bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Non‐aqueous Partitioning System for Predicting the Oral Absorption Potential of Peptides
Authors: Paterson D. Andrew , Conradi Robert A. , Hilgers Allen R. , Vidmar Thomas J. , Burton Philip S. 
Published: October 2006

AbstractIn the search for a better model of the rate limiting processes in peptide transport we studied the partitioning of solutes between heptane and ethylene glycol. Methods for determining the log partition coefficient (logPH/G) in this solvent system were developed and the reproducibility and ruggedness of such determinations were assessed. The partition coefficients in this system were found to correlate (r2 = 0.86, n = 11) with the permeability coefficients for a group of model peptides. To understand the physical forces governing this partitioning process, the influence of four solvatochromic parameters: hydrogen bond donor strength (α) hydrogen bond acceptor strength (β), polarity (π*), and molecular volume (V1), was evaluated for a set of 20 benzene derivatives. Multiple regression analysis revealed that the solute hydrogen bonding parameters, especially α, were the most important determinants. Molecular volume of the solute was about half as influential compared with partitioning systems in which water is the polar phase. These results suggest that the requirement for hydrogen bond breaking is the principal deterrent to peptide transport and that log PH/G is useful in predicting permeance.
A Classification Model for Allergic Contact Dermatitis
Authors: Magee Philip S. , Hostynek Jurij J. , Maibach Howard I. 
Published: October 2006

AbstractA classification model based on 36 compounds inducing allergic contact dermatitis and 36 non‐allergens was developed by the discriminant technique of two‐value multiple regression analysis. One outlier was observed and several of the compounds fell in the indeterminate region between the classes. Based on variable results of clinical data (human and animal), some overlap in the model was considered more reasonable than perfect separation. The descriptors in this model clearly imply intercellular transport (LogP derived) and various forms of binding (London forces [MR] and hydrogen‐bonding [HBA, HBD]) as part of the allergic contact dermatitis (ACD) response mechanism. In addition, substructure descriptors related to the epidermal reactivity of the ACD inducers were statistically important. These include directly reactive functional groups from haptens and metabolizable precursor groups of prohaptens.The model was developed from carefully selected compounds of diverse structure, representing a broad range of hapten and prohapten substructures without undue molecular complexity. Validation of the model is in progress on a broad range of molecular structures far beyond those used in construction.
The Use of Procrustes Analysis to Compare Different Property Sets for the Characterization of a Diverse Set of Compounds
Authors: Rose Valerie S. , Rahr Elizabeth , Hudson Brian D. 
Published: October 2006

AbstractProcrustes analysis has been used to compare the similarity of 14 different sets of property descriptors for characterizing a diverse set of pharmaceutical compounds. The analysis generated 3 distinct clusters from the property sets, which could be generally described as a) mostly 2D physicochemical properties, b) physicochemical properties based on overlaid 3D molecular structures, c) connectivity indices. Compound clustering and selection methods based on similarity measures calculated from a property set in one cluster would therefore give quite different results to those from a set in a different cluster.
Study of the Effects of Basic Di‐ and Tri‐phenyl Derivatives on Malignant Cell Proliferation: An Example of the Application of Correspondence Factor Analysis to Structure‐Activity Relationships (SAR)
Authors: Gilbert Jacques , Doré Jean‐Christophe , Bignon Eric , Pons Michel , Ojasoo Tiiu 
Published: October 2006

AbstractThe descriptive multivariate method known as Correspondence Factor Analysis (CFA) was used to establish correlations between the structures of three chemical classes of compounds (triphenyl‐acrylonitriles (TPEs), diphenylethylenes (DPEs), and diphenylalkyls) substituted in the para position by either hydroxy or basic groups and their responses in a battery of three biochemical tests, namely the induction of the proliferation of the MCF7 human breast cancer cell‐line, the estrogen‐irreversible inhibition of MCF7 cell proliferation (herein denoted cytotoxicity), and binding to the estrogen receptor (ER). The power of CFA was illustrated by performing several analyses: (a) Construction of factorial maps that described only the specificity of the response of the TPE population in the tests or both the specificity and amplitude of the response; (b) Use of the factorial maps as mathematical models for the introduction of new variables. These variables were either further biochemical tests (cytotoxicity under different conditions, inhibition of the activation of protein kinase C) on which the TPE population had been screened or further compounds (DPEs and diphenylalkyls). Relationships among the different tests were thus assessed as well as affiliations of the new compounds with TPEs. The analyses revealed the importance of the presence and configuration of hydroxy groups in ER binding and cell proliferation, but also the ability of non‐hydroxylated compounds to induce cell growth independently of their relative affinity for ER. Cytotoxicity could be related to the presence of basic groups but also to resonance of conjugated bis‐para‐hydroxy diphenyl derivatives. Overall, the analyses stressed the complexity of the relationships between growth‐promoting and growth‐inhibitory potential of the test‐compound populations and suggested the involvement of multiple mechanisms of action.
Dynamic QSAR: A New Search for Active Conformations and Significant Stereoelectronic Indices
Authors: Mekenyan Ovanes G. , Ivanov Julian M. , Veith Gilman D. , Bradbury Steven P. 
Published: October 2006

AbstractA new approach called “dynamic” QSAR is introduced to enhance the exploration of active chemicals and relevant molecular descriptors. In contrast to conventional QSAR methods where chemical structure is described by a single, low energy conformer, “dynamic” QSAR simulates the multiplicity of 3‐D molecular shapes that a molecule can assume in complex reaction environments. The core of the new methodology is the coupling of the 3DGEN algorithm which exhaustively generates conformers and a rule‐based system to rapidly screen conformers for desired properties. Hypotheses regarding receptor shape and interaction mechanisms are conveniently incorporated into the screening algorithm. A full array of Stereoelectronic parameters available to OASIS can be combined with conventional topological and physicochemical indices for all conformations and explored using a variety of mathematical and visualization techniques. The “dynamic” QSAR method is illustrated by modeling the acute toxicity of a series of unsaturated alcohols in fish.
Subcellular Pharmacokinetics and Drug Properties: Numerical Simulations in Multicompartment Systems
Authors: Baláž Štefan 
Published: October 2006

AbstractThe methodology and results of numerical simulations of drug distribution in multicompartment systems, represented by a catenary set of alternating aqueous and lipid compartments, are reviewed. Transport, membrane accumulation, protein binding, first order elimination (biotransformation or excretion), but not ionisation have been considered as the processes determining the drug distribution. The simulations provide the time courses of the drug concentrations in individual compartments as dependent on hydrophobicity and elimination rate parameters of drugs because the model parameters are substituted by their relationships to the drug properties. The simulation results are fitted with empirical functions, mostly in the form of the hydrophobicity‐concentration profiles for a pre‐defined time of exposure. The shape of the profiles is different for open and closed biological systems (with and without elimination, respectively) as well as for individual periods of the drug distribution in closed systems (non‐equilibrium, mixed, equilibrium). Fitting the empirical functions to experimental data enables one to verify quantitatively the simulation results. The use of the approach for formulation of mechanistic conclusions is exemplified.
The QSAR Discriminant‐Regression Model
Authors: Raevsky Oleg , Sapegin Alexei , Zefirov Nikolai 
Published: October 2006

AbstractThe DIscriminant‐REgression Model (DIREM) belongs to the ordinary discrete‐continuous QSAR approach, and has been proposed to explore SAR's for compounds with the same type of activity but different features of biological action. As a function scaling method, DIREM reveals the correspondence between structure descriptions and the distribution of compounds on a scale of biological activity. Model building is an iterative process that includes cluster formation using a stepwise procedure of linear discriminant analysis (LDA), and the discovery of quantitative relationships within each cluster by means of stepwise multiple regression analysis (MRA). DIREM is available in the software packages CLARAS (CLAssification and Recognition of Active Structure) and DNESTR (Design of New Effective STRuctures). Examples of DIREM application (guppy toxicity of aliphatic compounds, and β‐adrenergic activities of phenethylamines) are discussed.
QSAR in Toxicology. 1. Prediction of Aquatic Toxicity
Authors: Cronin Mark T. D. , Dearden John C. 
Published: October 2006

AbstractA critical review is given of quantitative and qualitative structure‐activity relationships (QSAR) for the prediction of some acute aquatic toxicological endpoints. Consideration is given to sources of biological data and, as in all areas of toxicology, there is concern over the validity, quality and quantity of toxicological data to model. Despite these problems it is now possible to predict the acute aquatic toxicity of unreactive chemicals to many species with considerable accuracy. Predictions for other mechanisms of toxic action become less accurate as more specific toxicities are investigated. Surprisingly little work has been performed on the prediction of toxicity of inorganic elements and their complexes, to both aquatic species and other organisms.
A CoMFA Analysis of Selected Physical Properties of Amino Acids in Water
Authors: Steinmetz Wayne E. 
Published: October 2006

AbstractThe CoMFA methodology was applied successfully to the analysis of logD, the logarithm of the octanol‐water distribution coefficient, of free amino acids and their amino acetylated, carboxy amidated derivatives. A learning set of 38 molecules and a test set of 9 molecules was used. ‐logS, the negative logarithm of the solubility in water, was also examined with a learning set of 19 amino acids. In each case the best results were obtained with the backbone of the residues on an extended conformation and the NCαCβCγ dihedral angle set to −60.0°. A combination of fields was used in the calculations: the default Tripos steric and electrostatic fields with the default probe, a sp3 carbon atom with a + 1 charge, and a GRID field with a water probe. The GRID field which measures hydrogen bonding makes the sole contribution to the optimal model for logD. This result is consistent with the importance of the hydrophobic effect. An electrostatic field is also required in the model for ‐logS. The inclusion of the electrostatic term may reflect the contribution to ‐logS made by crystal‐packing forces.
3D‐Quantitative Structure‐Activity Relationships for Hydrophobic Interactions: Comparative Molecular Field Analysis (CoMFA) including Molecular Lipophilicity Potentials as Applied to the Glycine Conjugation of Aromatic as well as Aliphatic Carboxylic Acids
Authors: Masuda Takashi , Nakamura Katsuhiko , Jikihara Takahiro , Kasuya Fumiyo , Igarashi Kazuo , Fukui Miyoshi , Takagi Tatsuya , Fujiwara Hideaki 
Published: October 2006

AbstractHydrophobic interactions sometimes play an important role in enzymatic reactions. In order to interpret such reaction data on the basis of comparative molecular field analysis (CoMFA) some method of introducing lipophilic parameters is necessary, since in the conventional CoMFA approach only electrostatic and steric fields are included in the original version. In the present study, the idea of Molecular Lipophilicity Potential (MLP) was introduced into the original CoMFA algorithm and the glycine conjugation reactions were analyzed. The conjugation data used were the whole reaction of glycine conjugation as well as the initial step of the reaction where substrates bind to coenzyme CoA. The substrates used include aromatic as well as aliphatic carboxylic acids. The CoMFA approach can explain data of aromatic and aliphatic carboxylic acids with a single model, whereas the multiple linear regression (MLR) analysis affords separated results for these two kinds of carboxylic acids. Thus, wide applicability of the CoMFA approach is supported and the aromatic and aliphatic carboxylic acids are suggested to behave in a common fashion in the conjugation reaction of the first process.
New Analgesics Designed by Molecular Topology
Authors: García‐Domenech R. , García‐March F. J. , Soler R. M. , Galvez J. , Antón‐Fos G. M. , De Julián‐Ortiz J. V. 
Published: October 2006

AbstractMolecular topology has been applied to the design of new analgesic drugs, utilizing linear discriminant analysis and connectivity functions using different topological descriptors. Of a total of 26 compounds selected, 17 showed analgesic activity. The following stood out particularly, showing analgesic values greater than 75% regarding ASA (acetylsalicylic acid), the reference drug: 2‐(1‐propenyl)phenol, 2′4′ dimethylacetophenone, p‐chlorobenzohydrazide, 1‐(p‐chlorophenyl) propanol and 4‐benzoyl‐3‐methyl‐1‐phenyl‐2‐pyrazolin‐5‐one. The usefulness of the design method has been demonstrated in the search of new chemical structures having analgesic effects, some of which could become “lead drugs”.
An on‐line handwritten mathematical equation recognition system that can process matrix expressions by referring to the relative positions of matrix elements
Authors: Toyozumi Kenichi , Suzuki Takahiro , Mori Kensaku , Suenaga Yasuhito 
Published: October 2006

AbstractIn this paper we describe a method for performing recognition of matrix expressions in an on‐line handwritten mathematical equation recognition system. This system incrementally performs recognition of numerical expressions and text input as handwriting and outputs the recognition results as LATEX source code. In previous work we developed the functionality of the system to make it capable of recognizing other two‐dimensional structures including subscripts, square root symbols, summation notation, and fractions, but we had not previously been able to deal with matrix structures. We believe that a specialized recognition system is necessary for dealing with matrix structures because they are not expressed using any declarative symbols and involve numerical elements positioned vertically on the page. In this paper we add matrix expression recognition functionality that can be used in real time to the system; this implementation makes use of both geometric features and the relative positions of numerical elements. We performed recognition experiments using the expanded system with input containing matrix expressions and confirmed the effectiveness of the proposed method. © 2006 Wiley Periodicals, Inc. Syst Comp Jpn, 37(14): 87–96, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.10684
Adaptive understanding of proposal‐requesting expressions for conversational information retrieval system
Authors: Hosokawa Kenichiro , Fujie Shinya , Kobayashi Tetsunori 
Published: October 2006

AbstractThis paper considers a conversational system in which information is provided in accordance with the conditions presented by the user, and proposes a method that can adequately deal even with unknown expressions. In most conventional systems, the relation between the expression and the intention of the utterance by the user is built into the system beforehand. Thus, it is difficult to deal adequately with unknown expressions which have not been learned. We propose a framework which adaptively manages on‐line the relation between the expression and the intention by interaction with the user. The proposed method produces a framework in which the connection between the expression and the intention is dynamically modified according to the explicitness or implicitness of the affirmative or negative attitude shown by the user to the proposal made by the system. It is verified by an evaluation experiment that the system can adequately learn the relation between the expression and the intention of the user by the proposed method, and can deal adequately with unknown expressions. © 2006 Wiley Periodicals, Inc. Syst Comp Jpn, 37(14): 62–72, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.20514
A distributed algorithm for constructing minimum delay spanning trees under bandwidth constraints on overlay networks
Authors: Baduge Thilmee M. , Hiromori Akihito , Yamaguchi Hirozumi , Higashino Teruo 
Published: October 2006

AbstractIn this paper, we propose a new protocol that constructs a spanning tree on an overlay network given by a complete graph, in a decentralized manner. This algorithm consists of two decentralized operations, which support joining of and leaving of the overlay network at any time in the session (though there are some constraints). Whenever a node joins or leaves, the rest of the nodes (or node itself in case of join) can be repositioned (or positioned) to minimize the maximum delay from a certain set of nodes in the current tree without violating the degree constraint at each node, by applying these operations. We have confirmed the usefulness of this algorithm by performing simulation and real‐world experiments. © 2006 Wiley Periodicals, Inc. Syst Comp Jpn, 37(14): 15–24, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.20655
Development of face‐to‐face communication function for a humanoid robot
Authors: Shiomi Masahiro , Kanda Takayuki , Miralles Nicolas , Miyashita Takahiro , Fasel Ian , Movellan Javier , Ishiguro Hiroshi 
Published: October 2006

AbstractIn this paper the authors report on the creation of a face tracking function that combines foveal vision and peripheral vision for communications between a humanoid robot and a person. In the authors' approach, by combining foveal vision and peripheral vision using a particle filter, a function for robust face tracking and attention direction can be achieved. In particular, the authors used peripheral vision when the robot was looking at an object other than a human being in order to make a deliberate gesture, and were able to achieve robust face tracking at all times by combining foveal vision and peripheral vision when the robot was paying attention to the person's face. Moreover, robust face tracking can also be applied to conventional technologies for facial expression recognition and utterance detection during interactive communication. © 2006 Wiley Periodicals, Inc. Syst Comp Jpn, 37(14): 1–14, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.20680
Optical microarray biosensing techniques
Authors: Bally Marta , Halter Martin , Vörös Janos , Grandin H. Michelle 
Published: October 2006

AbstractMicroarrays provide a powerful analytical tool for the simultaneous analyses of thousands of parameters, be they DNA or proteins, in a single experiment. However, a number of challenges continue to hinder the widespread application of microarray assays for analytical and diagnostic purposes. Advances in detection methods can help overcome some of these challenges by improving sensitivity and reliability in signal detection and by enabling real‐time detection of binding events. Thus, the aim of this review is to highlight the most promising optical microarray biosensing techniques. The principles of techniques making use of labels, including scanner type, total internal reflection type, fiber‐optics‐based, and SPR‐enhanced fluorescence, are described, along with a brief summary of labeling strategies. State of the art label‐free techniques, including imaging SPR and imaging ellipsometry, are also reviewed. Examples of microarray‐based assays using each technique are given to illustrate both their usefulness and their limits of detection. Furthermore, the most competitive commercial microarray systems are presented and compared with one another in the context of their detection system. Finally, a discussion of the remaining challenges as well as trends and future applications of microarrays are presented in the context of optical sensing. Copyright © 2006 John Wiley & Sons, Ltd.
C60, Buckminsterfullerene: its impact on biological ToF‐SIMS analysis
Authors: Fletcher John S. , Lockyer Nicholas P. , Vickerman John C. 
Published: October 2006

AbstractThe desire to apply the analytical abilities of the time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) experiment to increasingly diverse samples, particularly those of a biological nature, has provided the impetus for development of new technologies to overcome some of the inherent difficulties associated with such studies. Of these, one of the most important is the widespread introduction of polyatomic ion beams to increase the secondary ion yields of the higher mass, more chemically characteristic species. The introduction of the C60 ion beam for routine analysis has made arguably the greatest impact, providing new possibilities for analysing molecular compounds present both on the surface and in some cases in the bulk of samples such as biological tissue sections and single cells. Copyright © 2006 John Wiley & Sons, Ltd.
Applications of XPS in bioengineering
Authors: McArthur Sally L. 
Published: October 2006

AbstractXPS has been used extensively to characterise the surface chemistry of materials used in bioengineering. Its ability to characterise both the elemental and chemical structure of the surface makes it particularly useful, as it can be used to identify the chemical functional groups present on the surface of virtually any material. This review is intended to profile both traditional applications of XPS in bioengineering as well as highlight areas where the incorporation of XPS may be able to give insight into biointerfacial interactions. Copyright © 2006 John Wiley & Sons, Ltd.
Evidence of genotoxic substances in the Niagara river watershed
Authors: Lan Que , Dickman Mike , Alvarez Mar 
Published: October 2006

AbstractThe SOS chromotest was used to detect genotoxicity of sediment samples from seven locations in the Welland River, Ontario, Canada, in December 1986 and April 1987. DMSO extracts of sediment samples from one location situated directly below the discharge pipe of a polyvinyl chloride plant showed a statistically significant (p < 0.01) genotoxic effect. It was concluded that genotoxic contaminants were associated with vinyl chloride contaminated sediments from this location.At a distance of 5 m downstream of the polyvinyl chloride plant's discharge, the mean SOS induction factor was 2.05, while 100 m further downstream the SOS induction factor had dropped to 1.54.The Ames test was used to detect genotoxicity of samples that gave positive responses in the SOS chromotest. The results of the Ames test were negative. This may suggest that the SOS chromotest is more sensitive than the Ames test for testing genotoxicity in these types of samples.