N‐Benzyl‐4‐((heteroaryl)methyl)benzamides: A New Class of Direct NADH‐Dependent 2‐trans Enoyl–Acyl Carrier Protein Reductase (InhA) Inhibitors with Antitubercular Activity

Isoniazid (INH) remains one of the cornerstones of antitubercular chemotherapy for drug‐sensitive strains of M. tuberculosis bacteria. However, the increasing prevalence of multidrug‐resistant (MDR) and extensively drug‐resistant (XDR) strains containing mutations in the KatG enzyme, which is responsible for the activation of INH into its antitubercular form, have rendered this drug of little or no use in many cases of drug‐resistant tuberculosis. Presented herein is a novel family of antitubercular direct NADH‐dependent 2‐trans enoyl–acyl carrier protein reductase (InhA) inhibitors based on an N‐benzyl‐4‐((heteroaryl)methyl)benzamide template; unlike INH, these do not require prior activation by KatG. Given their direct InhA target engagement, these compounds should be able to circumvent KatG‐related resistance in the clinic. The lead molecules were shown to be potent inhibitors of InhA and showed activity against M. tuberculosis bacteria. This new family of inhibitors was found to be chemically tractable, as exemplified by the facile synthesis of analogues and the establishment of structure–activity relationships. Furthermore, a co‐crystal structure of the initial hit with the enzyme is disclosed, providing valuable information toward the design of new InhA inhibitors for the treatment of MDR/XDR tuberculosis.     

Co-Expression and Co-Localization of Cartilage Glycoproteins CHI3L1 and Lubricin in Osteoarthritic Cartilage: Morphological,Immunohistochemical and Gene Expression Profiles

Osteoarthritis is the most common human arthritis characterized by degeneration of articular cartilage. Several studies reported that levels of human cartilage glycoprotein chitinase 3-like-1 (CHI3L1) are known as a potential marker for the activation of chondrocytes and the progression of Osteoarthritis (OA), whereas lubricin appears to be chondroprotective. The aim of this study was to investigate the co-expression and co-localization of CHI3L1 and lubricin in normal and osteoarthritic rat articular cartilage to correlate their modified expression to a specific grade of OA. Samples of normal and osteoarthritic rat articular cartilage were analyzed by the Kellgren–Lawrence OA severity scores, the Kraus’ modified Mankin score and the Histopathology Osteoarthritis Research Society International (OARSI) system for histomorphometric evaluations, and through CHI3L1 and lubricin gene expression, immunohistochemistry and double immuno-staining analysis. The immunoexpression and the mRNA levels of lubricin increased in normal cartilage and decreased in OA cartilage (normal vs. OA, p < 0.01). By contrast, the immunoexpression and the mRNA levels of CHI3L1 increased in OA cartilage and decreased in normal cartilage (normal vs. OA, p < 0.01). Our findings are consistent with reports suggesting that these two glycoproteins are functionally associated with the development of OA and in particular with grade 2/3 of OA, suggesting that in the future they could be helpful to stage the severity and progression of the disease.     

Hydrogenation of vegetable oil using highly dispersed Pt/γ-Al2O3 catalyst: Effects of key operating parameters and deactivation study

In the present work, Pt/γ-Al₂O₃ catalysts with high metal dispersion were prepared and characterized using chloroplatinic acid and platinum acetylacetonate as metal precursors. The activity and selectivity of the catalysts were evaluated in the hydrogenation of sunflower oil. A comprehensive analysis of the effects of key operational parameters on catalytic performance was carried out. The experimental variables were hydrogen pressure (275.8–551.6 kPa), temperature (160–200°C), and catalyst loading (0.005–0.015 kg Pt_exp/m³_oil). Platinum catalysts were active, with a double bond conversion of 28% at 2 h. The metal precursor affected catalyst selectivity. The catalyst prepared with chloroplatinic acid exhibited a lower formation of trans-isomers compared with Pt acetylacetonate. The γ-Al₂O₃ supported platinum catalyst with a metal loading of 0.51 wt.% and a metal dispersion of 98% maintained its initial catalyst activity and selectivity after 10 consecutive uses (1200 min accumulate operation time), without changes in its catalytic properties. The obtained results suggested that Pt catalysts are an attractive alternative to conventional nickel catalysts for the hydrogenation of vegetable oil.     

Selenocarbamates As a Prodrug-Based Approach to Carbonic Anhydrase Inhibition

A study on the activity of selenocarbamates as a novel chemotype acting as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors is reported. Undergoing CA-mediated hydrolysis, selenocarbamates release selenolates behaving as zinc binding groups and effectively inhibiting CAs. A series of selenocarbamates characterised by high molecular diversity and complexity have been studied against different human CA isoforms such as hCA I, II, IX and XII. Selenocarbamates behave as masked selenols with potential biological applications as prodrugs for CAs inhibition-based strategies. X-ray studies provided insights into the binding mode of this novel class of CA inhibitors.     

Fast Separation of Capsaicinoids from Peppers by Reversed Phase Ultra-Performance Liquid Chromatography: Comparation with Traditional High-Performance Liquid Chromatography Methods

A new chromatographic method for the separation of major capsaicinoids in peppers has been developed. Nordihydrocapsaicin, capsaicin, dihydrocapsaicin, homocapsaicin, and homodihydrocapsaicin have been separated by reversed-phase ultra-performance liquid chromatography. A gradient method has been developed using two solvents: 0.1% acetic acid in water and 0.1% acetic acid in methanol. The developed method allows the full separation of capsaicinoids in less than 3 min, with high reproducibility (relative standard deviation < 4.3%) and repeatability (relative standard deviation < 3.6%). Robustness regarding the total amount of methanol in the sample was determined. Comparison with previous reversed-phase high-performance liquid chromatography methods using both monolithic and conventional columns was also studied. Finally, the method was applied in the determination of major capsaicinoids in 16 hot pepper samples produced in Spain.     

Passive adaptation or active engagement? The challenges of Housing First internationally and in the Italian case

In recent years, a peculiar homelessness policy that goes under the name of ‘Housing First’ has become increasingly popular all over the world. Epitomising a quintessential case of policy-mobility, Housing First can today be considered an heterogeneous assemblage of experiences and approaches that sometimes have little in common with each other. Introducing and commenting upon this heterogeneity, the paper critically analyses why and how Housing First has become a planetary success and what are the issues at stake with its widespread implementation. If recent scholarship published in this journal has granted us a fine understanding of Housing First’s functioning in the US, this paper offers something currently absent from the debate: a nuanced and critical understanding of the ambiguities related to the international success of this policy, with specific references to the challenges associated to its translation in the Italian case.     

N‐Oligo(3‐hydroxybutyrate)‐functionalized polypyrroles: towards bio‐erodible conducting copolymers

New copolymer materials have been prepared by chemical grafting of oligomeric 3‐hydroxybutyric acid (OHB) onto polypyrrole (PPy) derivatives. The influence of grafting density and molecular weight of OHB brushes on the physicochemical properties of prepared copolymers was investigated. PPy substrates were prepared by FeCl₃‐driven oxidative homopolymerization of N‐(2‐carboxyethyl)pyrrole or its copolymerization with pyrrole. The grafting method employed involved controlled anionic polymerization of β‐butyrolactone on pyrrole‐tethered potassium carboxylate active sites. Obtained PPy‐g‐OHB copolymers of varying grafting density and pendant polyester chain length were characterized and the observed structure–property relationships discussed. The impact of real time exposure to phosphate‐buffered saline environment was investigated and the residue products were characterized. Cross‐correlation of spectroscopic, thermal, electrical and elemental analysis data afforded comprehensive evaluation of the structure of prepared materials and their behaviour in hydrolytic medium. Erosion and degradation pathways have been identified, indicating ways to consciously tailor the physicochemical properties of these new biomimetic materials. © 2016 Society of Chemical Industry     

Difference equation matrix model (DEMM) for the control of wind turbines

In this paper, a new algorithm, difference equation matrix model (DEMM), in the framework of model predictive control (MPC) is introduced. Instead of the standard dynamic matrix control (DMC), which is based upon step response method that has been used in most research works, we propose a new approach based upon a DEMM for model prediction. It has shown that DEMM has proven to be less computational and thus faster than the original DMC for real time applications. Thus, the drawbacks of DMC for online identification or adaptive design could be avoided. The control of wind turbines is carried out in order to decrease the cost of wind energy by increasing the efficiency, and thus the energy capture, or by reducing structural loading and increasing the lifetimes of the components and turbine structures. Modeling of wind turbine has been carried out. Effect of noise and disturbance on the system has been also studied. The results obtained show that the proposed DEMM minimizes the effect of the disturbance and produces an accurate and smooth control. Significant improvements in the regulation of rotor speed at high wind speeds are obtained from the proposed DEMM, where control set points are obtained ahead of the disturbance, saving the turbine of the negative effects of them and thus increasing its lifetime. Copyright © 2012 John Wiley & Sons, Ltd.