PPM1D phosphatase, a target of p53 and RBM38 RNA-binding protein, inhibits p53 mRNA translation via dephosphorylation of RBM38.

PPM1D phosphatase, also called wild-type p53-induced phosphatase 1, promotes tumor development by inactivating the p53 tumor suppressor pathway. RBM38 RNA-binding protein, also called RNPC1 and a target of p53, inhibits p53 messenger RNA (mRNA) translation, which can be reversed by GSK3 protein kinase via phosphorylation of RBM38 at serine 195. Here we showed that ectopic expression of RBM38 increases, whereas knockdown of RBM38 inhibits, PPM1D mRNA translation. Consistent with this, we found that RBM38 directly binds to PPM1D 3'-untranslated region (3'-UTR) and promotes expression of a heterologous reporter gene that carries PPM1D 3'-UTR in a dose-dependent manner. Interestingly, we showed that PPM1D directly interacts with and dephosphorylates RBM38 at serine 195. Furthermore, we showed that PPM1D modulates p53 mRNA translation and p53-dependent growth suppression through dephosphorylation of RBM38. These findings provide evidence that the crosstalk between PPM1D and RBM38, both of which are targets and modulators of p53, has a critical role in p53 expression and activity

Singularity points for first passage percolation

Let $0<a<b<\infty$ be fixed scalars. Assign independently to each edge in the lattice $\mathbb{Z}^2$ the value $a$ with probability $p$ or the value $b$ with probability $1-p$. For all $u,v\in\mathbb{Z}^2$, let $T(u,v)$ denote the first passage time between $u$ and $v$. We show that there are points $x\in\mathbb{R}^2$ such that the ``time constant'' in the direction of $x$, namely, $\lim_{n\to\infty}n^{-1}\mathbf{E}_p[T(\mathbf{0},nx)],$ is not a three times differentiable function of $p$.Comment: Published at http://dx.doi.org/10.1214/009117905000000819 in the Annals of Probability (http://www.imstat.org/aop/) by the Institute of Mathematical Statistics (http://www.imstat.org

Sequential variable selection as Bayesian pragmatism in linear factor models

We examine a popular practitioner methodology used in the construction of linear factor models whereby particular factors are increased/decreased in relative importance within the model. This allows model builders to customise models and, as such, reflect those factors that the client/modeller may think important. We call this process Pragmatic Bayesianism (or prag-Bayes for short) and we provide analysis which shows when such a procedure is likely to be successful

Finite-Temperature Monte Carlo Calculations For Systems With Fermions

We present a quantum Monte Carlo method which allows calculations on many-fermion systems at finite temperatures without any sign decay. This enables simulations of the grand-canonical ensemble at large system sizes and low temperatures. Both diagonal and off-diagonal expectations can be computed straightforwardly. The sign decay is eliminated by a constraint on the fermion determinant. The algorithm is approximate. Tests on the Hubbard model show that accurate results on the energy and correlation functions can be obtained.Comment: 5 pages, RevTex; to appear in Phys. Rev. Let