Skeletal growth is enhanced by a shared role for SOX8 and SOX9 in promoting reserve chondrocyte commitment to columnar proliferation.

SOX8 was linked in a genome-wide association study to human height heritability, but roles in chondrocytes for this close relative of the master chondrogenic transcription factor SOX9 remain unknown. We undertook here to fill this knowledge gap. High-throughput assays demonstrate expression of human SOX8 and mouse Sox8 in growth plate cartilage. In situ assays show that Sox8 is expressed at a similar level as Sox9 in reserve and early columnar chondrocytes and turned off when Sox9 expression peaks in late columnar and prehypertrophic chondrocytes. Sox8-/- mice and Sox8fl/flPrx1Cre and Sox9fl/+Prx1Cre mice (inactivation in limb skeletal cells) have a normal or near normal skeletal size. In contrast, juvenile and adult Sox8fl/flSox9fl/+Prx1Cre compound mutants exhibit a 15 to 20% shortening of long bones. Their growth plate reserve chondrocytes progress slowly toward the columnar stage, as witnessed by a delay in down-regulating Pthlh expression, in packing in columns and in elevating their proliferation rate. SOX8 or SOX9 overexpression in chondrocytes reveals not only that SOX8 can promote growth plate cell proliferation and differentiation, even upon inactivation of endogenous Sox9, but also that it is more efficient than SOX9, possibly due to greater protein stability. Altogether, these findings uncover a major role for SOX8 and SOX9 in promoting skeletal growth by stimulating commitment of growth plate reserve chondrocytes to actively proliferating columnar cells. Further, by showing that SOX8 is more chondrogenic than SOX9, they suggest that SOX8 could be preferred over SOX9 in therapies to promote cartilage formation or regeneration in developmental and degenerative cartilage diseases.

Frequency-Dependent Squeezed Vacuum Source for the Advanced Virgo Gravitational-Wave Detector.

In this Letter, we present the design and performance of the frequency-dependent squeezed vacuum source that will be used for the broadband quantum noise reduction of the Advanced Virgo Plus gravitational-wave detector in the upcoming observation run. The frequency-dependent squeezed field is generated by a phase rotation of a frequency-independent squeezed state through a 285 m long, high-finesse, near-detuned optical resonator. With about 8.5 dB of generated squeezing, up to 5.6 dB of quantum noise suppression has been measured at high frequency while close to the filter cavity resonance frequency, the intracavity losses limit this value to about 2 dB. Frequency-dependent squeezing is produced with a rotation frequency stability of about 6 Hz rms, which is maintained over the long term. The achieved results fulfill the frequency dependent squeezed vacuum source requirements for Advanced Virgo Plus. With the current squeezing source, considering also the estimated squeezing degradation induced by the interferometer, we expect a reduction of the quantum shot noise and radiation pressure noise of up to 4.5 dB and 2 dB, respectively.

Consolidation of the clinical and genetic definition of a SOX4-related neurodevelopmental syndrome.

BACKGROUND: A neurodevelopmental syndrome was recently reported in four patients with SOX4 heterozygous missense variants in the high-mobility-group (HMG) DNA-binding domain. The present study aimed to consolidate clinical and genetic knowledge of this syndrome. METHODS: We newly identified 17 patients with SOX4 variants, predicted variant pathogenicity using in silico tests and in vitro functional assays and analysed the patients' phenotypes. RESULTS: All variants were novel, distinct and heterozygous. Seven HMG-domain missense and five stop-gain variants were classified as pathogenic or likely pathogenic variant (L/PV) as they precluded SOX4 transcriptional activity in vitro. Five HMG-domain and non-HMG-domain missense variants were classified as of uncertain significance (VUS) due to negative results from functional tests. When known, inheritance was de novo or from a mosaic unaffected or non-mosaic affected parent for patients with L/PV, and from a non-mosaic asymptomatic or affected parent for patients with VUS. All patients had neurodevelopmental, neurological and dysmorphic features, and at least one cardiovascular, ophthalmological, musculoskeletal or other somatic anomaly. Patients with L/PV were overall more affected than patients with VUS. They resembled patients with other neurodevelopmental diseases, including the SOX11-related and Coffin-Siris (CSS) syndromes, but lacked the most specific features of CSS. CONCLUSION: These findings consolidate evidence of a fairly non-specific neurodevelopmental syndrome due to SOX4 haploinsufficiency in neurogenesis and multiple other developmental processes.

Antioxidant, Anti-Inflammatory, and Anti-Cancer Properties of Amygdalin Extracted from Three Cassava Varieties Cultivated in Benin.

Given that cancer is a disease that is rampant in the world and especially in Africa, where the population has enormous difficulty treating it, plants are a safer and less expensive alternative. Cassava is a plant species valued in Benin because of its numerous medicinal and nutritional virtues. This study evaluated the biological activities of amygdalin from the organs of three cassava varieties most commonly produced in Benin (BEN, RB, and MJ). HPLC analysis was used to quantify amygdalin in cassava organs and derivatives. Phytochemical screening was performed to determine secondary metabolite groups. DPPH and FRAP methods were used to assess antioxidant activity. Cytotoxicity of the extracts was tested on Artemia salina larvae. The anti-inflammatory activity was evaluated in vivo in an albino mouse paw edema model induced by 5% formalin. The anticancer activity was evaluated in vivo on Wistar rats rendered cancerous by 1,2-dimethylhydrazine (DMH) using 5-fluorouracil as a reference molecule. The results showed that the organs of all three-cassava varieties contained glycosides, flavonoids, saponosides, steroids, tannins, coumarins, and cyanogenic derivatives. Young stems and fresh cassava leaves had the highest amygdalin concentrations, with 11,142.99 µg 10 g-1 and 9251.14 µg 10 g-1, respectively. The Agbeli derivative was more concentrated in amygdalin, with a content of 401.56 µg 10 g-1 than the other derivatives. The antioxidant activity results showed that the amygdalin extracts were DPPH radical scavengers with IC50 values ranging from 0.18 mg mL-1 to 2.35 mg mL-1. The cytotoxicity test showed no toxicity of the extracts toward shrimp larvae. Administration of amygdalin extracts from the leaves of BEN and MJ varieties prevents inflammatory edema. The percentages of edema inhibition varied between 21.77% and 27.89%. These values are similar (p > 0.05) to those of acetylsalicylic acid (25.20%). Amygdalin extract of the BEN variety significantly (p < 0.0001) reduces edema. Both BEN extracts inhibited cancer induction with DMH. In preventive and curative treatments, rats fed with amygdalin extracts showed low anti-cancer activity under the effect of DMH and a significant difference in biochemical results. Thus, the organs of all three cassava varieties studied have secondary metabolites and good antioxidant activity. The leaves contain high levels of amygdalin and can be used as anti-inflammatory and anticancer agents.

Search for Subsolar-Mass Binaries in the First Half of Advanced LIGO's and Advanced Virgo's Third Observing Run.

We report on a search for compact binary coalescences where at least one binary component has a mass between 0.2 M_{⊙} and 1.0 M_{⊙} in Advanced LIGO and Advanced Virgo data collected between 1 April 2019 1500 UTC and 1 October 2019 1500 UTC. We extend our previous analyses in two main ways: we include data from the Virgo detector and we allow for more unequal mass systems, with mass ratio q≥0.1. We do not report any gravitational-wave candidates. The most significant trigger has a false alarm rate of 0.14 yr^{-1}. This implies an upper limit on the merger rate of subsolar binaries in the range [220-24200] Gpc^{-3} yr^{-1}, depending on the chirp mass of the binary. We use this upper limit to derive astrophysical constraints on two phenomenological models that could produce subsolar-mass compact objects. One is an isotropic distribution of equal-mass primordial black holes. Using this model, we find that the fraction of dark matter in primordial black holes in the mass range 0.2 M_{⊙}

Constraints on Cosmic Strings Using Data from the Third Advanced LIGO-Virgo Observing Run.

We search for gravitational-wave signals produced by cosmic strings in the Advanced LIGO and Virgo full O3 dataset. Search results are presented for gravitational waves produced by cosmic string loop features such as cusps, kinks, and, for the first time, kink-kink collisions. A template-based search for short-duration transient signals does not yield a detection. We also use the stochastic gravitational-wave background energy density upper limits derived from the O3 data to constrain the cosmic string tension Gµ as a function of the number of kinks, or the number of cusps, for two cosmic string loop distribution models. Additionally, we develop and test a third model that interpolates between these two models. Our results improve upon the previous LIGO-Virgo constraints on Gµ by 1 to 2 orders of magnitude depending on the model that is tested. In particular, for the one-loop distribution model, we set the most competitive constraints to date: Gµâ‰²4×10^{-15}. In the case of cosmic strings formed at the end of inflation in the context of grand unified theories, these results challenge simple inflationary models.

GW190521: A Binary Black Hole Merger with a Total Mass of 150 M_{⊙}.

On May 21, 2019 at 03:02:29 UTC Advanced LIGO and Advanced Virgo observed a short duration gravitational-wave signal, GW190521, with a three-detector network signal-to-noise ratio of 14.7, and an estimated false-alarm rate of 1 in 4900 yr using a search sensitive to generic transients. If GW190521 is from a quasicircular binary inspiral, then the detected signal is consistent with the merger of two black holes with masses of 85_{-14}^{+21} M_{⊙} and 66_{-18}^{+17} M_{⊙} (90% credible intervals). We infer that the primary black hole mass lies within the gap produced by (pulsational) pair-instability supernova processes, with only a 0.32% probability of being below 65 M_{⊙}. We calculate the mass of the remnant to be 142_{-16}^{+28} M_{⊙}, which can be considered an intermediate mass black hole (IMBH). The luminosity distance of the source is 5.3_{-2.6}^{+2.4} Gpc, corresponding to a redshift of 0.82_{-0.34}^{+0.28}. The inferred rate of mergers similar to GW190521 is 0.13_{-0.11}^{+0.30} Gpc^{-3} yr^{-1}.

Quantum Backaction on kg-Scale Mirrors: Observation of Radiation Pressure Noise in the Advanced Virgo Detector.

The quantum radiation pressure and the quantum shot noise in laser-interferometric gravitational wave detectors constitute a macroscopic manifestation of the Heisenberg inequality. If quantum shot noise can be easily observed, the observation of quantum radiation pressure noise has been elusive, so far, due to the technical noise competing with quantum effects. Here, we discuss the evidence of quantum radiation pressure noise in the Advanced Virgo gravitational wave detector. In our experiment, we inject squeezed vacuum states of light into the interferometer in order to manipulate the quantum backaction on the 42 kg mirrors and observe the corresponding quantum noise driven displacement at frequencies between 30 and 70 Hz. The experimental data, obtained in various interferometer configurations, is tested against the Advanced Virgo detector quantum noise model which confirmed the measured magnitude of quantum radiation pressure noise.

Prospects for observing and localizing gravitational-wave transients with Advanced LIGO, Advanced Virgo and KAGRA.

We present our current best estimate of the plausible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next several years, with the intention of providing information to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals for the third (O3), fourth (O4) and fifth observing (O5) runs, including the planned upgrades of the Advanced LIGO and Advanced Virgo detectors. We study the capability of the network to determine the sky location of the source for gravitational-wave signals from the inspiral of binary systems of compact objects, that is binary neutron star, neutron star-black hole, and binary black hole systems. The ability to localize the sources is given as a sky-area probability, luminosity distance, and comoving volume. The median sky localization area (90% credible region) is expected to be a few hundreds of square degrees for all types of binary systems during O3 with the Advanced LIGO and Virgo (HLV) network. The median sky localization area will improve to a few tens of square degrees during O4 with the Advanced LIGO, Virgo, and KAGRA (HLVK) network. During O3, the median localization volume (90% credible region) is expected to be on the order of 10 5 , 10 6 , 10 7 Mpc 3 for binary neutron star, neutron star-black hole, and binary black hole systems, respectively. The localization volume in O4 is expected to be about a factor two smaller than in O3. We predict a detection count of 1 - 1 + 12 ( 10 - 10 + 52 ) for binary neutron star mergers, of 0 - 0 + 19 ( 1 - 1 + 91 ) for neutron star-black hole mergers, and 17 - 11 + 22 ( 79 - 44 + 89 ) for binary black hole mergers in a one-calendar-year observing run of the HLV network during O3 (HLVK network during O4). We evaluate sensitivity and localization expectations for unmodeled signal searches, including the search for intermediate mass black hole binary mergers.

Increasing the Astrophysical Reach of the Advanced Virgo Detector via the Application of Squeezed Vacuum States of Light.

Current interferometric gravitational-wave detectors are limited by quantum noise over a wide range of their measurement bandwidth. One method to overcome the quantum limit is the injection of squeezed vacuum states of light into the interferometer's dark port. Here, we report on the successful application of this quantum technology to improve the shot noise limited sensitivity of the Advanced Virgo gravitational-wave detector. A sensitivity enhancement of up to 3.2±0.1 dB beyond the shot noise limit is achieved. This nonclassical improvement corresponds to a 5%-8% increase of the binary neutron star horizon. The squeezing injection was fully automated and over the first 5 months of the third joint LIGO-Virgo observation run O3 squeezing was applied for more than 99% of the science time. During this period several gravitational-wave candidates have been recorded.

Search for Subsolar Mass Ultracompact Binaries in Advanced LIGO's Second Observing Run.

We present a search for subsolar mass ultracompact objects in data obtained during Advanced LIGO's second observing run. In contrast to a previous search of Advanced LIGO data from the first observing run, this search includes the effects of component spin on the gravitational waveform. We identify no viable gravitational-wave candidates consistent with subsolar mass ultracompact binaries with at least one component between 0.2 M_{⊙}-1.0 M_{⊙}. We use the null result to constrain the binary merger rate of (0.2 M_{⊙}, 0.2 M_{⊙}) binaries to be less than 3.7×10^{5} Gpc^{-3} yr^{-1} and the binary merger rate of (1.0 M_{⊙}, 1.0 M_{⊙}) binaries to be less than 5.2×10^{3} Gpc^{-3} yr^{-1}. Subsolar mass ultracompact objects are not expected to form via known stellar evolution channels, though it has been suggested that primordial density fluctuations or particle dark matter with cooling mechanisms and/or nuclear interactions could form black holes with subsolar masses. Assuming a particular primordial black hole (PBH) formation model, we constrain a population of merging 0.2 M_{⊙} black holes to account for less than 16% of the dark matter density and a population of merging 1.0 M_{⊙} black holes to account for less than 2% of the dark matter density. We discuss how constraints on the merger rate and dark matter fraction may be extended to arbitrary black hole population models that predict subsolar mass binaries.

Tests of General Relativity with GW170817.

The recent discovery by Advanced LIGO and Advanced Virgo of a gravitational wave signal from a binary neutron star inspiral has enabled tests of general relativity (GR) with this new type of source. This source, for the first time, permits tests of strong-field dynamics of compact binaries in the presence of matter. In this Letter, we place constraints on the dipole radiation and possible deviations from GR in the post-Newtonian coefficients that govern the inspiral regime. Bounds on modified dispersion of gravitational waves are obtained; in combination with information from the observed electromagnetic counterpart we can also constrain effects due to large extra dimensions. Finally, the polarization content of the gravitational wave signal is studied. The results of all tests performed here show good agreement with GR.

Constraining the p-Mode-g-Mode Tidal Instability with GW170817.

We analyze the impact of a proposed tidal instability coupling p modes and g modes within neutron stars on GW170817. This nonresonant instability transfers energy from the orbit of the binary to internal modes of the stars, accelerating the gravitational-wave driven inspiral. We model the impact of this instability on the phasing of the gravitational wave signal using three parameters per star: an overall amplitude, a saturation frequency, and a spectral index. Incorporating these additional parameters, we compute the Bayes factor (lnB_{!pg}^{pg}) comparing our p-g model to a standard one. We find that the observed signal is consistent with waveform models that neglect p-g effects, with lnB_{!pg}^{pg}=0.03_{-0.58}^{+0.70} (maximum a posteriori and 90% credible region). By injecting simulated signals that do not include p-g effects and recovering them with the p-g model, we show that there is a ≃50% probability of obtaining similar lnB_{!pg}^{pg} even when p-g effects are absent. We find that the p-g amplitude for 1.4 M_{⊙} neutron stars is constrained to less than a few tenths of the theoretical maximum, with maxima a posteriori near one-tenth this maximum and p-g saturation frequency ∼70 Hz. This suggests that there are less than a few hundred excited modes, assuming they all saturate by wave breaking. For comparison, theoretical upper bounds suggest ≲10^{3} modes saturate by wave breaking. Thus, the measured constraints only rule out extreme values of the p-g parameters. They also imply that the instability dissipates ≲10^{51} erg over the entire inspiral, i.e., less than a few percent of the energy radiated as gravitational waves.

Search for Subsolar-Mass Ultracompact Binaries in Advanced LIGO's First Observing Run.

We present the first Advanced LIGO and Advanced Virgo search for ultracompact binary systems with component masses between 0.2 M_{⊙}-1.0 M_{⊙} using data taken between September 12, 2015 and January 19, 2016. We find no viable gravitational wave candidates. Our null result constrains the coalescence rate of monochromatic (delta function) distributions of nonspinning (0.2 M_{⊙}, 0.2 M_{⊙}) ultracompact binaries to be less than 1.0×10^{6} Gpc^{-3} yr^{-1} and the coalescence rate of a similar distribution of (1.0 M_{⊙}, 1.0 M_{⊙}) ultracompact binaries to be less than 1.9×10^{4} Gpc^{-3} yr^{-1} (at 90% confidence). Neither black holes nor neutron stars are expected to form below ∼1 M_{⊙} through conventional stellar evolution, though it has been proposed that similarly low mass black holes could be formed primordially through density fluctuations in the early Universe and contribute to the dark matter density. The interpretation of our constraints in the primordial black hole dark matter paradigm is highly model dependent; however, under a particular primordial black hole binary formation scenario we constrain monochromatic primordial black hole populations of 0.2 M_{⊙} to be less than 33% of the total dark matter density and monochromatic populations of 1.0 M_{⊙} to be less than 5% of the dark matter density. The latter strengthens the presently placed bounds from microlensing surveys of massive compact halo objects (MACHOs) provided by the MACHO and EROS Collaborations.

GW170817: Implications for the Stochastic Gravitational-Wave Background from Compact Binary Coalescences.

The LIGO Scientific and Virgo Collaborations have announced the event GW170817, the first detection of gravitational waves from the coalescence of two neutron stars. The merger rate of binary neutron stars estimated from this event suggests that distant, unresolvable binary neutron stars create a significant astrophysical stochastic gravitational-wave background. The binary neutron star component will add to the contribution from binary black holes, increasing the amplitude of the total astrophysical background relative to previous expectations. In the Advanced LIGO-Virgo frequency band most sensitive to stochastic backgrounds (near 25 Hz), we predict a total astrophysical background with amplitude Ω_{GW}(f=25 Hz)=1.8_{-1.3}^{+2.7}×10^{-9} with 90% confidence, compared with Ω_{GW}(f=25 Hz)=1.1_{-0.7}^{+1.2}×10^{-9} from binary black holes alone. Assuming the most probable rate for compact binary mergers, we find that the total background may be detectable with a signal-to-noise-ratio of 3 after 40 months of total observation time, based on the expected timeline for Advanced LIGO and Virgo to reach their design sensitivity.

GW170817: Measurements of Neutron Star Radii and Equation of State.

On 17 August 2017, the LIGO and Virgo observatories made the first direct detection of gravitational waves from the coalescence of a neutron star binary system. The detection of this gravitational-wave signal, GW170817, offers a novel opportunity to directly probe the properties of matter at the extreme conditions found in the interior of these stars. The initial, minimal-assumption analysis of the LIGO and Virgo data placed constraints on the tidal effects of the coalescing bodies, which were then translated to constraints on neutron star radii. Here, we expand upon previous analyses by working under the hypothesis that both bodies were neutron stars that are described by the same equation of state and have spins within the range observed in Galactic binary neutron stars. Our analysis employs two methods: the use of equation-of-state-insensitive relations between various macroscopic properties of the neutron stars and the use of an efficient parametrization of the defining function p(ρ) of the equation of state itself. From the LIGO and Virgo data alone and the first method, we measure the two neutron star radii as R_{1}=10.8_{-1.7}^{+2.0} km for the heavier star and R_{2}=10.7_{-1.5}^{+2.1} km for the lighter star at the 90% credible level. If we additionally require that the equation of state supports neutron stars with masses larger than 1.97 M_{⊙} as required from electromagnetic observations and employ the equation-of-state parametrization, we further constrain R_{1}=11.9_{-1.4}^{+1.4} km and R_{2}=11.9_{-1.4}^{+1.4} km at the 90% credible level. Finally, we obtain constraints on p(ρ) at supranuclear densities, with pressure at twice nuclear saturation density measured at 3.5_{-1.7}^{+2.7}×10^{34} dyn cm^{-2} at the 90% level.

First Search for Nontensorial Gravitational Waves from Known Pulsars.

We present results from the first directed search for nontensorial gravitational waves. While general relativity allows for tensorial (plus and cross) modes only, a generic metric theory may, in principle, predict waves with up to six different polarizations. This analysis is sensitive to continuous signals of scalar, vector, or tensor polarizations, and does not rely on any specific theory of gravity. After searching data from the first observation run of the advanced LIGO detectors for signals at twice the rotational frequency of 200 known pulsars, we find no evidence of gravitational waves of any polarization. We report the first upper limits for scalar and vector strains, finding values comparable in magnitude to previously published limits for tensor strain. Our results may be translated into constraints on specific alternative theories of gravity.

Search for Tensor, Vector, and Scalar Polarizations in the Stochastic Gravitational-Wave Background.

The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of generically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Ω_{0}^{T}<5.58×10^{-8}, Ω_{0}^{V}<6.35×10^{-8}, and Ω_{0}^{S}<1.08×10^{-7} at a reference frequency f_{0}=25 Hz.

First Evidence for cos2ß>0 and Resolution of the Cabibbo-Kobayashi-Maskawa Quark-Mixing Unitarity Triangle Ambiguity.

We present first evidence that the cosine of the CP-violating weak phase 2ß is positive, and hence exclude trigonometric multifold solutions of the Cabibbo-Kobayashi-Maskawa (CKM) Unitarity Triangle using a time-dependent Dalitz plot analysis of B^{0}→D^{(*)}h^{0} with D→K_{S}^{0}π^{+}π^{-} decays, where h^{0}∈{π^{0},η,ω} denotes a light unflavored and neutral hadron. The measurement is performed combining the final data sets of the BABAR and Belle experiments collected at the ϒ(4S) resonance at the asymmetric-energy B factories PEP-II at SLAC and KEKB at KEK, respectively. The data samples contain (471±3)×10^{6}BB[over ¯] pairs recorded by the BABAR detector and (772±11)×10^{6}BB[over ¯] pairs recorded by the Belle detector. The results of the measurement are sin2ß=0.80±0.14(stat)±0.06(syst)±0.03(model) and cos2ß=0.91±0.22(stat)±0.09(syst)±0.07(model). The result for the direct measurement of the angle ß of the CKM Unitarity Triangle is ß=[22.5±4.4(stat)±1.2(syst)±0.6(model)]°. The measurement assumes no direct CP violation in B^{0}→D^{(*)}h^{0} decays. The quoted model uncertainties are due to the composition of the D^{0}→K_{S}^{0}π^{+}π^{-} decay amplitude model, which is newly established by performing a Dalitz plot amplitude analysis using a high-statistics e^{+}e^{-}→cc[over ¯] data sample. CP violation is observed in B^{0}→D^{(*)}h^{0} decays at the level of 5.1 standard deviations. The significance for cos2ß>0 is 3.7 standard deviations. The trigonometric multifold solution π/2-ß=(68.1±0.7)° is excluded at the level of 7.3 standard deviations. The measurement resolves an ambiguity in the determination of the apex of the CKM Unitarity Triangle.

Prospects for observing and localizing gravitational-wave transients with Advanced LIGO, Advanced Virgo and KAGRA.

We present possible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals, and study the capability of the network to determine the sky location of the source. We report our findings for gravitational-wave transients, with particular focus on gravitational-wave signals from the inspiral of binary neutron star systems, which are the most promising targets for multi-messenger astronomy. The ability to localize the sources of the detected signals depends on the geographical distribution of the detectors and their relative sensitivity, and [Formula: see text] credible regions can be as large as thousands of square degrees when only two sensitive detectors are operational. Determining the sky position of a significant fraction of detected signals to areas of 5-[Formula: see text] requires at least three detectors of sensitivity within a factor of [Formula: see text] of each other and with a broad frequency bandwidth. When all detectors, including KAGRA and the third LIGO detector in India, reach design sensitivity, a significant fraction of gravitational-wave signals will be localized to a few square degrees by gravitational-wave observations alone.