Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Search for a new gauge boson in pi(0) decays

A search was made for a new light gauge boson X which might be produced in pi(0) -->, gamma + X decay from neutral pions generated by 450 GeV protons in the CERN SPS neutrino target. The X's would penetrate the downstream shielding and be observed in the NOMAD detector via the Primakoff effect, in the process of X --> pi(0) conversion in the external Coulomb field of a nucleus. With 1.45 x 10(18) protons on target, 20 candidate events with energy between 8 and 140 GeV were found from the analysis of neutrino data. This number is in agreement with the expectation of 18.1 +/- 2.8 background events from standard neutrino processes. A new 90% C.L. upper limit on the branching ratio Br(pi(0) --> Y + X)< (3.3 to 1.9)X 10(-5) for X masses ranging from 0 to 120 MeV/c(2) is obtained

Is bioelectrical impedance accurate for use in large epidemiological studies?

Percentage of body fat is strongly associated with the risk of several chronic diseases but its accurate measurement is difficult. Bioelectrical impedance analysis (BIA) is a relatively simple, quick and non-invasive technique, to measure body composition. It measures body fat accurately in controlled clinical conditions but its performance in the field is inconsistent. In large epidemiologic studies simpler surrogate techniques such as body mass index (BMI), waist circumference, and waist-hip ratio are frequently used instead of BIA to measure body fatness. We reviewed the rationale, theory, and technique of recently developed systems such as foot (or hand)-to-foot BIA measurement, and the elements that could influence its results in large epidemiologic studies. BIA results are influenced by factors such as the environment, ethnicity, phase of menstrual cycle, and underlying medical conditions. We concluded that BIA measurements validated for specific ethnic groups, populations and conditions can accurately measure body fat in those populations, but not others and suggest that for large epdiemiological studies with diverse populations BIA may not be the appropriate choice for body composition measurement unless specific calibration equations are developed for different groups participating in the study

TSPO ligand residence time influences human glioblastoma multiforme cell death/life balance

Abstract Ligands addressed to the mitochondrial Translocator Protein (TSPO) have been suggested as cell death/life and steroidogenesis modulators. Thus, TSPO ligands have been proposed as drug candidates in several diseases; nevertheless, a correlation between their binding affinity and in vitro efficacy has not been demonstrated yet, questioning the specificity of the observed effects. Since drug-target residence time is an emerging parameter able to influence drug pharmacological features, herein, the interaction between TSPO and irDE-MPIGA, a covalent TSPO ligand, was investigated in order to explore TSPO control on death/life processes in a standardized glioblastoma cell setting. After 90 min irDE-MPIGA cell treatment, 25 nM ligand concentration saturated irreversibly all TSPO binding sites; after 24 h, TSPO de-novo synthesis occurred and about 40 % TSPO binding sites resulted covalently bound to irDE-MPIGA. During cell culture treatments, several dynamic events were observed: (a) early apoptotic markers appeared, such as mitochondrial membrane potential collapse (at 3 h) and externalization of phosphatidylserine (at 6 h); (b) cell viability was reduced (at 6 h), without cell cycle arrest. After digitonin-permeabilized cell suspension treatment, a modulation of mitochondrial permeability transition pore was evidenced. Similar effects were elicited by the reversible TSPO ligand PIGA only when applied at micromolar dose. Interestingly, after 6 h, irDE-MPIGA cell exposure restored cell survival parameters. These results highlighted the ligand-target residence time and the cellular setting are crucial parameters that should be taken into account to understand the drug binding affinity and efficacy correlation and, above all, to translate efficiently cellular drug responses from bench to bedside

Variants in the <em>DDX6-CXCR5</em> autoimmune disease risk locus influence the regulatory network in immune cells and salivary gland

\ua9 2025 The Author(s). Objectives: Sj\uf6gren\u27s disease (SjD) and systemic lupus erythematosus (SLE) share genetic risk at the DDX6-CXCR5 locus (11q23.3). Identifying and functionally characterising shared SNPs spanning this locus can provide new insights into common genetic mechanisms of autoimmunity. Methods: Transdisease meta-analyses, fine-mapping, and bioinformatic analyses prioritised shared likely functional single nucleotide polymorphisms (SNPs) for allele-specific and cell type–specific functional interrogation using electromobility shift, luciferase reporter, and quantitative chromatin conformation capture assays and clustered regularly interspaced short palindromic repeat (CRISPR) gene regulation. Results: Five shared SNPs were identified as likely functional in primary human immune cells, salivary gland and kidney tissues: rs57494551, rs4936443, rs4938572, rs7117261, and rs4938573. All 5 SNPs exhibited cell type-specific and allele-specific effects on nuclear protein binding affinity and enhancer/promoter regulatory activity in immune, salivary gland epithelial, and kidney epithelial cell models. Mapping of chromatin–chromatin interactions revealed a chromatin regulatory network that expanded beyond DDX6 and CXCR5 to include PHLDB1, lnc-PHLDB1-1, BCL9L, TRAPPC4, among others. Coalescence of functional assays and multiomic data analyses indicated that these SNPs likely modulate the activity of 3 regulatory regions: intronic rs57494551 regulatory region, intergenic SNP haplotype (rs4938572, rs4936443, and rs7117261) regulatory region, and rs4938573 regulatory region upstream of the CXCR5 promoter. Conclusions: Shared genetic susceptibly at the DDX6-CXCR5 locus in SjD and SLE likely alters common mechanisms of autoimmunity, including interferon signalling (DDX6), autophagy (TRAPPC4), and lymphocytic infiltration of disease-target tissues (CXCR5). Further, using multiomic data from patients with SjD, combined with bioinformatic and in vitro functional studies, can provide mechanistic insights into how genetic risk influences the biological pathways that drive complex autoimmunity

Search for relativistic magnetic monopoles with five years of the ANTARES detector data

[EN] A search for magnetic monopoles using five years of data recorded with the ANTARES neutrino telescope from January 2008 to December 2012 with a total live time of 1121 days is presented. The analysis is carried out in the range b>0.6 of magnetic monopole velocities using a strategy based on run-by-run Monte Carlo simulations. No signal above the background expectation from atmospheric muons and atmospheric neutrinos is observed, and upper limits are set on the magnetic monopole flux ranging from 5.7x10-16 to 1.5x10-18 cm-2 . s-1.sr-1.The authors acknowledge the financial support of the funding agencies: Centre National de la Recherche Scientifique (CNRS), Commissariat a l'energie atomique et aux energies alternatives (CEA), 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), Labex OCEVU (ANR-11-LABX-0060) and the A*MIDEX project (ANR-11-IDEX-0001-02), Region Ile-de-France (DIM-ACAV), Region Alsace (contrat CPER), Region Provence-Alpes-Cote d'Azur, Departement du Var and Ville de La Seyne-sur-Mer, France; Bundesministerium fur Bildung und Forschung (BMBF), Germany; Istituto Nazionale di Fisica Nucleare (INFN), Italy; Stichting voor Fundamenteel Onderzoek der Materie (FOM), Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), the Netherlands; Council of the President of the Russian Federation for young scientists and leading scientific schools supporting grants, Russia; National Authority for Scientific Research (ANCS), Romania; Ministerio de Economia y Competitividad (MINECO): 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; Ministry of Higher Education, Scientific Research and Professional Training, Morocco. We also acknowledge the technical support of Ifremer, AIM and Foselev Marine for the sea operation and the CC-IN2P3 for the computing facilitiesAlbert, A.; Andre, M.; Anghinolfi, M.; Anton, G.; Ardid Ramírez, M.; Aubert, J.; Avgitas, T.... (2017). Search for relativistic magnetic monopoles with five years of the ANTARES detector data. Journal of High Energy Physics (Online). (7):1-16. https://doi.org/10.1007/JHEP07(2017)054S1167P.A.M. Dirac, Quantized Singularities in the Electromagnetic Field, Proc. Roy. Soc. Lond. A 133 (1931) 60 [ INSPIRE ].G. ’t Hooft, Magnetic Monopoles in Unified Gauge Theories, Nucl. Phys. B 79 (1974) 276 [ INSPIRE ].A.M. Polyakov, Particle Spectrum in the Quantum Field Theory, JETP Lett. 20 (1974) 194 [ INSPIRE ].G. Lazarides, C. Panagiotakopoulos and Q. Shafi, Magnetic Monopoles From Superstring Models, Phys. Rev. Lett. 58 (1987) 1707 [ INSPIRE ].Y.M. Cho and D. Maison, Monopoles in Weinberg-Salam model, Phys. Lett. B 391 (1997) 360 [ hep-th/9601028 ] [INSPIRE].Particle Data Group collaboration, C. Patrignani et al., Review of Particle Physics, Chin. Phys. C 40 (2016) 100001 [ INSPIRE ].L. Patrizii and M. Spurio, Status of Searches for Magnetic Monopoles, Ann. Rev. Nucl. Part. Sci. 65 (2015) 279 [ arXiv:1510.07125 ] [INSPIRE].ATLAS collaboration, Search for magnetic monopoles and stable particles with high electric charges in 8 TeV pp collisions with the ATLAS detector, Phys. Rev. D 93 (2016) 052009 [ arXiv:1509.08059 ] [ INSPIRE ].MoEDAL collaboration, B. Acharya et al., Search for magnetic monopoles with the MoEDAL prototype trapping detector in 8 TeV proton-proton collisions at the LHC, JHEP 08 (2016) 067 [ arXiv:1604.06645 ] [INSPIRE].MoEDAL collaboration, B. Acharya et al., Search for Magnetic Monopoles with the MoEDAL Forward Trapping Detector in 13 TeV Proton-Proton Collisions at the LHC, Phys. Rev. Lett. 118 (2017) 061801 [ arXiv:1611.06817 ] [INSPIRE].T.W.B. Kibble, Topology of Cosmic Domains and Strings, J. Phys. A 9 (1976) 1387 [ INSPIRE ].J. Preskill, Cosmological Production of Superheavy Magnetic Monopoles, Phys. Rev. Lett. 43 (1979) 1365 [ INSPIRE ].A.H. Guth, The Inflationary Universe: A Possible Solution to the Horizon and Flatness Problems, Phys. Rev. D 23 (1981) 347 [ INSPIRE ].D. Ryu, H. Kang and P.L. Biermann, Cosmic magnetic fields in large scale filaments and sheets, Astron. Astrophys. 335 (1998) 19 [ astro-ph/9803275 ] [ INSPIRE ].E.N. Parker, The Origin of Magnetic Fields, Astrophys. J 160 (1970) 383.ANTARES collaboration, M. Ageron et al., ANTARES: the first undersea neutrino telescope, Nucl. Instrum. Meth. A 656 (2011) 11 [ arXiv:1104.1607 ] [INSPIRE].ANTARES collaboration, S. Adrian-Martinez et al., Search for Relativistic Magnetic Monopoles with the ANTARES Neutrino Telescope, Astropart. Phys. 35 (2012) 634 [ arXiv:1110.2656 ] [ INSPIRE ].IceCube collaboration, M.G. Aartsen et al., Searches for Relativistic Magnetic Monopoles in IceCube, Eur. Phys. J. C 76 (2016) 133 [ arXiv:1511.01350 ] [INSPIRE].ANTARES collaboration, J.A. Aguilar et al., The data acquisition system for the ANTARES Neutrino Telescope, Nucl. Instrum. Meth. A 570 (2007) 107 [ astro-ph/0610029 ] [INSPIRE].D.R. Tompkins, Total energy loss and Čerenkov emission from monopoles, Phys. Rev. 138 (1965) B248.Y. Kazama, C.N. Yang and A.S. Goldhaber, Scattering of a Dirac Particle with Charge Ze by a Fixed Magnetic Monopole, Phys. Rev. D 15 (1977) 2287 [ INSPIRE ].S.P. Ahlen, Monopole Track Characteristics in Plastic Detectors, Phys. Rev. D 14 (1976) 2935 [ INSPIRE ].S.P. Ahlen, Stopping Power Formula for Magnetic Monopoles, Phys. Rev. D 17 (1978) 229 [ INSPIRE ].J. Derkaoui et al., Energy losses of magnetic monopoles and of dyons in the earth, Astropart. Phys. 9 (1998) 173 [ INSPIRE ].CERN Application Software Group, GEANT 3.21 Detector Description and Simulation Tool, CERN Program Library Long Writeup W5013 (1993).G. Carminati, A. Margiotta and M. Spurio, Atmospheric MUons from PArametric formulas: A fast GEnerator for neutrino telescopes (MUPAGE), Comput. Phys. Commun. 179 (2008) 915 [ arXiv:0802.0562 ] [INSPIRE].Y. Becherini, A. Margiotta, M. Sioli and M. Spurio, A parameterisation of single and multiple muons in the deep water or ice, Astropart. Phys. 25 (2006) 1 [ hep-ph/0507228 ] [INSPIRE].J. Brunner, ANTARES simulation tools, in proceedings of The VLVnT workshop, Amsterdam (2003), http://www.vlvnt.nl/proceedings.pdf .ANTARES collaboration, A. Margiotta, Common simulation tools for large volume neutrino detectors, Nucl. Instrum. Meth. A 725 (2013) 98 [ INSPIRE ].V. Agrawal, T.K. Gaisser, P. Lipari and T. Stanev, Atmospheric neutrino flux above 1-GeV, Phys. Rev. D 53 (1996) 1314 [ hep-ph/9509423 ] [INSPIRE].G.D. Barr, T.K. Gaisser, S. Robbins and T. Stanev, Uncertainties in Atmospheric Neutrino Fluxes, Phys. Rev. D 74 (2006) 094009 [ astro-ph/0611266 ] [INSPIRE].L. Fusco and A. Margiotta, The Run-by-Run Monte Carlo simulation for the ANTARES experiment, EPJ Web Conf. 116 (2016) 02002.ANTARES collaboration, J.A. Aguilar et al., A fast algorithm for muon track reconstruction and its application to the ANTARES neutrino telescope, Astropart. Phys. 34 (2011) 652 [ arXiv:1105.4116 ] [INSPIRE].ANTARES collaboration, S. Adrian-Martinez et al., Searches for Point-like and extended neutrino sources close to the Galactic Centre using the ANTARES neutrino Telescope, Astrophys. J. 786 (2014) L5 [ arXiv:1402.6182 ] [INSPIRE].G.J. Feldman and R.D. Cousins, A unified approach to the classical statistical analysis of small signals, Phys. Rev. D 57 (1998) 3873 [ physics/9711021 ] [INSPIRE].G.C. Hill and K. Rawlins, Unbiased cut selection for optimal upper limits in neutrino detectors: The model rejection potential technique, Astropart. Phys. 19 (2003) 393 [ astro-ph/0209350 ] [ INSPIRE ].ANTARES collaboration, J.A. Aguilar et al., Zenith distribution and flux of atmospheric muons measured with the 5-line ANTARES detector, Astropart. Phys. 34 (2010) 179 [ arXiv:1007.1777 ] [ INSPIRE ].ANTARES collaboration, S. Adrian-Martinez et al., Measurement of the atmospheric ν μ energy spectrum from 100 GeV to 200 TeV with the ANTARES telescope, Eur. Phys. J. C 73 (2013) 2606 [ arXiv:1308.1599 ] [INSPIRE].ANTARES collaboration, S. Adrian-Martinez et al., First Search for Point Sources of High Energy Cosmic Neutrinos with the ANTARES Neutrino Telescope, Astrophys. J. 743 (2011) L14 [ arXiv:1108.0292 ] [INSPIRE].ANTARES collaboration, P. Amram et al., The ANTARES optical module, Nucl. Instrum. Meth. A 484 (2002) 369 [ astro-ph/0112172 ] [INSPIRE].ANTARES collaboration, J.A. Aguilar et al., Transmission of light in deep sea water at the site of the ANTARES Neutrino Telescope, Astropart. Phys. 23 (2005) 131 [ astro-ph/0412126 ] [ INSPIRE ].MACRO collaboration, M. Ambrosio et al., Final results of magnetic monopole searches with the MACRO experiment, Eur. Phys. J. C 25 (2002) 511 [ hep-ex/0207020 ] [INSPIRE].BAIKAL collaboration, K. Antipin et al., Search for relativistic magnetic monopoles with the Baikal Neutrino Telescope, Astropart. Phys. 29 (2008) 366 [ INSPIRE ].KM3Net collaboration, S. Adrian-Martinez et al., Letter of intent for KM3NeT 2.0, J. Phys. G 43 (2016) 084001 [ arXiv:1601.07459 ] [INSPIRE]

Role of IL-1β in experimental cystic fibrosis upon P. aeruginosa Infection

Cystic fibrosis is associated with increased inflammatory responses to pathogen challenge. Here we revisited the role of IL-1β in lung pathology using the experimental F508del-CFTR murine model on C57BL/6 genetic background (Cftrtm1eur or d/d), on double deficient for d/d and type 1 interleukin-1 receptor (d/d X IL-1R1-/-), and antibody neutralization. At steady state, young adult d/d mice did not show any signs of spontaneous lung inflammation. However, IL-1R1 deficiency conferred partial protection to repeated P. aeruginosa endotoxins/LPS lung instillation in d/d mice, as 50% of d/d mice succumbed to inflammation, whereas all d/d x IL-1R1-/- double mutants survived with lower initial weight loss and less pulmonary collagen and mucus production, suggesting that the absence of IL-1R1 signaling is protective in d/d mice in LPS-induced lung damage. Using P. aeruginosa acute lung infection we found heightened neutrophil recruitment in d/d mice with higher epithelial damage, increased bacterial load in BALF, and augmented IL-1β and TNF-α in parenchyma as compared to WT mice. Thus, F508del-CFTR mice show enhanced IL-1β signaling in response to P. aeruginosa. IL-1β antibody neutralization had no effect on lung homeostasis in either d/d or WT mice, however P. aeruginosa induced lung inflammation and bacterial load were diminished by IL-1β antibody neutralization. In conclusion, enhanced susceptibility to P. aeruginosa in d/d mice correlates with an excessive inflammation and with increased IL-1β production and reduced bacterial clearance. Further, we show that neutralization of IL-1β in d/d mice through the double mutation d/d x IL-1R1-/- and in WT via antibody neutralization attenuates inflammation. This supports the notion that intervention in the IL-1R1/IL-1β pathway may be detrimental in CF patients

Sensitivity of the Cherenkov Telescope Array to a dark matter signal from the Galactic centre

We provide an updated assessment of the power of the Cherenkov Telescope Array (CTA) to search for thermally produced dark matter at the TeV scale, via the associated gamma-ray signal from pair-annihilating dark matter particles in the region around the Galactic centre. We find that CTA will open a new window of discovery potential, significantly extending the range of robustly testable models given a standard cuspy profile of the dark matter density distribution. Importantly, even for a cored profile, the projected sensitivity of CTA will be sufficient to probe various well-motivated models of thermally produced dark matter at the TeV scale. This is due to CTA's unprecedented sensitivity, angular and energy resolutions, and the planned observational strategy. The survey of the inner Galaxy will cover a much larger region than corresponding previous observational campaigns with imaging atmospheric Cherenkov telescopes. CTA will map with unprecedented precision the large-scale diffuse emission in high-energy gamma rays, constituting a background for dark matter searches for which we adopt state-of-the-art models based on current data. Throughout our analysis, we use up-to-date event reconstruction Monte Carlo tools developed by the CTA consortium, and pay special attention to quantifying the level of instrumental systematic uncertainties, as well as background template systematic errors, required to probe thermally produced dark matter at these energies