Synthesis and Pharmacological In Vitro Investigations of Novel Shikonin Derivatives with a Special Focus on Cyclopropane Bearing Derivatives

Melanoma is the deadliest form of skin cancer and accounts for about three quarters of all skin cancer deaths. Especially at an advanced stage, its treatment is challenging, and survival rates are very low. In previous studies, we showed that the constituents of the roots of Onosma paniculata as well as a synthetic derivative of the most active constituent showed promising results in metastatic melanoma cell lines. In the current study, we address the question whether we can generate further derivatives with optimized activity by synthesis. Therefore, we prepared 31, mainly novel shikonin derivatives and screened them in different melanoma cell lines (WM9, WM164, and MUG-Mel2 cells) using the XTT viability assay. We identified (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl 2-cyclopropyl-2-oxoacetate as a novel derivative with even higher activity. Furthermore, pharmacological investigations including the ApoToxGlo^TM Triplex assay, LDH assay, and cell cycle measurements revealed that this compound induced apoptosis and reduced cells in the G1 phase accompanied by an increase of cells in the G2/M phase. Moreover, it showed hardly any effects on the cell membrane integrity. However, it also exhibited cytotoxicity against non-tumorigenic cells. Nevertheless, in summary, we could show that shikonin derivatives might be promising drug leads in the treatment of melanoma.     

Etude electrochimique de differentes ilmenites

The electrochemical behaviour of several natural ilmenites has been studied by cyclic voltammetry. From the analysis of the current-voltage curves it was concluded that the valences of the metal ions in FeTiO₃ are Fe^II and Ti^IV. It was also found that little amounts of Fe^III and excess of Ti^IV (probably TiO₂) can enter into the composition of the ilmenites.     

Characterization of Precursor-Derived Silicon-Carbon-Nitrogen Ceramics after Creep Testing

Precursor-derived Si-C-N ceramics after creep testing in air were characterized using X-ray diffractometry (XRD) and transmission electron microscopy (TEM). XRD analysis showed that the crept Si-C-N ceramics were covered by an α-cristobalite layer. TEM observations revealed that the precipitated nanocrystallites in the crept Si-C-N ceramics were β-SiC. Between α-cristobalite and crept Si-C-N ceramic, there was an intermediate zone in which Si₂N₂O nanocrystallites were distributed homogeneously. Moreover, Si₂N₂O nanocrystallites were often found covering the surface of nanosized gas channels in the crept Si-C-N ceramics, where no α-cristobalite phase was detected. Based on these observations, a two-step oxidation mechanism of Si-C-N ceramics during creep testing in air was proposed.     

An axisymmetric model for thread forming in polycarbonate and polypropylene screw and boss fasteners

Plastic boss and screw fasteners are an economical means of securing automotive components, such as instrument or body panels. However, new materials and/or suboptimal design present challenges to the boss/screw effectiveness. Failure of a boss/screw can result is loss of functional performance or increased squeak and rattle. Failure is often controlled by what occurs during the initial thread‐forming process. Thus, the goal of this paper is to develop an FEA model to elucidate the thread‐forming process so that we can facilitate subsequent design and/or process optimization, and understand potential failure modes. The FEA must accommodate nonlinear couplings, such as large strain and heat transfer. Heat generation is present in the forms of interfacial shear heating and plastic work associated with the large deformation of the interface between the boss and screw. Strain rate‐dependent materials are included using the Eyring theory for plastic flow of polymeric materials. Results of the model are presented and compared to experimentally determined torque curves and temperatures. Polym. Eng. Sci. 44:1498–1508, 2004. © 2004 Society of Plastics Engineers.     

Is the particle deposition in a cell exposure facility comparable to the lungs? A computer model approach

Abstract

Cell exposure experiments at the air-liquid interface (ALI) are used increasingly as indicators for health effects and for the impact of aerosols on the lung. Thereby the aerosol particles are kept airborne and can deposit on a cell surface area similar to the human respiratory tract (RT). However, geometry and air flow rates of an ALI system deviate considerably from the RT. As the tissue-delivered particle dose to the lungs (TD) can hardly be measured, computer models of particle deposition are used here to mimic both the particle deposition at ALI and in the RT. An ALI exposure setup (VitroCell GmbH) for an airflow rate of 100 cm³ min^?1 is selected, where the particle deposition model has been verified experimentally. For the RT we use the hygroscopic lung deposition model of Ferron et al. (2013 Ferron, G. A., S. Upadhyay, R. Zimmermann, and E. Karg. 2013. Model of the deposition of aerosol particles in the respiratory tract of the rat. II. Hygroscopic particle deposition. J. Aerosol Med. Pulm. Drug Deliv. 26 (2):101–19. doi:10.1089/jamp.2011.0965.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]). Model runs are performed for the particle deposition and for the deposited particles per surface area in both the ALI and the RT. The results show that the ALI-deposited mass is 1-2 orders of magnitude higher than in the alveolar region, because the surface area of the lung region is substantially larger. A particle size range from 40 to 450 nm is identified, where the ratio of both the deposition in a lung region and the deposition at the ALI varies by a factor less than two. Mean values for this ratio are 31 and 101 for the tracheo-bronchial and the alveolar region, respectively. The same size range is found for the ratio of the deposited particles per surface area in a lung region and at the ALI. For this range the mean surface deposition at the ALI is 23- and 1575-times larger than in the tracheo-bronchial and the alveolar lung region, respectively. The effect is partly compensated by different flow rate and cell size.

Copyright © 2020 American Association for Aerosol Research     

Smoothed Particle Hydrodynamics (SPH) simulation of a high-pressure homogenization process

High-pressure homogenization is a widely used process in the food, pharmaceutical, and cosmetic industry for producing emulsions. Because of small dimensions and high velocities, the experimental and numerical investigation of such a process is challenging. Hence, the development of products is mostly based on trial and error. In this paper, simulations of a generic high-pressure homogenization process using the Lagrangian, mesh-free smoothed particle hydrodynamics (SPH) method are presented and compared to experimental findings using Micro-Particle Image Velocimetry (μ-PIV). The SPH code has been developed and validated with the scope of simulating technical relevant multi-phase problems (Höfler et al. 2012). The present simulations cover the investigation of two different dynamic viscosities of the dispersed phase as well as different droplet trajectories. The comparison between the simulations and the experiments focusses on the velocity distribution of the continuous phase and the droplet deformation and breakup. In both cases a qualitatively good agreement is observed, demonstrating the ability of our SPH implementation for simulating technical relevant two-phase flows.     

A Python extension for the massively parallel multiphysics simulation framework waLBerla

We present a Python extension to the massively parallel HPC simulation toolkit waLBerla. waLBerla is a framework for stencil based algorithms operating on block-structured grids, with the main application field being fluid simulations in complex geometries using the lattice Boltzmann method. Careful performance engineering results in excellent node performance and good scalability to over 400,000 cores. To increase the usability and flexibility of the framework, a Python interface was developed. Python extensions are used at all stages of the simulation pipeline: they simplify and automate scenario setup, evaluation, and plotting. We show how our Python interface outperforms the existing text-file-based configuration mechanism, providing features like automatic nondimensionalization of physical quantities and handling of complex parameter dependencies. Furthermore, Python is used to process and evaluate results while the simulation is running, leading to smaller output files and the possibility to adjust parameters dependent on the current simulation state. C++ data structures are exported such that a seamless interfacing to other numerical Python libraries is possible. The expressive power of Python and the performance of C++ make development of efficient code with low time effort possible.