Functional genomics in age-related macular degeneration: From genetic associations to understanding disease mechanisms.

Genome-wide association studies have been remarkably successful in identifying genetic variants associated with age-related macular degeneration (AMD), demonstrating a strong genetic component largely driven by common variants. However, progress in translating these genetic findings into a deeper understanding of disease mechanisms and new therapies has been slow. Slow progress in this area can be attributed to limited knowledge of the functional impact of AMD-associated non-coding variants on gene function, the molecular mechanisms and cell types underlying disease.

Direct Mass Measurements of Neutron-Rich Zinc and Gallium Isotopes: An Investigation of the Formation of the First r-Process Peak.

The prediction of isotopic abundances resulting from the rapid neutron capture process (r process) requires high-precision mass measurements. Using TITAN's on-line time-of-flight spectrometer, first time mass measurements are performed for ^{83}Zn and ^{86}Ga. These measurements reduced uncertainties, and are used to calculate isotopic abundances near the first r-process abundance peak using astrophysical conditions present during a binary neutron star (BNS) merger.

Hydropersulfide (RSSH)-Mediated Hydrothiolation of Alkenes.

A hydropersulfide-mediated hydrothiolation reaction of alkenes has been developed for C-S bond formation with Markovnikov selectivity. This new approach is a transition-metal-, additive-, and solvent-free reaction under mild conditions. The reaction is postulated to proceed by an ionic mechanism with the release of elemental sulfur based on our control experiments and density functional theory calculations.

Toward Dose Prediction at Point of Design.

Human dose prediction (HDP) is a useful tool for compound optimization in preclinical drug discovery. We describe here our exclusively in silico HDP strategy to triage compound designs for synthesis and experimental profiling. Our goal is a model that provides a preliminary estimate of the dose for a given exposure target based on chemical structure.