4,4‐Dimethyl‐ and Diastereomeric 4‐Hydroxy‐4‐methyl‐ (2S)‐Glutamate Analogues Display Distinct Pharmacological Profiles at Ionotropic Glutamate Receptors and Excitatory Amino Acid Transporters

Subtype‐selective ligands are of great interest to the scientific community, as they provide a tool for investigating the function of one receptor or transporter subtype when functioning in its native environment. Several 4‐substituted (S)‐glutamate (Glu) analogues were synthesized, and altogether this approach has provided important insight into the structure–activity relationships (SAR) for ionotropic and metabotropic glutamate receptors (iGluRs and mGluRs), as well as the excitatory amino acid transporters (EAATs). In this work, three 4,4‐disubstituted Glu analogues 1 – 3 , which are hybrid structures of important 4‐substituted Glu analogues 4 – 8 , were investigated at iGluRs and EAATs. Collectively, their pharmacological profiles add new and valuable information to the SAR for the iGluRs and EAAT1–3.     

The reaction of NiO/NiAl2O4 particles with alternating methane and oxygen

The reduction and oxidation behaviour of oxygen carrier particles of NiO and NiAl₂O₄ has been investigated in a fluidized bed reactor as well as a thermogravimetric analyzer (TGA). The particles showed high reactivity and gas yield to CO₂ with methane in the temperature interval 750–950°C. In the fluidized bed the yield to CO₂ was between 90 and 99% using bed masses corresponding to 16–57 kg/MW_fuel. Complementary experiments in a TGA at 750 and 950°C showed a clear reaction of the NiAl₂O₄ with CH₄ at the higher temperature. There was methane released from the reactor at high degrees of solid oxidation, which is likely associated with the lack of Ni‐sites on the particles which can reform the methane. There was some carbon formation during the reduction, although the amount was minor when the gas yield to carbon dioxide and degree of oxidation of the solid was high. A simple reactor model using kinetic data from a previous study predicted the gas yield during the reduction in the fluidized bed experiments with reasonable accuracy. The oxygen carrier system investigated in this work shows high promise for use in a real CLC system, provided that the particle manufacturing process can be scaled up with reasonable cost.     

Intumescent foams—A novel flame retardant system for flexible polyurethane foams

A combination of intumescent components was evaluated as a novel flame retardant system in a flexible polyurethane foam, and the incorporation of these components gave rise to a significant enhancement of the flame retardant properties of the foam. The heat release rate was lowered at an early stage as well as throughout the fire, the total heat production was decreased and the time to ignition was prolonged. Mechanical measurements of the foam revealed enhanced properties in terms of stiffness accompanied by a large decrease in elongation at break as compared with a reference foam. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2008     

CFD simulation of the high shear mixing process using kinetic theory of granular flow and frictional stress models

In order to enhance process understanding and to develop predictive process models in high shear granulation, there is an ongoing search for simulation tools and experimental methods to model and measure the velocity and shear fields in the mixer. In this study, the Eulerian-Eulerian approach to model multiphase flows has been used to simulate the mixer flow. Experimental velocity profiles for the solid phase at the wall in the mixer have been obtained using a high speed camera following the experimental procedure as described by Darelius et al. [2007a. Measurement of the velocity field and frictional properties of wet masses in a high shear mixer. Chemical Engineering Science, 62, 2366-2374]. The governing equations for modelling the dense mixer flow have been closed by using closure relations from the kinetic theory of granular flow (KTGF) combined with frictional stress models. The free slip and partial slip boundary conditions for the solid phase velocity at the vessel wall have been utilized. The partial slip model originally developed for dilute flows by Tu and Fletcher [1995. Numerical computation of turbulent gas-solid particle flow in a 90^° bend. A.I.Ch.E. Journal, 41, 2187-2197] has been employed. It was found that the bed height could be well predicted by implementing the partial slip model, whereas the free slip model could not capture the experimentally found bed height satisfactorily. In the simulation, the swirling motion of the rotating torus formed was over-predicted and the tangential wall velocity was under-predicted, probably due to the fact that the frictional stress model needs to be further developed, e.g. to tackle cohesive particles in dense flow. The advantage of using the Eulerian-Eulerian approach compared to discrete element methods is that there is no computational limitation on the number of particles being modelled, and thus manufacturing scale granulators can be modelled as well.     

The Influence of Temperature on Oxide-Scale Formation during Erosion--Corrosion

Four steels (Fe2.25Cr1Mo, Fe9Cr1Mo, AISI 304, 353 MA) and one Ni-based superalloy (Inconel 625) were exposed in an erosion--corrosion test rig at the temperatures 20, 350, 550 and 700°C for 1 week. The atmosphere was air and the particle velocity 1.2 m/s. The composition and thickness of the developed surface layers were determined by Auger electron spectroscopy and X-ray photoelectron spectroscopy. The ferritic and Ni-based alloys investigated show a minimum in wastage rate around 350°C due to the development of a particle strengthened/toughened composite layer on the surface. The greatest wastage rates were measured at 700°C. Rapid diffusion paths created in the oxide from the particle bombardment results in the growth of oxide nodules at the oxide/metal-interface causing protruding oxide flakes which are chipped away. At this temperature the ferritic steel Fe9Cr1Mo is degraded to a larger extent than the austenitic steels.     

A virtual machine concept for real-time simulation of machine tool dynamics

When designing CNC machine tools it is important to consider the dynamics of the control, the electrical components and the mechanical structure of the machine simultaneously. This paper describes the structure and implementation of a concept for real-time simulation of such machine tools using a water jet cutting machine as an application. The concept includes a real control system, simulation models of the dynamics of the machine and a virtual reality model for visualisation. The real-time capability of the concept, including the simulation of electrical and rather detailed mechanical component models is proofed. The validation process indicates good agreement between simulation and measurement, but suggests further studies on servo motor, connection and flexibility modelling. However, already from the initial simulation results presented in this paper it can be concluded that the influence of structural flexibility on manufacturing accuracy is of importance at desired feeding rates and accelerations. The fully automated implementation developed in this work is a promising base for dealing with this trade-off between productivity and accuracy of the manufacturing process through multidisciplinary optimisation.     

Structure-Activity Relationship Explorations and Discovery of a Potent Antagonist for the Free Fatty Acid Receptor 2

Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, there is still a need for improved compounds. One of the most potent and frequently used antagonists is the amide-substituted phenylbutanoic acid known as CATPB ( 1 ). We here report the structure-activity relationship exploration of this compound, leading to the identification of homologues with increased potency. The preferred compound 37 (TUG-1958) was found, besides improved potency, to have high solubility and favorable pharmacokinetic properties.     

Subcellular Localization of Acyl-CoA: Lysophosphatidylethanolamine Acyltransferases (LPEATs) and the Effects of Knocking-Out and Overexpression of Their Genes on Autophagy Markers Level and Life Span of A. thaliana

Arabidopsis thaliana possesses two acyl-CoA:lysophosphatidylethanolamine acyltransferases, LPEAT1 and LPEAT2, which are encoded by At1g80950 and At2g45670 genes, respectively. Both single lpeat2 mutant and double lpeat1 lpeat2 mutant plants exhibit a variety of conspicuous phenotypes, including dwarfed growth. Confocal microscopic analysis of tobacco suspension-cultured cells transiently transformed with green fluorescent protein-tagged versions of LPEAT1 or LPEAT2 revealed that LPEAT1 is localized to the endoplasmic reticulum (ER), whereas LPEAT2 is localized to both Golgi and late endosomes. Considering that the primary product of the reaction catalyzed by LPEATs is phosphatidylethanolamine, which is known to be covalently conjugated with autophagy-related protein ATG8 during a key step of the formation of autophagosomes, we investigated the requirements for LPEATs to engage in autophagic activity in Arabidopsis. Knocking out of either or both LPEAT genes led to enhanced accumulation of the autophagic adaptor protein NBR1 and decreased levels of both ATG8a mRNA and total ATG8 protein. Moreover, we detected significantly fewer membrane objects in the vacuoles of lpeat1 lpeat2 double mutant mesophyll cells than in vacuoles of control plants. However, contrary to what has been reported on autophagy deficient plants, the lpeat mutants displayed a prolonged life span compared to wild type, including delayed senescence.     

A mechanistic study of electrodeposition of bismuth telluride on stainless steel substrates

Miniaturization of Bi₂Te₃ compounds is of great interest in semiconductor industries due to their distinct anisotropic thermoelectric properties at room temperature. The aim of the present work was to investigate the mechanism of the electrodeposition of Bi₂Te₃ compounds on stainless steel substrates and relate the morphology and composition of the resulting deposits to experimental parameters. Cyclic voltammetry (CV) experiments in acidic solutions containing Bi³⁺ and/or HTeO₂⁺ ions show that the deposition potential for the Bi₂Te₃ compound is more positive than either of the single elements alone. A detailed mechanism of the co-deposition was obtained by varying the concentrations of the two elements and evaluating the corresponding morphological and compositional changes of the deposits. The results show that the deposition of Te is kinetically hindered and that Bi deposition plays a major role during the co-deposition.     

Exposure to diesel exhaust induces changes in EEG in human volunteers

Background  

Ambient particulate matter and nanoparticles have been shown to translocate to the brain, and potentially influence the central nervous system. No data are available whether this may lead to functional changes in the brain.