Discovery of Rogaratinib (BAY 1163877): a pan‐FGFR Inhibitor

Rogaratinib (BAY 1163877) is a highly potent and selective small‐molecule pan‐fibroblast growth factor receptor (FGFR) inhibitor (FGFR1–4) for oral application currently being investigated in phase 1 clinical trials for the treatment of cancer. In this publication, we report its discovery by de novo structure‐based design and medicinal chemistry optimization together with its pharmacokinetic profile.     

An Alternating Skin–Core Structure in Melt Multi‐Injection‐Molded Polyethylene

Shish‐kebab, which is endowed with superior strength and modulus, provides the potential to fabricate self‐reinforced polymer products. However, the injection‐molded product usually exhibits a typical skin–core structure, and the shish‐kebab is only located in an extremely thin shear layer. Therefore, the controlling and tailoring of crystal structures in complex flow field to improve the mechanical properties of the injection‐molded sample are still a great challenge. Herein, for the first time, high‐density polyethylene sample with a novel macroscopic alternating skin–core structure is achieved using a melt multi‐injection molding technique. Results show that, with increasing the amount of melt injection, the layers of skin–core structure increase in the form of arithmetic progression, and therefore the tensile strength of the samples progressively increases due to an increase of shish‐kebab content. This study demonstrates a new approach to achieve multilayer homogeneous materials with excellent tensile strength via macroscopic structural design during the practical molding process.     

An emission-potential multislice approximation to simulate thermal diffuse scattering in high-resolution transmission electron microscopy

Thermal diffuse scattered electrons significantly contribute to high-resolution transmission electron microscopy images. Their intensity adds to the background and is peaked at positions of atomic columns. In this paper we suggest an approximation to simulate intensity of thermal diffuse scattered electrons in plane-wave illumination transmission electron microscopy using an emission-potential multislice algorithm which is computationally less intensive than the frozen lattice approximation or the mutual intensity approach. Intensity patterns are computed for Au and InSb for different crystal orientations. These results are compared with intensities from the frozen lattice approximation based on uncorrelated vibration of atoms as well as with the frozen phonon approximation for Au. The frozen phonon method uses a detailed phonon model based on force constants we computed by a density functional theory approach. The comparison shows that our suggested emission-potential method is in close agreement with both the frozen lattice and the frozen phonon approximations.     

Mass spectrometry in bioinorganic analytical chemistry

A considerable momentum has recently been gained by in vitro and in vivo studies of interactions of trace elements in biomolecules due to advances in inductively coupled plasma mass spectrometry (ICP MS) used as a detector in chromatography and capillary and planar electrophoresis. The multi-isotopic (including non-metals such as S, P, or Se) detection capability, high sensitivity, tolerance to matrix, and large linearity range regardless of the chemical environment of an analyte make ICP MS a valuable complementary technique to electrospray MS and MALDI MS. This review covers different facets of the recent progress in metal speciation in biochemistry, including probing in vitro interactions between metals and biomolecules, detection, determination, and structural characterization of heteroatom-containing molecules in biological tissues, and protein monitoring and quantification via a heteroelement (S, Se, or P) signal. The application areas include environmental chemistry, plant and animal biochemistry, nutrition, and medicine.     

Note: Piezoelectric polymers as transducers for the ultrasonic-reflection method and the application in mechanical property-screening of coatings

In the last years, non-destructive ultrasonic testing methods are more and more frequently employed in order to investigate the drying and curing processes of different coatings. Among them an ultrasonic reflection method was developed allowing the simultaneous measurement with longitudinal and transversal waves. In order to generate the ultrasonic pulse, piezoelectric ceramics or oxides are usually used as transducer materials which are connected to a delay line. Here, we demonstrate a similar approach for the ultrasonic reflection method installing piezoelectric polymers as ultrasonic transducer materials. In detail, poly(vinylidene fluoride and trifluoroethylene) [P(VDF-TrFE)] copolymers were prepared as piezoelectric transducer layers directly onto the metallization of glass delay lines avoiding additional bonding processes. The film preparation was carried out by solvent casting the polymer onto an area with a diameter of 12 mm and is optimized so that relatively homogeneous polymer layers with thicknesses between 14 and 35 μm are adjusted by the deposited amount of the polymer. Electrical poling renders the polymer piezoelectric. The ultrasonic properties of the P(VDF-TrFE) transducer and their usability for the ultrasonic reflection method are described also in comparison to previous measurements using LiNbO(3) transducer.     

A complementary-metal-oxide-semiconductor-field-effect-transistor-compatible atomic force microscopy tip fabrication process and integrated atomic force microscopy cantilevers fabricated with this process

A complementary-metal-oxide-semiconductor-field-effect-transistor-compatible process for the fabrication of atomic force microscopy cantilevers with integrated tips has been developed. For the first time, the tips are fabricated after the completion of the regular complementary metal-oxide-semiconductor-field-effect-transistor fabrication process sequence. On-chip circuit components, such as piezoresistive deflection sensors, deflection actuators, and amplifiers, are fabricated on the mirror-polished surface of the wafer, ensuring optimal performance. The tip fabrication process is based on anisotropic silicon etching at low temperature using a tetramethylammonium hydroxide solution. The anisotropic etching process has been optimized to ensure process controllability. Using the described process, complementary-metal-oxide-semiconductor-field-effect-transistor-based cantilevers with piezoresistive deflection sensors and integrated tips have been successfully fabricated. Force-distance curves and scanning images in constant-force mode have been recorded.     

Applying an information transmission approach to extract valence electron information from reconstructed exit waves

The knowledge of the valence electron distribution is essential for understanding the properties of materials. However this information is difficult to obtain from HREM images because it is easily obscured by the large scattering contribution of core electrons and by the strong dynamical scattering process. In order to develop a sensitive method to extract the information of valence electrons, we have used an information transmission approach to describe the electron interaction with the object. The scattered electron wave is decomposed in a set of basic functions, which are the eigen functions of the Hamiltonian of the projected electrostatic object potential. Each basic function behaves as a communication channel that transfers the information of the object with its own transmission characteristic. By properly combining the components of the different channels, it is possible to design a scheme to extract the information of valence electron distribution from a series of exit waves. The method is described theoretically and demonstrated by means of computer simulations.     

Designing for collaboration: a study in intergenerational social game design

This paper presents a study of a computer game designed for the elderly, allowing them to train their memory while playing the game. The game supports both a single-player and a multiplayer mode, in which the elderly can play with their friends or family using an embedded video chat application. The main question that is addressed in this paper is how the elderly gamers’ experience is influenced by the possibility to communicate directly with the other players. The study presents a comparison of the game experience and appreciation of older users and their (grand)children playing the game together, with or without the video chat application. Most importantly, the study shows that the added value of video chat is not limited to social contact, but that it also provides opportunities for the younger generation to assist the elderly during the game. In conclusion, the paper points out some intergenerational game design implications, and some future research suggestions.