Identification and Optimization of the First Highly Selective GLUT1 Inhibitor BAY‐876

Despite the long‐known fact that the facilitative glucose transporter GLUT1 is one of the key players safeguarding the increase in glucose consumption of many tumor entities even under conditions of normal oxygen supply (known as the Warburg effect), only few endeavors have been undertaken to find a GLUT1‐selective small‐molecule inhibitor. Because other transporters of the GLUT1 family are involved in crucial processes, these transporters should not be addressed by such an inhibitor. A high‐throughput screen against a library of ～3 million compounds was performed to find a small molecule with this challenging potency and selectivity profile. The N‐(1H‐pyrazol‐4‐yl)quinoline‐4‐carboxamides were identified as an excellent starting point for further compound optimization. After extensive structure–activity relationship explorations, single‐digit nanomolar inhibitors with a selectivity factor of >100 against GLUT2, GLUT3, and GLUT4 were obtained. The most promising compound, BAY‐876 [N⁴‐[1‐(4‐cyanobenzyl)‐5‐methyl‐3‐(trifluoromethyl)‐1H‐pyrazol‐4‐yl]‐7‐fluoroquinoline‐2,4‐dicarboxamide], showed good metabolic stability in vitro and high oral bioavailability in vivo.     

Electrochemical investigations on amorphous Fe-base alloys for alkaline water electrolysis

In this work different amorphous melt-spun Fe-alloys (Fe₈₂B₁₈, Fe₈₀Si₁₀B₁₀, Fe₆₀Co₂₀Si₁₀B₁₀) were investigated as cathode materials for the alkaline electrolysis of water. In particular, the influence of cobalt as well as the metalloids boron and silicon on the activity for the hydrogen evolution reaction (HER) was studied in 1 M KOH at 298 K using cyclic voltammetric, galvanostatic and polarization techniques. The electrocatalytic activity was evaluated in the view of the overpotential. It was found that cyclic voltammetric techniques can be used to activate the melt-spun Fe-alloys strongly. Different cyclic voltammetric activation procedures are discussed and the influence of the sweep rate and the potential window on the HER activity was elucidated. The experimental data indicate that the addition of metalloids and, most importantly, of cobalt improves the HER activity of the materials. Thus, the overpotential can be reduced by 200 mV compared to polycrystalline Ni.     

Modeling planar slider-crank mechanisms with clearance joints in RecurDyn

Revolute joints in applications always show clearance between pin and bushing due to manufacturing tolerances, the need of relative motion or progressing wear. Many researchers developed and investigated methodologies to calculate the dynamic behavior of mechanisms with such imperfect joints. Very often they use a simple slider-crank mechanism to test or demonstrate the capability of their approaches. In this paper, a methodology for simulating a slider-crank mechanism with an imperfect revolute joint in RecurDyn, a commercial multibody simulation tool, is presented. Therefore, a thorough investigation of existing contact, damping and friction force models as well as different ways of modeling revolute joints in RecurDyn was conducted. For the investigation of the damping models, a special program for calculating the model parameters for a given coefficient of restitution was developed. Only one damping model was capable of reproducing the experimental results, which were found in literature. Some characteristic results of the slider-crank mechanism are presented in a way that they can be compared to results in other papers. Thereby. a good correlation was achieved, demonstrating the capabilities of the methodology.     

Methacrylated calix[4]arene phosphonic acids as functionalized crosslinker for radical polymerization

We describe the synthesis of 5,11,17,23‐tetra‐tert‐butyl‐25,27‐dioxypropylphosphonic acid‐26,28‐dimethacryloyloxy‐calix [4]arene and 5,11,17,23‐tetra‐tert‐butyl‐25‐oxypropylphosphonic acid‐27‐hydroxy‐26,28‐dimethacryloyloxy‐calix[4]arene starting from para‐tert‐butyl‐calix[4]arene. The complete reaction was proved by matrix‐assisted laser desorption ionization time of flight mass spectrometry and nuclear magnetic resonance spectroscopy. The influence of these compounds on the kinetics of the radical polymerization of methyl methacrylate was shown by dilatometry. Furthermore, the adhesive properties of dental adhesives containing these calix[4]arene derivatives were investigated. Copyright © 2012 Society of Chemical Industry     

p‐TCOs für Transparente Elektronik

p‐type TCOs for use in transparent electronics In this article, a new type of semiconducting material is introduced. Transparent conducting thin films are already established in our everydaylife. But the type of these so‐called ?TCOs”? is dominated by electron transport, that means they are n‐type. To get transparent p‐n‐junctions and therefore transparent electronics, the missing part is a transparent p‐type material. Researchers all over the world have found different approach to produce this new generation of materials. At the Fraunhofer Institute for Surface Engineering and Thin Films (IST) in Braunschweig it is now possible to produce these kind of thin films as well.     

Market penetration analysis of electric vehicles in the German passenger car market towards 2030

There is currently intensive public discussion of fuel cell electric vehicles (FCEV) and other electric powertrains, such as battery electric vehicles (BEV), plug-in hybrid electric vehicles (PHEV) and hybridized combustion engine vehicles (HEV). In this context, the German government has set the target of one million electric vehicles on the road by 2020, and six million by 2030 [1]. The goal of this paper is to identify the possible market share of electric vehicles in the German new car fleet in three scenarios in the timeframe from 2010 to 2030. The VECTOR21 vehicle technology scenario model is used to model the fleet in three scenarios. In the reference scenario with business-as-usual parameters, 189,000 electric vehicles will be sold in Germany by 2020. Scenario two with purchase price incentives from 5000 EUR, high oil prices, and low prices for hydrogen and electricity will result in 727,000 vehicles. In the last scenario with substantial OEM mark-up reductions and external conditions as in the business-as-usual scenario, 3.28 million vehicles will be sold.     

Austenitic stainless steel for separating safeguards: development of an FEA-model for the simulation of impact tests in reference to material specific parameters

Austenitic stainless steels have a high potential for the use in separating safeguards of machine tools based on the TRIP (Transformation Induced Plasticity) effect. The problem with these materials is the high variance of the alloy composition. Therefore, the specific penetration resistance W _D,spec varies significantly. The presented research analyses the impact of material specific parameters on the specific penetration resistance W _D,spec and the FEA simulation of impact tests. The result of the project is the knowledge of the penetration resistance and hence the security (factor of safety) against penetration.     

Analysis of the Stakeholder Engagement in the Deployment of Renewables and Smart Grid Technologies

The implementation of higher shares of renewables in a global energy mix has to be accompanied by simultaneous deployment of enabling smart grid technologies (SGTs). This combination will inevitably lead to a revolutionary change in a conventional energy system, particularly, the shifting role of consumers to prosumers. But resistance may arise from such a dramatic shift, since it is associated with high uncertainty in conjunction with increasing responsibilities of all stakeholders, the urgent need of effective control, and the development of a process. To ensure the positive influence, coherent actions of all players, and appropriate treatment of the spots of resistance, the analysis of the interplay between key stakeholders has been done. The paper introduces the framework for stakeholders' analysis, applies it on the European Union (EU) example, and provides recommendations to reduce the resistance of SGTs deployment.