Joint profiling of DNA methylation and chromatin architecture in single cells.

We report a molecular assay, Methyl-HiC, that can simultaneously capture the chromosome conformation and DNA methylome in a cell. Methyl-HiC reveals coordinated DNA methylation status between distal genomic segments that are in spatial proximity in the nucleus, and delineates heterogeneity of both the chromatin architecture and DNA methylome in a mixed population. It enables simultaneous characterization of cell-type-specific chromatin organization and epigenome in complex tissues

Stress Propagation through Frictionless Granular Material

We examine the network of forces to be expected in a static assembly of hard, frictionless spherical beads of random sizes, such as a colloidal glass. Such an assembly is minimally connected: the ratio of constraint equations to contact forces approaches unity for a large assembly. However, the bead positions in a finite subregion of the assembly are underdetermined. Thus to maintain equilibrium, half of the exterior contact forces are determined by the other half. We argue that the transmission of force may be regarded as unidirectional, in contrast to the transmission of force in an elastic material. Specializing to sequentially deposited beads, we show that forces on a given buried bead can be uniquely specified in terms of forces involving more recently added beads. We derive equations for the transmission of stress averaged over scales much larger than a single bead. This derivation requires the Ansatz that statistical fluctuations of the forces are independent of fluctuations of the contact geometry. Under this Ansatz, the $d(d+1)/2$-component stress field can be expressed in terms of a d-component vector field. The procedure may be generalized to non-sequential packings. In two dimensions, the stress propagates according to a wave equation, as postulated in recent work elsewhere. We demonstrate similar wave-like propagation in higher dimensions, assuming that the packing geometry has uniaxial symmetry. In macroscopic granular materials we argue that our approach may be useful even though grains have friction and are not packed sequentially.=17Comment: 15 pages, 4 figures, revised vertion for Phys. Rev.

Nodal quasiparticle meltdown in ultra-high resolution pump-probe angle-resolved photoemission

High-$T_c$ cuprate superconductors are characterized by a strong momentum-dependent anisotropy between the low energy excitations along the Brillouin zone diagonal (nodal direction) and those along the Brillouin zone face (antinodal direction). Most obvious is the d-wave superconducting gap, with the largest magnitude found in the antinodal direction and no gap in the nodal direction. Additionally, while antinodal quasiparticle excitations appear only below $T_c$, superconductivity is thought to be indifferent to nodal excitations as they are regarded robust and insensitive to $T_c$. Here we reveal an unexpected tie between nodal quasiparticles and superconductivity using high resolution time- and angle-resolved photoemission on optimally doped Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$. We observe a suppression of the nodal quasiparticle spectral weight following pump laser excitation and measure its recovery dynamics. This suppression is dramatically enhanced in the superconducting state. These results reduce the nodal-antinodal dichotomy and challenge the conventional view of nodal excitation neutrality in superconductivity.Comment: 7 pages, 3 figure. To be published in Nature Physic

Performance breakdown effects dissociate from error detection effects in typing

Mistakes in skilled performance are often observed to be slower than correct actions. This error slowing has been associated with cognitive control processes involved in performance monitoring and error detection. A limited literature on skilled actions, however, suggests that preerror actions may also be slower than accurate actions. This contrasts with findings from unskilled, discrete trial tasks, where preerror performance is usually faster than accurate performance. We tested 3 predictions about error-related behavioural changes in continuous typing performance. We asked participants to type 100 sentences without visual feedback. We found that (a) performance before errors was no different in speed than that before correct key-presses, (b) error and posterror key-presses were slower than matched correct key-presses, and (c) errors were preceded by greater variability in speed than were matched correct key-presses. Our results suggest that errors are preceded by a behavioural signature, which may indicate breakdown of fluid cognition, and that the effects of error detection on performance (error and posterror slowing) can be dissociated from breakdown effects (preerror increase in variability). © 2013 © 2013 The Experimental Psychology Society

Well dispersed fractal aggregates as filler in polymer-silica nanocomposites: long range effects in rheology

We are presenting a new method of processing polystyrene-silica nanocomposites, which results in a very well-defined dispersion of small primary aggregates (assembly of 15 nanoparticles of 10 nm diameter) in the matrix. The process is based on a high boiling point solvent, in which the nanoparticles are well dispersed, and controlled evaporation. The filler's fine network structure is determined over a wide range of sizes, using a combination of Small Angle Neutron Scattering (SANS) and Transmission Electronic Microscopy (TEM). The mechanical response of the nanocomposite material is investigated both for small (ARES oscillatory shear and Dynamical Mechanical Analysis) and large deformations (uniaxial traction), as a function of the concentration of the particles. We can investigate the structure-property correlations for the two main reinforcement effects: the filler network contribution, and a filler-polymer matrix effect. Above a silica volume fraction threshold, we see a divergence of the modulus correlated to the build up of a connected network. Below the threshold, we obtain a new additional elastic contribution of much longer terminal time than the matrix. Since aggregates are separated by at least 60 nm, this new filler-matrix contribution cannot be described solely with the concept of glassy layer (2nm)

Models and metaphors: complexity theory and through-life management in the built environment

Complexity thinking may have both modelling and metaphorical applications in the through-life management of the built environment. These two distinct approaches are examined and compared. In the first instance, some of the sources of complexity in the design, construction and maintenance of the built environment are identified. The metaphorical use of complexity in management thinking and its application in the built environment are briefly examined. This is followed by an exploration of modelling techniques relevant to built environment concerns. Non-linear and complex mathematical techniques such as fuzzy logic, cellular automata and attractors, may be applicable to their analysis. Existing software tools are identified and examples of successful built environment applications of complexity modelling are given. Some issues that arise include the definition of phenomena in a mathematically usable way, the functionality of available software and the possibility of going beyond representational modelling. Further questions arising from the application of complexity thinking are discussed, including the possibilities for confusion that arise from the use of metaphor. The metaphor of a 'commentary machine' is suggested as a possible way forward and it is suggested that an appropriate linguistic analysis can in certain situations reduce perceived complexity

High-throughput screening of monoclonal antibodies against plant cell wall glycans by hierarchical clustering of their carbohydrate microarray binding profiles

Antibody-producing hybridoma cell lines were created following immunisation with a crude extract of cell wall polymers from the plant Arabidopsis thaliana. In order to rapidly screen the specificities of individual monoclonal antibodies (mAbs), their binding to microarrays containing 50 cell wall glycans immobilized on nitrocellulose was assessed. Hierarchical clustering of microarray binding profiles from newly produced mAbs, together with the profiles for mAbs with previously defined specificities allowed the rapid assignments of mAb binding to antigen classes. mAb specificities were further investigated using subsequent immunochemical and biochemical analyses and two novel mAbs are described in detail. mAb LM13 binds to an arabinanase-sensitive pectic epitope and mAb LM14, binds to an epitope occurring on arabinogalactan-proteins. Both mAbs display novel patterns of recognition of cell walls in plant materials

Agent based modelling helps in understanding the rules by which fibroblasts support keratinocyte colony formation

Background: Autologous keratincoytes are routinely expanded using irradiated mouse fibroblasts and bovine serum for clinical use. With growing concerns about the safety of these xenobiotic materials, it is desirable to culture keratinocytes in media without animal derived products. An improved understanding of epithelial/mesenchymal interactions could assist in this. Methodology/Principal Findings: A keratincyte/fibroblast o-culture model was developed by extending an agent-based keratinocyte colony formation model to include the response of keratinocytes to both fibroblasts and serum. The model was validated by comparison of the in virtuo and in vitro multicellular behaviour of keratinocytes and fibroblasts in single and co-culture in Greens medium. To test the robustness of the model, several properties of the fibroblasts were changed to investigate their influence on the multicellular morphogenesis of keratinocyes and fibroblasts. The model was then used to generate hypotheses to explore the interactions of both proliferative and growth arrested fibroblasts with keratinocytes. The key predictions arising from the model which were confirmed by in vitro experiments were that 1) the ratio of fibroblasts to keratinocytes would critically influence keratinocyte colony expansion, 2) this ratio needed to be optimum at the beginning of the co-culture, 3) proliferative fibroblasts would be more effective than irradiated cells in expanding keratinocytes and 4) in the presence of an adequate number of fibroblasts, keratinocyte expansion would be independent of serum. Conclusions: A closely associated computational and biological approach is a powerful tool for understanding complex biological systems such as the interactions between keratinocytes and fibroblasts. The key outcome of this study is the finding that the early addition of a critical ratio of proliferative fibroblasts can give rapid keratinocyte expansion without the use of irradiated mouse fibroblasts and bovine serum