Coordinated ras and rac activity shapes macropinocytic cups and enables phagocytosis of geometrically diverse bacteria

Engulfment of extracellular material by phagocytosis or macropinocytosis depends on the ability of cells to generate specialized cup-shaped protrusions. To effectively capture and internalize their targets, these cups are organized into a ring or ruffle of actin-driven protrusion encircling a non-protrusive interior domain. These functional domains depend on the combined activities of multiple Ras and Rho family small GTPases, but how their activities are integrated and differentially regulated over space and time is unknown. Here, we show that the amoeba Dictyostelium discoideum coordinates Ras and Rac activity using the multidomain protein RGBARG (RCC1, RhoGEF, BAR, and RasGAP-containing protein). We find RGBARG uses a tripartite mechanism of Ras, Rac, and phospholipid interactions to localize at the protruding edge and interface with the interior of both macropinocytic and phagocytic cups. There, we propose RGBARG shapes the protrusion by expanding Rac activation at the rim while suppressing expansion of the active Ras interior domain. Consequently, cells lacking RGBARG form enlarged, flat interior domains unable to generate large macropinosomes. During phagocytosis, we find that disruption of RGBARG causes a geometry-specific defect in engulfing rod-shaped bacteria and ellipsoidal beads. This demonstrates the importance of coordinating small GTPase activities during engulfment of more complex shapes and thus the full physiological range of microbes, and how this is achieved in a model professional phagocyte

New evidence for strong nonthermal effects in Tycho's supernova remnant

For the case of Tycho's supernova remnant (SNR) we present the relation between the blast wave and contact discontinuity radii calculated within the nonlinear kinetic theory of cosmic ray (CR) acceleration in SNRs. It is demonstrated that these radii are confirmed by recently published Chandra measurements which show that the observed contact discontinuity radius is so close to the shock radius that it can only be explained by efficient CR acceleration which in turn makes the medium more compressible. Together with the recently determined new value $E_{sn}=1.2\times 10^{51}$ erg of the SN explosion energy this also confirms our previous conclusion that a TeV gamma-ray flux of $(2-5)\times 10^{-13}$ erg/(cm$^2$s) is to be expected from Tycho's SNR. Chandra measurements and the HEGRA upper limit of the TeV gamma-ray flux together limit the source distance $d$ to $3.3\leq d\leq 4$ kpc.Comment: 5 pages, 4 figures. Accepted for publication in Astrophysics and Space Science, Proc. of "The Multi-Messenger Approach to High-Energy Gamma-ray Sources (Third Workshop on the Nature of Unidentified High-Energy Sources)", Barcelona, July 4-7, 200

A PI(3,5)P2 reporter reveals PIKfyve activity and dynamics on macropinosomes and phagosomes

Phosphoinositide signaling lipids (PIPs) are key regulators of membrane identity and trafficking. Of these, PI(3,5)P2 is one of the least well-understood, despite key roles in many endocytic pathways including phagocytosis and macropinocytosis. PI(3,5)P2 is generated by the phosphoinositide 5-kinase PIKfyve, which is critical for phagosomal digestion and antimicrobial activity. However PI(3,5)P2 dynamics and regulation remain unclear due to lack of reliable reporters. Using the amoeba Dictyostelium discoideum, we identify SnxA as a highly selective PI(3,5)P2-binding protein and characterize its use as a reporter for PI(3,5)P2 in both Dictyostelium and mammalian cells. Using GFP-SnxA, we demonstrate that Dictyostelium phagosomes and macropinosomes accumulate PI(3,5)P2 3 min after engulfment but are then retained differently, indicating pathway-specific regulation. We further find that PIKfyve recruitment and activity are separable and that PIKfyve activation stimulates its own dissociation. SnxA is therefore a new tool for reporting PI(3,5)P2 in live cells that reveals key mechanistic details of the role and regulation of PIKfyve/PI(3,5)P

The First VERITAS Telescope

The first atmospheric Cherenkov telescope of VERITAS (the Very Energetic Radiation Imaging Telescope Array System) has been in operation since February 2005. We present here a technical description of the instrument and a summary of its performance. The calibration methods are described, along with the results of Monte Carlo simulations of the telescope and comparisons between real and simulated data. The analysis of TeV $\gamma$-ray observations of the Crab Nebula, including the reconstructed energy spectrum, is shown to give results consistent with earlier measurements. The telescope is operating as expected and has met or exceeded all design specifications.Comment: Accepted by Astroparticle Physic

Complete fuzzy scheduling and fuzzy earned value management in construction projects

Complete fuzzy scheduling and fuzzy earned value management in construction projects Por: Luis Ponz-Tienda, Jose; Pellicer, Eugenio; Yepes, Victor JOURNAL OF ZHEJIANG UNIVERSITY-SCIENCE A Volumen: 13 Número: 1 Páginas: 56-68 Fecha de publicación: JAN 2012 Search For Full Text Cerrar abstractCerrar abstract This paper aims to present a comprehensive proposal for project scheduling and control by applying fuzzy earned value. It goes a step further than the existing literature: in the formulation of the fuzzy earned value we consider not only its duration, but also cost and production, and alternatives in the scheduling between the earliest and latest times. The mathematical model is implemented in a prototypical construction project with all the estimated values taken as fuzzy numbers. Our findings suggest that different possible schedules and the fuzzy arithmetic provide more objective results in uncertain environments than the traditional methodology. The proposed model allows for controlling the vagueness of the environment through the adjustment of the alpha-cut, adapting it to the specific circumstances of the project. © Zhejiang University and Springer-Verlag Berlin Heidelberg 2012.The authors want to thank Ms. Doria GIL-SENABRE, Universitat Politecnica de Valencia, Spain, for the support provided.Ponz Tienda, JL.; Pellicer Armiñana, E.; Yepes Piqueras, V. (2012). Complete fuzzy scheduling and fuzzy earned value management in construction projects. Journal of Zhejiang University Science A. 13(1):56-68. https://doi.org/10.1631/jzus.A1100160S566813

Application of activated barrier hopping theory to viscoplastic modeling of glassy polymers

YesAn established statistical mechanical theory of amorphous polymer deformation has been incorporated as a plastic mechanism into a constitutive model and applied to a range of polymer mechanical deformations. The temperature and rate dependence of the tensile yield of PVC, as reported in early studies, has been modeled to high levels of accuracy. Tensile experiments on PET reported here are analyzed similarly and good accuracy is also achieved. The frequently observed increase in the gradient of the plot of yield stress against logarithm of strain rate is an inherent feature of the constitutive model. The form of temperature dependence of the yield that is predicted by the model is found to give an accurate representation. The constitutive model is developed in two-dimensional form and implemented as a user-defined subroutine in the finite element package ABAQUS. This analysis is applied to the tensile experiments on PET, in some of which strain is localized in the form of shear bands and necks. These deformations are modeled with partial success, though adiabatic heating of the instability causes inaccuracies for this isothermal implementation of the model. The plastic mechanism has advantages over the Eyring process, is equally tractable,and presents no particular difficulties in implementation with finite elements.F. Boutenel acknowledges an Erasmus Programme Scholarshi

Cichlid biogeography: comment and review

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72313/1/j.1467-2979.2004.00148.x.pd

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results