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The tidal triggering of earthquakes has been studied for many years. The discovery of slow earthquakes in the early 2000s, including slow slip, has urged scientists to investigate the tidal responses of these earthquakes due to their sensitivity to weak stress perturbations. Previous studies have shown that slow earthquakes correlate with diurnal and semidiurnal tides and seasonal variations in surface loads more clearly than ordinary earthquakes. However, little is known about long-term responses to external stresses. In this paper, based on a widely accepted frictional law for faults, a mechanism is proposed by which nontidal variations in ocean bottom pressure, when combined with tides, promote the occurrence of slow earthquakes. Because slow earthquakes accompany a slip on the plate interface, this mechanism allows one to estimate slip modulations. A one-degree-of-freedom slip model is constructed and applied to Ise Bay in the Tonankai region of southwestern Japan, where large-scale ocean mass redistributions have occurred. The model calculated with parameters determined from the observation of tectonic tremors is quantitatively consistent with the slip during 1997–2013 inferred from GNSS data, suggesting that the decrease in the sea-level change in approximately 2006 could cause the acceleration of a slip observed after that. This result implies that the decreases in sea level in approximately 1996 and 2014 could also cause subsequent slip accelerations. These three slip acceleration periods temporally coincide with the increases in background seismicity in a shallower portion of the plate interface. These changes in seismicity are common to shallow earthquakes in the Tokai area, and a similar model can reproduce them. Further studies are expected to reveal causality between shallow earthquakes and long-term slip fluctuations based on modeling that considers changes in the frictional property along the plate interface.

Abstract Molnupiravir (MK‐4482) is an oral prodrug of the antiviral ribonucleoside analog, N‐hydroxycytidine (NHC), which has activity against RNA viruses, including severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). We conducted a phase I safety and pharmacokinetic study of molnupiravir in healthy Japanese adult participants. A sample size larger than typically used in pharmacokinetic studies was implemented to collect additional safety data in the Japanese population to support special approval for emergency use in Japan. Single doses of molnupiravir up to 1600 mg and multiple doses of 400 and 800 mg administered every 12 h (q12h) for 5.5 days were generally well‐tolerated. NHC appeared rapidly in plasma and reached maximum concentration (Cmax), with a median time to Cmax (Tmax) between 1.00 and 2.00 h. Area under the concentration versus time curve from zero to infinity (AUC0–inf), area under the concentration versus time curve from zero to 12 h (AUC0–12), and Cmax of plasma NHC increased approximately dose proportionally. With q12h dosing, the geometric mean (GM) accumulation ratios for NHC AUC0–12 and Cmax were ~1 for 400 and 800 mg. Pharmacokinetics of NHC triphosphate (NHC‐TP), the active metabolite of NHC was assessed in peripheral blood mononuclear cells and also demonstrated roughly dose proportional pharmacokinetics. The GM accumulation ratios for NHC‐TP AUC0–12 and Cmax were ~2.5 for 400 and 800 mg. Following administration with food, only a modest reduction (24%) in plasma NHC Cmax with comparable AUC0–inf was seen, supporting administration without regard to food.

The catalytic mechanism of hammerhead ribozymes (HHRzs) attracted great attention in relation to the chemical origin of life. However, the basicity (pKa) of the catalytic sites of HHRzs has not been studied so far. As a result, the investigation of the currently assumed mechanism from an experimentally derived pKa value has been impossible. In HHRzs, there exists a highly functionalized structural unit (A9-G10.1 site) with a catalytic residue (G12) for the nucleophile activation and metal ion-binding residue (G10.1). As inferred from this fact, there might be a possibility that HHRzs may utilize specific functions of the A9-G10.1 motif for the catalytic reaction. Therefore, here we studied the basicity of G12/G10.1-corresponding residues using RNA duplexes including the A9-G10.1 motif without other conserved residues of HHRzs. From the pH-titration experiments with NMR spectra, we have obtained the intrinsic basicity of the G12/G10.1-corresponding residues in the motif, with pKa > 11.5 (N1 of G12) and pKa 4.5 (N7 of G10.1) for the first time. Based on the derived irregular basicity, their correlation with a catalytic activity and a metal affinity were investigated. In total, the derived thermodynamic properties are an intrinsic nature of the exclusive catalytic unit of HHRzs, which will be an outstanding pivot point for the mechanistic analyses.

Abstract Capsicum fruits synthesize capsaicin from vanillylamine, which is produced from vanillin in a reaction catalyzed by a putative aminotransferase (pAMT). Capsiate, a non-pungent compound that is structurally similar to capsaicin, is synthesized from vanillyl alcohol rather than vanillylamine. Vanillyl alcohol is possibly generated by the enzymatic reduction of vanillin, but the enzyme responsible for this reaction is unknown. In the present study, we revealed that the vanillin reductase in the capsiate biosynthetic pathway is cinnamyl alcohol dehydrogenase (CAD), which is an enzyme involved in lignin synthesis. The reduction of vanillin to vanillyl alcohol was greater in the mature red fruit placental extract than in the immature green fruit placental extract. This reduction was suppressed by both N-(O-hydroxyphenyl) sulfinamoyltertiobutyl acetate, a specific inhibitor of CAD, and ethylenediaminetetraacetic acid, a metalloenzyme inhibitor. The CaCAD1 transcript levels in the placenta were higher in the red fruits than in the green fruits. A recombinant CaCAD1 protein obtained using an Escherichia coli expression system reduced vanillin to vanillyl alcohol. This reaction was suppressed by the CAD inhibitors. These results strongly suggest that CAD is the enzyme that catalyzes the reduction of vanillin to vanillyl alcohol during capsiate biosynthesis. Syntenic analyses indicated that genes encoding CAD and capsaicin synthase (Pun1) involved in capsiate biosynthesis were acquired before the pAMT gene during the evolution of the family Solanaceae. This raises the possibility that in the genus Capsicum, the capsiate biosynthetic pathway emerged before the pAMT-encoding gene was acquired as the final trigger for capsaicin biosynthesis.

This study examined the quantitative relationship between lesson study and non-cognitive skills in Vietnam, using t-test analysis for comparison before and after. We also looked at the relationship between lesson study and cognitive skills, teacher engagement and parental involvement. Unlike former studies, we found no relationship between lesson study and cognitive skills, however that is consistent with the general finding in the literature that lesson study seems to have more of an impact on academic performance at the primary than at the secondary level. Nonetheless, and most importantly, we did find a statistically significant relationship between lesson study and non-cognitive skills, specifically extraversion and conscientiousness, two of the Big Five traits that psychologists generally agree make up the taxonomy of non-cognitive traits. We also found that lesson study led teachers to have more dialogue with their students and parents to engage more with their children on their academic progress. In light of the correlation between lower secondary education and non-cognitive skills, these results suggest that lesson study at the lower secondary level may lead to improved academic outcomes at the upper secondary and higher education levels as well as improved life outcomes including behavioral and labor market outcomes.

The title compound, N′1,N′4-bis(2-(7,8-dimethyl-2,4-dioxo-3,4-dihydrobenzo[g]pteridin-10(2H)-yl)ethylidene)succinohydrazide (1), was obtained by the reaction of formylmethylflavin and succinic acid dihydrazide. The product 1 was characterized by 1H-NMR, 13C-NMR, HRMS and UV.

To improve the transmission efficiency of a continuously variable transmission (CVT) system, it is effective to form a tribofilm with higher friction coefficient. Therefore, understanding of the correlation between the tribofilm formation and friction coefficient in a CVT fluid has been a great deal. In this study, the tribofilm formation on a bearing steel ball surface under the simulated additive oil was investigated. We used ball-on-disk tribological test and optical microscopy imaging to observe the temporal changes in the tribofilm growth. Atomic force microscopy and energy-dispersive X-ray spectrometry analyses revealed that the tribofilm consisted of pad-like structures derived by tricresyl phosphate and calcium sulfonate additives. A binary imaging analysis showed that the total area of the pad-like structure was a key parameter determining the friction coefficient. The pads were repeatedly desorbed and reformed during the sliding test. These results improve the design of future CVT systems and lubricants.

The arrival and departure dates and the daily maximum populations of migrating swans (Cygnus cygnus) on the Asadokoro tidal flat, Hiranai town, Aomori Prefecture, Japan, were recorded by elementary school students for more than 50 years between 1956 and 2010. The Asadokoro tidal flat, which lies along the coast of Mutsu Bay, has been designated a National Special Natural Monument, known as “The swans of Kominato and their migration grounds.” This long history of observation unfortunately came to an end with the closure of the elementary school in 2012. If analyzed together with data on environmental factors, such as temperature changes or the effects of avian influenza, this dataset could provide a potentially valuable source of information, and consequently, future secondary use of the data is anticipated.

Aim: The quadrivalent human papillomavirus (4vHPV) vaccine has demonstrated efficacy and immunogenicity and was generally well tolerated in clinical trials conducted in Japan. We report a detailed safety analysis of injection-site reactions in female Japanese 4vHPV clinical trial participants. Methods: This post-hoc analysis included data from 2 double-blind, placebo-controlled phase II clinical trials of a 3-dose (Day 1, Month 2, Month 6) regimen of 4vHPV vaccine in Japanese young women aged 18–26 years (N = 1021; NCT00378560) and girls aged 9–17 years (N = 107; NCT00411749). Injection-site and systemic adverse events (AEs) were monitored using vaccination report cards for 15 days after each vaccine dose; serious AEs were reported throughout the trials. Post-hoc analyses of data from these trials were performed to examine details of injection-site AEs, including day of onset, time from onset to resolution, and maximum intensity. Results: Injection-site AEs were reported by 85.6% of 4vHPV vaccine recipients and 72.4% of placebo recipients, most commonly erythema, pain, pruritus, and swelling (each >5% of 4vHPV vaccine recipients). The majority of injection-site AEs had an onset within 3 days of vaccination and were mild to moderate in intensity; few 4vHPV vaccine recipients reported severe injection-site AEs (2.0% overall). All injection-site AEs resolved, and most (4vHPV: 87.5%; placebo: 92.7%) resolved within 5 days of onset. Conclusions: Most injection-site reactions are mild or moderate in intensity and of short duration. The 3-dose regimen of 4vHPV vaccine is well tolerated in Japanese female clinical trial participants based on this post-hoc analysis. These results will further support safety communication between healthcare providers and vaccine recipients regarding the HPV vaccine. Trial registration: Clinicaltrials. gov: NCT00378560 and NCT00411749.

Hepatitis B vaccines are highly effective in preventing hepatitis B virus infection and have been included in the national immunization program of Japan since 2016. Heptavax®-II is one of two hepatitis B vaccine products licensed in Japan, and its manufacturing process is being modified to reduce variability of manufacturing and optimize immunogenicity. In this study (NCT01463683), the immunogenicity and safety of a modified-process hepatitis B vaccine (mpHBV) were compared to those of the licensed Heptavax®-II. Overall, 722 Japanese adults aged 20-to-35 years old were randomized in a 3:3:1 ratio to either the mpHBV subcutaneous (SC) injection group (mpHBV SC), the Heptavax®-II SC injection group (Heptavax®-II SC), or the mpHBV intramuscular (IM) injection group (mpHBV IM). All participants received a 3-dose series of either mpHBV or Heptavax®-II at Day 1, Month 1, and Month 6. Serum antibody to hepatitis B virus surface antigen (anti-HBs) was assayed on Day 1 prior to the first vaccination and Month 7 (1 month Postdose 3). Seroprotection rates in mpHBV SC were non-inferior to that in Heptavax®-II SC and anti-HBs geometric mean titers were numerically higher in mpHBV SC as compared to Heptavax®-II SC. The incidences of injection-site and systemic adverse events (AEs) observed in mpHBV SC were comparable to those in Heptavax®-II SC, except for erythema which was higher in mpHBV SC than in Heptavax®-II SC. Most injection-site and systemic AEs were mild-to-moderate in intensity and there were no reports of vaccine-related serious AEs in any group. IM administration of mpHBV was well-tolerated and more immunogenic compared to SC administration. In conclusion, mpHBV and Heptavax®-II were well-tolerated and elicited satisfactory immune responses for the prevention against hepatitis B virus-associated diseases.

Abstract The water in Earth’s mantle is closely related with plate subduction and volcanism. Recent studies revealed that the mantle wedge corner at approximately 30 km depth holds high-pressure water, where many slow earthquakes occur. To quantify how such water behaves during slow earthquakes helps us understand the mechanisms of these earthquakes and (eventually) a part of the long-term water cycle between the interior and surface of the Earth. However, little evidence has thus far been reported on the transient flows of such deep water. Here, we report anomalous, negative mass anomalies during two recent long-term slow slip events in the Tokai area in Japan, which were detected by absolute gravity measurements over 20 years. We present a poroelastic fluid flow model assuming a localized deformation within the fault fracture zone. The model can reproduce the gravity change with a permeability range between those suggested by laboratory experiments and numerical simulations of slow earthquakes.

Rotavirus is the leading cause of severe acute gastroenteritis in infants and young children. Most children are infected with rotavirus, and the health and economic burdens of rotavirus gastroenteritis on healthcare systems and families are considerable. In 2012 pentavalent rotavirus vaccine (RV5) and diphtheria, tetanus, acellular pertussis and inactivated poliovirus vaccine derived from Sabin strains (DTaP-sIPV) were licensed in Japan. We examined the immunogenicity and safety of DTaP-sIPV when administrated concomitantly with RV5 in Japanese infants. A total of 192 infants 6 to 11 weeks of age randomized to Group 1 (N = 96) received DTaP-sIPV and RV5 concomitantly, and Group 2 (N = 96) received DTaP-sIPV and RV5 separately. Antibody titer to diphtheria toxin, pertussis antigens (PT and FHA), tetanus toxin, and poliovirus type 1, 2, and 3 were measured at 4 to 6 weeks following 3-doses of DTaP-sIPV. Seroprotection rates for all components of DTaP-sIPV were 100% in both groups, and the geometric mean titers for DTaP-sIPV in Group 1 were comparable to Group 2. Incidence of systemic AEs (including diarrhea, vomiting, fever, and nasopharyngitis) were lower in Group 1 than in Group 2. All vaccine-related AEs were mild or moderate in intensity. There were no vaccine-related serious AEs, no deaths, and no cases of intussusception during the study. Concomitant administration of DTaP-sIPV and RV5 induced satisfactory immune responses to DTaP-sIPV and acceptable safety profile. The administration of DTaP-sIPV given concomitantly with RV5 is expected to facilitate compliance with the vaccination schedule and improve vaccine coverage in Japanese infants.

The greatest earthquake in the modern history of Japan and probably the fourth greatest in the last 100 years in the world occurred on March 11, 2011 off the Pacific coast of Tohoku. Large tsunami and ground motions caused severe damage in wide areas, particularly many towns along the Pacific coast. So far, gravity change caused by such a great earthquake has been reported for the 1964 Alaska and the 2010 Maule events. However, the spatial-temporal resolution of the gravity data for these cases is insufficient to depict a co-seismic gravity field variation in a spatial scale of a plate subduction zone. Here, we report an unequivocal co-seismic gravity change over the Japanese Island, obtained from a hybrid gravity observation (combined absolute and relative gravity measurements). The time interval of the observation before and after the earthquake is within 1 year at almost all the observed sites, including 13 absolute and 16 relative measurement sites, which deduced tectonic and environmental contributions to the gravity change. The observed gravity agrees well with the result calculated by a dislocation theory based on a self-gravitating and layered spherical earth model. In this computation, a co-seismic slip distribution is determined by an inversion of Global Positioning System (GPS) data. Of particular interest is that the observed gravity change in some area is negative where a remarkable subsidence is observed by GPS, which can not be explained by simple vertical movement of the crust. This indicated that the mass redistribution in the underground affects the gravity change. This result supports the result that Gravity Recovery and Climate Experiment (GRACE) satellites detected a crustal dilatation due to the 2004 Sumatra earthquake by the terrestrial observation with a higher spatial and temporal resolution.

Indonesia has prioritized upper secondary vocational education since 2006. This study examines the labour market outcomes of upper secondary vocational education in terms of decent work (DW), using Indonesian Family Life Survey data and a research framework that links DW into the broader labour economics of the school to work transition. We compare urban and rural workers with upper secondary vocational education to those with general education, using both simple regressions and propensity score matching. Workers with upper secondary vocational education do not earn higher wages or have better employment conditions than workers with general education. An exception is for workplace-provided training and pensions, where vocational graduates did better than general ones in 2014-15, a change from 2007; this effect was also much stronger in urban than in rural areas. Our findings raise questions about Indonesia's policy of expanding upper secondary vocational education without also focusing on its quality.

The relative contributions of environmental and spatial processes in macroinvertebrate community structure (i.e., β-diversity) for three functional groups classified on the basis of dispersal ability and microhabitat selection (seagrass-associated [SA], drift-faunal [DF], and benthic-faunal [BF] groups) were examined in a seagrass ecosystem along the Sanriku coast of Japan. Variation partitioning was conducted to explain the environmental heterogeneity and spatial arrangement of local communities (i.e., degree of variation in the community) for each functional group. Processes determining community structure and metacommunity type differed among the functional groups. The SA group was under greater influence of environmental control, whereas the fractions of β-diversity in the DF and BF groups were explained by only spatial predictors. Thus, even if macroinvertebrate communities live in the same ecosystem, different mechanisms may determine the functional community structure, which depends on ecological traits such as dispersal ability and microhabitat. Ecological processes underlying community assembly differ among functional groups, indicating that the existence and/or dynamics of seagrass patches may affect the variation of faunal functions in an ecosystem. Keywords: Assembly rule, Metacommunity, Spatial autocorrelation, Variation partitioning (VP), Macroinvertebrate, Sanriku coats of Japan

Human can realize flexible and skillful movements by controlling his/her musculoskeletal system and the interactive force with environments appropriately. However it still exist many uncertain biological motor characteristics in human movements even for a simple task. This paper aims to analyze and evaluate acceleration characteristics of the human hand during quick arm motion. First, the dynamic manipulability of end-point via muscle forces, called Human Muscular Mobility Ellipsoid (HMME), is newly defined. Next, the direction-dependent acceleration characteristic of the human hand motion is examined and analyzed its geometrical properties with an approximation ellipses of measured data. It is also discussed the problem that the conventional measures relative to the performance of end-point acceleration cannot represent the geometrical properties of human generated hand acceleration in good agreement with the measured data. Finally, the merits of HMME compared with the conventional measures is then demonstrated with a set of experimental results and computed results: HMME can be utilized in representing the geometric properties of human hand acceleration.

As the urgency to reduce carbon emission increases, seagrass ecosystems have recently received attention due to their capacity to take up and store high amounts of carbon. Protection of this ecosystem is key to increase resilience to climate change. However, in some of the Marine Protected Areas (MPAs), seagrass ecosystems are still under threat. This study aims to investigate the current condition of seagrass ecosystems and compare it to the previous study before MPA was established in the Berau coastal water. SeagrassWatch method was used to measure seagrass community structure. Other proxies were also used to explain factors affecting seagrass condition such as total suspended solid (TSS) and sedimentary stable isotopes to identify the source of organic carbon. The percentage cover of seagrass in this study were categorized as not healthy (<29-59.9%), which was statistically related to TSS. The higher TSS resulted in the lower seagrass cover, as observed in the Rabu Rabu island located adjacent to mainland. Changes in seagrass composition were observed, including the emergence of larger species of E. acoroides and T. hemprichii in the islands located adjacent to mainland. The spatial and temporal changes of seagrass ecosystems observed in Berau MPA should be taken into consideration that conservation on seagrass ecosystems needs to be prioritized by improving the MPA function to avoid further loss of carbon from seagrass ecosystems. [ABSTRACT FROM AUTHOR]