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Abstract Wood products function as carbon storage even after being harvested from forests. This has garnered attention in relevance to climate change countermeasures. In the progress of efforts toward climate change mitigation by private companies, the effective use of wood products has been an important measure. However, the methodology for accounting carbon stocks in wood products for private companies has not been established. Therefore, this study investigated methods for estimating carbon stocks in wood products used in wooden houses built by private enterprises, targeting a major company in the Japanese building industry. The results indicated that both the direct inventory method and flux data method (FDM) were applicable for estimating the carbon stocks. These two methods use data that can be obtained from many other building companies, thus, indicating high versatility. The log-normal, Weibull, normal, and logistic distributions, in descending order, proved to be suitable lifetime functions of wooden houses under the FDM, with a half-life of 66–101 years. It is important to continuously acquire time-series data on the floor areas of both newly built and existing houses and the amount of wood products used to improve the accuracy of estimates and explore future predictions.

BackgroundSustainable forest management (SFM), which has been recently introduced to tropical natural production forests, is beneficial in maintaining timber resources, but information about the co-benefits for biodiversity conservation and carbon sequestration is currently lacking.Methodology/principal findingsWe estimated the diversity of medium to large-bodied forest-dwelling vertebrates using a heat-sensor camera trapping system and the amount of above-ground, fine-roots, and soil organic carbon by a combination of ground surveys and aerial-imagery interpretations. This research was undertaken both in SFM applied as well as conventionally logged production forests in Sabah, Malaysian Borneo. Our carbon estimation revealed that the application of SFM resulted in a net gain of 54 Mg C ha(-1) on a landscape scale. Overall vertebrate diversity was greater in the SFM applied forest than in the conventionally logged forest. Specifically, several vertebrate species (6 out of recorded 36 species) showed higher frequency in the SFM applied forest than in the conventionally logged forest.Conclusions/significanceThe application of SFM to degraded natural production forests could result in greater diversity and abundance of vertebrate species as well as increasing carbon storage in the tropical rain forest ecosystems.

We have synthesized imidazopyridine-type ionic liquids and evaluated their properties. [Cnimpy][Br] (n = 4, 6, 8, 10), in which an alkyl group was introduced at the N1 position of imidazo[1,2-a]pyridine, were all solid at room temperature. Exchange of the counteranions of [Cnimpy][Br] with N(CN)2− and FSI− gave the ionic liquids [Cnimpy][N(CN)2] and [Cnimpy][FSI] in the liquid state at room temperature. In particular, the DSC thermogram of [C10impy][FSI] showed a clear melting point at 22 °C. In [Cnimpy][TFSI], ionic liquids consisting of cations with short alkyl chain lengths (n = 4,6) were solids at room temperature, while those with long alkyl chain lengths (n = 8,10) were liquids. [Cnimpy][FSI] has lower viscosity than other anion-consisting ionic liquids which showed a liquid state at room temperature. [Cnimpy][FSI] has lower viscosity than other anion-containing ionic liquids. In particular, [C4impy][FSI], with its relatively short alkyl chain length, exhibited a viscosity of 101 mPa·s at 25 °C, which renders it suitable for practical applications. [C4impy] [FSI] (50 μM acetonitrile solution) showed fluorescence with maximum absorption at 336 nm. Its fluorescence wavelength was shorter than that of imidazo[1,2-a]pyridine, whereas its fluorescence quantum yield (ΦF 0.39) was higher. Therefore, it is expected to be used as a composite material by employing FRET with a substance that exhibits fluorescence in the visible region.

Hammer forging is a traditional manufacturing technology to produce high stiffness product and is widely used in heavy industries. In the hammer forging, the product is produced through several blows. Unlike forging using mechanical press, the product is produced by the energy in the hammer forging, and consequently the energy distribution in blows plays a crucial role for producing highly accurate product. Conventionally, the energy distribution is determined by the trial-and-error method. This paper proposes a methodology to determine the optimal energy distribution using numerical simulation and design optimization technique. It is important to minimize the total energy for energy saving and the risk of crack for product quality. To produce the highly accurate product, underfill should be avoided, which is handled as the design constraint. Therefore, multi-objective design optimization is performed to minimize the total energy and the risk of crack without underfill. The numerical simulation is so intensive that sequential approximate optimization that response surface is repeatedly constructed and optimized is adopted to identify the pareto-frontier between the total energy and the risk of crack. It is clarified through the numerical result that the proposed approach can determine the energy at each blow effectively. The experiment is also conducted to examine the validity of the proposed approach.

Background and aims: Randomized clinical trials have demonstrated the ability of glucagon-like peptide-1 analogues (GLP-1RAs) to reduce atherosclerotic cardiovascular disease events in patients with type 2 diabetes (T2D). How GLP-1RAs modulate diabetic atherosclerosis remains to be determined yet. Methods: The OPTIMAL study was a prospective randomized controlled study to compare the efficacy of 48-week continuous glucose monitoring- and HbA1c-guided glycemic control on near infrared spectroscopty (NIRS)/intravascular ultrasound (IVUS)-derived plaque measures in 94 statin-treated patients with T2D (jRCT1052180152, UMIN000036721). Of these, 78 patients with evaluable serial NIRS/IVUS images were analyzed to compare plaque measures between those treated with (n = 16) and without GLP-1RAs (n = 72). Results: All patients received a statin, and on-treatment LDL-C levels were similar between the groups (66.9 ± 11.6 vs. 68.1 ± 23.2 mg/dL, p = 0.84). Patients receiving GLP-1RAs demonstrated a greater reduction of HbA1c [-1.0 (-1.4 to −0.5) vs. −0.4 (-0.6 to −0.2)%, p = 0.02] and were less likely to demonstrate a glucose level >180 mg/dL [-7.5 (-14.9 to −0.1) vs. 1.1 (-2.0 - 4.2)%, p = 0.04], accompanied by a significant decrease in remnant cholesterol levels [-3.8 (-6.3 to −1.3) vs. −0.1 (-0.8 - 1.1)mg/dL, p = 0.008]. On NIRS/IVUS imaging analysis, the change in percent atheroma volume did not differ between the groups (−0.9 ± 0.25 vs. −0.2 ± 0.2%, p = 0.23). However, GLP-1RA treated patients demonstrated a greater frequency of maxLCBI4mm regression (85.6 ± 0.1 vs. 42.0 ± 0.6%, p = 0.01). Multivariate analysis demonstrated that the GLP-1RA use was independently associated with maxLCBI4mm regression (odds ratio = 4.41, 95%CI = 1.19–16.30, p = 0.02). Conclusions: In statin-treated patients with T2D and CAD, GLP-1RAs produced favourable changes in lipidic plaque materials, consistent with its stabilization.

Hepatitis E virus (HEV) is a pathogen that causes hepatitis. There are few reports of HEV seroprevalence among people with human immunodeficiency virus (PWH) in Japan. This study aimed to determine the HEV seroprevalence among PWH at our hospital. Anti-HEV IgG was tested for using enzyme immunoassays and immunoblot assays. Clinical information was obtained from medical records and additional patient questionnaires. Sixty-eight PWH were included in this study. Four patients (5.9 %) showed HEV IgG seropositivity with both methods, while one patient (1.5 %) was seropositive using only the immunoblot assay, and three patients (4.4 %) were seropositive using only the enzyme immunoassay. There was a significant difference in age between anti-HEV IgG-seropositive and -negative individuals (median, 57.5 and 48.0 years, respectively; p = 0.012). There were no significant differences in the other clinical characteristics. Our results revealed that age is a risk factor for HEV infection among PWH.

Abstract Background According to 2023 ESC Guideline, conservative medical management is generally recommended for the treatment of spontaneous coronary artery dissection (SCAD) except for patients with signs of ongoing myocardial ischemia. However, in some cases, invasive treatment (coronary artery bypass graft surgery or percutaneous coronary intervention (PCI)) is performed because of the progression of aneurysm in SCAD. Although there is no established strategy for the management of coronary aneurysm in SCAD, we report a case of successful healing of aneurysmal false lumen (AFL) using a second-generation drug-eluting stent (DES) in SCAD. Case presentation A 44-year-old woman without any cardiovascular risk factors was transferred to our hospital due to inferior myocardial infarction. Coronary angiography (CAG) showed multiple SCADs in the coronary artery. We performed PCI to the distal right coronary artery (RCA) because the RCA showed severe stenosis (99%) with bradycardia. Six days after the first PCI, SCAD relapsed in the mid left anterior descending artery (LAD). Furthermore, AFL was observed by intravascular ultrasound imaging. To avoid enlargement of the AFL and progression of the dissection toward the proximal site of the LAD, we performed PCI to the mid LAD to seal the entry tear of the dissection using a second-generation DES. CAG revealed that the AFL in the mid LAD completely diminished at 1 year after PCI. Conclusions The implantation of a second-generation DES might be one of therapeutic options for sealing AFL in SCAD patients.

Background: Blood blister-like aneurysms (BBAs) are a rare but clinically important cause of subarachnoid hemorrhage. Although regrowth or repeat rupture can occur following reconstructive endovascular treatment of BBAs, there is currently a lack of studies reporting the surgical exploration of BBAs after endovascular management. Herein, we present the first case report of a ruptured BBA treated with reconstructive endovascular treatment followed by surgical exploration. Case Presentation: A 42-year-old woman with subarachnoid hemorrhage was found to have the following: a saccular aneurysm of the lateral wall of the right supraclinoid internal carotid artery (ICA); and irregular vessel wall of the anterior wall of the right supraclinoid ICA on angiography. Based on intraoperative findings, the patient was diagnosed with a ruptured BBA of the right ICA. She underwent coating of the dissected ICA followed by overlapping stents; however, angiography showed rapid regrowth of the aneurysm. After high-flow bypass, surgical exploration was performed under proximal control of the cervical ICA. The deployed stent was directly observed through a vessel wall defect of the anterior wall which was consistent with angiographical irregular vessel wall. There was a clear positional discrepancy between angiographical base of the aneurysm and intraoperative laceration site. Conclusions: Surgical exploration indicates there is a potential risk of regrowth and/or repeat rupture of BBAs until the stent is fully endothelialized. Moreover, stent should be deployed to ensure that the irregular vessel wall is included when reconstructive endovascular treatment is employed for ruptured BBAs associated with irregular vessel wall.

The Japanese sardine (Sardinops sagax melanostictus) is a small pelagic fish found in the Sea of Japan, the marginal sea of the western North Pacific. It is an important species for regional fisheries, but their dispersal and migration patterns during early life stages remain unclear. In this study, we analyzed the stable oxygen isotope ratios of otoliths of young-of-the-year (age 0) Japanese sardines collected from the northern offshore and southern coastal areas of the Sea of Japan in 2015 and 2016. The ontogenetic shifts of the geographic distribution were estimated by comparing the profiles of life-long isotope ratios and temporally varying isoscape, which was calculated using the temperature and salinity fields produced by an ocean data assimilation model. Individuals that were collected in the northern and southern areas hatched and stayed in the southern areas (west offshore of Kyushu) until late June, and thereafter, they can be distinguished into two groups: one that migrated northward at shallow layer and one that stayed around the southern area in the deep layer. A comparison of somatic growth trajectories of the two groups, which was reconstructed based on otolith microstructure analysis, suggested that individuals that migrated northward had significantly larger body lengths in late June than those that stayed in the southern area. These results indicate that young-of-the-year Japanese sardines that hatched in the southern area may have been forced to choose one of two strategies to avoid extremely high water temperatures within seasonal and geographical limits. These include migrating northward or moving to deeper layers. Our results indicate that the environmental variabilities in the southern area could critically impact sardine population dynamics in the Sea of Japan.

This study addresses an issue arising during requests to intervene, usually focused on the direct shift of control from the system to an unprepared driver. We explore an approach based on the concept of adaptive automation. The approach is utilized to establish a strategy that the automated driving system can modulate between different driving states (Level 0 (L0) to Level 3 (L3) driving automation) based on traffic situations. Furthermore, we aim to design Human-Machine Interface (HMI) instructions that align with two design perspectives: system-centered (Implicit) and human-centered (Explicit). These HMI instructions critical to the strategy implemented are intended to sustain awareness on driver roles and decrease inappropriate driver responses during transitions. In the experiment, we utilized two approaches (adaptive control transition strategy and fixed control transition strategy) and two HMI designs. The experiment with a driving simulator was conducted with 60 drivers. The research questions explored include the influence of HMI design on drivers’ awareness during shifts from L3 to L2/L1. Also, we examine how different combinations of a strategy and HMI design affect reaction times from L3 to L0 scenarios. Compared to Implicit-HMI, the use of Explicit-HMI did not lead to inappropriate actions associated with their driving roles. This indicates that Explicit-HMI facilitates accurate response to state changes during the implementation of the adaptive approach. In terms of the comparison of the combinations, it is found that the adaptive approach provides initial guidance for drivers to monitor the environment, thereby providing earlier reaction time for the transition to manual.

Abstract Ionizing radiation induces genetic variations in plants, which makes it useful for plant breeding. A theory that the induced mutations occur randomly in the genome has long been accepted, but is now controversial. Nevertheless, a comparative analysis of the mutations at multiple loci has not been conducted using irradiated M1 genomes that contain all types of mutations. In this study, we identified Arabidopsis mutants (pab2 and pab3) in a mutagenized population of an anthocyanin-positive seed mutant (ban). Both pab2 and pab3 were revealed to be double mutants (tt4 ban and tt8 ban, respectively) that produced similar anthocyanin-less immature seeds, but differentially colored mature seeds. These features enabled the seed color-based detection of de novo M1 mutations in TT4 or TT8 following the irradiation of double heterozygous plants (TT4/tt4 TT8/tt8 ban/ban). Most of the irradiated double heterozygous plants produced anthocyanin-positive immature seeds, but 19 plants produced anthocyanin-less immature seeds. Of these 19 mutants, 2 and 17 exhibited tt4- and tt8-type mature seed coloration, respectively. The molecular analysis of the seed coat DNA from randomly selected anthocyanin-less seeds detected mutations at the locus predicted on the basis of the phenotype. Thus, the simple system developed in this study can reliably detect radiation-induced mutations at multiple loci in irradiated Arabidopsis M1 plants.

IntroductionAcetamiprid (ACE) and imidacloprid (IMI), the neonicotinoid chemicals, are widely used as pesticides because of their rapid insecticidal activity. Although these neonicotinoids exert very low toxicity in mammals, the effects of early, low-level, chronic exposure on the adult central nervous system are largely unclear. This study investigated the effects of low-level, chronic neonicotinoids exposure in early life on the brain functions of adult mice, using environmentally relevant concentrations.MethodsWe exposed mice to an acceptable daily intake level of neonicotinoids in drinking water during the prenatal and postnatal periods. Additionally, we also exposed mice to nicotine (NIC) as a positive control. We then examined the effects on the central nervous system in adult male offspring.ResultsIn the IMI and NIC exposure groups, we detected behavior that displayed impairment in learning and memory. Furthermore, immunohistochemical analysis revealed a decrease in SOX2 (as a neural stem cell marker) and GFAP (as an astrocyte marker) positive cells of the hippocampal dentate gyrus in the IMI and NIC exposure groups compared to the control group.DiscussionThese results suggest that exposure to neonicotinoids at low levels in early life affects neural circuit base formation and post-maturation behavior. Therefore, in the central nervous system of male mice, the effects of low-level, chronic neonicotinoids exposure during the perinatal period were different from the expected effects of neonicotinoids exposure in mature animals.

Background: Approaches to the prescription behavior of broad-spectrum antibiotics, including preauthorization and prospective audit and feedback (PAF), are a focus of antimicrobial stewardship (ASP). However, preprescription behavior, such as blood-culture collection before empiric prescription, is understudied and merits more attention given its influence on the usage of broad-spectrum antibiotics. At the University of Tokyo Hospital, carbapenems are subject to PAF, which has resulted in a compensatory increase in piperacillin-tazobactam use. To evaluate the inherent preprescription behavior associated with a broad-spectrum antibiotic, we investigated the initial blood-culture collection practices upon hospitalization in patients who were continued on empiric piperacillin-tazobactam. Methods: A retrospective observational study was conducted at the University of Tokyo Hospital, a tertiary-care hospital in Tokyo, Japan. Patients who were administered piperacillin-tazobactam on the day of hospitalization between April 2016 and December 2017 were included. Patients aged

Background Zooplankton plays an important role in the marine ecosystem. A high level of taxonomic expertise is necessary for accurate species identification based on morphological characteristics. As an alternative method to morphological classification, we focused on a molecular approach using 18S and 28S ribosomal RNA (rRNA) gene sequences. This study investigates how the accuracy of species identification by metabarcoding improves when taxonomically verified sequences of dominant zooplankton species are added to the public database. The improvement was tested by using natural zooplankton samples. Methods rRNA gene sequences were obtained from dominant zooplankton species from six sea areas around Japan and registered in the public database for improving the accuracy of taxonomic classifications. Two reference databases with and without newly registered sequences were created. Comparison of detected OTUs associated with single species between the two references was done using field-collected zooplankton samples from the Sea of Okhotsk for metabarcoding analysis to verify whether or not the newly registered sequences improved the accuracy of taxonomic classifications. Results A total of 166 sequences in 96 species based on the 18S marker and 165 sequences in 95 species based on the 28S marker belonging to Arthropoda (mostly Copepoda) and Chaetognatha were registered in the public database. The newly registered sequences were mainly composed of small non-calanoid copepods, such as species belonging to Oithona and Oncaea. Based on the metabarcoding analysis of field samples, a total of 18 out of 92 OTUs were identified at the species level based on newly registered sequences in the data obtained by the 18S marker. Based on the 28S marker, 42 out of 89 OTUs were classified at the species level based on taxonomically verified sequences. Thanks to the newly registered sequences, the number of OTUs associated with a single species based on the 18S marker increased by 16% in total and by 10% per sample. Based on the 28S marker, the number of OTUs associated with a single species increased by 39% in total and by 15% per sample. The improved accuracy of species identification was confirmed by comparing different sequences obtained from the same species. The newly registered sequences had higher similarity values (mean >0.003) than the pre-existing sequences based on both rRNA genes. These OTUs were identified at the species level based on sequences not only present in the Sea of Okhotsk but also in other areas. Discussion The results of the registration of new taxonomically verified sequences and the subsequent comparison of databases based on metabarcoding data of natural zooplankton samples clearly showed an increase in accuracy in species identification. Continuous registration of sequence data covering various environmental conditions is necessary for further improvement of metabarcoding analysis of zooplankton for monitoring marine ecosystems.

Abstract Existing methods for biopsy of intraparenchymal brain lesions, including stereotactic biopsy and open block biopsy, have advantages and disadvantages. We propose a novel biopsy method, called “boring biopsy,” which aims to overcome the drawbacks of each conventional method. This method is less invasive and allows obtaining continuous specimens of sufficient volume. We aimed to assess the feasibility and efficacy of using boring biopsy for intraparenchymal brain lesions. We included 26 consecutive patients who underwent boring biopsy for intraparenchymal lesions. Columnar continuous specimens from the surface of the normal brain tissue to the tumor margin and the center of the lesion were obtained using the boring biopsy method. We used a catheter introducer with original modifications to create a cylindrical biopsy tool for surgery. Columnar continuous specimens were successfully obtained. Histopathological diagnosis was based on cellular changes and differentiation from normal tissues to the core of the lesion and established in all cases. No permanent deficits, major adverse outcomes, or deaths were observed. This novel technique may improve diagnostic accuracy and reduce invasiveness associated with brain biopsy. This method may become the next standard procedure, particularly in some cases where histological evaluation is paramount, and conventional biopsy methods are not suitable.

The molecular nature of mutations induced by ionizing radiation and chemical mutagens in plants is becoming clearer owing to the availability of high-throughput DNA sequencing technology. However, few studies have compared the induced mutations between different radiation qualities and between different irradiated materials with the same analysis method. To compare mutation induction between dry-seeds and seedlings irradiated with carbon ions and gamma rays in Arabidopsis, in this study we detected the mutations induced by seedling irradiation with gamma rays and analyzed the data together with data previously obtained for the other irradiation treatments. Mutation frequency at the equivalent dose for survival reduction was higher with gamma rays than with carbon ions, and was higher with dry-seed irradiation than with seedling irradiation. Carbon ions induced a higher frequency of deletions (2−99 bp) than gamma rays in the case of dry-seed irradiation, but this difference was less evident in the case of seedling irradiation. This result supported the inference that dry-seed irradiation under a lower water content more clearly reflects the difference in radiation quality. However, the ratio of rearrangements (inversions, translocations, and deletions larger than 100 bp), which are considered to be derived from the rejoining of two distantly located DNA breaks, was significantly higher with carbon ions than gamma rays irrespective of the irradiated material. This finding suggested that high-linear energy transfer radiation induced closely located DNA damage, irrespective of the water content of the material, that could lead to the generation of rearrangements. Taken together, the results provide an overall picture of radiation-induced mutation in Arabidopsis and will be useful for selection of a suitable radiation treatment for mutagenesis.

Plastic injection molding (PIM) is a manufacturing technology to plastic products, and it is important to determine optimal process parameters for high product quality and high productivity. Weldline that are formed when two or more melt fronts meet should be reduced for high strength and high surface quality. Rapid heating cycle molding (RHCM) that the mold is heated up is an attracted PIM technology for weldline reduction, but long cycle time is generally required. In this paper, an RHCM incorporating a heater system is used, and the process parameters optimization is performed. To determine the optimal process parameters, multi-objective optimization for minimizing both weldline and cycle time is considered. The numerical simulation in RHCM is computationally so expensive that sequential approximate optimization that the response surface is repeatedly constructed and optimized is adopted for the design optimization. The pareto-frontier is identified through the numerical simulation, and the experiment using PIM machine (MS100, Sodick) is also conducted. It is found from the numerical and experimental result that the RHCM using the heater system is effective to the weldline reduction.

The intestinal epithelial Caco-2 cell monolayer is a well-established in vitro model useful for predicting intestinal drug absorption in humans. Coculture models of Caco-2 and goblet-cell-like HT29-MTX cells have been developed to overcome the lack of a mucus layer; however, those models are much leakier compared to the intestinal epithelium. Here, we developed a partially laminated culture model where HT29-MTX cells were superimposed onto a Caco-2 monolayer to overcome this issue. A morphological study showed that the piled HT29-MTX cells were voluntarily incorporated into the Caco-2 monolayer, and mucus production was confirmed via periodic acid-Schiff and mucin protein 2 staining. Permeability was evaluated in terms of transepithelial electrical resistance (TEER) and the apparent permeability of paracellular markers with different molecular sizes. The partially laminated model maintained the high barrier function of the Caco-2 monolayer, whose permeability appeared adjustable according to the HT29-MTX/Caco-2 cell ratio. In contrast, the coculture models showed abnormally high permeability of those markers, correlated with low TEER. Thus, the partially laminated model enabled in vitro recapitulation of effective mucosal barrier function. Consequently, this novel model may be useful as an in vitro high-throughput evaluation system for enteral mucosal permeability and mucus-penetrating efficiency of drugs and nanocarriers.

Abstract Background Staphylococcus schleiferi is a gram-positive pathogenic coccus which causes canine skin and ear infections. Only four cases of human infection caused by Staphylococcus schleiferi subspecies coagulans have been reported. Herein, we present the first case of catheter-related bloodstream infection caused by S. schleiferi subspecies coagulans. Case presentation A 62-year-old Japanese man was admitted to our hospital for examination of sigmoid colon tumor. During hospitalization, he had fever, shaking chills, and swelling at the peripheral venous catheter insertion site. Two sets of blood cultures were positive for S. schleiferi subspecies coagulans which was confirmed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), 16S ribosomal RNA sequencing and the coagulase test. The patient was successfully treated without relapse. Conclusion To our knowledge, this is the first report of catheter-related bloodstream infection caused by S. schleiferi subspecies coagulans. S. schleiferi subsp. coagulans can be pathogenic in humans, and MALDI-TOF MS can contribute to accurate identification of S. schleiferi subspecies coagulans.

Heat exchangers (HEs) are used in process industries such as power plants and petroleum refineries. It is important to minimize flow maldistribution as well as pressure drop for high performance of HE. A baffle is often installed in the header part of HE in order to achieve the flow uniformity, but the hole sizes of baffle are determined by the engineer’s experience. In this paper, a multi-objective design optimization for minimizing both the flow maldistribution and the pressure drop is performed using numerical simulation. The hole sizes in the baffle are taken as the design variables. In addition, the angle of baffle is newly considered. By introducing the angle of baffle, it is expected that fluid will smoothly flow into the edge of the header. The numerical simulation using computational fluid dynamics (CFD) is so intensive that sequential approximate optimization that response surface is repeatedly constructed and optimized is adopted to determine the optimal solution with a small number of simulations. Through the numerical result, the pareto-frontier between the flow maldistribution and the pressure drop is identified. It is found from the numerical result that several small vortexes are generated in the optimal configuration. This indicates that generating small vortexes will play an important role for improving the performance of HE.

In plastic injection molding (PIM), weldline affects the strength and surface quality of products, and it is then important to determine the optimal process parameters for the weldline reduction. Rapid heat cycle molding (RHCM) that actively controls the mold temperatures is an effective PIM technology to weldline reduction, but requires long cycle time. In this paper, variable pressure profile that packing pressure varies during the PIM process is incorporated in the RHCM in order to shorten the cycle time. To determine the process parameters in the proposed RHCM, multi-objective design optimization is performed. The mold temperature is maximized for the weldline reduction, whereas the cycle time is minimized for high productivity. Numerical simulation in the proposed RHCM is computationally so expensive that sequential approximate optimization is used to identify the pareto-frontier. Based on the numerical result, the experiment using PIM machine (MS100, Sodick) is also conducted to examine the validity of the proposed RHCM.

Octacalcium phosphate is a precursor to a key component of human bone and tooth enamel which can incorporate carboxylate species, but the effect of multivalent carboxylates is not well understood. Here the incorporation of tetracarboxylic acids into OCP is shown to influence the structural and optical properties of the resultant composite.

Abstract Background Jamestown Canyon virus (JCV) is a mosquito-borne orthobunyavirus that causes acute febrile illness, meningitis, and meningoencephalitis, mainly among adults. JCV is widely distributed in North America and the number of JCV cases in the U.S. has increased in recent years. Therefore, the central nervous system disease caused by JCV can be considered a potentially re-emerging viral disease. However, the seroprevalence of JCV is unknown in Japan. The purpose of this study is to evaluate the seroprevalence of JCV in the Japanese population. Methods We used an IgG enzyme-linked immunosorbent assay (IgG-ELISA) with JCV-infected cell-lysates and/or a neutralizing (NT) antibody assay. The cut-off value of IgG-ELISA was determined using IgG-ELISA to analyze serum specimens from 37 healthy Japanese donors. IgG-ELISA was validated by assessing its sensitivity and specificity, using 38 human serum samples previously tested for the presence or absence of antibodies against JCV and snowshoe hare virus (SSHV), in an in-house NT antibody assay conducted by the Public Health Agency of Canada. The seroepidemiological study was performed using IgG-ELISA and NT antibody assay to analyze 246 human serum samples from the serum bank of the National Institute of Infectious Diseases (NIID) in Japan. Results The cut-off value of IgG-ELISA was determined at 0.20, based on the mean (− 0.075) and standard deviation (0.092) values using Japanese donors’ sera. The sensitivity and the specificity of IgG-ELISA determined using 25 JCV-positive and 4 JCV-negative serum samples were 96 and 100%, respectively. Analysis of the 246 Japanese serum samples revealed that no specimen showed a higher value than the cut-off value of IgG-ELISA, and no sample tested positive by the NT antibody assay. Conclusions Our results showed that JCV is not circulating significantly in Japan. To the best of our knowledge, this is the first report to demonstrate the seroprevalence of JCV in the general population in Japan.

l-3,4-dihydroxyphenylalanine (l-DOPA) is a candidate neurotransmitter. l-DOPA is released by nicotine through nicotinic receptors. Recently, G-protein coupled receptor GPR143, was identified as a receptor for l-DOPA. In this study, genetic association studies between GPR143 genetic polymorphisms and smoking behaviors revealed that the single-nucleotide polymorphism rs6640499, in the GPR143 gene, was associated with traits of smoking behaviors in Japanese individuals. In Gpr143 gene-deficient mice, nicotine-induced hypolocomotion and rewarding effect were attenuated compared to those in wild-type mice. Our findings suggest the involvement of GPR143 in the smoking behaviors.

Summary: The number of man-made chemicals has increased exponentially recently, and exposure to some of them can induce fetal malformations. Because complex and precisely programmed signaling pathways play important roles in developmental processes, their disruption by external chemicals often triggers developmental toxicity. However, highly accurate and high-throughput screening assays for potential developmental toxicants are currently lacking. In this study, we propose a reporter assay that utilizes human-induced pluripotent stem cells (iPSCs) to detect changes in fibroblast growth factor signaling, which is essential for limb morphogenesis. The dynamics of this signaling after exposure to a chemical were integrated to estimate the degree of signaling disruption, which afforded a good prediction of the capacity of chemicals listed in the ECVAM International Validation Study that induce limb malformations. This study presents an initial report of a human iPSC-based signaling disruption assay, which could be useful for the screening of potential developmental toxicants.

Radiation-induced mutations have been detected by whole-genome sequencing analyses of self-pollinated generations of mutagenized plants. However, large DNA alterations and mutations in non-germline cells were likely missed. In this study, in order to detect various types of mutations in mutagenized M1 plants, anthocyanin pigmentation was used as a visible marker of mutations. Arabidopsis seeds heterozygous for the anthocyanin biosynthetic genes were irradiated with gamma-rays. Anthocyanin-less vegetative sectors resulting from a loss of heterozygosity were isolated from the gamma-irradiated M1 plants. The whole-genome sequencing analysis of the sectors detected various mutations, including structural variations (SVs) and large deletions (≥100 bp), both of which have been less characterized in the previous researches using gamma-irradiated plant genomes of M2 or later generations. Various types of rejoined sites were found in SVs, including no-insertion/deletion (indel) sites, only-deletion sites, only-insertion sites, and indel sites, but the rejoined sites with 0-5 bp indels represented most of the SVs. Examinations of the junctions of rearrangements (SVs and large deletions), medium deletions (10-99 bp), and small deletions (2-9 bp) revealed unique features (i.e., frequency of insertions and microhomology) at the rejoined sites. These results suggest that they were formed preferentially via different processes. Additionally, mutations that occurred in putative single M1 cells were identified according to the distribution of their allele frequency. The estimated mutation frequencies and spectra of the M1 cells were similar to those of previously analyzed M2 cells, with the exception of the greater proportion of rearrangements in the M1 cells. These findings suggest there are no major differences in the small mutations (

We propose a boron–rhodamine-containing carboxylic acid (BRhoC) substance as a new sugar chemosensor. BRhoC was obtained by the Friedel–Crafts reaction of 4-formylbenzoic acid and N,N-dimethylphenylboronic acid, followed by chloranil oxidation. In an aqueous buffer solution at pH 7.4, BRhoC exhibited an absorption maximum (Absmax) at 621 nm. Its molar absorption coefficient at Absmax was calculated to be 1.4 × 105 M−1 cm−1, and it exhibited an emission maximum (Emmax) at 644 nm for the excitation at 621 nm. The quantum yield of BRhoC in CH3OH was calculated to be 0.16. The borinate group of BRhoC reacted with a diol moiety of sugar to form a cyclic ester, which induced a change in the absorbance and fluorescence spectra. An increase in the D-fructose (Fru) concentration resulted in the red shift of the Absmax (621 nm without sugar and 637 nm with 100 mM Fru) and Emmax (644 nm without sugar and 658 nm with 100 mM Fru) peaks. From the curve fitting of the plots of the fluorescence intensity ratio at 644 nm and 658 nm, the binding constants (K) were determined to be 2.3 × 102 M−1 and 3.1 M−1 for Fru and D-glucose, respectively. The sugar-binding ability and presence of a carboxyl group render BRhoC a suitable building block for the fabrication of highly advanced chemosensors.

Recent findings have revealed that extracellular vesicles (EVs) are secreted from cells and circulate in the blood. EVs are classified as exosomes (40−100 nm), microvesicles (50−1,000 nm) or apoptotic bodies (500−2,000 nm). EVs contain mRNAs, microRNAs, and DNAs and have the ability to transfer them from cell to cell. Recently, especially in humans, the diagnostic accuracy of tumor cell type-specific EV-associated miRNAs as biomarkers has been found to be more than 90 %. In addition, microRNAs contained in EVs in blood are being identified as specific biomarkers of chemical-induced inflammation and organ damage.Therefore, microRNAs contained in the EVs released into the blood from tissues and organs in response to adverse events such as exposure to chemical substances and drugs are expected to be useful as novel biomarkers for toxicity assessment. In this study, C57BL/6 J male mice orally dosed with carbon tetrachloride (CCl4) were used as a hepatotoxicity animal model. Here, we report that not only the known hepatotoxicity biomarkers miR-122 and miR-192 but also 42 novel EV-associated biomarkers were upregulated in mice dosed with CCl4. Some of these novel biomarkers may be expected to be able to use for better understanding the mechanism of toxicity. These results suggest that our newly developed protocol using EV-associated miRNAs as a biomarker would accelerate the rapid evaluation of toxicity caused by chemical substances and/or drugs.

Abstract The high density nucleation of α-Al2O3 nanocrystallites was observed by rapid heating of the aluminum formate hydroxide-based precursor powder at 1200 °C for 50 s. The nucleation of α-Al2O3 nanocrystallites with less 10 nm in size from high purity aluminum oxide matrix has not been observed to our knowledge. Based on the results of XRD and TEM, α-Al2O3 nanocrystallites nucleated from the amorphous phase which formed after thermal decomposition of the precursor powder. Subsequently, α-Al2O3 with hollow rod-like morphology formed through coalescence and growth of nanocrystallites after heating at 1200 °C for 1 min. The results obtained in this paper indicates a possible beneficial effect of the rapid heating and cooling of the aluminum formate hydroxide-based precursor powder on the precipitation of α-Al2O3 nanocrystallites.