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Abstract Lepton-number violation (LNV) is required in leptogenesis to explain why the observable universe has more matter than antimatter. There exist two theoretical predictions about nuclear $\\beta$ decay with LNV: one is neutrinoless double $\\beta$ decay ($0\\nu 2\\beta$) and the other neutrinoless quadruple $\\beta$ decay ($0\\nu 4\\beta$). In order to search for these events, we have been developing a magnetic drift chamber beta-ray analyzer (DCBA) at KEK. It consists of self-triggered drift chambers for $\\beta$-ray tracking, nuclear decay source plates, and a superconducting solenoid magnet. The $\\beta$-ray momentum is obtained by measuring the helical radius, the pitch angle, and the magnetic field density, and then its kinetic energy is calculated from the momentum. The test facility DCBA-T2.5 has measured the half-life of the two-neutrino double beta decay ($2\\nu 2\\beta$) of $^{100}$Mo to the ground state of $^{100}$Ru as $T^{2\\nu 2\\beta }_{1/2}=[7.23^{+0.99}_{-0.77}(\\mathrm{stat})\\pm 0.76(\\mathrm{syst})]\\times 10^{18}\\, \\mathrm{yr}$. The DCBA-T3 has been proposed to search for LNV events, especially for $0\\nu 4\\beta$ of the $^{150}$Nd transition to $^{150}$Gd. It is essential to detect four $\\beta$-rays with a sum energy of 2.08 MeV (Q-value) from a common start point in the source plate. This article describes the present status and the future prospects of DCBA.

Lymphocystis disease virus (LCDV) is the causative agent of lymphocystis disease. In this study, nucleotide sequences of the major capsid protein (MCP) gene were analyzed among LCDV isolates from Japanese flounder and rockfish. A phylogenetic tree revealed three clusters for lymphocystiviruses. The first cluster included Japanese flounder isolates; the second cluster consisted of rockfish isolates; and the remaining one consisted of LCDV-1. Nucleotide sequence identities were > or =99.6% among Japanese flounder isolates and 100% among rockfish isolates, while between each cluster they were < or =85.2%. Experimental infections with Japanese flounder and rockfish isolates revealed that Japanese flounder and rockfish were infected by the respective homologous isolate but not by the heterologous isolate. These findings suggest that at least three genotypes exist in the genus Lymphocystivirus.

This research investigates mixing phenomena in bottom gas-stirred ladles using water modeling, which incorporates hexane as the top layer. The effects of slag thickness, nozzle position, number of nozzles, and gas flow rate on mixing time have been investigated. Conditions to improve mixing time have been identified. A single nozzle located at two-thirds of the ladle radius was found to produce the shortest mixing time. Under extremely low gas flow rates, an unusual behavior was observed, where the top layer promoted a decrease in mixing time.

Previous studies have demonstrated that the serotonin transporter gene-linked polymorphic region (5-HTTLPR) affects the recognition of facial expressions and attention to them. However, the relationship between 5-HTTLPR and the perceptual detection of others' facial expressions, the process which takes place prior to emotional labeling (i.e., recognition), is not clear. To examine whether the perceptual detection of emotional facial expressions is influenced by the allelic variation (short/long) of 5-HTTLPR, happy and sad facial expressions were presented at weak and mid intensities (25% and 50%). Ninety-eight participants, genotyped for 5-HTTLPR, judged whether emotion in images of faces was present. Participants with short alleles showed higher sensitivity (d') to happy than to sad expressions, while participants with long allele(s) showed no such positivity advantage. This effect of 5-HTTLPR was found at different facial expression intensities among males and females. The results suggest that at the perceptual stage, a short allele enhances the processing of positive facial expressions rather than that of negative facial expressions.

It has been shown that positive emotions can facilitate integrative and associative information processing in cognitive functions. The present study examined whether emotions in observers can also enhance perceptual integrative processes. We tested 125 participants in total for revealing the effects of emotional states and traits in observers on the multisensory binding between auditory and visual signals. Participants in Experiment 1 observed two identical visual disks moving toward each other, coinciding, and moving away, presented with a brief sound. We found that for participants with lower depressive tendency, induced happy moods increased the width of the temporal binding window of the sound-induced bounce percept in the stream/bounce display, while no effect was found for the participants with higher depressive tendency. In contrast, no effect of mood was observed for a simple audiovisual simultaneity discrimination task in Experiment 2. These results provide the first empirical evidence of a dependency of multisensory binding upon emotional states and traits, revealing that positive emotions can facilitate the multisensory binding processes at a perceptual level.

BackgroundUpadacitinib (UPA) is an oral, JAK1-selective inhibitor found to be effective in Phase 2 and 3 studies in rheumatoid arthritis (RA) patients with inadequate response or intolerance to csDMARDs and bDMARDs.1–4 ObjectivesTo evaluate the efficacy and safety of UPA in Japanese active RA patients with inadequate response to csDMARDs (csDMARD-IR).MethodsDuring the 12 week double-blind period, patients on stable csDMARDs were randomised to receive UPA 7.5,15 or 30 mg once daily or PBO (1:1:1:1). The primary endpoint was proportion of patients achieving ACR20 at Wk 12 (NRI).ResultsOf 197 patients treated, 187 completed the double-blind period. At Week 12, more patients receiving UPA 7.5, 15 and 30 mg vs PBO met ACR20 (75.5%, 83.7%,80% vs 42.9%, p<0.001). A significant difference in ACR20 was observed as early as Week 1 (table 1). The more stringent responses, such as ACR50/70, DAS28-CRP≤3.2, were achieved by significantly higher proportions of patients on UPA vs PBO with more patients on UPA 15 mg and 30 mg achieving these responses vs UPA 7.5 mg (Table). At Week 12, patients receiving UPA vs PBO had greater improvements from baseline (p<0.001) in DAS28-CRP (−2.08,–2.39, −2.41 vs −0.79) and HAQ-DI (−0.41,–0.45, −0.49 vs −0.10).Overall adverse events (AE), serious AEs, infections (including serious infections, opportunistic infections and herpes zoster) were numerically higher in UPA 30 mg. There were no events of pulmonary embolism, deep vein thrombosis, tuberculosis or malignancy and there were no deaths. Mean haemoglobin levels improved with UPA 7.5 (+0.35 g/dL) and remained stable with UPA 15 (-0.03 g/dL) vs UPA 30 (-0.54 g/dL) and PBO (−0.17 g/dL). CPK elevations and lymphopenia occurred more frequently in UPA 30 mg.ConclusionsIn this Japanese RA csDMARD-IR population, the efficacy of UPA was demonstrated, with better responses for more stringent endpoints on UPA 15 mg and 30 mg vs 7.5 mg. The frequency of overall AEs was numerically higher in UPA 30 mg. Overall, safety and tolerability were consistent with Phase 2 and 3 studies to date.References[1] Burmester, et al. Arth Rheum2017;69:S10.[2] Genovese, et al. Arth Rheum2017;69:S10.[3] Kremer, et al. Arth Rheum2016;68(12).[4] Genovese, et al. Arth Rheum2016;68(12).AcknowledgementsAbbVie, Inc was the study sponsor, contributed to study design, data collection, analysis and interpretation, and to writing, reviewing, and approval of final version. Statistical support: Masuyuki Yokoyama, Medical writing support:Naina Barretto, both employees of AbbVie.Disclosure of InterestY. Tanaka Grant/research support from: Mitsubishi-Tanabe Pharma Corporation, Takeda Pharmaceutical Company Ltd, Bristol-Myers Squibb Company, Chugai Pharmaceutical Co Ltd, Astellas Pharma Inc, AbbVie GK, MSD K.K., Daiichi Sankyo Company Ltd, Pfizer Japan Inc., Kyowa Hakko Kirin Co., Ltd, Eisai Co., Ltd, Ono Pharmaceutical Co., Ltd, Speakers bureau: Daiichi Sankyo Company Ltd, Astellas Pharma Inc, Pfizer Japan Inc., Mitsubishi-Tanabe Pharma Corporation, Bristol-Myers Squibb Company, Chugai Pharmaceutical Co Ltd, YL Biologics, Eli Lilly Japan KK, Sanofi KK, Janssen Pharmaceutical KK, UCB Japan Co., Ltd, T. Takeuchi Grant/research support from: Pfizer Japan Inc., Eisai Co., Ltd, Astellas Pharma Inc., AbbVie GK, Asahi Kasei Pharma Corporation, Nippon Kayaku Co., Ltd, Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Ltd, AYUMI Pharmaceutical Corporation, Takahashi Industrial and Economic Research Foundation, Paid instructor for: Astellas Pharma Inc., AbbVie GK, Eisai Co., Mitsubishi-Tanabe Pharma Corporation, Chugai Pharmaceutical Co Ltd, Bristol-Myers Squibb Company, UCB Japan Co., Ltd, Speakers bureau: Mitsubishi-Tanabe Pharma Corporation, Janssen Pharmaceutical KK, Chugai Pharmaceutical Co Ltd, Astellas Pharma Inc., AbbVie GK, Eisai Co., Ltd, Bristol-Myers Squibb Company, Daiichi Sankyo Company Ltd, Eli Lilly Japan KK, Pfizer Japan Inc., K. Yamaoka Speakers bureau: Pfizer Japan Inc., Chugai Pharmaceutical Co Ltd, Takeda Pharmaceutical Company Ltd, Astellas Pharma Inc, AbbVie GK, Bristol-Myers Squibb Company, Mitsubishi-Tanabe Pharma Corporation, M. Oribe: None declared, M. Kawano: None declared, Y. Zhou Shareholder of: AbbVie, Employee of: AbbVie, A. Othman Shareholder of: AbbVie, Employee of: AbbVie, A. Pangan Shareholder of: AbbVie, Employee of: AbbVie, S. Kitamura Shareholder of: AbbVie, Employee of: AbbVie, N. Matsuda Shareholder of: AbbVie, Employee of: AbbVie, S. Meerwein Shareholder of: AbbVie, Employee of: AbbVie, H. Kameda Grant/research support from: AbbVie GK, Astellas Pharma Inc, Bristol-Myers Squibb Company, Chugai Pharmaceutical Co Ltd, Mitsubishi-Tanabe Pharma Corporation and Novartis Pharma KK., Speakers bureau: AbbVie GK, Bristol-Myers Squibb Company, Chugai Pharmaceutical Co Ltd, Eli Lilly Japan KK, Janssen Pharmaceutical KK, Mitsubishi-Tanabe Pharma Corporation, Novartis Pharma KK and Sanofi KK

We evaluated the circadian phenotypes of patients with delayed sleep–wake phase disorder (DSWPD) and non-24-hour sleep–wake rhythm disorder (N24SWD), two different circadian rhythm sleep disorders (CRSDs) by measuring clock gene expression rhythms in fibroblast cells derived from individual patients. Bmal1-luciferase ( Bmal1 - luc ) expression rhythms were measured in the primary fibroblast cells derived from skin biopsy samples of patients with DSWPD and N24SWD, as well as control subjects. The period length of the Bmal1 - luc rhythm ( in vitro period) was distributed normally and was 22.80±0.47 (mean±s.d.) h in control-derived fibroblasts. The in vitro periods in DSWPD-derived fibroblasts and N24SWD-derived fibroblasts were 22.67±0.67 h and 23.18±0.70 h, respectively. The N24SWD group showed a significantly longer in vitro period than did the control or DSWPD group. Furthermore, in vitro period was associated with response to chronotherapy in the N24SWD group. Longer in vitro periods were observed in the non-responders (mean±s.d.: 23.59±0.89 h) compared with the responders (mean±s.d.: 22.97±0.47 h) in the N24SWD group. Our results indicate that prolonged circadian periods contribute to the onset and poor treatment outcome of N24SWD. In vitro rhythm assays could be useful for predicting circadian phenotypes and clinical prognosis in patients with CRSDs.