Ανάλυση οικιστικού δικτύου νήσου Αντίπαρου, προβλήματα και προοπτικές

Εθνικό Μετσόβιο Πολυτεχνείο--Μεταπτυχιακή Εργασία. Διεπιστημονικό-Διατμηματικό Πρόγραμμα Μεταπτυχιακών Σπουδών (Δ.Π.Μ.Σ.) “Γεωπληροφορική

Carcinogenicity of Styrene Oxide: Calculation of Chemical Reactivity

In this article the calculations of the activation free energy for a chemical reaction between styrene-7,8-oxide and DNA, in particular guanine at position N7, are reported. Calculations were performed by Hartree-Fock and DFT methods in conjunction with flexible basis sets. Effects of solvation were considered using the Langevin dipoles method. The calculated activation free energies are in good agreement with the experimental value of 26.52 kcal mol−1

An Overview of the Anticoagulant Drugs Used in Routine Clinical Practice

Anticoagulant drugs directly or indirectly influence coagulation factors preventing fibrin formation thus preventing blot clotting. They are classified into two groups according to the mode of application, namely parenteral and oral drugs. Among the latter, vitamin K antagonists (most often warfarin) were the only available oral drugs and were widely used for almost a century. In the recent years, new oral anticoagulant drugs became available that directly target either factor IIa or Xa. This chapter provides an overview of both parenteral and oral anticoagulant drugs used in clinical practice with description of the mode of action and management of therapy in different clinical settings

The Use of Multiscale Molecular Simulations in Understanding a Relationship between the Structure and Function of Biological Systems of the Brain: The Application to Monoamine Oxidase Enzymes

Computational techniques provide accurate descriptions of the structure and dynamics of biological systems, contributing to their understanding at an atomic level.Classical MD simulations are a precious computational tool for the processes where no chemical reactions take place.QM calculations provide valuable information about the enzyme activity, being able to distinguish among several mechanistic pathways, provided a carefully selected cluster model of the enzyme is considered.Multiscale QM/MM simulation is the method of choice for the computational treatment of enzyme reactions offering quantitative agreement with experimentally determined reaction parameters.Molecular simulation provide insight into the mechanism of both the catalytic activity and inhibition of monoamine oxidases, thus aiding in the rational design of their inhibitors that are all employed and antidepressants and antiparkinsonian drugs. Aging society and therewith associated neurodegenerative and neuropsychiatric diseases, including depression, Alzheimer's disease, obsessive disorders, and Parkinson's disease, urgently require novel drug candidates. Targets include monoamine oxidases A and B (MAOs), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and various receptors and transporters. For rational drug design it is particularly important to combine experimental synthetic, kinetic, toxicological, and pharmacological information with structural and computational work. This paper describes the application of various modern computational biochemistry methods in order to improve the understanding of a relationship between the structure and function of large biological systems including ion channels, transporters, receptors, and metabolic enzymes. The methods covered stem from classical molecular dynamics simulations to understand the physical basis and the time evolution of the structures, to combined QM, and QM/MM approaches to probe the chemical mechanisms of enzymatic activities and their inhibition. As an illustrative example, the later will focus on the monoamine oxidase family of enzymes, which catalyze the degradation of amine neurotransmitters in various parts of the brain, the imbalance of which is associated with the development and progression of a range of neurodegenerative disorders. Inhibitors that act mainly on MAO A are used in the treatment of depression, due to their ability to raise serotonin concentrations, while MAO B inhibitors decrease dopamine degradation and improve motor control in patients with Parkinson disease. Our results give strong support that both MAO isoforms, A and B, operate through the hydride transfer mechanism. Relevance of MAO catalyzed reactions and MAO inhibition in the context of neurodegeneration will be discussed

Photodissociation Dynamics of the Iodine-Arene Charge-Transfer Complex

The photodissociation reaction of the molecular iodine:arene charge-transfer (CT) complex into an iodine atom and an iodine atom-arene fragment has been investigated using femtosecond pump-probe, resonance Raman, and molecular dynamics simulations. In the condensed phase the reaction proceeds on a time scale of less than 25 fs, in sharp contrast to the gas phase where the excited state lifetime of the complex is about 1 ps. Since little CT resonance enhancement is found in Raman studies on the I2-stretch vibration, it is concluded that rapid curve crossing occurs from the CT state to a dissociative surface. Of particular interest is the finding that the polarization anisotropy of the iodine atom:arene (I:ar) photoproduct decays on a time scale of 350 fs both in pure arene solvents as well as in mixed arene/cyclohexane solutions. This latter finding rules out that secondary I:ar complex formation is the main cause of this ultrafast depolarization effect. The initial polarization anisotropy is found to be ~0.12 in pure mesitylene and ~0.34 in mixed mesitylene/cyclohexane solutions. Semiempirical configuration-interaction calculations show that, except for the axial CT complex, the transition dipole is aligned almost parallel to the normal of the arene plane. The oscillator strength of the CT transition is found to be maximal in the oblique conformation with the I2 molecule positioned at an angle of about 30° with respect to the arene normal. This iodine angular dependence of the oscillator strength leads to photoselection of bent I2:ar complexes in pump-probe experiments. Molecular dynamics simulations confirm earlier findings that the I2:benzene complex is a fragile entity and that it persists only for a few hundred femtoseconds. These simulations also provide the proper time scale for the decay of the polarization anisotropy. The fact that the photoproduct experiences a substantial torque in the dissociation process explains the absence of a cage effect in this reaction.

Hydrogen Bond Dynamics of Histamine Monocation in Aqueous Solu-tion: How Geometric Parameters Influence the Hydrogen Bond Strength

Chemometric statistical approaches involving multiple linear regression (MLR) and principal compo-nent analysis (PCA) were employed on a set of 42 distinct snapshot structures of the physiological histamine monocation in aqueous solution along the Car-Parrinello molecular dynamics trajectory, in order to obtain a better insight into the relationship between the geometry parameters of the system and the resulting νNH stretching frequencies. A simple 2D linear regression of νNH with Namino•••Owater distances gave a very poor correlation (R2 = 0.42), but both MLR and PCA with the inclusion of four directly bonded water molecules offered a notably predictive model that is even able to distinguish two classes of structures based on the Cl– counterion position. Taking into account waters from the first, second and third solvation shells, sequentially diminished the overall predictive ability of the model, yet increased the number of useful predictors that, in the largest model with 51 solvent mole-cules, all correspond to bulk water, implying that both chemometric methods are consistent in suggest-ing that fundamental histamine N–H stretching vibrations are very complex in nature and strongly coupled to the fluctuating environ-ment

Sustainable planning of outdoor recreation in the Triglav National Park with emphasis on social carrying capacity

The article presents the aspects of sustainable planning of outdoor recreation in the protected areas with the emphasis on social carrying capacity. The starting points for the design of measures in the process of sustainable planning of outdoor recreation are presented and promote regular monitoring and directing of outdoor recreation in the protected areas in Slovenia and abroad, especially on the example of Triglav National Park. In the article we are trying to define which forms of outdoor recreation are from the local‘s and visitor‘s perspective recognised as sustainable

Removal of Ochratoxin A in Saccharomyces cerevisiae Liquid Cultures

The capacity for removal of ochratoxin A (OTA) during alcoholic fermentation was evaluated in batch systems withone commercial strain and one wild strain of Saccharomyces cerevisiae. Batch alcoholic fermentations were carriedout in yeast extract-malt extract broth (YM) medium, with 18.0% glucose and OTA added to final concentrationsof 3.48 and 4.95 ng/mL respectively. The removal capacity of each yeast strain was examined after completion offermentation in batch culture and after extended contact with yeast biomass. The removal capacity of the yeaststrains was also examined in stationary phase cultures. Stationary phase yeasts were studied with biomass harvestedfrom the stationary phase of anaerobic fermentation, by incubation in phosphate buffer, with the addition of 5.00 ng/mL of OTA. Removal studies with stationary phase cells were performed with viable and non-viable cells inactivatedwith Na-azide. The study showed that in growing phase cultures, OTA removal was significant only after extendedcontact with yeast biomass; up to 29.7% and 25.4% for wild yeast ZIM 1927 and commercial yeast Lalvin EC-1118respectively, but not during alcoholic fermentation. In stationary phase cultures, viable and non-viable cells werenot significantly different in OTA removal from the medium. This demonstrated that OTA was not metabolised, butpossibly adsorbed by the yeast cells. The presence of OTA in synthetic media influenced yeast metabolism, causingthe production of higher volatile acidity by 0.08 and 0.13 g/L for Lalvin EC-1118 and ZIM 1927 respectively, andlower concentrations of reducing sugar, by 0.32 g/L, but only for ZIM 1927

Miniaturized Aptamer-Based Assays for Protein Detection

The availability of devices for cancer biomarker detection at early stages of the disease is one of the most critical issues in biomedicine. Towards this goal, to increase the assay sensitivity, device miniaturization strategies empowered by the employment of high affinity protein binders constitute a valuable approach. In this work we propose two different surface-based miniaturized platforms for biomarker detection in body fluids: the first platform is an atomic force microscopy (AFM)-based nanoarray, where AFM is used to generate functional nanoscale areas and to detect biorecognition through careful topographic measurements; the second platform consists of a miniaturized electrochemical cell to detect biomarkers through electrochemical impedance spectroscopy (EIS) analysis. Both devices rely on robust and highly-specific protein binders as aptamers, and were tested for thrombin detection. An active layer of DNA-aptamer conjugates was immobilized via DNA directed immobilization on complementary single-stranded DNA self-assembled monolayers confined on a nano/micro area of a gold surface. Results obtained with these devices were compared with the output of surface plasmon resonance (SPR) assays used as reference. We succeeded in capturing antigens in concentrations as low as a few nM.We put forward ideas to push the sensitivity further to the pM range, assuring low biosample volume (L range) assay conditions