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Background The construction of linkage maps is a first step in exploring the genetic basis for adaptive phenotypic divergence in closely related species by quantitative trait locus (QTL) analysis. Linkage maps are also useful for comparative genomics in non-model organisms. Advances in genomics technologies make it more feasible than ever to study the genetics of adaptation in natural populations. Restriction-site associated DNA (RAD) sequencing in next-generation sequencers facilitates the development of many genetic markers and genotyping. We aimed to construct a linkage map of the gudgeons of the genus Gnathopogon (Cyprinidae) for comparative genomics with the zebrafish Danio rerio (a member of the same family as gudgeons) and for the future QTL analysis of the genetic architecture underlying adaptive phenotypic evolution of Gnathopogon . Results We constructed the first genetic linkage map of Gnathopogon using a 198 F 2 interspecific cross between two closely related species in Japan: river-dwelling Gnathopogon elongatus and lake-dwelling Gnathopogon caerulescens . Based on 1,622 RAD-tag markers, a linkage map spanning 1,390.9 cM with 25 linkage groups and an average marker interval of 0.87 cM was constructed. We also identified a region involving female-specific transmission ratio distortion (TRD). Synteny and collinearity were extensively conserved between Gnathopogon and zebrafish. Conclusions The dense SNP-based linkage map presented here provides a basis for future QTL analysis. It will also be useful for transferring genomic information from a “traditional” model fish species, zebrafish, to screen candidate genes underlying ecologically important traits of the gudgeons.

Understanding temporally attention fluctuations can benefit scientific knowledge and real-life applications. Temporal attention studies have typically used the reaction time (RT), which can be measured only after a target presentation, as an index of attention level. We have proposed the Micro-Pupillary Unrest Index (M-PUI) based on pupillary fluctuation amplitude to estimate RT before the target presentation. However, the kind of temporal attention effects that the M-PUI reflects remains unclear. We examined if the M-PUI shows two types of temporal attention effects initially reported for RTs in the variable foreperiod tasks: the variable foreperiod effect (FP effect) and the sequential effect (SE effect). The FP effect refers to a decrease in the RT due to an increase in the foreperiod of the current trial, whereas the SE effect refers to an increase in the RT in the early part of the foreperiod of the current trial due to an increase in the foreperiod of the previous trial. We used a simple reaction task with the medium-term variable foreperiods (Psychomotor Vigilance Task) and found that the M-PUI primarily reflects the FP effect. Inter-individual analyses showed that the FP effect on the M-PUI, unlike other eye movement indices, is correlated with the FP effect on RT. These results suggest that the M-PUI is a potentially powerful tool for investigating temporal attention fluctuations for a partly unpredictable target.

Our daily activities require vigilance. Therefore, it is useful to externally monitor and predict our vigilance level using a straightforward method. It is known that the vigilance level is linked to pupillary fluctuations via Locus Coeruleus and Norepinephrine (LC-NE) system. However, previous methods of estimating long-term vigilance require monitoring pupillary fluctuations at rest over a long period. We developed a method of predicting the short-term vigilance level by monitoring pupillary fluctuation for a shorter period consisting of several seconds. The LC activity also fluctuates at a timescale of seconds. Therefore, we hypothesized that the short-term vigilance level could be estimated using pupillary fluctuations in a short period and quantified their amplitude as the Micro-Pupillary Unrest Index (M-PUI). We found an intra-individual trial-by-trial positive correlation between Reaction Time (RT) reflecting the short-term vigilance level and M-PUI in the period immediately before the target onset in a Psychomotor Vigilance Task (PVT). This relationship was most evident when the fluctuation was smoothed by a Hanning window of approximately 50 to 100 ms (including cases of down-sampled data at 100 and 50 Hz), and M-PUI was calculated in the period up to one or two seconds before the target onset. These results suggest that M-PUI can monitor and predict fluctuating levels of vigilance. M-PUI is also useful for examining pupillary fluctuations in a short period for elucidating the psychophysiological mechanisms of short-term vigilance.

From the viewpoints of the advantage depths (ADs), peak tumor dose and skin dose, we evaluated the effect on the dose distribution of neutron beam properties, namely the ratio between thermal and epithermal neutron fluxes (thermal/epithermal ratio), fast neutron component and γ-ray component. Several parameter surveys were conducted with respect to the beam properties of neutron sources for boron neutron capture therapy assuming boronophenylalanine as the boron agent using our dose calculation tool, called SiDE. The ADs decreased by 3% at a thermal/epithermal ratio of 20–30% compared with the current recommendation of 5%. The skin dose increased with the increasing thermal/epithermal ratio, reaching a restricted value of 14 Gyeq at a thermal/epithermal ratio of 48%. The fast neutron component was modified using two different models, namely the ‘linear model’, in which the fast neutron intensity decreases log-linearly with the increasing neutron energy, and the ‘moderator thickness (MT) model’, in which the fast neutron component is varied by adjusting the MT in a virtual beam shaping assembly. Although a higher fast neutron component indicated a higher skin dose, the increment was <10% at a fast neutron component of <1 × 10−12 Gy cm2 for both models. Furthermore, in the MT model, the epithermal neutron intensity at a fast neutron component of 6.8 × 10−13 Gy cm2 was 41% higher compared with that of 2 × 10−13 Gy cm2. The γ-ray component also caused no significant disadvantages up to several times larger compared with the current recommendation.

The accelerator-based boron neutron capture therapy (BNCT) system has been approved for specific cases covered by health insurance, and clinical trials for new cases in Japan are currently being conducted on other systems. Owing to the progress of accelerator-based BNCT, the operation of medical physics must be rendered more efficient. A water phantom is used for the quality assurance (QA) of the BNCT beam output procedure; however, a solid phantom is preferred for routine QA because of its ease of use. Additionally, because water phantoms cannot be readily used in some facilities owing to structural problems, solid phantoms are preferred for unified measurements at different facilities to compare beam outputs. In this study, we perform irradiation tests using an acrylic phantom and verify that an acrylic phantom can be used for QA. The distribution of thermal neutron flux and gamma-ray dose rate inside the acrylic phantom are evaluated through experiments and simulations. The results indicate that the acrylic phantom is suitable for routine QA and for comparing beam outputs among different systems. In the future, the same irradiation tests will be conducted at other facilities.

Marine ecosystem degradation due to microplastic pollution is a significant environmental problem, as acknowledged by Sustainable Development Goal 14. Decomposition of plastics using near critical or supercritical water is a promising method to remove microplastics. To optimize this method for realizing environmental benefits, it is necessary to clarify the structural change of materials during the process. Thus, we investigated the decomposition processes of polystyrene particles dispersed in deuterated water (D2O) during heating under near critical or supercritical conditions by using in situ small-angle neutron scattering. Under subcritical conditions, the PS particles were swollen by D2O due to increased compatibility with temperature. In subcritical conditions near the critical point, cleavage of PS chains in the particles occurred, so that the swollen ratio was enhanced despite the PS particles keeping their shapes. Under supercritical conditions, the PS particles were degraded into oil, including oligomers or monomers and phase-separated structures with styrene-rich and D2O-rich regions.The decomposition process of polystyrene particles dispersed in D2O was analyzed by in situ small-angle neutron scattering under near critical and supercritical conditions. Upon heating in the subcritical state, the particles were swollen by D2O because of enhanced miscibility between polystyrene and D2O. In the supercritical state, the particles were completely degraded and formed monomer- or oligomer-rich domains due to phase separation. The findings and utilized techniques provide essential knowledge about the ways to elucidate the structural change of plastics in sub- and supercritical fluids.

Background DCV-TRIO, a fixed-dose combination of daclatasvir (pangenotypic NS5A inhibitor), asunaprevir (NS3/4A protease inhibitor), and beclabuvir (non-nucleoside NS5B inhibitor), has achieved high rates of sustained virologic response at post-treatment Week 12 (SVR12) in phase 3 studies. Methods In this phase 3 study, DCV-TRIO for 12 weeks and daclatasvir plus asunaprevir (DUAL) for 24 weeks were studied in Japanese patients infected with HCV genotype 1 (99 % genotype 1b). Results SVR12 rates ≥95 % were achieved in both treatment-naive ( N  = 152) and interferon-experienced ( N  = 65) cohorts treated with DCV-TRIO for 12 weeks and were comparable across patient subgroups, including patients aged ≥65 years and those with cirrhosis. DUAL recipients ( N  = 75) had an SVR12 rate of 87 %. In the absence of baseline resistance-associated polymorphisms at positions NS5A-Y93H or -L31, SVR12 rates were 98 % with DCV-TRIO or DUAL. Among genotype 1b-infected patients with baseline Y93H or L31 polymorphisms, 35/38 (92 %) DCV-TRIO recipients, and 7/16 (44 %) DUAL recipients achieved SVR12. Adverse events, mostly liver related, led to treatment discontinuation in 10 % of DCV-TRIO recipients. In this group, SVR12 was achieved by 3/9 patients who discontinued before Week 4 and by 12/12 patients who completed ≥4 weeks of DCV-TRIO. Treatment-related serious adverse events occurred in 4 and 3 % of DCV-TRIO and DUAL recipients, respectively. Seven patients (9 %) discontinued DUAL due to adverse events. No deaths occurred. Conclusion SVR12 was achieved by 96 % of Japanese patients with HCV genotype 1 infection after 12 weeks of treatment with the DCV-TRIO regimen. DCV-TRIO and DUAL exhibited comparable safety profiles.

BackgroundHepatitis C virus (HCV) infection is common in hemodialysis patients and worsens their prognosis, while antiviral therapy options are limited. Recently, clinical trial and real-world, small-scale studies have reported excellent responses to direct-acting antivirals in patients with advanced chronic kidney diseases. However, real-world, large-scale data were lacking. This large multicenter analysis included HCV-infected hemodialysis patients receiving combination therapy with a nonstructural protein 5A (NS5A) inhibitor, daclatasvir (DCV), and a protease inhibitor, asunaprevir (ASV).MethodsTwenty-three centers in Japan participated in this study of 123 hemodialysis patients with genotype 1 HCV infection, who received DCV/ASV combination therapy between November 2014 and March 2016. We collected and analyzed data relating to treatment outcome, baseline clinical information, laboratory measurements (during and after the treatment), and adverse events.ResultsThirty-nine patients (31.7%) had advanced liver fibrosis, 12 (9.8%) had histories of hepatocellular carcinoma (HCC), and 18 (14.6%) had baseline resistance-associated variants (RAVs) of NS5A. The overall sustained virological response (SVR)12 rate was 95.9% (118/123). Notably, all patients with HCC and 94.4% (17/18) of those with NS5A RAVs achieved SVR12. Significant factors associated with non-SVR were advanced fibrosis and the interleukin-28B non-TT genotype at rs8099917. Four patients (3.3%) discontinued therapy because of adverse events including elevated serum alanine transaminase levels (n = 2), rash (n = 1), and HCC (n = 1); all of these achieved SVR12.ConclusionsThis real-world, nationwide study revealed that DCV/ASV combination therapy was safe and highly effective for hemodialysis patients with genotype 1 HCV infections. This study was registered at the UMIN Clinical Trials Registry (UMIN000024227).

Plasmons, which are collective charge oscillations, could provide a means of confining electromagnetic field to nanoscale structures. Recently, plasmonics using graphene have attracted interest, particularly because of the tunable plasmon dispersion, which will be useful for tunable frequency in cavity applications. However, the carrier density dependence of the dispersion is weak (proportional to n 1/4 ) and it is difficult to tune the frequency over orders of magnitude. Here, by exploiting electronic excitation and detection, we carry out time-resolved measurements of a charge pulse travelling in a plasmon mode in graphene corresponding to the gigahertz range. We demonstrate that the plasmon velocity can be changed over two orders of magnitude by applying a magnetic field B and by screening the plasmon electric field with a gate metal; at high B , edge magnetoplasmons, which are plasmons localized at the sample edge, are formed and their velocity depends on B , n and the gate screening effect. In metals, plasmon properties are fixed once the structure is built, but in graphene they can be altered by electric or magnetic fields. Using electrical time-of-flight measurements, Kumada et al . show wide plasmon velocity tunability in graphene with a varying magnetic field.

BackgroundIn the UNITY-3 study, 96% sustained virologic response (SVR12) rate was observed in Japanese patients with hepatitis C virus (HCV) genotype (GT)-1 infection treated for 12 weeks with fixed-dose daclatasvir, asunaprevir, and beclabuvir (DCV-TRIO). As HCV clearance may improve liver outcomes, we assessed hepatic fibrosis and alpha-fetoprotein (AFP), a hepatocellular carcinoma risk marker, pre- and post-treatment in UNITY-3.MethodsTreatment-naive or interferon-experienced UNITY-3 patients with HCV GT-1 who received twice-daily DCV-TRIO were assessed for fibrosis [FibroTest; FibroScan; fibrosis-4 index (FIB-4), aspartate-aminotransferase-to-platelet-ratio index] and AFP at baseline and Weeks 4 (FIB-4 only), 12 or 24 post-treatment.ResultsOf 217 patients, 99% had GT-1b infection, 46% were aged > 65 years, 21% had compensated cirrhosis, and 26% baseline HCV-RNA > 107 IU/mL. All GT-1b patients treated ≥ 4 weeks achieved SVR12 with (n = 54) or without (n = 144) baseline NS5A polymorphisms associated with DCV resistance (positions 28/30/31/93). Statistically significant post-treatment reductions from baseline were observed for all fibrosis measures and AFP, with numerically greater reductions in cirrhotic patients. FibroTest category improved in 44%, remained stable in 50%, and worsened in 6% of patients; 98% with baseline AFP < 6 μg/L remained < 6 μg/L and 51% with baseline AFP ≥ 6 μg/L were < 6 μg/L post-treatment.ConclusionsDCV-TRIO administered for 12 weeks to Japanese patients with primarily GT-1b infection achieved a high SVR12 rate and resulted in improved measures of hepatic fibrosis and serum AFP that may reduce the risk of future liver disease progression and hepatocellular carcinoma, particularly in those with compensated cirrhosis.