New huprine derivatives functionalized at position 9 as highly potent acetylcholinesterase inhibitors

A series of 24 huprine derivatives diversely functionalized at position 9 have been synthesized and evaluated for their inhibitory activity against human recombinant acetylcholinesterase (AChE). These derivatives were prepared in one to five steps from huprine 1 bearing an ester function at position 9. Ten analogues ( 1 , 2 , 6 – 9 , 13 – 15 , and 23 ) are active in the low nanomolar range (IC₅₀ <5 nM ), very close to the parent compound huprine X. Compounds 2 , 6 , and 7 show a very good selectivity for AChE, with AChE inhibitory activities 700–1160‐fold higher than those for butyrylcholinesterase (BChE). The inhibitory potency of these compounds decreases with the steric bulk of the substituents at position 9. According to docking simulations, small substituents fit into the acyl‐binding pocket, whereas the larger ones stick out of the active site gorge of AChE. Determination of the kinetic parameters of three of the most potent huprines ( 2 , 6 , and 7 ) showed that most of the difference in K_D is accounted by a decrease in k_on, which is correlated to the increase of the substituent size. A first in vivo evaluation has been performed in mice for the most active compound 2 (IC₅₀=1.1 nM ) and showed a rather weak toxicity (LD₅₀=40 mg kg^?1) and an ability to cross the blood–brain barrier with doses above 15 mg kg^?1.     

Discrete element analysis of experiments on mixing and stoking of monodisperse spheres on a grate

Understanding the details of the mixing and stoking process on grate firing systems is crucial for the optimization of the combustion process in waste or biomass incineration plants. The Discrete Element Method (DEM) can help to obtain further information on the mixing process within a bed of fuel particles. Especially the influence of a change in operational parameters can be examined avoiding large experimental effort. In the current paper five simulations for a generic grate are compared with the corresponding experiments. The experiments were carried out throughout an anterior parameter study on mixing and stoking on a grate [Sudbrock F.; Simsek E.; Wirtz S.; Scherer V.: “An experimental analysis of the influence of operational parameters on mixing and stoking of a monodisperse granulate on a grate”, Powder Technology 198, Issue 1, 29-37, 2010] [19]. The system considered is equipped with vertically moving bars which induce stoking. In a first approach monodisperse plastic spheres are used. The grate is encased by a transparent polycarbonate housing which provides optical access to the movement of the particles in the wall planes. The mixing process is measured and quantified by image analysis of the front wall of the grate. The mixing behaviour of the particle assembly observed in experiments and simulation appears to be very similar indicating that DEM is able to predict the particle mixing in the bed. In order to quantify the visual observations the mixing behaviour has been evaluated by different mixing parameters. They are compared in dependence of the number of strokes of the grate bars. A good agreement between measurements and simulations could be observed.     

Analysis and optimal design of an ethylene oxide reactor

In this work, a recently proposed multi-level reactor design methodology (Peschel et al., 2010) is extended and applied for the optimal design of an ethylene oxide reactor. In a first step, the optimal reaction route is calculated taking various process intensification concepts into account. The potential of each reaction concept can be efficiently quantified, which is the economic basis for the design of advanced reactors. Based on these results, a promising concept is further investigated and a technical reactor is designed. As an extension to the design method, reactor design criteria for external and internal heat and mass transfer limitations are directly included in the optimization approach in order to design the catalyst packing. The derived reactor concept is investigated with a detailed 2D reactor model accounting for radial concentration and temperature gradients in addition to a radial velocity profile.The example considered in this work is the production of ethylene oxide which is one of the most important bulk chemicals. Due to the high ethylene costs, the selectivity is the main factor for the economics of the process. A membrane reactor with an advanced cooling strategy is proposed as best technical reactor. With this reactor design it is possible to increase the selectivity of the ethylene epoxidation by approximately 3% compared to an optimized reference case.     

In‐Depth Study of Mass Transfer in Nanoporous Materials by Micro‐Imaging

The first application of interference microscopy to monitoring mass transfer in nanoporous materials dates back to late 1970s when Caro and colleagues reported results of investigations of water uptake by LTA type zeolites. It was, however, not before the beginning of the new millennium that the developments in both the measuring technique and computational power have enabled the recording of transient guest profiles during molecular uptake and release under well‐defined conditions, leading to the establishment of a novel access to diffusion studies, now referred to as micro‐imaging. In the present contribution, the thus accessible novel type of information is illustrated by an in‐depth analysis of the uptake kinetics of methanol in an all‐silica ferrierite. In particular, two remarkable experimental findings are reported, which may be tracked back to their microstructural and/or microdynamic origin, namely a pronounced asymmetry in the transient concentration profiles and a slowing down of guest uptake with increasing temperature.     

Cuticular hydrocarbons of Tetramorium ants from central Europe: analysis of GC-MS data with self-organizing maps (SOM) and implications for systematics

Cuticular hydrocarbons were extracted from workers of 63 different nests of five species of Tetramorium ants (Hymenoptera: Formicidae) from Austria, Hungary, and Spain. The GC-MS data were classified (data mining) by self-organizing maps (SOM). SOM neurons derived from primary neuron separation were subjected to hierarchical SOM (HSOM) and were grouped to neuron areas on the basis of vicinity in the hexagonal output grid. While primary neuron separation and HSOM resulted in classifications on a level more sensitive than species differences, neuron areas resulted in chemical phenotypes apparently of the order of species. These chemical phenotypes have implications for systematics: while the chemical phenotypes for T. ferox and T. moravicum correspond to morphological determination, in T. caespitum and T. impurum a total of six chemical phenotypes is found. Three hypotheses are discussed to explain this disparity between morphological and chemical classifications, including in particular the possibility of hybridization and the existence of cryptic species. Overall, the GC-MS profiles classified by SOM prove to be a practical alternative to morphological determination (T. ferox, T. moravicum) and indicate the need to revisit systematics (T. caespitum, T. impurum).     

Reexamination of the Ergothioneine Biosynthetic Methyltransferase EgtD from Mycobacterium tuberculosis as a Protein Kinase Substrate

Ergothioneine has emerged as a crucial cytoprotectant in the pathogenic lifestyle of Mycobacterium tuberculosis. Production of this antioxidant from primary metabolites may be regulated by phosphorylation of Thr213 in the active site of the methyltransferase EgtD. The structure of mycobacterial EgtD suggests that this post-translational modification would require a large-scale change in conformation to make the active-site residue accessible to a protein kinase. In this report, we show that, under in vitro conditions, EgtD is not a substrate of protein kinase PknD.     

Modelling of solid formation by heterogeneous reactions through a multicomponent transport model of diluted ionic species: Simulation of barite fouling in a geothermal heat exchanger

A general model is proposed in order to describe the growth of a deposit by heterogeneous reactions. The hydrodynamics in the fluid is described by a multicomponent transport model for ionic species diluted in a solvent and heat transfer is taken into account in both liquid and solid domains. The boundary condition at the interface where the reaction takes place is described thoroughly. It involves the reaction kinetics and gives access to the velocity of the interface, ie, the mass rate of the solid deposit. The model is then applied to the case of barite crystallization in a heat exchanger. The liquid phase is therefore composed of two ionic species Ba²⁺ and SO₄²⁻ diluted in water. The solid phase is modelled as a homogeneous barite deposit. The fully dynamic CFD simulation of the model is made using Comsol Multiphysics, in a cylindrical pipe. The solid growth is analyzed over time and space in terms of the relevant variables of the model.     

Ag2O–Al2O3–ZrO2 Trimetallic Nanocatalyst for High Performance Photodegradation of Nicosulfuron Herbicide

Topics in Catalysis - In the present study, Ag2O–Al2O3–ZrO2 based trimetallic oxide nanocatalyst was designed using simple microwave assisted reduction method. It was characterized...     

Homoserine Lactones,Methyl Oligohydroxybutyrates,and Other Extracellular Metabolites of Macroalgae‐Associated Bacteria of the Roseobacter Clade: Identification and Functions

Twenty‐four strains of marine Roseobacter clade bacteria were isolated from macroalgae and investigated for the production of quorum‐sensing autoinducers, N‐acylhomoserine lactones (AHLs). GC/MS analysis of the extracellular metabolites allowed us to evaluate the release of other small molecules as well. Nineteen strains produced AHLs, ranging from 3‐OH‐C10:0‐HSL (homoserine lactone) to (2E,11Z)‐C18:2‐HSL, but no specific phylogenetic or ecological pattern of individual AHL occurrence was observed when cluster analysis was performed. Other identified compounds included indole, tropone, methyl esters of oligomers of 3‐hydroxybutyric acid, and various amides, such as N‐9‐hexadecenoylalanine methyl ester (9‐C16:1‐NAME), a structural analogue of AHLs. Several compounds were tested for their antibacterial and antialgal activity on marine isolates likely to occur in the habitat of the macroalgae. Both AHLs and 9‐C16:1‐NAME showed high antialgal activity against Skeletonema costatum, whereas their antibacterial activity was low.     

Temperature Stability of Lead‐Free Niobate Piezoceramics with Engineered Morphotropic Phase Boundary

The temperature dependence of piezoelectric properties (direct piezoelectric coefficient d₃₃, converse piezoelectric coefficient d₃₃(E = 0), strain S and electromechanical coupling coefficient k_p) for two niobate‐based lead‐free piezoceramics have been contrasted. 0.92(Na_0.5K_0.5)NbO₃–0.02(Bi_1/2Li_1/2)TiO₃–0.06BaZrO₃ (6BZ/2BLT/92NKN) has a morphotropic phase boundary (MPB) between rhombohedral and tetragonal at room temperature and 0.92(Na_0.5K_0.5)NbO₃–0.03(Bi_1/2Li_1/2)TiO₃–0.05BaZrO₃ (5BZ/3BLT/92NKN) features an MPB engineered to be located below room temperature. At 30°C, d₃₃, d₃₃(E = 0), S (at 2 kV/mm), and k_p are 252 pC/N, 230 pm/V, 0.069%, 0.51 for 5BZ/3BLT/92NKN; and 348 pC/N, 380 pm/V, 0.106%, 0.57 for 6BZ/2BLT/92NKN, respectively. With increasing temperature, the piezoelectric properties decrease. At 200°C, d₃₃, d₃₃(E = 0), S (at 2 kV/mm), and k_p are 170 pC/N, 160 pm/V, 0.059%, 0.36 for 5BZ/3BLT/92NKN; and 181 pC/N, 190 pm/V, 0.061%, 0.39 for 6BZ/2BLT/92NKN. It is found that the electromechanical coupling coefficient has a better temperature stability than the piezoelectric coefficient in the studied system due to a large temperature‐dependent compliance change. The results demonstrate that engineering an MPB is highly effective in tailoring temperature stability of piezoceramics.