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.     

Shape Factor Effect on Inclusion Sedimentation in Aluminum Melts

Metallurgical and Materials Transactions B - The quality requirements of aluminum products are steadily increasing, and the presence of non-metallic inclusions have a large impact on the quality of...     

Implicit–Explicit Schemes for BGK Kinetic Equations

In this work a new class of numerical methods for the BGK model of kinetic equations is presented. In principle, schemes of any order of accuracy in both space and time can be constructed with this technique. The methods proposed are based on an explicit–implicit time discretization. In particular the convective terms are treated explicitly, while the source terms are implicit. In this fashion even problems with infinite stiffness can be integrated with relatively large time steps. The conservation properties of the schemes are investigated. Numerical results are shown for schemes of order 1, 2 and 5 in space, and up to third-order accurate in time.     

Water uptake of water-borne paint resin films as studied by impedance spectroscopy and gravimetry

Impedance spectroscopy and gravimetry were employed to characterize alkyd-acrylate and styrene-acrylate water-borne resin film properties during wetting-through (i.e. during water uptake).     

Synthesis and characterization of hydroxyl terminated poly(butadiene)-g-poly(glycidyl azide) copolymer as a new energetic propellant binder

Summary Poly(glycidyl azide), PGA, was grafted onto Hydroxyl Terminated Poly(butadiene), HTPB, via free radical mechanism. PGA-macro azoinitator and HTPB polymer mixture was casted from solution and the polymer film was kept at 90°C for 4 hours. The grafted polymer was isolated from the product by fractional precipitation and characterized by NMR and FT-IR spectroscopy. Graft copolymer structure was also confirmed that volume ratio of nonsolvent to the solution of the graft copolymer was between those of corresponding homopolymers. TGA traces of the block polymers were containing two different maxima at 253°C (for PGA units) and 469°C (for HTPB units). Because of the incompatibility of the blocks, DSC curve showed two T_g's which belong to the related segments.     

Synthesis and properties of chitosan-modified poly(vinyl butyrate)

Modification of chitosan by grafting of vinyl butyrate was carried out in homogeneous phase using potassium persulfate as redox initator and 1.5% acetic acid as solvent. The percent grafting and grafting efficiency were analysed and the high grafting efficiency up to 94% was observed. The effects of reaction variables such as monomer concentration, initiator concentration, temperature and reaction time were investigated. It was observed that the solubility of chitosan was markedly reduced after grafting with vinyl butyrate. The grafted product is insoluble in common organic solvents as well in dilute organic and inorganic acids. Characterization of the graft copolymers were carried out by using Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC) and Scanning Electron Microscopy (SEM) technics. Characteristic signal of carbonyl group was observed at 1,731 cm⁻¹ which belongs to the poly vinyl butyrate segments in the graft copolymer. The melting transition of the chitosan main chain in the copolymer shifted to 124°C from its original value 101°C. In addition to these, we have also studied topology of the graft copolymer and the SEM micrograph showed continuous homogenous matrix which means there is no phase separation.     

Multi‐agent collaboration based on enhanced cognitive awareness: an architecture for agents' profiling on the semantic web

This paper applies cognitive models, inspired by cognitive science, with the aim to propose architectural and knowledge‐based requirements to structure ontological models for the cognitive profiling of agents. The proposed architecture aims to address the lack of flexibility that most agent‐based collaborations are affected by. The resulting agents, equipped with advanced cognitive profiling, have an increased cognitive awareness of themselves and are more capable of interacting with other agents in a multi‐agents based environment. In this research, cognitive awareness identifies the ability of the web agents to diagnose their processing limitations and to establish interactions with the external environment. The outcome is the enhanced flexibility, reusability and predictability of the agent behaviour; thus contributing towards minimizing human cognitive demands. The concept of cognitive profiling presented in this paper considers the semantic web as an action mediating space, where ontological models provide affordances for improving cognitive awareness through shared knowledge‐base. The conceptual model for the cognitive profile architecture is developed with Protégé Ontology editor to generate OWL Ontology and evaluated through a proof of concept. The results show that agents equipped with cognitive awareness can undertake complex tasks more dynamically.