Biliary Bicarbonate Secretion Constitutes a Protective Mechanism against Bile Acid-Induced Injury in Man

Background: Cholangiocytes expose a striking resistance against bile acids: while other cell types, such as hepatocytes, are susceptible to bile acid-induced toxicity and apoptosis already at micromolar concentrations, cholangiocytes are continuously exposed to millimolar concentrations as present in bile. We present a hypothesis suggesting that biliary secretion of HCO(3)(-) in man serves to protect cholangiocytes against bile acid-induced damage by fostering the deprotonation of apolar bile acids to more polar bile salts. Here, we tested if bile acid-induced toxicity is pH-dependent and if anion exchanger 2 (AE2) protects against bile acid-induced damage. Methods: A human cholangiocyte cell line was exposed to chenodeoxycholate (CDC), or its glycine conjugate, from 0.5 mM to 2.0 mM at pH 7.4, 7.1, 6.7 or 6.4, or after knockdown of AE2. Cell viability and apoptosis were determined by WST and caspase-3/-7 assays, respectively. Results: Glycochenodeoxycholate (GCDC) uptake in cholangiocytes is pH-dependent. Furthermore, CDC and GCDC (pK(a) 4-5) induce cholangiocyte toxicity in a pH-dependent manner: 0.5 mM CDC and 1 mM GCDC at pH 7.4 had no effect on cell viability, but at pH 6.4 decreased viability by >80% and increased caspase activity almost 10- and 30-fold, respectively. Acidification alone had no effect. AE2 knockdown led to 3- and 2-fold enhanced apoptosis induced by 0.75 mM CDC or 2 mM GCDC at pH 7.4. Discussion: These data support our hypothesis of a biliary HCO(3)(-) umbrella serving to protect human cholangiocytes against bile acid-induced injury. AE2 is a key contributor to this protective mechanism. The development and progression of cholangiopathies, such as primary biliary cirrhosis, may be a consequence of genetic and acquired functional defects of genes involved in maintaining the biliary HCO(3)(-) umbrella. Copyright (C) 2011 S. Karger AG, Base

A First Search for coincident Gravitational Waves and High Energy Neutrinos using LIGO, Virgo and ANTARES data from 2007

We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.Comment: 19 pages, 8 figures, science summary page at http://www.ligo.org/science/Publication-S5LV_ANTARES/index.php. Public access area to figures, tables at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p120000

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

Virgo Detector Characterization and Data Quality during the O3 run

The Advanced Virgo detector has contributed with its data to the rapid growth of the number of detected gravitational-wave signals in the past few years, alongside the two LIGO instruments. First, during the last month of the Observation Run 2 (O2) in August 2017 (with, most notably, the compact binary mergers GW170814 and GW170817) and then during the full Observation Run 3 (O3): an 11 months data taking period, between April 2019 and March 2020, that led to the addition of about 80 events to the catalog of transient gravitational-wave sources maintained by LIGO, Virgo and KAGRA. These discoveries and the manifold exploitation of the detected waveforms require an accurate characterization of the quality of the data, such as continuous study and monitoring of the detector noise. These activities, collectively named {\em detector characterization} or {\em DetChar}, span the whole workflow of the Virgo data, from the instrument front-end to the final analysis. They are described in details in the following article, with a focus on the associated tools, the results achieved by the Virgo DetChar group during the O3 run and the main prospects for future data-taking periods with an improved detector.Comment: 86 pages, 33 figures. This paper has been divided into two articles which supercede it and have been posted to arXiv on October 2022. Please use these new preprints as references: arXiv:2210.15634 (tools and methods) and arXiv:2210.15633 (results from the O3 run

Virgo Detector Characterization and Data Quality: results from the O3 run

The Advanced Virgo detector has contributed with its data to the rapid growth of the number of detected gravitational-wave (GW) signals in the past few years, alongside the two Advanced LIGO instruments. First during the last month of the Observation Run 2 (O2) in August 2017 (with, most notably, the compact binary mergers GW170814 and GW170817), and then during the full Observation Run 3 (O3): an 11-months data taking period, between April 2019 and March 2020, that led to the addition of about 80 events to the catalog of transient GW sources maintained by LIGO, Virgo and now KAGRA. These discoveries and the manifold exploitation of the detected waveforms require an accurate characterization of the quality of the data, such as continuous study and monitoring of the detector noise sources. These activities, collectively named {\em detector characterization and data quality} or {\em DetChar}, span the whole workflow of the Virgo data, from the instrument front-end hardware to the final analyses. They are described in details in the following article, with a focus on the results achieved by the Virgo DetChar group during the O3 run. Concurrently, a companion article describes the tools that have been used by the Virgo DetChar group to perform this work.Comment: 57 pages, 18 figures. To be submitted to Class. and Quantum Grav. This is the "Results" part of preprint arXiv:2205.01555 [gr-qc] which has been split into two companion articles: one about the tools and methods, the other about the analyses of the O3 Virgo dat

Virgo Detector Characterization and Data Quality: tools

Detector characterization and data quality studies -- collectively referred to as {\em DetChar} activities in this article -- are paramount to the scientific exploitation of the joint dataset collected by the LIGO-Virgo-KAGRA global network of ground-based gravitational-wave (GW) detectors. They take place during each phase of the operation of the instruments (upgrade, tuning and optimization, data taking), are required at all steps of the dataflow (from data acquisition to the final list of GW events) and operate at various latencies (from near real-time to vet the public alerts to offline analyses). This work requires a wide set of tools which have been developed over the years to fulfill the requirements of the various DetChar studies: data access and bookkeeping; global monitoring of the instruments and of the different steps of the data processing; studies of the global properties of the noise at the detector outputs; identification and follow-up of noise peculiar features (whether they be transient or continuously present in the data); quick processing of the public alerts. The present article reviews all the tools used by the Virgo DetChar group during the third LIGO-Virgo Observation Run (O3, from April 2019 to March 2020), mainly to analyse the Virgo data acquired at EGO. Concurrently, a companion article focuses on the results achieved by the DetChar group during the O3 run using these tools.Comment: 44 pages, 16 figures. To be submitted to Class. and Quantum Grav. This is the "Tools" part of preprint arXiv:2205.01555 [gr-qc] which has been split into two companion articles: one about the tools and methods, the other about the analyses of the O3 Virgo dat

Advanced Virgo Plus: Future Perspectives

While completing the commissioning phase to prepare the Virgo interferometer for the next joint Observation Run (O4), the Virgo collaboration is also finalizing the design of the next upgrades to the detector to be employed in the following Observation Run (O5). The major upgrade will concern decreasing the thermal noise limit, which will imply using very large test masses and increased laser beam size. But this will not be the only upgrade to be implemented in the break between the O4 and O5 observation runs to increase the Virgo detector strain sensitivity. The paper will cover the challenges linked to this upgrade and implications on the detector's reach and observational potential, reflecting the talk given at 12th Cosmic Ray International Seminar - CRIS 2022 held in September 2022 in Napoli

The Advanced Virgo+ status

The gravitational wave detector Advanced Virgo+ is currently in the commissioning phase in view of the fourth Observing Run (O4). The major upgrades with respect to the Advanced Virgo configuration are the implementation of an additional recycling cavity, the Signal Recycling cavity (SRC), at the output of the interferometer to broaden the sensitivity band and the Frequency Dependent Squeezing (FDS) to reduce quantum noise at all frequencies. The main difference of the Advanced Virgo + detector with respect to the LIGO detectors is the presence of marginally stable recycling cavities, with respect to the stable recycling cavities present in the LIGO detectors, which increases the difficulties in controlling the interferometer in presence of defects (both thermal and cold defects). This work will focus on the interferometer commissioning, highlighting the control challenges to maintain the detector in the working point which maximizes the sensitivity and the duty cycle for scientific data taking

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

First measurement of the Hubble Constant from a Dark Standard Siren using the Dark Energy Survey Galaxies and the LIGO/Virgo Binary–Black-hole Merger GW170814

International audienceWe present a multi-messenger measurement of the Hubble constant H 0 using the binary–black-hole merger GW170814 as a standard siren, combined with a photometric redshift catalog from the Dark Energy Survey (DES). The luminosity distance is obtained from the gravitational wave signal detected by the Laser Interferometer Gravitational-Wave Observatory (LIGO)/Virgo Collaboration (LVC) on 2017 August 14, and the redshift information is provided by the DES Year 3 data. Black hole mergers such as GW170814 are expected to lack bright electromagnetic emission to uniquely identify their host galaxies and build an object-by-object Hubble diagram. However, they are suitable for a statistical measurement, provided that a galaxy catalog of adequate depth and redshift completion is available. Here we present the first Hubble parameter measurement using a black hole merger. Our analysis results in , which is consistent with both SN Ia and cosmic microwave background measurements of the Hubble constant. The quoted 68% credible region comprises 60% of the uniform prior range [20, 140] km s−1 Mpc−1, and it depends on the assumed prior range. If we take a broader prior of [10, 220] km s−1 Mpc−1, we find (57% of the prior range). Although a weak constraint on the Hubble constant from a single event is expected using the dark siren method, a multifold increase in the LVC event rate is anticipated in the coming years and combinations of many sirens will lead to improved constraints on H 0