Spontaneous Jamming in One-Dimensional Systems

We study the phenomenon of jamming in driven diffusive systems. We introduce a simple microscopic model in which jamming of a conserved driven species is mediated by the presence of a non-conserved quantity, causing an effective long range interaction of the driven species. We study the model analytically and numerically, providing strong evidence that jamming occurs; however, this proceeds via a strict phase transition (with spontaneous symmetry breaking) only in a prescribed limit. Outside this limit, the nearby transition (characterised by an essential singularity) induces sharp crossovers and transient coarsening phenomena. We discuss the relevance of the model to two physical situations: the clustering of buses, and the clogging of a suspension forced along a pipe.Comment: 8 pages, 4 figures, uses epsfig. Submitted to Europhysics Letter

Type IV Pili Can Mediate Bacterial Motility within Epithelial Cells.

Pseudomonas aeruginosa is among bacterial pathogens capable of twitching motility, a form of surface-associated movement dependent on type IV pili (T4P). Previously, we showed that T4P and twitching were required for P. aeruginosa to cause disease in a murine model of corneal infection, to traverse human corneal epithelial multilayers, and to efficiently exit invaded epithelial cells. Here, we used live wide-field fluorescent imaging combined with quantitative image analysis to explore how twitching contributes to epithelial cell egress. Results using time-lapse imaging of cells infected with wild-type PAO1 showed that cytoplasmic bacteria slowly disseminated throughout the cytosol at a median speed of >0.05 μm s-1 while dividing intracellularly. Similar results were obtained with flagellin (fliC) and flagellum assembly (flhA) mutants, thereby excluding swimming, swarming, and sliding as mechanisms. In contrast, pilA mutants (lacking T4P) and pilT mutants (twitching motility defective) appeared stationary and accumulated in expanding aggregates during intracellular division. Transmission electron microscopy confirmed that these mutants were not trapped within membrane-bound cytosolic compartments. For the wild type, dissemination in the cytosol was not prevented by the depolymerization of actin filaments using latrunculin A and/or the disruption of microtubules using nocodazole. Together, these findings illustrate a novel form of intracellular bacterial motility differing from previously described mechanisms in being directly driven by bacterial motility appendages (T4P) and not depending on polymerized host actin or microtubules.IMPORTANCE Host cell invasion can contribute to disease pathogenesis by the opportunistic pathogen Pseudomonas aeruginosa Previously, we showed that the type III secretion system (T3SS) of invasive P. aeruginosa strains modulates cell entry and subsequent escape from vacuolar trafficking to host lysosomes. However, we also showed that mutants lacking either type IV pili (T4P) or T4P-dependent twitching motility (i) were defective in traversing cell multilayers, (ii) caused less pathology in vivo, and (iii) had a reduced capacity to exit invaded cells. Here, we report that after vacuolar escape, intracellular P. aeruginosa can use T4P-dependent twitching motility to disseminate throughout the host cell cytoplasm. We further show that this strategy for intracellular dissemination does not depend on flagellin and resists both host actin and host microtubule disruption. This differs from mechanisms used by previously studied pathogens that utilize either host actin or microtubules for intracellular dissemination independently of microbe motility appendages

Infrared spectroscopy of Nova Cassiopeiae 1993 (V705 Cas). IV. A closer look at the dust

Nova Cassiopeiae 1993 (V705 Cas) was an archetypical dust-forming nova. It displayed a deep minimum in the visual light curve, and spectroscopic evidence for carbon, hydrocarbon and silicate dust. We report the results of fitting the infrared spectral energy distribution with the DUSTY code, which we use to determine the properties and geometry of the emitting dust. The emission is well described as originating in a thin shell whose dust has a carbon:silicate ratio of ~2:1 by number (1.26:1 by mass) and a relatively flat size distribution. The 9.7micron and 18micron silicate features are consistent with freshly-condensed dust and, while the lower limit to the grain size distribution is not well constrained, the largest grains have dimensions \~0.06micron; unless the grains in V705 Cas were anomalously small, the sizes of grains produced in nova eruptions may previously have been overestimated in novae with optically thick dust shells. Laboratory work by Grishko & Duley may provide clues to the apparently unique nature of nova UIR features.Comment: 11 pages, 9 fugure

Jamming transition in a homogeneous one-dimensional system: the Bus Route Model

We present a driven diffusive model which we call the Bus Route Model. The model is defined on a one-dimensional lattice, with each lattice site having two binary variables, one of which is conserved (``buses'') and one of which is non-conserved (``passengers''). The buses are driven in a preferred direction and are slowed down by the presence of passengers who arrive with rate lambda. We study the model by simulation, heuristic argument and a mean-field theory. All these approaches provide strong evidence of a transition between an inhomogeneous ``jammed'' phase (where the buses bunch together) and a homogeneous phase as the bus density is increased. However, we argue that a strict phase transition is present only in the limit lambda -> 0. For small lambda, we argue that the transition is replaced by an abrupt crossover which is exponentially sharp in 1/lambda. We also study the coarsening of gaps between buses in the jammed regime. An alternative interpretation of the model is given in which the spaces between ``buses'' and the buses themselves are interchanged. This describes a system of particles whose mobility decreases the longer they have been stationary and could provide a model for, say, the flow of a gelling or sticky material along a pipe.Comment: 17 pages Revtex, 20 figures, submitted to Phys. Rev.

Degenerate dispersive equations arising in the study of magma dynamics

An outstanding problem in Earth science is understanding the method of transport of magma in the Earth's mantle. Models for this process, transport in a viscously deformable porous media, give rise to scalar degenerate, dispersive, nonlinear wave equations. We establish a general local well-posedness for a physical class of data (roughly $H^1$) via fixed point methods. The strategy requires positive lower bounds on the solution. This is extended to global existence for a subset of possible nonlinearities by making use of certain conservation laws associated with the equations. Furthermore, we construct a Lyapunov energy functional, which is locally convex about the uniform state, and prove (global in time) nonlinear dynamic stability of the uniform state for any choice of nonlinearity. We compare the dynamics to that of other problems and discuss open questions concerning a larger range of nonlinearities, for which we conjecture global existence.Comment: 27 Pages, 7 figures are not present in this version. See http://www.columbia.edu/~grs2103/ for a PDF with figures. Submitted to Nonlinearit

Concentrating Membrane Proteins Using Asymmetric Traps and AC Electric Fields

Membrane proteins are key components of the plasma membrane and are responsible for control of chemical ionic gradients, metabolite and nutrient transfer, and signal transduction between the interior of cells and the external environment. Of the genes in the human genome, 30% code for membrane proteins (Krogh et al. J. Mol. Biol.2001, 305, 567). Furthermore, many FDA-approved drugs target such proteins (Overington et al. Nat. Rev. Drug Discovery2006, 5, 993). However, the structure-function relationships of these are notably sparse because of difficulties in their purification and handling outside of their membranous environment. Methods that permit the manipulation of membrane components while they are still in the membrane would find widespread application in separation, purification, and eventual structure-function determination of these species (Poo et al. Nature1977, 265, 602). Here we show that asymmetrically patterned supported lipid bilayers in combination with AC electric fields can lead to efficient manipulation of charged components. We demonstrate the concentration and trapping of such components through the use of a “nested trap” and show that this method is capable of yielding an approximately 30-fold increase in the average protein concentration. Upon removal of the field, the material remains trapped for several hours as a result of topographically restricted diffusion. Our results indicate that this method can be used for concentrating and trapping charged membrane components while they are still within their membranous environment. We anticipate that our approach could find widespread application in the manipulation and study of membrane proteins

Oxidation of tertiary amine-derivatized surfaces to control protein adhesion

Selective oxidation of omega-tertiary amine self-assembled thiol monolayers to tertiary amine N-oxides is shown to transform the adhesion of model proteins lysozyme and fibrinogen upon them. Efficient preparation of both secondary and tertiary linker amides as judged by X-ray photoelectron spectroscopy (XPS) and water droplet contact angle was achieved with an improved amide bond formation on gold quartz crystal microbalance (QCM) sensors using 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyl hexafluorophosphate methanaminium uronium (HATU). Oxidation with hydrogen peroxide was similarly assessed, and adhesion of lysozyme and fibrinogen from phosphate buffered saline was then assayed by QCM and imaged by AFM. Tertiary amine-functionalized sensors adsorbed multilayers of aggregated lysozyme, whereas tertiary amine N-oxides and triethylene glycol-terminated monolayers are consistent with small protein aggregates. The surface containing a dimethylamine N-oxide headgroup and ethyl secondary amide linker showed the largest difference in adsorption of both proteins. Oxidation of tertiary amine decorated surfaces therefore holds the potential for selective deposition of proteins and cells through masking and other patterning techniques

Generalized dynamical density functional theory for classical fluids and the significance of inertia and hydrodynamic interactions

We study the dynamics of a colloidal fluid including inertia and hydrodynamic interactions, two effects which strongly influence the non-equilibrium properties of the system. We derive a general dynamical density functional theory (DDFT) which shows very good agreement with full Langevin dynamics. In suitable limits, we recover existing DDFTs and a Navier-Stokes-like equation with additional non-local terms.Comment: 5 pages, 4 figures, 4 supplementary movie files, I supplementary pd

Hepatitis C Virus Indirectly Disrupts DNA Damage-Induced p53 Responses by Activating Protein Kinase R

ABSTRACT Many DNA tumor viruses promote cellular transformation by inactivating the critically important tumor suppressor protein p53. In contrast, it is not known whether p53 function is disrupted by hepatitis C virus (HCV), a unique, oncogenic RNA virus that is the leading infectious cause of liver cancer in many regions of the world. Here we show that HCV-permissive, liver-derived HepG2 cells engineered to constitutively express microRNA-122 (HepG2/miR-122 cells) have normal p53-mediated responses to DNA damage and that HCV replication in these cells potently suppresses p53 responses to etoposide, an inducer of DNA damage, or nutlin-3, an inhibitor of p53 degradation pathways. Upregulation of p53-dependent targets is consequently repressed within HCV-infected cells, with potential consequences for cell survival. Despite this, p53 function is not disrupted by overexpression of the complete HCV polyprotein, suggesting that altered p53 function may result from the host response to viral RNA replication intermediates. Clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated ablation of double-stranded RNA (dsRNA)-activated protein kinase R (PKR) restored p53 responses while boosting HCV replication, showing that p53 inhibition results directly from viral activation of PKR. The hepatocellular abundance of phosphorylated PKR is elevated in HCV-infected chimpanzees, suggesting that PKR activation and consequent p53 inhibition accompany HCV infection in vivo . These findings reveal a feature of the host response to HCV infection that may contribute to hepatocellular carcinogenesis. IMPORTANCE Chronic infection with hepatitis C virus (HCV) is the leading cause of liver cancer in most developed nations. However, the mechanisms whereby HCV infection promotes carcinogenesis remain unclear. Here, we demonstrate that HCV infection inhibits the activation of p53 following DNA damage. Contrary to previous reports, HCV protein expression is insufficient to inhibit p53. Rather, p53 inhibition is mediated by cellular protein kinase R (PKR), which is activated by HCV RNA replication and subsequently suppresses global protein synthesis. These results redefine our understanding of how HCV infection influences p53 function. We speculate that persistent disruption of p53-mediated DNA damage responses may contribute to hepatocellular carcinogenesis in chronically infected individuals