ε/ζ systems: their role in resistance, virulence, and their potential for antibiotic development

Cell death in bacteria can be triggered by activation of self-inflicted molecular mechanisms. Pathogenic bacteria often make use of suicide mechanisms in which the death of individual cells benefits survival of the population. Important elements for programmed cell death in bacteria are proteinaceous toxin–antitoxin systems. While the toxin generally resides dormant in the bacterial cytosol in complex with its antitoxin, conditions such as impaired de novo synthesis of the antitoxin or nutritional stress lead to antitoxin degradation and toxin activation. A widespread toxin–antitoxin family consists of the ε/ζ systems, which are distributed over plasmids and chromosomes of various pathogenic bacteria. In its inactive state, the bacteriotoxic ζ toxin protein is inhibited by its cognate antitoxin ε. Upon degradation of ε, the ζ toxin is released allowing this enzyme to poison bacterial cell wall synthesis, which eventually triggers autolysis. ε/ζ systems ensure stable plasmid inheritance by inducing death in plasmid-deprived offspring cells. In contrast, chromosomally encoded ε/ζ systems were reported to contribute to virulence of pathogenic bacteria, possibly by inducing autolysis in individual cells under stressful conditions. The capability of toxin–antitoxin systems to kill bacteria has made them potential targets for new therapeutic compounds. Toxin activation could be hijacked to induce suicide of bacteria. Likewise, the unique mechanism of ζ toxins could serve as template for new drugs. Contrarily, inhibition of virulence-associated ζ toxins might attenuate infections. Here we provide an overview of ε/ζ toxin–antitoxin family and its potential role in the development of new therapeutic approaches in microbial defense

The labor market effects of technology shocks

We analyze the effects of neutral and investment-specific technology shocks on hours worked and unemployment. We characterize the response of unemployment in terms of job separation and job finding rates. We find that job separation rates mainly account for the impact response of unemployment while job finding rates for movements along its adjustment path. Neutral shocks increase unemployment and explain a substantial portion of unemployment and output volatilityinvestment-specific shocks expand employment and hours worked and mostly contribute to hours worked volatility. We show that this evidence is consistent with the view that neutral technological progress prompts Schumpeterian creative destruction, while investment specific technological progress has standard neoclassical feature

The Eighteenth Data Release of the Sloan Digital Sky Surveys: Targeting and First Spectra from SDSS-V

The eighteenth data release of the Sloan Digital Sky Surveys (SDSS) is the first one for SDSS-V, the fifth generation of the survey. SDSS-V comprises three primary scientific programs, or "Mappers": Milky Way Mapper (MWM), Black Hole Mapper (BHM), and Local Volume Mapper (LVM). This data release contains extensive targeting information for the two multi-object spectroscopy programs (MWM and BHM), including input catalogs and selection functions for their numerous scientific objectives. We describe the production of the targeting databases and their calibration- and scientifically-focused components. DR18 also includes ~25,000 new SDSS spectra and supplemental information for X-ray sources identified by eROSITA in its eFEDS field. We present updates to some of the SDSS software pipelines and preview changes anticipated for DR19. We also describe three value-added catalogs (VACs) based on SDSS-IV data that have been published since DR17, and one VAC based on the SDSS-V data in the eFEDS field.Comment: Accepted to ApJ

The eighteenth data release of the Sloan Digital Sky Surveys : targeting and first spectra from SDSS-V

The eighteenth data release of the Sloan Digital Sky Surveys (SDSS) is the first one for SDSS-V, the fifth generation of the survey. SDSS-V comprises three primary scientific programs, or "Mappers": Milky Way Mapper (MWM), Black Hole Mapper (BHM), and Local Volume Mapper (LVM). This data release contains extensive targeting information for the two multi-object spectroscopy programs (MWM and BHM), including input catalogs and selection functions for their numerous scientific objectives. We describe the production of the targeting databases and their calibration- and scientifically-focused components. DR18 also includes ~25,000 new SDSS spectra and supplemental information for X-ray sources identified by eROSITA in its eFEDS field. We present updates to some of the SDSS software pipelines and preview changes anticipated for DR19. We also describe three value-added catalogs (VACs) based on SDSS-IV data that have been published since DR17, and one VAC based on the SDSS-V data in the eFEDS field.Publisher PDFPeer reviewe

The KM3NeT potential for the next core-collapse supernova observation with neutrinos

The authors acknowledge the financial support of the funding agencies: Agence Nationale de la Recherche (contract ANR-15-CE31-0020), Centre National de la Recherche Scientifique (CNRS), Commission Europeenne (FEDER fund and Marie Curie Program), Institut Universitaire de France (IUF), LabEx UnivEarthS (ANR-10-LABX-0023 and ANR-18-IDEX-0001), Paris Ile-de-France Region, France; Shota Rustaveli National Science Foundation of Georgia (SRNSFG, FR-18-1268), Georgia; Deutsche Forschungsgemeinschaft (DFG), Germany; The General Secretariat of Research and Technology (GSRT), Greece; Istituto Nazionale di Fisica Nucleare (INFN), Ministero dell'Universita e della Ricerca (MIUR), PRIN 2017 program (Grant NAT-NET 2017W4HA7S) Italy; Ministry of Higher Education Scientific Research and Professional Training, ICTP through Grant AF-13, Morocco; Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), the Netherlands; The National Science Centre, Poland (2015/18/E/ST2/00758); National Authority for Scientific Research (ANCS), Romania; Ministerio de Ciencia, Innovacion, Investigacion y Universidades (MCIU): Programa Estatal de Generacion de Conocimiento (refs. PGC2018-096663-B-C41, -A-C42, -B-C43, -B-C44) (MCIU/FEDER), Severo Ochoa Centre of Excellence and MultiDark Consolider (MCIU), Junta de Andalucia (ref. SOMM17/6104/UGR), Generalitat Valenciana: Grisolia (ref. GRISO-LIA/2018/119) and GenT (ref. CIDEGENT/2018/034 and CIDE-GENT/2019/043) programs, La Caixa Foundation (ref. LCF/BQ/IN17/11620019), EU: MSC program (ref. 713673), Spain. This work has also received funding from the European Union'sHorizon 2020 research and innovation program under Grant agreement no 739560.The KM3NeT research infrastructure is under construction in the Mediterranean Sea. It consists of two water Cherenkov neutrino detectors, ARCA and ORCA, aimed at neutrino astrophysics and oscillation research, respectively. Instrumenting a large volume of sea water with similar to 6200 optical modules comprising a total of similar to 200,000 photomultiplier tubes, KM3NeT will achieve sensitivity to similar to 10 MeV neutrinos from Galactic and near-Galactic core-collapse supernovae through the observation of coincident hits in photomultipliers above the background. In this paper, the sensitivity of KM3NeT to a supernova explosion is estimated from detailed analyses of background data from the first KM3NeT detection units and simulations of the neutrino signal. The KM3NeT observational horizon (for a 5 sigma discovery) covers essentially the Milky-Way and for the most optimistic model, extends to the Small Magellanic Cloud (similar to 60 kpc). Detailed studies of the time profile of the neutrino signal allow assessment of the KM3NeT capability to determine the arrival time of the neutrino burst with a few milliseconds precision for sources up to 5-8 kpc away, and detecting the peculiar signature of the standing accretion shock instability if the core-collapse supernova explosion happens closer than 3-5 kpc, depending on the progenitor mass. KM3NeT's capability to measure the neutrino flux spectral parameters is also presented.French National Research Agency (ANR) ANR-15-CE31-0020Centre National de la Recherche Scientifique (CNRS)Commission Europeenne, FranceInstitut Universitaire de France (IUF), FranceLabEx UnivEarthS, France ANR-10-LABX-0023 ANR-18-IDEX-0001Paris Ile-de-France Region, FranceShota Rustaveli National Science Foundation of Georgia (SRNSFG), Georgia FR-18-1268German Research Foundation (DFG)Greek Ministry of Development-GSRTGreek Ministry of Development-GSRTIstituto Nazionale di Fisica Nucleare (INFN)Ministry of Education, Universities and Research (MIUR)PRIN 2017 program, Italy NAT-NET 2017W4HA7SMinistry of Higher Education Scientific Research and Professional Training, ICTP, Morocco AF-13Netherlands Organization for Scientific Research (NWO)Netherlands GovernmentNational Science Centre, Poland 2015/18/E/ST2/00758National Authority for Scientific Research (ANCS), RomaniaMinisterio de Ciencia, Innovacion, Investigacion y Universidades (MCIU): Programa Estatal de Generacion de Conocimiento, Spain PGC2018-096663-B-C41 PGC2018-096663-A-C42 PGC2018-096663-B-C43 PGC2018-096663-B-C44Severo Ochoa Centre of Excellence and MultiDark Consolider (MCIU), SpainJunta de Andalucia European Commission SOMM17/6104/UGRGeneralitat Valenciana: Grisolia, Spain GRISO-LIA/2018/119 GenT program, Spain CIDEGENT/2018/034 CIDE-GENT/2019/043La Caixa Foundation LCF/BQ/IN17/11620019 EU: MSC program, Spain 713673European Commission 73956

Deep-sea deployment of the KM3NeT neutrino telescope detection units by self-unrolling

KM3NeT is a research infrastructure being installed in the deep Mediterranean Sea. It will house a neutrino telescope comprising hundreds of networked moorings — detection units or strings — equipped with optical instrumentation to detect the Cherenkov radiation generated by charged particles from neutrino-induced collisions in its vicinity. In comparison to moorings typically used for oceanography, several key features of the KM3NeT string are different: the instrumentation is contained in transparent and thus unprotected glass spheres; two thin Dyneema® ropes are used as strength members; and a thin delicate backbone tube with fibre-optics and copper wires for data and power transmission, respectively, runs along the full length of the mooring. Also, compared to other neutrino telescopes such as ANTARES in the Mediterranean Sea and GVD in Lake Baikal, the KM3NeT strings are more slender to minimise the amount of material used for support of the optical sensors. Moreover, the rate of deploying a large number of strings in a period of a few years is unprecedented. For all these reasons, for the installation of the KM3NeT strings, a custom-made, fast deployment method was designed. Despite the length of several hundreds of metres, the slim design of the string allows it to be compacted into a small, re-usable spherical launching vehicle instead of deploying the mooring weight down from a surface vessel. After being lowered to the seafloor, the string unfurls to its full length with the buoyant launching vehicle rolling along the two ropes. The design of the vehicle, the loading with a string, and its underwater self-unrolling are detailed in this paper.French National Research Agency (ANR) ANR-15-CE31-0020Centre National de la Recherche Scientifique (CNRS)European Union (EU)Institut Universitaire de France (IUF)LabEx UnivEarthS ANR-10-LABX-0023 ANR-18-IDEX-0001Paris Ile-de-France Region, FranceShota Rustaveli National Science Foundation of Georgia (SRNSFG), Georgia FR-18-1268German Research Foundation (DFG)Greek Ministry of Development-GSRTIstituto Nazionale di Fisica Nucleare (INFN), Ministero dell'Universita e della Ricerca (MUR), PRIN Italy NAT-NET 2017W4HA7SMinistry of Higher Education, Scientific Research and Professional Training, MoroccoNetherlands Organization for Scientific Research (NWO) Netherlands GovernmentNational Science Center, Poland National Science Centre, Poland 2015/18/E/ST2/00758National Authority for Scientific Research (ANCS), RomaniaMinisterio de Ciencia, Innovación, Investigación y Universidades (MCIU): Programa Estatal de Generación de Conocimiento (MCIU/FEDER) PGC2018-096663-B-C41 PGC2018-096663-B-A-C42 PGC2018-096663-B-BC43 PGC2018-096663-B-B-C44Severo Ochoa Centre of Excellence and MultiDark Consolider (MCIU), Junta de Andalucía SOMM17/6104/UGRGeneralitat Valenciana GRISOLIA/2018/119 CIDEGENT/2018/034La Caixa Foundation LCF/BQ/IN17/11620019EU: MSC program, Spain 71367

The Control Unit of the KM3NeT Data Acquisition System

The KM3NeT Collaboration runs a multi-site neutrino observatory in the Mediterranean Sea. Water Cherenkov particle detectors, deep in the sea and far off the coasts of France and Italy, are already taking data while incremental construction progresses. Data Acquisition Control software is operating off-shore detectors as well as testing and qualification stations for their components. The software, named Control Unit, is highly modular. It can undergo upgrades and reconfiguration with the acquisition running. Interplay with the central database of the Collaboration is obtained in a way that allows for data taking even if Internet links fail. In order to simplify the management of computing resources in the long term, and to cope with possible hardware failures of one or more computers, the KM3NeT Control Unit software features a custom dynamic resource provisioning and failover technology, which is especially important for ensuring continuity in case of rare transient events in multi-messenger astronomy. The software architecture relies on ubiquitous tools and broadly adopted technologies and has been successfully tested on several operating systems

Characterisation of the Hamamatsu photomultipliers for the KM3NeT Neutrino Telescope

[EN] The Hamamatsu R12199-02 3-inch photomultiplier tube is the photodetector chosen for the first phase of the KM3NeT neutrino telescope. About 7000 photomultipliers have been characterised for dark count rate, timing spread and spurious pulses. The quantum eÿciency, the gain and the peak-to-valley ratio have also been measured for a sub-sample in order to determine parameter values needed as input to numerical simulations of the detector.The authors acknowledge the financial support of the funding agencies: Agence Nationale de la Recherche (contract ANR-15-CE31-0020), Centre National de la Recherche Scientifique (CNRS), Commission Europeenne (FEDER fund and Marie Curie Program), Institut Universitaire de France (IUF), IdEx program and UnivEarthS Labex program at Sorbonne Paris Cite (ANR-10-LABX-0023 and ANR-11-IDEX-0005-02), France; 'Helmholtz Alliance for Astroparticle Physics' funded by the Initiative and Networking Fund of the Helmholtz Association, Germany; The General Secretariat of Research and Technology (GSRT), Greece; Istituto Nazionale di Fisica Nucleare (INFN), Ministero dell'Istruzione, dell'Universita e della Ricerca (MIUR), Italy; Agence de l'Oriental and CNRST, Morocco; Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), the Netherlands; National Authority for Scientific Research (ANCS), Romania; Plan Estatal de Investigacion (refs. FPA2015-65150-C3-1-P, -2-P and -3-P, (MINECO/FEDER)), Severo Ochoa Centre of Excellence and MultiDark Consolider (MINECO), and Prometeo and Grisolia programs (Generalitat Valenciana), Spain.Aiello, S.; Akrame, SE.; Ameli, F.; Anassontzis, EG.; Andre, M.; Androulakis, G.; Anghinolfi, M.... (2018). Characterisation of the Hamamatsu photomultipliers for the KM3NeT Neutrino Telescope. Journal of Instrumentation. 13:1-17. https://doi.org/10.1088/1748-0221/13/05/P05035S11713Adrián-Martínez, S., Ageron, M., Aharonian, F., Aiello, S., Albert, A., Ameli, F., … Anghinolfi, M. (2016). Letter of intent for KM3NeT 2.0. Journal of Physics G: Nuclear and Particle Physics, 43(8), 084001. doi:10.1088/0954-3899/43/8/084001Adrián-Martínez, S., Ageron, M., Aharonian, F., Aiello, S., Albert, A., Ameli, F., … Anvar, S. (2014). Deep sea tests of a prototype of the KM3NeT digital optical module. The European Physical Journal C, 74(9). doi:10.1140/epjc/s10052-014-3056-3Adrián-Martínez, S., Ageron, M., Aharonian, F., Aiello, S., Albert, A., Ameli, F., … Anton, G. (2016). The prototype detection unit of the KM3NeT detector. The European Physical Journal C, 76(2). doi:10.1140/epjc/s10052-015-3868-9Herold, B., Kalekin, O., & Reubelt, J. (2011). PMT characterisation for the KM3NeT project. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 639(1), 70-72. doi:10.1016/j.nima.2010.09.018Timmer, P., Heine, E., & Peek, H. (2010). Very low power, high voltage base for a Photo Multiplier Tube for the KM3NeT deep sea neutrino telescope. Journal of Instrumentation, 5(12), C12049-C12049. doi:10.1088/1748-0221/5/12/c12049Mollo, C. M., Bozza, C., Chiarusi, T., Costa, M., Capua, F. D., Kulikovskiy, V., … Vivolo, D. (2016). A new instrument for high statistics measurement of photomultiplier characteristics. Journal of Instrumentation, 11(08), T08002-T08002. doi:10.1088/1748-0221/11/08/t08002Adrián-Martínez, S., Ageron, M., Aiello, S., Albert, A., Ameli, F., Anassontzis, E. G., … Anton, G. (2016). A method to stabilise the performance of negatively fed KM3NeT photomultipliers. Journal of Instrumentation, 11(12), P12014-P12014. doi:10.1088/1748-0221/11/12/p12014Lubsandorzhiev, B. K., Vasiliev, R. V., Vyatchin, Y. E., & Shaibonov, B. A. J. (2006). Photoelectron backscattering in vacuum phototubes. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 567(1), 12-16. doi:10.1016/j.nima.2006.05.04

Deep sea tests of a prototype of the KM3NeT digital optical module

The first prototype of a photo-detection unit of the future KM3NeT neutrino telescope has been deployed in the deepwaters of the Mediterranean Sea. This digital optical module has a novel design with a very large photocathode area segmented by the use of 31 three inch photomultiplier tubes. It has been integrated in the ANTARES detector for in-situ testing and validation. This paper reports on the first months of data taking and rate measurements. The analysis results highlight the capabilities of the new module design in terms of background suppression and signal recognition. The directionality of the optical module enables the recognition of multiple Cherenkov photons from the same (40)Kdecay and the localisation of bioluminescent activity in the neighbourhood. The single unit can cleanly identify atmospheric muons and provide sensitivity to the muon arrival directions

Letter of intent for KM3NeT 2.0

The main objectives of the KM3NeT Collaboration are ( i ) the discovery and subsequent observation of high-energy neutrino sources in the Universe and ( ii ) the determination of the mass hierarchy of neutrinos. These objectives are strongly motivated by two recent important discoveries, namely: ( 1 ) the high- energy astrophysical neutrino signal reported by IceCube and ( 2 ) the sizable contribution of electron neutrinos to the third neutrino mass eigenstate as reported by Daya Bay, Reno and others. To meet these objectives, the KM3NeT Collaboration plans to build a new Research Infrastructure con- sisting of a network of deep-sea neutrino telescopes in the Mediterranean Sea. A phased and distributed implementation is pursued which maximises the access to regional funds, the availability of human resources and the syner- gistic opportunities for the Earth and sea sciences community. Three suitable deep-sea sites are selected, namely off-shore Toulon ( France ) , Capo Passero ( Sicily, Italy ) and Pylos ( Peloponnese, Greece ) . The infrastructure will consist of three so-called building blocks. A building block comprises 115 strings, each string comprises 18 optical modules and each optical module comprises 31 photo-multiplier tubes. Each building block thus constitutes a three- dimensional array of photo sensors that can be used to detect the Cherenkov light produced by relativistic particles emerging from neutrino interactions. Two building blocks will be sparsely con fi gured to fully explore the IceCube signal with similar instrumented volume, different methodology, improved resolution and complementary fi eld of view, including the galactic plane. One building block will be densely con fi gured to precisely measure atmospheric neutrino oscillations. Original content from this work may be used under the ter