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.     

Graphical Methodology to Study the Corona Onset Voltage for Electrostatic Precipitation of Nanoparticles

Theoretical Foundations of Chemical Engineering - The corona onset voltage is an important operating parameter in the electrostatic precipitation of nanoparticulate, however, its experimental...     

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...     

Dielectric relaxation of vegetable-based polyurethane

Vegetable-based polyurethane (PU) was prepared in the thin film form by spin coating. This polymer is synthesised from castor oil, which can be extracted from the seeds of a native plant in Brazil called mamona. This polymer is biocompatible and is being used as material for artificial bone. The PU was characterised by dielectric spectroscopy in a wide range of frequency (10^–5 Hz to 10⁵ Hz) and by thermally stimulated discharge current (TSDC) measurements. The glass transition temperature (T _g = 39°C) was determined and using the initial rise method the activation energy was found to be 1.58 eV.     

Doped silicon and NIS junctions for bolometer applications

We discuss the performance, of a normal metal hot electron bolometer (NHEB) that we have measured at 0.3 K. We found that the noise equivalent power was limited by the amplifier noise. To improve the NHEB power response and to make it more robust and reliable we propose to substitute the normal metal with heavily doped silicon. The heavily doped silicon behaves like a metal with lower carrier concentration and has a smaller electron–phonon thermal coupling. We have fabricated superconductor-doped silicon-superconductor contacts (S-Sm-S) and we have used them as thermometers and coolers.     

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.     

Zirconium recovery from zircaloy shavings

A chlorination process for recovering Zr from zircaloy scrap has been studied. Zircaloy chlorination was possible at temperatures as low as 220 °C. The scale microstructure and its effect on the zircaloy reactivity was analysed using Thermogravimetric analysis (TGA), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDXS) and scanning electron microscopy (SEM) techniques. A solid-solid phase transformation took place into the oxide scale during the zircaloy chlorination. Zirconium, as ZrCl₄(g), was separated from the oxide scale and chlorides of Cr and Fe. The effect of the reaction temperature was also analysed.