Discovery of Heterocyclic Nonacetamide Synaptic Vesicle Protein 2A (SV2A) Ligands with Single‐Digit Nanomolar Potency: Opening Avenues towards the First SV2A Positron Emission Tomography (PET) Ligands

The role of the synaptic vesicle protein 2A (SV2A) protein, target of the antiepileptic drug levetiracetam, is still mostly unknown. Considering its potential to provide in vivo functional insights into the role of SV2A in epileptic patients, the development of an SV2A positron emission tomography (PET) tracer has been undertaken. Using a 3D pharmacophore model based on close analogues of levetiracetam, we report the rationale design of three heterocyclic non‐acetamide lead compounds, UCB‐A, UCB‐H and UCB‐J, the first single‐digit nanomolar SV2A ligands with suitable properties for development as PET tracers.     

Pairwise testing for software product lines: comparison of two approaches

Software Product Lines (SPL) are difficult to validate due to combinatorics induced by variability, which in turn leads to combinatorial explosion of the number of derivable products. Exhaustive testing in such a large products space is hardly feasible. Hence, one possible option is to test SPLs by generating test configurations that cover all possible t feature interactions (t-wise). It dramatically reduces the number of test products while ensuring reasonable SPL coverage. In this paper, we report our experience on applying t-wise techniques for SPL with two independent toolsets developed by the authors. One focuses on generality and splits the generation problem according to strategies. The other emphasizes providing efficient generation. To evaluate the respective merits of the approaches, measures such as the number of generated test configurations and the similarity between them are provided. By applying these measures, we were able to derive useful insights for pairwise and t-wise testing of product lines.     

Hot-Water Extraction Optimization of Sugar Maple (Acer saccharum Marsh.) and Red Maple (Acer rubrum L.) Bark Applying Principal Component Analysis

In the forest industry, bark is an abundant residue, predominantly converted into calorific energy. As the antioxidant potential of phenolic compounds from sugar maple (Acer saccharum Marsh.) and red maple (Acer rubrum L.) bark has previously been established, the present study focused on the hot-water extraction optimization of these barks. Several process parameters (maple species, temperature, duration, ratio bark/water, particle size) were thus studied and large disparities were found between the two species. Extraction yield, phenolic content, and antioxidant capacity of red maple extracts were several times higher than those of sugar maple extracts. Principal component analysis, applied to the selected best extraction conditions, identified 3–4 clusters depending on the maple species. These groups were sorted from the highest extraction yield and energy consumption combined with the lowest phenolic content and antioxidant capacity, to moderate extraction yield and energy consumption with the highest phenolic content and antioxidant capacity.     

The methionine precursor dl-2-hydroxy-(4-methylthio)butanoic acid protects intestinal epithelial barrier function

dl-2-hydroxy-(4-methylthio)butanoic acid (HMTBA) is a source of dietary methionine (Met) that is widely used in poultry nutrition. We have previously shown that HMTBA is preferentially diverted to the transsulfuration pathway, which gives antioxidant metabolites such as taurine and glutathione. Therefore, here we hypothesize that this Met source can protect epithelial barrier function in an in vitro model of intestinal inflammation of Caco-2 cells. The results show that HMTBA prevents the increase in paracellular permeability induced by H₂O₂ or tumour necrosis factor-α. This effect can be attributed to the increased production of taurine and reduced glutathione. Similar results were obtained for dl-Met, although the protective role of the amino acid was less pronounced than that of the hydroxy analogue. In conclusion, the diversion to the transsulfuration pathway means that this Met precursor is of greater value than previously thought, due to its capacity to improve intestinal homeostasis and the quality of poultry products destined for human consumption.     

Characterizing hydrocyclone performance for grit removal from wastewater treatment activated sludge plants

Typically, 15–45% of the mixed liquor (sludge) in biological wastewater treatment plants (WWTPs) consists of inorganic (fixed) suspended solids. A portion of these inorganic compounds is grit (sand) originating from the influent. Grit accumulation impacts WWTP design and operating costs as these unbiodegradable solids reduce the effective treatment capacity of the bioreactor and other unit operations that must be sized to carry this material.The goal of this study was to characterize the performance of a hydrocyclone to selectively separate grit from activated sludge. Laboratory experiments were conducted with a 13 mm diameter Krebs hydrocyclone treating sludge from eight WWTPs. Reduced efficiencies of 17 ± 7% on fixed suspended solids and 9 ± 6% on volatile suspended solids were obtained. Grade efficiency curves enabled the development of a modified definition for cut size useful for this application. The characterization of hydrocyclone performance for grit removal from activated sludge will enable modelling of the process for integration into wastewater treatment simulators used for process performance prediction and design.     

A Novel Technology for Natural Gas Conversion by Means of Integrated Oxidative Coupling and Dry Reforming of Methane

A novel process concept for the oxidative coupling of methane followed by the oligomerization to liquids has been developed within the frame of the EU integrated project OCMOL. This technology is based on process intensification principles via cutting‐edge structured microreactor technology. It is also a fully integrated industrial process through the re‐use and the recycling of by‐products, in particular CO₂, at every process stage. The focus of this contribution is on the reaction engineering aspects of the core steps, i.e., catalysts, kinetics and reactor design for the methane coupling and reforming.     

Role of strain induced crystallization and oxidative crosslinking in fracture properties of rubbers

Tensile properties and crack propagation properties, especially critical strain energy release rate in mode I, G_IC, have been used to investigate fracture properties of elastomers and their relationships with microstructure. These investigations were mainly based on a series of comparisons: first, the behaviour of polychloroprene rubber (CR), undergoing stress hardening due to strain induced crystallization (SIC) and oxidative crosslinking (OCL) was compared with that of chlorinated polyethylene (CPE), which undergoes SIC but not OCL, and with a polyurethane based on hydroxyl terminated polybutadiene (PU) which undergoes OCL but not SIC. Comparisons were also made on CR between fracture behaviour at ambient temperature, where SIC occurs and at 100 °C where there is no SIC. Finally, oxidative crosslinking was used to vary in a continuous way the crosslink density in CR and PU, in order to evaluate the role of crosslinking in fracture behaviour.     

Interlinking Music-Related Data on the Web

This article describes how Semantic Web technologies can be used to interlink musical data sources that have traditionally been isolated and difficult to integrate.