The role of three-body interactions in two-dimensional polymer collapse

Various interacting lattice path models of polymer collapse in two dimensions demonstrate different critical behaviours. This difference has been without a clear explanation. The collapse transition has been variously seen to be in the Duplantier-Saleur $\theta$-point university class (specific heat cusp), the interacting trail class (specific heat divergence) or even first-order. Here we study via Monte Carlo simulation a generalisation of the Duplantier-Saleur model on the honeycomb lattice and also a generalisation of the so-called vertex-interacting self-avoiding walk model (configurations are actually restricted trails known as grooves) on the triangular lattice. Crucially for both models we have three and two body interactions explicitly and differentially weighted. We show that both models have similar phase diagrams when considered in these larger two-parameter spaces. They demonstrate regions for which the collapse transition is first-order for high three body interactions and regions where the collapse is in the Duplantier-Saleur $\theta$-point university class. We conjecture a higher order multiple critical point separating these two types of collapse.Comment: 17 pages, 20 figure

Long-term physical evolution of an elastomeric ultrasound contrast microbubble

Hypothesis: One of the main assets of crosslinked polymer-shelled microbubbles (MBs) as ultrasound-active theranostic agents is the robustness of the shells, combined with the chemical versatility in modifying the surface with ligands and/or drugs. Despite the long shelf-life, subtle modifications occur in the MB shells involving shifts in acoustic, mechanical and structural properties. Experiments: We carried out a long-term morphological and acoustic evolution analysis on elastomeric polyvinyl-alcohol (PVA)-shelled MBs, a novel platform accomplishing good acoustic and surface performances in one agent. Confocal laser scanning microscopy, acoustic spectroscopy and AFM nanomechanics were integrated to understand the mechanism of PVA MBs ageing. The changes in the MB acoustic properties were framed in terms of shell thickness and viscoelasticity using a linearised oscillation theory, and compared to MB morphology and to nanomechanical analysis. Findings: We enlightened a novel, intriguing ageing time evolution of the PVA MBs with double behaviour with respect to a crossover time of ∼50 days. Before, significant changes occur in MB stiffness and shell thickness, mainly due to a massive release of entangled PVA chains. Then, the MB resonance frequency increases together with shell thickening and softening. Our benchmark study is of general interest for emerging viscoelastomeric bubbles towards personalised medicine

Quantitative Systems Pharmacology and Biased Agonism at Opioid Receptors: A Potential Avenue for Improved Analgesics

Chronic pain is debilitating and represents a significant burden in terms of personal and socio-economic costs. Although opioid analgesics are widely used in chronic pain treatment, many patients report inadequate pain relief or relevant adverse effects, highlighting the need to develop analgesics with improved efficacy/safety. Multiple evidence suggests that G protein-dependent signaling triggers opioid-induced antinociception, whereas arrestin-mediated pathways are credited with modulating different opioid adverse effects, thus spurring extensive research for G protein-biased opioid agonists as analgesic candidates with improved pharmacology. Despite the increasing expectations of functional selectivity, translating G protein-biased opioid agonists into improved therapeutics is far from being fully achieved, due to the complex, multidimensional pharmacology of opioid receptors. The multifaceted network of signaling events and molecular processes underlying therapeutic and adverse effects induced by opioids is more complex than the mere dichotomy between G protein and arrestin and requires more comprehensive, integrated, network-centric approaches to be fully dissected. Quantitative Systems Pharmacology (QSP) models employing multidimensional assays associated with computational tools able to analyze large datasets may provide an intriguing approach to go beyond the greater complexity of opioid receptor pharmacology and the current limitations entailing the development of biased opioid agonists as improved analgesics

Correlated Component Analysis for diffuse component separation with error estimation on simulated Planck polarization data

We present a data analysis pipeline for CMB polarization experiments, running from multi-frequency maps to the power spectra. We focus mainly on component separation and, for the first time, we work out the covariance matrix accounting for errors associated to the separation itself. This allows us to propagate such errors and evaluate their contributions to the uncertainties on the final products.The pipeline is optimized for intermediate and small scales, but could be easily extended to lower multipoles. We exploit realistic simulations of the sky, tailored for the Planck mission. The component separation is achieved by exploiting the Correlated Component Analysis in the harmonic domain, that we demonstrate to be superior to the real-space application (Bonaldi et al. 2006). We present two techniques to estimate the uncertainties on the spectral parameters of the separated components. The component separation errors are then propagated by means of Monte Carlo simulations to obtain the corresponding contributions to uncertainties on the component maps and on the CMB power spectra. For the Planck polarization case they are found to be subdominant compared to noise.Comment: 17 pages, accepted in MNRA

A tree-decomposed transfer matrix for computing exact Potts model partition functions for arbitrary graphs, with applications to planar graph colourings

Combining tree decomposition and transfer matrix techniques provides a very general algorithm for computing exact partition functions of statistical models defined on arbitrary graphs. The algorithm is particularly efficient in the case of planar graphs. We illustrate it by computing the Potts model partition functions and chromatic polynomials (the number of proper vertex colourings using Q colours) for large samples of random planar graphs with up to N=100 vertices. In the latter case, our algorithm yields a sub-exponential average running time of ~ exp(1.516 sqrt(N)), a substantial improvement over the exponential running time ~ exp(0.245 N) provided by the hitherto best known algorithm. We study the statistics of chromatic roots of random planar graphs in some detail, comparing the findings with results for finite pieces of a regular lattice.Comment: 5 pages, 3 figures. Version 2 has been substantially expanded. Version 3 shows that the worst-case running time is sub-exponential in the number of vertice

Opioid activity profiles of oversimplified peptides lacking in the protonable N-terminus

Recently, we described cyclopeptide opioid agonists containing the D-Trp-Phe sequence. To expand the scope of this atypical pharmacophore, we tested the activity profiles of the linear peptides Ac-Xaa-Phe-Yaa (Xaa = L/D-Trp, D-His/Lys/Arg; Yaa = H, GlyNH2). Ac-D-Trp-PheNH2 appeared to be the minimal binding sequence, while Ac-D-Trp-Phe-GlyNH 2 emerged as the first noncationizable short peptide (partial) agonist with high \u3bc-opioid receptor affinity and selectivity. Conformational analysis suggested that 5 adopts in solution a \u3b2-turn conformation. \ua9 2012 American Chemical Society

Ultrasound delivery of Surface Enhanced InfraRed Absorption active gold-nanoprobes into fibroblast cells: a biological study via Synchrotron-based InfraRed microanalysis at single cell level

Ultrasound (US) induced transient membrane permeabilisation has emerged as a hugely promising tool for the delivery of exogenous vectors through the cytoplasmic membrane, paving the way to the design of novel anticancer strategies by targeting functional nanomaterials to specific biological sites. An essential step towards this end is the detailed recognition of suitably marked nanoparticles in sonoporated cells and the investigation of the potential related biological effects. By taking advantage of Synchrotron Radiation fourier transform infrared micro-spectroscopy (SR-microftiR) in providing highly sensitive analysis at the single cell level, we studied the internalisation of a nanoprobe within fibroblasts (NIH-3T3) promoted by low-intensity US. To this aim we employed 20 nm gold nanoparticles conjugated with the IR marker 4-aminothiophenol. The significant Surface Enhanced Infrared Absorption provided by the nanoprobes, with an absorbance increase up to two orders of magnitude, allowed us to efficiently recognise their inclusion within cells. Notably, the selective and stable SR- microftiR detection from single cells that have internalised the nanoprobe exhibited clear changes in both shape and intensity of the spectral profile, highlighting the occurrence of biological effects. Flow cytometry, immunofluorescence and murine cytokinesis-block micronucleus assays confirmed the presence of slight but significant cytotoxic and genotoxic events associated with the US-nanoprobe combined treatments. our results can provide novel hints towards US and nanomedicine combined strategies for cell spectral imaging as well as drug delivery-based therapies