Dynophore-Based Approach in Virtual Screening: A Case of Human DNA Topoisomerase IIα

In this study, we utilized human DNA topoisomerase IIα as a model target to outline a dynophore-based approach to catalytic inhibitor design. Based on MD simulations of a known catalytic inhibitor and the native ATP ligand analog, AMP-PNP, we derived a joint dynophore model that supplements the static structure-based-pharmacophore information with a dynamic component. Subsequently, derived pharmacophore models were employed in a virtual screening campaign of a library of natural compounds. Experimental evaluation identified flavonoid compounds with promising topoisomerase IIα catalytic inhibition and binding studies confirmed interaction with the ATPase domain. We constructed a binding model through docking and extensively investigated it with molecular dynamics MD simulations, essential dynamics, and MM-GBSA free energy calculations, thus reconnecting the new results to the initial dynophore-based screening model. We not only demonstrate a new design strategy that incorporates a dynamic component of molecular recognition, but also highlight new derivates in the established flavonoid class of topoisomerase II inhibitors.     

Active beating modes of two clamped filaments driven by molecular motors

Biological cilia pump the surrounding fluid by asymmetric beating that is driven by dynein motors between sliding microtubule doublets. The complexity of biological cilia raises the question about minimal systems that can re-create similar patterns of motion. One such system consists of a pair of microtubules that are clamped at the proximal end. They interact through dynein motors that cover one of the filaments and pull against the other one. Here, we study theoretically the static shapes and the active dynamics of such a system. Using the theory of elastica, we analyse the shapes of two filaments of different lengths with clamped ends. Starting from equal lengths, we observe a transition similar to Euler buckling leading to a planar shape. When further increasing the length ratio, the system assumes a non-planar shape with spontaneously broken chiral symmetry after a secondary bifurcation and then transitions to planar again. The predicted curves agree with experimentally observed shapes of microtubule pairs. The dynamical system can have a stable fixed point, with either bent or straight filaments, or limit cycle oscillations. The latter match many properties of ciliary motility, demonstrating that a two-filament system can serve as a minimal actively beating model.     

Newtonian power curve and drop size distributions for vibromixers

Power input data are presented for a twin flat disk up-and-down moving (vibromixer) impeller operating in a small vessel with a range of Newtonian liquids. Vibromixer power number and Reynolds number are defined and are used to establish the Newtonian power curve for this type of mixer. Drop size distributions are presented for xylene-in-water dispersions under turbulent flow conditions in the vibromixer and are shown to vary with the maximum velocity of the disk (2πAf). The Sauter mean drop diameter of the distribution is related to the vibromixer Weber number, (We =ρ(2πAf)²D/σ), by an equation of the type d₃₂/D = C (We)^?3/5 with the coefficient C = 0.37.     

Modified Diglycolamides for the An(III) + Ln(III) Co-separation: Evaluation by Solvent Extraction and Time-Resolved Laser Fluorescence Spectroscopy

The use of two recently developed diglycolamide-based extractants for the co-separation of trivalent actinides (An(III)) and lanthanides (Ln(III)) is described and compared to the well-known extractant TODGA (N,N,N’,N’-tetraoctyl diglycolamide). The addition of one or two methyl groups to the central methylene carbon atoms of the TODGA molecule leads to a reduction of the extraction efficiency for An(III) and Ln(III). This is attributed to a lower complex formation constant, which was proven by Time-Resolved Laser Fluorescence Spectroscopy (TRLFS). Conditional stability constants were determined by solvent extraction and TRLFS. The reduction in extraction efficiency leads to overall reduced distribution ratios of all tested metal ions, including Sr(II). The reduced Sr(II) extraction is beneficial as a co-extraction in a solvent extraction process could be avoided, while an efficient extraction of the desired An(III) and Ln(III) is still achieved. Furthermore, this might be a benefit, as the stripping behavior might be improved, even at moderate nitric acid concentrations. The slightly higher affinity of the diglycolamides towards Eu(III) over Am(III) is represented by all ligands, although the selectivity is rather low. This results in promising extraction properties of the modified diglycolamides towards the development of continuous solvent extraction processes.     

Rheological behavior of polyester blend and mechanical properties of the polypropylene–polyester blend fibers

The article deals with method of preparation, rheological properties, phase structure, and morphology of binary blend of poly(ethylene terephthalate) (PET)/poly(butylene terephthalate) (PBT) and ternary blends of polypropylene (PP)/(PET/PBT). The ternary blend of PET/PBT (PES) containing 30 wt % of PP is used as a final polymer additive (FPA) for blending with PP and subsequent spinning. In addition commercial montane (polyester) wax Licowax E (LiE) was used as a compatibilizer for spinning process enhancement. The PP/PES blend fibers containing 8 wt % of polyester as dispersed phase were prepared in a two‐step procedure: preparation of FPA using laboratory twin‐screw extruder and spinning of the PP/PES blend fibers after blending PP and FPA, using a laboratory spinning equipment. DSC analysis was used for investigation of the phase structure of the PES components and selected blends. Finally, the mechanical properties of the blend fibers were analyzed. It has been found that viscosity of the PET/PBT blends is strongly influenced by the presence of the major component. In addition, the major component suppresses crystallinity of the minor component phase up to a concentration of 30 wt %. PBT as major component in dispersed PES phase increases viscosity of the PET/PBT blend melts and increases the tensile strength of the PP/PES blend fibers. The impact of the compatibilizer on the uniformity of phase dispersion of PP/PES blend fibers was demonstrated. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 4222–4227, 2006     

Application of the SUSAN filter to wavelet video-coding artifact removal

This paper proposes the application of the Single Univalve Segment Assimilating Nucleus (SUSAN) algorithm for the reduction of coding artifacts in wavelet video-coding schemes. The SUSAN filter is as an image-structure preserving non-linear filter with low computational complexity. The filter adapts its bandwidth and stop-band attenuation based on a simple pixel classification procedure. In addition to this initial proposition, the paper provides two extensions of the original 2-D filter to the temporal domain: a two-stage 2-D+T SUSAN filter and a pure 3-D SUSAN filter. Experimental results provided in the paper provide substantial evidence of the effectiveness of the proposed approaches in terms suppression of artifacts that are typical in wavelet coding. Comparative tests show that SUSAN and its proposed extensions outperform state-of-the-art post-processing algorithms both in terms of objective (PSNR) and perceptual (PQS) quality comparisons.     

Droplet detachment regimes in annular laser beam droplet generation from a metal wire

Pendant droplet detachment regimes in the novel annular laser beam droplet generation from a metal wire are analyzed. In drop-on-demand generation, droplet detachment can be achieved via Rayleigh–Plateau instability based molten wire column break-up. Detachment dynamics are influenced by the distance between the annular laser beam focus and the pendant droplet neck. In the continuous generation of a droplet sequence, droplet detachment is governed by the laser pulse frequency, resulting in a spontaneous, resonant, or Rayleigh–Plateau instability based detachment regime. In addition to drop-on-demand generation, continuous droplet generation with spontaneous and mass-spring resonant detachment are suitable for metal droplet based engineering applications where accurate droplet diameter and deposition position are required.