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).     

Centroid index: Cluster level similarity measure

In clustering algorithm, one of the main challenges is to solve the global allocation of the clusters instead of just local tuning of the partition borders. Despite this, all external cluster validity indexes calculate only point-level differences of two partitions without any direct information about how similar their cluster-level structures are. In this paper, we introduce a cluster level index called centroid index. The measure is intuitive, simple to implement, fast to compute and applicable in case of model mismatch as well. To a certain extent, we expect it to generalize other clustering models beyond the centroid-based k-means as well.     

K-means: Clustering by gradual data transformation

Traditional approach to clustering is to fit a model (partition or prototypes) for the given data. We propose a completely opposite approach by fitting the data into a given clustering model that is optimal for similar pathological data of equal size and dimensions. We then perform inverse transform from this pathological data back to the original data while refining the optimal clustering structure during the process. The key idea is that we do not need to find optimal global allocation of the prototypes. Instead, we only need to perform local fine-tuning of the clustering prototypes during the transformation in order to preserve the already optimal clustering structure.     

A study of 3D Network-on-Chip design for data parallel H.264 coding

In this paper, we implement, analyze and compare different Network-on-Chip (NoC) architectures aiming at higher efficiencies for MPEG-4/H.264 coding. Two-dimensional (2D) and three-dimensional (3D) NoCs based on Non-Uniform Cache Access (NUCA) are analyzed. We present results using a full system simulator with realistic workloads. Experiments show the average network latencies in two 3D NoCs are reduced by 28% and 34% respectively, comparing with 2D design. It is also shown that heat dissipation is a trade-off in improving performance of 3D chips. Our analysis and experiment results provide a guideline to design efficient 3D NoCs for data parallel H.264 coding applications.     

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.