Chemoselective, regioselective, and positionally selective fluorogenic stapling of unprotected peptides for cellular uptake and direct cell imaging.

Peptide stapling reactions represent powerful methods for structuring native α-helices to improve their bioactivity in targeting protein-protein interactions (PPIs). In light of a growing need for regio- and positionally selective stapling methods involving natural amino acid residues in their unprotected states, we report a rapid, mild, and highly chemoselective three-component stapling reation using a class of molecular linchpins based on 2-arylketobenzaldehydes (ArKBCHOs) that create a fluorescent staple, hereafter referred to as a Fluorescent Isoindole Crosslink (FlICk). This methodology offers positional selectivity favouring , + 4 helical staples comprising a lysine and cysteine, in the presence of competing nucleophiles on unprotected peptides.

AAPM task group report 314: Fault recovery in external beam radiation therapy.

Task Group (TG) 314 of the American Association of Physicists in Medicine (AAPM) was charged to develop guidance for recovering from fault states in radiation therapy, specifically regarding the delivery of photon or electron beams using a linear accelerator (linac) including ancillary systems. The fault conditions addressed may involve software, hardware, or a combination of causes. The report provides detailed recommendations for the proactive steps to be taken before a fault, the actions to be taken at the time of a fault, and the safety steps before returning a linac to clinical service, as well as the activities that device manufacturers and standard organizations can do to prevent and resolve the faults.

Pyruvate dehydrogenase kinase 1 controls triacylglycerol hydrolysis in cardiomyocytes.

Pyruvate dehydrogenase kinase (PDK) 1 is one of four isozymes that inhibit the oxidative decarboxylation of pyruvate to acetyl-CoA via pyruvate dehydrogenase. PDK activity is elevated in fasting or starvation conditions to conserve carbohydrate reserves. PDK has also been shown to increase mitochondrial fatty acid utilization.

Image-based simulation of mitral valve dynamic closure including anisotropy.

Simulation of the dynamic behavior of mitral valve closure could improve clinical treatment by predicting surgical procedures outcome. We propose here a method to achieve this goal by using the immersed boundary method. In order to go towards patient-based simulation, we tailor our method to be adapted to a valve extracted from medical image data.

Synthesis of (2,3,4)-Dihydroxyisoleucine for Use in Amatoxin Synthesis.

We report a streamlined synthesis of (2,3,4)-4,5-dihydroxy isoleucine (DHIle), an amino acid found in α-amanitin, which appears to be critical for toxicity. This synthetic route is transition metal-free and enables the production of significant quantities of DHIle with suitable protection for use in peptide synthesis. Its incorporation into a cytotoxic amatoxin analog is reported.