Biomedical subjects

R Todeschini

Publications and source records attributed to R Todeschini.

16 recordsLinked to original sources

PubMed2004

Total ranking models by the genetic algorithm variable subset selection (GA-VSS) approach for environmental priority settings.

Total order ranking (TOR) strategies, which are mathematically based on elementary methods of discrete mathematics, seem to be attractive and simple tools for performing data analysis. Moreover order-ranking strategies seem to be a very useful tool not only to perform data exploration but also to develop order ranking models, a possible alternative to conventional quantitative structure-activity relationship (QSAR) methods. In fact, when data material is characterised by uncertainties, order methods can be used as alternative to statistical methods such as multilinear regression (MLR), because they do not require specific functional relationships between the independent and dependent variables (responses). A ranking model is a relationship between a set of dependent attributes, experimentally investigated, and a set of independent attributes, i.e. model attributes, which are calculated attributes. As in regression and classification models, the variable selection model is one of the main steps in finding predictive models. In this work the genetic algorithm-variable subset selection (GA-VSS) approach is proposed as the variable selection method for searching for the best ranking models within a wide set of variables. The models based on the selected subsets of variables are compared with the experimental ranking and evaluated by the Spearman's rank index. A case study application is presented on a TOR model developed for polychlorinated biphenyl (PCB) compounds, which have been analysed according to some of their physicochemical properties which play an important role in their environmental impact.

Journal Article↗

PubMed2003

Study on anaerobic and aerobic degradation of different non-ionic surfactants.

Six alcohol ethoxylates (C5E2, C6E4, C7E4, C8E2, C8E4, C10E4) and two fatty acid esters were tested at lab-scale for degradation in anaerobic and aerobic conditions and oxygen uptake rate (OUR). Anaerobic removal of C5E2, C6E4 and C7E4 improved with increasing number of ethoxy groups (E) and decreasing length of the alkyl chain (C). Their aerobic removal was also great but lower than the anaerobic values. C8E2, C8E4 and C10E4 were adsorbed on sludge but not degraded in anaerobic conditions, while they were efficiently removed under aerobiosis. The fatty acid esters were removed to a level between the two alcohol ethoxylates groups in both anaerobiosis and aerobiosis. The measured OUR confirmed the different behaviours of the three groups of compounds.

Alcohols↗

PubMed2003

Application of the Kohonen artificial neural network in the identification of proteinaceous binders in samples of panel painting using gas chromatography-mass spectrometry.

Historically, three types of proteinaceous matter--casein, egg and animal glue--were used as binders for pigments or as adhesives in easel and wall painting. The relative percentage content of alanine, glycine, valine, leucine, isoleucine, serine, tyrosine, phenylalanine, aspartic acid, glutamic acid, lysine, methionine, proline and hydroxyproline, as determined by GC-MS, is used for binder identification. In this paper we analyse the viability of a multivariate modelling using Kohonen's neural network to characterise the wood adhesive in 16 old samples from Italian panel paintings of the 12-16th centuries. As a training set we use the amino acid composition of 141 samples contributed by the Opificio delle Pietre Dure of Florence (Cultural Heritage Ministry, Italy). Of the 141 samples, 113 were used to train the Kohonen neural network and the remaining 28 as the evaluation set. A specificity and sensitivity of 100% was achieved in training and 92-100% in prediction depending on the assignation criteria employed. The neural network thus trained and evaluated was applied to the old samples, achieving identification of all of them. In addition, the map obtained for each amino acid provides relevant information as to its importance in the characterisation of the sample.

Journal Article↗

PubMed2001

QSAR and chemometric approaches for setting water quality objectives for dangerous chemicals.

In order to evaluate environmentally safe levels of dangerous chemicals, there is the need for a set of toxicological data on organisms representative of the ecosystems, which is often unavailable or inadequate. In this article, a predictive approach was applied to a set of 125 chemicals (derived from the European priority list in compliance with Directive 76/464/EEC), for which water quality objectives were available. Toxicological data on organisms representative of the aquatic environment (algae, Daphnia, and fish) were taken from the literature or predicted by means of quantitative structure--activity relationships. This provided toxicological data on all three organisms for 97 of 125 chemicals and on at least two organisms (Daphnia and fish) for the whole data set. Principal Component Analysis was applied in order to perform an a priori classification of chemicals based on toxicity data. Then several classification models, based on traditional and nontraditional molecular descriptors, were applied. Classification models gave results in agreement with the a priori classification as well as with the original water quality objectives classification. The behavior of some outliers was explained. The approach described appears to be a useful tool for the preliminary classification of chemicals that are dangerous to the aquatic environment for which toxicological data are inadequate.

Animals↗

PubMed2001

QSAR approach for the selection of congeneric compounds with a similar toxicological mode of action.

The selection of compounds with a similar toxicological mode of action is a key problem in the study of chemical mixtures. In this paper, an approach for the selection of chemicals with similar mode of action, based on the analysis of structural similarities by means of QSAR and chemometric methods, is described. As a first step, a complete representation of chemical structures for examined chemicals (phenylureas and triazines) by different sets of molecular descriptors allows a preliminary exploration of similarity using multi-dimensional scaling (MDS). The use of genetic algorithm (GA) to select the most relevant molecular descriptors in modeling toxicity data makes it possible to develop predictive toxicity models. The final step is a similarity analysis, based again on MDS, using selected molecular descriptors, really relevant in describing the toxicological effect.

Humans↗

PubMed2001

Traditional versus WHIM molecular descriptors in QSAR approaches applied to fish toxicity studies.

Quantitative structure-activity relationships (QSAR) were performed on nine congenetic aromatic hydrocarbons. Acute response was evaluated in freshwater fish species. QSAR were built by Hansch's approaches and weighted holistic invariant molecular (WHIM) indices. The prediction power of QSAR from both approaches was evaluated. Single regression analysis derivated by Hansch's approach seem suitable for non-polar compounds. However, for all species, it has not a high predictive power (Q2(LOO)) of the biological activity from only K(ow) as molecular descriptor. Multiple regression analysis obtained from WHIM descriptors showed Q2(LOO) higher than 80%, indicating that molecular descriptors have a prediction power greater than K(ow).

Animals↗

PubMed1997

Hydroxylamine-induced cleavage of the asparaginyl-glycine motif in the production of recombinant proteins: the case of insulin-like growth factor I.

Hydroxylamine-induced cleavage at the asparaginyl-glycine dipeptide site inserted between the two moieties of recombinant fusion proteins has been used at both the analytical and the preparative scale to obtain the mature protein. In this study a model protein containing a fusion precursor of insulin-like growth factor I was used to investigate the influence of the operating conditions on the cleavage reaction and the formation of undesired side products such as hydroxamate and deamidated analogs. Moreover, the stability of the cleavage site toward deamidation was examined and a chemometric study performed to define the effect of the reaction conditions on the cleavage yield and on the formation of side products.

Amino Acid Sequence↗

PubMed1997

MS-WHIM, new 3D theoretical descriptors derived from molecular surface properties: a comparative 3D QSAR study in a series of steroids.

The recently proposed WHIM (Weighted Holistic Invariant Molecular) approach [Todeschini, R., Lasagni, M. and Marengo, E., J. Chemometrics, 8 (1994) 263] has been applied to molecular surfaces to derive new 3D theoretical descriptors, called MS-WHIM. To test their reliability, a 3D QSAR study has been performed on a series of steroids, comparing the MS-WHIM description to both the original WHIM indices and CoMFA fields. The analysis of the statistical models obtained shows that MS-WHIM descriptors provide meaningful quantitative structure-activity correlations. Thus, the results obtained agree well with those achieved using CoMFA fields. The concise number of indices, the ease of their calculation and their invariance to the coordinate system make MS-WHIM an attractive tool for 3D QSAR studies.

Computer Simulation↗

PubMed1997

3D-modelling and prediction by WHIM descriptors. Part 8. Toxicity and physico-chemical properties of environmental priority chemicals by 2D-TI and 3D-WHIM descriptors.

In environmental and ecotoxicological problems, the need for more general predictive models is one of the aims of the science. To reach this objective, the models, even if capable of producing more approximate values, must be applicable to the huge number of chemicals put on the market that are discharged in the environment, at least for setting priority lists among potentially hazardous substances. Theoretically, the problem is not insurmountable if one assumes that all properties of a chemical (physico-chemical, biological, toxicological) are related to its structural features. The challenge is to describe and represent, on a quantitative basis, all molecular structural features in order to use them as independent variables in a quantitative structure-activity model. In this paper, structural, topological, and 3D-WHIM descriptors are used for modelling toxicological and physico-chemical properties of compounds that are included in the European Union's so-called "List 1" of priority chemicals dangerous for the aquatic environment.

Animals↗

PubMed1995

Determination of platinum in plasma of patients affected by inoperable lung carcinoma treated with radiotherapy and concurrent low-dose continuous infusion of cis-dichlorodiammine platinum(II).

Platinum microquantities were determined in plasma of patients affected by lung carcinoma during treatment with radiotherapy (RT) and concurrent low-dose continuous infusion of cis-dichlorodiammineplatinum(II) (CDDP). RT was given at 50 Gy in continuous course; CDDP was continuously infused at 4 mg/m2 daily for 100 h/week for 5 weeks, and the infusions were separated by 68 h of rest. The percentage of free drug versus total drug in plasma was about 3%. It did not vary with therapy duration and was not significantly different from that found in 5-day continuous infusions at much higher daily doses. Nevertheless, maximal values of free Pt in plasma were very low and agreed with the low level of CDDP toxicity encountered on the present administration schedule.

Carcinoma↗

PubMed1994

A 3D QSAR approach to the search for geometrical similarity in a series of nonpeptide angiotensin II receptor antagonists.

A 3D QSAR methodology based on the combined use of conformational analysis and chemometrics was applied to perform a comparative analysis of the 3D conformational features of 13 nonpeptide angiotensin II receptor antagonists showing different levels of binding affinity. Conformational analysis by using a molecular mechanics MM2 method was carried out for each of these structures to obtain conformational minima. These minima were described by ten interatomic distances which define the relative spatial disposition of five significant atoms belonging to relevant functional groups present in all the 13 molecules. The structure-activity relationship between the interatomic distances and the biological activity was then assessed by using chemometric methods (cluster analysis, principal component analysis, classification methods). With our indirect approach based on the search for geometrical similarity it was possible, even though structural information on the receptor active site was lacking, to identify the 3D geometrical requirements for the binding affinity of nonpeptide angiotensin II receptor inhibitors.

Amino Acid Sequence↗

PubMed1992

Pharmacophore identification by molecular modeling and chemometrics: the case of HMG-CoA reductase inhibitors.

A methodology based on molecular modeling and chemometrics is applied to identify the geometrical pharmacophore and the stereoelectronic requirements for the activity in a series of inhibitors of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase, an enzyme involved in cholesterol biosynthesis. These inhibitors present two common structural features - a 3,5-dihydroxy hepatanoic acid which mimics the active portion of the natural substrate HMG-CoA and a lipophilic region which carries both polar and bulky groups. A total of 432 minimum energy conformations of 11 homologous compounds showing different levels of biological activity are calculated by the molecular mechanics MM2 method. Five atoms are selected as representatives of the relevant fragments of these compounds and three interatomic distances, selected among 10 by means of a Principal Component Analysis (PCA), are used to describe the three-dimensional disposition of these atoms. A cluster analysis procedure, performed on the whole set of conformations described by these three distances, allows the selection of one cluster whose centroid represents a geometrical model for the HMG-CoA reductase pharmacophore and the conformations included are candidates as binding conformations. To obtain a refinement of the geometrical model and to have a better insight into the requirements for the activity of these inhibitors, the Molecular Electrostatic Potential (MEP) distributions are determined by the MNDO semiempirical method.

Electrochemistry↗

PubMed1991

Structure-activity relationship of Ca2+ channel blockers: a study using conformational analysis and chemometric methods.

A structure-activity relationship study has been done on 8 compounds with the activity known as 'Ca2+ channel blockers'. Conformational analysis was carried out using a molecular mechanics method. The 3D-QSAR approach was used and the most polar functional groups present in all the molecules were considered. Eight interatomic distances are necessary to define the relative spatial disposition of these relevant molecular fragments. The structure-activity relationship between interatomic distances and biological activity was performed using statistic and chemometric methods. In particular, with Principal Component Analysis, it was possible to reduce the number of interatomic distances: only six of the eight distances are sufficient to describe the system in a useful way. A classification method was iteratively used to select the most probable conformations linked to the biological activity and to build a model able to classify conformations according to their biological behaviour. Cluster analysis on the active selected conformations subsequently allowed the identification of two different geometrical patterns for the active compounds. Finally the validity of the model was verified by correctly predicting the activity of other molecules not used in the construction of the model but possessing known activity.

Calcium Channel Blockers↗

PubMed1987

External ophthalmomyiasis. Report of four cases.

Four cases of external ocular myiasis caused by larvae of Oestrus ovis are reported. Each patient showed some degree of inflammation in the lids and conjunctiva. Regression was only subsequent to removal of parasites from the eye. Two patients had respiratory signs, i.e. rhinitis. For one of these two cases, a short-time admission in the resuscitation unit was recommended following a noticeable bronchospasm. The pathogenetic mechanism of this respiratory distress is not known. Two hypotesis are made.

Adult↗

PubMedDate not supplied

Toward an in vitro test for the diagnosis of allergy to penicillins. Synthesis, characterization, and use of beta-lactam and beta-lactam metabolite poly-L-lysines which recognize human IgE antibodies.

Conjugates of poly-L-lysine (PLL) containing a penicillin or a penicilloyl residue were prepared and characterized by 1H NMR and by size-exclusion (SE) HPLC. These conjugates were used in a radio allergo sorbent tests (RAST) test for the determination of allergy toward beta-lactams. The chemiometric evaluation of the data indicates that allergy to amoxycillin is different from allergy to the other beta-lactams tested. Furthermore, careful chemical characterization of the conjugates appears to be crucial to obtain meaningful information from the RAST data.

Chromatography, High Pressure Liquid↗

PubMedDate not supplied

Characterization of DNA primary sequences by a new similarity/diversity measure based on the partial ordering.

The similarity/diversity measures play a fundamental role in library searching, virtual screening, and quantitative structure-activity relationship/quantitative structure-property relationship modeling as well as in genomics and proteomics. In this paper, a new similarity/diversity measure is proposed as a new approach for the analysis of sequential data, where useful information can be also obtained by the ordering relationships between the sequence elements. This methodology can be applied for evaluating molecular similarity/diversity, using sets of sequential descriptors, and for evaluating the similarity between spectra, sensor arrays, and other sequential data such as DNA and protein sequences. The new proposed distance (weighted standardized Hasse distance) is evaluated between pairs of Hasse matrices derived from the classical partial-ordering rules. It can be naturally standardized, thus allowing the interpretation of these distances as absolute values (e.g., percentage) and deriving simple similarity and correlation indices. A simple example is taken to highlight the behavior of the new similarity/diversity measure on DNA sequences taken from the first exons of the beta-globins for eight different species. Sensitivity analysis has been also performed, showing the high capability of this measure to take into account small modifications of the DNA sequences. Finally, a comparison with results obtained from the literature is given, together with a comparison with matrix invariants derived from the Hasse matrix.

Base Sequence↗