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.     

Simultaneously determination of methyl and inorganic mercury in fish species by cold vapour generation atomic absorption spectrometry

A simple and rapid non-chromatographic method was developed to determine methylmercury (MeHg) and inorganic mercury (iHg) levels in muscles tissues of 10 freshwater fish species. The MeHg and iHg were determined by cold vapour atomic absorption spectrometry after alkaline wet digestion of samples. The digested samples were reduced sequentially with stannous chloride and sodium tetrahydroborate for iHg and MeHg, respectively. Parameters such as carrier gas flow rate (argon), volume of oxidizing and potassium persulphate solutions were investigated in detail. The accuracy of the technique was evaluated by using certified reference material (DORM-2) and spiking the both Hg species in muscles tissue of a fish. The limits of detection were 0.117 and 0.133 μg kg⁻¹ for MeHg and iHg, respectively. The concentrations of MeHg and iHg in muscles tissues of ten fish species were found in the range of (28.4–56.3) and (3.01–8.11) μg kg⁻¹, respectively.     

Minimum required angular resolution of smartphone displays for the human visual system

There has been a rapid increase in the resolution of small‐sized and medium‐sized displays. This study determines an upper discernible limit for display resolution. A range of resolutions varying from 254–1016 PPI were evaluated using simulated display by 49 subjects at 300 mm viewing distance. The results of the study conclusively show that users can discriminate between 339 and 508 PPI and in many cases between 508 and 1016 PPI.     

油井管特殊扣产品拧接的自动判定法

在油井管特殊扣产品的加工过程中,拧接是一个重要工序,而拧接设备是否具有自动判定的功能,自动判定方法合适与否,都会对生产节奏和质量控制产生影响。本文介绍了一种自动判定的方法,通过对拐点的扭矩数值、圈数的判断,再加上一些防错手段,实现对特殊扣拧接曲线的自动判定。     

Development of the all‐vanadium redox flow battery for energy storage: a review of technological,financial and policy aspects

The commercial development and current economic incentives associated with energy storage using redox flow batteries (RFBs) are summarised. The analysis is focused on the all‐vanadium system, which is the most studied and widely commercialised RFB. The recent expiry of key patents relating to the electrochemistry of this battery has contributed to significant levels of commercialisation in, for example, Austria, China and Thailand, as well as pilot‐scale developments in many countries. The potential benefits of increasing battery‐based energy storage for electricity grid load levelling and MW‐scale wind/solar photovoltaic‐based power generation are now being realised at an increasing level. Commercial systems are being applied to distributed systems utilising kW‐scale renewable energy flows. Factors limiting the uptake of all‐vanadium (and other) redox flow batteries include a comparatively high overall internal costs of $217 kW^?1 h^?1 and the high cost of stored electricity of ≈ The commercial development and current economic incentives associated with energy storage using redox flow batteries (RFBs) are summarised. The analysis is focused on the all‐vanadium system, which is the most studied and widely commercialised RFB. The recent expiry of key patents relating to the electrochemistry of this battery has contributed to significant levels of commercialisation in, for example, Austria, China and Thailand, as well as pilot‐scale developments in many countries. The potential benefits of increasing battery‐based energy storage for electricity grid load levelling and MW‐scale wind/solar photovoltaic‐based power generation are now being realised at an increasing level. Commercial systems are being applied to distributed systems utilising kW‐scale renewable energy flows. Factors limiting the uptake of all‐vanadium (and other) redox flow batteries include a comparatively high overall internal costs of $217 kW^?1 h^?1 and the high cost of stored electricity of ≈ $0.10 kW^?1 h^?1. There is also a low‐level utility scale acceptance of energy storage solutions and a general lack of battery‐specific policy‐led incentives, even though the environmental impact of RFBs coupled to renewable energy sources is favourable, especially in comparison to natural gas‐ and diesel‐fuelled spinning reserves. Together with the technological and policy aspects associated with flow batteries, recent attempts to model redox flow batteries are considered. The issues that have been addressed using modelling together with the current and future requirements of modelling are outlined. Copyright © 2011 John Wiley & Sons, Ltd.     

Fabrication and characterisation of bulk micromachined ZnO energy transducer with interdigitated electrodes

The proposed research work deals with the design, fabrication and characterisation of a ZnO cantilever energy transducer on Si(c) without the use of SOI wafers, thereby, reducing the cost of fabrication. The energy transducer is operated in the longitudinal mode through the interdigitated electrodes. This is for the first time, we have attempted to fabricate a cantilever transducer with interdigitated electrodes on Si(c) in our lab. The design frequency has been chosen in the range of 700–1000 Hz for a typical tire pressure monitoring system application in mind. The experimentally obtained frequency is 876.25 Hz and d₃₃ was calculated as 3.9 pC/N from the measurements. The experimental results are further validated by simulation and the feasibility of its application as energy harvester is demonstrated. The fabrication process is being optimised to fabricate devices with higher piezoelectric coefficients.