Forever Young: Structural Stability of Telomeric Guanine Quadruplexes in the Presence of Oxidative DNA Lesions**

Human telomeric DNA, in G-quadruplex (G4) conformation, is characterized by a remarkable structural stability that confers it the capacity to resist to oxidative stress producing one or even clustered 8-oxoguanine (8oxoG) lesions. We present a combined experimental/computational investigation, by using circular dichroism in aqueous solutions, cellular immunofluorescence assays and molecular dynamics simulations, that identifies the crucial role of the stability of G4s to oxidative lesions, related also to their biological role as inhibitors of telomerase, an enzyme overexpressed in most cancers associated to oxidative stress.     

G-Quadruplex Recognition by DARPIns through Epitope/Paratope Analogy**

We investigated the mechanisms leading to the specific recognition of Guanine Guadruplex (G4) by DARPins peptides, which can lead to the design of G4 s specific sensors. To this end we carried out all-atom molecular dynamic simulations to unravel the interactions between specific nucleic acids, including human-telomeric (h-telo), Bcl-2, and c-Myc, with different peptides, forming a DARPin/G4 complex. By comparing the sequences of DARPin with that of a peptide known for its high affinity for c-Myc, we show that the recognition cannot be ascribed to sequence similarity but, instead, depends on the complementarity between the three-dimensional arrangement of the molecular fragments involved: the α-helix/loops domain of DARPin and the G4 backbone. Our results reveal that DARPins tertiary structure presents a charged hollow region in which G4 can be hosted, thus the more complementary the structural shapes, the more stable the interaction.     

A truncated Newton method in an augmented Lagrangian framework for nonlinear programming

In this paper we propose a primal-dual algorithm for the solution of general nonlinear programming problems. The core of the method is a local algorithm which relies on a truncated procedure for the computation of a search direction, and is thus suitable for large scale problems. The truncated direction produces a sequence of points which locally converges to a KKT pair with superlinear convergence rate.     

Chaos in Black Holes Surrounded by Electromagnetic Fields

In this paper we study the occurrence of chaos for charged particles moving around a Schwarzschild black hole, perturbed by uniform electric and magnetic fields. The appearance of chaos is analyzed resorting to the Poincaré-Melnikov method.     

Synthesis of 1-alkyl-4-imidazolecarboxylates: a catch and release strategy

The novel alkyl N-methyl-N-polystyreneamino-2-isocyanoacrylate was used for the synthesis of 1-substituted imidazole-4-carboxylates utilizing a "catch and release" methodology. The reactions were performed under microwave irradiation, affording the title compounds in both high yields and chemical purity directly to solution, from the solid phase support.     

A magnetic resonance device designed via global optimization techniques

In this paper we are concerned with the design of a small low-cost, low-field multipolar magnet for Magnetic Resonance Imaging with a high field uniformity. By introducing appropriate variables, the considered design problem is converted into a global optimization one. This latter problem is solved by means of a new derivative free global optimization method which is a distributed multi-start type algorithm controlled by means of a simulated annealing criterion. In particular, the proposed method employs, as local search engine, a derivative free procedure. Under reasonable assumptions, we prove that this local algorithm is attracted by global minimum points. Additionally, we show that the simulated annealing strategy is able to produce a suitable starting point in a finite number of steps with probability one.This work was supported by CNR/MIUR Research Program Metodi e sistemi di supporto alle decisioni, Rome, Italy.Mathematics Subject Classification (1991):65K05, 62K05, 90C56     

Anomalous transport: a deterministic approach

We introduce a cycle-expansion (fully deterministic) technique to compute the asymptotic behavior of arbitrary order transport moments. The theory is applied to different kinds of one-dimensional intermittent maps and Lorentz gas with an infinite horizon, confirming the typical appearance of phase transitions in the transport spectrum.