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.     

全新控制系统--压铸过程的心脏

全新的工艺数据永久记录,对压铸过程进行最优化控制满足适用并易于使用的市场需求.布勒公司新的dat@net控制系统(见图1和图2),综合了传统技术,实时操作,工业耐用性和稳定性,以及当今最先进的PCj技术的优点.精心的硬、软件匹配允许使自动化方案不受约束.也是首次,这种控制系统使压铸设备能够按照客户需求完全协调.     

Isobutylene polymerization in the presence of t-BuCl/SnCl4

Summary The effect of tert-butyl chloride in the polymerizations of isobutylene carried out in the presence of SnCl₄ in dichloromethane at temperatures-20°C and-78°C was investigated. Synthesized polyisobutylene samples showed a bimodal molecular weight distribution (MWD) and it was found that the weight content of the lowermolecular weight (LMW) fraction increased with increasing t-BuCl concentration in the polymerization mixture. The effect of ageing of the initiation mixture t-BuCl/SnCl₄ in CH₂Cl₂ prepared in advance on MWD of the PIB samples was also studied. Ageing of the initiation system supports the formation of the LMW fraction and this oily PIB is the only product of the polymerization at-20°C, .     

Expert judgement on the long term possibilities of conventional emission abatement technologies for passenger cars

Topics in Catalysis - This paper presents the results of a quantitatively substantiated “expert judgement” concerning the potential for further reduction of the exhaust emissions of...     

Zur optimierung der Polymerfraktionierung auf der Grundlage von Lösungsgleichgewichten in Lösungsmittel-Fällungsmittel-Systemen

The phase separation behavior of dilute polydisperse polymer solutions primarily depends on the partial concentration of each polymer component. So the equilibrium data obtained by turbidimetric titration with “calibration” fractions and their mixtures can be used for the construction of a solubility diagram (Claesson-diagram) which generally allows to describe fractionation processes. It can be shown that the characteristic features of precipitation fractionations can well be derived from the solubility diagram. This diagram then offers the possibility for a complete discussion of parameter variation (concentration, step of γ-variation, process-scheme, temperature, solvent/nonsolvent-system) on the efficiency of a fractionation step. On one hand these results correspond – as for the concentration variation – to well known experimentell experiences. On the other hand it is possible for the first time to give definite predictions for the influence of temperature and the solvent/nonsolvent system. The temperature selection can be shown to be inconsiderable for the separation effect. The usual characterization of solvents and nonsolvents as “good” or “poor” is absolutely insufficient, if not misleading, for there is no connection between these properties and the shape of the solubility diagram. Based on the analysis of the single parameters the optimum conditions for the preparation of narrow preparation of narrow precipitation fractions can be derived.     

Über den Einfluß der Grenzflächenspannung auf die Haftfestigkeit

The values of adhesion between four diffrent adhesive,and (i) steel substrates whose surface energy had been altered by adsorption, and (ii) several polymer having different surface energies, had been measured. The results show that the adhesion has a maximum value when the surface energy of the hardened adhesive is equals to that of the substrate, i.e. when the interfacial energy adhesive/substrate is a minimum. The adhesion of the adhesives to the polymer was much smaller than to the steel sprcimens and the dependence of the adhesion onm the interfacial energy was sharper in the case of the polymers. The decrease of the adhesion with increasing interfacial energy was fiund to be greater if the liquid adhesive wets the substrate badly than the steel speciman.     

On a generalization of Bernstein polynomials and Bézier curves based on umbral calculus

In Winkel (2001) a generalization of Bernstein polynomials and Bézier curves based on umbral calculus has been introduced. In the present paper we describe new geometric and algorithmic properties of this generalization including: (1) families of polynomials introduced by Stancu (1968) and Goldman (1985), i.e., families that include both Bernstein and Lagrange polynomial, are generalized in a new way, (2) a generalized de Casteljau algorithm is discussed, (3) an efficient evaluation of generalized Bézier curves through a linear transformation of the control polygon is described, (4) a simple criterion for endpoint tangentiality is established.     

Fault-Tolerant Formation Driving Mechanism Designed for Heterogeneous MAVs-UGVs Groups

A fault-tolerant method for stabilization and navigation of 3D heterogeneous formations is proposed in this paper. The presented Model Predictive Control (MPC) based approach enables to deploy compact formations of closely cooperating autonomous aerial and ground robots in surveillance scenarios without the necessity of a precise external localization. Instead, the proposed method relies on a top-view visual relative localization provided by the micro aerial vehicles flying above the ground robots and on a simple yet stable visual based navigation using images from an onboard monocular camera. The MPC based schema together with a fault detection and recovery mechanism provide a robust solution applicable in complex environments with static and dynamic obstacles. The core of the proposed leader-follower based formation driving method consists in a representation of the entire 3D formation as a convex hull projected along a desired path that has to be followed by the group. Such an approach provides non-collision solution and respects requirements of the direct visibility between the team members. The uninterrupted visibility is crucial for the employed top-view localization and therefore for the stabilization of the group. The proposed formation driving method and the fault recovery mechanisms are verified by simulations and hardware experiments presented in the paper.     

Bestimmung des molekulargewichts von „mikrogelhaltigem”︁ polystyrol mit der ultrazentrifuge (methode archibald)

The weight average molecular weight M_w of a mixture of two polystyrenes with very high and relatively low molecular weights (M_w = 16.1 · 10⁶ and 98 · 10³ g/mole), as a model for polymers containing microgel, was determined by ultracentrifugation with the ARCHIBALD-methode. M_w decreases with increasing number of rotation N. The exact molecular weight can only be determined by extrapolation to N = 0. This value depends nearly completely on the molecular weight and weight percentage of the “microgel”. It is not suitable for the characterization of the whole sample.