Phase transitions in contagion processes mediated by recurrent mobility patterns

Human mobility and activity patterns mediate contagion on many levels, including the spatial spread of infectious diseases, diffusion of rumors, and emergence of consensus. These patterns however are often dominated by specific locations and recurrent flows and poorly modeled by the random diffusive dynamics generally used to study them. Here we develop a theoretical framework to analyze contagion within a network of locations where individuals recall their geographic origins. We find a phase transition between a regime in which the contagion affects a large fraction of the system and one in which only a small fraction is affected. This transition cannot be uncovered by continuous deterministic models due to the stochastic features of the contagion process and defines an invasion threshold that depends on mobility parameters, providing guidance for controlling contagion spread by constraining mobility processes. We recover the threshold behavior by analyzing diffusion processes mediated by real human commuting data.Comment: 20 pages of Main Text including 4 figures, 7 pages of Supplementary Information; Nature Physics (2011

Quantitative In Vivo Magnetic Resonance Spectroscopy Using Synthetic Signal Injection

Accurate conversion of magnetic resonance spectra to quantitative units of concentration generally requires compensation for differences in coil loading conditions, the gains of the various receiver amplifiers, and rescaling that occurs during post-processing manipulations. This can be efficiently achieved by injecting a precalibrated, artificial reference signal, or pseudo-signal into the data. We have previously demonstrated, using in vitro measurements, that robust pseudo-signal injection can be accomplished using a second coil, called the injector coil, properly designed and oriented so that it couples inductively with the receive coil used to acquire the data. In this work, we acquired nonlocalized phosphorous magnetic resonance spectroscopy measurements from resting human tibialis anterior muscles and used pseudo-signal injection to calculate the Pi, PCr, and ATP concentrations. We compared these results to parallel estimates of concentrations obtained using the more established phantom replacement method. Our results demonstrate that pseudo-signal injection using inductive coupling provides a robust calibration factor that is immune to coil loading conditions and suitable for use in human measurements. Having benefits in terms of ease of use and quantitative accuracy, this method is feasible for clinical use. The protocol we describe could be readily translated for use in patients with mitochondrial disease, where sensitive assessment of metabolite content could improve diagnosis and treatment

The Role of Glypicans in Wnt Inhibitory Factor-1 Activity and the Structural Basis of Wif1's Effects on Wnt and Hedgehog Signaling

Proper assignment of cellular fates relies on correct interpretation of Wnt and Hedgehog (Hh) signals. Members of the Wnt Inhibitory Factor-1 (WIF1) family are secreted modulators of these extracellular signaling pathways. Vertebrate WIF1 binds Wnts and inhibits their signaling, but its Drosophila melanogaster ortholog Shifted (Shf) binds Hh and extends the range of Hh activity in the developing D. melanogaster wing. Shf activity is thought to depend on reinforcing interactions between Hh and glypican HSPGs. Using zebrafish embryos and the heterologous system provided by D. melanogaster wing, we report on the contribution of glypican HSPGs to the Wnt-inhibiting activity of zebrafish Wif1 and on the protein domains responsible for the differences in Wif1 and Shf specificity. We show that Wif1 strengthens interactions between Wnt and glypicans, modulating the biphasic action of glypicans towards Wnt inhibition; conversely, glypicans and the glypican-binding “EGF-like” domains of Wif1 are required for Wif1's full Wnt-inhibiting activity. Chimeric constructs between Wif1 and Shf were used to investigate their specificities for Wnt and Hh signaling. Full Wnt inhibition required the “WIF” domain of Wif1, and the HSPG-binding EGF-like domains of either Wif1 or Shf. Full promotion of Hh signaling requires both the EGF-like domains of Shf and the WIF domains of either Wif1 or Shf. That the Wif1 WIF domain can increase the Hh promoting activity of Shf's EGF domains suggests it is capable of interacting with Hh. In fact, full-length Wif1 affected distribution and signaling of Hh in D. melanogaster, albeit weakly, suggesting a possible role for Wif1 as a modulator of vertebrate Hh signaling

Iontophoretic skin permeation of peptides: an investigation into the influence of molecular properties, iontophoretic conditions and formulation parameters

The transdermal route offers advantages for delivery of peptides and proteins. However, these polar and large molecules do not permeate the skin barrier well. Various enhancement methods have been employed to address this problem. Iontophoresis is one of the methods that shows promise but its application to peptide delivery has yet to be fully explored. This study investigates the effects of different molecular properties and iontophoretic conditions on the skin permeation of peptides. In this study, the permeation of alanine-tryptophan dipeptide (MW 276 Da), alanine–alanine–proline–valine tetrapeptide (MW 355 Da), Argireline® (Acetyl hexapeptide-3, MW 889 Da) and Triptorelin acetate (decapeptide, MW 1311 Da) through excised human skin under passive or iontophoretic current of 0.4 mA was investigated. The effects of pH change (3.0–7.4, to provide different net negative, neutral, and positive charges) to the peptide, donor concentration (1–10 mg/ml), background electrolyte (34–137 mM NaCl and/or 5–20 mM HEPES) and current direction (anodal vs cathodal) were also studied.Peptides were analysed by high-performance liquid chromatography or liquid scintillation counting. Iontophoresis led up to a 30 times increase in peptide permeation relative to passive permeation for the peptides. Electroosmosis was an important determinant of the total flux for the high molecular weight charged peptides. Electrorepulsion was found to be considerable for low molecular weight charged moieties. Permeation was decreased at lower pH, possibly due to decreased electroosmosis. Results also showed that 10 times increase in donor peptide concentration increases permeation of peptides by about 2–4 times and decreases iontophoretic permeability coefficients by about 2.5–5 times. The addition of extra background electrolyte decreased the iontophoretic permeation coefficient of peptides by 2–60 times. This study shows that iontophoretic permeation of peptides is affected by a number of parameters that can be optimized for effective transdermal peptide delivery