Synthesis of Stable NAD+ Mimics as Inhibitors for the Legionella pneumophila Phosphoribosyl Ubiquitylating Enzyme SdeC

Stable NAD⁺ analogues carrying single atom substitutions in either the furanose ring or the nicotinamide part have proven their value as inhibitors for NAD⁺-consuming enzymes. To investigate the potential of such compounds to inhibit the adenosine diphosphate ribosyl (ADPr) transferase activity of the Legionella SdeC enzyme, we prepared three NAD⁺ analogues, namely carbanicotinamide adenosine dinucleotide (c-NAD⁺), thionicotinamide adenosine dinucleotide (S-NAD⁺) and benzamide adenosine dinucleotide (BAD). We optimized the chemical synthesis of thionicotinamide riboside and for the first time used an enzymatic approach to convert all three ribosides into the corresponding NAD⁺ mimics. We thus expanded the known scope of substrates for the NRK1/NMNAT1 enzyme combination by turning all three modified ribosides into NAD⁺ analogues in a scalable manner. We then compared the three NAD⁺ mimics side-by-side in a single assay for enzyme inhibition on Legionella effector enzyme SdeC. The class of SidE enzymes to which SdeC belongs was recently identified to be important in bacterial virulence, and we found SdeC to be inhibited by S-NAD⁺ and BAD with IC₅₀ values of 28 and 39 μM, respectively.     

Investigation of thermoluminescence and kinetic parameters of gamma ray exposed LiF: Sm3+, Eu3+ nanophosphors for dosimetric applications

Thermoluminescence (TL) properties of LiF: Sm³⁺ (0.05?mol%) co-doped with Eu³⁺ (0.02, 0.04, 0.06, 0.08?mol%) nanophosphor for the applications of TL dosimetry have been studied. The nanophosphors have been synthesized by chemical co-precipitation method at 8?pH value. The phase purity of the prepared samples has been confirmed by using X-ray diffraction (XRD) data. The XRD peaks broadening revealed the formation of the nanostructure, complemented by the TEM image. For TL studies, the samples have been irradiated with gamma rays using ⁶⁰Co source in the irradiation dose range of 0.1?kGy to 30?kGy. In gamma exposed samples, the TL glow curve consists of single glow peak at 410?K and three shoulder peaks at 475?K, 550?K and 632?K. The dosimetry properties such as the effects of exposure doses, heating rates and fading characteristics have also been studied. The kinetic parameters such as activation energy (E), the frequency factors (s) and order of kinetic (b) of the glow curves have also been calculated by using Chen's peak shape method. The linear behavior of TL intensity with radiation doses and low fading shows that the LiF: Sm³⁺, Eu³⁺ Nanophosphor is a potential candidate for dosimetry applications.     

Mycobacterial Membrane Protein Large 3 (MmpL3) Inhibitors: A Promising Approach to Combat Tuberculosis

Tuberculosis is a prominent aliment throughout the world and a leading cause of mortality among infectious diseases. Drug development for multi-drug resistance and reducing the current therapy time is the top priority. Mycobacterial membrane protein large 3 (MmpL3) is a promising target with high potential, however, it has not been explored to its greatest potential. It is a membrane transporter that translocates trehalose-monomycolate which is a precursor for the synthesis of mycolic acid that is essential for the synthesis of the bacterial cell wall and is pathogenic in nature. In this review, we have discussed the current development of MmpL3 inhibitors, different scaffolds, their derivatives, and their synthetic schemes and provide insight into the challenges in developing these inhibitors.     

Minimum reflux calculation for multicomponent distillation in multi-feed,multi-product columns: Mathematical model

Multi-feed, multi-product distillation columns are ubiquitous in multicomponent distillation systems. The minimum reflux ratio of a distillation column is directly related to its energy consumption and capital cost. Thus, it is a key parameter for distillation systems design, operation, and comparison. In this series, we present the first accurate shortcut based algorithmic method to determine the minimum reflux condition for any general multi-feed, multi-product (MFMP) distillation column separating any ideal multicomponent mixture. The classic McCabe-Thiele or Underwood method is a special case of this general approach. Compared with existing techniques, this method does not involve any rigorous tray-by-tray calculation, nor does it require guessing of key components. In this first part of the series, we present the mathematical model for a general MFMP column, derive constraints for feasible separation and minimum reflux condition, discuss their geometric interpretations, and present an illustrative example to demonstrate the effectiveness of our approach.     

A novel technique for image classification using short-time Fourier transform and local binary pattern

Multimedia Tools and Applications - Machine Learning (ML) has been widely used for Image processing. The pertinent feature extraction and feature selection techniques can help us to accomplish many...     

Heazlewoodite,Ni3S2: An electroactive material for supercapacitor application

Engineering of nanostructured materials with a unique and uniform morphological design is considered to be a competent candidate for a diverse range of electrochemical energy applications. However, the construction of ball-in-ball transition metal sulfide via the vaporization process remains a big challenge of today's research community. In this work, carbon encapsulated nickel sulfide (Ni₃S₂@C) with a complex hollow interior was synthesized and further studied with nitrogen-doped carbon encapsulated nickel sulfide (Ni₃S₂@NC) for comparison basis. We used metal salt (nickel nitrate) and organic linker (trimesic acid, TMA) as a precursor to synthesize Ni-TMA via a solvothermal method. Next, the sulfidation process was done under 5% H₂ balanced argon gas in a tubular furnace to convert into Ni₃S₂ with encapsulation of carbon. The prepared hybrid material showed ball-in-ball morphology and heazlewoodite mineral phase structure. Furthermore, the prepared materials were examined for electrochemical energy storage properties owing to their well-known faradaic dominant (battery-type) charge storage features and key positive electroactive material for today's growing hybrid electrochemical capacitor. The nitrogen-doped carbon encapsulated nickel sulfide has demonstrated good electrochemical features like a specific capacity of 442.45 F g^?1 at 5 mV s^?1 of scan rate and 373.52 F g^?1 at 2 A g^?1 of current density. Moreover, the material showed excellent capacitance retention of 81% and 70% after 5000 and 10,000 cycles run with 100% of coulombic efficiency at 8 A g^?1.     

The effect of using the turbulence enhancement unit before the catalytic converter in diesel engine emissions

This research focuses on reducing the toxic emissions from the exhaust by installing a turbulence enhancement unit just before the three-way catalytic converter. This unit creates turbulence in the gases flowing through the combustion chamber when fitted with the Tata Indica V2 diesel engine (1405cc). Turbulence leads to the rising in the contact area of the exhaust gases going to the catalytic converter for the reactions to take place. Experimentally, it was found that swirl venturi gives the best results in the overall emission test. Although the overall best device is swirl venturi, swirl blades also give better results on higher rpm of the engine. This paper shows the detailed research on the emission test performed.