CCN proteins as potential actionable targets in scleroderma

Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease combining inflammatory, vasculopathic and fibrotic manifestations. Skin features, which give their name to the disease and are considered as diagnostic as well as prognostic markers, have not been thoroughly investigated in terms of therapeutic targets. CCN proteins (CYR61/CCN1, CTGF/CCN2, NOV/CCN3 and WISP1â 2â 3 as CCN4â 5â 6) are a family of secreted matricellular proteins implicated in major cellular processes such as cell growth, migration, differentiation. They have already been implicated in key pathophysiological processes of SSc, namely fibrosis, vasculopathy and inflammation. In this review, we discuss the possible implication of CCN proteins in SSc pathogenesis, with a special focus on skin features, and identify the potential actionable CCN targets.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147777/1/exd13806.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/147777/2/exd13806_am.pd

Exact Asymptotic Results for Persistence in the Sinai Model with Arbitrary Drift

We obtain exact asymptotic results for the disorder averaged persistence of a Brownian particle moving in a biased Sinai landscape. We employ a new method that maps the problem of computing the persistence to the problem of finding the energy spectrum of a single particle quantum Hamiltonian, which can be subsequently found. Our method allows us analytical access to arbitrary values of the drift (bias), thus going beyond the previous methods which provide results only in the limit of vanishing drift. We show that on varying the drift, the persistence displays a variety of rich asymptotic behaviors including, in particular, interesting qualitative changes at some special values of the drift.Comment: 17 pages, two eps figures (included

Brownian Motion in wedges, last passage time and the second arc-sine law

We consider a planar Brownian motion starting from $O$ at time $t=0$ and stopped at $t=1$ and a set $F= \{OI_i ; i=1,2,..., n\}$ of $n$ semi-infinite straight lines emanating from $O$. Denoting by $g$ the last time when $F$ is reached by the Brownian motion, we compute the probability law of $g$. In particular, we show that, for a symmetric $F$ and even $n$ values, this law can be expressed as a sum of $\arcsin$ or $(\arcsin)^2$ functions. The original result of Levy is recovered as the special case $n=2$. A relation with the problem of reaction-diffusion of a set of three particles in one dimension is discussed

About the Functional Form of the Parisi Overlap Distribution for the Three-Dimensional Edwards-Anderson Ising Spin Glass

Recently, it has been conjectured that the statistics of extremes is of relevance for a large class of correlated system. For certain probability densities this predicts the characteristic large $x$ fall-off behavior $f(x)\sim\exp (-a e^x)$, $a>0$. Using a multicanonical Monte Carlo technique, we have calculated the Parisi overlap distribution $P(q)$ for the three-dimensional Edward-Anderson Ising spin glass at and below the critical temperature, even where $P(q)$ is exponentially small. We find that a probability distribution related to extreme order statistics gives an excellent description of $P(q)$ over about 80 orders of magnitude.Comment: 4 pages RevTex, 3 figure

Determinants of urinary concentrations of dialkyl phosphates among pregnant women in Canada — Results from the MIREC study

AbstractOrganophosphate (OP) insecticides are commonly used in agriculture. Their use decreased in recent years as they were gradually replaced by other pesticides, but some OPs are still among the insecticides most used in Canada. Exposure to elevated levels of OPs during pregnancy has been associated with adverse birth outcomes and poorer neurodevelopment in children. The objective of the present study was to examine the relationship between the concentrations of OP pesticides urinary dialkyl phosphate (DAP) metabolites and various factors that are potential sources of exposure or determinants of DAP levels. In the Maternal-Infant Research on Environmental Chemicals (MIREC) Study, six DAPs were measured in 1st trimester urine samples of 1884 pregnant women living in Canada. They were grouped into sums of dimethyl alkyl phosphates (DMAP) and diethyl alkyl phosphates (DEAP) for statistical analysis. We found that 93% of women had at least one DAP detected in their urine. Geometric means (GM) of specific gravity-corrected levels for urine dilution were 59 (95% CI 56–62) and 21 (95% CI 20–22) nmol/L for DMAP and DEAP, respectively. The following characteristics were significantly associated with higher urinary concentrations of DMAP or DEAP: higher education, nulliparous, normal pre-pregnancy body mass index, non-smoker, not fasting at sampling, winter season at sampling, and early and late day collection times. Dietary items that were significantly related with higher urinary concentrations included higher intake of citrus fruits, apple juice, sweet peppers, tomatoes, beans and dry peas, soy and rice beverages, whole grain bread, white wine and green and herbal teas. This study indicates that exposure to these compounds is quasi-ubiquitous. The factors associated with greater DAP levels identified here could be useful to regulatory agencies for risk analysis and management. However, some exposure misclassification might occur due to the single DAP measurement available, and to the presence of preformed DAPs in the environment

Toroidal automorphic forms, Waldspurger periods and double Dirichlet series

The space of toroidal automorphic forms was introduced by Zagier in the 1970s: a GL_2-automorphic form is toroidal if it has vanishing constant Fourier coefficients along all embedded non-split tori. The interest in this space stems (amongst others) from the fact that an Eisenstein series of weight s is toroidal for a given torus precisely if s is a non-trivial zero of the zeta function of the quadratic field corresponding to the torus. In this paper, we study the structure of the space of toroidal automorphic forms for an arbitrary number field F. We prove that it decomposes into a space spanned by all derivatives up to order n-1 of an Eisenstein series of weight s and class group character omega precisely if s is a zero of order n of the L-series corresponding to omega at s, and a space consisting of exactly those cusp forms the central value of whose L-series is zero. The proofs are based on an identity of Hecke for toroidal integrals of Eisenstein series and a result of Waldspurger about toroidal integrals of cusp forms combined with non-vanishing results for twists of L-series proven by the method of double Dirichlet series.Comment: 14 page

Three-phase point in a binary hard-core lattice model?

Using Monte Carlo simulation, Van Duijneveldt and Lekkerkerker [Phys. Rev. Lett. 71, 4264 (1993)] found gas-liquid-solid behaviour in a simple two-dimensional lattice model with two types of hard particles. The same model is studied here by means of numerical transfer matrix calculations, focusing on the finite size scaling of the gaps between the largest few eigenvalues. No evidence for a gas-liquid transition is found. We discuss the relation of the model with a solvable RSOS model of which the states obey the same exclusion rules. Finally, a detailed analysis of the relation with the dilute three-state Potts model strongly supports the tricritical point rather than a three-phase point.Comment: 17 pages, LaTeX2e, 13 EPS figure