Neuropilins 1 and 2 mediate neointimal hyperplasia and re-endothelialization following arterial injury

AIMS: Neuropilins 1 and 2 (NRP1 and NRP2) play crucial roles in endothelial cell migration contributing to angiogenesis and vascular development. Both NRPs are also expressed by cultured vascular smooth muscle cells (VSMCs) and are implicated in VSMC migration stimulated by PDGF-BB, but it is unknown whether NRPs are relevant for VSMC function in vivo. We investigated the role of NRPs in the rat carotid balloon injury model, in which endothelial denudation and arterial stretch induce neointimal hyperplasia involving VSMC migration and proliferation. METHODS AND RESULTS: NRP1 and NRP2 mRNAs and proteins increased significantly following arterial injury, and immunofluorescent staining revealed neointimal NRP expression. Down-regulation of NRP1 and NRP2 using shRNA significantly reduced neointimal hyperplasia following injury. Furthermore, inhibition of NRP1 by adenovirally overexpressing a loss-of-function NRP1 mutant lacking the cytoplasmic domain (ΔC) reduced neointimal hyperplasia, whereas wild-type (WT) NRP1 had no effect. NRP-targeted shRNAs impaired, while overexpression of NRP1 WT and NRP1 ΔC enhanced, arterial re-endothelialization 14 days after injury. Knockdown of either NRP1 or NRP2 inhibited PDGF-BB-induced rat VSMC migration, whereas knockdown of NRP2, but not NRP1, reduced proliferation of cultured rat VSMC and neointimal VSMC in vivo. NRP knockdown also reduced the phosphorylation of PDGFα and PDGFβ receptors in rat VSMC, which mediate VSMC migration and proliferation. CONCLUSION: NRP1 and NRP2 play important roles in the regulation of neointimal hyperplasia in vivo by modulating VSMC migration (via NRP1 and NRP2) and proliferation (via NRP2), independently of the role of NRPs in re-endothelialization

Exact results for the star lattice chiral spin liquid

We examine the star lattice Kitaev model whose ground state is a a chiral spin liquid. We fermionize the model such that the fermionic vacua are toric code states on an effective Kagome lattice. This implies that the Abelian phase of the system is inherited from the fermionic vacua and that time reversal symmetry is spontaneously broken at the level of the vacuum. In terms of these fermions we derive the Bloch-matrix Hamiltonians for the vortex free sector and its time reversed counterpart and illuminate the relationships between the sectors. The phase diagram for the model is shown to be a sphere in the space of coupling parameters around the triangles of the lattices. The abelian phase lies inside the sphere and the critical boundary between topologically distinct Abelian and non-Abelian phases lies on the surface. Outside the sphere the system is generically gapped except in the planes where the coupling parameters are zero. These cases correspond to bipartite lattice structures and the dispersion relations are similar to that of the original Kitaev honeycomb model. In a further analysis we demonstrate the three-fold non-Abelian groundstate degeneracy on a torus by explicit calculation.Comment: 7 pages, 8 figure

Obesity independently predicts responders to biphasic insulin 50/50 (Humalog Mix50 and Insuman Comb 50) following conversion from other insulin regimens: a retrospective cohort study

Aims This study aims to examine the metabolic effects of intensification or initiation of insulin treatment with biphasic insulin 50/50, and determine the predictors of responders or non-responders to biphasic insulin 50/50.Methods A cohort of 2183 patients ≥18 years with diabetes, newly treated with biphasic insulin 50/50 between January 2000 and May 2012, were sourced from UK General Practices via The Health Improvement Network (THIN) database. Baseline clinical parameters of 1267 patients with suboptimal glycated hemoglobin (HbA1c) >7.5% (>58 mmol/mol) who had received background insulin regimens for at least 6 months preceding biphasic insulin 50/50 were compared against 12-month outcome data. Responders were defined as those with HbA1c 30 kg/m2), treatment duration for ≥9 months, and baseline HbA1c are independent determinants of responders. In addition, stratified for baseline HbA1c levels, HM50 was associated with better HbA1c outcome compared with IC50.Conclusions biphasic insulin 50/50 is effective for achieving glycemic control in suboptimal HbA1c levels, especially among obese patients with insulin-treated diabetes. Stratified for baseline HbA1c, HM50 was associated with improved HbA1c outcome compared with IC50

Solitons in the Calogero model for distinguishable particles

We consider a large $- N,$ two-family Calogero model in the Hamiltonian, collective-field approach. The Bogomol'nyi limit appears and the corresponding solutions are given by the static-soliton configurations. Solitons from different families are localized at the same place. They behave like a paired hole and lump on the top of the uniform vacuum condensates, depending on the values of the coupling strengths. When the number of particles in the first family is much larger than that of the second family, the hole solution goes to the vortex profile already found in the one-family Calogero model.Comment: 14 pages, no figures, late

Ergodicity of the Δ3\Delta_3 statistic and purity of neutron resonance data

The $\Delta_3(L)$ statistic characterizes the fluctuations of the number of levels as a function of the length of the spectral interval. It is studied as a possible tool to indicate the regular or chaotic nature of underlying dynamics, detect missing levels and the mixing of sequences of levels of different symmetry, particularly in neutron resonance data. The relation between the ensemble average and the average over different fragments of a given realization of spectra is considered. A useful expression for the variance of $\Delta_3(L)$ which accounts for finite sample size is discussed. An analysis of neutron resonance data presents the results consistent with a maximum likelihood method applied to the level spacing distribution.Comment: 24 pages, 19 figures, 1 tabl

Energy localization in two chaotically coupled systems

We set up and analyze a random matrix model to study energy localization and its time behavior in two chaotically coupled systems. This investigation is prompted by a recent experimental and theoretical study of Weaver and Lobkis on coupled elastomechanical systems. Our random matrix model properly describes the main features of the findings by Weaver and Lobkis. Due to its general character, our model is also applicable to similar systems in other areas of physics -- for example, to chaotically coupled quantum dots.Comment: 20 pages, 15 figure

Spectral fluctuations of tridiagonal random matrices from the beta-Hermite ensemble

A time series delta(n), the fluctuation of the nth unfolded eigenvalue was recently characterized for the classical Gaussian ensembles of NxN random matrices (GOE, GUE, GSE). It is investigated here for the beta-Hermite ensemble as a function of beta (zero or positive) by Monte Carlo simulations. The fluctuation of delta(n) and the autocorrelation function vary logarithmically with n for any beta>0 (1<<n<<N). The simple logarithmic behavior reported for the higher-order moments of delta(n) for the GOE (beta=1) and the GUE (beta=2) is valid for any positive beta and is accounted for by Gaussian distributions whose variances depend linearly on ln(n). The 1/f noise previously demonstrated for delta(n) series of the three Gaussian ensembles, is characterized by wavelet analysis both as a function of beta and of N. When beta decreases from 1 to 0, for a given and large enough N, the evolution from a 1/f noise at beta=1 to a 1/f^2 noise at beta=0 is heterogeneous with a ~1/f^2 noise at the finest scales and a ~1/f noise at the coarsest ones. The range of scales in which a ~1/f^2 noise predominates grows progressively when beta decreases. Asymptotically, a 1/f^2 noise is found for beta=0 while a 1/f noise is the rule for beta positive.Comment: 35 pages, 10 figures, corresponding author: G. Le Cae

Calculation of some determinants using the s-shifted factorial

Several determinants with gamma functions as elements are evaluated. This kind of determinants are encountered in the computation of the probability density of the determinant of random matrices. The s-shifted factorial is defined as a generalization for non-negative integers of the power function, the rising factorial (or Pochammer's symbol) and the falling factorial. It is a special case of polynomial sequence of the binomial type studied in combinatorics theory. In terms of the gamma function, an extension is defined for negative integers and even complex values. Properties, mainly composition laws and binomial formulae, are given. They are used to evaluate families of generalized Vandermonde determinants with s-shifted factorials as elements, instead of power functions.Comment: 25 pages; added section 5 for some examples of application

Minimizing Higgs Potentials via Numerical Polynomial Homotopy Continuation

The study of models with extended Higgs sectors requires to minimize the corresponding Higgs potentials, which is in general very difficult. Here, we apply a recently developed method, called numerical polynomial homotopy continuation (NPHC), which guarantees to find all the stationary points of the Higgs potentials with polynomial-like nonlinearity. The detection of all stationary points reveals the structure of the potential with maxima, metastable minima, saddle points besides the global minimum. We apply the NPHC method to the most general Higgs potential having two complex Higgs-boson doublets and up to five real Higgs-boson singlets. Moreover the method is applicable to even more involved potentials. Hence the NPHC method allows to go far beyond the limits of the Gr\"obner basis approach.Comment: 9 pages, 4 figure

A vector equilibrium problem for the two-matrix model in the quartic/quadratic case

We consider the two sequences of biorthogonal polynomials (p_{k,n})_k and (q_{k,n})_k related to the Hermitian two-matrix model with potentials V(x) = x^2/2 and W(y) = y^4/4 + ty^2. From an asymptotic analysis of the coefficients in the recurrence relation satisfied by these polynomials, we obtain the limiting distribution of the zeros of the polynomials p_{n,n} as n tends to infinity. The limiting zero distribution is characterized as the first measure of the minimizer in a vector equilibrium problem involving three measures which for the case t=0 reduces to the vector equilibrium problem that was given recently by two of us. A novel feature is that for t < 0 an external field is active on the third measure which introduces a new type of critical behavior for a certain negative value of t. We also prove a general result about the interlacing of zeros of biorthogonal polynomials.Comment: 60 pages, 9 figure