A unified design space of synthetic stripe-forming networks

Synthetic biology is a promising tool to study the function and properties of gene regulatory networks. Gene circuits with predefined behaviours have been successfully built and modelled, but largely on a case-by-case basis. Here we go beyond individual networks and explore both computationally and synthetically the design space of possible dynamical mechanisms for 3-node stripe-forming networks. First, we computationally test every possible 3-node network for stripe formation in a morphogen gradient. We discover four different dynamical mechanisms to form a stripe and identify the minimal network of each group. Next, with the help of newly established engineering criteria we build these four networks synthetically and show that they indeed operate with four fundamentally distinct mechanisms. Finally, this close match between theory and experiment allows us to infer and subsequently build a 2-node network that represents the archetype of the explored design space

Determination of solid mass fraction in partially frozen hydrocarbon fuels

Filtration procedures alone are insufficient to determine the amounts of crystalline solid in a partially frozen hydrocarbon distillate fraction. This is due to the nature of the solidification process by which a large amount of liquid becomes entrapped within an interconnected crystalline structure. A technique has been developed to supplement filtration methods with an independent determination of the amount of liquid in the precipitate thereby revealing the actual value of mass percent crystalline solid, %S. A non-crystallizing dye is injected into the fuel and used as a tracer during the filtration. The relative concentrations of the dye in the filtrate and precipitate fractions is subsequently detected by a spectrophotometric comparison. The filtration apparatus was assembled so that the temperature of the sample is recorded immediately above the filter. Also, a second method of calculation has been established which allows significant reduction in test time while retaining acceptable accuracy of results. Data have been obtained for eight different kerosene range hydrocarbon fuels

Stress field around arbitrarily shaped cracks in two-dimensional elastic materials

The calculation of the stress field around an arbitrarily shaped crack in an infinite two-dimensional elastic medium is a mathematically daunting problem. With the exception of few exactly soluble crack shapes the available results are based on either perturbative approaches or on combinations of analytic and numerical techniques. We present here a general solution of this problem for any arbitrary crack. Along the way we develop a method to compute the conformal map from the exterior of a circle to the exterior of a line of arbitrary shape, offering it as a superior alternative to the classical Schwartz-Cristoffel transformation. Our calculation results in an accurate estimate of the full stress field and in particular of the stress intensity factors K_I and K_{II} and the T-stress which are essential in the theory of fracture.Comment: 7 pages, 4 figures, submitted for PR

Spiral cracks in drying precipitates

We investigate the formation of spiral crack patterns during the desiccation of thin layers of precipitates in contact with a substrate. This symmetry-breaking fracturing mode is found to arise naturally not from torsion forces, but from a propagating stress front induced by the fold-up of the fragments. We model their formation mechanism using a coarse-grain model for fragmentation and successfully reproduce the spiral cracks. Fittings of experimental and simulation data show that the spirals are logarithmic, corresponding to constant deviation from a circular crack path. Theoretical aspects of the logarithmic spirals are discussed. In particular we show that this occurs generally when the crack speed is proportional to the propagating speed of stress front.Comment: 4 pages, 5 figures, RevTe

Statistical Physics of Fracture Surfaces Morphology

Experiments on fracture surface morphologies offer increasing amounts of data that can be analyzed using methods of statistical physics. One finds scaling exponents associated with correlation and structure functions, indicating a rich phenomenology of anomalous scaling. We argue that traditional models of fracture fail to reproduce this rich phenomenology and new ideas and concepts are called for. We present some recent models that introduce the effects of deviations from homogeneous linear elasticity theory on the morphology of fracture surfaces, succeeding to reproduce the multiscaling phenomenology at least in 1+1 dimensions. For surfaces in 2+1 dimensions we introduce novel methods of analysis based on projecting the data on the irreducible representations of the SO(2) symmetry group. It appears that this approach organizes effectively the rich scaling properties. We end up with the proposition of new experiments in which the rotational symmetry is not broken, such that the scaling properties should be particularly simple.Comment: A review paper submitted to J. Stat. Phy

PAR2 modulators derived from GB88

PAR2 antagonists have potential for treating inflammatory, respiratory, gastrointestinal, neurological, and metabolic disorders, but few antagonists are known. Derivatives of GB88 (3) suggest that all four of its components bind at distinct PAR2 sites with the isoxazole, cyclohexylalanine, and isoleucine determining affinity and selectivity, while the C-terminal substituent determines agonist/antagonist function. Here we report structurally similar PAR2 ligands with opposing functions (agonist vs antagonist) upon binding to PAR2. A biased ligand AY117 (65) was found to antagonize calcium release induced by PAR2 agonists trypsin and hexapeptide 2f-LIGRLO-NH2 (IC50 2.2 and 0.7 mu M, HT29 cells), but it was a selective PAR2 agonist in inhibiting cAMP stimulation and activating ERK1/2 phosphorylation. It showed antiinflammatory properties both in vitro and in vivo

Genetically encoded sender-receiver system in 3D mammalian cell culture

Engineering spatial patterning in mammalian cells, employing entirely genetically encoded components, requires solving several problems. These include how to code secreted activator or inhibitor molecules and how to send concentration-dependent signals to neighboring cells, to control gene expression. The Madin-Darby Canine Kidney (MDCK) cell line is a potential engineering scaffold as it forms hollow spheres (cysts) in 3D culture and tubulates in response to extracellular hepatocyte growth factor (HGF). We first aimed to graft a synthetic patterning system onto single developing MDCK cysts. We therefore developed a new localized transfection method to engineer distinct sender and receiver regions. A stable reporter line enabled reversible EGFP activation by HGF and modulation by a secreted repressor (a truncated HGF variant, NK4). By expanding the scale to wide fields of cysts, we generated morphogen diffusion gradients, controlling reporter gene expression. Together, these components provide a toolkit for engineering cell-cell communication networks in 3D cell culture.Facultad de Ciencias Exacta

Effects of the neonicotinoid pesticide thiamethoxam at field-realistic levels on microcolonies of Bombus terrestris worker bumble bees

Copyright © 2013 Elsevier. Notice: this is the author’s version of a work that was accepted for publication in Ecotoxicology and Environmental Safety. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Ecotoxicology and Environmental Safety, 2014, Vol. 100, pp. 153-158 at: http://dx.doi.org/10.1016/j.ecoenv.2013.10.027Neonicotinoid pesticides are currently implicated in the decline of wild bee populations. Bumble bees, Bombus spp., are important wild pollinators that are detrimentally affected by ingestion of neonicotinoid residues. To date, imidacloprid has been the major focus of study into the effects of neonicotinoids on bumble bee health, but wild populations are increasingly exposed to alternative neonicotinoids such as thiamethoxam. To investigate whether environmentally realistic levels of thiamethoxam affect bumble bee performance over a realistic exposure period, we exposed queenless microcolonies of Bombus terrestris L. workers to a wide range of dosages up to 98 μg kg−1 in dietary syrup for 17 days. Results showed that bumble bee workers survived fewer days when presented with syrup dosed at 98 μg thiamethoxam kg−1, while production of brood (eggs and larvae) and consumption of syrup and pollen in microcolonies were significantly reduced by thiamethoxam only at the two highest concentrations (39, 98 μg kg−1). In contrast, we found no detectable effect of thiamethoxam at levels typically found in the nectars of treated crops (between 1 and 11 μg kg−1). By comparison with published data, we demonstrate that during an exposure to field-realistic concentrations lasting approximately two weeks, brood production in worker bumble bees is more sensitive to imidacloprid than thiamethoxam. We speculate that differential sensitivity arises because imidacloprid produces a stronger repression of feeding in bumble bees than thiamethoxam, which imposes a greater nutrient limitation on production of brood.Natural Environment Research Council (NERC