Direct Observation of Magnetic Metastability in Individual Iron Nanoparticles

X-ray photoemission electron microscopy combined with x-ray magnetic circular dichroism is used to study the magnetic properties of individual iron nanoparticles with sizes ranging from 20 down to 8 nm. While the magnetocrystalline anisotropy of bulk iron suggests superparamagnetic behavior in this size range, ferromagnetically blocked particles are also found at all sizes. Spontaneous transitions from the blocked state to the superparamagnetic state are observed in single particles and suggest that the enhanced magnetic energy barriers in the ferromagnetic particles are due to metastable, structurally excited states with unexpected life times

Direct Observation of Magnetic Metastability in Individual Iron Nanoparticles

X-ray photoemission electron microscopy combined with x-ray magnetic circular dichroism is used to study the magnetic properties of individual iron nanoparticles with sizes ranging from 20 down to 8 nm. While the magnetocrystalline anisotropy of bulk iron suggests superparamagnetic behavior in this size range, ferromagnetically blocked particles are also found at all sizes. Spontaneous transitions from the blocked state to the superparamagnetic state are observed in single particles and suggest that the enhanced magnetic energy barriers in the ferromagnetic particles are due to metastable, structurally excited states with unexpected life times

The use of the SeDeM diagram expert system for the formulation of Captopril SR matrix tablets by direct compression

The SeDeM Diagram Expert System has been used to study excipients, Captopril and designed formulations for their galenic characterization and to ascertain the critical points of the formula affecting product quality to obtain suitable formulations of Captopril Direct Compression SR Matrix Tablets. The application of the Sedem Diagram Expert System enables selecting excipients with in order to optimize the formula in the preformulation and formulation studies. The methodology is based on the implementation of ICH Q8, establishing the design space of the formula with the use of experiment design, using the parameters of the SeDeM Diagram Expert System as system responses.

Structural Insight into the Mode of Action of a Direct Inhibitor of Coregulator Binding to the Thyroid Hormone Receptor.

The development of nuclear hormone receptor antagonists that directly inhibit the association of the receptor with its essential coactivators would allow useful manipulation of nuclear hormone receptor signaling. We previously identified 3-(dibutylamino)-1-(4-hexylphenyl)-propan-1-one (DHPPA), an aromatic β-amino ketone that inhibits coactivator recruitment to thyroid hormone receptor β (TRβ), in a high-throughput screen. Initial evidence suggested that the aromatic β-enone 1-(4-hexylphenyl)-prop-2-en-1-one (HPPE), which alkylates a specific cysteine residue on the TRβ surface, is liberated from DHPPA. Nevertheless, aspects of the mechanism and specificity of action of DHPPA remained unclear. Here, we report an x-ray structure of TRβ with the inhibitor HPPE at 2.3-Å resolution. Unreacted HPPE is located at the interface that normally mediates binding between TRβ and its coactivator. Several lines of evidence, including experiments with TRβ mutants and mass spectroscopic analysis, showed that HPPE specifically alkylates cysteine residue 298 of TRβ, which is located near the activation function-2 pocket. We propose that this covalent adduct formation proceeds through a two-step mechanism: 1) β-elimination to form HPPE; and 2) a covalent bond slowly forms between HPPE and TRβ. DHPPA represents a novel class of potent TRβ antagonist, and its crystal structure suggests new ways to design antagonists that target the assembly of nuclear hormone receptor gene-regulatory complexes and block transcription.