Computer Aided Aroma Design. II. Quantitative structure-odour relationship

Computer Aided Aroma Design (CAAD) is likely to become a hot issue as the REACH EC document targets many aroma compounds to require substitution. The two crucial steps in CAMD are the generation of candidate molecules and the estimation of properties, which can be difficult when complex molecular structures like odours are sought and their odour quality are definitely subjective or their odour intensity are partly subjective as stated in Rossitier’s review (1996). The CAAD methodology and a novel molecular framework were presented in part I. Part II focuses on a classification methodology to characterize the odour quality of molecules based on Structure – Odour Relation (SOR). Using 2D and 3D molecular descriptors, Linear Discriminant Analysis (LDA) and Artificial Neural Network are compared in favour of LDA. The classification into balsamic / non balsamic quality was satisfactorily solved. The classification among five sub notes of the balsamic quality was less successful, partly due to the selection of the Aldrich’s Catalog as the reference classification. For the second case, it is shown that the sweet sub note considered in Aldrich’s Catalog is not a relevant sub note, confirming the alternative and popular classification of Jaubert et al., (1995), the field of odours

Quantitative structure-activity relationship for antimalarial activity of artemisinin

The increase in resistance to older drugs and the emergence of new types of infection have created an urgent need for discovery and development of new compounds with antimalarial activity. Quantitative-Structure Activity Relationship (QSAR) methodology has been performed to develop models that correlate antimalarial activity of artemisinin analogs and their molecular structures. In this study, the data set consisted of 197 compounds with their activities expressed as log RA (relative activity). These compounds were randomly divided into training set (n=157) and test set (n=40). The initial stage of the study was the generation of a series of descriptors from three-dimensional representations of the compounds in the data set. Several types of descriptors which include topological, connectivity indices, geometrical, physical properties and charge descriptors have been generated. The number of descriptors was then reduced to a set of relevant descriptors by performing a systematic variable selection procedure which includes zero test, pairwise correlation analysis and genetic algorithm (GA). Several models were developed using different combinations of modelling techniques such as multiple linear regression (MLR) and partial least square (PLS) regression. Statistical significance of the final model was characterized by correlation coefficient, r2 and root-mean-square error calibration, RMSEC. The results obtained were comparable to those from previous study on the same data set with r2 values greater than 0.8. Both internal and external validations were carried out to verify that the models have good stability, robustness and predictive ability. The cross-validated regression coefficient (r2 cv) and prediction regression coefficient (r2 test) for the external test set were consistently greater than 0.7. The QSAR models developed in this study should facilitate the search for new compounds with antimalarial activity

Can HRCT be used as a marker of airway remodelling in children with difficult asthma?

BACKGROUND: Whole airway wall thickening on high resolution computed tomography (HRCT) is reported to parallel thickening of the bronchial epithelial reticular basement membrane (RBM) in adult asthmatics. A similar relationship in children with difficult asthma (DA), in whom RBM thickening is a known feature, may allow the use of HRCT as a non-invasive marker of airway remodelling. We evaluated this relationship in children with DA. METHODS: 27 children (median age 10.5 [range 4.1-16.7] years) with DA, underwent endobronchial biopsy from the right lower lobe and HRCT less than 4 months apart. HRCTs were assessed for bronchial wall thickening (BWT) of the right lower lobe using semi-quantitative and quantitative scoring techniques. The semi-quantitative score (grade 0-4) was an overall assessment of BWT of all clearly identifiable airways in HRCT scans. The quantitative score (BWT %; defined as [airway outer diameter - airway lumen diameter]/airway outer diameter x100) was the average score of all airways visible and calculated using electronic endpoint callipers. RBM thickness in endobronchial biopsies was measured using image analysis. 23/27 subjects performed spirometry and the relationships between RBM thickness and BWT with airflow obstruction evaluated. RESULTS: Median RBM thickness in endobronchial biopsies was 6.7(range 4.6-10.0) microm. Median qualitative score for BWT of the right lower lobe was 1(range 0-1.5) and quantitative score was 54.3 (range 48.2-65.6)%. There was no relationship between RBM thickness and BWT in the right lower lobe using either scoring technique. No relationship was found between FEV1 and BWT or RBM thickness. CONCLUSION: Although a relationship between RBM thickness and BWT on HRCT has been found in adults with asthma, this relationship does not appear to hold true in children with D

A researcher's dilemma- philosphical and methodological pluralism

In many research textbooks the distinction between qualitative and quantitative research is inadvertently linked with philosophical perspectives. This in essence creates a mutually exclusive relationship between method and philosophy. Initially researchers are led to believe, from these textbooks, that research is neatly divided into mutually exclusive categories, these being quantitative and qualitative research and ‘never the twain shall meet’. This divide is further strengthened with the inference that the relationship extends further; associating deduction with quantitative methods and similarly induction with qualitative methods. What happens in most texts is that qualitative research methods and quantitative research methods are set against each other as polar opposites (Crotty 1998, p19). This paper argues that methodological pluralism is acceptable but what is not acceptable is philosophical pluralism. By naively linking methods and approaches to specific philosophy researchers and students may miss out on potentially innovative or creative data collection methods. Alternatively and more importantly by feeling tied or constrained by their philosophical stance to particular methods and approaches, associated with them by textbooks, they may in fact reduce the credibility, validity, and or significance of the research. There maybe an elective affinity between certain philosophies and methods but this should not necessarily constrain the methods chosen

Examining the Relationship Between Road Structure and Burglary Risk Via Quantitative Network Analysis

OBJECTIVES: To test the hypothesis that the spatial distribution of residential burglary is shaped by the configuration of the street network, as predicted by, for example, crime pattern theory. In particular, the study examines whether burglary risk is higher on street segments with higher usage potential. METHODS: Residential burglary data for Birmingham (UK) are examined at the street segment level using a hierarchical linear model. Estimates of the usage of street segments are derived from the graph theoretical metric of betweenness, which measures how frequently segments feature in the shortest paths (those most likely to be used) through the network. Several variants of betweenness are considered. The geometry of street segments is also incorporated—via a measure of their linearity—as are several socio-demographic factors. RESULTS: As anticipated by theory, the measure of betweenness was found to be a highly-significant predictor of the burglary victimization count at the street segment level for all but one of the variants considered. The non-significant result was found for the most localized measure of betweenness considered. More linear streets were generally found to be at lower risk of victimization. CONCLUSIONS: Betweenness offers a more granular and objective means of measuring the street network than categorical classifications previously used, and its meaning links more directly to theory. The results provide support for crime pattern theory, suggesting a higher risk of burglary for streets with more potential usage. The apparent negative effect of linearity suggests the need for further research into the visual component of target choice, and the role of guardianship

Application of Hansch’s Model to Capsaicinoids and Capsinoids: A Study Using the Quantitative Structure−Activity Relationship. A Novel Method for the Synthesis of Capsinoids

We describe a synthetic approach for two families of compounds, the capsaicinoids and capsinoids, as part of a study of the quantitative relationship between structure and activity