291 research outputs found

    Morphologic and functional correlates of synaptic pathology in the cathepsin D knockout mouse model of congenital neuronal ceroid lipofuscinosis

    No full text
    Mutations in the cathepsin D (CTSD) gene cause an aggressive neurodegenerative disease (congenital neuronal ceroid lipofuscinosis) that leads to early death. Recent evidence suggests that presynaptic abnormalities play a major role in the pathogenesis of CTSD deficiencies. To identify the early events that lead to synaptic alterations, we investigated synaptic ultrastructure and function in presymptomatic CTSD knockout (Ctsd) mice. Electron microscopy revealed that there were significantly greater numbers of readily releasable synaptic vesicles present in Ctsd mice than in wild-type control mice as early as postnatal day 16. The size of this synaptic vesicle pool continued to increase with disease progression in the hippocampus and thalamus of the Ctsd mice. Electrophysiology revealed a markedly decreased frequency of miniature excitatory postsynaptic currents (mEPSCs) with no effect on paired-pulse modulation of the evoked excitatory post synaptic potentials in the hippocampus of Ctsd mice. The reduced mEPSCs frequency was observed before the appearance of epilepsy or any morphologic sign of synaptic degeneration. Taken together, these data indicate that CTSD is required for normal synaptic function and that a failure in synaptic trafficking or recycling may bean early and important pathologic mechanism in Ctsd mice; these presynaptic abnormalities may initiate synaptic degeneration in advance of subsequent neuronal loss

    Electron cyclotron maser emission mode coupling to the z-mode on a longitudinal density gradient in the context of solar type III bursts

    No full text
    Copyright 2012 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. This article appeared in Physics of Plasmas 19, 110702 (2012) and may be found at .supplemental material at http://astro.qmul.ac.uk/~tsiklauri/sp.htmlsupplemental material at http://astro.qmul.ac.uk/~tsiklauri/sp.htm

    An extracellular steric seeding mechanism for Eph-ephrin signaling platform assembly

    No full text
    Erythropoetin-producing hepatoma (Eph) receptors are cell-surface protein tyrosine kinases mediating cell-cell communication. Upon activation, they form signaling clusters. We report crystal structures of the full ectodomain of human EphA2 (eEphA2) both alone and in complex with the receptor-binding domain of the ligand ephrinA5 (ephrinA5 RBD). Unliganded eEphA2 forms linear arrays of staggered parallel receptors involving two patches of residues conserved across A-class Ephs. eEphA2-ephrinA5 RBD forms a more elaborate assembly, whose interfaces include the same conserved regions on eEphA2, but rearranged to accommodate ephrinA5 RBD. Cell-surface expression of mutant EphA2s showed that these interfaces are critical for localization at cell-cell contacts and activation-dependent degradation. Our results suggest a 'nucleation' mechanism whereby a limited number of ligand-receptor interactions 'seed' an arrangement of receptors which can propagate into extended signaling arrays

    Consumer's welfare and change in stochastic partial-equilibrium price

    No full text
    Welfare Economics;Stochastic Processes

    D-SCIDS: Distributed soft computing intrusion detection system

    No full text
    An Intrusion Deusiony Syste (IDS) is a program thatanalyze whathappeL or has happe.L during aney.F11qy andtrie to find indications thatthe compute has bey misuseq A Distribute IDS (DIDS) consists ofseqEq1 IDS ove alarge negeF (s), all of which communicate with eth othe. or with aceFF.q seFF. thatfacilitate advance neance monitoring. In a distribute estributefi DIDSare imple.L4y; using co-ope./Ey; intepe./E agee distribute acrossthe nessy./FFThispapeepeq4fi1threfuzzyrulebaseclassifieetode.FfiintrusionsinaneqfifiqyReqfifiqarethecomparewithothemachinelehinetenefi4Eylikedeeefitreesupportvepormachineandline/gee/fiprogramming.FurthemwemodeeDistributeSoftComputingbaseIDS(DSCIDS)asacombinationofdiffe/.yclassifie.tomodelightwe;.Eandmoreaccurate(heatey;.E/IDS.Empiricalrericaclecaly..Ethatsoftcomputingapproachcouldplayamajorroleforintrusiondeusiony/FF This pape epeq4fi1 thre fuzzyrule base classifiee tode.Ffi intrusions in aneqfifiqy Reqfifiq are the compare with othe machine lehine tenefi4Ey like deeefi tree supportvepor machine andline/ gee/fi programming.Furthem we modee Distribute SoftComputing-base IDS (D-SCIDS) as a combination ofdiffe/.y classifie. tomode lightwe;.E andmore accurate (heatey;.E/ IDS. Empiricalrerica clecaly..E that soft computing approach could playa majorrole for intrusiondeusiony r 2005Else4/L Ltd. All rightsrehtsy.1 PRES S www.efiyfiye r.com/locate ca 1084-8045/$ -se front matte r 2005Else.41 Ltd. All rightsrehtsyq/ doi:10.1016/j.jnca.2005.06.001 Corre;L.. ing author

    Vascular endothelial growth factor restores delayed tumor progression in tumors depleted of macrophages

    No full text
    Genetic depletion of macrophages in Polyoma Middle T oncoprotein (PyMT)-induced mammary tumors in mice delayed the angiogenic switch and the progression to malignancy. To determine whether vascular endothelial growth factor A (VEGF-A) produced by tumor-associated macrophages regulated the onset of the angiogenic switch, a genetic approach was used to restore expression of VEGF-A into tumors at the benign stages. This stimulated formation of a high-density vessel network and in macrophage-depleted mice, was followed by accelerated tumor progression. The expression of VEGF-A led to a massive infiltration into the tumor of leukocytes that were mostly macrophages. This study suggests that macrophage-produced VEGF regulates malignant progression through stimulating tumor angiogenesis, leukocytic infiltration and tumor cell invasion

    Does exchange rate volatility hinder export growth? Additional evidence

    No full text
    The authors examine the impact of exchange rate volatility on trade, using and ARCH-in-mean model. The advantages of this statistical approach over earlier approaches is that it provides more efficient coefficient estimates and it prevents the problem of spurious regressions. They applied the model to six countries, estimating both bilateral and aggregate exports. The results led to the hypothesis that the impact of exchange rate volatility may be influenced by the invoicing of exports. Also, one can argue that the effect of exchange rate volatility on trade is overstated, for the following reasons: exchange rate volatility does not measure the added riskiness of a firm's portfolio;exchange rates can provide a natural hedge in a firm's portfolio; exchange rates may be negatively correlated with each other or with the firm's other assets; and finally, the use of forward markets can provide a useful short-term hedge.Economic Stabilization,Environmental Economics&Policies,Macroeconomic Management,Fiscal&Monetary Policy,Economic Theory&Research

    High diagnostic yield of tuberculosis from screening urine samples from HIV-infected patients with advanced immunodeficiency using the Xpert MTB/RIF assay.

    No full text
    : ABSTRACT:: We determined the diagnostic yield of the Xpert MTB/RIF assay for tuberculosis (TB) when testing small volumes of urine from ambulatory HIV-infected patients prior to starting antiretroviral therapy (ART) in South Africa. Compared to a gold standard of sputum culture, the sensitivity of urine Xpert among those with CD4 cell counts of <50, 50-100 and >100 cells/?L were 44.4%, 25.0% and 2.7% (P=0.001), respectively. Urine Xpert testing provides a means of rapid TB diagnosis in patients with advanced immunodeficiency and poor prognosis. These data are indicative of high rates of TB dissemination and renal involvement in this clinical population

    Classification of solar wind structures and intense geomagnetic storm alarms with self-organizing maps

    No full text
    Intense geomagnetic storms (D-st <-100nT) usually occur when a large interplanetary duskward-electric field (with Ey > 5 mV m(-1)) lasts for more than 3 h. In this article, a self-organizing map (SOM) neural network is used to recognize different patterns in the temporal variation of hourly averaged Ey data and to predict intense storms. The input parameters of SOM are the hourly averaged Ey data over 3 h. The output layer of the SOM has a total of 400 neurons. The hourly Ey data are calculated from solar wind data, which are provided by NSSDC OMNIWeb and ACE spacecraft and contain information on 143 intense storms and a fair number of moderate storms, weak storms and quiet periods between September 3, 1966 and June 30, 2002. Our results show that SOM is able to classify solar wind structures and therefore to give timely intense storm alarms. In our SOM, 21 neurons out of 400 are identified to be closely associated with the intense storms and they successfully predict 134 intense storms out of the 143 ones selected. In particular, there are 14 neurons for which, if one or more of them are present, the occurrence probability of intense storms is about 90%. In addition, several of these 14 neurons can predict big magnetic storm (D-st <= - 180 nT). In summary, our method achieves high accuracy in predicting intense geomagnetic storms and could be applied in space environment prediction. (c) 2005 COSPAR. Published by Elsevier Ltd. All rights reserved.Engineering, AerospaceAstronomy & AstrophysicsGeosciences, MultidisciplinaryMeteorology & Atmospheric SciencesSCI(E)EI1ARTICLE12,20052372-23773

    Potential leafhopper vectors of phytoplasma in carrots.- International Journal of Tropical Insect Science, 24: 228-235. Authors’ addresses: Bojan DUDUK (corresponding author, [email protected]

    No full text
    Abstract. Phytoplasmas are insect-vectored pathogens that cause characteristic and destructive diseases in carrots and other vegetables. A phytoplasma disease was first observed in Israeli carrot fields in 1995. Analysis of infected carrots showed the presence of aster yellows and western-X phytoplasmas. In this study, commercial and experimental fields in the western Negev region of Israel were monitored for three years using yellow sticky traps and vacuum sampling. Potential vectors of leafhoppers and planthoppers were analysed by PCR for the presence of phytoplasma DNA. Infected plants were also assayed for phytoplasma DNA. Extracted phytoplasma DNA was subjected to RFLP analysis to determine groups to which the phytoplasmas belonged. It was determined that carrots and leafhoppers from the experimental station were infected with a phytoplasma belonging to the Elm Yellows (EY) group; this is the first report of EY infecting carrots. Based on our findings, the two most probable insect vectors are Circulifer haematoceps complex (Mulsant & Rey) and Neoaliturus fenestratus (Herrich-Schäffer). Key words: carrot, phytoplasma, vectors, Circulifer haematoceps, Neoaliturus fenestratus Résumé. Les phytoplasmas sont des pathogènes transmis par des insectes vecteurs, responsables de maladies destructives et caractéristiques sur les carottes et d'autres légumes. Une maladie à phytoplasma a été observée pour la première fois en Israël en 1995 dans des champs de carottes. L'analyse des carottes infectées à révélé la présence des phytoplasmas aster jaunes et western-X. Dans cette étude, des parcelles expérimentales et commerciales situées dans la région Ouest du Negev en Israël ont été suivis pendant 3 ans en utilisant des pièges englués jaunes et des pièges à succion. Les vecteurs potentiels, des cicadelles et les jassides, ont été analysés par PCR afin de contrô ler la présence du DNA de phytoplasma. Les plantes infectées ont également été contrô lées pour le DNA de phytoplasma. Le DNA extrait a été soumis à une analyse par RFLP afin de déterminer le groupe d'appartenance des phytoplasmas. On a ainsi pu déterminer que les carottes et les jassides de la station expérimentale étaient infectés par des phytoplasmas du groupe Elm Yellows (EY); Il s'agit du premier signalement de carottes infectées par des phytoplasmas du groupe EY. Sur la base de nos résultats, le complexe Circulifer haematoceps (Mulsant et Rey) et Neoaliturus fenestratus (Herrich-Schäffer) sont probablement les deux principaux vecteurs
    corecore