Assessing seizure liability in vitro with voltage-sensitive dye imaging in mouse hippocampal slices

Non-clinical toxicology is a major cause of drug candidate attrition during development. In particular, drug-induced seizures are the most common finding in central nervous system (CNS) toxicity. Current safety pharmacology tests for assessing CNS functions are often inadequate in detecting seizure-inducing compounds early in drug development, leading to significant delays. This paper presents an in vitro seizure liability assay using voltage-sensitive dye (VSD) imaging techniques in hippocampal brain slices, offering a powerful alternative to traditional electrophysiological methods. Hippocampal slices were isolated from mice, and VSD optical responses evoked by stimulating the Schaffer collateral pathway were recorded and analyzed in the stratum radiatum (SR) and stratum pyramidale (SP). VSDs allow for the comprehensive visualization of neuronal action potentials and postsynaptic potentials on a millisecond timescale. By employing this approach, we investigated the in vitro drug-induced seizure liability of representative pro-convulsant compounds. Picrotoxin (PiTX; 1–100 μM), gabazine (GZ; 0.1–10 μM), and 4-aminopyridine (4AP; 10–100 μM) exhibited seizure-like responses in the hippocampus, but pilocarpine hydrochloride (Pilo; 10–100 μM) did not. Our findings demonstrate the potential of VSD-based assays in identifying seizurogenic compounds during early drug discovery, thereby reducing delays in drug development and providing insights into the mechanisms underlying seizure induction and the associated risks of pro-convulsant compounds

One-Step Synthesis of Copper and Cupric Oxide Particles from the Liquid Phase by X-Ray Radiolysis Using Synchrotron Radiation

The deposition of copper (Cu) and cupric oxide (Cu4O3, Cu2O, and CuO) particles in an aqueous copper sulfate (CuSO4) solution with additive alcohol such as methanol, ethanol, 2-propanol, and ethylene glycol has been studied by X-ray exposure from synchrotron radiation. An attenuated X-ray radiation time of 5 min allows for the synthesis of Cu, Cu4O3, Cu2O, and CuO nano/microscale particles and their aggregation into clusters. The morphology and composition of the synthesized Cu/cupric oxide particle clusters were characterized by scanning electron microscopy, scanning transmission electron microscopy, and high-resolution transmission electron microscopy with energy dispersive X-ray spectroscopy. Micro-Raman spectroscopy revealed that the clusters comprised cupric oxide core particles covered with Cu particles. Neither Cu/cupric oxide particles nor their clusters were formed without any alcohol additives. The effect of alcohol additives is attributed to the following sequential steps: photochemical reaction due to X-ray irradiation induces nucleation of the particles accompanying redox reaction and forms a cluster or aggregates by LaMer process and DLVO interactions. The procedure offers a novel route to synthesize the Cu/cupric oxide particles and aggregates. It also provides a novel additive manufacturing process or lithography of composite materials such as metal, oxide, and resin

Measurement of a Phase of a Radio Wave Reflected from Rock Salt and Ice Irradiated by an Electron Beam for Detection of Ultra-High-Energy Neutrinos

We have found a radio-wave-reflection effect in rock salt for the detection of ultra-high energy neutrinos which are expected to be generated in Greisen, Zatsepin, and Kuzmin (GZK) processes in the universe. When an UHE neutrino interacts with rock salt or ice as a detection medium, a shower is generated. That shower is formed by hadronic and electromagnetic avalanche processes. The energy of the UHE neutrino shower converts to thermal energy through ionization processes. Consequently, the temperature rises along the shower produced by the UHE neutrino. The refractive index of the medium rises with temperature. The irregularity of the refractive index in the medium leads to a reflection of radio waves. This reflection effect combined with the long attenuation length of radio waves in rock salt and ice would yield a new method to detect UHE neutrinos. We measured the phase of the reflected radio wave under irradiation with an electron beam on ice and rock salt powder. The measured phase showed excellent consistence with the power reflection fraction which was measured directly. A model taking into account the temperature change explained the phase and the amplitude of the reflected wave. Therefore the reflection mechanism was confirmed. The power reflection fraction was compared with that calculated with the Fresnel equations, the ratio between the measured result and that obtained with the Fresnel equations in ice was larger than that of rock salt.Comment: 6 Pages, 5th International Workshop on Acoustic and Radio EeV Neutrino Detection Activitie

Hyper-luminous Dust Obscured Galaxies discovered by the Hyper Suprime-Cam on Subaru and WISE

We present the photometric properties of a sample of infrared (IR) bright dust obscured galaxies (DOGs). Combining wide and deep optical images obtained with the Hyper Suprime-Cam (HSC) on the Subaru Telescope and all-sky mid-IR (MIR) images taken with Wide-Field Infrared Survey Explorer (WISE), we discovered 48 DOGs with $i - K_\mathrm{s} > 1.2$ and $i - [22] > 7.0$, where $i$, $K_\mathrm{s}$, and [22] represent AB magnitude in the $i$-band, $K_\mathrm{s}$-band, and 22 $\mu$m, respectively, in the GAMA 14hr field ($\sim$ 9 deg$^2$). Among these objects, 31 ($\sim$ 65 %) show power-law spectral energy distributions (SEDs) in the near-IR (NIR) and MIR regime, while the remainder show a NIR bump in their SEDs. Assuming that the redshift distribution for our DOGs sample is Gaussian, with mean and sigma $z$ = 1.99 $\pm$ 0.45, we calculated their total IR luminosity using an empirical relation between 22 $\mu$m luminosity and total IR luminosity. The average value of the total IR luminosity is (3.5 $\pm$ 1.1) $\times$ $10^{13}$ L$_{\odot}$, which classifies them as hyper-luminous infrared galaxies (HyLIRGs). We also derived the total IR luminosity function (LF) and IR luminosity density (LD) for a flux-limited subsample of 18 DOGs with 22 $\mu$m flux greater than 3.0 mJy and with $i$-band magnitude brighter than 24 AB magnitude. The derived space density for this subsample is log $\phi$ = -6.59 $\pm$ 0.11 [Mpc$^{-3}$]. The IR LF for DOGs including data obtained from the literature is well fitted by a double-power law. The derived lower limit for the IR LD for our sample is $\rho_{\mathrm{IR}}$ $\sim$ 3.8 $\times$ 10$^7$ [L$_{\odot}$ Mpc$^{-3}$] and its contributions to the total IR LD, IR LD of all ultra-luminous infrared galaxies (ULIRGs), and that of all DOGs are $>$ 3 %, $>$ 9 %, and $>$ 15 %, respectively.Comment: 15 pages, 15 figures, and 3 tables, accepted for publication in PASJ (Subaru special issue

Subaru high-z exploration of low-luminosity quasars (SHELLQs). I. Discovery of 15 quasars and bright galaxies at 5.7 < z < 6.9

We report the discovery of 15 quasars and bright galaxies at 5.7 < z < 6.9. This is the initial result from the Subaru High-z Exploration of Low-Luminosity Quasars (SHELLQs) project, which exploits the exquisite multiband imaging data produced by the Subaru Hyper Suprime-Cam (HSC) Strategic Program survey. The candidate selection is performed by combining several photometric approaches including a Bayesian probabilistic algorithm to reject stars and dwarfs. The spectroscopic identification was carried out with the Gran Telescopio Canarias and the Subaru Telescope for the first 80 deg2 of the survey footprint. The success rate of our photometric selection is quite high, approaching 100 % at the brighter magnitudes (zAB < 23.5 mag). Our selection also recovered all the known high-z quasars on the HSC images. Among the 15 discovered objects, six are likely quasars, while the other six with interstellar absorption lines and in some cases narrow emission lines are likely bright Lyman-break galaxies. The remaining three objects have weak continua and very strong and narrow Ly alpha lines, which may be excited by ultraviolet light from both young stars and quasars. These results indicate that we are starting to see the steep rise of the luminosity function of z > 6 galaxies, compared with that of quasars, at magnitudes fainter than M1450 ~ -22 mag or zAB ~24 mag. Follow-up studies of the discovered objects as well as further survey observations are ongoing.Comment: Published in ApJ (828:26, 2016

Discovery of the First Low-Luminosity Quasar at z > 7

We report the discovery of a quasar at z = 7.07, which was selected from the deep multi-band imaging data collected by the Hyper Suprime-Cam (HSC) Subaru Strategic Program survey. This quasar, HSC J124353.93+010038.5, has an order of magnitude lower luminosity than do the other known quasars at z > 7. The rest-frame ultraviolet absolute magnitude is M1450 = -24.13 +/- 0.08 mag and the bolometric luminosity is Lbol = (1.4 +/- 0.1) x 10^{46} erg/s. Its spectrum in the optical to near-infrared shows strong emission lines, and shows evidence for a fast gas outflow, as the C IV line is blueshifted and there is indication of broad absorption lines. The Mg II-based black hole mass is Mbh = (3.3 +/- 2.0) x 10^8 Msun, thus indicating a moderate mass accretion rate with an Eddington ratio 0.34 +/- 0.20. It is the first z > 7 quasar with sub-Eddington accretion, besides being the third most distant quasar, known to date. The luminosity and black hole mass are comparable to, or even lower than, those measured for the majority of low-z quasars discovered by the Sloan Digital Sky Survey, and thus this quasar likely represents a z > 7 counterpart to quasars commonly observed in the low-z universe.Comment: Accepted for publication in ApJ Letter

First Data Release of the Hyper Suprime-Cam Subaru Strategic Program

The Hyper Suprime-Cam Subaru Strategic Program (HSC-SSP) is a three-layered imaging survey aimed at addressing some of the most outstanding questions in astronomy today, including the nature of dark matter and dark energy. The survey has been awarded 300 nights of observing time at the Subaru Telescope and it started in March 2014. This paper presents the first public data release of HSC-SSP. This release includes data taken in the first 1.7 years of observations (61.5 nights) and each of the Wide, Deep, and UltraDeep layers covers about 108, 26, and 4 square degrees down to depths of i~26.4, ~26.5, and ~27.0 mag, respectively (5sigma for point sources). All the layers are observed in five broad bands (grizy), and the Deep and UltraDeep layers are observed in narrow bands as well. We achieve an impressive image quality of 0.6 arcsec in the i-band in the Wide layer. We show that we achieve 1-2 per cent PSF photometry (rms) both internally and externally (against Pan-STARRS1), and ~10 mas and 40 mas internal and external astrometric accuracy, respectively. Both the calibrated images and catalogs are made available to the community through dedicated user interfaces and database servers. In addition to the pipeline products, we also provide value-added products such as photometric redshifts and a collection of public spectroscopic redshifts. Detailed descriptions of all the data can be found online. The data release website is https://hsc-release.mtk.nao.ac.jp/.Comment: 34 pages, 20 figures, 7 tables, moderate revision, accepted for publication in PAS