Docking-based comparative intermolecular contacts analysis as new 3-D QSAR concept for validating docking studies and in silico screening: NMT and GP inhibitors as case studies

The significant role played by docking algorithms in drug discovery combined with their serious pitfalls prompted us to envisage a novel concept for validating docking solutions, namely, docking-based comparative intermolecular contacts analysis (dbCICA). This novel approach is based on the number and quality of contacts between docked ligands and amino acid residues within the binding pocket. It assesses a particular docking configuration on the basis of its ability to align a set of ligands within a corresponding binding pocket in such a way that potent ligands come into contact with binding site spots distinct from those approached by low-affinity ligands and vice versa. In other words, dbCICA evaluates the consistency of docking by assessing the correlation between ligands' affinities and their contacts with binding site spots. Optimal dbCICA models can be translated into valid pharmacophore models that can be used as 3-D search queries to mine structural databases for new bioactive compounds. dbCICA was implemented to search for new inhibitors of candida N-myristoyl transferase as potential antifungal agents and glycogen phosphorylase (GP) inhibitors as potential antidiabetic agents. The process culminated in five selective micromolar antifungal leads and nine GP inhibitory leads.     

Experimental investigation of natural convection heat transfer characteristics in MWCNT-thermal oil nanofluid

Journal of Thermal Analysis and Calorimetry - The carbon nanotubes are considered as one of the highest thermal conductive material which is having a variety of heat transfer applications. The...     

Synthesis of (1R,4S,5R)-endo-N,N-dimethyl-2-azabicyclo[2.2.1]methanamine

Starting from trans-4-hydroxy-L-proline, (1R,4S,5R)-endo-N,N-dimethyl-2-azabicyclo[2.2.1]methanamine 1 has been synthesized. The target compound is precursor of antibacterial quinolone carboxylic acids.     

Modular Adder Designs Using Optimal Reversible and Fault Tolerant Gates in Field-Coupled QCA Nanocomputing

The challenges which the CMOS technology is facing toward the end of the technology roadmap calls for an investigation of various logical and technological solutions to CMOS at the nano scale. Two such paradigms which are considered in this paper are the reversible logic and the quantum-dot cellular automata (QCA) nanotechnology. Firstly, a new 3 × 3 reversible and universal gate, RG-QCA, is proposed and implemented in QCA technology using conventional 3-input majority voter based logic. Further the gate is optimized by using explicit interaction of cells and this optimized gate is then used to design an optimized modular full adder in QCA. Another configuration of RG-QCA gate, CRG-QCA, is then proposed which is a 4 × 4 gate and includes the fault tolerant characteristics and parity preserving nature. The proposed CRG-QCA gate is then tested to design a fault tolerant full adder circuit. Extensive comparisons of gate and adder circuits are drawn with the existing literature and it is envisaged that our proposed designs perform better and are cost efficient in QCA technology.     

Design of Ultra-Efficient Reversible Gate Based 1-bit Full Adder in QCA with Power Dissipation Analysis

The difficulties which the CMOS technology is facing at the nano scale has led to the investigation of quantum-dot cellular automata (QCA) nanotechnology and reversible logic as an alternative to conventional CMOS technology. In this paper, these two paradigms have been combined. Firstly, a new 3 × 3 reversible gate, SSG-QCA, which is universal and multifunctional in nature, is proposed and implemented in QCA using conventional 3-input majority voter based logic. By using the concept of explicit interaction of cells, the proposed gate is further optimized and then used to design an ultra-efficient 1-bit full adder in QCA. The universal nature has been verified by designing all the logic gates from the proposed SSG-QCA gate whereas the multifunctional nature is verified by implementing all the 13 standard Boolean functions. The proposed 3 × 3 gate and adder designs are then extensively compared with the existing literature and it is observed that the proposed designs are ultra-efficient in terms of both area and cost in QCA technology. In addition to this energy dissipation analysis for different scenarios is also done on all the designs and it is observed that the proposed designs dissipate minimum energy thereby making them suitable for ultra-low power designs.

     

Integer Fuzzy Programming Approach in Bi-objective Selective Maintenance Allocation Problem

An attempt has been made to obtain a compromise allocation based on maximization of individual reliabilities of repairable and replaceable components with in the subsystems, using the information of failed and operational components and a non linear cost function with fixed budget. A solution algorithm of fuzzy programming technique is used to solve the Bi-Objective Selective Maintenance Allocation Problem (BSMAP). Also, the problem has been solved by two other suggested methods; “Weighted Criterion Technique” and “Desirability Function Technique”. A numerical example is also presented to illustrate the computational details.     

Ultrasensitive NOX Detection in Simulated Exhaled Air: Enhanced Sensing via Alumina Modification of In‐Situ Grown WO3 Nanoblocks

Seedless growth of vertically aligned nanostructures, which can induce smoother transport and minimize Ohmic contact between substrate and semiconductor, can be fabricated by in situ growth utilizing modified hydrothermal methods. Such devices can be useful in designing non‐invasive ultrasensitive hand‐held sensors for diagnostic identification of volatile organic compounds (VOCs) in exhaled air, offering pain‐free and easier detection of long‐term diseases such as asthma. In the present work, WO₃ nanoblocks, with a high surface area and porosity, have been grown directly over transparent conducting oxide to minimize Ohmic resistance, facilitating smoother electron transfer and enhanced current response. Further modification with porous alumina (γ‐Al₂O₃), by electrodeposition, resulted in the selective and ultrasensitive detection of NO_X in simulated exhaled air. Crystal phase purity of as‐fabricated pristine as well modified samples is validated with X‐ray diffraction analysis. Morphological and microstructural analyses reveal the successful deposition of porous alumina over the surface of WO₃. Improved surface area and porosity is presented by porous alumina in the modified WO₃ device, suggesting more active sites for the gas molecules to get adsorbed and diffuse through the pores. Oxygen vacancies, which are detrimental in the transport phenomenon in the presented sensors, have been studied using X‐ray photoelectron spectroscopic (XPS) analysis. Gas sensing studies have been performed by fabricating chemiresistor devices based on bare WO₃ and Al₂O₃‐modified WO₃. The higher sensitivity for NO_X gas in case of γ‐Al₂O₃‐modified WO₃ based devices, as compared to bare WO₃‐based devices, is attributed to the better surface area and charge transport kinetics. The presented device strategy offers crucial understanding in the design and development of non‐invasive, hand‐held devices for NO gas present in the human breath, with potential application in medical diagnostics.     

Strawberry Decreases Intraluminal and Intestinal Wall Hydrolysis of Testosterone Undecanoate

Male hypogonadism is often treated by testosterone (T) replacement therapy such as oral administration of the ester prodrug, testosterone undecanoate (TU). However, the systemic exposure to T following oral TU is very low due to esterase-mediated metabolism, particularly in the small intestine. The aim of this work was to examine the esterase-inhibitory effect of natural fruit extract of strawberry (STW) on the intestinal degradation of TU as a potential approach to increasing the oral bioavailability of T. Herein, the hydrolysis of TU was assessed in fasted state simulated intestinal fluid with added esterase activity (FaSSIF/ES) and Caco-2 cell homogenates in the presence of STW extract. It is noteworthy that STW substantially inhibited the degradation of TU in FaSSIF/ES and Caco-2 cell homogenates at concentrations that could be achieved following oral consumption of less than one serving of STW fruit. This can significantly increase the fraction of unhydrolyzed TU in the intestinal lumen as well as in enterocytes. In addition, it was demonstrated that TU has high intestinal lymphatic transport potential as the association of TU with plasma-derived human chylomicrons was in the range of 84%. Therefore, oral co-administration of TU with STW could potentially increase the intestinal stability of TU and consequently the contribution of lymphatically delivered TU to the systemic exposure of T in vivo.