Design and synthesis of new bicyclic diketopiperazines as scaffolds for receptor probes of structurally diverse functionality

Diketopiperazines (DKPs) are a common motif in various biologically active natural products, and hence they may be useful scaffolds for the rational design of receptor probes and therapeutic agents. We constructed a new bicyclic scaffold that combines a DKP bridged with a 10-membered ring. In this way we obtained a three-dimensional molecular skeleton, with several amendable sites that provide a starting point to design a new combinatorial library having diverse substituent groups. Structural variation is based upon the flexibility of alkylation of the nitrogen atoms of the DKP and on the side-chain olefin. We obtained a 10-membered secondary ring through a ring-closure metathesis reaction using the second generation Grubbs catalyst. Rings containing both O-ethers and S-ethers were compared. N-Alkyl or arylalkyl groups were introduced optionally at the two Nalpha-atoms. This is a general scheme that will allow us to test rings of varying sizes, linkages, and stereochemical parameters. The DKP derivatives were tested for activity in astrocytoma cells expressing receptors coupled to phospholipase C. Inhibitory effects were observed for signaling elicited by activation of human nucleotide P2Y receptors but not m3 muscarinic receptors. Compound 20 selectively inhibited calcium mobilization (IC50 value of 486 +/- 16 nM) and phosphoinositide turnover elicited by a selective P2Y1 receptor agonist, but this compound did not compete for binding of a radiolabeled nucleotide-competitive receptor antagonist. Therefore, the new class of DKP derivatives shows utility as pharmacological tools for P2Y receptors.     

3-methylthiophene self-assembled monolayers on planar and nanoparticle Au surfaces

In this article the adsorption of 3-methylthiophene on planar and nanoparticle Au surfaces is investigated. The resulting systems are compared with a benchmark system based on 1-decanethiol. The characterization data collected evidence the formation of a packed 3-methylthiophene SAM on the planar surface. In particular, spectroscopic investigations suggest that 3-methylthiophene aromatic system is not adsorbed on the surface through the pi-electron system but rather through the S atom alone. On the other hand, the behavior of 3-methylthiophene on nanoparticle surfaces is notably different from that of the alkanethiol. Only a limited fraction of the surface of Au nanoparticles results to be actually coated after purification; this notwithstanding, the nanoparticle growth seems to be strongly influenced by the presence of such a labile encapsulating agent.     

Synthesis of gold nanoparticles by laser ablation in toluene: quenching and recovery of the surface plasmon absorption

Gold nanoparticles are synthesized by laser ablation of a gold plate in toluene. The nanoparticles do not show their characteristic surface plasmon absorption (SPA) and are found to be included in a graphitic matrix. The absence of this absorption is found to derive from the presence of the matrix which prevents the growth of large nanoparticles and covers them, suppressing the SPA according to the Mie model for core@shell particles. It is possible to recover the nanoparticle SPA by oxidizing the carbon matrix, obtaining, therefore, some control on the activity of this absorption.     

Lossy data compression with random gates

We introduce a new protocol for a lossy data compression algorithm which is based on constraint satisfaction gates. We show that the theoretical capacity of algorithms built from standard parity-check gates converges exponentially fast to the Shannon's bound when the number of variables seen by each gate increases. We then generalize this approach by introducing random gates. They have theoretical performances nearly as good as parity checks, but they offer the great advantage that the encoding can be done in linear time using the survey inspired decimation algorithm, a powerful algorithm for constraint satisfaction problems derived from statistical physics.     

Dynamic localization and Bloch oscillations in the spectrum of a frequency mode-locked laser

It is shown that a frequency mode-locked laser with a sinusoidal sweep of modulation frequency around a mode-locking condition represents an ideal optical system for observing in the spectral domain the phenomena of dynamic localization and Bloch oscillations of electrons in an ideal solid placed in an external ac electric field.     

On Mobility and Einstein Relation for Tracers in Time-Mixing Random Environments

In this paper we rigorously establish the existence of the mobility coefficient for a tagged particle in a simple symmetric exclusion process with adsorption/desorption of particles, in a presence of an external force field interacting with the particle. The proof is obtained using a perturbative argument. In addition, we show that, for a constant external field, the mobility of a particle equals to the self-diffusivity coefficient, the so-called Einstein relation. The method can be applied to any system where the environment has a Markovian evolution with a fast convergence to equilibrium (spectral gap property). In this context we find a necessary relation between forward and backward velocity for the validity of the Einstein relation. This relation is always satisfied by reversible systems. We provide an example of a non-reversible system, where the Einstein relation is valid.This revised version was published online in March 2005 with corrections to the page numbers.     

Spin-flop ordering from frustrated ferro- and antiferromagnetic interactions: a combined theoretical and experimental study of a Mn/Fe(100) monolayer

The occurrence of a noncollinear magnetic structure at a Mn monolayer grown epitaxially on Fe(100) is predicted theoretically, using spinor density-functional theory, and observed experimentally, using x-ray magnetic circular dichroism (XMCD) and linear dichroism (XMLD) spectroscopies. The combined use of XMCD and XMLD at the Mn-absorption edge allows us to assess the existence of ferromagnetic and antiferromagnetic order at the interface, and also to determine the moment orientations with element specificity. The experimental results thus obtained are in excellent agreement with the magnetic structure determined theoretically.     

Self-imaging and modulational instability in an array of periodically curved waveguides

Linear and nonlinear light propagation in an array of waveguides with a periodically bent axis is theoretically investigated. In the linear propagation regime, it is shown that a self-imaging effect at periodic planes may occur, a phenomenon analogous to that of dynamic localization observed when an electron in a periodic potential is subjected to an ac field. In the nonlinear propagation regime, it is shown that periodic waveguide bending under the self-imaging condition inhibits the phenomenon of discrete modulational instability.     

Invariant surfaces of a three-dimensional manifold with constant Gauss curvature

We give a reduction procedure to determine (locally) the surfaces with constant Gauss curvature in a three-dimensional manifold which are invariant under the action of a one-parameter subgroup of the isometry group of the ambient space. We apply this procedure to describe the invariant surfaces with constant Gauss curvature in $H^2\times R$ and in $H_3$.     

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