Identification of Natural Products as Potential Pharmacological Chaperones for Protein Misfolding Diseases

Defective protein folding and accumulation of misfolded proteins is associated with neurodegenerative, cardiovascular, secretory, and metabolic disorders. Efforts are being made to identify small-molecule modulators or structural-correctors for conformationally destabilized proteins implicated in various protein aggregation diseases. Using a metastable-reporter-based primary screen, we evaluated pharmacological chaperone activity of a diverse class of natural products. We found that a flavonoid glycoside ( C-10 , chrysoeriol-7-O-β-D-glucopyranoside) stabilizes metastable proteins, prevents its aggregation, and remodels the oligomers into protease-sensitive species. Data was corroborated with additional secondary screen with disease-specific pathogenic protein. In vitro and cell-based experiments showed that C-10 inhibits α-synuclein aggregation which is implicated in synucleinopathies-related neurodegeneration. C-10 interferes in its structural transition into β-sheeted fibrils and mitigates α-synuclein aggregation-associated cytotoxic effects. Computational modeling suggests that C-10 binds to unique sites in α-synuclein which may interfere in its aggregation amplification. These findings open an avenue for comprehensive SAR development for flavonoid glycosides as pharmacological chaperones for metastable and aggregation-prone proteins implicated in protein conformational diseases.     

Nanomaterials based biofuel cells: A review

Biofuel cells (BFCs) are the devices made to transform the chemical energy of organic matter to electrical energy utilizing metabolic reactions occurring in microorganisms during degradation of organic contaminants. In spite of having many applications such as waste water treatment, biosensors and portable uses of BFCs, promoting the uses of BFCs is very challenging because of short life-time and low-power density. Most of the BFC developed till date is only capable to fulfill energy needs of biomedical short-term implanted devices. Use of materials with nano dimensions in the construction of BFCs has been studied extensively and reported as a worthwhile strategy to increase its efficiency. Usually, it is difficult to achieve efficient electron transfer on planar electrode from biocatalyst due to its non-specific orientational the interface. Nonmaterials provide close wiring for the electron transfer between biocatalyst and electrode. Use of various nanomaterials is the most effective way to decrease the gap between active sites (electron producing area)deep inside the enzyme or proteins and the electrodes to achieve better electron transfer. Also, various nanomaterials are utilized to improve the membrane materials for better electron barrier. Many carbon nanostructures, conducting polymers, metal and metal oxides are promising nonmaterials to enhance the current output from BFC. This review highlights recent progress registered in the development of various nanomaterials for construction of electrode and membranes of biofuel cells for better efficiency. It also emphasized the utilization of different metallic nanomaterials, inorganic nanomaterials, conducting polymer-based nanomaterials and carbon-based nanomaterials such as graphene, fullerenes, and carbon nanotubes.     

Two-stage iterations based on composite splittings for rectangular linear systems

In this paper, we introduce a two-stage method to solve rectangular linear systems that exhibits faster convergence than typical stationary iterative methods. Under suitable conditions, we prove convergence of the new method. The number of outer iterations can be reduced by using a few significant number of inner iterations for efficient computations. Further, we perform a comparison analysis, and establish that a higher number of inner iterations ensures a smaller spectral radius of the global iteration matrix. We also discuss the uniqueness of a proper splitting, and illustrate different comparison theorems for different subclasses of proper splittings.     

Characterisation and oxidation of LVOF sprayed Al2O3–40%TiO2 coating on superni 601 and superni 718 superalloys at 800 and 900°C

Failure of components due to high temperature oxidation is the major degradation mechanism in boiler and gas turbine industries. Superalloys having superior mechanical properties and creep resistance are used in these applications but lack resistance to oxidation under aggressive environments. Protective coatings are used to improve their oxidation resistance in such applications. In the present investigation, Al₂O₃–40%TiO₂ coating was deposited on superni 718 and superni 601 superalloys by low velocity oxy fuel process. The as sprayed coating was characterised for microhardness, surface roughness, scanning electron microscopy and X-ray diffraction analysis. High temperature oxidation behaviour of Al₂O₃–40%TiO₂ coated and uncoated superni 718 and superni 601 superalloys has been evaluated at the elevated temperatures of 800 and 900°C for total duration of 50 cycles under cyclic conditions. Each cycle consisted of keeping the samples for 1 h at the elevated temperature followed by 20 min cooling in ambient air. Al₂O₃–40TiO₂ coating in the as sprayed condition showed the presence of Al₂O₃–TiO₂, α-Al₂O₃, TiO₂ as the main phases. Al₂O₃–40%TiO₂ coating on superni 718 and superni 601 superalloys has shown a lower oxidation rate as compared to those of uncoated superalloys. However, the oxidation rate of the coating was not steady due to the occurrence of spallation/sputtering at various stages. The coating was found adherent on the substrate superalloys throughout the study.     

Frequency channeling: a concept to increase the frequency and control the PPV of blast-induced ground vibration waves in multi-hole blast in a surface mine

Bulletin of Engineering Geology and the Environment - Vibrations induced due to blasting in mines may damage the nearby houses and disturb the habitants. The monitoring, prediction, and control of...     

Vortex characteristics due to nozzle clogging in water caster mould: modelling and validation

In continuous slab casting, clogging in the submerged entry nozzle (SEN) ports leads to flow asymmetry and vortex formation in the mould. Knowledge of vortexing and its influence on product quality is fundamental for defect-free production. In this study, the interconnected effects of nozzle clogging and SEN submergence depth, variation on flow asymmetry and vortex characteristics in a 0.4 scale water caster have been characterised by CFD investigation and validated with experimental results from the authors’ previous work. Mean flow velocities at the sub-meniscus and near the port exit predicted by the computational model are compared with the time-averaged values of the impeller probe velocity measurements and found to be in reasonable agreement. Three different clogging conditions (0, 33 and 66% in the left port of the SEN) for SEN submergence depth of 60?mm are studied and the 66% clogging produced vortices having largest diameter, which is consistent with the experimental observations. The effects of SEN submergence depth on flow asymmetry and vortexing are investigated with three different conditions – 40, 60 and 80?mm. It is found that the shallow SEN submergence depth (40?mm) produces vortices of largest diameter and the flow is most stable for a SEN submergence depth of 60?mm among the three cases. Vortex bending towards the SEN as noticed in the experimental observations is also observed in the computational study. This work illustrates the possibility of capturing features of vortexing using validated CFD model.     

An environmentally sustainable manufacturing network model under an international ecosystem

Clean Technologies and Environmental Policy - There is a growing consensus that the increase in greenhouse gases results in unfavorable changes to the Earth’s climate and is responsible for...     

Physico‐mechanical properties of nano‐polystyrene‐decorated graphene oxide–epoxy composites

Nano‐polystyrene (nPS)‐decorated graphene oxide (GO) hybrid nanostructures were successfully synthesized using stepwise microemulsion polymerization, and characterized using Fourier transform infrared (FTIR) spectroscopy, X‐ray diffraction (XRD), field‐emission scanning electron microscopy and transmission electron microscopy. XRD and FTIR spectra revealed the existence of a strong interaction between nPS and GO, which implied that the polymer chains were successfully grafted onto the surface of the GO. The nPS‐decorated GO hybrid nanostructures were compounded with epoxy using a hand lay‐up technique, and the effect of the nPS‐decorated GO on the mechanical, thermal and surface morphological properties of the epoxy matrix was investigated using a universal tensile machine, Izod impact tester, thermogravimetric analysis and contact angle measurements with a goniometer. It was observed that in the epoxy matrix, GO improved the compatibility. © 2017 Society of Chemical Industry