Endothelial Wnt/β-catenin signaling inhibits glioma angiogenesis and normalizes tumor blood vessels by inducing PDGF-B expression

Endothelial Wnt/β-catenin signaling is necessary for angiogenesis of the central nervous system and blood–brain barrier (BBB) differentiation, but its relevance for glioma vascularization is unknown. In this study, we show that doxycycline-dependent Wnt1 expression in subcutaneous and intracranial mouse glioma models induced endothelial Wnt/β-catenin signaling and led to diminished tumor growth, reduced vascular density, and normalized vessels with increased mural cell attachment. These findings were corroborated in GL261 glioma cells intracranially transplanted in mice expressing dominant-active β-catenin specifically in the endothelium. Enforced endothelial β-catenin signaling restored BBB characteristics, whereas inhibition by Dkk1 (Dickkopf-1) had opposing effects. By overactivating the Wnt pathway, we induced the Wnt/β-catenin–Dll4/Notch signaling cascade in tumor endothelia, blocking an angiogenic and favoring a quiescent vascular phenotype, indicated by induction of stalk cell genes. We show that β-catenin transcriptional activity directly regulated endothelial expression of platelet-derived growth factor B (PDGF-B), leading to mural cell recruitment thereby contributing to vascular quiescence and barrier function. We propose that reinforced Wnt/β-catenin signaling leads to inhibition of angiogenesis with normalized and less permeable vessels, which might prove to be a valuable therapeutic target for antiangiogenic and edema glioma therapy

LHCb Alignment Strategy

In this note, we review the alignment strategy for the LHCb detector. We discuss the internal alignment stategy for each subdetector and the alignment of each of the subdetectors relative to one another

Determination of the Deep Inelastic Contribution to the Generalised Gerasimov-Drell-Hearn Integral for the Proton and Neutron

The virtual photon absorption cross section differences [sigma_1/2-sigma_3/2] for the proton and neutron have been determined from measurements of polarised cross section asymmetries in deep inelastic scattering of 27.5 GeV longitudinally polarised positrons from polarised 1H and 3He internal gas targets. The data were collected in the region above the nucleon resonances in the kinematic range nu < 23.5 GeV and 0.8 GeV**2 < Q**2 < 12 GeV**2. For the proton the contribution to the generalised Gerasimov-Drell-Hearn integral was found to be substantial and must be included for an accurate determination of the full integral. Furthermore the data are consistent with a QCD next-to-leading order fit based on previous deep inelastic scattering data. Therefore higher twist effects do not appear significant.Comment: 6 pages, 3 figures, 1 table, revte

The Flavor Asymmetry of the Light Quark Sea from Semi-inclusive Deep-inelastic Scattering

The flavor asymmetry of the light quark sea of the nucleon is determined in the kinematic range 0.02<x<0.3 and 1 GeV^2<Q^2<10 GeV^2, for the first time from semi-inclusive deep-inelastic scattering. The quantity (dbar(x)-ubar(x))/(u(x)-d(x)) is derived from a relationship between the yields of positive and negative pions from unpolarized hydrogen and deuterium targets. The flavor asymmetry dbar-ubar is found to be non-zero and x dependent, showing an excess of dbar over ubar quarks in the proton.Comment: 7 Pages, 2 figures, RevTeX format; slight revision in text, small change in extraction of dbar-ubar and comparison with a high q2 parameterizatio

Inferential Role Semantics for Natural Language

Cognitive models have long been used to study linguistic phe-nomena spanning the domains of phonology, syntax, and se-mantics. Of these domains, semantics is somewhat unique inthat there is little clarity concerning what a model needs to beable to do in order to provide an account of how the mean-ings of complex linguistic expressions, such as sentences, areunderstood. To help address this problem, we introduce a tree-structured neural model that is trained to generate further sen-tences that follow from an input sentence. These further sen-tences chart out the “inferential role” of the input sentence,which we argue constitutes an important part of its meaning.The model is trained using the Stanford Natural Language In-ference (SNLI) dataset, and to evaluate its performance, we re-port entailment prediction accuracies on a set of test sentencesnot present in the training data. We also report the results of asimple study that compares human plausibility ratings for bothground-truth and model-generated entailments for a randomselection of sentences in this test set. Finally, we examine anumber of qualitative features of the model’s ability to gener-alize. Taken together, these analyses indicate that our modelis able to accurately account for important inferential relation-ships amongst linguistic expressions

Observation of a Coherence Length Effect in Exclusive Rho^0 Electroproduction

Exclusive incoherent electroproduction of the rho^0(770) meson from 1H, 2H, 3He, and 14N targets has been studied by the HERMES experiment at squared four-momentum transfer Q**2>0.4 GeV**2 and positron energy loss nu from 9 to 20 GeV. The ratio of the 14N to 1H cross sections per nucleon, known as the nuclear transparency, was found to decrease with increasing coherence length of quark-antiquark fluctuations of the virtual photon. The data provide clear evidence of the interaction of the quark- antiquark fluctuations with the nuclear medium.Comment: RevTeX, 5 pages, 3 figure