Design,Synthesis, and in vitro Evaluation of P2X7 Antagonists

The P2X7 receptor is a promising target for the treatment of various diseases due to its significant role in inflammation and immune cell signaling. This work describes the design, synthesis, and in vitro evaluation of a series of novel derivatives bearing diverse scaffolds as potent P2X7 antagonists. Our approach was based on structural modifications of reported (adamantan-1-yl)methylbenzamides able to inhibit the receptor activation. The adamantane moieties and the amide bond were replaced, and the replacements were evaluated by a ligand-based pharmacophore model. The antagonistic potency of the synthesized analogues was assessed by two-electrode voltage clamp experiments, using Xenopus laevis oocytes that express the human P2X7 receptor. SAR studies suggested that the replacement of the adamantane ring by an aryl-cyclohexyl moiety afforded the most potent antagonists against the activation of the P2X7 cation channel, with analogue 2-chloro-N-[1-(3-(nitrooxymethyl)phenyl)cyclohexyl)methyl]benzamide ( 56 ) exhibiting the best potency with an IC₅₀ value of 0.39 μM.     

Flame extension and the near field under the ceiling for travelling fires inside large compartments

Structures need to be designed to maintain their stability in the event of a fire. The travelling fire methodology (TFM) defines the thermal boundary condition for structural design of large compartments of fires that do not flashover, considering near field and far field regions. TFM assumes a near field temperature of 1200°C, where the flame is impinging on the ceiling without any extension and gives the temperature of the hot gases in the far field from Alpert correlations. This paper revisits the near field assumptions of the TFM and, for the first time, includes horizontal flame extension under the ceiling, which affects the heating exposure of the structural members thus their load-bearing capacity. It also formulates the thermal boundary condition in terms of heat flux rather than in terms of temperature as it is used in TFM, which allows for a more formal treatment of heat transfer. The Hasemi, Wakamatsu, and Lattimer models of heat flux from flame are investigated for the near field. The methodology is applied to an open-plan generic office compartment with a floor area of 960 m² and 3.60 m high with concrete and with protected and unprotected steel structural members. The near field length with flame extension (fTFM) is found to be between 1.5 and 6.5 times longer than without flame extension. The duration of the exposure to peak heat flux depends on the flame length, which is 53 min for fTFM compared with 17 min for TFM, in the case of a slow 5% floor area fire. The peak heat flux is from 112 to 236 kW/m² for the majority of fire sizes using the Wakamatsu model and from 80 to 120 kW/m² for the Hasemi and Lattimer models, compared with 215 to 228 kW/m² for TFM. The results show that for all cases, TFM results in higher structural temperatures compared with different fTFM models (600°C for concrete rebar and 800°C for protected steel beam), except for the Wakamatsu model that for small fires, leads to approximately 20% higher temperatures than TFM. These findings mitigate the uncertainty around the TFM near field model and confirm that it is conservative for calculation of the thermal load on structures. This study contributes to the creation of design tools for better structural fire engineering.     

Economic model predictive control of nonlinear time‐delay systems: Closed‐loop stability and delay compensation

Closed‐loop stability of nonlinear time‐delay systems under Lyapunov‐based economic model predictive control (LEMPC) is considered. LEMPC is initially formulated with an ordinary differential equation model and is designed on the basis of an explicit stabilizing control law. To address closed‐loop stability under LEMPC, first, we consider the stability properties of the sampled‐data system resulting from the nonlinear continuous‐time delay system with state and input delay under a sample‐and‐hold implementation of the explicit controller. The steady‐state of this sampled‐data closed‐loop system is shown to be practically stable. Second, conditions such that closed‐loop stability, in the sense of boundedness of the closed‐loop state, under LEMPC are derived. A chemical process example is used to demonstrate that indeed closed‐loop stability is maintained under LEMPC for sufficiently small time‐delays. To cope with performance degradation owing to the effect of input delay, a predictor feedback LEMPC methodology is also proposed. The predictor feedback LEMPC design employs a predictor to compute a prediction of the state after the input delay period and an LEMPC scheme that is formulated with a differential difference equation (DDE) model, which describes the time‐delay system, initialized with the predicted state. The predictor feedback LEMPC is also applied to the chemical process example and yields improved closed‐loop stability and economic performance properties. © 2015 American Institute of Chemical Engineers AIChE J, 61: 4152–4165, 2015     

<Superscript>1</Superscript>H-NMR Spectroscopy as a New Tool in the Assessment of the Oxidative State in Edible Oils

Within the course of lipid peroxidation, hydroperoxides are formed as primary products. They can be used as analytical markers to assess the deterioration status of oils and fats. Here a new ¹H-NMR assay to determine the hydroperoxide amount in edible oils is presented. We were able to show that the analytical performance of the method is similar to that of the commonly used peroxide value (PV) according to Wheeler. A total of 290 edible oil samples were analyzed using both methods. For some oil varieties considerable discrepancies were found between the results obtained. In the case of black seed and olive oil, two substances could be identified that cause positive (black seed oil) and negative (olive oils) deviations from the theoretical PV expected from the NMR values.     

Chemical, leaching and toxicity characteristics of CFB combustion residues

Within the last years, attention has been focused on the development of clean coal technologies, based on the pulverized coal fired once-through boiler technology and the circulating fluidised bed combustion (CFBC) systems. The environmental problems provoked from those wastes due to their toxic trace element contents necessitate their detailed characterisation. Within the scope of this concept, two different coal types were used in a series of experimental trials. Fly and bottom ash samples were collected and characterised in terms of morphology, mineralogy, leaching and toxicity behaviour. According to the results, toxic trace elements are preferentially concentrated in the fly ash particles since they presented the smaller particles size. However, the chemical analysis of the ash leachates showed that are acceptable for safe disposal, since none of them exceeds the maximum EPA limits. Additionally, the Microtox toxicity test proved that fly ash leachates, which presented the higher heavy metals concentrations, caused the higher toxic effects.     

Regulation of film thickness, surface roughness and porosity in thin film growth using deposition rate

This work focuses on distributed control of film thickness, surface roughness and porosity in a porous thin film deposition process using the deposition rate as the manipulated input. The deposition process includes adsorption and migration processes and it is modeled via kinetic Monte Carlo simulation on a triangular lattice with vacancies and overhangs allowed to develop inside the film. A distributed parameter (partial differential equation) dynamic model is derived to describe the evolution of the surface height profile of the thin film accounting for the effect of deposition rate. The dynamics of film porosity, evaluated as film site occupancy ratio, are described by an ordinary differential equation. The developed dynamic models are then used as the basis for the design of a model predictive control algorithm that includes penalty on the deviation of film thickness, surface roughness and film porosity from their respective set-point values. Simulation results demonstrate the applicability and effectiveness of the proposed modeling and control approach in the context of the deposition process under consideration.     

Photooxidation Products of Ethanol During Photoelectrochemical Operation Using a Nanocrystalline Titania Anode and a Two Compartment Chemically Biased Cell

ZnMe^IIIFeO₄ catalysts with different trivalent metal (Me^III = Fe, Al, Cr, Mn, and Co) were prepared by a co-precipitation method, and were applied to the oxidative dehydrogenation of n-butene to 1,3-butadiene. Successful formation of ZnMe^IIIFeO₄ catalysts was confirmed by XRD and ICP-AES analyses. Catalytic performance of ZnMe^IIIFeO₄ catalysts in the oxidative dehydrogenation of n-butene strongly depended on the identity of trivalent metal (Me^III). Acid properties of ZnMe^IIIFeO₄ catalysts were measured by NH₃-TPD experiments, with an aim of correlating the catalytic performance with the surface acid property of the catalysts. It was revealed that yield for 1,3-butadiene increased with increasing surface weak-acid density of ZnMe^IIIFeO₄ catalyst. Among the catalysts tested, ZnFeFeO₄ catalyst with the largest surface weak-acid density showed the best catalytic performance in the oxidative dehydrogenation of n-butene.     

Cornet‐Like Phosphotriazine/Diamine Polymers as Reductant and Matrix for the Synthesis of Silver Nanocomposites with Antimicrobial Activity

The synthesis of silver nanoparticles attached on the surface of a hollow cornet‐like polymer matrix which served as a reductant and host matrix is described. This hybrid organic/inorganic macromolecular matrix is exhibiting anion‐exchange properties, porous structure and hollow morphologies, and absorptions in the visible light region. Due to the anion‐exchange property and the 3D orientation of the macromolecular chains the material is defining a new functional organic/inorganic hybrid. For the synthesis of nanoparticles, no other reducing agents were used and silver nanoparticles with a mean diameter of less than 20 nm were attached on the surface of the polymer, thus inheriting the composite with high antibacterial activity tested in bacterial strains and yeasts.

     

Identification and quantification of polyphenolic compounds from okra seeds and skins

The aims of the present work were to identify and quantify the polyphenolic profile of okra (Abelmoschus esculentus), a vegetable almost worldwide consumed. Since the knowledge about the okra polyphenolic compounds is limited, the seeds and the skins of okra were separately analyzed. The seeds, which represent the 17% of the vegetable and are richer in phenolic compounds, were mainly composed by oligomeric catechins (2.5 mg/g of seeds) and flavonol derivatives (3.4 mg/g of seeds). The skins polyphenolic profile was composed principally by hydroxycinnamic and quercetin derivatives (0.2 and 0.3 mg/g of skins). These findings in associations with the high content of okra in carbohydrates and proteins enhance the importance of this foodstuff in the human diet.     

Hydrocaffeic acid oxidation by a peroxidase homogenate from onion solid wastes

A very large amount of phenol-polluted waters are formed from the production of olive oil (olive mill waste water, OMWW), and the main problem associated with their disposal is a viable means of effective treatment. Biochemical processes used for treating OMWW are generally considered to be of high capital and operating costs with limited efficiency. This is mainly due to particularly high levels of phenolic compounds, which are considered major contributors to the toxicity and antibacterial activity of OMWW, and limit their microbial treatment and/or use as fertilizers. Although the use of bacterial and fungal enzymes has gained interest in studies pertaining to bioremediation applications, plant enzymes have been given less attention or even disregarded. In this view, this study aimed at investigating the use of a crude peroxidase preparation from onion solid by-products for oxidising hydrocaffeic acid, a typical o-diphenol with a structure very similar to various phenolic derivatives that may occur in OMWW. Increased enzyme activity was observed at a pH value of 4, but considerable activity was also retained for pH upto 7. Favourable temperatures for increased activity varied between 30 and 50 °C, 40 °C being the optimal. Liquid chromatography–mass spectrometry analysis of a homogenate/H₂O₂-treated hydrocaffeic acid solution revealed the existence of three major oxidation products, which were identified as dehydrodimers. Based on the data generated, a putative pathway for the formation of the peroxidase-mediated hydrocaffeic dehydrodimers was proposed.