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.     

On an f(R) theory of gravity based on non-conformal invariance of gravitational waves

Gravitational waves are an inevitable consequence of Einstein’s theory of gravitation, which are meaningfully comparable with electromagnetic waves except for their non-conformal invariance. So, Einstein’s field equations aremodified by a straightforward generalization of the Lagrangian in the Einstein-Hilbert action by choosing a polynomial in the scalar R of a finite number of terms. In this modified theory of gravity, conformally invariant gravitational waves are obtained. Besides this, cosmological aspects and the gravitational field surrounding a spherically symmetric mass distribution are studied to understand the features of this theory. It reveals that the deviations are not so significant at the observational level, and the features are more or less similar to those of Einstein’s theory.     

Development of High-Strength High-Temperature Cast Al-Ni-Cr Alloys Through Evolution of a Novel Composite Eutectic Structure

Aiming to develop high-strength Al-based alloys with high material index (strength/density) for structural application, this article reports a new class of multiphase Al alloys in the Al-Ni-Cr system that possess impressive room temperature and elevated temperature (≥ 200 °C) mechanical properties. The ternary eutectic and near eutectic alloys display a complex microstructure containing intermetallic phases displaying hierarchically arranged plate and rod morphologies that exhibit extraordinary mechanical properties. The yield strengths achieved at room temperatures are in excess of 350 MPa with compressive plastic strains of more than 30 pct (without fracturing) for these alloys. The stability of the complex microstructure also leads to a yield stress of 191 ± 8 to 232 ± 5 MPa at 250 °C. It is argued that the alloys derive their high strength and impressive plasticity through synergic effects of refined nanoeutectics of two different morphologies forming a core shell type of architecture.     

Toughening of Polylactic Acid: An Overview of Research Progress

To overcome the limitations of polylactic acid, alterations are needed to enhance its toughness, to improve handling and for various applications. Extensive studies were reported, mainly in the area of blends with renewable resource polymer blends. Better phase dispersion between the blend materials is achieved either by reactive mixing of the two components or by incorporation of a block copolymer compatibilizer, finally showing highly enhanced property. In this article, the recent research progress of different toughening processes of PLA via blending is reviewed and a detailed understanding about toughening of PLA using biodegradable or renewable polymers has been established.     

New sinusoidal oscillator configurations using operational transresistance amplifier

The objective of this brief is to introduce four new structures of electronically tunable sinusoidal oscillators (SOs) designed using operational transresistance amplifier (OTRA). Each of the proposed SO consists of forward path derived from a generic structure along with one/two OTRA-based resistive gain stages or differentiator in its feedback path. All the proposed SOs enjoy independent tuning of the frequency of oscillation (FO) through resistors without affecting the condition of oscillation (CO). Further, all topologies are found to exhibit low f_o sensitivities at all frequencies with respect to circuit parameters, and the second topology is capable of achieving very low frequencies (VLFs) using less RC component spread and provides linear tuning too. The fourth circuit provides quadrature output. The proposed SOs have been successfully implemented and verified in 180-nm CMOS technology node using ADE (analog design environment) tool Cadence Virtuoso. Both prelayout and postlayout simulation results have been included. To assess the oscillator prefabrication performances, Monte Carlo and process-voltage-temperature (PVT) analyses have been performed. The total harmonic distortion (THD) is observed to be less than 3.5%.     

In vitro cellular response and hydrothermal aging of two-step sintered Nb2O5 doped ceria stabilized zirconia ceramics

Niobia (1 mol. %) doped Ceria Stabilized Zirconia (NbCSZ) powders were synthesized using a co-precipitation method. The synthesized powders were uniaxially compacted and sintered in air. The two-step sintering method was adopted to sinter the samples, and the sintering schedule was optimized based on density, grain size, the phase present, and the hardness of the sintered sample. It was observed that the two-step sintering method effectively suppressed the grain growth of NbCSZ samples and helped in achieving a finer grain size of 1.57 μm along with the hardness of 1195 HV10 and optimum fracture toughness value 6.20 MPa m^1/2. The Low-Temperature Degradation (LTD) behavior of the sintered samples was estimated through an accelerated hydrothermal aging test, which revealed that the samples are highly resistant to LTD and shown no phase change even after 150 h of study. Moreover, the cytocompatibility of the NbCSZ was tested by culturing MG63 cells on the samples for 7 days. The NbCSZ was found to be highly biocompatible as evident from cell viability and metabolic activity assay.     

Effect of hydrogen enrichment on performance,combustion, and emission of a methanol fueled SI engine

The study of potentially high rated alternative fuel (Methanol) for the IC engines is an exciting topic in the recent research advancement. However, the study of combination of methanol and hydrogen is considered to address both economic and environmental needs. Hydrogen with best combustion characteristics will compensate for the drawbacks of methanol as a fuel. In the present investigation hydrogen enrichment to methanol has shown a significant enhancement in performance and combustion; the overall emission has reduced substantially. The experiments for a different set of trials, including hydrogen enrichment ranging between 5% and 20% with 2.5% increment, the engine is operated with wide-open throttle (WOT) condition for different speeds. The increase in enrichment of hydrogen has shown a rise in BTE, BP, and a reduced BSEC value. The percentage increase in BTE is between 20 and 30%, and an increase in hydrogen beyond 12.5% would affect the volumetric efficiency, and thus performance declines after that. The exhaust emissions have a huge impact on hydrogen enrichment; CO, HC, and CO₂ emission are reduced by 30–40%; however, an increase in cylinder temperature due to rapid combustion slightly increases the NO_x emission. Thus hydrogen enriched methanol operating at higher compression ratio can improve the overall engine characteristics significantly.     

Novel Approach for Mobile Based App Development Incorporating MAAF

Wireless Personal Communications - Increased dominance of mobile applications (henceforth, app) over conventional software applications is quite apparent; however, there is a lack of structured...     

A new controller for boost dc–dc converters based on a novel sliding surface

ABSTRACT

In this paper, two control schemes for boost converters affected by uncertainties in input voltage and load are proposed. The boost converter dynamics is redefined in terms of new state variables to facilitate the use of a disturbance observer that can estimate matched and unmatched disturbances. A sliding surface, which is new in the context of boost converters, is proposed to enable tracking and regulation of output voltage without requiring measurement of input voltage and load current. The stability of the overall system including the disturbance observer, the sliding variable and the output is proved. The performance of the schemes is assessed for regulation of output voltage and tracking of reference voltage by simulation as well as experimentation in which various types of uncertainties and various types of reference voltages are considered.