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...     

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.     

The equilibrium partitioning of titanium between Ti3+ and Ti4+ valency states in CaO-SiO2-TiO x slags

The redox behavior of titanium in CaO-SiO₂-TiO _x melts was investigated using a slag-gas equilibrium technique. Titanium partitioning between Ti³⁺ and Ti⁴⁺ valency states and the ratio of activity coefficients of TiO_1.5 and TiO₂ were determined as functions of oxygen partial pressure, temperature, and slag composition. The equilibrium experiments were carried out at temperatures between 1783 and 1903 K under CO-CO₂-Ar gas atmosphere with oxygen partial pressure ranging from 10⁻¹² to 10⁻⁷ atm (1.01×10⁻¹⁰ kPa to 1.01×10⁻⁵ kPa). The slags had CaO/SiO₂ ratios between 0.55 and 1.35 and total titanium oxide concentrations from 7 to 50 mass pct. Experimental results showed that the Ti³⁺/Ti⁴⁺ ratio in CaO-SiO₂-TiO _x slags, containing up to 50 mass pct TiO _x , increased with decreasing oxygen partial pressure and decreased with increasing CaO/SiO₂ ratio and decreasing temperature. Measured variation of the redox ratio Ti³⁺/Ti⁴⁺ with oxygen partial pressure closely followed the ideal behavior. Increasing the CaO/SiO₂ ratio increased the ratio of activity coefficients of TiO_1.5 and TiO₂. The effect of total titania content on this ratio was more complex and in accord with Raman spectroscopy data.     

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).     

Progesterone bioconversion by microalgal cultures

Ten different strains of unicellular microalgae have been used in the bioconversion of progesterone. Regio and stereoselective reduction and hydroxylation of the title compound were induced. A 9,10-seco derivative was obtained in high yield by using Scenedesmus quadricauda.     

Fibrolamellar carcinoma of the liver: composition of the extracellular matrix and expression of cell-matrix and cell-cell adhesion molecules

We have analyzed the composition of the tumor stroma and the expression of cell-matrix and cell-cell adhesion molecules in 11 cases of fibrolamellar carcinoma of the liver (FLC), in comparison with 34 cases of hepatocellular carcinoma and 8 cases of focal nodular hyperplasia. Fibrolamellar carcinoma was characterized by the presence of large amounts of tenascin in tumor stroma and by the scarce expression of basement membrane components at the contact of neoplastic clusters. Like normal hepatocytes, neoplastic cells constantly expressed the alpha1 integrin chain, lacked the beta4 integrin chain, and coexpressed E-cadherin and the hepatocyte N-related cadherin. Abnormalities in the expression of cell adhesion molecules, including altered cadherin expression, alphaV integrin chain induction, and CD44 expression, were detected in the majority of cases. The composition of the tumor stroma and the pattern of expression of cell adhesion molecules in fibrolamellar carcinoma were reminiscent of those observed in grade III and grade IV hepatocellular carcinomas. Our results therefore show that, despite its slow local growth and good prognosis, fibrolamellar carcinoma expresses many characteristics usually associated with clinically aggressive malignancies. Further studies are needed to identify the factors responsible for the apparent dissociation between clinical behavior and biological characteristics in this tumor.