EVALUATION OF THRUST FORCE IN DRILLING OF BD-CFRP COMPOSITE USING TAGUCHI ANALYSIS, RESPONSE SURFACE METHODOLOGY AND NEURAL NETWORK

Drilling is the most frequently used machining operation in carbon fiber reinforced polymer (CFRP) composite materials. The quality of the drilled holes is significantly affected by the thrust force generated during drilling of CFRP composite materials. In the present work, an attempt has been made to study the effects of process parameters such as feed rate, spindle speed, drill diameter and point angle on thrust force in drilling of bi-directional carbon fiber reinforced polymer (BD-CFRP) composite laminate using Taguchi design of experiments (DOE), the response surface methodology (RSM) and the genetic algorithm optimized radial basis function neural network (GA-RBFNN). The analysis of variance (ANOVA) is also performed for investigating the influence of process parameters on machining process using high speed steel (HSS) drills. The results reveal that the drill diameter is the most significant design factor influencing the thrust force followed by the spindle speed. It is evident from the investigation that the experimental results of the thrust force in drilling of BD-CFRP composite laminate are in good agreement with the predicted results as per RSM and GA-RBFNN

The isolation and culture of endothelial colony forming cells from human and rat lungs

Blood vessels are crucial for the normal development, lifelong repair and homeostasis of tissues. Recently, vascular progenitor cell–driven 'postnatal vasculogenesis' has been suggested as an important mechanism that contributes to new blood vessel formation and organ repair. Among several described progenitor cell types that contribute to blood vessel formation, endothelial colony-forming cells (ECFCs) have received widespread attention as lineage-specific 'true' vascular progenitors. Here we describe a protocol for the isolation of pulmonary microvascular ECFCs from human and rat lung tissue. Our technique takes advantage of an earlier protocol for the isolation of circulating ECFCs from the mononuclear cellular fraction of peripheral blood. We adapted the earlier protocol to isolate resident ECFCs from the distal lung tissue. After enzymatic dispersion of rat or human lung samples into a cellular suspension, CD31-expressing cells are positively selected using magnetic-activated cell sorting and plated in endothelial-specific growth conditions. The colonies arising after 1–2 weeks in culture are carefully separated and expanded to yield pure ECFC cultures after a further 2–3 weeks. The resulting cells demonstrate the defining characteristics of ECFCs such as (i) 'cobblestone' morphology of cultured cell monolayers; (ii) acetylated low-density lipoprotein uptake and Ulex europaeus lectin binding; (iii) tube-like network formation in Matrigel; (iv) expression of endothelial cell–specific surface markers and the absence of hematopoietic or myeloid surface antigens; (v) self-renewal potential displayed by the most proliferative cells; and (vi) contribution to de novo vessel formation in an in vivo mouse implant model. Assuming typical initial cell adhesion and proliferation rates, the entire procedure can be completed within 4 weeks. Isolation and culture of lung vascular ECFCs will allow assessment of the functional state of these cells in experimental and human lung diseases, providing newer insights into their pathophysiological mechanisms

A nano-MgO and ionic liquid-catalyzed 'green' synthesis protocol for the development of adamantyl-imidazolo-thiadiazoles as anti-tuberculosis agents targeting sterol 14α-demethylase (CYP51)

In this work, we describe the 'green' synthesis of novel 6-(adamantan-1-yl)-2-substitutedimidazo2,1-b1,3,4thiadiazoles (AITs) by ring formation reactions using 1-(adamantan-1-yl)-2-bromoethanone and 5-alkyl/aryl-2-amino1,3,4-thiadiazoles on a nano material base in ionic liquid media. Given the established activity of imidazothiadiazoles against M. tuberculosis, we next examined the anti-TB activity of AITs against the H37Rv strain using Alamar blue assay. Among the tested compounds 6-(adamantan-1-yl)-2-(4-methoxyphenyl)imidazo2,1-b1,3,4thiadiazole (3f) showed potent inhibitory activity towards M. tuberculosis with an MIC value of 8.5 μM. The inhibitory effect of this molecule against M. tuberculosis was comparable to the standard drugs such as Pyrazinamide, Streptomycin, and Ciprofloxacin drugs. Mechanistically, an in silico analysis predicted sterol 14α-demethylase (CYP51) as the likely target and experimental activity of 3f in this system corroborated the in silico target prediction. In summary, we herein report the synthesis and biological evaluation of novel AITs against M. tuberculosis that likely target CYP51 to induce their antimycobacterial activity. © 2015 Anusha et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

A Nano-Mgo and Ionic Liquid-Catalyzed ‘Green’ Synthesis Protocol for the Development of Adamantyl-Imidazolo-Thiadiazoles as Anti-Tuberculosis Agents Targeting Sterol 14α-Demethylase (CYP51)

In this work, we describe the ‘green’ synthesis of novel 6-(adamantan-1-yl)-2-substitutedimidazo[2,1-b][1,3,4]thiadiazoles (AITs) by ring formation reactions using 1-(adamantan-1-yl)-2-bromoethanone and 5-alkyl/aryl-2-amino1,3,4-thiadiazoles on a nano material base inionic liquid media. Given the established activity of imidazothiadiazoles against M. tuberculosis,we next examined the anti-TB activity of AITs against the H37Rv strain using Alamarblue assay. Among the tested compounds 6-(adamantan-1-yl)-2-(4-methoxyphenyl)imidazo[2,1-b][1,3,4]thiadiazole (3f) showed potent inhibitory activity towards M. tuberculosis with an MIC value of 8.5 μM. The inhibitory effect of this molecule against M. tuberculosis was comparable to the standard drugs such as Pyrazinamide, Streptomycin, and Ciprofloxacin drugs. Mechanistically, an in silico analysis predicted sterol 14α-demethylase (CYP51)as the likely target and experimental activity of 3f in this system corroborated the in silico target prediction. In summary, we herein report the synthesis and biological evaluation of novel AITs against M. tuberculosis that likely target CYP51 to induce their antimycobacterial activity

Molprint 2D-Based Identification and Synthesis of Novel Chromene Based Small Molecules that Target Pla2: Validation through Chemo-And Bioinformatics Approaches

Phospholipase A2 (PLA2) is known to regulate inflammation and hence it is considered as a validated drug-target by medicinal chemists. In this report, we have identified and considered a highly ranked ligand from the ZINC-drug-like compounds database that targets PLA2 via the MOLPRINT-2D based chemoinformatics drug-design approach. The computationally predicted lead molecule was found to contain a core moiety of a chromene ring, which is well known for its varied biological properties. Here, a novel and efficient retro-synthetic protocol for the synthesis of highly substituted chromene libraries was made. A one-pot synthesis of chromene was carried out using different aromatic primary alcohols, malononitrile and 4-hydroxy coumarin in the presence of a mild oxidant mixture called T3P®–DMSO, followed by a Suzuki coupling reaction to obtain the lead molecules. All of the tested compounds of the chromene series displayed inhibition of the venom PLA2 in the range of 12 to 68 μM. Among the tested compounds, 2-amino-4-(2′-methyl-[1,1′-biphenyl]-4-yl)-5-oxo-4,5-dihydropyrano[3,2-c]chromene-3-carbonitrile (7b) showed maximum inhibitory efficacy against venom PLA2 with an IC50 value of 12.5 μM. Furthermore, the designed PLA2 ligands bound to the active site of venom PLA2, whose binding affinity was comparable to nimesulide, indicating that the chromene moiety containing ligands could be novel lead-structures that serve as anti-inflammatory agents