Radiation Type- and Dose-Specific Transcriptional Responses across Healthy and Diseased Mammalian Tissues.

Ionizing radiation (IR) is a genuine genotoxic agent and a major modality in cancer treatment. IR disrupts DNA sequences and exerts mutagenic and/or cytotoxic properties that not only alter critical cellular functions but also impact tissues proximal and distal to the irradiated site. Unveiling the molecular events governing the diverse effects of IR at the cellular and organismal levels is relevant for both radiotherapy and radiation protection.

Agonists for the adenosine A1 receptor with tunable residence time. A Case for nonribose 4-amino-6-aryl-5-cyano-2-thiopyrimidines.

We report the synthesis and evaluation of previously unreported 4-amino-6-aryl-5-cyano-2-thiopyrimidines as selective human adenosine A1 receptor (hA1AR) agonists with tunable binding kinetics, this without affecting their nanomolar affinity for the target receptor. They show a very diverse range of kinetic profiles (from 1 min (compound 52) to 1 h (compound 43)), and their structure-affinity relationships (SAR) and structure-kinetics relationships (SKR) were established. When put in perspective with the increasing importance of binding kinetics in drug discovery, these results bring new evidence of the consequences of affinity-only driven selection of drug candidates, that is, the potential elimination of slightly less active compounds that may display preferable binding kinetics.

Direct evidence for the participation of band-tails and excited-state tunnelling in the luminescence of irradiated feldspars.

The significance and extent of band-tail states in the luminescence and dosimetry properties of natural aluminosilicates (feldspars) is investigated by means of studies using low temperature (10 K) irradiation and optically stimulated luminescence (OSL) stimulation spectroscopy, and thermoluminescence (TL) in the range 10-200 K, made in comparison with high temperature (300 K) irradiation and photo-transferred OSL and TL investigations undertaken at low temperature. These measurements allow mappings of the band-tails to be made; they are found to be ∼0.4 eV in extent in the typical materials studied.