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).     

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.     

A hypergraph model for constraint logic programming and applications to bus drivers' scheduling

In a previous paper, a hypergraph model for the satisfiability of Datalog formulas was proposed. Here, we extend that approach in order to deal with a class ofconstraint logic programming (CLP) formulas, that is, Datalog formulas in the presence of constraints. A CLP formula is represented by means of a weighted hypergraph and the problem of evaluating this formula is reduced to a sequence of shortest path computations on hypergraphs. To evaluate the performance of this approach, the bus drivers' scheduling problem is formulated as the problem of checking the satisfiability of a CLP formula and it is solved by means of the hypergraph-based algorithm embedded within a local search procedure. Preliminary experimental results are quite encouraging and suggest that the proposed approach may provide an efficient way to tackle hard real-life combinatorial problems.This research was partially supported by the Progetto Finalizzato Trasporti 2 of the Italian National Research Council, under Contract No. 91.02479.PF74.     

Design of an active-passive device for human ankle movement during functional magnetic resonance imaging analysis

Functional magnetic resonance imaging analysis has made major strides in recent years, both because of the development of new scanners and owing to magnetic resonance compatible systems that make it possible to stimulate parts of the human body during analysis. The significant gains in our knowledge of the brain that can thus be achieved justify efforts to construct machines with control circuits suitable for this purpose. This paper presents a magnetic resonance compatible mechatronic device with electropneumatic control that can be used to move one or both feet during functional magnetic resonance imaging analysis of the cerebral motor zones. The system is innovative and original. The results obtained at the end of the investigation were good, and demonstrated that the design is feasible.     

Thiol–Ene Clickable Gelatin: A Platform Bioink for Multiple 3D Biofabrication Technologies

Bioprinting can be defined as the art of combining materials and cells to fabricate designed, hierarchical 3D hybrid constructs. Suitable materials, so called bioinks, have to comply with challenging rheological processing demands and rapidly form a stable hydrogel postprinting in a cytocompatible manner. Gelatin is often adopted for this purpose, usually modified with (meth‐)acryloyl functionalities for postfabrication curing by free radical photopolymerization, resulting in a hydrogel that is cross‐linked via nondegradable polymer chains of uncontrolled length. The application of allylated gelatin (GelAGE) as a thiol–ene clickable bioink for distinct biofabrication applications is reported. Curing of this system occurs via dimerization and yields a network with flexible properties that offer a wider biofabrication window than (meth‐)acryloyl chemistry, and without additional nondegradable components. An in‐depth analysis of GelAGE synthesis is conducted, and standard UV‐initiation is further compared with a recently described visible‐light‐initiator system for GelAGE hydrogel formation. It is demonstrated that GelAGE may serve as a platform bioink for several biofabrication technologies by fabricating constructs with high shape fidelity via lithography‐based (digital light processing) 3D printing and extrusion‐based 3D bioprinting, the latter supporting long‐term viability postprinting of encapsulated chondrocytes.