Exploring structure–selectivity relationships of biogenic amine GPCR antagonists using similarity searching and dynamic compound mapping

We design and analyze compound selectivity sets of antagonists with differential selectivity against seven biogenic amine G-protein coupled receptors. The selectivity sets consist of a total of 267 antagonists and contain a spectrum of in part closely related molecular scaffolds. Each set represents a different selectivity profile. Using these com- pound sets, a systematic computational analysis of structure-selectivity relationships is carried out with different 2D similarity methods including fingerprints, recursive partitioning, clustering, and dynamic compound mapping. Screening calculations are performed in a background database containing nearly four million molecules. Fingerprint searching and compound mapping are found to enrich target-selective antagonists over family-selective ones. Dynamic compound mapping effectively discriminates database compounds from GPCR antagonists and consistently retains target-selective antagonists during the final dimension extension levels. Furthermore, the widely used MACCS key fingerprint displays a strong tendency to distinguish between target- and family-selective GPCR antagonists. Taken together, the results indicate that different types of 2D similarity methods are capable of distinguishing closely related molecules having different selectivity. The reported compound benchmark system is made freely available in order to enable selectivity-oriented analyses using other computational approaches.     

Exclusive B→K<Subscript>1</Subscript>ℓ<Superscript>+</Superscript>ℓ<Superscript>-</Superscript> decay in model with single universal extra dimension

Decay rate and forward–backward asymmetries in B→K₁ℓ⁺ℓ^-, where K₁ is the axial vector meson, are calculated in the universal extra dimension (UED) model. The dependence of these physical quantities on the compactification radius R, the only unknown parameter in UED model, is studied, and it is shown that the zero of the forward–backward asymmetry is sensitive to the UED model; therefore they can be a very useful tool to establish new physics predicted by the UED model. This work is briefly extended to B→K^*l⁺l^-.     

Cluster Model Analysis of Pion Elastic and Inelastic Scattering from 12C

Angular distributions of differential cross sections for the ¹²C(π ^±, π ^±)¹²C and ¹²C(π ^±, π ^±)¹²C^* reactions at pion kinetic energy ranging from 50 to 260 MeV have been analyzed with the 3α-particle model of ¹²C. The model provides good fits to a wide range of data. Differential cross sections for inelastic transitions to the (2^?+?; 4.44 MeV) and (3^???; 9.64 MeV) states in ¹²C are computed and the deformation lengths δ ₂ and δ ₃ are extracted. It is found that the extracted deformation lengths are sensitive to the nuclear model used and similar to the corresponding values found with other probes and nuclear models.     

Surface energies of metals in both liquid and solid states

Although during the last years one has seen a number of systematic studies of the surface energies of metals, the aim and the scientific meaning of this research is to establish a simple and a straightforward theoretical model to calculate accurately the mechanical and the thermodynamic properties of metal surfaces due to their important application in materials processes and in the understanding of a wide range of surface phenomena. Through extensive theoretical calculations of the surface tension of most of the liquid metals, we found that the fraction of broken bonds in liquid metals (f) is constant which is equal to 0.287. Using our estimated f value, the surface tension (γ_m), surface energy (γ_SV), surface excess entropy (−dγ/dT), surface excess enthalpy (H_s), coefficient of thermal expansion (α_m and α_b), sound velocity (c_m) and its temperature coefficient (−dc/dT) have been calculated for more than sixty metals. The results of the calculated quantities agree well with available experimental data.     

The water-silicas interfacial interaction energies

The water-silicas interfacial interaction energies were calculated for samples of quartz, silicas and silicas outgassed at high temperatures using own and published data of the spreading pressure of water, its surface tension, its contact angle and using formulas obtained by the combination of the Young equation with a general equation of pair interaction. The values obtained for 18 different samples were in the range 7.80-6.92 kJ mol⁻¹. Lower values of energies are for samples that contain relatively less amounts of water at P/P₀ = 0.25 and are characterized also by relatively low values of surface pressures.     

Study of nonlinear system stability using eigenvalue analysis: Gyroscopic motion

General computational multibody system (MBS) algorithms allow for the linearization of the highly nonlinear equations of motion at different points in time in order to obtain the eigenvalue solution. This eigenvalue solution of the linearized equations is often used to shed light on the system stability at different configurations that correspond to different time points. Different MBS algorithms, however, employ different sets of orientation coordinates, such as Euler angles and Euler parameters, which lead to different forms of the dynamic equations of motion. As a consequence, the forms of the linearized equations and the eigenvalue solution obtained strongly depend on the set of orientation coordinates used. This paper addresses this fundamental issue by examining the effect of the use of different orientation parameters on the linearized equations of a gyroscope. The nonlinear equations of motion of the gyroscope are formulated using two different sets of orientation parameters: Euler angles and Euler parameters. In order to obtain a set of linearized equations that can be used to define the eigenvalue solution, the algebraic equations that describe the MBS constraints are systematically eliminated leading to a nonlinear form of the equations of motion expressed in terms of the system degrees of freedom. Because in MBS applications the generalized forces can be highly nonlinear and can depend on the velocities, a state space formulation is used to solve the eigenvalue problem. It is shown in this paper that the independent state equations formulated using Euler angles and Euler parameters lead to different eigenvalue solutions. This solution is also different from the solution obtained using a form of the Newton-Euler matrix equation expressed in terms of the angular accelerations and angular velocities. A time-domain solution of the linearized equations is also presented in order to compare between the solutions obtained using two different sets of orientation parameters and also to shed light on the important issue of using the eigenvalue analysis in the study of MBS stability. The validity of using the eigenvalue analysis based on the linearization of the nonlinear equations of motion in the study of the stability of railroad vehicle systems, which have known critical speeds, is examined. It is shown that such an eigenvalue analysis can lead to wrong conclusions regarding the stability of nonlinear systems.     

Higher order representation of the beam cross section deformation in large displacement finite element analysis

Most existing beam formulations assume that the cross section of the beam remains rigid regardless of the amplitude of the displacement. The absolute nodal coordinate formulation (ANCF); however, allows for the deformation of the cross section and leads to a more general beam models that capture the coupling between different modes of displacement. This paper examines the effect of the order of interpolation on the modes of deformation of the beam cross section using ANCF finite elements. To this end, a new two-dimensional shear deformable ANCF beam element is developed. The new finite element employs a higher order of interpolation, and allows for new cross section deformation modes that cannot be captured using previously developed shear deformable ANCF beam elements. The element developed in this study relaxes the assumption of planar cross section; thereby allowing for including the effect of warping as well as for different stretch values at different points on the element cross section. The displacement field of the new element is assumed to be cubic in the axial direction and quadratic in the transverse direction. Using this displacement field, more expressions for the element extension, shear and the cross section stretch can be systematically defined. The change in the cross section area is measured using Nanson’s formula. Measures of the shear angle, extension, and cross section stretch can also be systematically defined using coordinate systems defined at the element material points. Using these local coordinate systems, expressions for a nominal shear angle are obtained. The differences between the cross section deformation modes obtained using the new higher order element and those obtained using the previously developed lower order elements are highlighted. Numerical examples are presented in order to compare the results obtained using the new finite element and the results obtained using previously developed ANCF finite elements.     

Measurement of the total active 8B solar neutrino flux at the Sudbury Neutrino Observatory with enhanced neutral current sensitivity

The Sudbury Neutrino Observatory has precisely determined the total active (nu(x)) 8B solar neutrino flux without assumptions about the energy dependence of the nu(e) survival probability. The measurements were made with dissolved NaCl in heavy water to enhance the sensitivity and signature for neutral-current interactions. The flux is found to be 5.21 +/- 0.27(stat)+/-0.38(syst) x 10(6) cm(-2) s(-1), in agreement with previous measurements and standard solar models. A global analysis of these and other solar and reactor neutrino results yields Deltam(2)=7.1(+1.2)(-0.6) x 10(-5) eV(2) and theta=32.5(+2.4)(-2.3) degrees. Maximal mixing is rejected at the equivalent of 5.4 standard deviations.     

Fe2P2O7 and Fe2P4O12 studied between 5–800 K

Mössbauer spectra of triclinic Fe₂P₂O₇ indicate the existence of two crystallographic metal positions in the structure. In the paramagnetic region the two Mössbauer doublets are closely overlapping. The magnetic transition takes place at ≈ 21 K and the saturated fields are around 12 tesla for the two positions. In monoclinic Fe₂P₄O₁₂ the two octahedrally coordinated metal positions give quite different quadrupole splittings (1.5 and 3 mm/s at room temperature) and hyperfine field values (42 and 12.5 Tesla at 5 K). The transition temperature is at ≈ 18.5 K.