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.     

One-step purification of lactoperoxidase from bovine milk by affinity chromatography

Sulphanilamide was determined to be a new inhibitor of lactoperoxidase (LPO) with an IC₅₀ of 0.848.10⁻⁵ M. The K_i for sulphanilamide was determined to be 3.57.10⁻⁵ M and sulphanilamide showed competitive inhibition, which makes it a suitable ligand for constructing a Sepharose 4B-l-tyrosine affinity matrix. The affinity matrix was synthesised by coupling sulphanilamide as the ligand and l-tyrosine as the spacer arm to a cyanogen bromide (CNBr)-activated-Sepharose 4B matrix. Lactoperoxidase was purified 409-fold from the synthesized affinity matrix in a single step, with a yield of 62.3% and a specific activity of 40.9 EU/mg protein. The enzyme activity was measured using ABTS as a chromogenic substrate (pH 6.0). The degree of LPO purification was monitored by SDS–PAGE and its R_z (A₄₁₂/A₂₈₀) value. The R_z value for the purified LPO was found to be 0.7. Maximum binding was achieved and K_m and V_max values were determined.     

Entropy generation minimization on electromagnetohydrodynamic radiative Casson nanofluid flow over a melting Riga plate

Minimizing entropy generation is a technique that helps improve the effectiveness of real processes by studying the associated irreversibility of system performance of nanofluid. This study examines the entropy generation analysis of electromagnetohydrodynamic radiative Casson flow induced by a stretching Riga plate in a non-Darcian porous medium under the influence of internal energy change, Arrhenius activation energy, chemical reaction, and melting heat transfer. The thermophysical features of the fluid are assumed constant in most of the literature. However, this current research bridges this gap by considering viscosity, conductivity, and diffusivity as temperature-dependent variables. Also, the exponential decaying Grinberg term is used as a resistive force in this investigation due to the electromagnetic properties of the Riga plate in the momentum conservation equation. Some suitable dimensionless variables are introduced to remodel the transport equations into unitless ones and then solved numerically by employing Galerkin Weighted Residual Method. Analyses reveal that the Casson parameter declines the fluid velocity, while the existence of the melting parameter has the opposite effect. Also, this article includes some future recommendations.     

Three-dimensional non-isothermal model development of high temperature PEM Fuel Cells

A three-dimensional non-isothermal mathematical model is developed in a triple mixed serpentine flow multichannel domain for a high temperature PEM Fuel Cell having a phosphoric acid doped PBI membrane as electrolyte and an active area of 25 cm² within Comsol Multiphysics. The inlet temperatures of cathode and anode reactants are taken as 438 K. Model predicts pressure, and temperature distribution along the channels and membrane current density distribution over the membrane electrodes. The model results are obtained at two different operation voltages, 0.45 V and 0.60 V. Resulting average current densities are respectively 0.313 A cm^?2 and 0.224 A cm^?2. The non-isothermal model results are compared to isothermal model results from a previous study and various other single channel non-isothermal model results available in the literature. The pressure drop at cathode compartment is predicted to be 6500 Pa, whereas it is found to be 6400 Pa for the isothermal model. The temperature difference within the system is found to be 0.18 K for the operation voltage of 0.6 V, whereas this value increases to 0.31 K for the operation voltage of 0.45 V. The temperature difference isocontours are illustrated for the whole cell. Considering changes in temperature, one can employ isothermal operation assumption for this system as an approximation and simplification for the governing equations, since the variation in the temperature within the cell is less than 1 K. It should be emphasized that multichannel model predictions are more realistic compared to single channel models. The model developed here can be extended to larger electrode active area and different multichannel configurations.     

Ultrathin polypyrrole films on self-assembled monolayers as an efficient ultramicroelectrode assay

In this work, we investigated the effect of electrodeposition of polypyrrole (PPy) films on two different self-assembled monolayers (SAMs) modified gold electrode for the electrochemical construction of ultramicroelectrode (UME). In order to obtain SAM modified surfaces, 4-mercapto-1-butanol and 11-mercaptoundecanoic acid were used. The effect of these two chains on pyrrole electropolymerization was compared. Electropolymerization of pyrrole on SAM modified Au electrode was carried out by using cyclic voltammetry (CV) and constant potential electrolysis. To investigate the UME formation, the obtained surfaces were tested in Fe(CN)₆^3−/4− redox system. UMEs were characterized using scanning electron microscopy energy-dispersive X-ray spectroscopy, attenuated total reflectance fourier transform infrared spectroscopy and electrochemical impedance spectroscopy. The designed UME was applied as an immobilization matrix to entrap a redox protein, Hemoglobin (Hb), as a model. Direct electron transfer between this protein and the fabricated thiol modified PPy based UME was achieved, which is very challenging on bare electrode surfaces. With this study, a simple, low-cost and reproducible UME production way has been successfully accomplished and Hb modified UME is promising for different bioanalytical applications, for instance; cellular hydrogen peroxide or nitrite sensing.     

Evaluating Bar Coding‐Aided Medication Administration through Identification of Nursing Work Deficiencies

Health care information technology (IT) systems manage administrative and clinical processes more accurately and efficiently. However, their effects on clinical work flow are still not fully understood. In this article, we investigate the bar‐coded medication administration (BCMA) system for its effect on nurses working in inpatient departments. Evaluation is applied by examining work deficiencies before and after the IT system implementation based on a proposed nursing work model. A list of nurse‐perceived risks of work deficiencies related to the current BCMA system has been identified. Results show five main deficiencies that are mainly related to aspects of the IT environment and work schedule/process, including increased workload, IT systems downtime, unclear orders/task schedules, reduced time for patient‐care tasks, and redundant documentation. This study emphasizes the importance of understanding the reciprocal relationship between IT implementation and health care work system. © 2012 Wiley Periodicals, Inc.     

Optimization of Adaptive Fuzzy Controller for Maximum Power Point Tracking Using Whale Algorithm

The advantage of fuzzy controllers in working with inaccurate and nonlinear inputs is that there is no need for an accurate mathematical model and fast convergence and minimal fluctuations in the maximum power point detector. The capability of online fuzzy tracking systems is maximum power, resistance to radiation and temperature changes, and no need for external sensors to measure radiation intensity and temperature. However, the most important issue is the constant changes in the amount of sunlight that cause the maximum power point to be constantly changing. The controller used in the maximum power point tracking (MPPT) circuit must be able to adapt to the new radiation conditions. Therefore, in this paper, to more accurately track the maximum power point of the solar system and receive more electrical power at its output, an adaptive fuzzy control was proposed, the parameters of which are optimized by the whale algorithm. The studies have repeated under different irradiation conditions and the proposed controller performance has been compared with perturb and observe algorithm (P&O) method, which is a practical and high-performance method. To evaluate the performance of the proposed algorithm, the particle swarm algorithm optimized the adaptive fuzzy controller. The simulation results show that the adaptive fuzzy control system performs better than the P&O tracking system. Higher accuracy and consequently more production power at the output of the solar panel is one of the salient features of the proposed control method, which distinguishes it from other methods. On the other hand, the adaptive fuzzy controller optimized by the whale algorithm has been able to perform relatively better than the controller designed by the particle swarm algorithm, which confirms the higher accuracy of the proposed algorithm.     

Optimal Operation of Distributed Generations Considering Demand Response in a Microgrid Using GWO Algorithm

The widespread penetration of distributed energy sources and the use of load response programs, especially in a microgrid, have caused many power system issues, such as control and operation of these networks, to be affected. The control and operation of many small-distributed generation units with different performance characteristics create another challenge for the safe and efficient operation of the microgrid. In this paper, the optimum operation of distributed generation resources and heat and power storage in a microgrid, was performed based on real-time pricing through the proposed gray wolf optimization (GWO) algorithm to reduce the energy supply cost with the microgrid. Distributed generation resources such as solar panels, diesel generators with battery storage, and boiler thermal resources with thermal storage were used in the studied microgrid. Also, a combined heat and power (CHP) unit was used to produce thermal and electrical energy simultaneously. In the simulations, in addition to the gray wolf algorithm, some optimization algorithms have also been used. Then the results of 20 runs for each algorithm confirmed the high accuracy of the proposed GWO algorithm. The results of the simulations indicated that the CHP energy resources must be managed to have a minimum cost of energy supply in the microgrid, considering the demand response program.     

Conductive Supramolecular Polymer Nanocomposites with Tunable Properties to Manipulate Cell Growth and Functions

Synthetic bioactive nanocomposites show great promise in biomedicine for use in tissue growth, wound healing and the potential for bioengineered skin substitutes. Hydrogen-bonded supramolecular polymers (3A-PCL) can be combined with graphite crystals to form graphite/3A-PCL composites with tunable physical properties. When used as a bioactive substrate for cell culture, graphite/3A-PCL composites have an extremely low cytotoxic activity on normal cells and a high structural stability in a medium with red blood cells. A series of in vitro studies demonstrated that the resulting composite substrates can efficiently interact with cell surfaces to promote the adhesion, migration, and proliferation of adherent cells, as well as rapid wound healing ability at the damaged cellular surface. Importantly, placing these substrates under an indirect current electric field at only 0.1 V leads to a marked acceleration in cell growth, a significant increase in total cell numbers, and a remarkable alteration in cell morphology. These results reveal a newly created system with great potential to provide an efficient route for the development of multifunctional bioactive substrates with unique electro-responsiveness to manipulate cell growth and functions.