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Biomedical subjects

F Darvas

Publications and source records attributed to F Darvas.

At least 19 recordsLinked to original sources
PubMed2005

Application of main component fraction collection method for purification of compound libraries.

In order to support high-throughput library purification, a novel UV triggered fraction collection method was developed in which a maximum-seeking-algorithm-driven, six-port valve collects the largest chromatographic peak. This straightforward strategy achieves the one sample-one fraction approach, thus resulting in a simpler and less error prone workup procedure. The effectiveness of this main component fraction collection method will be illustrated here by the results of the purification of compound libraries (altogether 6086 compounds, having an averaged success rate of 79.4%). Advanced applications, where the desired component differs from the main component, will also be discussed.

Chemical Fractionation↗
PubMed2005

Investigations of dipole localization accuracy in MEG using the bootstrap.

We describe the use of the nonparametric bootstrap to investigate the accuracy of current dipole localization from magnetoencephalography (MEG) studies of event-related neural activity. The bootstrap is well suited to the analysis of event-related MEG data since the experiments are repeated tens or even hundreds of times and averaged to achieve acceptable signal-to-noise ratios (SNRs). The set of repetitions or epochs can be viewed as a set of independent realizations of the brain's response to the experiment. Bootstrap resamples can be generated by sampling with replacement from these epochs and averaging. In this study, we applied the bootstrap resampling technique to MEG data from somatotopic experimental and simulated data. Four fingers of the right and left hand of a healthy subject were electrically stimulated, and about 400 trials per stimulation were recorded and averaged in order to measure the somatotopic mapping of the fingers in the S1 area of the brain. Based on single-trial recordings for each finger we performed 5000 bootstrap resamples. We reconstructed dipoles from these resampled averages using the Recursively Applied and Projected (RAP)-MUSIC source localization algorithm. We also performed a simulation for two dipolar sources with overlapping time courses embedded in realistic background brain activity generated using the prestimulus segments of the somatotopic data. To find correspondences between multiple sources in each bootstrap, sample dipoles with similar time series and forward fields were assumed to represent the same source. These dipoles were then clustered by a Gaussian Mixture Model (GMM) clustering algorithm using their combined normalized time series and topographies as feature vectors. The mean and standard deviation of the dipole position and the dipole time series in each cluster were computed to provide estimates of the accuracy of the reconstructed source locations and time series.

Brain Mapping↗
PubMed2004

Mapping human brain function with MEG and EEG: methods and validation.

We survey the field of magnetoencephalography (MEG) and electroencephalography (EEG) source estimation. These modalities offer the potential for functional brain mapping with temporal resolution in the millisecond range. However, the limited number of spatial measurements and the ill-posedness of the inverse problem present significant limits to our ability to produce accurate spatial maps from these data without imposing major restrictions on the form of the inverse solution. Here we describe approaches to solving the forward problem of computing the mapping from putative inverse solutions into the data space. We then describe the inverse problem in terms of low dimensional solutions, based on the equivalent current dipole (ECD), and high dimensional solutions, in which images of neural activation are constrained to the cerebral cortex. We also address the issue of objective assessment of the relative performance of inverse procedures by the free-response receiver operating characteristic (FROC) curve. We conclude with a discussion of methods for assessing statistical significance of experimental results through use of the bootstrap for determining confidence regions in dipole-fitting methods, and random field (RF) and permutation methods for detecting significant activation in cortically constrained imaging studies.

Brain Mapping↗
PubMed2004

Recent advances in chemical genomics.

Chemical genomics, which utilizes specially designed small chemical compounds early in the discovery phase of new drugs to explore the life science at various levels, can address biological questions that are not amenable to genetic manipulation or functional genomics/proteomics approaches. Following the development of HT phenotypic assays and DNA expression analysis, the integration of cell-based assays with activity / affinity-based approaches allows us to interrogate the cells by analyzing phenotypic alterations, changes of transcript signature or detecting the differences in protein expression levels. Furthermore, activity / affinity-based techniques directly provide a druggable subset of gene products, which interact with small molecules, greatly reducing the complexity of analyzing the proteome. In this paper, we give an account of the recent advances (approaches and strategies) in the field of chemical genomics, and discuss how these approaches enable the investigator to obtain a novel therapeutically relevant target as well as drug candidates acting on them in a target-specific manner. This novel post-genomic discovery strategy, where target identification/ validation is carried out by interactions with small molecules, could significantly reduce the time-scale for early drug discovery, and increase the success rate of finding novel, druggable targets, as well as more specific drug candidates.

Animals↗
PubMed2002

Spatiotemporal imaging of electrical activity related to attention to somatosensory stimulation.

The aim of the present study was to localize the effects of spatial attention on somatosensory stimulation in EEG. Median and tibial nerve were stimulated at all four limbs in a random order. Subjects were instructed to count the events on either the right median or the right tibial nerve. Attention-induced changes in the somatosensory evoked potentials (SEP) were revealed by subtracting the median nerve SEPs recorded while subjects attended to stimuli applied to the tibial nerve from those obtained during attention to the stimulated hand. In a current density reconstruction approach source maxima in the time range from 30 to 260 ms after median nerve stimulation were localized and the time courses of activation were elaborated by dipole modeling. Six regions were identified which contribute significant source activity related to selective spatial attention: contralateral postcentral gyrus (Brodman area (BA) 3), contralateral mesial frontal gyrus (BA 6), right posterior parietal cortex (BA 7), anterior cingulate gyrus (BA 32), and bilateral middle temporal gyrus (BA 21). Activation started at the right posterior parietal cortex, followed by the contralateral middle temporal gyrus, probably representing SII activity, and the middle frontal and anterior cingulate gyrus. Similar regions of source activation were revealed by tibial nerve SEP, but the effect was less pronounced and restricted almost entirely to activation of the contralateral postcentral gyrus (BA 3), anterior cingulate gyrus (BA 32), and ipsilateral middle temporal gyrus (BA 21). Our data provide evidence for a spatially separated frontal generator within the anterior cingulum, dependent on selective attention in the somatosensory modality.

Adult↗
PubMed2001

Spatio-temporal source imaging reveals subcomponents of the human auditory mismatch negativity in the cingulum and right inferior temporal gyrus.

We investigated the generators of the mismatch negativity by means of spatio-temporal source imaging on the basis of 64-channel electroencephalography data in order to study the time course and localization of proposed frontal sources. Results indicate that there are additional generators located both within the anterior cingulate gyrus and in the right inferior temporal gyrus, clearly separated from the supratemporal generators in space and time course. The cingulate generator is activated later than the temporal ones, which supports the hypothesis of a frontally located mechanism of involuntary switching of attention triggered by the temporal change detection system. Evidence for an additional right inferior temporal generator supports the hypothesis of right hemispheric dominance in early sound discrimination.

Acoustic Stimulation↗
PubMed2001

Spatio-temporal current density reconstruction (stCDR) from EEG/MEG-data.

Among the different approaches to the bioelectromagnetic inverse problem, the current-density reconstruction methods (CDR) provide the most general solutions. Since the inverse problem does not have a unique solution, model assumptions have to be taken into account. Multi-channel measurements contain not only spatial, but also temporal information about the sources, so a naturally extension to existing methods leads to spatio-temporal model constraints. Spatio-temporal CDR's (stCDR) have been tested in simplified volume conductor models, assuming different spatial model constraints and a smooth temporal activation model. Comparison to existing spatial model constraints showed a significant improvement of spatial and temporal resolution of the reconstructed sources for the spatio-temporal models especial in noisy data.

Algorithms↗
PubMed2001

Numerical aspects of spatio-temporal current density reconstruction from EEG-/MEG-data.

The determination of the sources of electric activity inside the brain from electric and magnetic measurements on the surface of the head is known to be an ill-posed problem. In this paper, a new algorithm which takes temporal a priori information modeled by the smooth activation model into account is described and compared with existing algorithms such as Tikhonov-Phillips.

Algorithms↗
PubMed1997

Prediction of distribution coefficient from structure. 1. Estimation method.

A method has been developed for the estimation of the distribution coefficient (D), which considers the microspecies of a compound. D is calculated from the microscopic dissociation constants (microconstants), the partition coefficients of the microspecies, and the counterion concentration. A general equation for the calculation of D at a given pH is presented. The microconstants are calculated from the structure using Hammett and Taft equations. The partition coefficients of the ionic microspecies are predicted by empirical equations using the dissociation constants and the partition coefficient of the uncharged species, which are estimated from the structure by a Linear Free Energy Relationship method. The algorithm is implemented in a program module called PrologD.

Algorithms↗
PubMed1997

Prediction of distribution coefficient from structure. 2. Validation of Prolog D, an expert system.

Prolog D is a program that formalizes, in a controllable and reproducible manner, an algorithm developed to predict distribution coefficients of ionizable compounds at a given pH and varying counterion concentrations. Its predictive power has been evaluated with experimental log D values measured under standard conditions of buffers and ionic strength. Calculations were performed with the three different options for the estimation of partition coefficients (log P) implemented in the program. Considering the diversity of test compounds as well as the present state of the art in log P and pKa predictions, Prolog D proved to be very efficient and can be used as a tool to provide lipophilicity data. Prediction patterns and correlations with the observed data are of almost equal quality for all options, permitting acceptable results for 80% of the data.

Chemistry, Physical↗
PubMed1985

Quantitative structure-stability relationships among inclusion complexes of cyclodextrins. I: Barbituric acid derivatives.

Quantitative structure-stability relationships (QSSRs) are formulated for the inclusion complexation of 17 barbituric acid derivatives with alpha- and beta-cyclodextrin. The variation in the complex stability constants K alpha and K beta is found to be partly accounted for by the molar refractivity or the hydrophobicity of the substituent R1 at position 5 of the barbiturate ring. In addition, K alpha also depends upon whether or not R1 is branching or cyclic, and K beta also depends upon whether the guest molecule is a barbiturate or a thiobarbiturate. The results suggest that in alpha-cyclodextrin-barbiturate complexes the cyclodextrin cavity includes only R1, while in beta-cyclodextrin complexes both R1 and (part of) the barbiturate ring are included. This complexation model is compared with those proposed by other authors.

Barbiturates↗
PubMed1983

Homologous partial sequences in dehydrogenases.

Such details of the primary structure were sought that are common in all dehydrogenases of known amino acid sequence. Twenty-six sequences of eight kinds of dehydrogenase (D-glyceraldehyde-3-phosphate dehydrogenase, alcohol dehydrogenase, lactate dehydrogenase, glutamate dehydrogenase, glycerol-3-phosphate dehydrogenase, ribitol dehydrogenase, L-hydroxyacyl-CoA dehydrogenase and homoserine dehydrogenase) have been compared by the aid of the artificial intelligence language Prolog, the amino acids being classified into groups according to their chemical properties, and alpha-helix or beta-sheet-forming abilities. We found tetrapeptides that occurred in all dehydrogenases examined. By using these tetrapeptides as markers a population of 84 partial sequences has been described. The partial sequences constituting this population are peptides comprising 35 residues. It has been shown statistically that these peptides form a homogeneous sample as regards the frequency of occurrence of amino acid groups. This statistically homogeneous partial sequences can be regarded as homologous and it is assumed that their presence is characteristic of dehydrogenases.

Amino Acid Sequence↗
PubMed1979

Investigation of the common mechanism of action of antibacterial compounds containing gamma-pyridone-beta-carboxylic acid structure by principal component.

On the basis of 576 in vitro antibacterial positive results of 99 compounds containing gamma-pyridone-beta-carboxylic acid structure conclusions have been drawn on the mechanism of action of the derivatives by principal component analysis. It has been found that the compounds exert their effect essentially by influencing two types of physiological processes or series of processes. The more important of the two "mechanisms", responsible for 50-95% of the activity of the compounds, is common for the compounds investigated, and is associated with the gamma-pyridone-beta-carboxylic acid structure.

Anti-Bacterial Agents↗
PubMed1978

Logic-based program system for predicting drug interactions.

This paper deals with the application of an AI language, based on mechanical theorem prover (PROLOG), to deduce drug interactions. One hundred and thirty-one drug interactions were predicted by logical deduction with a program system comprising about 52 drugs in practice and 32 independent possibilities of deduction. The database of the system contains the chemical and pharmaceutical characteristics of the active components of the drug preparations, and the deductions are based on general pharmacokinetic, pharmacodynamic or other biochemical relationships concerning interactions.

Computers↗
PubMed1975

Substituted cycloalkanol ethers of psychostimulant activity: studies on quantitative structure-activity relationships.

Quantitative relationships between chemical structures and locomotor activities of 20 substituted cycloalcanol basic ethers have been investigated using Hansch- and Free-Wilson methods. The Hansch-type regression analysis performed on 10 compounds having different cycloalkyl-rings revealed the highly significant role of the hydrophobic characteristics on the activity tested. The QSAR-study of 20 cycloalcanol-ethers according to Free and Wilson gave a significant equation with good statistical indices. On the basis of the results the compounds under study appear not to exert their activity through interaction with receptor raising strict sterical and electrical requirements.

Animals↗