The atomic scale structure of CXV carbon: wide-angle x-ray scattering and modeling studies.

The disordered structure of commercially available CXV activated carbon produced from finely powdered wood-based carbon has been studied using the wide-angle x-ray scattering technique, molecular dynamics and density functional theory simulations. The x-ray scattering data has been converted to the real space representation in the form of the pair correlation function via the Fourier transform. Geometry optimizations using classical molecular dynamics based on the reactive empirical bond order potential and density functional theory at the B3LYP/6-31g* level have been performed to generate nanoscale models of CXV carbon consistent with the experimental data. The final model of the structure comprises four chain-like and buckled graphitic layers containing a small percentage of four-fold coordinated atoms (sp(3) defects) in each layer. The presence of non-hexagonal rings in the atomic arrangement has been also considered.

Structural studies of water in hydrophilic and hydrophobic mesoporous silicas: an x-ray and neutron diffraction study at 297 K.

Water confined in a sol-gel network has been characterized by x-ray and neutron diffraction for two samples of mesoporous silica: one with a hydrophilic character (a nonmodified one) and another with a hydrophobic character (a modified one with a methylated internal pore surface). The pore size has been previously characterized [J. Jelassi et al., Phys. Chem. Chem. Phys. 134, 1039 (2010)] to have a mean pore diameter of approximately 55 Å. The diffraction measurements presented in this paper have been made at room temperature [293 K] for a filling factor of 0.45, giving a mean thickness of 8-9 Å for the water layer. The results show that the local order of the confined water molecules in the intermediate region of 3-6 Å is significantly different from that of the bulk water and also for the two different environments. For the hydrophilic sample, the siloxyl groups at the surface modify the water structure through the effects of interfacial hydrogen-bonding, which influences the orientational configuration of local water molecules and creates a modified spatial arrangement in the pore. In the case of the hydrophobic sample, there is no specific interaction with the pore wall, which is primarily van der Waals type, and the water molecules at the interface are differently oriented to create a hydrogen-bonded network linked more directly to the rest of the water volume. In the present circumstances, the thickness of the water layer has a relatively small dimension so that the interpretation of the measured diffraction pattern is not as straightforward as for the bulk liquids, and it is necessary to consider the effects of diffraction-broadening from a distributed sample volume and also the contribution from cross-terms that remain after conducting a "wet-minus-dry" analysis procedure. These analytic difficulties are discussed in the context of the present measurements and compared with the work of other groups engaged in the study of water confined in different environments. The present results, again, emphasize the complexity influencing the properties of water in a confined geometry and the strong influence of surface interactions on its behavior.

Prediction of biological activity profiles of cyanobacterial secondary metabolites.

Over the past decade cyanobacteria have become an interesting source of new classes of pharmacologically active natural products. Some cyanobacterial secondary metabolites (CSMs) are also well known for their toxic effects on living species. The PASS (Prediction of Activity Spectra for Substances) computer program, which is able to simultaneously predict more than one thousand biological and toxicological activities from only the structural formulas of the chemicals, was used to predict the biological activity profile of 681 CSMs. Multivariate methods were employed to structure and analyse this wealth of biological and chemical information. PASS predictions were successfully compared to the available information on the pharmacological and toxicological activity of these compounds.

Endocrine disruption profile analysis of 11,416 chemicals from chemometrical tools.

A number of chemicals released into the environment have the potential to disturb the normal functioning of the endocrine system. These chemicals termed endocrine disruptors (EDs) act by mimicking or antagonizing the normal functions of natural hormones and may pose serious threats to the reproductive capability and development of living species. Batteries of laboratory bioassays exist for detecting these chemicals. However, due to time and cost limitations, they cannot be used for all the chemicals which can be found in the ecosystems. SAR and QSAR models are particularly suited to overcome this problem but they only deal with specific targets/endpoints. The interest to account for profiles of endocrine activities instead of unique endpoints to better gauge the complexity of endocrine disruption is discussed through a SAR study performed on 11,416 chemicals retrieved from the US-NCI database and for which 13 different PASS (Prediction of Activity Spectra for Substances) endocrine activities were available. Various multivariate analyses and graphical displays were used for deriving structure-activity relationships based on specific structural features.

Typology of secondary cyanobacterial metabolites from minimum spanning tree analysis.

Recently, two main events have spurred a rapid increase in cyanobacteria chemical, toxicological, and ecological research. The first deals with the interest in isolating compounds from these organisms as source of active products with potential therapeutic applications. The second pertains the crucial problem of harmful cyanobacterial blooms in the aquatic environments. In this context, 594 secondary metabolites belonging to more than 30 genera of cyanobacteria were retrieved from literature. In order to perform their typology, they were first associated with 87 different molecular archetypes and two orphan classes. These 89 groups of molecular structures were then confronted to minimum spanning tree analysis. Attempts were made to graphically derive chemotaxonomical relationships. The interest of QSAR models for estimating the potential pharmacological interest of the cyanobacterial secondary metabolites was also discussed.

Chemometrical analysis of 18 metallic and nonmetallic elements found in honeys sold in france.

The elemental analysis of 86 honeys sold in France was performed with an inductively coupled plasma atomic emission spectrometer in order to measure significant concentrations of Ag, Ca, Cr, Co, Cu, Fe, Li, Mg, Mn, Mo, P, S, Zn, Al, Cd, Hg, Ni, and Pb. Principal component analysis, correspondence factor analysis, and hierarchical cluster analysis were used to rationalize and interpret the analytical data. Crude relationships were found between the elemental profiles of the honeys and their botanical origin. Some honeys were highly polluted by heavy metals and/or other xenobiotics. Explanations for these contaminations are proposed.

e-statistics for deriving QSAR models.

This paper presents some freeware, shareware, and commercial statistical tools available via the Internet and which could be used in QSAR for deriving models. Programming environments useful in Statistics, newsgroups and FAQs are also introduced due to their interest for the discipline.

An evaluation of NMR cryoporometry, density measurement and neutron scattering methods of pore characterisation.

Sol-gel silicas with nominal pore diameters ranging from 25A to 500A were studied by NMR cryoporometry, and by neutron diffraction and small angle scattering from dry silicas over the Q range 8. 10(-4)A(-1) < or = Q < or = 17A(-1). Density and imbibation experiments were also performed. Geometric models of porous systems were constructed and were studied by both analytic techniques and Monte-Carlo integration. These models, combined with the information from the above measurements, enabled the calculation of the fully density corrected solid-solid density correlation functions G(r) for the sol-gel silicas, deduction of the (voidless) silica matrix density, measurement of the silica fraction in the grain and of the packing fraction of the silica grains and an estimation of the water equivalent residual hydrogen on the dried silica surface. In addition, the pore diameter D, pore diameter to lattice spacing ratio D/a, and pore and lattice variance sigma could also be measured. While the NMR cryoporometry pore diameter measurements for the sol-gel silicas show excellent co-linearity with the nominal pore diameters as measured by gas adsorption, and the calculated pore diameters from the measured neutron scattering show surprisingly good agreement with these measurements at large pore diameters, there is a divergence between the calibrations for pore diameters below about 100A.

Lipids of three microsporidian species and multivariate analysis of the host-parasite relationship.

Sporal lipids of 3 microsporidia, Encephalitozoon cuniculi from mammals and Glugea atherinae and Spraguea lophii from fishes, were investigated. High phospholipid levels were found (54.8-64.5% of total lipids), which is in agreement with the presence of highly developed internal membranes in microsporidian spores. Sphingomyelin was not detected in G. atherinae. Triglycerides (less than 10% of total lipids), cholesterol, and free fatty acids were identified in all species. Analysis of fatty acids from the phospholipid fraction revealed the predominance of docosahexaenoic acid (30-40% of total phospholipid fatty acids) in G. atherinae and S. lophii and oleic acid (25.8% of total phospholipid fatty acids) in E. cuniculi. The 3 microsporidia possessed a significant amount of branched-chain fatty acids (iso and anteiso forms) not found in the hosts, supporting the existence of some parasite-specific metabolic steps for these fatty acids. On the basis of phospholipid fatty acid profiles, host-parasite relationships were investigated through correspondence factorial analysis. It shows 3 distinct clusters with the first corresponding to fishes, the second to fish parasites, and the third to E. cuniculi and its host cell. These data suggest that the mammal microsporidia developing within parasitophorous vacuoles are more dependent on host cells than the fish microsporidia that induce cystlike structures.

Deaths from breast cancer: tackling multidimensionality and non-linearity by correspondence analysis.

AIM: We investigated the use of non-linear, multidimensional factor analysis for the study of observational data on death from breast cancer. These data were obtained in the context of a clinical practice and not in a clinical trial. We looked into the correlations between patient characteristics and time of death and/or disease-free interval. PATIENTS AND METHODS: We first analyzed the characteristics of a population of patients that had died from breast cancer (n = 295), then of a population including patients still alive 7 years after surgery (n = 344). We used correspondence analysis (CA) which is based on chi(2)-metrics, does not assume linear relationships, and provides graphic overviews. RESULTS: The CA mapped variables (clinical stage, histoprognostic grade, node status, receptor positivity) in a way that fits in well with available knowledge on their importance as prognostic factors. We observed, however, that death occurred during three main periods (1-3, 4-7, < OR = 8 years after surgery) defined by different mixes of variables as if the disease progressed by stage rather than continuously. The CA distinguished long-term survivors (>7 years) from patients who died 8-10 years after surgery. Long-term survivors tended to be node-negative; those who died at 8-10 years tended to be the youngest patients (under 40). CONCLUSIONS: Because correspondence analysis combines the advantages of multidimensional and non-linear methods, it is a valuable exploratory tool for describing multiple correlations within a population before attempting to establish statistical significance of selected variables by more classic methods.

Multivariate analysis of metal concentration profiles in mushrooms.

The present work is an overview of the levels of contamination of 92 macromycetes by 15 metals. Data were collected around Paris (France) in 1989 and 1990. A progressive approach involving the use of univariate followed by multivariate statistical analyses allowed to fully exploit the resulting data matrix. Thus, conclusions regarding the origin of the metals, the toxicological implications and the possible use of mushrooms as environmental markers of pollutions are drawn.

Inhibition of chemiluminescence in human PMNs by monocyclic phenolic acids and flavonoids.

Flavonoids are metabolized in vivo to monocyclic phenolic acids. We investigated whether 18 phenolic acids of the benzoic, phenylacetic, phenylpropanoic or cinnamic series-known or potential metabolites of flavonoids-inhibit reactive oxygen species (ROS) released by human polymorphonuclear neutrophils (PMNs). Chemiluminescence was measured after PMN stimulation with three agents (N-fMetLeuPhe, phorbol myristate acetate (PMA), or opsonised zymosan) using two probes (lucigenin or luminol) with or without horseradish peroxidase (HRP) in order to derive specificity profiles for each test compound. The profiles of the phenolic acids and flavonoids were compared by a multivariate (correspondence) factor analysis. Overall, the phenolic acids were less specific than the flavonoids and, with a few exceptions, less potent. Phenolic acids had virtually no effect on the chemiluminescence related to O2- formation that is measured by lucigenin but inhibited luminol luminescence. Inhibition for all but two phenolic acids was sensitive to HRP and might be explained by a scavenger mechanism. Few structure-activity relationships emerged suggesting that simple properties such as radical scavenging and/or redox activity rather than overall structure might be the key determinants of chemiluminescence inhibition. Whatever the mechanism, however, we conclude that part of the in vivo pharmacological activity of flavonoids may readily be accounted for by phenolic acids.

Update on metal content profiles in mushrooms--toxicological implications and tentative approach to the mechanisms of bioaccumulation.

Fifteen metals (macroelements, heavy metals and trace elements) have been investigated using inductively coupled plasma-atomic emission spectrometry (ICP-AES) on 92 specimens of mushrooms collected in France, in the Paris region. Their levels and distributions are given. Taking in account the respective contents and bioaccumulation abilities, the data reveal that different mechanisms are involved depending on fungi species and genera besides physicochemical influences. Moreover, they suggest that the different elements might accumulate through various ways that are successively mentioned. Metabolic, toxicological and environmental significances are discussed.

Study of the age and sex dependence of trace elements in hair by correspondence analysis.

The aim of the study was to examine the potential of multidimensional analysis, and in particular of correspondence analysis (CA), in bringing to light the influence of sex and age on trace element (TE) concentrations in hair from an unselected French population. Sixteen elements (S, Hg, Se, Zn, Pb, Cd, Ni, Co, Mn, Fe, Cr, Mg, Al, Ca, Cu, Ag) were assayed by inductively coupled argon plasma (ICAP) emission spectroscopy in the scalp hair of 135 men and 346 women. In spite of the high background noise, CA was able to reveal the differing patterns in males and females. For instance, in this population, higher relative levels of the essential elements, Ca, Mg, Zn, and Cu, but also of Ag, characterized women's hair, whereas higher relative levels of the heavy metals, Fe and Pb, were associated with men's hair. Al and Ag were unexplainedly high in the hair of the youngest members of the population. The Cu and Co of youth seemed to give way to a predominance of Zn in maturity. The hair of individuals in their forties tended to be richest in Ca and Mg, but these elements decreased with advancing age. Heavy metals (Hg, Pb, Fe) accumulated with age, whereas Se, Mn, and Cr seemed independent of age. CA is manifestly a very useful tool for revealing underlying dimensions in complex dynamic systems and unsuspected relationships among variables. Clearly, the significance of the high Al and Ag contents in the hair of certain members of the population, especially of the very young, needs to be investigated from both physiological and toxicological aspects.

Nonlinear neural mapping analysis of the adverse effects of drugs.

Numerous drugs have been identified as presenting adverse effects towards the driving of vehicles. A large set of these drugs was compiled and classified into ten categories. Nonlinear neural mapping (N2M) was used to derive a typology of these molecules and also to link their adverse effects to therapeutic categories and structural information.

Correspondence analysis of protein kinase C (PKC) inhibition by bis-basic substituted benzamides.

We describe the synthesis of a novel series of bis-basic substituted benzamides and their relative potency in inhibiting rat brain protein kinase alpha (PKC alpha) activity. None of the compounds inhibited enzyme activity via the catalytic domain but several did via the regulatory domain at 1-5 microM concentrations. Inhibition was comparable to that of several di- and triphenylacrylonitriles and triphenylethylenes. According to a multivariate factor (correspondence) analysis of QSAR descriptors, hydrophobicity (log p) and hydration energy were the most discriminant descriptors, much more so than molecular mass, molar refractivity, polarizability, molecular volume and solvent-accessible surface. Inhibitory activity was correlated with high hydrophobicity and low hydration energy. The higher potency of GL9 (N,N'-oxalyl-bis[(o-amino)[2-(diethylamino)ethyl]-benzamide]) that differed from its congener (GL25) by the presence of an oxamide rather than succinamide moiety was tentatively explained by the greater negative charges associated with the carbonyl groups of its oxamide residue. The higher potency of GL22 (N,N'-tere-phthalyl-bis[(o-amino)[2-(diethylamino)ethyl]-benzamide ] in which an aromatic ring is inserted between two benzamide moieties in para, para' rather than ortho, ortho' positions as in GL23 might be due to a planar conformation facilitating membrane insertion. In conclusion, correspondence analysis is a neat way of highlighting similarities and differences in molecular properties (QSAR descriptors and potency). Therapeutic doses of many classes of drug might interfere with the regulatory domain of PKC alpha if, like our test-compounds, they have basic side-chain(s), high hydrophobicity, low hydration energy, a planar conformation and/or a highly charged reactive (oxamide) moiety.

Cytotoxicity and antiestrogenicity of a novel series of basic diphenylethylenes.

On the premise that it is necessary to develop antiestrogens with a higher cytotoxic component in order to reduce the risks of the development of heterogeneous malignant cell populations in breast cancer, we studied a novel series of basic diphenylethylenes, for the most part devoid of estrogenic activity, with low antiestrogenicity but much enhanced cytotoxicity compared to the reference drug tamoxifen. The main structural features associated with cytotoxicity were E isomery, substituents of five to eight carbons on the ethylene bond, and dibasicity.

Taxonomy of nuclear receptors and SERPINS by multivariate analysis of amino-acid composition.

The global amino-acid composition of a protein, although a cruder variable than sequence, is nevertheless informative and has been correlated with protein structural class. In the present study, we have applied complementary multivariate methods based on chi 2-metrics (correspondence factor analysis (CFA), minimum spanning tree (MST), ascending hierarchical classification (AHC)) to the analysis of the amino-acid frequency patterns of the C-terminal domain of 39 members of the nuclear receptor superfamily. The correlations we observed among receptors by this simple approach were, with few exceptions, in line with published phylogenetic dendrograms derived by sequence alignment. Further multivariate analyses were performed on the receptor population combined with 26 serine protease inhibitors (SERPINS) in view of the analogies detected between these superfamilies by hydrophobic cluster analysis (HCA), which were at the origin of the choice of alpha 1-antitrypsin as a 3-dimensional (3D) model for the receptor hormone-binding domain. Both the MST and AHC identified two distinct protein populations which in the principal phi 1 phi 2 CFA plot showed virtually no overlap, thus suggesting that receptors and SERPINS have different overall folding patterns, although the lower-order phi 3 phi 4 plot did reveal some similarities, essentially in the use of hydrophobic amino acids, that might account for analogies in HCA patterns. Receptors had a preference for those amino acids that are more frequent in alpha-helices and SERPINS for those in beta-strands and also tended to use different amino acids in turns. We therefore propose that multivariate analysis of amino-acid composition may prove helpful in identifying proteins for subsequent HCA.

[Proposition of chemical topology of principal antiviral molecules by a multiparameter mathematic model: the minimal length graph]. / Proposition d'une typologie chimique des principales molécules antivirales au moyen d'un modèle mathématique multiparamétrique: le graphe de longueur minimale.

The developed formula of some 200 antiviral molecules were treated by molecular connectivity matrix method. This technic allows the search and the automatically count of structural binary fragments of these molecules. It has been possible to establish a spanning tree (Prim's arborescent squeleton) which gathers the different molecules and permits to put a priori some new structures.

[A multivariate analysis approach to antineoplastic and antiviral structure-activity relationships to a series of podophyllotoxins]. / Approche par analyse multivariée des relations structure-activités antitumorale et antivirale dans la série de la podophyllotoxine.

In this work, the authors have used technics of multivariate analysis to determine the structure-activity relationships of 46 podophyllotoxin derivatives and analogs studied for their antineoplastic and antiviral activities. The obtained results allow to envisage the possible synthesis of more specific molecules by making modifications in the structure of the model molecular archetype.