288 research outputs found

    Using dense seismo-acoustic network to provide timely warning of the 2019 paroxysmal Stromboli eruptions

    Get PDF
    Stromboli Volcano is well known for its persistent explosive activity. On July 3rd and August 28th 2019, two paroxysmal explosions occurred, generating an eruptive column that quickly rose up to 5 km above sea level. Both events were detected by advanced local monitoring networks operated by Istituto Nazionale di Geofisica e Vulcanologia (INGV) and Laboratorio di Geofisica Sperimentale of the University of Firenze (LGS-UNIFI). Signals were also recorded by the Italian national seismic network at a range of hundreds of kilometres and by infrasonic arrays up to distances of 3700 km. Using state-of-the-art propagation modeling, we identify the various seismic and infrasound phases that are used for precise timing of the eruptions. We highlight the advantage of dense regional seismo-acoustic networks to enhance volcanic signal detection in poorly monitored regions, to provide timely warning of eruptions and reliable source amplitude estimate to Volcanic Ash Advisory Centres (VAAC)

    Non-cytotoxic 1,2,3-triazole tethered fused heterocyclic ring derivatives display Tax protein inhibition and impair HTLV-1 infected cells

    Get PDF
    Human T cell lymphotropic virus type 1 (HTLV-1) is a human retrovirus that infects approximately 10–20 million people worldwide and causes an aggressive neoplasia (adult T-cell leukemia/lymphoma - ATL). Therapeutic approaches for the treatment of ATL have variable effectiveness and poor prognosis, thus requiring strategies to identify novel compounds with activity on infected cells. In this sense, we initially screened a small series of 25 1,2,3-triazole derivatives to discover cell proliferation inhibitors and apoptosis inducers in HTLV-1-infected T-cell line (MT-2) for further assessment of their effect on viral tax activity through inducible-tax reporter cell line (Jurkat LTR-GFP). Eight promising compounds (02, 05, 06, 13, 15, 21, 22 and 25) with activity ≥70% were initially selected, based on a suitable cell-based assay using resazurin reduction method, and evaluated towards cell cycle, apoptosis and Tax/GFP expression analyses through flow cytometry. Compound 02 induced S phase cell cycle arrest and compounds 05, 06, 22 and 25 promoted apoptosis. Remarkably, compounds 22 and 25 also reduced GFP expression in an inducible-tax reporter cell, which suggests an effect on Tax viral protein. More importantly, compounds 02, 22 and 25 were not cytotoxic in human hepatoma cell line (Huh-7). Therefore, the discovery of 3 active and non-cytotoxic compounds against HTLV-1-infected cells can potentially contribute, as an initial promising strategy, to the development process of new drugs against ATL

    Controlling Tungiasis in an Impoverished Community: An Intervention Study

    Get PDF
    Tungiasis is a disease caused by the sand flea Tunga penetrans, a parasite prevalent in many impoverished communities in developing countries. The female sand flea penetrates into the skin of animals and humans where it grows rapidly in size, feeds on the host's blood, produces eggs which are expelled into the environment, and eventually dies in situ. The lesions become frequently superinfected and the infestation is associated with considerable morbidity. Clearly, tungiasis is a neglected disease of neglected populations. We investigated the impact of a package of intervention measures targeted against on-host and off-host stages of T. penetrans in a fishing community in Northeast Brazil. These measures decreased disease occurrence only temporarily, but had a sustained effect on the intensity of the infestation. Since infestation intensity and morbidity are correlated, presumably the intervention also lowered tungiasis-associated morbidity. Control measures similar to the ones used in this study may help to effectively control tungiasis in impoverished communities

    De novo fragment-based design of inhibitors of DXS guided by spin-diffusion-based NMR spectroscopy

    Get PDF
    We applied for the first time an innovative ligand-based NMR methodology (STI) to a medicinal-chemistry project aimed at the development of inhibitors for the enzyme 1-deoxy-D-xylulose-5-phosphate synthase (DXS). DXS is the first enzyme of the 2C-methyl-D-erythritol-4-phosphate (MEP) pathway, present in most bacteria (and not in humans) and responsible for the synthesis of the essential isoprenoid precursors. We designed de novo a first generation of fragments, using Deinococcus radiodurans DXS as a model enzyme, targeting the thiamine diphosphate (TDP) pocket of DXS whilst also exploring the putative substrate-binding pocket, where selectivity over other human TDP-dependent enzymes could be gained. The STI methodology – suitable for weak binders – was essential to determine the binding mode in solution of one of the fragments, circumventing the requirement for an X-ray co-crystal structure, which is known to be particularly challenging for this specific enzyme and in general for weak binders. Based on this finding, we carried out fragment growing and optimisation, which led to a three-fold more potent fragment, about as potent as the well-established thiamine analogue deazathiamine. The STI methodology proved therefore its strong potential as a tool to support medicinal-chemistry projects in their early stages, especially when dealing with weak binders

    EXPERIMENT OPERATIONS PLAN FOR A LOSS-OF-COOLANT ACCIDENT SIMULATION IN THE NATIONAL RESEARCH UNIVERSAL REACTOR

    Get PDF
    Pressurized water reactor loss-of-coolant accident phenomena are being simulated with a series of experiments in the U-2 loop of the National Research Universal Reactor at Chalk River, Ontario, Canada. The first of these experiments includes up to 45 parametric thermal-hydraulic tests to establish the relationship between the reflood delay time of emergency coolant, the reflooding rate, and the resultant fuel rod cladding peak temperature. This document contains both experiment proposal and assembly proposal information. The intent of this document is to supply information required by the Chalk River Nuclear Laboratories (CRNL), and to identify the planned procedures and data that will be used both to establish readiness to proceed from one test phase to the next and to operate the experiment. Operating control settings and limits are provided for both experimenter systems and CRNL systems. A hazards review summarizes safety issues that have been addressed during the development of the experiment plan

    A multi-technology analysis of the 2017 North Korean nuclear test

    Get PDF
    On 3 September 2017 official channels of the Democratic People's Republic of Korea announced the successful test of a thermonuclear device. Only seconds to minutes after the alleged nuclear explosion at the Punggye-ri nuclear test site in the mountainous region in the country's northeast at 03:30:02 (UTC), hundreds of seismic stations distributed all around the globe picked up strong and distinct signals associated with an explosion. Different seismological agencies reported body wave magnitudes of well above 6.0, consequently estimating the explosive yield of the device on the order of hundreds of kT TNT equivalent. The 2017 event can therefore be assessed as being multiple times larger in energy than the two preceding North Korean events in January and September 2016. This study provides a multi-technology analysis of the 2017 North Korean event and its aftermath using a wide array of geophysical methods. Seismological investigations locate the event within the test site at a depth of approximately 0.6&thinsp;km below the surface. The radiation and generation of P- and S-wave energy in the source region are significantly influenced by the topography of the Mt. Mantap massif. Inversions for the full moment tensor of the main event reveal a dominant isotropic component accompanied by significant amounts of double couple and compensated linear vector dipole terms, confirming the explosive character of the event. The analysis of the source mechanism of an aftershock that occurred around 8&thinsp;min after the test in the direct vicinity suggest a cavity collapse. Measurements at seismic stations of the International Monitoring System result in a body wave magnitude of 6.2, which translates to an yield estimate of around 400&thinsp;kT TNT equivalent. The explosive yield is possibly overestimated, since topography and depth phases both tend to enhance the peak amplitudes of teleseismic P waves. Interferometric synthetic aperture radar analysis using data from the ALOS-2 satellite reveal strong surface deformations in the epicenter region. Additional multispectral optical data from the Pleiades satellite show clear landslide activity at the test site. The strong surface deformations generated large acoustic pressure peaks, which were observed as infrasound signals with distinctive waveforms even at distances of 401&thinsp;km. In the aftermath of the 2017 event, atmospheric traces of the fission product 133Xe were detected at various locations in the wider region. While for 133Xe measurements in September 2017, the Punggye-ri test site is disfavored as a source by means of atmospheric transport modeling, detections in October 2017 at the International Monitoring System station RN58 in Russia indicate a potential delayed leakage of 133Xe at the test site from the 2017 North Korean nuclear test.</p
    corecore