firms maintain a positive momentum of change when champions' efforts decline in the face of premature failure signals. Copyright © 2004 John Wiley & Sons, Ltd.
Firms' technological resources and the performance effects of diversification: a longitudinal study
Authors: Miller Douglas J. 
Published: September 2004

AbstractWhile agency theory claims managerial self‐interest creates a diversification discount, strategic theory explains that firms with certain kinds of resources should diversify. Longitudinal data on 227 firms that diversify between 1980 and 1992 reveal that the sample firms invest less in R&D and have greater breadth of technology (based on patent citations) than their industry peers prior to the diversification event. Also, acquiring firms may appear to have lower performance because of accounting conventions and because firms that use internal growth rather than acquisition pursue less extensive diversification. These findings help explain how diversification and financial performance are endogenous. Copyright © 2004 John Wiley & Sons, Ltd.
Non‐additivity in portfolios of exploration activities: a real options‐based analysis of equity alliances in biotechnology
Authors: Vassolo Roberto S. , Anand Jaideep , Folta Timothy B. 
Published: September 2004

AbstractFirms invest in exploration‐oriented activities to seek competitive advantage and in response to changing environments. Real options formulations represent an emerging strand of thinking on such investments. In this paper we begin with the observation that firms often simultaneously invest in multiple exploration projects. We identify two sources of potential interactions among these real options investments. First, we investigate the effects of correlations between the outcomes in different options. Second, we analyze the effects of investments that are fungible across project options. We show that under different conditions multiple options can be sub‐additive (due to redundancies in outcomes) or super‐additive (due to fungible inputs). We test the implications of our model with data from the biotech industry and find supporting evidence. Our model and results have some interesting implications for the exploration literature and real options lens. Copyright © 2004 John Wiley & Sons, Ltd.
Characterizing specific phage–protein interactions by fluorescence correlation spectroscopy
Authors: Bahns John T. , Liu Chin‐Mei , Chen Liaohai 
Published: September 2004

AbstractThe interactions of several affinity reagent displayed T7 and M13 phage particles with their corresponding target molecules were examined using Fluorescence Correlation Spectroscopy (FCS). Diffusion times, relative fractions of each component in the recognition reactions at the equilibrium state, and ultimately the dissociation constants were deduced from analyzing the fluorescence autocorrelation curves. Although the sample preparation and FCS characterization of icosahedral T7‐related systems were relatively straight forward, procedures with filamentous M13‐related systems were complicated by the physical size of M13 and its aggregate formation. Methods that accommodate the FCS measurement of the M13 phage via changing confocal optics, fitting procedures, and aggregate discrimination are presented and discussed.
Comparison of TFII‐I gene family members deleted in Williams‐Beuren syndrome
Authors: Hinsley Timothy A. , Cunliffe Pamela , Tipney Hannah J. , Brass Andrew , Tassabehji May 
Published: September 2004

AbstractWilliams‐Beuren syndrome (WBS) is a neurological disorder resulting from a microdeletion, typically 1.5 megabases in size, at 7q11.23. Atypical patients implicate genes at the telomeric end of this multigene deletion as the main candidates for the pathology of WBS in particular the unequal cognitive profile associated with the condition. We recently identified a gene (GTF2IRD2) that shares homology with other members of a unique family of transcription factors (TFII‐I family), which reside in the critical telomeric region. Using bioinformatics tools this study focuses on the detailed assessment of this gene family, concentrating on their characteristic structural components such as the leucine zipper (LZ) and I‐repeat elements, in an attempt to identify features that could aid functional predictions. Phylogenetic analysis identified distinct I‐repeat clades shared between family members. Linking functional data to one such clade has implicated them in DNA binding. The identification of PEST, synergy control motifs, and sumoylation sites common to all family members suggest a shared mechanism regulating the stability and transcriptional activity of these factors. In addition, the identification/isolation of short truncated isoforms for each TFII‐I family member implies a mode of self‐regulation. The exceptionally high identity shared between GTF2I and GTF2IRD2, suggests that heterodimers as well as homodimers are possible, and indicates overlapping functions between their respective short isoforms. Such cross‐reactivity between GTF2I and GTF2IRD2 short isoforms might have been the evolutionary driving force for the 7q11.23 chromosomal rearrangement not present in the syntenic region in mice.
In silico protein design by combinatorial assembly of protein building blocks
Authors: Tsai Hui‐Hsu (Gavin) , Tsai Chung‐Jung , Ma Buyong , Nussinov Ruth 
Published: September 2004

AbstractUtilizing concepts of protein building blocks, we propose a de novo computational algorithm that is similar to combinatorial shuffling experiments. Our goal is to engineer new naturally occurring folds with low homology to existing proteins. A selected protein is first partitioned into its building blocks based on their compactness, degree of isolation from the rest of the structure, and hydrophobicity. Next, the protein building blocks are substituted by fragments taken from other proteins with overall low sequence identity, but with a similar hydrophobic/hydrophilic pattern and a high structural similarity. These criteria ensure that the designed protein has a similar fold, low sequence identity, and a good hydrophobic core compared with its native counterpart. Here, we have selected two proteins for engineering, protein G B1 domain and ubiquitin. The two engineered proteins share ∼20% and ∼25% amino acid sequence identities with their native counterparts, respectively. The stabilities of the engineered proteins are tested by explicit water molecular dynamics simulations. The algorithm implements a strategy of designing a protein using relatively stable fragments, with a high population time. Here, we have selected the fragments by searching for local minima along the polypeptide chain using the protein building block model. Such an approach provides a new method for engineering new proteins with similar folds and low homology.
Apo‐azurin folds via an intermediate that resembles the molten‐globule
Authors: Sandberg Anders , Leckner Johan , Karlsson B. Göran 
Published: September 2004

AbstractThe folding of Pseudomonas aeruginosa apo‐azurin was investigated with the intent of identifying putative intermediates. Two apo‐mutants were constructed by replacing the main metal‐binding ligand C112 with a serine (C112S) and an alanine (C112A). The guanidinium‐induced unfolding free energies (ΔGU−NH2O) of the C112S and C112A mutants were measured to 36.8 ± 1 kJ mole−1 and 26.1 ± 1 kJ mole−1, respectively, and the m‐value of the transition to 23.5 ± 0.7 kJ mole−1 M−1. The difference in folding free energy (ΔΔGU−NH2O) is largely attributed to the intramolecular hydrogen bonding properties of the serine Oγ in the C112S mutant, which is lacking in the C112A structure. Furthermore, only the unfolding rates differ between the two mutants, thus pointing to the energy of the native state as the source of the observed Δ ΔGU−NH2O. This also indicates that the formation of the hydrogen bonds present in C112S but absent in C112A is a late event in the folding of the apo‐protein, thus suggesting that formation of the metal‐binding site occurs after the rate‐limiting formation of the transition state. In both mutants we also noted a burst‐phase intermediate. Because this intermediate was capable of binding 1‐anilinonaphtalene‐8‐sulfonate (ANS), as were an acid‐induced species at pH 2.6, we ascribe it molten globule‐like status. However, despite the presence of an intermediate, the folding of apo‐azurin C112S is well approximated by a two‐state kinetic mechanism.
Design, expression, and purification of a Flaviviridae polymerase using a high‐throughput approach to facilitate crystal structure determination
Authors: Choi Kyung H. , Groarke James M. , Young Dorothy C. , Rossmann Michael G. , Pevear Daniel C. , Kuhn Richard J. , Smith Janet L. 
Published: September 2004

AbstractBovine viral diarrhea virus (BVDV) nonstructural protein 5B is an RNA‐dependent RNA polymerase, essential for viral replication. Initial attempts to crystallize a soluble form of the 695‐residue BVDV polymerase did not produce any crystals. Limited proteolysis, homology modeling, and mutagenesis data were used to aid the design of polymerase constructs that might crystallize more readily. Limited proteolysis of the polymerase with trypsin identified a domain boundary within the protein. Homology modeling of the polymerase, based on the structure of hepatitis C virus polymerase, indicated that the two polymerases share a 23% identical “core,” although overall sequence identity is low. Eighty‐four expression clones of the BVDV polymerase were designed by fine‐sampling of chain termini at the boundaries of domain and of active truncated forms of the polymerase. The resulting constructs were expressed in Escherichia coli and purified using high‐throughput methods. Soluble truncated proteins were subjected to crystallization trials in a 96‐well format, and two of these proteins were successfully crystallized.
A united residue force‐field for calcium–protein interactions
Authors: Khalili Mey , Saunders Jeffrey A. , Liwo Adam , Ołdziej Stanislaw , Scheraga Harold A. 
Published: September 2004

AbstractUnited‐residue potentials are derived for interactions of the calcium cation with polypeptide chains in energy‐based prediction of protein structure with a united‐residue (UNRES) force‐field. Specific potentials were derived for the interaction of the calcium cation with the Asp, Glu, Asn, and Gln side chains and the peptide group. The analytical expressions for the interaction energies for each of these amino acids were obtained by averaging the electrostatic interaction energy, expressed by a multipole series over the dihedral angles not considered in the united‐residue model, that is, the side‐chain dihedral angles χ and the dihedral angles λ for the rotation of peptide groups about the Cα•••Cα virtual‐bond axes. For the side‐chains that do not interact favorably with calcium, simple excluded‐volume potentials were introduced. The parameters of the potentials were obtained from ab initio quantum mechanical calculations of model systems at the Restricted Hartree‐Fock (RHF) level with the 6–31G(d,p) basis set. The energy surfaces of pairs consisting of Ca2+‐acetate, Ca2+‐propionate, Ca2+‐acetamide, Ca2+‐propionamide, and Ca2+‐N‐methylacetamide systems (modeling the Ca2+‐Asp−, Ca2+‐Glu−, Ca2+‐Asn, Ca2+‐Gln, and Ca2+‐peptide group interactions) at different distances and orientations were calculated. For each pair, the restricted free energy (RFE) surfaces were calculated by numerical integration over the degrees of freedom lost when switching from the all‐atom model to the united‐residue model. Finally, the analytical expressions for each pair were fitted to the RFE surfaces. This force‐field was able to distinguish the EF‐hand motif from all potential binding sites in the crystal structures of bovine α‐lactalbumin, whiting parvalbumin, calbindin D9K, and apo‐calbindin D9K.
High‐pressure refolding of bikunin: Efficacy and thermodynamics
Authors: Seefeldt Matthew B. , Ouyang Jun , Froland Wayne A. , Carpenter John F. , Randolph Theodore W. 
Published: September 2004

AbstractBikunin is a glycosylated protein that aggregates extensively during mammalian cell culture, resulting in loss of activity, loss of native secondary structure, and the formation of nonnative disulfide bonds. We investigated the use of high hydrostatic pressure (1000–3000 bar) for the refolding of bikunin aggregates. The refolding yield obtained with pressure‐modulated refolding at 2000 bar was 70 (±5%) by reverse‐phase chromatography (RP‐HPLC), significantly higher than the value of 55 (±6%) (RP‐HPLC) obtained with traditional guanidine HCl “dilution‐refolding.” In addition, we determined the thermodynamics of pressure‐modulated refolding. The change in volume for the transition of aggregate to monomer ΔVrefolding was calculated to be −28 (±5) mL/mole. Refolding was accompanied by a loss of hydrophobic exposure, resulting in a positive contribution to the ΔVrefolding. These findings suggest that the disruption of electro‐static interactions or the differences in size of solvent‐free cavities between the aggregate and the monomer are the prevailing contributions to the negative ΔVrefolding.
The C terminus of the nuclear protein NuMA: Phylogenetic distribution and structure
Authors: Abad Patricia C. , Mian I. Saira , Plachot Cedric , Nelpurackal Aniysha , Bator‐Kelly Carol , Lelièvre Sophie A. 
Published: September 2004

AbstractThe C terminus of the nuclear protein NuMA, NuMA‐CT, has a well‐known function in mitosis via its proximal segment, but it seems also involved in the control of differentiation. To further investigate the structure and function of NuMA, we exploited established computational techniques and tools to collate and characterize proteins with regions similar to the distal portion of NuMA‐CT (NuMA‐CTDP). The phylogenetic distribution of NuMA‐CTDP was examined by PSI‐BLAST‐ and TBLASTN‐based analysis of genome and protein sequence databases. Proteins and open reading frames with a NuMA‐CTDP‐like region were found in a diverse set of vertebrate species including mammals, birds, amphibia, and early teleost fish. The potential structure of NuMA‐CTDP was investigated by searching a database of protein sequences of known three‐dimensional structure with a hidden Markov model (HMM) estimated using representative (human, frog, chicken, and pufferfish) sequences. The two highest scoring sequences that aligned to the HMM were the extracellular domains of β3‐integrin and Her2, suggesting that NuMA‐CTDP may have a primarily β fold structure. These data indicate that NuMA‐CTDP may represent an important functional sequence conserved in vertebrates, where it may act as a receptor to coordinate cellular events.
Arm–domain interactions can provide high binding cooperativity
Authors: Schleif Robert , Wolberger Cynthia 
Published: September 2004

AbstractPeptidyl arms extending from one protein domain to another protein domain mediate many important interactions in biology. A well‐studied example of this type of protein–protein interaction occurs between the yeast homeodomain proteins, MAT α2 and MAT a1, which form a high‐affinity heterodimer on DNA. The carboxyl‐terminal arm extending from MAT α2 to MAT a1 has been proposed to produce an allosteric conformational change in the a1 protein that generates a very large increase in the DNA binding affinity of a1. Although early studies lent some support to this model, a more recent crystal structure determination of the free a1 protein argues against any allosteric change. This note presents a thermodynamic argument that accounts for the proteins' binding behavior, so that allosteric conformational changes are not required to explain the large affinity increase. The analysis presented here should be useful in analyzing binding behavior in other systems involving arm interactions.
The reaction of α‐crystallin with the cross‐linker 3,3′‐dithiobis(sulfosuccinimidyl propionate) demonstrates close proximity of the C termini of αA and αB in the native assembly
Authors: Swaim Catherine L. , Smith David L. , Smith Jean B. 
Published: September 2004

AbstractThe chaperone‐like activity of human lens α‐crystallin in inhibiting the aggregation of denatured proteins suggests a role for α‐crystallin in cataract prevention. Although a variety of techniques have generated structural information relevant to its chaperone‐like activity, the size and heterogeneity of α‐crystallin have prevented determination of its crystal structure. Even though synthetic cross‐linkers have provided considerable information about protein structures, they have not previously been used to study the proximity and orientation of subunits within human α‐crystallin. Cross‐linkers provide structural insight into proteins by binding the side chains of amino acids within close proximity. To identify the cross‐linked residues, the modified protein is digested and the resulting peptides are analyzed by mass spectrometry. Analysis of products from the reaction of α‐crystallin with 3,3′dithiobis(sulfosuccinimidyl propionate), DTSSP, identified several modifications to both αA and αB. The most structurally informative of these modifications was a cross‐link between lysine 166 of αA and lysine 175 of αB. This cross‐link provides experimental evidence supporting theoretical structural models that place the C termini of αA and αB within close proximity in the native aggregate.
Urinary complications and sexual function after the tension‐free vaginal tape procedure
Authors: Mazouni Chafika , Karsenty Gilles , Bretelle Florence , Bladou Franck , Gamerre Marc , Serment Gerard 
Published: September 2004

Objective.  The purpose of this prospective study was to evaluate urinary and sexual function after the tension‐free vaginal tape (TVT) support procedure for stress urinary incontinence (SUI).Methods.  Between January 1999 and July 2002 a total of 71 patients underwent comprehensive examination including urodynamics and a mailed self‐administered questionnaire for assessment of voiding and sexual function before and after treatment of SUI by TVT.Results.  Based on objective findings TVT was considered as curative in 48 patients (87.3%). Comparison of preoperative and postoperative urodynamic evidence demonstrated a significant outflow obstruction (<12 ml/s) in 19 patients (34.5%). A significant decrease in peak urinary flow during voiding (p < 0.001) was also observed. Of the 55 women (78.5%) who responded to the questionnaire before and after TVT, 42 (76.3%) reported satisfaction with the outcome. Postoperatively, 60% of patients reported voiding difficulty, 47.2% complained of urgency, and 32.7% of frequency. Regarding sexual function 20% reported impairment after surgery including dyspareunia in 14.5% (none preoperatively vs. eight postoperatively, <0.01) and loss of libido in 5.4%.Conclusion.  The TVT procedure is an effective treatment for SUI. However, it can lead to postoperative voiding and sexual impairment.