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.     

An optimal control of a wastewater treatment reactor by catalytic ozonation

This paper deals with the control of a wastewater treatment pilot by catalytic ozonation. In general, catalytic ozonation processes operate with a deliberate ozone overproduction to obtain a treated water which respects discharge standards. But, in this case, the oxygen consumption is not optimal and the operating costs are important. The objective of this study focuses on the optimization of the catalytic ozonation reactor. A continuous-time transfer function model is identified to represent the pilot behavior, and an optimal control is proposed to obtain a significant abatement of the pollutant. In this application, the pollutant abatement is represented by the absorbance.     

Modulation of Cellular Fate of Vinyl Triarylamines through Structural Fine Tuning: To Stay or Not To Stay in the Mitochondria?

Mitochondria are involved in many cellular pathways and dysfunctional mitochondria are linked to various diseases. Hence efforts have been made to design mitochondria-targeted fluorophores for monitoring the mitochondrial status. However, the factors that govern the mitochondria-targeted potential of dyes are not well-understood. In this context, we synthesized analogues of the TP-2Bzim probe belonging to the vinyltriphenylamine (TPA) class and already described for its capacity to bind nuclear DNA in fixed cells and mitochondria in live cells. These analogues ( TP-1Bzim, TPⁿ-2Bzim, TP¹⁺-2Bzim, TN-2Bzim ) differ in the cationic charge, the number of vinylbenzimidazolium branches and the nature of the triaryl core. Using microscopy, we demonstrated that the cationic derivatives accumulate in mitochondria but do not reach mtDNA. Under depolarisation of the mitochondrial membrane, TP-2Bzim and TP¹⁺-2Bzim translocate to the nucleus in direct correlation with their strong DNA affinity. This reversible phenomenon emphasizes that these probes can be used to monitor ΔΨ_m variations.     

Transient and steady states of Gd2Zr2O7 and 2ZrO2∙Y2O3 (ss) interactions with calcium magnesium aluminium silicates

Reactions between calcium magnesium aluminium silicates (CMAS) and Gd₂Zr₂O₇ or 2ZrO₂?Y₂O₃ (ss) are investigated within a temperature range of 1200–1300 °C and for durations of 1 h–100 h. The evolution of CMAS penetration depth in Gd₂Zr₂O₇ and 2ZrO₂?Y₂O₃ (ss) pellets varies considerably depending on the interaction time. A quantitative analysis of the nature and composition of phases observed in stationary conditions (powder/powder interaction) is performed by SEM-FEG coupled with WDS analyses using micro-agglomerated nanoparticles of Gd₂Zr₂O₇ and 2ZrO₂?Y₂O₃. Faster kinetics of the gadolinium-based system are illustrated through an analysis of the morphology of the reaction area and of the resulting CMAS tightness of reaction products. The compositions and quantities of reaction products observed at equilibrium are very similar for the two systems, but transient states are significantly different.     

Structural,Micromechanical and Tribological Characterization of Zn–Ni Coatings: Effect of Sulfate Bath Composition

Zn and Zn–Ni alloy coatings were electrodeposited on mild steel from sulfate-based bath containing Sn as additive. The effect of Ni content on the microstructure, morphology, microhardness and the tribological behavior of these coatings were studied and discussed. Adding Sn in the sulfate bath had a significant effect on the surface morphology, particularly on the Zn–8 wt% Ni coatings. By increasing the Ni concentration from 8 to 14 wt%, the X-ray patterns showed that the phase structure of Zn–Ni alloy coatings was changed from η-phase Ni₃Zn₂₂ to γ-phase Ni₅Zn₂₁. The plastic deformation and delamination were found to be wear mechanisms for the investigated coatings. While the Zn–14 wt% Ni alloys had the best wear resistance, Zn films had the most severe wear volume loss and the highest friction coefficient.     

Predicting construction firm performance: an empirical assessment of the differential impact between industry‐ and firm‐specific factors

It is obvious that the performance of firms hinges upon the dynamics of both industry‐ and firm‐specific factors. A less obvious, and perhaps a more important, line of inquiry is that to the extent that they have a bearing on firm performance, how much do these two groups of factors respectively predict firm performance? To date, performance differences among construction firms that stem from industry‐ and firm‐specific differential effect has remained largely unexplored. Using a dataset comprising 526 firms across various construction‐related sectors, the sector‐by‐sector firm performance variation that is attributable to the heterogeneity of both industry‐ and firm‐specific characteristics was empirically examined. That statistically significant results of different effect sizes are found indicates that although these factors are often assumed to be intertwined it is possible to study their respective impact on firm performance. Future studies could usefully replicate and extend this study to construction firms in other countries to further investigate what drives firm performance under different national, industry and firm contexts.     

Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors

Neglected tropical diseases caused by parasitic infections are an ongoing and increasing concern. They are a burden to human and animal health, having the most devastating effect on the world′s poorest countries. Building upon our previously reported triazole analogues, in this study we describe the synthesis and biological testing of other novel heterocyclic acetogenin‐inspired derivatives, namely 3,5‐isoxazoles, furoxans, and furazans. Several of these compounds maintain low‐micromolar levels of inhibition against Trypanosoma brucei, whilst having no observable inhibitory effect on mammalian cells, leading to the possibility of novel lead compounds for selective treatment.     

Energetics and Structure of Polymer‐Derived Si–(B–)O–C Glasses: Effect of the Boron Content and Pyrolysis Temperature

The structure and properties of polymer‐derived Si–(B–)O–C glasses have been shown to be significantly influenced by the boron content and pyrolysis temperature. This work determined the impact of these two parameters on the thermodynamic stability of these glasses. High‐temperature oxide melt solution calorimetry was performed on a series of amorphous samples, with varying boron contents (0–7.7 at.%), obtained by pyrolysis of precursors made by a sol–gel technique. Thermodynamic analysis of the calorimetric results demonstrated that at a constant pyrolysis temperature, adding boron makes the materials energetically less stable. While the B‐containing glasses pyrolyzed at 1000°C were energetically less stable than the competitive crystalline components, increasing the pyrolysis temperature to 1200°C led to their enthalpic stability. ²⁹Si and ¹¹B MAS nuclear magnetic resonance (NMR) spectroscopy measurements on selected samples confirmed a decrease in the concentrations of mixed Si‐centered SO_iC_4?i and B‐centered BO_jC_3?j bonds at the expense of formation of SiO₄ and B(OSi)₃ species (indicating a tendency toward phase separation) when the boron content and pyrolysis temperature increased. In light of the findings from calorimetry and NMR spectroscopy, we propose a structure–energetic relationship in Si–(B–)O–C glasses.     

The heat treatment and the gelation are strong determinants of the kinetics of milk proteins digestion and of the peripheral availability of amino acids

This study aimed to determine the kinetics of milk protein digestion and amino acid absorption after ingestion of four dairy matrices by six minipigs: unheated or heated skim milk and corresponding rennet gels. Digestive contents and plasma samples were collected over a 7 h-period after meal ingestion. Gelation of milk slowed down the outflow of the meal from the stomach and the subsequent absorption of amino acids, and decreased their bioavailability in peripheral blood. The gelled rennet matrices also led to low levels of milk proteins at the duodenum. Caseins and β-lactoglobulin, respectively, were sensitive and resistant to hydrolysis in the stomach with the unheated matrices, but showed similar digestion with the heated matrices, with a heat-induced susceptibility to hydrolysis for β-lactoglobulin. These results suggest a significant influence of the meal microstructure (resulting from heat treatment) and macrostructure (resulting from gelation process) on the different steps of milk proteins digestion.