Biomedical subjects

M Novic

Publications and source records attributed to M Novic.

15 recordsLinked to original sources

PubMed2006

Novel numerical and graphical representation of DNA sequences and proteins.

We have introduced novel numerical and graphical representations of DNA, which offer a simple and unique characterization of DNA sequences. The numerical representation of a DNA sequence is given as a sequence of real numbers derived from a unique graphical representation of the standard genetic code. There is no loss of information on the primary structure of a DNA sequence associated with this numerical representation. The novel representations are illustrated with the coding sequences of the first exon of beta-globin gene of half a dozen species in addition to human. The method can be extended to proteins as is exemplified by humanin, a 24-aa peptide that has recently been identified as a specific inhibitor of neuronal cell death induced by familial Alzheimer's disease mutant genes.

Cell Death↗

PubMed2004

Prediction of selectivity of alpha1-adrenergic antagonists by counterpropagation neural network (CP-ANN).

A quantitative structure-selectivity relationships of series of structurally diverse alpha1-adrenergic antagonists was performed by using counter-propagation neural network (CP-ANN). The theoretical molecular descriptors have been calculated and selected using CODESSA program. The results obtained for a highly non-congeneric set of molecules have confirmed the potential of use of CP-ANN approach in prediction of relative activity (selectivity) of alpha1-adrenergic antagonists.

Adrenergic alpha-Antagonists↗

PubMed2002

Novel matrix invariants for characterization of changes of proteomics maps.

Previous studies on mathematical characterization of proteomics maps by sets of map invariants were based on the construction of a set of distance-related matrices obtained by matrix multiplication of a single matrix by itself. Here we consider an alternative characterization of proteomics maps based on a set of matrices characterizing local features of an embedded zigzag curve over the map. It is shown that novel invariants can well characterize proteomics maps. Advantages of the novel approach are discussed.

Models, Theoretical↗

PubMed2001

Computer simulation of ion chromatography separation: an algorithm enabling continuous monitoring of anion distribution on an ion-exchange chromatography column.

A computer algorithm for the calculation of ion chromatography separation is presented. It is based on the calculation of equilibrium concentrations of present analyte in discrete column segments. The continuous column is treated as a number of discrete cells or segments where the equilibration process between the stationary phase and the eluent is simulated. The ion-exchange equilibration process is supposed to be instantaneous and quantitative. The continuous flow of the eluent is rendered by discrete transfers. The size of each transfer of the eluent corresponds to a portion of the volume contained in one column segment. The equilibrium calculations in all column segments are repeated for each transfer of the eluent, through all the stages of the chromatographic process. The distribution of the analytes between the stationary phase and the eluent can be monitored at any step and in any column segment which means that the described algorithm provides the spatial and time concentration profiles. The simulated chromatogram is acquired as a time-concentration profile in the last column segment. The obtained chromatograms are in good agreement with the experimental ones. The distribution of ions between the stationary phase and the eluent in the early stages of the ion chromatographic process can thus be studied with confidence.

Algorithms↗

PubMed2001

Effect of organic solvents in the on-line thermal lens spectrometric detection of chromium(III) and chromium(VI) after ion chromatographic separation.

The effect of methanol, acetone and acetonitrile on the sensitivity, selectivity and the detection limits (LODs) of the determination of chromium species by ion chromatography was investigated. A collinear dual-beam thermal lens spectrometer was used for the direct detection of chromium complexes [pre-column derivatized Cr(III)-pyridine-2,6-dicarboxylic acid, and post-column derivatized Cr(VI)-1,5-diphenylcarbazide] following the ion chromatographic separation on a Dionex HPIC-CS5A solvent compatible column. Different amounts of organic solvents were added directly to the eluent (up to 30%) and to the post-column reagent (up to 60%) to improve the thermooptical properties of the solvents. Consequently, the sensitivity of the technique was increased by a factor of 2-3 and LODs of 0.1 and 10 microg dm(-3) were achieved for Cr(VI) and Cr(III), respectively, when the eluent reaching the detector contained 30% of acetonitrile. The addition of organic solvents also resulted in significant changes in retention times, which improved the Cr(III)/Cr(VI) separation.

Chromatography, Liquid↗

PubMed2001

Ion-exchange-based eluent-free preconcentration of some anions.

Preconcentration procedures based on ion-exchange methods are often used to enhance the sensitivities of analytical techniques where the eluent used for eluting the preconcentrated ions does not influence the subsequent analytical step. Until recently, only a limited use of ion-exchange-based sample preconcentration procedures has been found in those analytical techniques where the eluent components strongly influence the separation procedure [e.g., capillary electrophoresis (CE)]. In this paper, we present a preconcentration procedure based on (i) the preconcentration of anions on an ion-exchange resin, (ii) the subsequent elution of analytes, and (iii) on-line removal of eluent components by chemical suppression using an appropriate suppressor device (either packed-bed suppressor column or micromembrane suppressor). The adjustment of the system parameters, combined with a computer-controlled, sensing/switching system, resulted in a minimal additional dilution of the eluted preconcentrated anions. The efficiency of the proposed enrichment/matrix removal procedure was tested by using off-line CE analysis of collected preconcentrated samples, reaching a LOD of 1 microg/l for a selected anion.

Anions↗

PubMed2000

Ion exchange-based preconcentration for the determination of anions by capillary electrophoresis.

In the present paper a capillary zone electrophoresis (CZE)-compatible preconcentration technique for anions, based on ion exchange, is described. The described preconcentration approach has found limited use until recently because of the inherent elution step that leads to contamination of the sample with eluent components. In this paper, we describe an improved anion exchange-based preconcentration technique in which contamination of the sample with the eluent constituents, which occurs during anion elution from the preconcentration column, is eliminated by on-line chemical suppression on a packed-bed suppressor column. In the present communication, the basic principles of the proposed anion enrichment system are presented. The system was optimized, resulting in a minimal additional dilution of the eluted sample plug. This was achieved by the use of a computer-controlled, sensing/switching system. The effectiveness of the developed method was later tested on the determination of some anions in a synthetic sample using CE apparatus.

Anion Exchange Resins↗

PubMed2000

Automatic calibration in capillary electrophoresis.

A direct, completely automated calibration procedure in capillary electrophoresis (CE) is presented. The manual calibration operations involved in analytical methods, such as external calibration, standard addition, and internal standard, were accomplished with a continuous flow system (CFS) coupled to commercial capillary electrophoresis equipment via a programmable arm. The system was managed by the proper CE microprocessor and allowed automatic calibration and direct quantification of the analytes in the sample without any manual pretreatment, therefore avoiding or minimizing manually associated errors. The whole system including peristaltic pumps and the programmable arm was connected via an electronic interface and completely controlled by a computer using a program written in GW-BASIC. The potential of this new CFS-CE arrangement was assessed by applying it to samples containing selected compounds.

Automation↗

PubMed1999

Determination of bromide, bromate and other anions with ion chromatography and an inductively coupled plasma mass spectrometer as element-specific detector.

An implementation of the Dionex IonPac AS12A analytical column with an element-specific ICP-MS detection is described for the simultaneous determination of halogen and oxyhalogen anions, sulfate, phosphate, selenite, selenate and arsenate. The chromatographic separation was achieved in less than 4 min with an aqueous 11 mM (NH4)2CO3 (pH 11.2, adjusted with aqueous ammonia) as eluent. Special emphasis was given to optimize the ICP-MS detection conditions for the reliable detection (RSD<5%) of bromate and bromide at a bromine concentration level of 1.0 microg l(-1) with 50 microl sample injection volume. In order to achieve the highest detector response for bromine species an ultrasonic nebulizer equipped with a membrane desolvator had to be employed. The detection limits (S/N=3, sample injection volume 50 microl) obtained with the IC-ICP-MS after the optimization were 0.67 microg l(-1) for BrO3-, 0.47 microg l(-1) for Br-, 69 microg l(-1) for ClO2-, 4 microg l(-1) for Cl-, 47 microg l(-1) for ClO3-, 13 microg l(-1) for SO4(2-), 36 microg l(-1) for PO4(3-), 0.4 microg l(-1) for SeO3(2-), 0.3 microg l(-1) for SeO4(2-), and 0.4 microg l(-1) for AsO4(3-).

Anions↗

PubMed1997

Carbonate interferences by ion chromatographic determination of anions in mineral waters.

The high content of hydrogen carbonate anions and dissolved CO2 in some mineral waters interfere with the determination of anions in such samples by ion chromatography. It was found that the irreproducibility of retention times of all anions present in the samples was caused by on-column neutralisation of CO(3)2- to HCO3- by CO2. Microbubbles of CO2 released downstream by the suppressor inhibited exchange of Na+ with H3O+ resulting in lower conductivity and consequently in the decrease of chloride peak. To avoid peak deformation and overlapping caused by carbonate species, they should be removed by acidification followed by CO2 elimination in a gas separation unit. To prevent sample contamination by the anion of the added acid, the electrodialytic clean-up procedure was applied. The liberated CO2 was removed in a microporous Gore-Tex semipermeable tubing connected in series with the dialytic cell. The developed dialytic clean-up procedure was applied to the analysis of some typical mineral waters.

Anions↗

PubMed1996

Solid-phase extraction coupled with electrochemical detection for the determination of the herbicide bromofenoxim in water samples at low- and sub-microgram l-1 levels.

The application of solid-phase extraction (SPE) as a preconcentration and clean-up step with subsequent off-line flow injection amperometric (FI-AD) or batch square-wave voltammetric (SWV) detection of the herbicide bromofenoxim was developed. The selection of an appropriate organic eluent, some parameters influencing the efficiency of the SPE and the electrochemical detection of bromofenoxim in the organic effluent solution were thoroughly investigated. Undiluted acetonitrile with SWV and acetonitrile-water (80 + 20) with FI-AD, both containing 0.1 mol l-1 LiClO4, were chosen as the most appropriate SPE eluents. The addition of LiClO4 as supporting electrolyte to the eluent and acidification of a water sample to 1 x 10(-3) mol l-1 HClO4 (pH 3) prior to the SPE procedure were found to improve greatly the current response on mercury drop (SWV) and mercury film (FI-AD) electrodes. Subsequent to the SPE procedure, the effluents were transferred to the voltammetric cell or injected into the flow injection system without any further treatment. The calibration plots obtained for bromofenoxim in pure water samples were linear over the ranges 0.2-12.0 micrograms l-1 and 3.0-120 micrograms l-1, with calculated detection limits of 0.05 and 1.5 micrograms l-1 (100 ml samples), for the SPE-SWV and SPE-FI-AD procedures, respectively. The actual detection capabilities of the proposed methods depend on the water sample volumes applied to the extraction cartridges. The recoveries of the over-all procedures, applying spiked tap water samples, and the corresponding RSDs were 92% and 6% (n = 6) and 121% and 9% (n = 7) for SPE-SWV and SPE-FI-AD, respectively. The practical applicability of the proposed methods for the analysis of ground and tap water samples was confirmed via an inter-laboratory test on a tap water sample containing five common pesticides including bromofenoxim.

Benzaldehydes↗

PubMedDate not supplied

Prediction of enzyme binding: human thrombin inhibition study by quantum chemical and artificial intelligence methods based on X-ray structures.

Thrombin is a serine protease which plays important roles in the human body, the key one being the control of thrombus formation. The inhibition of thrombin has become a target for new antithrombotics. The aim of our work was to (i) construct a model which would enable us to predict Ki values for the binding of an inhibitor into the active site of thrombin based on a database of known X-ray structures of inhibitor-enzyme complexes and (ii) to identify the structural and electrostatic characteristics of inhibitor molecules crucially important to their effective binding. To retain as much of the 3D structural information of the bound inhibitor as possible, we implemented the quantum mechanical/molecular mechanical (QM/MM) procedure for calculating the molecular electrostatic potential (MEP) at the van der Waals surfaces of atoms in the protein's active site. The inhibitor was treated quantum mechanically, while the rest of the complex was treated by classical means. The obtained MEP values served as inputs into the counter-propagation artificial neural network (CP-ANN), and a genetic algorithm was subsequently used to search for the combination of atoms that predominantly influences the binding. The constructed CP-ANN model yielded Ki values predictions with a correlation coefficient of 0.96, with Ki values extended over 7 orders of magnitude. Our approach also shows the relative importance of the various amino acid residues present in the active site of the enzyme for inhibitor binding. The list of residues selected by our automatic procedure is in good correlation with the current consensus regarding the importance of certain crucial residues in thrombin's active site.

Algorithms↗

PubMedDate not supplied

On 3-D graphical representation of proteomics maps and their numerical characterization.

We consider numerical characterization of proteomics maps by representing a map as a three-dimensional graphical object based on x, y coordinates of the spots and using their relative abundance as the z coordinate. In our representation the protein spots are first ordered based on their relative abundance and labeled accordingly. In the next step a 3-D path is constructed connecting spots having adjacent labels. Finally a matrix is constructed by assigning to each pairs of labels (i, j) matrix element, the numerical value of which is based on the quotients of the Euclidean distance and the distance along the 3-D zigzag between the two points. The approach has been illustrated on a fragment of a proteomics map and compared with 2-D graphical representation of proteomics maps.

Computer Graphics↗

PubMedDate not supplied

Enzyme binding selectivity prediction: alpha-thrombin vs trypsin inhibition.

In the present work we explore the possibility of an in-depth computational analysis of available experimental X-ray structures in the specific case of a series of alpha-thrombin and trypsin complexes with their respective inhibitors for the development of a novel scoring function based on molecular electrostatic potential computed at the contact surface in the enzyme-inhibitor molecular complex. We subsequently employ the chemometrical approach to determine which are the interactions in the large volume of data that determine the resulting experimental binding constant between ligand and receptor. The results of the model evaluated with molecules in the independent validation set show that a reasonable average error of 1.30 log units of the difference between experimental and calculated binding constants was achieved in the system thrombin-trypsin, which is comparable with those of methods from the literature. Furthermore, by a careful preparation of the Kohonen top layer in the artificial neural network approach that is normally perceived as a "black box device", we have been able to follow the implications of the structure of the inhibitor-enzyme complex for the inhibitor's binding constant. The method appears to be suitable for evaluation of selectivity in structurally similar enzymatic systems, which is currently an important problem in drug design.

Algorithms↗

PubMedDate not supplied

Application of counterpropagation artificial neural network for modelling properties of fish antibiotics.

The present study focuses on fish antibiotics which are an important group of pharmaceuticals used in fish farming to treat infections and, until recently, most of them have been exposed to the environment with very little attention. Information about the environmental behaviour and the description of the environmental fate of medical substances are difficult or expensive to obtain. The experimental information in terms of properties is reported when available, in other cases, it is estimated by standard tools as those provided by the United States Environmental Protection Agency EPISuite software and by custom quantitative structure-activity relationship (QSAR) applications. In this study, a QSAR screening of 15 fish antibiotics and 132 xenobiotic molecules was performed with two aims: (i) to develop a model for the estimation of octanol--water partition coefficient (logP) and (ii) to estimate the relative binding affinity to oestrogen receptor (log RBA) using a model constructed on the activities of 132 xenobiotic compounds. The custom models are based on constitutional, topological, electrostatic and quantum chemical descriptors computed by the CODESSA software. Kohonen neural networks (self organising maps) were used to study similarity between the considered chemicals while counter-propagation artificial neural networks were used to estimate the properties.

Animals↗