Publications by authors named "Todorov N"

A 60-year-old polymorbid patient developed severe metabolic acidosis during weeks of treatment with flucloxacillin and paracetamol. The acidosis was triggered by an accumulation of 5-oxoproline due to pre-existing risk factors for glutathione deficiency as well as a ketoacidosis due to starvation. After treatment with N-acetylcysteine and hemofiltration, the acidosis completely resolved.

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Micro- and nanoflowers are a class of materials composed of particles with high surface-to-volume ratio. They have been extensively studied in the last decade due to simple preparation protocols and promising applications in biosensing, as drug delivery agents, for water purification, and so on. Flowerlike objects, due to their highly irregular surface, may act also as plasmonic materials, providing resonant coupling between optical waves and surface plasmon excitations.

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Objective: Greater hope and self-compassion have individually been associated with lower psychological distress in women with breast cancer. Self-compassion is also associated with lower body image distress in this population, yet it is unknown whether hope also has this association. This study aimed to investigate the extent to which hope accounts for body image distress and psychological distress in breast cancer survivors alone, and in direct comparison to self-compassion.

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Aim: The aim of this publication is to present a case of CMV infection during pregnancy, with clinical manifestations of the development of microcephaly and simultaneous dilatation of the 3rd and 4th brain ventricle at 23 weeks gestation. This article discusses the role of ultrasound screening in the second trimester of pregnancy.

Case Presentation: We present the case of a 25-year-old woman with the initials S.

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[EARLY DETECTION OF PREECLAMPSIA].

Akush Ginekol (Sofiia)

September 2016

Unlabelled: The preeclampsia is one of the most serious complications in the second half of the pregnancy with a high risk of perinatal maternal and neonatal mortality. The study is aiming to determine which pregnant women have a higher risk of developing preeclampsia with a view to the subsequent antenatal care, on the base of the individual factors.

Material And Metods: From prospectively followed pacients is collected information by a questionnaire and sonographic examination at 11-13 weeks of gestation/w.

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Background And Objectives: Forgiveness has been found to be a useful intervention for past trauma across a variety of situations. However, this has yet to be experimentally tested in victims of bullying. The aim of the current study was to evaluate the impact of imagining forgiveness, avoidance, or revenge responses towards a perpetrator among young adult victims of bullying.

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Forgiveness has been shown to be a helpful strategy for victims of many different forms of abuse and trauma. It has also been theoretically linked to positive outcomes for victims of bullying. However, it has never been experimentally manipulated in a school bullying context.

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The structural data and Raman spectra of distorted R(3+)B(3+)O(3) perovskites (R(3+)-rare earth, B(3+)=Al, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Ga) with BO(6) octahedral tilts were critically reviewed in order to obtain the frequency (ω) versus BO(6) tilt angle (α) dependence of the quasi-soft vibrational modes. It was found that the relation ω = ϰα is satisfied in a good approximation for each RBO(3) family with fixed B atom, despite the different spatial tilt orientations for compounds of the same series with either orthorhombic Pnma or rhombohedral R ̅3c structure. The dependence of the proportionality coefficient ϰ on the averaged octahedral distance can be described using different functions (power, linear and exponential ones).

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Samples, representing Si matrix with nanoformations of the semiconducting silicides beta-FeSi2 and Mg2Si are studied by Raman scattering. The unpolarized Raman spectra of the samples are interpreted in the framework of the appearance of interface-phonon polaritons. The theoretical dispersion relations of the interface-phonon polaritons in the system Si/silicide/Si are obtained from the Maxwell equations.

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We present two comparative models of the GABA(A) receptor. Model 1 is based on the 4-A resolution structure of the nicotinic acetylcholine receptor from Torpedo marmorata and represents the unliganded receptor. Two agonists, GABA and muscimol, two benzodiazepines, flunitrazepam and alprazolam, together with the general anaesthetic halothane, have been docked to this model.

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The structure of many receptors is unknown, and only information about diverse ligands binding to them is available. A new method is presented for the superposition of such ligands, derivation of putative receptor site models and utilization of the models for screening of compound databases. In order to generate a receptor model, the similarity of all ligands is optimized simultaneously taking into account conformational flexibility and also the possibility that the ligands can bind to different regions of the site and only partially overlap.

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The recent lapse in productivity in the pharmaceutical industry has facilitated the emergence of experimental and in silico structure-based design methodologies, based on identification of biologically active low molecular weight fragments that can be exploited to produce potential drug candidates with diverse chemistries. SkelGen, an in silico example of this methodology, is reviewed. The ability of this algorithm to identify chemically diverse low molecular weight fragments that would potentially bind to DNA gyrase is recounted, as is the first purely de novo structure-based design of five compounds that show at least micromolar activity against the estrogen receptor.

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We present a de novo design approach to generating small fragments in the DNA-gyrase ATP-binding site using the computational drug design platform SkelGen. We have generated an exhaustive number of structural possibilities, which were subsequently filtered for site complementarity and synthetic tractability. A number of known active fragments are found, but most of the species created are potentially novel and could be valuable for further elaboration and development into lead-like structures.

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We investigate the influence of variations of ligand protonation and tautomeric states on the protein-ligand binding energy landscape by applying the concept of structural consensus. In docking simulations, allowing full flexibility of the ligand, we explore whether the native binding mode could be successfully recovered using a non-native ligand protonation state. Here, we consider three proteins, dihydrofolate reductase, transketolase, and alpha-trichosanthin, complexed with ligands having multiple tautomeric forms.

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We describe a combinatorial method for de novo ligand design to an ensemble of receptor structures. Receptor conformations, protonation states, and structural water molecules are considered consistently within the framework of de novo ligand design. The method relies on Monte Carlo optimization to search the space of ligand structures, conformations, and rigid-body movements as well as receptor models.

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One of the major problems in computational drug design is incorporation of the intrinsic flexibility of protein binding sites. This is particularly crucial in ligand binding events, when induced fit can lead to protein structure rearrangements. As a consequence of the huge conformational space available to protein structures, receptor flexibility is rarely considered in ligand design procedures.

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We describe a method to create ligands specific for a given protein family. The method is applied to generate ligand candidates for the cyclin-dependent kinase (CDK) family. The CDK family of proteins is involved in regulating the cell cycle by alternately activating and deactivating the cell's progression through the cycle.

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The importance of the consideration of water molecules in the structural interpretation of ligand-derived pharmacophore models is explored. We compare and combine results from recently introduced methods for bound-water molecule identification in protein binding sites and ligand-superposition-based pharmacophore derivation, for the interpretation of ligand-derived pharmacophore models. In the analysis of thymidine kinase (HSV-1) and poly (ADP-ribose) polymerase (PARP), the concurrent application of both methods leads to an agreement in the prediction of tightly bound water molecules as key pharmacophoric points in the binding site of these proteins.

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Structure-based and ligand-based methods are used to derive predictive models in de novo drug design. Structure-based methods rely exclusively on prior knowledge of a protein structure to derive novel ligands, while ligand-based methods are traditionally used when no protein structure is available. Where there is sufficient information, these methods can be used in conjunction to increase the accuracy of simulation and enhance the drug design process.

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Computational ligand-protein docking is routinely used for binding mode prediction. We have quantified the effect of considering multiple docking solutions on the success rate of obtaining the crystallographic binding mode. By selection of a small set of representatives, the experimentally observed binding mode can be predicted with a higher probability after a ligand-protein docking simulation.

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A major difficulty in structure-based molecular design is the prediction of the structure of the protein-ligand complex because of the enormous number of degrees of freedom. Commonly, the target protein is kept rigid in a single low-energy conformation. However, this does not reflect the dynamic nature of protein structures.

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A novel hybrid optimization method called quantum stochastic tunneling has been recently introduced. Here, we report its implementation within a new docking program called EasyDock and a validation with the CCDC/Astex data set of ligand-protein complexes using the PLP score to represent the ligand-protein potential energy surface and ScreenScore to score the ligand-protein binding energies. When taking the top energy-ranked ligand binding mode pose, we were able to predict the correct crystallographic ligand binding mode in up to 75% of the cases.

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We report here the de novo generation of chemotypes and scaffolds for the estrogen receptor, without use of the receptor structure in the assembly phase. Through use of ligand superpositions or a single bound conformation of a known active, a pseudoreceptor can be generated as a design envelope, within which novel structures are readily assembled. Many of these structures have high similarity to known chemotypes.

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The de novo design program Skelgen has been used to design inhibitor structures for four targets of pharmaceutical interest. The designed structures are compared to modeled binding modes of known inhibitors (i) visually and (ii) by means of a novel similarity measure considering the size and spatial proximity of the maximum common substructure of two small molecules. It is shown that the Skelgen algorithm generates representatives of many inhibitor classes within a very short time and that the new similarity measure is useful for comparing and clustering designed structures.

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Calculation of signal detection theory measures.

Behav Res Methods Instrum Comput

February 1999

Signal detection theory (SDT) may be applied to any area of psychology in which two different types of stimuli must be discriminated. We describe several of these areas and the advantages that can be realized through the application of SDT. Three of the most popular tasks used to study discriminability are then discussed, together with the measures that SDT prescribes for quantifying performance in these tasks.

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