Oncogenic KSHV induces ALT to facilitate break-induced viral genome replication

Infection with Kaposi’s Sarcoma herpesvirus (KSHV) has been linked to multiple cancers including Kaposi’s sarcoma (KS), Primary effusion lymphoma (PEL), and Multicentric Castleman’s disease (MCD). One of the hallmarks of transformed cancer cells is the activity of telomere maintenance mechanisms. The present study uncovers the onset of Alternative lengthening of telomeres (ALT) in response to KSHV infection from a proteomic screen of telomere-associated DNA damage response proteins by Proteomics of isolated chromatin fragments (PICh). In several initially telomerase+ cell lines, features of ALT activation are present in response to KSHV infection including increased telomere sister-chromatid exchanges, C-circles, telomere clustering in interphase, ALT-associated proteins at telomere clusters, and telomere fragility. Binding of shelterin to telomeric DNA was increased upon infection with KSHV. Interestingly, cells which are latently infected with KSHV are dependent on ALT factors for their efficient proliferation in clonogenic assays and such factors may be essential for the maintenance of viral episomes in infected cells as shown by episome qPCR. Moreover, preliminary experiments by ChIP indicate an increase in heterochromatin marks at telomeres upon infection, similar to the marks documented on the KSHV episome. Analysis of primary tumour material from 8 KS and 7 PEL patients suggests that this not limited to the in vitro systems considered in this study. Taken together, this work demonstrates for the first time the capability of latent KSHV to trigger telomere maintenance via ALT and suggests a model in which KSHV episomes are replicated in tandem with telomeres by BIR in such cells. This provides a unique susceptibility of KSHV infected cancer cells to inhibition of ALT, which may be utilized for the trial of future treatment for KSHV-associated cancers.Open Acces

Decorrelating Topology with HMC

The investigation of the decorrelation efficiency of the HMC algorithm with respect to vacuum topology is a prerequisite for trustworthy full QCD simulations, in particular for the computation of topology sensitive quantities. We demonstrate that for mpi/mrho ratios <= 0.69 sufficient tunneling between the topological sectors can be achieved, for two flavours of dynamical Wilson fermions close to the scaling region beta=5.6. Our results are based on time series of length 5000 trajectories.Comment: change of comments: LATTICE98(confine

Sparse Probit Linear Mixed Model

Linear Mixed Models (LMMs) are important tools in statistical genetics. When used for feature selection, they allow to find a sparse set of genetic traits that best predict a continuous phenotype of interest, while simultaneously correcting for various confounding factors such as age, ethnicity and population structure. Formulated as models for linear regression, LMMs have been restricted to continuous phenotypes. We introduce the Sparse Probit Linear Mixed Model (Probit-LMM), where we generalize the LMM modeling paradigm to binary phenotypes. As a technical challenge, the model no longer possesses a closed-form likelihood function. In this paper, we present a scalable approximate inference algorithm that lets us fit the model to high-dimensional data sets. We show on three real-world examples from different domains that in the setup of binary labels, our algorithm leads to better prediction accuracies and also selects features which show less correlation with the confounding factors.Comment: Published version, 21 pages, 6 figure

MA 220 Supplement: Applied Calculus for Business & Life Sciences

The MA220 Supplement workbook is designed to support the concepts learned in MA220. There are business and life science applications for students majoring in business and/or life science. The MA220 supplement supports, but does not replace the textbook required for the MA220 course

A High Precision Study of the QQ(bar) Potential from Wilson Loops in the Regime of String Breaking

For lattice QCD with two sea quark flavours we compute the static quark antiquark potential V(R) in the regime where string breaking is expected. In order to increase statistics, we make full use of the lattice information by including all lattice vectors R to any possible lattice separation in the infrared regime. The corresponding paths between the lattice points are constructed by means of a generalized Bresenham algorithm as known from computer graphics. As a results we achieve a determination of the unquenched potential in the range .8 to 1.5 fm with hitherto unknown precision. Furthermore, we demonstrate some error reducing methods for the evaluation of the transition matrix element between two- and four-quark states.Comment: 6 pages, 7 figure

An Estimate of alpha_S from Bottomonium in Unquenched QCD

We estimate the strong coupling constant from the perturbative expansion of the plaquette. The scale is set by the 2S-1S and 1P-1S splittings in bottomonium which are computed in NRQCD on dynamical gauge configurations with nf=2 degenerate Wilson quarks at intermediate masses. We have increased the statistics of our spectrum calculation in order to reliably extrapolate in the sea-quark mass. We find a value of alpha_MS(m_Z) = 0.1118(26) which is somewhat lower than previous estimates within NRQCD.Comment: LATTICE98(heavyqk

APENet: LQCD clusters a la APE

Developed by the APE group, APENet is a new high speed, low latency, 3-dimensional interconnect architecture optimized for PC clusters running LQCD-like numerical applications. The hardware implementation is based on a single PCI-X 133MHz network interface card hosting six indipendent bi-directional channels with a peak bandwidth of 676 MB/s each direction. We discuss preliminary benchmark results showing exciting performances similar or better than those found in high-end commercial network systems.Comment: Lattice2004(machines), 3 pages, 4 figure

Finite Size Analysis of the U(1) Background Field Effective Action

We apply the finite size scaling analysis to the derivative of the density of the effective action for the lattice U(1) pure gauge theory in an external constant magnetic field. We found the presence of a continuous phase transition. Moreover, our extimate of of the critical parameters gives values consistent with those extracted from the analysis of the specific heat.Comment: LaTeX2e, 12 pages (5 figures