Tetrahydroindoles as Multipurpose Screening Compounds and Novel Sirtuin Inhibitors

Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp³ hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC₅₀ value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling.     

Experimental and numerical analysis of the influence of cable tray arrangements on the resulting mass loss rate and fire spreading

In the context of industrial buildings and power plants, electrical installations and cable trays represent a main fuel load and a potential initial fire source due to possible short circuits or comparable malfunction. Furthermore, a fire can spread from one tray to additional trays mounted above and/or horizontally on one tray. Because of the high significance of cable fires, several research projects have been carried out, investigating the fire behaviour of cables from small‐scale tests, eg, the cone calorimeter, up to large‐scale tests, analysing complete cable tray constructions. The goal of the work presented in this paper is the extension of the knowledge regarding the influence of geometrical parameters like the packing density and tray distance on the burning behaviour and fire spread of cable tray installations. The results are considered, together with test results from the literature, to quantify the main physical parameters describing the burning behaviour. In a next step, the general applicability of these parameters as input data for the parametrization of the source term of numerical simulations is shown. The test results show that the burning behaviour and the fire spreading highly depend on the cable arrangement of the cables on the cable tray, in combination with other boundary conditions. By applying the results as input for a fire simulation, the mass loss rate is considered appropriately.     

Dielectric relaxation of vegetable-based polyurethane

Vegetable-based polyurethane (PU) was prepared in the thin film form by spin coating. This polymer is synthesised from castor oil, which can be extracted from the seeds of a native plant in Brazil called mamona. This polymer is biocompatible and is being used as material for artificial bone. The PU was characterised by dielectric spectroscopy in a wide range of frequency (10^–5 Hz to 10⁵ Hz) and by thermally stimulated discharge current (TSDC) measurements. The glass transition temperature (T _g = 39°C) was determined and using the initial rise method the activation energy was found to be 1.58 eV.     

Test Case Generation as an AI Planning Problem

While Artificial Intelligence techniques have been applied to a variety of software engineering applications, the area of automated software testing remains largely unexplored. Yet, test cases for certain types of systems (e.g., those with command language interfaces and transaction based systems) are similar to plans. We have exploited this similarity by constructing an automated test case generator with an AI planning system at its core. We compared the functionality and output of two systems, one based on Software Engineering techniques and the other on planning, for a real application: the StorageTek robot tape library command language. From this, we showed that AI planning is a viable technique for test case generation and that the two approaches are complementary in their capabilities.     

Comment and discussion on digital processing of PD pulses

Some of the more salient aspects of the digital processing technology of PD signals are examined. Most of the efforts in this field are concentrated on the application of digital analyzers for pulse height analysis, pattern recognition and identification of the physical phenomena. It is demonstrated that errors in the signal processing unit can lead to dominant mistakes in the interpretation of the test results