bluuebunny/crossref_metadata_2025 huggingface dataset:
A double‐blind study with a new monodrug Kan Jang: Decrease of symptoms and improvement in the recovery from common colds
Authors: Hancke Juan , Burgos Rafael , Caceres Dante , Wikman Georg
Published: October 2006

In a placebo‐controlled double‐blind study, the therapeutic effect of Kan Jang tablets made from Andrographis paniculata (Barm. F.) (Ness) dried extract was tested in patients with common colds. The patients were divided in two groups, in which group 1 (n = 33) received 1200 mg of Andrographis paniculata and group 2 (n = 28) a placebo (P).

On day 3–4 after treatment the possible effect of Kan Jang tablets on selected symptoms and clinical signs of common cold was evaluated. A significant reduction in clinical symptoms at day 4 of administration of the Kan Jang tablets was observed. A better efficacy against the placebo is discussed.

The differences in the total ‘sumscores’ of clinical and symptomatic findings indicate that the Kan Jang treated group did far better than the placebo group. We conclude that Kan Jang in a dose of 1200 mg daily has the capacity to significantly shorten the course/duration of the disease and therefore is indicated for an enhanced resistance to common colds.
Clinical evaluation of lecithin as a lipid‐lowering agent
Authors: Wójcicki J. , Pawlik A. , Samochowiec L. , Kaldoǹska M. , Myśliwiec Z.
Published: October 2006

The purpose of this investigation was to measure plasma lipid composition following oral administration of soybean lecithin in 32 patients with primary hyperlipidaemia. Lecithin granulate (Sternpur) was given for 30 days. Before starting the treatment and after 30 days of mangement blood was taken to establish the lipid concentration. Mean total cholesterol concentration was significantly decreased by 33%, while LDL‐level was diminished by 38%. HDL‐cholesterol concentration at the same time was increased significantly by 46%. Mean triglyceride concentration in these persons was significantly decreased by 33%. In conclusion, lecithin, a preparation obtained from soya, should be administered for the prevention and treatment of atherosclerosis.
Cochlospermum planchonii rhizome extract with hepatoprotective activity inhibits cytochrome P‐450 monooxygenases
Authors: Aliyu Roseline , Okoye Z. S. C. , Shier W. Thomas
Published: October 2006

An aqueous extract of Cochlospermum planchonii rhizomes prepared in the manner used by native medical practitioners in northern Nigeria to treat jaundice protects CCI4‐treated rats from liver damage measured as elevated serum levels of diagnostic enzymes. The extract inhibits cytochrome P‐450 monoxygenases aminopyrine‐N‐demethylase and aniline hydroxylase, suggesting a plausible hepatoprotective mechanism.
Development and evaluation of antimicrobial natamycin‐incorporated film in gorgonzola cheese conservation
Authors: de Oliveira Talita Moreira , de Fátima Ferreira Soares Nilda , Pereira Rodrigo Magela , de Freitas Fraga Kátia
Published: October 2006

Conservation of food products depends on product quality and packaging suitability. The objective of this work was to develop and evaluate the antimicrobial efficiency of natamycin‐incorporated film in the production process of Gorgonzola cheese. It aims to optimize the production process and increase shelf‐life and food safety for the consumer. Films with different concentrations of natamycin were produced and tested in Gorgonzola cheeses to evaluate its efficiency against Penicillium roqueforti on the cheese surface. Films with 2 and 4% natamycin presented satisfactory results for fungus inhibition and the amount of natamycin released to the cheese was below that allowed by the legislation. Copyright © 2006 John Wiley & Sons, Ltd.
Multivariate Data Analysis of Various Biological Test Systems Used for the Quantification of Ecotoxic Compounds
Authors: Nendza M. , Seydel J. K.
Published: October 2006

The toxic effects of ecotoxicologically relevant chemicals (phenols, anilines, aliphatic hydrocarbons) have been determined using several in vitro testing procedures which are assumed to represent relevant biological systems. These test systems selected within a collaborative study supply information about toxic effects on different levels of interference with ecosystems. Other selection criteria were reliability of the procedures, exact quantification of the observed effects, and low cost. Subsequently the toxicity data obtained in the different biological systems for more than 50 phenol‐, aniline derivatives and hydrocarbons were used to derive quantitative structure‐toxicity relationships. The regression equations obtained were compared. For all biosystems under study a dependence of toxic potency on the lipophilic properties of the compounds was found. With the same data set principal component analysis has been performed and the results give evidence that the ranking of toxicants is similar in the different testing systems used.

These results are further supported by the analysis of literature data from test systems of various complexity.
Quantitative Structure‐Activity Study of the Inhibition of Acetylcholinesterase with Aliphatic Ammonium Ions
Authors: Takayama Chiyozo , Akamatsu Miki , Fujita Toshio
Published: October 2006

To understand the role of the interaction between the positively charged quaternary nitrogen of the acetylcholine molecule and the anionic site of acetylcholinesterase, we measured the affinity of a number of aliphatic ammonium ions with bovine erythrocyte acetylcholinesterase in terms of the inhibition constant Ki and quantitatively analyzed the affinity index, log (1/Ki), with free‐energy‐related substituent and structural parameters and the multiple regression technique. Since the interaction of ammonium ions with the anionic site is regarded as being a type of ion‐pair formation in a hydrophobic milieu, we expected that the total steric effect of N‐substituents should be similar to that previously studied for the ion‐pair formation‐partition equilibrium of ammonium ions with picrate in the 1‐octanol/water system. By taking all of the steric effect terms in this ion‐pairing system as a single independent variable, the analysis was made to separate the specific hydrophobic effect of four N‐substituents on the affinity from their steric effect. The ammonium ions were suggested to interact with the anionic site so that the hydrophobic interaction of N‐substituents is dependent on their relative size while the total steric congestion is lowest. The hydrophobic nature of the enzymic milieu surrounding the anionic site was not uniform. The NH hydrogens in ions other than the quaternary were shown to lower the inhibitory activity nearly in proportion to their number. Being hydrated, the positively charged NH group could work to hold the ions in the bulk aqueous phase rather than on the enzyme.
Relationships Between Octanol/Water Partition Coefficients and Total Molecular Surface Area and Total Molecular Volume of Hydrophobic Organic Chemicals
Authors: de Bruijn Jack , Hermens Joop
Published: October 2006

Relationships between octanol/water partition coefficients (Kow) and parameters for molecular surface area or molecular volume are examined with new Kow data determined by the slow‐stirring method. It is shown that Kow values of chlorobenzenes (PCBz's) and polychlorinated biphenyls (PCBs) can be described well using a single parameter regression equation. However, separate equations are established for the different groups of compounds. For 18 PCBs a very significant equation was obtained using data for the solvent accessible surface area (SASA) that was calculated according to a full quantum chemical geometry optimization of the chemicals. With a corrected shorthand method for the calculation of the total molecular surface area (TSA) or volume (TMV), also very significant relationships were obtained.

An attempt was made to combine the Kow data for both PCBz's and PCBs within one equation by adding the solvatochromic parameters. However, there remained differences between the experimental and calculated results for the chlorobenzenes and the PCBs.

All linear correlations showed a deflection from the calculated values at high molecular areas or volumes which is probably caused by a solubilizing effect of the octanol present in the aqueous phase. Based on these observed deflections we estimate that the octanol/water partition coefficient (log Kow) will not exceed a value of 9.
Determination of Productive Conformation of Acetylcholinesterase Substrates Using Molecular Mechanics
Authors: Zhorov Boris S. , Shestakova Natalya N. , Rozengart Evgeniy V.
Published: October 2006

All equilibrium conformations (conformers) of 23 acetylcholinesterase substrates, conformationally flexible or semirigid derivatives of acetylcholine, were calculated using molecular mechanics. In a series of α‐alkyl‐β‐alkyl derivatives of acetylcholine, a correlation was found between the rate of hydrolysis of substrates and population of their completely extended tt‐conformers. Among cyclic analogs of acetylcholine, only those substrates which are compatible with the tt‐conformer of acetylcholine by the spatial disposition of the ammonium group, carbonyl oxygen and carbonyl carbon, are hydrolyzed at a high rate. In acetylcholine derivatives with elongated chain between acetyl and cationic groups, the hydrolysis rate varies directly with the population of conformers compatible with the tt‐conformer of acetylcholine. It is concluded that the tt‐conformer of acetylcholine is productive for the hydrolysis by acetylcholinesterase.
Comparative Molecular Field Analysis on a Set of Muscarinic Agonists
Authors: Greco Giovanni , Novellino Ettore , Silipo Carlo , Vittoria Antonio
Published: October 2006

A three‐dimensional quantitative structure‐activity relationship (3D‐QSAR) was carried out on a set of 39 non‐congeneric muscarinic agonists using Comparative Molecular Field Analysis (CoMFA). The compounds were tested on the M3 receptor subtype. However, since most of these ligands are reported as unspecific muscarinic agents, the proposed pharmacophore model accounts for features common to all the receptor populations (M1, M2 and M3). In order to define an alignment rule for the superimposition of the ligands, a common pharmacophore frame was derived with a preliminary conformational search performed on four typical muscarinic agonists. Both the steric and the electrostatic fields were used in CoMFA as molecular descriptors and were found relevant with almost the same statistical weight. The CoMFA coefficient contour maps revealed consistency with our postulated mechanism of interaction.

Several 3D‐QSARs were derived by means of the Partial Least Squares (PLS) method choosing the proper dimensionality with a cross‐validation procedure.
Theoretical Prediction of Antigenic Determinants Based on Protein‐Water Interaction Energies
Authors: Hofmann Hans‐Jörg , Hädge Dietlind , Höltje Monika , Höltje Hans‐Dieter
Published: October 2006

Goodford's GRIN/GRID method is used for the prediction of protein antigenic determinants by calculation of the interaction energy between proteins and water. The comparison of the regions of high interaction energy for the proteins lysozyme, myohemerythrin and tobacco mosaic virus protein with experimentally determined contact surfaces in antigen‐antibody complexes and epitopes obtained by cross‐reactivity measurements shows remarkable agreement. Accessible surface regions of considerable attraction for polar probes seem to be of special importance for antigen‐antibody recognition.
Structure‐activity Relations in Gestagenic Steroids by the MTD Method. The Case of Hard Molecules and Soft Receptors
Authors: Simon Z. , Bohl M.
Published: October 2006

A QSAR is obtained for affinity towards the gestagenic receptor for a series of 55 progesterone derivatives (r = 0.935), using the MTD‐method, with MTD for steric misfit and f a corrected relative hydrophobicity. Acceptable stability of regression coefficients of vertex attributions are obtained when this QSAR is compared with previous QSAR's for a reduced series of progesterone derivatives and for testosterone derivatives. Acceptable predicted activities for test molecules (r2 = 0.71) and acceptable results in a cross validation‐like procedure (r2 = 0.76) were obtained. These are strong arguments that our MTD results correspond to some real features of the gestagenic receptor site. In order to explain relative success of the MTD‐method in QSAR's for steroids, as compared to other methods, molecular aspects of the receptor‐effector interaction are discussed in relation to QSAR‐methodology. Recent computational chemistry approaches are based upon drug molecule‐receptor site energy calculations, assuming a fixed conformation for the receptor site. If the drug molecules are “hard” (rigid), the steric misfit with a “soft” (conformationally flexible) receptor site may be avoided by induction of different local conformational changes in the latter.
Drug Lipophilicity in QSAR Practice: II. Aspects of RM‐Determinations; Critics of RM‐Corrections; Interrelations with Partition Coefficients
Authors: Dross Karl P. , Mannhold Raimund , Rekker Roelof F.
Published: October 2006

Experimental conditions for the derivation of precise RM‐values are examined; the importance and the theoretical background of the extrapolation to modifyer‐free conditions as well as the generally proposed pK‐correction for RM are discussed. Compounds included in this study stem from the following four classes of drugs: antiarrhythmics, β‐blockers, phenothiazines and benzamides.

RM‐values of these compounds (determined in acetonitrile/buffer) are compared with experimentally determined (log Pobs, log P*) as well as calculated log P values (∑f, C log P). Best interrelation is found with non‐pK corrected data derived in a buffer to modifyer mixture 50/50. Comparison of the calculative approaches indicates a slight superiority of ∑f over C log P.
An Interaction Model for Tiotidine and Analogues with the Histamine H2‐Receptor
Authors: Haaksma Eric E. J. , Voss Hans‐Peter , Den Kelder Gabriëlle M. Donné‐Op , Timmerman Hendrik
Published: October 2006

For studying the interaction of compounds with a receptor it is important to have a pharmacophoric model which describes the possible sites of interaction. The high flexibility of H2‐antagonists such as cimetidine, ranitidine and tiotidine hampered the definition of such a 3D interaction model for the H2‐receptor. However, for tiotidine a number of analogues are known which do not only have different substituents at various parts of the molecule, but which are rigid as well. This makes these compounds suitable for the purpose of defining a pharmacophoric model. Based upon a comparison of the various tiotidine analogues it was possible to determine four sites of interaction. Two receptor binding sites interact with the two NH2 groups present in the 2‐guanidine group of tiotidine. The third site at the receptor interacts with the NH2 group of the cyanoguanidine moiety which is connected to the ethylthiomethyl chain; this NH2 group functions as a proton donor. The fourth binding site was found via a tiotidine analogue in which the flexible side chain had been replaced by a 4(5) imidazole group. One of the nitrogens of this imidazole ring functions as a proton donor. The orientation of this proton donor parallels the orientation of the proton donor function present in the cyanoguanidine group of tiotidine itself, leading to the suggestion that these two proton donor functions interact with the same receptor site. The results from these structural considerations, are summarized in a schematic model that can be used for subsequent studies on different groups of H2‐antagonists.
The History of Drug Research: From Overton to Hansch
Authors: Rekker Roelof F.
Published: October 2006

The paper overviews part of the history of Drug Research, the period from Overton to and including Hansch, and pays special attention to the development of parameter sets describing electronic, lipophilic and steric substituent effects. Extra emphasis is given to the evolution in the methodology of log P calculation. The sequence of π, f (Rekker – original), f (Hansch), f (Rekker – revised) is not yet closed but open for further developments, such as development of hydrophobic fragmental sets especially designed for the study of blood‐brain barrier transfer.
The History of Drug Research: From Hansch to the Present
Authors: van De Waterbeemd Han
Published: October 2006

The introduction by Hansch of the QSAR concept in the design of bioactive molecules opened new perspectives in organic chemistry. In the present contribution we will briefly review a number of factors contributing to the development of modern medicinal chemistry, particularly focussing on the increasing role of computers.
Modelling the Cytotoxicity of Halogenated Aliphatic Hydrocarbons. Quantitative Structure‐Activity Relationships for the IC50 to Human HeLa Cells
Authors: Eriksson Lennart , Sandström Björn E. , Sjöström Michael , Tysklind Mats , Wold Svante
Published: October 2006

The cytotoxicity towards human HeLa cells has been determined for a series of halogenated aliphatic hydrocarbons. The cytotoxicity, expressed as the inhibitory concentration lowering cell viability by 50%, IC50, is modelled by means of calculating a multivariate quantitative structure‐activity relationship based on a training set comprising ten chemicals. It is shown that the cytotoxicity of the compounds critically depends on their hydrophobic and steric properties. The QSAR is validated by making predictions for an external validation set consisting of six substances. In this context, a comparison between internal validation, that is crossvalidation, and external validation of the predictability of a QSAR, is made. The results obtained indicate that the latter method is the more demanding and likely leads to a model exhibiting optimal predictive power. Subsequently, the validated QSAR is also used for making predictions for 40 non‐tested compounds of similar chemical properties. The question of variable selection in the context of QSAR calculations is also addressed. Finally, the cytotoxicity endpoint is multivariately related to eight other biological variables for the training set compounds. This, so called, multivariate biological profiling, indicates that the cytotoxicity endpoint mediates information not conveyed by the other eight variables.
The Probability of Chance Correlation Using Partial Least Squares (PLS)
Authors: Clark Matthew , Cramer Richard D.
Published: October 2006

The frequency of chance correlation using partial least squares (PLS) has been measured experimentally for variously dimensioned data, comprising either completely random numbers, random numbers containing a perfect correlation within, and CoMFA field descriptors. This frequency, much lower than that for stepwise multiple regression, is maximal for datasets in which the number of descriptors equals the number of compounds, and surprisingly decreases indefinitely as the number of descriptors becomes much greater than the number of compounds. However, perfect correlations involving descriptor subsets are not detected by PLS if the number of irrelevant descriptors is excessive. In CoMFA applications, the probability of chance correlation is usually negligible. For example with 21 compounds a crossvalidated r2 value greater than 0.25 will occur by chance in less than 5% of trials.
Multiconformational Minimal Steric Difference. Structure‐Acetylcholinesterase Hydrolysis Rates Relations for Acetic Acid Esters
Authors: Ciubotariu D. , Deretey E. , Oprea T. I. , Sulea T. , Simon Z. , Kurunczi L. , Chiriac A.
Published: October 2006

This note presents the multiconformational MTD method and its application in a QSAR for acetylcholinesterase catalysed hydrolysis rates of a series of 25 acetic acid esters. Multiconformational MTD allows consideration of molecules with several low energy conformations, as the mostly aliphatic alcohol esters of this series, for QSAR. Conformations were selected for the QSAR study according to their energies calculated by the COSMIC modelling program. Information from an X‐ray crystallography study, together with results of conformational energy calculations was used in constructing the hypermolecule for the 25 acetic acid ester molecules. A classical Hansch QSAR, with σ*‐Taft constants, π‐hydrophobicities and Es‐steric constants yields r2 = 0.779 and r2cv = 0.577 in a crossvalidation procedure. The multiconformational MTD, with σ* and MTD as structural parameters yields, for the corelational equation r2 = 0.868 and r2cv = 0.661 in a cross validation procedure. Both correlational equations indicate an appreciable positive effect of electron withdrawing ester groups. The optimised receptor map indicates a receptor cavity with certain similarities to acetylcholine, but somewhat larger. QSAR studies are able, thus, to yield supplementary details to those given by X‐ray studies.
The Generation of Molecular Structures from a Graph‐Based QSAR Equation
Authors: Kier Lemont B. , Hall Lowell H.
Published: October 2006

The concept of the generation of molecular structures directly from a QSAR equation using topological indices is presented. The equations relating the path counts to the graph atom degree counts is presented as a linkage in the flow of information. The multiple candidate molecules are derived from target indices using a quality QSAR equation. An example is developed to illustrate the process using molecular connectivity indices.
Analysis of Distance Matrices for Studying Data Structures and Separating Classes
Authors: Benigni R. , Giuliani A.
Published: October 2006

This paper demonstrates that the computation of Euclidian distances between objects generates an intrinsic geometry, which, besides containing all the information explicitly present in the original space, also provides new information about the object interrelationships. In other words, by computing distances the data are mapped onto a new, and more flexible, reference frame. Such properties of the distance function also permit the derivation of non linear descriptors of the data space, and can be usefully exploited for pattern recognition purposes. In particular, it is demonstrated that this approach is able to separate embedded classes, which have been repeatedly reported in QSAR research.
Quantitative Structure‐Activity Relationships of Phencyclidine Receptor Ligands. Part 2 [1]. Extension of the Scope of the DVDP Parameter
Authors: Hayakawa Naohiro , Inami Yoshiharu , Terada Yukimasa
Published: October 2006

The validity of a parameter, which represents the direction of the molecular dipole vector of phencyclidine (PCP) derivatives, was reviewed. This parameter, named DVDP, quantitatively predicted the receptor binding activity of various PCP analogues. DVDP also effectively explained the activity of remarkably different compounds such as the MK‐801 derivatives. For the comparison of the dipole direction, the arrangement of the molecules was investigated by superimposition. The molecules were superimposed on hypothetical receptor points that were assumed on the characteristic pharmacophores of centrally acting drugs. However, for the MK‐801 derivatives, the superimposition based on the steric overlapping volume and the electrostatic repulsion was dominant. The study confirmed the importance of the hydrocarbon portion of the PCP piperidine ring and suggested an opposite orientation of MK‐801 to the conventional 3‐point model.
Hydrophobicity of Heterocycles: Determination of the π Values of Substituents on N‐Phenylpyrazoles
Authors: Gago Federico , Pastor Manuel , Pérez‐Butragueño Javier , López Raquel , Alvarez‐Builla Julio , Elguero Joseé
Published: October 2006

HPLC retention (log k′) and hydrophobic parameter (log Po/w) have been determined for 66 N‐phenylpyrazole derivatives with different substitution patterns, and πpyrazole constants have been calculated for several substituents in the positions 3‐, 4‐ and 5‐ of pyrazole. A linear relationship has been found between πpyrazole and the classical πbenzene constants. The data obtained can greatly improve the quality of QSAR equations involving pyrazole derivatives.
A QSAR Study of Quinolones Based on Electrotopological State Index for Atoms
Authors: Llorente B. , Rivero N. , Carrasco R. , Martinez R. S. , Estrada E.
Published: October 2006

A series of 18 quinolone antibacterials were used in a quantitative structure‐activity relationship (QSAR) study based on electrotopological state (E‐state) index for atoms. The results were correlated with minimum inhibitory concentrations (MICs) against E. coli H560 and the DNA gyrase cleavage values. The QSAR equations indicated that the in vitro antibacterial activity was strongly dependent on the E‐state indexes for the atom at position 6 and the O(sp2) of the carbonyl and carboxyl groups. This suggests the possibility of an electrostatic interaction between the atom at position 6 and the receptor; as well as the formation of hydrogen bonds between the carbonyl groups of the quinolone and the receptor.
Computer‐Assisted Analysis of Histamine H2− and H3‐Receptor Agonists
Authors: Sippl Wolfgang , Stark Holger , Höltje Hans‐Dieter
Published: October 2006

Using molecular modelling methods the structural and conformational requirements for receptor affinity and activity of histamine H2‐ and H3‐receptor agonists have been investigated. Two pharmacophore models were derived which indicate the different sterical requirements for the two histamine receptor subtypes. On the basis of these results we suggest that histamine may interact in different bioactive conformations with the corresponding receptor subtypes. Subsequent investigations of the molecular interaction potentials support the described orientations and conformations of H2‐ and H3‐agonists. The derived pharmacophore models together with the molecular interaction patterns of the agonists may serve as basis for amino acid models of the binding regions of H2‐ and H3‐receptor sites.
QSAR Modelling of the Toxicity of some Technical Non‐ionic Surfactants towards Fairy Shrimps
Authors: Lindgren Åsa , Sjöström Michael , Wold Svante
Published: October 2006

The toxicity of a number of non‐ionic surfactants towards Thamnocephalus platyurus (sweet water fairy shrimp) has been examined. The measurements have been performed with the use of so‐called Toxkits, and the results have been expressed both as a mean LC50 value for each of the surfactants, and with a relative scale estimated using of multi dimensional scaling (MDS). An algorithm is shown in matlab code, with which it is possible to perform MDS on a difference matrix with a lot of systematically missing values. The thus obtained results have been combined with the physico‐chemical data for the surfactants, and QSAR models have been estimated for the toxicity (log(LC50)) of the surfactants. The physico‐chemical properties with the main influence on the models were the hydrophilic‐lipophilic‐balance (HLB), the hydrophobicity (log P), the critical micellar concentration (CMC) and the number of carbon atoms in the hydrophobic part (C) of the surfactant.
Three‐dimensional Quantitative Structure–Activity Relationships of Hallucinogenic Phenylalkanamine and Tryptamine Derivatives: Studies using Comparative Molecular Field Analysis (CoMFA)
Authors: Beuerle Gerald , Kovar Karl‐Artur , Schulze‐Alexandru Meike
Published: October 2006

Investigations of the quantitative structure–activity relationships of a data set comprising 66 phenylalkanamines have been carried out using the CoMFA method. This yielded a cross‐validated correlation coefficient (q2 value) of more than 0.8. The target parameter used was the hallucinogenic effect on humans, since this variable is of particular importance for research into addictive substances. It was possible to confirm the reliability of the CoMFA analysis by using a second, independent phenylalkanamine data set. It was found that models with good predictive properties are obtained if up to ten components are taken into account. In a further step it was possible to include hallucinogenic tryptamine derivatives in a common QSAR analysis with the phenylalkanamines and this in spite of their differing basic structures. The final model from that the CoMFA plots were extracted is based on 148 compounds and permits precise inferences to be made concerning the relationships between structural elements and hallucinogenic effects.
Enhancing the Effectiveness of Ligand‐Based Virtual Screening Using Data Fusion
Authors: Willett Peter
Published: October 2006

Data fusion is being increasingly used to combine the outputs of different types of sensors. This paper reviews the application of the approach to ligand‐based virtual screening, where the sensors to be combined are functions that score molecules in a database on their likelihood of exhibiting some required biological activity. Much of the literature to date involves the combination of multiple similarity searches, although there is also an increasing interest in the combination of multiple machine‐learning techniques. Both approaches are reviewed here, focusing on the extent to which fusion can improve the effectiveness of searching when compared with a single screening mechanism, and on the reasons that have been suggested for the observed performance enhancement.
Implementation of a framework for development of teaching material using distributed sharing virtual space
Authors: Sasaki Hitoshi , Iwasaki Shoichi , Takeya Makoto
Published: October 2006

Recently, computer networks have been actively used at educational sites for WBT (Web‐based teaching) and the like. Teachers are trying to develop teaching materials and actively use them in the classroom. The development of teaching materials by 3D CG, actively utilizing the computer graphics functions, has also been started. However, since specialized knowledge and viewpoints are required in developing 3D teaching materials, this development is not easy compared to teaching materials development for WBT and the like. Nor is the environment for utilizing the materials unified. From this viewpoint, this paper proposes a framework for teaching materials development which facilitates the development of 3D teaching materials in the distributed sharing virtual space and realizes the collaborative utilization of multiple teaching materials on a network. The proposed scheme and the teaching materials developed by conventional methods are compared and the effectiveness of the proposed system in the development of teaching materials is discussed. © 2006 Wiley Periodicals, Inc. Syst Comp Jpn, 37(14): 97–106, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/scj.10607
Manipulating and imaging individual membrane proteins by AFM
Authors: Gonçalves Rui Pedro , Scheuring Simon
Published: October 2006

Membrane proteins are nanometric machines fulfilling defined functions in the membranes of all living cells. They work as transporters, linkers, adhesion molecules, channels, pumps, receptors and enzymes, and in bio‐energetic machineries, to name only a few tasks. In agreement with their multiple functions and importance, it was found that about 25% of all genes code for membrane proteins in organisms ranging from bacteria to humans. Biologists now have a set of techniques such as X‐ray crystallography, electron microscopy, and atomic force microscopy to analyze membrane protein structure, and techniques such as patch‐clamp, black lipid membrane and spectroscopy on membrane vesicles to analyze membrane function. Atomic force microscopy is widely used for imaging and force measurements, and here, its use as a unique tool to nano‐manipulate individual membrane proteins is reviewed. In this ‘mode’, additional loading forces are applied to an imaging tip, and scan rates and feedback parameters are adjusted to deliberately act on the surface of the biological object. When additional loading forces are relatively high (∼500 pN), stacked membrane layers can be dissected to give access to underlying membranes. Similarly, subunits from a multi‐protein complex can be dissected at slightly increased forces (∼200 pN) allowing the analysis of underlying protein structures, and hence that of the complex architecture. At low additional loading forces (∼100 pN), individual protein loops can be manipulated. Importantly, this process is nondestructive and provides access for the analysis of flexible protein surface domains. Copyright © 2006 John Wiley & Sons, Ltd.
The application of two‐dimensional correlation spectroscopy to surface and interfacial analysis
Authors: Dluhy Richard , Shanmukh Saratchandra , Morita Shin‐Ichi
Published: October 2006

Generalized two‐dimensional correlation spectroscopy (2D COS) is a modern analytical tool that is increasingly being used in the interpretation of complex spectra that have broad, multiply overlapped spectral features. Besides functioning as a spectral resolution–enhancement tool similar to curve‐fitting or deconvolution, 2D COS possesses an additional advantage in that it is capable of discerning temporal relationships between intensity variations within a set of spectra. Infrared reflection‐absorbance spectroscopy (IRRAS) at the air–water interface has been a very useful technique in studying the structure of biologically relevant molecules and the interaction between components of biological membranes in an environment close to what is found in nature. To better understand interfacial bio‐mimetic structure, 2D COS can be applied to the IRRAS spectra to analyze changes in infrared intensities as a function of an environmental perturbation such as a change in temperature or surface pressure. To overcome some of the inherent limitations of the generalized 2D method, model‐based approaches such as βν‐ and kν‐correlation analyses and the global 2D phase angle method were developed. This review discusses some of the recent applications of these novel methods to Langmuir monolayers of phospholipids and proteins at the air–water interface and Langmuir–Blodgett polymer films. Copyright © 2006 John Wiley & Sons, Ltd.
Controlling protein retention on enzyme‐responsive surfaces
Authors: Rawsterne Rachel E. , Gough Julie E. , Rutten Frank J. M. , Pham Nhan T. , Poon Wilson C. K. , Flitsch Sabine L. , Maltman Beatrice , Alexander Morgan R. , Ulijn Rein V.
Published: October 2006

The ability to change the properties of solid surfaces on demand is a key component of a multitude of established and emerging technologies. Stimuli that have previously been used to trigger changes in surface properties include changes in solvent, light, pH, ionic strength, temperature and magnetic or electric fields. We are interested in developing surfaces that can be triggered by the catalytic action of enzymes. We demonstrate the selective protease (α‐chymotrypsin and thermolysin) catalysed peptide hydrolysis of surface‐tethered fluorenylmethoxycarbonyl‐dipeptides. We highlight some of the challenges evident from surface analysis in overcoming enzyme retention to the surface addressed by physical adsorption of soluble PEG200 to the surface prior to enzyme exposure. Analysis by ToF‐SIMS and XPS shows that α‐chymotrypsin is deposited and retained on the surfaces and that thermolysin, a much more stable enzyme, selectively cleaves the tethered peptides as intended, and is removed from the surface by washing. Copyright © 2006 John Wiley & Sons, Ltd.
Biodegradation of recalcitrant chlorophenols by cometabolism
Authors: Liu D. , Maguire R. J. , Pacepavicius G. , Dutka B. J.
Published: October 2006

Under normal conditions in the environment a significant proportion of xenobiotic biodegradation involves cometabolism. Using the cometabolic principle, a procedure was developed to achieve accelerated biodegradation of persistent chemicals. Three stable chlorophenols [3,5‐dichlorophenol (DCP), 3,4,5‐trichlorophenol (TCP), and 2,3,5,6‐tetrachlorophenol (TRCP)], which showed a total resistance to the biodegradation potential of a pentachlorophenol‐degrading bacterial culture, were found to be biodegradable using the cometabolic technique. When a low‐chlorinated monochlorophenol (3‐MCP) was the cometabolite, only the medium‐low chlorinated 3,5‐DCP was biodegraded, while the medium chlorinated 3,4,5‐TCP and the medium‐high chlorinated 2,3,5,6,‐TRCP were not degraded by the culture. However, all three stable chlorophenols could be rapidly biodegraded when a highly chlorinated pentachlorophenol (PCP) cometabolite was used. If dual cometabolites (3‐MCP and PCP) were used, all three stable chlorophenols were biodegraded, but at much slower rate. Maximizing biodegradation by use of the cometabolic technique to achieve accelerated biodegradation of stable chemicals is discussed.
Microbial water quality concerns for water supply use
Authors: Geldreich Edwin E.
Published: October 2006

The greatest impact of water pollution on public health comes through drinking water, the source of which may be degraded by point and nonpoint pollution sources including municipal wastewater, storm water runoff, agricultural drainage, and food processing. While water treatment technology can successfully process poor quality source waters containing in excess of 2000 fecal coliforms/100 mL to produce potable water that meets the accepted drinking water standards, there is serious concern that the barriers to microbial breakthrough in the finished water may prove to be dangerously thin. Any momentary break in the treatment train could allow substantial levels of microorganisms to enter the final product—potable water.

The burden of water quality enhancement should be a shared responsibility among all discharges and downstream users of these irreplaceable resources. Much can be accomplished through the application of a multiple barrier approach in wastewater treatment, controlled storm water releases, and water supply enhancement. Dischargers must seek to minimize pathogen releases, reduce particulate dispersion, and diminish organics in effluents. These factors impact heavily on the effectiveness of wastewater disinfection. Furthermore, with passage downstream to the water intake, these organic residuals may be the precursors of disinfection by‐products created during drinking water treatment. Some water supply operations must revise their treatment practices to provide better protection from the passage of protozoan cysts and enhance the removal of organics before applying disinfection. Disinfection of water supply is critical and will only be consistently effective in a clean processed water.
Influence of combined chemicals on prodigiosin Synthesis of Serratia marcescens
Authors: Blessing Brigitte , Süssmuth Roland
Published: October 2006

The influences of pesticides (Imugan, Diuron, 2,4‐D. Simazin, Benodanil, E 600, Parathion, Eserin, Aldrin), heavy metals (ZnCl2, CdCl2, CuSO4, HgCl2), and mixtures of these two chemical groups on the rate of prodigiosin synthesized by Serratia marcescens in liquid medium have been studied. Prodigiosin synthesis showed a high sensitivity to toxicants. Therefore, a method is suggested using prodigiosin synthesis of S. marcescens for toxicity testing. The amount of prodigiosin and the inhibition zones in cup plate assays were tested in addition. In mixture, various effects depending on the toxin concentrations, used in the test, could be found: The activation of prodigiosin synthesis in submerged cultures by 0.3 mg Benodanil/L was more than 100% in the presence of Imugan or Diuron, and 256% in the presence of 1.5 mg HgCl2/L.
Assessment of mutagenic activity in drinking water from São Paulo City, Brazil
Authors: Sanchez Petra S. , Coimbrao Carlos A. , Coelho Maria C. L. , Valent Gisela U. , Sato Maria I. Z. , Martins Maria T.
Published: October 2006

During the last decade, studies carried out in several countries throughout the world have disclosed the presence of halogenated hydrocarbons and other potentially carcinogenic compounds in drinking water, causing public concern with respect to the quality of drinking water. Considering this problem, chlorinated drinking water from seven water treatment plants in São Paulo and from its water sources were tested for mutagenicity in the Ames/Salmonella assay. Different volumes of raw and treated waters were concentrated by XAD‐2 resin, and eluted in methanol and methylene chloride. Organic extracts ressuspended in DMSO were assayed for dose response in Salmonella typhimrium strains TA98 and TA100, with and without metabolic activation, using the plate incorporation technique. Results showed higher incidence of mutagenic activity in water samples after chlorination than in raw water. The majority of positive responses were decreased by addition of metabolic activation, confirming the presence of direct‐acting mutagens, produced during water chlorination, although significant mutagenicity was also observed in the presence of S9. Mutagenic levels ranged from 104 to 569 revertants/L in raw water, and in chlorinated drinking water, between 10 and 418 revertants/L. Based on the results obtained in this study, it is essential to study and identify mutagenic compounds evolving from the chlorination processes, and to determine, for water treatment plants with high incidence of mutagenic compounds, the procedures to avoid or eliminate this problem, as well as to establish an effective monitoring program.
Cadmium as an uncoupler of respiration in Ulva lactuca
Authors: Webster Elizabeth A. , Gadd Geoffrey M.
Published: October 2006

The effect of cadmium on the respiration of Ulva lactuca was examined using an oxygen electrode. Discs of U. lactuca thallus in filtered seawater were either incubated in the dark for 24 h or treated with 20 μM 3(3,4‐dichlorophenyl) 1,1‐dimethylurea to inhibit photosystem II dependent noncyclic electron transfer. In both cases, the addition of cadmium, as sulphate, increased respiration, with maximum stimulation occurring at approximately 15 mM; above this concentration respiration declined and at >21 mM inhibitory effects were significant. Dinitrophenol (DNP, 50 μM) and carbonyl cyanide m‐chlorophenylhydrazone (CCCP, 10 μM) also uncoupled respiration of U. lactuca, and when these compounds were used in conjunction with Cd the effects were found to be additive. Oligomycin (12.5 μ mL−1), which inhibits the mitochondrial ATPase, inhibited U. lactuca respiration but subsequent Cd addition (to 6 mM) resulted in a 2.5 × increase in respiration over control values. DNP had a similar effect when used with oligomycin. DNP and CCCP had a negligible effect on the respiration of KCN‐treated discs but the addition of Cd restored respiration to control values, probably because of the formation of insoluble Cd(CN)2. These results demonstrate that Cd can act as a respiratory uncoupler in U. lactuca.
Seasonal variations of microcystis species and toxic heptapeptide microcystins in lake suwa
Authors: Park Ho‐Dong , Watanabe Mariyo F. , Harada Ken‐Ichi , Suzuki Makoto , Hayashi Hidetake , Okino Tokio
Published: October 2006

Seasonal changes in species composition of Microcystis and concentrations of toxic heptapeptide microcystins, were investigated in Lake Suwa from June to October in 1991. Microcystins‐RR and ‐LR were the main components of the toxins contained in bloom samples of Microcystis and a very little quantity of ‐ YR was detected through this period. The high amounts of microcystins were estimated during the exponential growth phase of the bloom from June 11 to July 20. The highest concentrations of microcystins‐RR and ‐LR were estimated as 121 and 81.6 μg/100 mg cells on July 20, 1991, respectively. While the higher amounts of the toxins were estimated when M. aeruginosa predominated, the lower amounts were estimated during the predominate period of M. viridis. Since the dissolved inorganic nitrogen (DIN) concentration may well affect the dominance of M. aeruginosa and M. viridis, the production of the toxins by Microcystis may be associated with the DIN concentration. © 1993 John Wiley & Sons, Inc.
Interactive toxic effect and distribution of heavy metals in phytoplankton
Authors: Okamura Hideo , Aoyama Isao
Published: October 2006

Assessing the interactive toxic effect of chemicals in the environment is becoming a matter of increasing public focus on and concern with ecotoxicological aspects. The purpose of this study is to find the relationship between an interactive toxic effect and distribution of heavy metals in algal cells. The green alga Chlorella ellipsoidea Gernec(IAMC‐27) was cultured for 6 days in the presence of cadmium and/or chromium. Algal cells were divided into 4 fractions by centrifugation after the cells were disrupted using a French press. The amounts of the metals in each fraction were determined.

The interaction effect between the two metals on algal growth was investigated. The amount of one metal taken up in the cells and the growth inhibition rate increased with the concentration of metals in the medium. The amount of one metal in the cells was increased due to the presence of the other metal. Accordingly, the growth inhibition rate also increased. The amounts of Cd accumulated in the soluble fraction and in the membrane fraction of algal cells were 50 and 20%, respectively, of the total amount in the cells. The presence of Cr changed the Cd concentration in both fractions to 40%. The amount of Cr accumulated in each fraction was almost the same in the absence of Cd. The amount of Cr accumulated in the cell wall fraction rose to 90% after 3 days of exposure and it stayed as high as 50% even at the end of the six‐day study period in the presence of Cd. It was assumed that the presence of one metal influenced the distribution of the other metal in the cells, which resulted in the synergistic toxic effect. © 1994 by John Wiley & Sons, Inc..
Soil respiration, ATP content, and Photobacterium toxicity test as indicators of metal pollution in soil
Authors: Vanhala P. T. , Ahtiainen J. H.
Published: October 2006

The effects of heavy metal deposition from four different metalworks on soil respiration, ATP content, and toxicity to Photobacterium phosphoreum were examined. Soil samples were collected along a transect through the pollution gradients. Vegetation and soil types were homogeneous throughout the transects. Soil respiration was measured as CO2 production in closed bottles using an IR‐gas analyzer. The ATP content was measured with a bioluminometric assay after trichloracetic acid extraction of soil. The toxicities of distilled water extracts of soil samples were evaluated by the standard P. phosphoreum toxicity test and the metal content of these water extracts was measured as the bioavailable fraction of the heavy metal pollution in the soil. Soil respiration and ATP content were strongly affected by the heavy metal content in the soil. The correlation between the methods was high. The P. phosphoreum procedure can be used to estimate the toxicity of soils heavily polluted by metals. However, soil respiration and ATP content appear to be more sensitive indicators of soil pollution. © 1994 by John Wiley & Sons, Inc..
Peroxidation levels in Eschericia coli as a potential toxicity marker: Effect of nickel and methyl‐parathion
Authors: Espigares M. , Lucadamo L. , Coca C. , Aloj E. , Gálvez R.
Published: October 2006

The effects of nickel and methyl‐parathion were studied in subinhibiting concentrations (40 and 62.5 μg/mL, respectively) on the levels of cellular peroxidation in Escherichia coli. These effects were evaluated using the thiobarbituric acid (TBA) test and the determination of lipofuscin‐like substances. Both toxicants caused an increase in cellular peroxidation levels, although at the concentrations used, nickel was shown to be a better inducer than methyl‐parathion. The TBA test gave more significant differences than the determination of lipofuscin‐like substances when the control cultures were compared to those containing the toxicant. This finding reveals that the TBA test could be used as a toxicity marker in E. coli for the development of ecotoxicity biotests. © 1994 by John Wiley & Sons, Inc..