Bioavailability Studies and in vitro Profiling of the Selective Excitatory Amino Acid Transporter Subtype 1 (EAAT1) Inhibitor UCPH‐102

Although the selective excitatory amino acid transporter subtype 1 (EAAT1) inhibitor UCPH‐101 has become a standard pharmacological tool compound for in vitro and ex vivo studies in the EAAT research field, its inability to penetrate the blood–brain barrier makes it unsuitable for in vivo studies. In the present study, per os (p.o.) administration (40 mg kg^?1) of the closely related analogue UCPH‐102 in rats yielded respective plasma and brain concentrations of 10.5 and 6.67 μm after 1 h. Three analogue series were designed and synthesized to improve the bioavailability profile of UCPH‐102, but none displayed substantially improved properties in this respect. In vitro profiling of UCPH‐102 (10 μm ) at 51 central nervous system targets in radioligand binding assays strongly suggests that the compound is completely selective for EAAT1. Finally, in a rodent locomotor model, p.o. administration of UCPH‐102 (20 mg kg^?1) did not induce acute effects or any visible changes in behavior.     

3D reconstruction of existing concrete bridges using optical methods

Routine bridge inspections usually consist of visual observations. These inspections are time-consuming and subjective. There is a need to identify new inspection techniques for infrastructure that reduce traffic disturbance, and improve the efficiency and reliability of the acquired data. This study compared the performance of three different imaging technologies for the three-dimensional (3D) geometric modeling of existing structures: terrestrial laser scanning, close-range photogrammetry, and infrared scanning. Each technology was used to assess six existing concrete railway bridges. The technologies were compared in terms of geometric deviations, visualization capabilities, the level of the inspector’s experience, and degree of automation. The results suggest that all methods investigated can be used to create 3D models, however, with different level of completeness. Measurements such as span length, deck widths, etc. can be extracted with good accuracy. Although promising, a full off-site inspection is currently not feasible as some areas of the bridges were difficult to capture mainly due to restricted access and narrow spaces. Measurements based on terrestrial laser scanning were closer to the reality compared to photogrammetry and infrared scanning. The study indicates the no special training is needed for photogrammetry and infrared scanning to generate a 3D geometric model.     

Mass Spectrometric Assays Reveal Discrepancies in Inhibition Profiles for the SARS-CoV-2 Papain-Like Protease

The two SARS-CoV-2 proteases, i. e. the main protease (M^pro) and the papain-like protease (PL^pro), which hydrolyze the viral polypeptide chain giving functional non-structural proteins, are essential for viral replication and are medicinal chemistry targets. We report a high-throughput mass spectrometry (MS)-based assay which directly monitors PL^pro catalysis in vitro. The assay was applied to investigate the effect of reported small-molecule PL^pro inhibitors and selected M^pro inhibitors on PL^pro catalysis. The results reveal that some, but not all, PL^pro inhibitor potencies differ substantially from those obtained using fluorescence-based assays. Some substrate-competing M^pro inhibitors, notably PF-07321332 (nirmatrelvir) which is in clinical development, do not inhibit PL^pro. Less selective M^pro inhibitors, e. g. auranofin, inhibit PL^pro, highlighting the potential for dual PL^pro/M^pro inhibition. MS-based PL^pro assays, which are orthogonal to widely employed fluorescence-based assays, are of utility in validating inhibitor potencies, especially for inhibitors operating by non-covalent mechanisms.     

Mayonnaise production in batch and continuous process exploiting magnetohydrodynamic force

Mayonnaise currently is produced using high shear stirrers. Here we present a new production method using a magnetic emulsification device. According to the new method a stable oil-in-water emulsion is formed by pumping the two immiscible liquids through a magnetohydrodynamic dispersion device consisting of a Venturi provided with an orthogonal permanent magnetic field. As a proof of concept, magnetically emulsified highly viscous mayonnaise was produced in a batch process and in a continuous process. The viscosity of the mayonnaise was significantly enhanced by applying the magnetic field. The oil droplet size distribution of mayonnaise produced using the magnetic emulsification method was similar to mayonnaise produced with conventional high shear mixers. In contrast to conventional processes no fast moving mixers were needed in this new mayonnaise production scheme.     

Optimization of Power Consumption in 4G LTE Networks Using a Novel Barebones Self-adaptive Differential Evolution Algorithm

The power consumption of wireless access networks is an important issue. In this paper, the power consumption of Long Term Evolution (LTE) base stations is optimized. We consider the city of Ghent, Belgium with 75 possible LTE base station locations. We optimize the network towards two objectives: the coverage maximization and the power consumption minimization. We propose a new Barebones Self-adaptive Differential Evolution. The results of the proposed method indicate the advantages and applicability of our approach.     

Injection à très haute pression

Un jet à très haute pression d'eau et d'air en même temps qu'une injection de pâte de ciment est en train de ?révolutionner? la pratique des injections dans le sol et consolidation des fondations. Cette technique développée en Suède est brièvement exposée ici. L'article s'appuie sur une note résumée publiée par le Conseil suédois pour la recherche sur la construction.     

Hydrogen refuelling stations in the Netherlands: An intercomparison of quantitative risk assessments used for permitting

As of 2003, 15 hydrogen refuelling stations (HRSs) have been deployed in the Netherlands. To become established, the HRS has to go through a permitting procedure. An important document of the permitting dossier is the quantitative risk assessment (QRA) as it assesses the risks of the HRS associated to people and buildings in the vicinity of the HRS. In the Netherlands, a generic prescribed approach exists on how to perform a QRA, however specific guidelines for HRSs do not exist. An intercomparison among the QRAs of permitted HRSs has revealed significant inconsistencies on various aspects of the QRA: namely the inclusion of HRS sub-systems and components, the HRS sub-system and component considerations as predefined components, the application of failure scenarios, the determination of failure frequencies, the application of input parameters, the consideration of preventive and mitigation measures as well as information provided regarding the HRS surroundings and the societal risk. It is therefore recommended to develop specific QRA guidelines for HRSs.     

Synthesis of complex lossless two-ports

A new synthesis algorithm is presented for the realization of a doubly terminated complex lossless two-port from a given canonic set of scattering polynomials. the synthesis algorithm is based entirely on polynomial evaluations and thus polynomial arithmetic and routines for zero finding are not needed. the accuracy problem due to coefficient sensitivity is avoided. In particular, explicit knowledge of the intermediate polynomials is not required. the simplicity and functionality of the algorithm are based on a new representation of elementary sections given by a set of canonic parameters, namely the transmission zero of the section, the reflectance evaluated at the transmission zero and, for reciprocal sections, the return group delay evaluated at the transmission zero. A great deal of freedom is available, since transmission zeros with any multiplicity and located anywhere in the complex plane are realized independently. Also, complex networks composed exclusively of either inductors or capacitors as the dynamic elements are possible. an example is given to illustrate the robustness of the algorithm.