bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conformational analysis by intersection: CONAN
Authors: Smellie Andrew , Stanton Robert , Henne Randy , Teig Steve 
Published: December 2002

AbstractAs high throughput techniques in chemical synthesis and screening improve, more demands are placed on computer assisted design and virtual screening. Many of these computational methods require one or more three‐dimensional conformations for molecules, creating a demand for a conformational analysis tool that can rapidly and robustly cover the low‐energy conformational spaces of small molecules. A new algorithm of intersection is presented here, which quickly generates (on average <0.5 seconds/stereoisomer) a complete description of the low energy conformational space of a small molecule. The molecule is first decomposed into nonoverlapping nodes N (usually rings) and overlapping paths P with conformations (N and P) generated in an offline process. In a second step the node and path data are combined to form distinct conformers of the molecule. Finally, heuristics are applied after intersection to generate a small representative collection of conformations that span the conformational space. In a study of ∼97,000 randomly selected molecules from the MDDR, results are presented that explore these conformations and their ability to cover low‐energy conformational space. © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 10–20, 2003
Cool walking: A new Markov chain Monte Carlo sampling method
Authors: Brown Scott , Head‐Gordon Teresa 
Published: December 2002

AbstractEffective relaxation processes for difficult systems like proteins or spin glasses require special simulation techniques that permit barrier crossing to ensure ergodic sampling. Numerous adaptations of the venerable Metropolis Monte Carlo (MMC) algorithm have been proposed to improve its sampling efficiency, including various hybrid Monte Carlo (HMC) schemes, and methods designed specifically for overcoming quasi‐ergodicity problems such as Jump Walking (J‐Walking), Smart Walking (S‐Walking), Smart Darting, and Parallel Tempering. We present an alternative to these approaches that we call Cool Walking, or C‐Walking. In C‐Walking two Markov chains are propagated in tandem, one at a high (ergodic) temperature and the other at a low temperature. Nonlocal trial moves for the low temperature walker are generated by first sampling from the high‐temperature distribution, then performing a statistical quenching process on the sampled configuration to generate a C‐Walking jump move. C‐Walking needs only one high‐temperature walker, satisfies detailed balance, and offers the important practical advantage that the high and low‐temperature walkers can be run in tandem with minimal degradation of sampling due to the presence of correlations. To make the C‐Walking approach more suitable to real problems we decrease the required number of cooling steps by attempting to jump at intermediate temperatures during cooling. We further reduce the number of cooling steps by utilizing “windows” of states when jumping, which improves acceptance ratios and lowers the average number of cooling steps. We present C‐Walking results with comparisons to J‐Walking, S‐Walking, Smart Darting, and Parallel Tempering on a one‐dimensional rugged potential energy surface in which the exact normalized probability distribution is known. C‐Walking shows superior sampling as judged by two ergodic measures. © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 68–76, 2003
Using PC clusters to evaluate the transferability of molecular mechanics force fields for proteins
Authors: Okur Asim , Strockbine Bentley , Hornak Viktor , Simmerling Carlos 
Published: December 2002

AbstractThe transferability of molecular mechanics parameters derived for small model systems to larger biopolymers such as proteins can be difficult to assess. Even for small peptides, molecular dynamics simulations are typically too short to sample structures significantly different than initial conformations, making comparison to experimental data questionable. We employed a PC cluster to generate large numbers of native and non‐native conformations for peptides with experimentally measured structural data, one predominantly helical and the other forming a β‐hairpin. These atomic‐detail sets do not suffer from slow convergence, and can be used to rapidly evaluate important force field properties. In this case a suspected bias toward α‐helical conformations in the ff94 and ff99 force fields distributed with the AMBER package was verified. The sets provide critical feedback not only on force field transferability, but may also predict modifications for improvement. Such predictions were used to modify the ff99 parameter set, and the resulting force field was used to test stability and folding of model peptides. Structural behavior during molecular dynamics with the modified force field is found to be very similar to expectations, suggesting that these basis sets of conformations may themselves have significant transferability among force fields. We continue to improve and expand this data set and plan to make it publicly accessible. The calculations involved in this process are trivially parallel and can be performed using inexpensive personal computers with commodity components. © 2002 Wiley Periodicals, Inc. J Comput Chem 24: 21–31, 2003
Inherent speedup limitations in multiple time step/particle mesh Ewald algorithms
Authors: Barash Danny , Yang Linjing , Qian Xiaoliang , Schlick Tamar 
Published: December 2002

AbstractMultiple time step (MTS) algorithms present an effective integration approach to reduce the computational cost of dynamics simulations. By using force splitting to allow larger time steps for the more slowly varying force components, computational savings can be realized. The Particle‐Mesh‐Ewald (PME) method has been independently devised to provide an effective and efficient treatment of the long‐range electrostatics interactions. Here we examine the performance of a combined MTS/PME algorithm previously developed for AMBER on a large polymerase β/DNA complex containing 40,673 atoms. Our goal is to carefully combine the robust features of the Langevin/MTS (LN) methodology implemented in CHARMM—which uses position rather than velocity Verlet with stochasticity to make possible outer time steps of 150 fs—with the PME formulation. The developed MTS/PME integrator removes fast terms from the reciprocal‐space Ewald component by using switch functions. We analyze the advantages and limitations of the resulting scheme by comparing performance to the single time step leapfrog Verlet integrator currently used in AMBER by evaluating different time‐step protocols using three assessors for accuracy, speedup, and stability, all applied to long (i.e., nanosecond) simulations to ensure proper energy conservation. We also examine the performance of the algorithm on a parallel, distributed shared‐memory computer (SGI Origin 2000 with 8 300‐MHz R12000 processors). Good energy conservation and stability behavior can be demonstrated, for Newtonian protocols with outer time steps of up to 8 fs and Langevin protocols with outer time steps of up to 16 fs. Still, we emphasize the inherent limitations imposed by the incorporation of MTS methods into the PME formulation that may not be widely appreciated. Namely, the limiting factor on the largest outer time‐step size, and hence speedup, is an intramolecular cancellation error inherent to PME. This error stems from the excluded‐nonbonded correction term contained in the reciprocal‐space component. This cancellation error varies in time and introduces artificial frequencies to the governing dynamics motion. Unfortunately, we find that this numerical PME error cannot be easily eliminated by refining the PME parameters (grid resolution and/or order of interpolating polynomial). We suggest that methods other than PME for fast electrostatics may allow users to reap the full advantages from MTS algorithms. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 77–88, 2003
Qualitative analysis of social support and conflict among Mexican and Mexican‐American disaster survivors
Authors: Ibañez Gladys E. , Khatchikian Nadya , Buck Chad A. , Weisshaar Deborah L. , Abush‐Kirsh Tsila , Lavizzo Evelyn A. , Norris Fran H. 
Published: December 2002

AbstractWe describe in this study the various ways that survivors may experience social support and conflict after a disaster. Using unstructured interviews, 25 Mexicans/Mexican Americans (14 women, 11 men) were asked to recount the ways that they received support, as well as the ways they experienced conflict. Interviews occurred across three cities: Guadalajara, Jalisco (n = 9), Homestead, Florida (n = 6), and Puerto Angel, Oaxaca (n = 10). Recurrent themes were found for both support and conflict. Survivors reported more support from informal sources (family, neighbors) than formal sources (government) and far more tangible (food, shelter) than emotional or informational support. Conflict themes were different for each city. In Mexico, reports of conflict were more likely to involve abuses by government officials while in Homestead conflict involved abuses by residents. Theoretical and practical implications for future disaster research in developing countries are discussed. © 2003 Wiley Periodicals, Inc.
Paths to psychological empowerment in an urban community: Sense of community and citizen participation in substance abuse prevention activities
Authors: Peterson N. Andrew , Reid Robert J. 
Published: December 2002

AbstractEmpowerment represents a promising intervention target for substance abuse prevention activities. To date, however, there has been a paucity of research examining the role of empowerment processes engaged in by citizens within substance abuse prevention contexts. Addressing this concern, this study tested a path model that included perceptions of person, situation, and environment‐related predictors of empowerment. The hypothesized model was found to fit data from a sample of randomly selected urban residents (n = 661) who participated in an evaluation of a Center for Substance Abuse Prevention (CSAP) Community Partnership. Findings elucidate the need for developing substance abuse prevention initiatives that promote empowerment by increasing participation in substance abuse prevention activities, with particular emphasis on incorporating strategies designed to improve sense of community. Limitations of the study and directions for future research are discussed. © 2003 Wiley Periodicals, Inc.
Spousal relations and well‐being: A comparative analysis of Jewish and Arab dual‐earner families in Israel
Authors: Kulik Liat , Rayyan Faisal 
Published: December 2002

AbstractThe study examined differences in division of household tasks and spousal support among a sample of educated dual‐earner families from two national groups in Israel: Jews (n = 116), and Arabs (n = 163). The contribution of the spousal interaction variables (household roles and spousal support) toward explaining two dimensions of psychological well‐being (burnout and life satisfaction) was also examined. The research findings indicate that in general, the Arabs maintain a more traditional orientation toward gender roles than their Jewish counterparts. Arab men showed a greater tendency to perform outside tasks than their Jewish counterparts who participate more in domestic chores. By contrast, no differences were found between the two groups with regard to the mutual support provided by spouses. Gender role attitudes were found to be a key predictor of the two psychological well‐being dimensions in both national groups. Regarding sex differences, men of both nationalities were more likely than women to report that they perform all types of household tasks. Concomitantly, the women reported higher levels of burnout, while no differences between the sexes were found with respect to life satisfaction. © 2003 Wiley Periodicals, Inc.
Participation in Boys and Girls Clubs and relationships to youth outcomes
Authors: Anderson‐Butcher Dawn , Newsome W. Sean , Ferrari Theresa M. 
Published: December 2002

AbstractParticipation is a key issue in youth development organizations. In fact, research suggests that youths who attend the programs offered by these agencies will experience numerous benefits. One such youth development organization is the Boys and Girls Clubs of America (BGCA). Much of the research pertaining to the BGCA examines the importance of participation in structured prevention and educational programs such as Project SMART and Project Learn. The everyday Club participant, however, does not necessarily attend these structured programs. As such, the present study was designed to gain a better understanding of “typical” Club participation and how overall attendance at the Club is related to positive outcomes among youth. A total of 139 youths (aged 10 to 18 years old) participated in the study. Overall participation in the Club and age were both independently related to enhanced academic achievement, as well as increased substance use. Additionally, significant age and participation interaction effects point to the importance of Club participation at nullifying risks and problem behaviors associated with increasing age, particularly in relation to academic outcomes. Implications are discussed pertaining to program strategies that may serve as hooks or magnets that sustain youths' interest and continued involvement in BGCA activities and other youth development programs. © 2003 Wiley Periodicals, Inc.
Prevention of dog bites: Evaluation of a brief educational intervention program for preschool children
Authors: Wilson Fiona , Dwyer Fleur , Bennett Pauleen C. 
Published: December 2002

AbstractDog bites are an underestimated societal problem. Victims suffer injuries, both physical and emotional, that sometimes end in death, and the economic cost to the community is high. The most frequent victims are children, many of whom are bitten at home. Current interventions, primarily aimed at the control of dogs in public areas, appear unlikely to reduce the incidence of dog bites within this group. In this study, parents' beliefs about their children's behavior around familiar and strange dogs were investigated using a questionnaire. The impact of a brief educational dog safety program on 192 kindergarten children (M = 4.68 years of age) was then evaluated. The questionnaire data revealed that many children engage in unsafe behaviors around dogs, and that parents are largely unaware of the dangers associated with such behaviors. The dog safety program resulted in a significant increase in the ability of children to identify high risk situations for up to 4 weeks, with the benefits being even greater in those children whose parents were also given information regarding safe behaviors around dogs. © 2003 Wiley Periodicals, Inc.
Exploring “personal” and “shared” sense of community identity in Durham City, England
Authors: Puddifoot John E. 
Published: December 2002

Abstract“Personal” and “shared” aspects of sense of community identity are explored in a an established community in Durham City, England. Durham City has a history of over 1,000 years of continuous settlement, and is generally viewed as a stable and relatively harmonious setting. In the study 102 residents responded to a Community Response Questionnaire based on Puddifoot's taxonomy of elements of sense of community. The findings suggest the existence of three underlying “personal” dimensions of Sense of Community Identity (SOCI), namely, “Sense of Personal Support,” “Sense of Personal Contentedness,” and “Personal Involvement,” and three “shared” dimensions of SOCI, namely, “Perceived Community Engagement,” “Perceived Neighborliness,” and “Perceived Settledness.” This article discusses these findings and the prospect of creating a measure for comparative analysis around these dimensions. © 2003 Wiley Periodicals, Inc.
Cyclin T: Three forms for different roles in physiological and pathological functions
Authors: De Luca Antonio , De Falco Maria , Baldi Alfonso , Paggi Marco G. 
Published: December 2002

AbstractCyclins are members of family of proteins involved in the cell cycle regulation. They are regulatory subunits of complexes with proteins called cyclin‐dependent kinases (CDKs). There are three forms of cyclin T: cyclin T1, cyclin T2a, and T2b. All cyclin T contain an N‐terminal “cyclin homology box,” the most conserved region among different members of the cyclin family that serves to bind CDK9. In addition to the N‐terminal cyclin domain, cyclin T contains a putative coiled‐coil motif, a His‐rich motif, and a C‐terminal PEST sequence. The CDK9/cyclin T complex is able to activate gene expression in a catalytic‐dependent manner, phosphorylating the carboxy‐terminal domain (CTD) of RNA polymerase II. In addition, only cyclin T1 supports interactions between Tat and TAR. The interaction of Tat with cyclin T1 alters the conformation of Tat to enhance the affinity and specificity of the Tat:TAR interaction. On the other hand, CDK9/cyclin T2 complexes are involved in the regulation of terminal differentiation in muscle cells. © 2002 Wiley‐Liss, Inc.
Analysis of hormone‐stimulated phosphatidylinositol synthesis
Authors: Monaco Marie E. , Moldover Nancy H. , Walden Paul D. 
Published: December 2002

AbstractAgonist‐stimulated phosphoinositide turnover is accompanied by compensatory resynthesis of these lipids. Several lines of evidence suggest that resynthesis of phosphatidylinositol (PtdIns) involves phosphorylation of diacylglycerol (DG) (salvage pathway) rather than acylation of glycerol phosphate (de novo pathway), although a contribution from the de novo pathway has not been ruled out. To determine the relative contribution of the de novo and salvage pathways in stimulated PtdIns resynthesis, an inhibitor of de novo synthesis (Triacsin C) was incubated simultaneously with the hormone agonist. Results indicate that at early times (90 min), hormone‐stimulated PtdIns synthesis proceeds predominantly via the salvage pathway, although some de novo synthesis is also taking place. At later times (24 h), stimulated synthesis is solely via the de novo pathway. Increasing cellular DG content by either adding exogenous DG or treating cells with bacterial phospholipase C (bPLC) results in deacylation of the DG rather than phosphorylation; however, inhibition of this deacylation fails to stimulate phosphorylation by DG kinase (DGK), suggesting channeling of the DG substrate between PLC and DG kinase. Receptor activation is not required for activation of DGK, since treatment with a calcium ionophore induces the same Triacsin C‐insensitive PtdIns synthesis. Depletion of the polyphosphoinositide pools by treatment with wortmannin prevents both hormone and A23187‐induced polyphosphoinositide hydrolysis; however, A23187 is still able to induce hydrolysis of PtdIns and subsequent compensatory resynthesis. The inability of R59949 to inhibit either hormone‐induced or ionophore‐induced PtdIns resynthesis suggests that the α isoform is not involved; however, its possible that the channeling phenomenon prevents the inhibitor from gaining access to the diacylglycerol kinase enzyme. Further study will be required to determine which isoform catalyzes hormone‐induced resynthesis of PtdIns. © 2002 Wiley‐Liss, Inc.
Epidermal growth factor induces intracellular Ca2+ oscillations in microvascular endothelial cells
Authors: Moccia Francesco , Berra‐Romani Roberto , Tritto Simona , Signorelli Silvia , Taglietti Vanni , Tanzi Franco 
Published: December 2002

AbstractAn increase in intracellular Ca2+ concentration ([Ca2+]i) may play a role in the proliferative effect of several growth factors. In this study, the changes in [Ca2+]i elicited by epidermal growth factor (EGF) in rat cardiac microvascular endothelial cells (CMEC) have been investigated by using fura‐2 conventional and confocal microscopy. A large heterogeneity in the latency and in the pattern of the Ca2+ response was found at each dose of EGF (2.5–100 ng/ml), whereas some cells displayed a non‐oscillatory behavior and others exhibited a variable number of Ca2+ oscillations. On average, the fraction of responsive cells, the total number of oscillations and the duration of the Ca2+ signal were higher at around 10 ng/ml EGF, while there was no dose‐dependence in the lag time and in the amplitude of the [Ca2+]i increase. EGF‐induced Ca2+ spikes were abolished by the tyrosine kinase inhibitor genistein, but not by its inactive analogue daidzein, and by the phospholipase C blocker NCDC. Only 1–2 transients could be elicited in Ca2+‐free solution, while re‐addition of extracellular Ca2+ recovered the spiking activity. The oscillatory signal was prevented by the SERCA inhibitor thapsigargin and abolished by the calcium entry blockers Ni2+ and La3+. Moreover, EGF‐induced Ca2+ transients were abolished by the InsP3 receptor blocker caffeine, while ryanodine was without effect. Confocal imaging microscopy showed that the Ca2+ response to EGF was localized both in the cytoplasm and in the nucleus. We suggest that EGF‐induced [Ca2+]i increase may play a role in the proliferative action of EGF on endothelial cells. © 2002 Wiley‐Liss, Inc.
Potential role of apoptotic macrophages in pulmonary inflammation and fibrosis
Authors: Wang Liying , Antonini James M. , Rojanasakul Yon , Castranova Vincent , Scabilloni James F. , Mercer Robert R. 
Published: December 2002

AbstractInduction of apoptosis has been associated with a variety of exposures which result in inflammatory and fibrotic lung disorders. Macrophages are key regulatory cells in the lung; however, the role of apoptotic macrophages in those pulmonary disorders is not well characterized. In the present investigation, apoptotic macrophages were instilled into the lungs of rats to study directly the pulmonary responses to apoptotic cells. The effects of apoptotic macrophages on lung inflammation and fibrosis, as well as associated protein expression of TNF‐α, TGF‐β, and matrix metalloproteinases (MMPs) were examined. Induction of macrophage apoptosis was carried out in vitro using a variety of known apoptosis inducers. Intratracheal administration of apoptotic macrophages (5 × 106 cells/rat) into the lung of rats caused an increase in pulmonary infiltration of macrophages and lung cell apoptosis 4 weeks after the treatment as indicated by terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐labeling (TUNEL) assay. In contrast, pulmonary instillation of saline or normal control macrophages had no effect. Histological analysis of lung sections showed collagen deposition and fibrotic lesions after apoptotic cell treatment but not in control groups. Immunohistochemical studies revealed increased expression of TNF‐α, TGF‐β, MMP2, and MMP9 in the treatment group 4 weeks after the treatment. These results suggest a role for macrophage apoptosis in the initiation of these lung disorders. This study provides direct evidence that apoptotic macrophages can induce lung inflammation and fibrosis and that this induction may be associated with increased expression of TNF‐α, TGF‐β, MMP2, and MMP9. Published 2002 Wiley‐Liss, Inc.