3D-QSAR,molecular docking and ADMET studies of thioquinazolinone derivatives against breast cancer

Breast cancer is a deadly disease and the second largest cause of mortality on a worldwide platform. Despite the availability of several cancer treatments, life expectancies stay relatively poor. Consequently, the medicinal chemistry community prioritizes the quick discovery of novel anticancer drugs. In recent years, computational approaches have been widely used to accelerate the drug development process. In light of this, in the current work, we performed three-dimensional quantitative structure-activity relationships (3D-QSAR) and molecular docking analyses on thioquinazolinone derivatives with aromatase enzyme (PDB: 3S7S). External validation was used to validate the prediction capabilities of the generated model. The best CoMSIA (comparative molecular similarity indices analysis) model exhibited the significant values of $Q^2$, $R^{2}and$ $R_{pred}^2$. These findings suggested that the electrostatic, hydrophobic and hydrogen bond donor and acceptor fields have a significant effect on inhibition of breast cancer. Thus, a number of innovative potent aromatase inhibitors were designed and their biological activities were predicted based on the best model. Furthermore, molecular docking studies were carried out for the designed compounds against breast cancer. Additionally, ADMET proprieties were used to evaluate drug-likeness of these novel drug candidates. The most active compounds found by these computational studies could be helpful for synthesis and testing as prospective future anti-cancer treatments.     

Relaxation Processes and Glass Transition in Polymer Filled with Nanoparticles

We report the results of the investigations of the influence of filling of polymer with Aerosil nanosize particles on the glass transition and dynamics of the α- and the β-relaxation processes in poly(n-octyl methacrylate) by dielectric spectroscopy and differential scanning calorimetry (DSC). The polymer was filled with hydrophilic and hydrophobic Aerosil particles of 12 nm diameter. In filled polymers the characteristic frequency of the alpha-process was shifted to higher frequencies in comparison with pure bulk polymer at the same temperature. This suggests that the filling of the polymer with nanoparticles has resulted in the shift of its glass transition temperature T_g. This change in T_g was mainly due to the existence of a developed solid particle-polymer interface and the difference in the dynamic behavior of the polymer in the surface layers at this interface compared to the bulk behavior. This result was in agreement with DSC experiments.     

Dynamic fracture instabilities in brittle crystals generated by thermal phonon emission: Experiments and atomistic calculations

Dynamic cleavage fracture experiments of brittle single crystal silicon revealed several length scales of surface and path instabilities: macroscale path selection, mesoscale crack deflection, and nanoscale surface ridges. These phenomena cannot be predicted or explained by any of the continuum mechanics based equations of motion of dynamic cracks, as presumably critical energy dissipation mechanisms are not fully accounted for in the theories. Experimentally measured maximum crack speed, always lower than the theoretical limit, is another phenomenon that is as yet not well understood.We suggest that these phenomena depend on velocity dependent and anisotropic material property that resists crack propagation. The basic approach is that the bond breaking mechanisms during dynamic crack propagation vibrate the atoms at the crack front to generate thermal phonon emission, or heat, which provides additional energy dissipation mechanisms. This energy dissipation mechanism is a material property that resists crack propagation. To evaluate this property, we combined the continuum based elastodynamic Freund equation of motion with molecular dynamics atomistic computer “experiments”.We analyzed the above experimental dynamic fracture instabilities in silicon with the obtained velocity dependent and anisotropic material property and show its importance in cleavage of brittle crystals.     

Output controllability and optimal output control of positive fractional order linear discrete system with multiple delays in state, input and output

The article concerns output controllability and optimal output control of positive fractional order discrete linear systems with multiple delays in state, input and output. Necessary and sufficient conditions for output reachability (output controllability from zero initial conditions) and null output controllability (output controllability to zero final output) are given and proven. We also prove that the positive system is output controllable if it is output reachable and null output controllable with the output reachability index is equal or less than the null output controllability index. Sufficient conditions for the solvability of the optimal output control problem are given. Numerical examples are presented to illustrate the theoretical results.     

Theoretical Complexity of Grid Cover Problems Used in Radar Applications

Modern radars are highly flexible systems, relying on digital antennas to dynamically control the radar beam shape and position through electronic circuits. Radar surveillance is performed by sequential emission of different radar beams. Optimization of radar surveillance requires finding a minimal subset of radar beams, which covers and ensures detection over the surveillance space, among a collection of available radar beams with different shapes and positions, thus minimizing the required scanning time. Optimal radar surveillance can be modelled by grid covering, a specific geometric case of set covering where the universe set is laid out on a grid, representing the radar surveillance space, which must be covered using available subsets, representing the radar beams detection areas. While the set cover problem is generally difficult to solve optimally, certain geometric cases can be optimized in polynomial time. This paper studies the theoretical complexity of grid cover problems used for modelling radar surveillance, proving that unidimensional grids can be covered by strongly polynomial algorithms based on dynamic programming, whereas optimal covering of bidimensional grids is generally non-deterministic polynomially hard.     

Tuning the electronic properties of the fullerene C<Subscript>20</Subscript> cage via silicon impurities

The fullerene C₂₀ represents one of the most active classes of nanostructures, and they have been widely used as active materials for important applications. In this study, we investigate and discuss the tuning of the electronic properties of the fullerene C₂₀ cage via various consternations and locations of silicon atoms. All calculations are based on the density functional theory (DFT) at the B3LYP/3-21G level through the Gaussian 09W program package. The optimized structures, density of state (DOS) analysis, total energies, dipole moments, HOMO energies, Fermi level energies, LUMO energies, energy gaps, and the work functions were performed and discussed. Our results show that the electronic properties of C₂₀ cage do not only depend on the silicon impurity concentrations, but also depend on the geometrical pattern of silicon impurities in the C₂₀ cage. The tuning of the electronic properties leads to significant changes in the charge transport and the absorption spectra for C₂₀ cage via engineering the energy gap. So, we suggest that substitutional impurities are the best viable option for enhancement of desired electronic properties of C₂₀ cage for using these structures in nanoelectronics and solar cell applications.     

Belief linear programming

This paper proposes solution approaches to the belief linear programming (BLP). The BLP problem is an uncertain linear program where uncertainty is expressed by belief functions. The theory of belief function provides an uncertainty measure that takes into account the ignorance about the occurrence of single states of nature. This is the case of many decision situations as in medical diagnosis, mechanical design optimization and investigation problems. We extend stochastic programming approaches, namely the chance constrained approach and the recourse approach to obtain a certainty equivalent program. A generic solution strategy for the resulting certainty equivalent is presented.     

A topological construction of the weight filtration

Let ${j: X \setminus Y\,\longrightarrow\,X}$ be the embedding of the complement of a Cartier divisor Y in a complex algebraic variety X, and let ${\mathbb K}$ be a perverse sheaf on X \ Y. With the aid of the specialization functor introduced by Verdier in Analyse et Topologie sur les espaces singuliers vol. II, III, Astérisque 101–102:332–364 [13], we define a filtration W of topological origin on the perverse complex ${Rj_{*}\mathbb K}$ which should play the role of the weight filtration when ${\mathbb K}$ is a local system underlying a polarised variation of Hodge structures.     

Structural characterisation of [Cu2(bptd) (H2O) Cl4] and [Ni2(bptd)2(H2O)4] Cl4·3H2O; evidence of null intramolecular exchanges by EPR and magnetic measurements

Using the 2,5-bis(2-pyridyl)-1,3,4-thiadiazole (bptd), we recently prepared [Cu₂(bptd) (H₂O) Cl₄] and [Ni₂(bptd)₂ (H₂O)₄] Cl₄, 3H₂O in which the magnetic centres are connected through one diazine+one chloro and two diazine ligand bridges, respectively. These two compounds are the first examples that show null intramolecular magnetic interactions despite M-M distances close to 3.7 Å within perfectly planar edifices:Down to , [Cu₂(bptd)Cl₄(H₂O)] is paramagnetic while, below T_t, half of the Cu²⁺ions interact, leading to residual paramagnetism of one Cu²⁺/f.u. Magnetic susceptibility measurements, EPR and pulsed EPR study indicate the original intermolecular nature of AF exchanges.[Ni₂(bptd)₂(H₂O)₄]Cl₄·3H₂O susceptibility obeys a Curie-law involving pure paramagnetism. Moreover, its EPR spectrum can be interpreted on the basis of virtual S=1 monomers. Below 70 K, Zero Field Splitting (D∼275 G) due to dipolar interactions without magnetic exchanges could be responsible for the LT spectra splitting. For both compounds, the thia role is suggested as partially responsible for the null-in-plane magnetic exchanges.