Recognizing drug targets using evolutionary information: implications for repurposing FDA-approved drugs against Mycobacterium tuberculosis H37Rv

Drug repurposing to explore target space has been gaining pace over the past decade with the upsurge in the use of systematic approaches for computational drug discovery. Such a cost and time-saving approach gains immense importance for pathogens of special interest, such as Mycobacterium tuberculosis H37Rv. We report a comprehensive approach to repurpose drugs, based on the exploration of evolutionary relationships inferred from the comparative sequence and structural analyses between targets of FDA-approved drugs and the proteins of M. tuberculosis. This approach has facilitated the identification of several polypharmacological drugs that could potentially target unexploited M. tuberculosis proteins. A total of 130 FDA-approved drugs, originally intended against other diseases, could be repurposed against 78 potential targets in M. tuberculosis. Additionally, we have also made an attempt to augment the chemical space by recognizing compounds structurally similar to FDA-approved drugs. For three of the attractive cases we have investigated the probable binding modes of the drugs in their corresponding M. tuberculosis targets by means of structural modelling. Such prospective targets and small molecules could be prioritized for experimental endeavours, and could significantly influence drug-discovery and drug-development programmes for tuberculosis.

Gradient echo single scan inversion recovery: application to proton and fluorine relaxation studies

Single scan longitudinal relaxation measurement experiments enable rapid estimation of the spin-lattice relaxation time (T-1) as the time series of spin relaxation is encoded spatially in the sample at different slices resulting in an order of magnitude saving in time. We consider here a single scan inversion recovery pulse sequence that incorporates a gradient echo sequence. The proposed pulse sequence provides spectra with significantly enhanced signal to noise ratio leading to an accurate estimation of T-1 values. The method is applicable for measuring a range of T-1 values, thus indicating the possibility of routine use of the method for several systems. A comparative study of different single scan methods currently available is presented, and the advantage of the proposed sequence is highlighted. The possibility of the use of the method for the study of cross-correlation effects for the case of fluorine in a single shot is also demonstrated. Copyright (C) 2015 John Wiley & Sons, Ltd.

Gradient echo single scan inversion recovery: application to proton and fluorine relaxation studies

Single scan longitudinal relaxation measurement experiments enable rapid estimation of the spin-lattice relaxation time (T-1) as the time series of spin relaxation is encoded spatially in the sample at different slices resulting in an order of magnitude saving in time. We consider here a single scan inversion recovery pulse sequence that incorporates a gradient echo sequence. The proposed pulse sequence provides spectra with significantly enhanced signal to noise ratio leading to an accurate estimation of T-1 values. The method is applicable for measuring a range of T-1 values, thus indicating the possibility of routine use of the method for several systems. A comparative study of different single scan methods currently available is presented, and the advantage of the proposed sequence is highlighted. The possibility of the use of the method for the study of cross-correlation effects for the case of fluorine in a single shot is also demonstrated. Copyright (C) 2015 John Wiley & Sons, Ltd.

Combustion and heat transfer characteristics of nanofluid fuel droplets: A short review

With the pressing need to meet an ever-increasing energy demand, the combustion systems utilizing fossil fuels have been the major contributors to carbon footprint. As the combustion of conventional energy resources continue to produce significant Green House gas (GHG) emissions, there is a strong emphasis to either upgrade or find an energy-efficient eco-friendly alternative to the traditional hydrocarbon fuels. With recent developments in nanotechnology, the ability to manufacture materials with custom tailored properties at nanoscale has led to the discovery of a new class of high energy density fuels containing reactive metallic nanoparticles (NPs). Due to the high reactive interfacial area and enhanced thermal and mass transport properties of nanomaterials, the high heat of formation of these metallic fuels can now be released rapidly, thereby saving on specific fuel consumption and hence reducing GHG emissions. In order to examine the efficacy of nanofuels in energetic formulations, it is imperative to first study their combustion characteristics at the droplet scale that form the fundamental building block for any combustion system utilizing liquid fuel spray. During combustion of such multiphase, multicomponent droplets, the phenomenon of diffusional entrapment of high volatility species leads to its explosive boiling (at the superheat limit) thereby leading to an intense internal pressure build-up. This pressure upsurge causes droplet fragmentation either in form of a microexplosion or droplet puffing followed by atomization (with formation of daughter droplets) featuring disruptive burning. Both these atomization modes represent primary mechanisms for extracting the high oxidation energies of metal NP additives by exposing them to the droplet flame (with daughter droplets acting as carriers of NPs). Atomization also serves as a natural mechanism for uniform distribution and mixing of the base fuel and enhancing burning rates (due to increase in specific surface area through formation of smaller daughter droplets). However, the efficiency of atomization depends on the thermo-physical properties of the base fuel, NP concentration and type. For instance, at dense loading NP agglomeration may lead to shell formation which would sustain the pressure upsurge and hence suppress atomization thereby reducing droplet gasification rate. Contrarily, the NPs may act as nucleation sites and aid boiling and the radiation absorption by NPs (from the flame) may lead to enhanced burning rates. Thus, nanoadditives may have opposing effects on the burning rate depending on the relative dominance of processes occurring at the droplet scale. The fundamental idea in this study is to: First, review different thermo-physical processes that occur globally at the droplet and sub-droplet scale such as surface regression, shell formation due to NP agglomeration, internal boiling, atomization/NP transport to flame zone and flame acoustic interaction that occur at the droplet scale and second, understand how their interaction changes as a function of droplet size, NP type, NP concentration and the type of base fuel. This understanding is crucial for obtaining phenomenological insights on the combustion behavior of novel nanofluid fuels that show great promise for becoming the next-generation fuels. (C) 2016 Elsevier Ltd. All rights reserved.