Synthesis and SAR Studies of Isoquinoline and Tetrahydroisoquinoline Derivatives as Melatonin Receptor Ligands

In our constant search for new successors of agomelatine, we report herein a new series of compounds resulting from bioisosteric modulation of the naphthalene ring. The isoquinoline and tetrahydroisoquinoline derivatives were synthesized and pharmacologically evaluated. This isosteric replacement of the naphthalene group of agomelatine has led to potent agonist and partial agonist compounds with nanomolar melatonergic binding affinities. Overall, the presence of a nitrogen atom was accompanied with a decrease in the binding affinity toward both MT₁ and MT₂ and the loss of 5HT_2C response, especially for tetrahydroisoquinoline in comparison with the parent compound. Interestingly, due to the presence of this nitrogen atom, a notable improvement in the pharmacokinetic properties was observed for all compounds.     

High efficiency UMG silicon solar cells: impact of compensation on cell parameters

High efficiency solar cells have been fabricated with wafers from an n‐type Czochralski grown (Cz) ingot using 100% Upgraded Metallurgical‐Grade (UMG) silicon feedstock. The UMG cells fabricated with a passivated emitter and rear totally diffused (PERT) structure have an independently confirmed cell efficiency of 19.8%. This is the highest efficiency reported for a cell based on 100% UMG silicon at the time of publication. The current and power losses are analysed as a function of measured material parameters, including carrier mobility, lifetime and the presence of the boron–oxygen defect. Dopant compensation is shown to reduce both the minority carrier lifetime and mobility, which significantly affects both the current and voltage of the device. Copyright © 2015 John Wiley & Sons, Ltd.     

Low Energy Blue Pulsed Light-Activated Injectable Materials for Restoring Thinning Corneas

Many alternatives to human donor corneas are being developed to meet the global shortage of donated tissues. However, corneal transplantation remains the gold standard for diseases resulting in thinning corneas. In this study, transparent low energy photoactivated extracellular matrix-mimicking materials are developed for intrastromal injection to restore stromal thickness. The injectable biomaterials are comprised of short peptides and glycosaminoglycans (chondroitin, hyaluronic acid) that assemble into a hydrogel when pulsed with low-energy blue light. The dosage of pulsed-blue light needed for material activation is minimal at 8.5 mW cm⁻², thus circumventing any blue light cytotoxicity. Intrastromal injection of these light-activated biomaterials in rat corneas shows that two iterations of the formulations remain stable in situ without stimulating significant inflammation or neovascularization. The use of low light intensities and the ability of the developed materials to stably rebuild and change the curvature of the cornea tissue make these formulations attractive for clinical translation.     

Gamifying model-based engineering: the PapyGame experience

Software and Systems Modeling - Modeling is an essential and challenging activity in any engineering environment. It implies some hard-to-train skills such as abstraction and communication....