A Shape Optimization Problem on Planar Sets with Prescribed Topology

We consider shape optimization problems involving functionals depending on perimeter, torsional rigidity and Lebesgue measure. The scaling free cost functionals are of the form \(P(\Omega )T^q(\Omega )|\Omega |^{-2q-1/2}\), and the class of admissible domains consists of two-dimensional open sets \(\Omega \) satisfying the topological constraints of having a prescribed number k of bounded connected components of the complementary set. A relaxed procedure is needed to have a well-posed problem, and we show that when \(q<1/2\) an optimal relaxed domain exists. When \(q>1/2\), the problem is ill-posed, and for \(q=1/2\), the explicit value of the infimum is provided in the cases \(k=0\) and \(k=1\).

     

Phenotyping Reveals Targets of a Pseudo-Natural-Product Autophagy Inhibitor

Pseudo-natural-product (NP) design combines natural product fragments to provide unprecedented NP-inspired compounds not accessible by biosynthesis, but endowed with biological relevance. Since the bioactivity of pseudo-NPs may be unprecedented or unexpected, they are best evaluated in target agnostic cell-based assays monitoring entire cellular programs or complex phenotypes. Here, the Cinchona alkaloid scaffold was merged with the indole ring system to synthesize indocinchona alkaloids by Pd-catalyzed annulation. Exploration of indocinchona alkaloid bioactivities in phenotypic assays revealed a novel class of azaindole-containing autophagy inhibitors, the azaquindoles. Subsequent characterization of the most potent compound, azaquindole-1, in the morphological cell painting assay, guided target identification efforts. In contrast to the parent Cinchona alkaloids, azaquindoles selectively inhibit starvation- and rapamycin-induced autophagy by targeting the lipid kinase VPS34.     

Influence of charged intramolecular hydrogen bonds in weak polyelectrolytes: A Monte Carlo study of flexible and extendible polymeric chains in solution and near charged spheres

For weak polyelectrolytes, the interplay between pH, solvent properties, and polymer structure affects the amount of charges, their distribution, and hence their conformations via Coloumb repulsion. Attractive interactions can also develop between charged and neutral sites counteracting the expected Coulomb‐induced expansion. To gauge how such competition affects polyelectrolyte structure and ionization, the titration of a single polyelectrolyte chain, isolated or close to a charged sphere, mimicked with a novel many‐body potential model is simulated with Monte Carlo. Apart from showing a 10‐fold higher ionization than isolated monomers at low pH, interacting species contracted forming short‐range clusters of charged and neutral ionizable groups. The presence of a charged sphere synergically boosted both effects due to monomer interactions, forcing the chains to condense onto its surface at much lower pH. Structural properties, however, seem to be controlled only by the ionization degree despite the presence of the topological restraint represented by the spherical surface. Using Monte Carlo titration results, the equilibrium ionization of isolated chains is also estimated; the results evidence that even weak interactions can easily lead to a doubling of the total charge. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 650–663     

In-flight antiproton annihilation on nuclei at low energies

The results of the annihilation cross sections measurement of 5.3 MeV antiprotons on nickel, tin, platinum and Mylar targets performed by the ASACUSA Collaboration at CERN are presented and compared with the existing data and models. From the experimental point of view the presented data are the first measurement of antinucleon annihilation cross sections at low energies obtained with a pulsed beam. This results open the road for the next measurements at the very low energies of the order of 100 keV that are in progress by the ASACUSA Collaboration. The experimental method foreseen for the 100 keV measurement is illustrated.