A strategy based on protein-protein interface motifs may help in identifying drug off-targets

Networks are increasingly used to study the impact of drugs at the systems level. From the algorithmic standpoint, a drug can "attack" nodes or edges of a protein-protein interaction network. In this work, we propose a new network strategy, "The Interface Attack", based on protein-protein interfaces. Similar interface architectures can occur between unrelated proteins. Consequently, in principle, a drug that binds to one has a certain probability of binding to others. The interface attack strategy simultaneously removes from the network all interactions that consist of similar interface motifs. This strategy is inspired by network pharmacology and allows inferring potential off-targets. We introduce a network model that we call "Protein Interface and Interaction Network (P2IN)", which is the integration of protein-protein interface structures and protein interaction networks. This interface-based network organization clarifies which protein pairs have structurally similar interfaces and which proteins may compete to bind the same surface region. We built the P2IN with the p53 signaling network and performed network robustness analysis. We show that (1) "hitting" frequent interfaces (a set of edges distributed around the network) might be as destructive as eleminating high degree proteins (hub nodes), (2) frequent interfaces are not always topologically critical elements in the network, and (3) interface attack may reveal functional changes in the system better than the attack of single proteins. In the off-target detection case study, we found that drugs blocking the interface between CDK6 and CDKN2D may also affect the interaction between CDK4 and CDKN2D.     

Boradiazaindacene (Bodipy)-based building blocks for the construction of energy transfer cassettes

Energy transfer cassettes composed entirely of boradiazaindacene (Bodipy) units were designed and synthesized to capture photonic energy and convert it to longer wavelength fluorescence emission. The new energy transfer systems obtained by simple condensation reactions are capable of elaborating efficient energy transfer from donor Bodipy units to the distyryl-Bodipy acceptor.     

Design, testing and two-dimensional flow modeling of a multiple-disk fan

A multiple-disk Tesla type fan has been designed, tested and analyzed two-dimensionally using the conservation of angular momentum principle. Experimental results showed that such multiple-disk fans exhibited exceptionally low performance characteristics, which could be attributed to the low viscosity, tangential nature of the flow, and large mechanical energy losses at both suction and discharge sections that are comparable to the total input power. By means of theoretical analysis, local and overall shearing stresses on the disk surfaces have been determined based on tangential and radial velocity distributions of the air flow of different volume flow rates at prescribed disk spaces and rotational speeds. Then the total power transmitted by rotating disks to air flow, and the power acquired by the air flow in the gap due to transfer of angular momentum have been obtained by numerically integrating shearing stresses over the disk surfaces. Using the measured shaft and hydraulic powers, these quantities were utilized to evaluate mechanical energy losses associated with the suction and discharge sections of the fan.     

Calculation of the stability and mechanical and phonon properties of NbRuB,TaRuB, and NbOsB compounds

The structural, mechanical, and phonon properties of NbRuB, TaRuB, and NbOsB compounds with orthorhombic space groups Pmma (No. 51) and Pbam (No. 55) are investigated by using first-principles calculations. The elastic constants and moduli, Debye temperature, Poisson’s ration, Pugh’s ratio, elastic anisotropy factors, and minimum thermal conductivities have been predicted to understand the mechanical behavior of these ternary compounds. The mechanical anisotropy is discussed via several anisotropy indices and two-dimensional (2D) surface constructions. We observe that all compounds ought to be classified as ductile materials and exhibit elastically anisotropy. Their mechanical and dynamical stability is confirmed via the calculated elastic constants and phonon dispersion curves, respectively. This work should provide a useful guide for designing ternary boride materials that have excellent thermoelectric performance.     

The effect of B2O3 addition to the microstructure and magnetic properties of Ni0.4Zn0.6Fe2O4 ferrite

The effects of 0.01 and 0.1 mol B₂O₃ addition to the microstructure and magnetic properties of a Ni–Zn ferrite composition expressed by a molecular formula of Ni_0.4Zn_0.6Fe₂O₄ were investigated. The toroid-shaped samples prepared by pressing the milled raw materials used in the preparation of the composition were sintered in the range of 1000–1300 °C. The addition of 0.01 mol B₂O₃ increased the grain growth and densification giving rise to reduced intergranular and intragranular porosity due to liquid-phase sintering. The sintered toroid sample at 1300 °C gave the optimum magnetic properties of B_r=170 mT, H_c=0.025 kA/m and a high initial permeability value of μ_i=4000. The increment of the B₂O₃ content to 0.1 mol resulted in a pronounced grain growth and also gave rise to large porosity due to the evaporation of B₂O₃ at higher sintering temperatures. Hence, it resulted in an air-gap effect in the hysteresis curves of these samples.     

Near‐IR‐Triggered,Remote‐Controlled Release of Metal Ions: A Novel Strategy for Caged Ions

A ligand incorporating a dithioethenyl moiety is cleaved into fragments which have a lower metal‐ion affinity upon irradiation with low‐energy red/near‐IR light. The cleavage is a result of singlet oxygen generation which occurs on excitation of the photosensitizer modules. The method has many tunable factors that could make it a satisfactory caging strategy for metal ions.     

An analytic method for strong motion studies in layered media2

An analytic method is presented for calculating strong motion spectra and response to arbitrary input in layered media. The method is based on the removal of secular terms at resonance of the equations with polynomial non-linearity. The non-linear effects are introduced by the frequency shifts calculated from the secular term according to the method by Millman and Keller. The procedure, through a convenient parametrizarion of the frequency, allows one to deal with linear equations. This possibility permits the extension of the method to multilayer systems by the use of transfer matrices. The response to an arbitrary input motion is obtained from the response spectrum in the frequency domain by the use of (Fast) Fourier Transform.