Local influence of boundary conditions on a confined supercooled colloidal liquid

We study confined colloidal suspensions as a model system which approximates the behavior of confined small molecule glass-formers. Dense colloidal suspensions become glassier when confined between parallel glass plates. We use confocal microscopy to study the motion of confined colloidal particles. In particular, we examine the influence particles stuck to the glass plates have on nearby free particles. Confinement appears to be the primary influence slowing free particle motion, and proximity to stuck particles causes a secondary reduction in the mobility of free particles. Overall, particle mobility is fairly constant across the width of the sample chamber, but a strong asymmetry in boundary conditions results in a slight gradient of particle mobility.Comment: For conference proceedings, "Dynamics in Confinement", Grenoble, March 201

On the study of jamming percolation

We investigate kinetically constrained models of glassy transitions, and determine which model characteristics are crucial in allowing a rigorous proof that such models have discontinuous transitions with faster than power law diverging length and time scales. The models we investigate have constraints similar to that of the knights model, introduced by Toninelli, Biroli, and Fisher (TBF), but differing neighbor relations. We find that such knights-like models, otherwise known as models of jamming percolation, need a ``No Parallel Crossing'' rule for the TBF proof of a glassy transition to be valid. Furthermore, most knight-like models fail a ``No Perpendicular Crossing'' requirement, and thus need modification to be made rigorous. We also show how the ``No Parallel Crossing'' requirement can be used to evaluate the provable glassiness of other correlated percolation models, by looking at models with more stable directions than the knights model. Finally, we show that the TBF proof does not generalize in any straightforward fashion for three-dimensional versions of the knights-like models.Comment: 13 pages, 18 figures; Spiral model does satisfy property

A polymerase mechanism-based strategy for viral attenuation and vaccine development

Live, attenuated vaccines have prevented morbidity and mortality associated with myriad viral pathogens. Development of live, attenuated vaccines has traditionally relied on empirical methods, such as growth in nonhuman cells. These approaches require substantial time and expense to identify vaccine candidates and to determine their mechanisms of attenuation. With these constraints, at least a decade is required for approval of a live, attenuated vaccine for use in humans. We recently reported the discovery of an active site lysine residue that contributes to the catalytic efficiency of all nucleic acid polymerases (Castro, C., Smidansky, E. D., Arnold, J. J., Maksimchuk, K. R., Moustafa, I., Uchida, A., Götte, M., Konigsberg, W., and Cameron, C. E. (2009) Nat. Struct. Mol. Biol. 16, 212-218). Here we use a model RNA virus and its polymerase to show that mutation of this residue from lysine to arginine produces an attenuated virus that is genetically stable and elicits a protective immune response. Given the conservation of this residue in all viral polymerases, this study suggests that a universal, mechanism-based strategy may exist for viral attenuation and vaccine development. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc

Transitions between Inherent Structures in Water

The energy landscape approach has been useful to help understand the dynamic properties of supercooled liquids and the connection between these properties and thermodynamics. The analysis in numerical models of the inherent structure (IS) trajectories -- the set of local minima visited by the liquid -- offers the possibility of filtering out the vibrational component of the motion of the system on the potential energy surface and thereby resolving the slow structural component more efficiently. Here we report an analysis of an IS trajectory for a widely-studied water model, focusing on the changes in hydrogen bond connectivity that give rise to many IS separated by relatively small energy barriers. We find that while the system \emph{travels} through these IS, the structure of the bond network continuously modifies, exchanging linear bonds for bifurcated bonds and usually reversing the exchange to return to nearly the same initial configuration. For the 216 molecule system we investigate, the time scale of these transitions is as small as the simulation time scale ($\approx 1$ fs). Hence for water, the transitions between each of these IS is relatively small and eventual relaxation of the system occurs only by many of these transitions. We find that during IS changes, the molecules with the greatest displacements move in small ``clusters'' of 1-10 molecules with displacements of $\approx 0.02-0.2$ nm, not unlike simpler liquids. However, for water these clusters appear to be somewhat more branched than the linear ``string-like'' clusters formed in a supercooled Lennar d-Jones system found by Glotzer and her collaborators.Comment: accepted in PR

Genomic RNA Elements Drive Phase Separation of the SARS-CoV-2 Nucleocapsid

We report that the SARS-CoV-2 nucleocapsid protein (N-protein) undergoes liquid-liquid phase separation (LLPS) with viral RNA. N-protein condenses with specific RNA genomic elements under physiological buffer conditions and condensation is enhanced at human body temperatures (33°C and 37°C) and reduced at room temperature (22°C). RNA sequence and structure in specific genomic regions regulate N-protein condensation while other genomic regions promote condensate dissolution, potentially preventing aggregation of the large genome. At low concentrations, N-protein preferentially crosslinks to specific regions characterized by single-stranded RNA flanked by structured elements and these features specify the location, number, and strength of N-protein binding sites (valency). Liquid-like N-protein condensates form in mammalian cells in a concentration-dependent manner and can be altered by small molecules. Condensation of N-protein is RNA sequence and structure specific, sensitive to human body temperature, and manipulatable with small molecules, and therefore presents a screenable process for identifying antiviral compounds effective against SARS-CoV-2

Monte Carlo Methods for Estimating Interfacial Free Energies and Line Tensions

Excess contributions to the free energy due to interfaces occur for many problems encountered in the statistical physics of condensed matter when coexistence between different phases is possible (e.g. wetting phenomena, nucleation, crystal growth, etc.). This article reviews two methods to estimate both interfacial free energies and line tensions by Monte Carlo simulations of simple models, (e.g. the Ising model, a symmetrical binary Lennard-Jones fluid exhibiting a miscibility gap, and a simple Lennard-Jones fluid). One method is based on thermodynamic integration. This method is useful to study flat and inclined interfaces for Ising lattices, allowing also the estimation of line tensions of three-phase contact lines, when the interfaces meet walls (where "surface fields" may act). A generalization to off-lattice systems is described as well. The second method is based on the sampling of the order parameter distribution of the system throughout the two-phase coexistence region of the model. Both the interface free energies of flat interfaces and of (spherical or cylindrical) droplets (or bubbles) can be estimated, including also systems with walls, where sphere-cap shaped wall-attached droplets occur. The curvature-dependence of the interfacial free energy is discussed, and estimates for the line tensions are compared to results from the thermodynamic integration method. Basic limitations of all these methods are critically discussed, and an outlook on other approaches is given

Enabling Practice-driven Innovation in the Animal Production Sector

Using the laying hen sector as a case study, the EU-H2020-funded Hennovation project has been testing mechanisms to enable practice-driven innovation through the establishment of innovation networks of farmers and within the laying-hen-processing industry that are facilitated to proactively search for, share and use new ideas to improve hen welfare, efficiency and sustainability. Networks are variably supported by scientists, veterinarians, advisors and others. Nineteen multi-actor networks have been mobilised on local and regional levels across the UK, Sweden, Netherlands, Spain and Czech-Republic.Practice-driven innovation processes were network specific and evolved as the actors within the network came together to share common problems, experiment with possible solutions and learn. Their success was also affected by the institutional context, the structure of the poultry sector, current market forces and wider Agricultural Innovation Systems in each country. This paper explores the circumstances considered necessary by the facilitators to enable practice-driven innovation, providing examples of conditions affecting the innovation process. Further influences included conditions for innovation to happen (e.g. shared opportunity, motivation and knowledge), conditions to work effectively as a network (e.g. trust, collective purpose and contacts) and conditions for successful application in practice (e.g. capacity within the production system and market and legislative ability)

Spatially heterogeneous ages in glassy dynamics

We construct a framework for the study of fluctuations in the nonequilibrium relaxation of glassy systems with and without quenched disorder. We study two types of two-time local correlators with the aim of characterizing the heterogeneous evolution: in one case we average the local correlators over histories of the thermal noise, in the other case we simply coarse-grain the local correlators. We explain why the former describe the fingerprint of quenched disorder when it exists, while the latter are linked to noise-induced mesoscopic fluctuations. We predict constraints on the pdfs of the fluctuations of the coarse-grained quantities. We show that locally defined correlations and responses are connected by a generalized local out-of-equilibrium fluctuation-dissipation relation. We argue that large-size heterogeneities in the age of the system survive in the long-time limit. The invariance of the theory under reparametrizations of time underlies these results. We relate the pdfs of local coarse-grained quantities and the theory of dynamic random manifolds. We define a two-time dependent correlation length from the spatial decay of the fluctuations in the two-time local functions. We present numerical tests performed on disordered spin models in finite and infinite dimensions. Finally, we explain how these ideas can be applied to the analysis of the dynamics of other glassy systems that can be either spin models without disorder or atomic and molecular glassy systems.Comment: 47 pages, 60 Fig