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 $$10^{5}, 10^{6}, 10^{7}\mathrm {\ Mpc}^3$$ 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 $$1^{+12}_{-1}$$ 1 - 1 + 12 ($$10^{+52}_{-10}$$ 10 - 10 + 52 ) for binary neutron star mergers, of $$0^{+19}_{-0}$$ 0 - 0 + 19 ($$1^{+91}_{-1}$$ 1 - 1 + 91 ) for neutron star–black hole mergers, and $$17^{+22}_{-11}$$ 17 - 11 + 22 ($$79^{+89}_{-44}$$ 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.

Stenotrophomonas maltophilia is a Gram-negative, biofilm-forming bacterium. Although generally regarded as an organism of low virulence, S. maltophilia is an emerging multi-drug resistant opportunistic pathogen in hospital and community settings, especially among immunocompromised hosts. Risk factors associated with S. maltophilia infection include underlying malignancy, cystic fibrosis, corticosteroid or immunosuppressant therapy, the presence of an indwelling central venous catheter and exposure to broad spectrum antibiotics. In this review, we provide a synthesis of information on current global trends in S. maltophilia pathogenicity as well as updated information on the molecular mechanisms contributing to its resistance to an array of antimicrobial agents. The prevalence of S. maltophilia infection in the general population increased from 0.8–1.4% during 1997–2003 to 1.3–1.68% during 2007–2012. The most important molecular mechanisms contributing to its resistance to antibiotics include β-lactamase production, the expression of Qnr genes, and the presence of class 1 integrons and efflux pumps. Trimethoprim/sulfamethoxazole (TMP/SMX) is the antimicrobial drug of choice. Although a few studies have reported increased resistance to TMP/SMX, the majority of studies worldwide show that S. maltophilia continues to be highly susceptible. Drugs with historically good susceptibility results include ceftazidime, ticarcillin-clavulanate, and fluoroquinolones; however, a number of studies show an alarming trend in resistance to those agents. Tetracyclines such as tigecycline, minocycline, and doxycycline are also effective agents and consistently display good activity against S. maltophilia in various geographic regions and across different time periods. Combination therapies, novel agents, and aerosolized forms of antimicrobial drugs are currently being tested for their ability to treat infections caused by this multi-drug resistant organism.

Nephrocystin mutations account for the vast majority of juvenile nephronophthisis, the most common inherited cause of renal failure in children. Nephrocystin has been localized to the ciliary transition zone of epithelial cells or its analogous structure, connecting cilium of retinal photoreceptors. Thus, the retinal degeneration associated with nephronophthisis may be explained by a functional ciliary defect. However, the function of nephrocystin in cilium assembly and maintenance of common epithelial cells and photoreceptors is still obscure. Here, we used Nphp1-targeted mutant mice and transgenic mice expressing EmGFP-tagged nephrocystin to demonstrate that nephrocystin located at connecting cilium axoneme can affect the sorting mechanism and transportation efficiency of the traffic machinery between inner and outer segments of photoreceptors. This traffic machinery is now recognized as intraflagellar transport (IFT); a microtubule-based transport system consisting of motors, IFT particles and associated cargo molecules. Nephrocystin seems to control some of the IFT particle components moving along the connecting cilia so as to regulate this inter-segmental traffic. Our novel findings provide a clue to unraveling the regulatory mechanism of nephrocystin in IFT machinery.

KAGRA is a newly built gravitational wave observatory, a laser interferometer with a 3 km arm length, located in Kamioka, Gifu, Japan. In this series of articles, we present an overview of the baseline KAGRA, for which we finished installing the designed configuration in 2019. This article describes the method of calibration (CAL) used for reconstructing gravitational wave signals from the detector outputs, as well as the characterization of the detector (DET). We also review the physical environmental monitors (PEM) system and the geophysics interferometer (GIF). Both are used for characterizing and evaluating the data quality of the gravitational wave channel. They play important roles in utilizing the detector output for gravitational wave searches. These characterization investigations will be even more important in the near future, once gravitational wave detection has been achieved, and in using KAGRA in the gravitational wave astronomy era.