Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis

Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases.     

Synergistic Effects of Polybenzimidazole and Aramide on Enhancing Flame-Retardancy and Solubility

Aromatic and functional polymers with processibility derived from biobased starting materials are prerequisite considering sustainable society. Poly(2,5-benzimidazole)s are rigid-rod polymers to show ultrahigh thermal stability such as flame retardance, while usually suffer from poor solubility. Here, poly(benzimidazole-co-amide)s are synthesized from two biobased monomers, 3,4-diaminobenzoic acid and a semirigid comonomer, 4-aminohydrocinnamic acid. The copolymers with an amide composition of 80 mol% and higher are soluble in widely used polar solvents to fabricate the films keeping high flame retardance, which is comparable with popular high-performance polymers such as aromatic polyimides, polyetheretherketone, polyphenylene sulfide, etc.     

Structural,optical and electronic characteristics of Cu and Mg-doped nano MnS sample prepared by molten salt solid state reaction

Journal of Materials Science: Materials in Electronics - Nano Mn0.95M0.05S (M ≡ Cu, Mg) samples were produced using molten salt solid state reaction method. Rietveld analysis of X-ray...     

CNTFET based voltage differencing current conveyor low power and universal filter

Analog Integrated Circuits and Signal Processing - This paper presents carbon nanotube field effect transistor (CNTFET) implementation of voltage differencing current conveyor (VDCC). We propose...     

A novel solution of deep learning for endoscopic ultrasound image segmentation: enhanced computer aided diagnosis of gastrointestinal stromal tumor

Multimedia Tools and Applications - Gastrointestinal stromal tumor is one of the critical tumors that doctors do not suggest to get frequent endoscopy, so there is a need for a diagnosis system...     

Transient-state Analytical Solution for Arbitrarily-Located Multiwells in Triangular-Shaped Unconfined Aquifer

Water Resources Management - This work presents an analytical solution for the linearized Boussinesq equation describing the nature of well hydraulics in equilateral triangular-shaped unconfined...     

Output feedback controller for polytopic systems exploiting the direct searching of the design space

This paper deals with the problem of designing a robust static output feedback controller for polytopic systems. The current research that tackled this problem is mainly based on LMI method, which is conservative by nature. In this paper, a novel approach is proposed, which considers the design space of the controller parameters and iteratively partitions the space to small simplexes. Then, by assessing the stability in each simplex, the solution space for design parameters is directly determined. It has been theoretically proved that, if there exists a feasible solution in the design space, the algorithm can find it. To validate the result of the proposed approach, comparative simulation examples are given to illustrate the performance of the design methodology as compared to those of previous approaches.