Clustering and the hyperbolic geometry of complex networks

Clustering is a fundamental property of complex networks and it is the mathematical expression of a ubiquitous phenomenon that arises in various types of self-organized networks such as biological networks, computer networks or social networks. In this paper, we consider what is called the global clustering coefficient of random graphs on the hyperbolic plane. This model of random graphs was proposed recently by Krioukov et al. as a mathematical model of complex networks, under the fundamental assumption that hyperbolic geometry underlies the structure of these networks. We give a rigorous analysis of clustering and characterize the global clustering coefficient in terms of the parameters of the model. We show how the global clustering coefficient can be tuned by these parameters and we give an explicit formula for this function.Comment: 51 pages, 1 figur

The prognostic value of systemic inflammation in patients undergoing surgery for colon cancer: comparison of composite ratios and cumulative scores

Introduction: The systemic inflammatory response has been proven to have a prognostic value. There are two methods of assessing the systemic inflammatory response composite ratios (R) and cumulative scores (S). The aim of this study was to compare the prognostic value of ratios and scores in patients undergoing surgery for colon cancer. Methods: Patients were identified prospectively in a single surgical unit. Preoperative neutrophil (N), lymphocyte (L), monocyte (M) and platelet (P) counts, CRP (C) and albumin (A) levels were recorded. The relationship between composite ratios neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), lymphocyte–monocyte ratio (LMR), C-reactive protein albumin ratio (CAR) and the cumulative scores neutrophil– lymphocyte score (NLS), platelet–lymphocyte score (PLS), lymphocyte–monocyte score (LMS), neutrophil– platelet score (NPS), modified Glasgow prognostic score (mGPS) and clinicopathological characteristics, cancer-specific survival (CSS) and overall survival (OS), were examined. Results: A total of 801 patients were examined. When adjusted for tumour node metastasis (TNM) stage, NLR >5 (p < 0.001), NLS (p < 0.01), PLS (p < 0.001), LMR <2.4 (p < 0.001), LMS (p < 0.001), NPS (p < 0.001), CAR >0.22 (p < 0.001) and mGPS (p < 0.001) were significantly associated with CSS. In patients undergoing elective surgery (n = 689), the majority of the composite ratios/scores correlated with age (p < 0.01), BMI (p < 0.01), T stage (p < 0.01), venous invasion (p < 0.01) and peritoneal involvement (p < 0.01). When NPS (myeloid) and mGPS (liver) were directly compared, their relationship with CSS and OS was similar. Conclusions: Both composite ratios and cumulative scores had prognostic value, independent of TNM stage, in patients with colon cancer. However, cumulative scores, based on normal reference ranges, are simpler and more consistent for clinical use

Natural killer cells attenuate cytomegalovirus-induced hearing loss in mice

<div><p>Congenital cytomegalovirus (CMV) infection is the most common non-hereditary cause of sensorineural hearing loss (SNHL) yet the mechanisms of hearing loss remain obscure. Natural Killer (NK) cells play a critical role in regulating murine CMV infection via NK cell recognition of the Ly49H cell surface receptor of the viral-encoded m157 ligand expressed at the infected cell surface. This Ly49H NK receptor/m157 ligand interaction has been found to mediate host resistance to CMV in the spleen, and lung, but is much less effective in the liver, so it is not known if this interaction is important in the context of SNHL. Using a murine model for CMV-induced labyrinthitis, we have demonstrated that the Ly49H/m157 interaction mediates host resistance in the temporal bone. BALB/c mice, which lack functional Ly49H, inoculated with mCMV at post-natal day 3 developed profound hearing loss and significant outer hair cell loss by 28 days of life. In contrast, C57BL/6 mice, competent for the Ly49H/m157 interaction, had minimal hearing loss and attenuated outer hair cell loss with the same mCMV dose. Administration of Ly49H blocking antibody or inoculation with a mCMV viral strain deleted for the m157 gene rendered the previously resistant C57BL/6 mouse strain susceptible to hearing loss to a similar extent as the BALB/c mouse strain indicating a direct role of the Ly49H/m157 interaction in mCMV-dependent hearing loss. Additionally, NK cell recruitment to sites of infection was evident in the temporal bone of inoculated susceptible mouse strains. These results demonstrate participation of NK cells in protection from CMV-induced labyrinthitis and SNHL in mice.</p></div

Snap evaporation of droplets on smooth topographies

Droplet evaporation on solid surfaces is important in many applications including printing, micro-patterning and cooling. While seemingly simple, the configuration of evaporating droplets on solids is difficult to predict and control. This is because evaporation typically proceeds as a “stick-slip” sequence—a combination of pinning and de-pinning events dominated by static friction or “pinning”, caused by microscopic surface roughness. Here we show how smooth, pinning-free, solid surfaces of non-planar topography promote a different process called snap evaporation. During snap evaporation a droplet follows a reproducible sequence of configurations, consisting of a quasi-static phase-change controlled by mass diffusion interrupted by out-of-equilibrium snaps. Snaps are triggered by bifurcations of the equilibrium droplet shape mediated by the underlying non-planar solid. Because the evolution of droplets during snap evaporation is controlled by a smooth topography, and not by surface roughness, our ideas can inspire programmable surfaces that manage liquids in heat- and mass-transfer applications

Molecular Valves for Controlling Gas Phase Transport Made from Discrete Angstrom-Sized Pores in Graphene

An ability to precisely regulate the quantity and location of molecular flux is of value in applications such as nanoscale 3D printing, catalysis, and sensor design. Barrier materials containing pores with molecular dimensions have previously been used to manipulate molecular compositions in the gas phase, but have so far been unable to offer controlled gas transport through individual pores. Here, we show that gas flux through discrete angstrom-sized pores in monolayer graphene can be detected and then controlled using nanometer-sized gold clusters, which are formed on the surface of the graphene and can migrate and partially block a pore. In samples without gold clusters, we observe stochastic switching of the magnitude of the gas permeance, which we attribute to molecular rearrangements of the pore. Our molecular valves could be used, for example, to develop unique approaches to molecular synthesis that are based on the controllable switching of a molecular gas flux, reminiscent of ion channels in biological cell membranes and solid state nanopores.Comment: to appear in Nature Nanotechnolog

Steady-state modulation of voltage-gated K+ channels in rat arterial smooth muscle by cyclic AMP-dependent protein kinase and protein phosphatase 2B

Voltage-gated potassium channels (Kv) are important regulators of membrane potential in vascular smooth muscle cells, which is integral to controlling intracellular Ca2+ concentration and regulating vascular tone. Previous work indicates that Kv channels can be modulated by receptor-driven alterations of cyclic AMP-dependent protein kinase (PKA) activity. Here, we demonstrate that Kv channel activity is maintained by tonic activity of PKA. Whole-cell recording was used to assess the effect of manipulating PKA signalling on Kv and ATP-dependent K+ channels of rat mesenteric artery smooth muscle cells. Application of PKA inhibitors, KT5720 or H89, caused a significant inhibition of Kv currents. Tonic PKA-mediated activation of Kv appears maximal as application of isoprenaline (a β-adrenoceptor agonist) or dibutyryl-cAMP failed to enhance Kv currents. We also show that this modulation of Kv by PKA can be reversed by protein phosphatase 2B/calcineurin (PP2B). PKA-dependent inhibition of Kv by KT5720 can be abrogated by pre-treatment with the PP2B inhibitor cyclosporin A, or inclusion of a PP2B auto-inhibitory peptide in the pipette solution. Finally, we demonstrate that tonic PKA-mediated modulation of Kv requires intact caveolae. Pre-treatment of the cells with methyl-β-cyclodextrin to deplete cellular cholesterol, or adding caveolin-scaffolding domain peptide to the pipette solution to disrupt caveolae-dependent signalling each attenuated PKA-mediated modulation of the Kv current. These findings highlight a novel, caveolae-dependent, tonic modulatory role of PKA on Kv channels providing new insight into mechanisms and the potential for pharmacological manipulation of vascular tone

A geometric network model of intrinsic grey-matter connectivity of the human brain

Network science provides a general framework for analysing the large-scale brain networks that naturally arise from modern neuroimaging studies, and a key goal in theoretical neuro- science is to understand the extent to which these neural architectures influence the dynamical processes they sustain. To date, brain network modelling has largely been conducted at the macroscale level (i.e. white-matter tracts), despite growing evidence of the role that local grey matter architecture plays in a variety of brain disorders. Here, we present a new model of intrinsic grey matter connectivity of the human connectome. Importantly, the new model incorporates detailed information on cortical geometry to construct ‘shortcuts’ through the thickness of the cortex, thus enabling spatially distant brain regions, as measured along the cortical surface, to communicate. Our study indicates that structures based on human brain surface information differ significantly, both in terms of their topological network characteristics and activity propagation properties, when compared against a variety of alternative geometries and generative algorithms. In particular, this might help explain histological patterns of grey matter connectivity, highlighting that observed connection distances may have arisen to maximise information processing ability, and that such gains are consistent with (and enhanced by) the presence of short-cut connections