The phase diagram of Yang-Mills theory with a compact extra dimension

We present a non-perturbative study of the phase diagram of SU(2) Yang-Mills theory in a five-dimensional spacetime with a compact extra dimension. The non-renormalizable theory is regularized on an anisotropic lattice and investigated through numerical simulations in a regime characterized by a hierarchy between the scale of low-energy physics, the inverse compactification radius, and the cutoff scale. We map out the structure of the phase diagram and the pattern of lines corresponding to fixed values of the ratio between the mass of the fifth component of the gauge field and the non-perturbative mass gap of the four-dimensional modes. We discuss different limits of the model, and comment on the implications of our findings.Comment: 17 pages, 9 figure

Measurements of neutrino oscillation in appearance and disappearance channels by the T2K experiment with 6.6 x 10(20) protons on target

111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee comments111 pages, 45 figures, submitted to Physical Review D. Minor revisions to text following referee commentsWe thank the J-PARC staff for superb accelerator performance and the CERN NA61/SHINE Collaboration for providing valuable particle production data. We acknowledge the support of MEXT, Japan; NSERC, NRC, and CFI, Canada; CEA and CNRS/IN2P3, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; RSF, RFBR and MES, Russia; MINECO and ERDF funds, Spain; SNSF and SER, Switzerland; STFC, UK; and the U. S. Deparment of Energy, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, GridPP, UK, and the Emerald High Performance Computing facility in the Centre for Innovation, UK. In addition, participation of individual researchers and institutions has been further supported by funds from ERC (FP7), EU; JSPS, Japan; Royal Society, UK; and DOE Early Career program, USA

Mast cell lineage diversion of T lineage precursors by the essential T cell transcription factor GATA-3

GATA-3 is essential for T cell development from the earliest stages. However, abundant GATA-3 can drive T lineage precursors to a non–T cell fate, depending on Notch signaling and developmental stage. Here, overexpression of GATA-3 blocked the survival of pro–T cells when Notch-Delta signals were present but enhanced viability in their absence. In fetal thymocytes at the double-negative 1 (DN1) stage and DN2 stage but not those at the DN3 stage, overexpression of GATA-3 rapidly induced respecification to the mast cell lineage with high frequency by direct transcriptional 'reprogramming'. Normal DN2 thymocytes also showed mast cell potential when interleukin 3 and stem cell factor were added in the absence of Notch signaling. Our results suggest a close relationship between the pro–T cell and mast cell programs and a previously unknown function for Notch in T lineage fidelity

Role of mitochondrial raft-like microdomains in the regulation of cell apoptosis

Lipid rafts are envisaged as lateral assemblies of specific lipids and proteins that dissociate and associate rapidly and form functional clusters in cell membranes. These structural platforms are not confined to the plasma membrane; indeed lipid microdomains are similarly formed at subcellular organelles, which include endoplasmic reticulum, Golgi and mitochondria, named raft-like microdomains. In addition, some components of raft-like microdomains are present within ER-mitochondria associated membranes. This review is focused on the role of mitochondrial raft-like microdomains in the regulation of cell apoptosis, since these microdomains may represent preferential sites where key reactions take place, regulating mitochondria hyperpolarization, fission-associated changes, megapore formation and release of apoptogenic factors. These structural platforms appear to modulate cytoplasmic pathways switching cell fate towards cell survival or death. Main insights on this issue derive from some pathological conditions in which alterations of microdomains structure or function can lead to severe alterations of cell activity and life span. In the light of the role played by raft-like microdomains to integrate apoptotic signals and in regulating mitochondrial dynamics, it is conceivable that these membrane structures may play a role in the mitochondrial alterations observed in some of the most common human neurodegenerative diseases, such as Amyotrophic lateral sclerosis, Huntington's chorea and prion-related diseases. These findings introduce an additional task for identifying new molecular target(s) of pharmacological agents in these pathologies

Ciliopathy is differentially distributed in the brain of a Bardet-Biedl syndrome mouse model

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous inherited human disorder displaying a pleotropic phenotype. Many of the symptoms characterized in the human disease have been reproduced in animal models carrying deletions or knock-in mutations of genes causal for the disorder. Thinning of the cerebral cortex, enlargement of the lateral and third ventricles, and structural changes in cilia are among the pathologies documented in these animal models. Ciliopathy is of particular interest in light of recent studies that have implicated primary neuronal cilia (PNC) in neuronal signal transduction. In the present investigation, we tested the hypothesis that areas of the brain responsible for learning and memory formation would differentially exhibit PNC abnormalities in animals carrying a deletion of the Bbs4 gene (Bbs4-/-). Immunohistochemical localization of adenylyl cyclase-III (ACIII), a marker restricted to PNC, revealed dramatic alterations in PNC morphology and a statistically significant reduction in number of immunopositive cilia in the hippocampus and amygdala of Bbs4-/- mice compared to wild type (WT) littermates. Western blot analysis confirmed the decrease of ACIII levels in the hippocampus and amygdala of Bbs4-/- mice, and electron microscopy demonstrated pathological alterations of PNC in the hippocampus and amygdala. Importantly, no neuronal loss was found within the subregions of amygdala and hippocampus sampled in Bbs4-/- mice and there were no statistically significant alterations of ACIII immunopositive cilia in other areas of the brain not known to contribute to the BBS phenotype. Considered with data documenting a role of cilia in signal transduction these findings support the conclusion that alterations in cilia structure or neurochemical phenotypes may contribute to the cognitive deficits observed in the Bbs4-/- mouse mode. © 2014 Agassandian et al

Measurement of the electron neutrino charged-current interaction rate on water with the T2K ND280 pi(0) detector

10 pages, 6 figures, Submitted to PRDhttp://journals.aps.org/prd/abstract/10.1103/PhysRevD.91.112010© 2015 American Physical Society11 pages, 6 figures, as accepted to PRD11 pages, 6 figures, as accepted to PRD11 pages, 6 figures, as accepted to PR

The Pathway Coexpression Network: Revealing pathway relationships.

A goal of genomics is to understand the relationships between biological processes. Pathways contribute to functional interplay within biological processes through complex but poorly understood interactions. However, limited functional references for global pathway relationships exist. Pathways from databases such as KEGG and Reactome provide discrete annotations of biological processes. Their relationships are currently either inferred from gene set enrichment within specific experiments, or by simple overlap, linking pathway annotations that have genes in common. Here, we provide a unifying interpretation of functional interaction between pathways by systematically quantifying coexpression between 1,330 canonical pathways from the Molecular Signatures Database (MSigDB) to establish the Pathway Coexpression Network (PCxN). We estimated the correlation between canonical pathways valid in a broad context using a curated collection of 3,207 microarrays from 72 normal human tissues. PCxN accounts for shared genes between annotations to estimate significant correlations between pathways with related functions rather than with similar annotations. We demonstrate that PCxN provides novel insight into mechanisms of complex diseases using an Alzheimer's Disease (AD) case study. PCxN retrieved pathways significantly correlated with an expert curated AD gene list. These pathways have known associations with AD and were significantly enriched for genes independently associated with AD. As a further step, we show how PCxN complements the results of gene set enrichment methods by revealing relationships between enriched pathways, and by identifying additional highly correlated pathways. PCxN revealed that correlated pathways from an AD expression profiling study include functional clusters involved in cell adhesion and oxidative stress. PCxN provides expanded connections to pathways from the extracellular matrix. PCxN provides a powerful new framework for interrogation of global pathway relationships. Comprehensive exploration of PCxN can be performed at http://pcxn.org/

Spatial Regulation and the Rate of Signal Transduction Activation

Of the many important signaling events that take place on the surface of a mammalian cell, activation of signal transduction pathways via interactions of cell surface receptors is one of the most important. Evidence suggests that cell surface proteins are not as freely diffusible as implied by the classic fluid mosaic model and that their confinement to membrane domains is regulated. It is unknown whether these dynamic localization mechanisms function to enhance signal transduction activation rate or to minimize cross talk among pathways that share common intermediates. To determine which of these two possibilities is more likely, we derive an explicit equation for the rate at which cell surface membrane proteins interact based on a Brownian motion model in the presence of endocytosis and exocytosis. We find that in the absence of any diffusion constraints, cell surface protein interaction rate is extremely high relative to cytoplasmic protein interaction rate even in a large mammalian cell with a receptor abundance of a mere two hundred molecules. Since a larger number of downstream signaling events needs to take place, each occurring at a much slower rate than the initial activation via association of cell surface proteins, we conclude that the role of co-localization is most likely that of cross-talk reduction rather than coupling efficiency enhancement

Sensitivity of the T2K accelerator-based neutrino experiment with an Extended run to 20×102120\times10^{21} POT

18 pages, 4 figures18 pages, 4 figures18 pages, 4 figures18 pages, 4 figures18 pages, 4 figuresRecent measurements at the T2K experiment indicate that CP violation in neutrino mixing may be observed in the future by long-baseline neutrino oscillation experiments. We explore the physics program of an extension to the currently approved T2K running of $7.8\times 10^{21}$ protons-on-target to $20\times 10^{21}$ protons-on-target,aiming at initial observation of CP violation with 3$\,\sigma$ or higher significance for the case of maximum CP violation. With accelerator and beam line upgrades, as well as analysis improvements, this program would occur before the next generation of long-baseline neutrino oscillation experiments that are expected to start operation in 2026.We acknowledge the support of MEXT, Japan; NSERC (Grant No. SAPPJ-2014-00031), NRC and CFI, Canada; CEA and CNRS/IN2P3, France; DFG, Germany; INFN, Italy; National Science Centre (NCN), Poland; RSF, RFBR and MES, Russia; MINECO and ERDF funds, Spain; SNSF and SERI, Switzerland; STFC, UK; and DOE, USA. We also thank CERN for the UA1/NOMAD magnet, DESY for the HERA-B magnet mover system, NII for SINET4, the WestGrid and SciNet consortia in Compute Canada, and GridPP in the United Kingdom. In addition, participation of individual researchers and institutions has been further supported by funds from ERC (FP7), H2020 Grant No. RISE-GA644294-JENNIFER, EU; JSPS, Japan; Royal Society, UK; and the DOE Early Career program, USA. CNRS/IN2P3: Centre National de la Recherche ScientifiqueInstitut National de Physique Nucleaire et de Physique des Particules RSF: Russian Science Foundation MES: Ministry of Education and Science, Russia ERDF: European Regional Development Fund SNSF: Swiss National Science Foundation SER (should be SERI): State Secretariat for Education, Research and Innovatio

Measurement of the neutrino-oxygen neutral-current interaction cross section by observing nuclear deexcitation gamma rays

We report the first measurement of the neutrino-oxygen neutral-current quasielastic (NCQE) cross section gamma It is obtained by observing nuclear deexcitation. rays which follow neutrino-oxygen interactions at the Super-Kamiokande water Cherenkov detector. We use T2K data corresponding to 3.01 x 10(20) protons on target. By selecting only events during the T2K beam window and with well-reconstructed vertices in the fiducial volume, the large background rate from natural radioactivity is dramatically reduced. We observe 43 events in the 4-30 MeV reconstructed energy window, compared with an expectation of 51.0, which includes an estimated 16.2 background events. The background is primarily nonquasielastic neutral-current interactions and has only 1.2 events from natural radioactivity. The flux-averaged NCQE cross section we measure is 1.55 x 10(-38) cm(2) with a 68% confidence interval of (1.22, 2.20) x 10(-38) cm(2) at a median neutrino energy of 630 MeV, compared with the theoretical prediction of 2.01 x 10(-38) cm(2)