Small-Molecule Inhibitors of METTL3, the Major Human Epitranscriptomic Writer

The RNA methylase METTL3 catalyzes the transfer of a methyl group from the cofactor S-adenosyl-L-methionine (SAM) to the N⁶ atom of adenine. We have screened a library of 4000 analogues and derivatives of the adenosine moiety of SAM by high-throughput docking into METTL3. Two series of adenine derivatives were identified in silico, and the binding mode of six of the predicted inhibitors was validated by protein crystallography. Two compounds, one for each series, show good ligand efficiency. We propose a route for their further development into potent and selective inhibitors of METTL3.     

Transport, chemical and electrochemical processes in a planar solid oxide fuel cell: Detailed three-dimensional modeling

A detailed numerical three-dimensional (3D) model for a planar solid oxide fuel cell (SOFC) is developed in this paper. The 3D model takes into account detailed processes including transport, chemical and electrochemical processes taking place in the cell. Moreover, effects of the composite electrodes are taken into account by considering an electrochemically active layer of finite thickness in each of the electrodes. The developed model is applied to a repeating unit of an anode-supported SOFC working under direct internal reforming conditions. Detailed results for chemical species, temperature, current density and electric potential distribution are presented and discussed. It was found that the temperature distribution across the cell is more uniform in the interconnects than in the inner part of the cell. However, only small differences in the electric potential between the electrode and the corresponding interconnect are found. The current density in the electrodes is found to be high near the electrolyte and low deep into the electrochemically active layer. The current density is also low under the ribs of the interconnects.     

Effect of thermal and mechanical factors on rheological properties of high performance inulin gels and spreads

The aim of this study was analysis of a number of factors affecting the rheological properties of high performance inulin gels and spreads in comparison with commercial products. Inulin gels (20%, 25%, 30%), commercial and inulin model spread (20% canola oil, 20% inulin, 3% emulsifier) were analysed. Inulin particles in water environment absorbed water which caused an increase in viscosity of the inulin suspensions. Different temperatures of preparation, cooling rates and viscosity increase which appeared during the stirring of inulin suspensions did not significantly change the rheological parameters of the final gels in contrast to heating rates (p ? 0.05). In spite of rigid laboratory conditions high standard deviation for hardness and apparent viscosity showed how difficult the process of an inulin crystallization is to control. Rheological properties of inulin model spread exhibited thixotropic and shear thinning behaviour which made it similar to commercial spread. The applied structure destruction step in the manufacturing process should be applied to make inulin model spread comparable to commercial spreads.     

Experimentelle Simulation der Oberflächenrissbildung beim Stranggießprozess mit Hilfe des IMC-B Versuchs

Continuous casting of steel free of surface cracks is still one of the major quality challenges in the whole steel production. The key roles for the phenomenon of surface cracking are played by the critical strain and the temperature-dependent material’s phenomena. The new In-Situ Characterization Bending (IMC-B) method will enable the investigation of the critical strains with respect to the cracking under the main continuous casting boundaries. This publication presents potential and interesting results of the IMC-B experiment.     

Simulations for the Development of Thermoelectric Measurements

In thermoelectricity, continuum theoretical equations are usually used for the calculation of the characteristics and performance of thermoelectric elements, modules or devices as a function of external parameters (material, geometry, temperatures, current, flow, load, etc.). An increasing number of commercial software packages aimed at applications, such as COMSOL and ANSYS, contain vkernels using direct thermoelectric coupling. Application of these numerical tools also allows analysis of physical measurement conditions and can lead to specifically adapted methods for developing special test equipment required for the determination of TE material and module properties. System-theoretical and simulation-based considerations of favorable geometries are taken into account to create draft sketches in the development of such measurement systems. Particular consideration is given to the development of transient measurement methods, which have great advantages compared with the conventional static methods in terms of the measurement duration required. In this paper the benefits of using numerical tools in designing measurement facilities are shown using two examples. The first is the determination of geometric correction factors in four-point probe measurement of electrical conductivity, whereas the second example is focused on the so-called combined thermoelectric measurement (CTEM) system, where all thermoelectric material properties (Seebeck coefficient, electrical and thermal conductivity, and Harman measurement of zT) are measured in a combined way. Here, we want to highlight especially the measurement of thermal conductivity in a transient mode. Factors influencing the measurement results such as coupling to the environment due to radiation, heat losses via the mounting of the probe head, as well as contact resistance between the sample and sample holder are illustrated, analyzed, and discussed. By employing the results of the simulations, we have developed an improved sample head that allows for measurements over a larger temperature interval with enhanced accuracy.     

How many protein‐coding genes are there in the Saccharomyces cerevisiae genome?

We have compared the results of estimations of the total number of protein-coding genes in the Saccharomyces cerevisiae genome, which have been obtained by many laboratories since the yeast genome sequence was published in 1996. We propose that there are 5300-5400 genes in the genome. This makes the first estimation of the number of intronless ORFs longer than 100 codons, based on the features of the set of genes with phenotypes known in 1997 to be correct. This estimation assumed that the set of the first 2300 genes with known phenotypes was representative for the whole set of protein-coding genes in the genome. The same method used in this paper for the approximation of the total number of protein-coding sequences among more than 40 000 ORFs longer than 20 codons gives a result that is only slightly higher. This suggests that there are still some non-coding ORFs in the databases and a few dozen small ORFs, not yet annotated, which probably code for proteins.     

Characterization of Combinatorially Independent Permutation Separability Criteria

The so-called permutation separability criteria are simple operational conditions that are necessary for separability of mixed states of multipartite systems: (1) permute the indices of the density matrix and (2) check if the trace norm of at least one of the resulting operators is greater than one. If it is greater than one then the state is necessarily entangled. A shortcoming of the permutation separability criteria is that many permutations give rise to equivalent separability criteria. Therefore, we introduce a necessary condition for two permutations to yield independent criteria called combinatorial independence. This condition basically means that the map corresponding to one permutation cannot be obtained by concatenating the map corresponding to the second permutation with a norm-preserving map. We characterize completely combina-torially independent criteria, and determine simple permutations that represent all independent criteria. The representatives can be visualized by means of a simple graphical notation. They are composed of three basic operations: partial transpose, and two types of so-called reshufflings. In particular, for a four-partite system all criteria except one are composed of partial transpose and only one type of reshuffling; the exceptional one requires the second type of reshuffling. Furthermore, we show how to obtain efficiently a simple representative for every permutation. This method allows to check easily if two permutations are Combinatorially equivalent or not.