Aluminium Metal Matrix Composite (MMC) is gradually gaining popularity in various engineering applications. This is due to their light weight and favourable physical and chemical properties. Weldability study of them is, therefore, important to facilitate fabrication of components. In this work, autogeneous bead-on-plate TIG welding of Al-7.7%-SiC MMC was performed using Argon as the shielding gas. Heat input and gas flow rate were input variables. Central Composite Design (CCD) of Response Surface Methodology (RSM) was the design of experiment followed in this work. Bead geometry (depth of penetration, height of reinforcement and bead width) and hardness of weld-bead were measured. At a low value of heat input (0.438 kJ/mm) and low value of gas flow rate (10 l/min), lowest height of reinforcement with a value of 0.112 mm is obtained. Both heat input and gas flow rate have effect on bead width. Lowest value of bead width of 4.836 mm may be the recommended one. Considering the variation of bead geometry with the two factors chosen, a high value of gas flow rate (14 l/min) with high heat input (0.702 kJ/mm) may be recommended for adoption that gives high depth of penetration of 2.238 mm.
Megalencephalic leukoencephalopathy with subcortical cysts (MLC), a rare and progressive neurodegenerative disorder involving the white matter, is not adequately recapitulated by current disease models. Somatic cell reprogramming, along with advancements in genome engineering, may allow the establishment of in-vitro human models of MLC for disease modeling and drug screening. In this study, we utilized cellular reprogramming and gene-editing techniques to develop induced pluripotent stem cell (iPSC) models of MLC to recapitulate the cellular context of the classical MLC-impacted nervous system. Somatic cell reprogramming of peripheral patient-derived blood mononuclear cells (PBMCs) was used to develop iPSC models of MLC. CRISPR-Cas9 system-based genome engineering was also utilized to create the MLC1 knockout model of the disease. Directed differentiation of iPSCs to neural stem cells (NSCs) and astrocytes was performed in a 2D cell culture format, followed by various cellular and molecular biology approaches, to characterize the disease model. MLC iPSCs established by somatic cell reprogramming and genome engineering were well characterized for pluripotency. iPSCs were subsequently differentiated to disease-relevant cell types: neural stem cells (NSCs) and astrocytes. RNA sequencing profiling of MLC NSCs revealed a set of differentially expressed genes related to neurological disorders and epilepsy, a common clinical finding within MLC disease. This gene set can serve as a target for drug screening for the development of a potential therapeutic for this disease. Upon differentiation to the more disease relevant cell type-astrocytes, MLC-characteristic vacuoles were clearly observed, which were distinctly absent from controls. This emergence recapitulated a distinguishing phenotypic marker of the disease. Through the creation and analyses of iPSC models of MLC, our work addresses a critical need for relevant cellular models of MLC for use in both disease modeling and drug screening assays. Further investigation can utilize MLC iPSC models, as well as generated transcriptomic data sets and analyses, to identify potential therapeutic interventions for this debilitating disease.
Effect of pH and lime on sulphate adsorption was investigated in five Alfisols of Orissa. Sulphate adsorption decreased with increase in equilibrium pH of the SO42− solutions added. Distribution coefficient of SO42−-S decreased sharply with increase in equilibrium pH indicating that the SO42− adsorption in these soils was highly pH-dependent. Liming the soils by Woodruff's buffer method increased the pH in different soils ranging between 7.3 and 8.1 and caused a drastic reduction in SO42− adsorption varying from 60 to 93.5% in different soils. There were significant reductions in Freundlich K, Langmuir adsorption maxima, equilibrium buffering capacity and maximum buffering capacity of the soils after liming.
There are surprisingly few RNA intramolecular triple helices known in the human transcriptome. The structure has been most well-studied as a stability-element at the 3' end of lncRNAs such as
The effect of organic matter on sulphate adsorption was investigated in four Alfisols of Orissa. There was increase in SO42- adsorption, equilibrium buffering capacity (EBC), maximum buffering capacity (MBC) and decrease in DGo of SO42- adsorption and supply parameter of SO42- (SP) due to removal of organic matter. The increase in SO42- adsorption capacity, EBC, MBC and decrease in SP were remarkably high in Suakati and Badbil soils, small in Sukinda soil and insignificant in Joshipur soil.
Kinetics of sulphate adsorption was studied in the surface soils and subsoils of five Alfisols of the state Orissa. Adsorption progressed at a faster rate for the initial 30 to 60 minutes in different soils with completion of 72 to 94% of total adsorption and then progressed slowly to attain equilibrium after 2 to 4 hours in different soils. The amounts of SO42−-S adsorbed at different time intervals and at equilibrium were higher in the subsoils than in the surface soils. The time-dependent SO42− adsorption was best described by the first order and Elovich equations. Clay, free Fe2O3, free Al2O3, exchangeable Ca2++Mg2+, pHw and organic carbon together accounted for 86.9% of variations in the first order apparent adsorption rate coefficient and 83.1% of variations in the Elovich adsorption rate coefficient.
Abstract The clinical success of CRISPR therapies hinges on the safety and efficacy of Cas proteins. The Cas9 from Francisella novicida (FnCas9) is highly precise, with a negligible affinity for mismatched substrates, but its low cellular targeting efficiency limits therapeutic use. Here, we rationally engineer the protein to develop enhanced FnCas9 (enFnCas9) variants and broaden their accessibility across human genomic sites by ~3.5-fold. The enFnCas9 proteins with single mismatch specificity expanded the target range of FnCas9-based CRISPR diagnostics to detect the pathogenic DNA signatures. They outperform Streptococcus pyogenes Cas9 (SpCas9) and its engineered derivatives in on-target editing efficiency, knock-in rates, and off-target specificity. enFnCas9 can be combined with extended gRNAs for robust base editing at sites which are inaccessible to PAM-constrained canonical base editors. Finally, we demonstrate an RPE65 mutation correction in a Leber congenital amaurosis 2 (LCA2) patient-specific iPSC line using enFnCas9 adenine base editor, highlighting its therapeutic utility.
Sulphate adsorption characteristics of the surface soils and sub-soils of five Alfisols of the state were studied. Adsorption of SO42− was higher in the sub-soils than in the surface soils which was attributed to higher clay, free Fe2O3, exchangeable Ca2+ + Mg2+ and lower organic matter contents in the former than in the latter. Free Fe2O3 had the dominant role in SO42− adsorption, followed by clay and exchangeable Ca2+ + Mg2+. These three factors alongwith free A12O3, pHw and organic carbon jointly contributed 99.2 to 99.9 per cent of variations in SO42− adsorption at different levels of SO42−-S added. Equilibrium buffering capacity and maximum buffering capacity for SO42−-S increased, whereas supply parameter of SO42−-S decreased from surface to the sub-soils.
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