Identification and Structure–Activity Relationship Studies of Small‐Molecule Inhibitors of the Methyllysine Reader Protein Spindlin1

The methyllysine reader protein Spindlin1 has been implicated in the tumorigenesis of several types of cancer and may be an attractive novel therapeutic target. Small‐molecule inhibitors of Spindlin1 should be valuable as chemical probes as well as potential new therapeutics. We applied an iterative virtual screening campaign, encompassing structure‐ and ligand‐based approaches, to identify potential Spindlin1 inhibitors from databases of commercially available compounds. Our in silico studies coupled with in vitro testing were successful in identifying novel Spindlin1 inhibitors. Several 4‐aminoquinazoline and quinazolinethione derivatives were among the active hit compounds, which indicated that these scaffolds represent promising lead structures for the development of Spindlin1 inhibitors. Subsequent lead optimization studies were hence carried out, and numerous derivatives of both lead scaffolds were synthesized. This resulted in the discovery of novel inhibitors of Spindlin1 and helped explore the structure–activity relationships of these inhibitor series.     

Prototype and Chimera-Type Galectins in Placentas with Spontaneous and Recurrent Miscarriages

Galectins are galactose binding proteins and, in addition, factors for a wide range of pathologies in pregnancy. We have analyzed the expression of prototype (gal-1, -2, -7, -10) and chimera-type (gal-3) galectins in the placenta in cases of spontaneous abortions (SPA) and recurrent abortions (RA) in the first trimester. Fifteen placental samples from healthy pregnancies were used as a control group. Nine placentas were examined for spontaneous abortions, and 12 placentas for recurrent abortions. For differentiation and evaluation of different cell types of galectin-expression in the decidua, immunofluorescence was used. For all investigated prototype galectins (gal-1, -2, -7, -10) in SPA and RA placenta trophoblast cells the expression is significantly decreased. In the decidua/extravillous trophoblast only gal-2 expression was significantly lowered, which could be connected to its role in angiogenesis. In trophoblasts in first-trimester placentas and in cases of SPA and RA, prototype galectins are altered in the same way. We suspect prototype galectins have a similar function in placental tissue because of their common biochemical structure. Expression of galectin 3 as a chimera type galectin was not found to be significantly altered in abortive placentas.     

The Significance of Epithelial-to-Mesenchymal Transition for Circulating Tumor Cells

Epithelial to mesenchymal transition (EMT) is a process involved in embryonic development, but it also plays a role in remote metastasis formation in tumor diseases. During this process cells lose their epithelial features and adopt characteristics of mesenchymal cells. Thereby single tumor cells, which dissolve from the primary tumor, are enabled to invade the blood vessels and travel throughout the body as so called “circulating tumor cells” (CTCs). After leaving the blood stream the reverse process of EMT, the mesenchymal to epithelial transition (MET) helps the cells to seed in different tissues, thereby generating the bud of metastasis formation. As metastasis is the main reason for tumor-associated death, CTCs and the EMT process are in the focus of research in recent years. This review summarizes what was already found out about the molecular mechanisms driving EMT, the consequences of EMT for tumor cell detection, and suitable markers for the detection of CTCs which underwent EMT. The research work done in this field could open new roads towards combating cancer.     

Oxidation of Cobalt Metal

By means of inert markers of radio-platinum, it has been shown that cobalt metal oxidizes by outward diffusion of cobalt atoms through the oxide. Oxidation rates have been measured at various temperatures and oxygen pressures and have been found to agree with the rates calculated from the Wagner equation and the authors’ values for the diffusion coefficient of cobalt in the oxide. The distribution of radio-cobalt in growing oxide layers has been accurately measured and found to be different from that predicted from the Wagner oxidation theory. Attempts have been made to measure the change of lattice parameter of the oxide with composition.     

Long‐term testing of a high temperature polymer electrolyte membrane fuel cell: The effect of reactant gases

The investigations have been conducted with different oxidants and fuels with the aim of determining the state‐of‐the‐art of commercially available high temperature polymer electrolyte fuel cells based on polybenzimidazole for its application in combined heat and power generation systems. The fuel cell test performed with synthetic reformate (?63 μV/h) showed an increase of anode charge and mass transfer resistances. This behavior has suggested that CO may be generated from the CO₂ included in the synthetic reformate via reverse water gas shift reaction. The fuel cell test performed with pure O₂ developed the highest degradation rates (?70 μV/h) due to fast oxidative degradation of membrane electrode assembly materials such as cathode catalyst and membrane. Fuel cell operation with H₂/air exhibited the lowest degradation rates (?57 μV/h) and it requires longer investigating times to identify the different degradation mechanisms. Moreover, fuel cell tests performed with air suggested longer break‐in procedures to complete catalyst activation and redistribution of electrolyte. © 2015 American Institute of Chemical Engineers AIChE J, 62: 217–227, 2016     

Tensile behavior of glass fiber-reinforced acetal polymer

The tensile stress-strain behavior of glass fiber-reinforced polyacetal resin was investigated for various fiber concentrations, fiber length distributions, and finishing agents. The polyacetal fiber blends change considerably in strength and elongation at break when treated with ammonium chloride, but otherwise similar specimens still follow a common stress-strain curve to a point shortly before failure. As the mean fiber length decreases, the modulus and tensile strength fall, but the elongation at break remains almost unchanged. The observed tensile behavior is discussed in terms of a simplified model, which assigns the fibers to two categories: a fraction α parallel to the applied load, and the remainder distributed in a plane perpendicular to the load axis. By fitting this model to the stress-strain curves, two other constants of each system are derived: a length-dependent efficiency factor β for parallel fibers, whose magnitude agrees with the predictions of Rosen and his co-workers, and a factor γ which expresses the constraint of the matrix resin by the “transverse” fibers. The behavior of γ is consistent with Tsai's theory of the transverse modulus of laminates, if a reasonable amount of fiber–fiber contact is assumed. In terms of this model, possible interpretations of the behavior under repeated loading and the mechanism of tensile failure are presented.     

ε-Caprolactam-Assoziate als Reaktivkomponenten in der Isocyanat-Chemie und als reaktive Lösungs- und Quellungsmittel bei Matrizen-Reaktionen

At room temperature water and organic mono- and polyhydroxyl compounds form – particularly with 5- to 7-membered lactams – associates of strikingly low viscosity. The present paper is concerned with significant aspects of the properties and practical applica-tions of these c-caprolactam associates. 6-caprolactam/water associates are of interest as solvents for materials which are difficult to dissolve, contain water or polyols rcsp. bound in activated form for reaction with isocyanates and exhibit interesting propertics as chain-lengthening and blowing agents in foaming processes. Because of their remarkable properties the associates may be considered as low-molecular weight cyclic structures with hydrogen bonding. Mono- and polyhydroxyl compounds and oximes are also highly activated by forming associates with 6-caprolactam and, being liquid systems completely free of solvent, they can be used in a wide variety of ways as structural elements in isocyanate chemistry which allow non-polluting techniques. 8:-Caprolactam associates can be employed for linearization of polyurethanes and polyurethane polyureas crosslinked by biuret and allophanate groups. Partial or quantitative linearization with elimination of biuret and allophanate crosslinking sites in foams yields new types of matrices similar to textiles with extremely reduced deflection hardness. The heavy swelling which takes place in linearized cellular polyurethane matrices is utilized for inducing matrix reactions and the cellular structure in the spaces newly created by the swelling pressure and the irreversible fixation of the swelling caused by rapid solids formation of the coreactants results in interesting foam combinations.