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The discrete element method (DEM) coupled with computational fluid dynamics (CFD) is regarded to be a standard approach in a numerical calculation of gas-solid flow. When the DEM-CFD method is applied to the simulation of industrial systems, we cannot shy away from the modeling of arbitrary shape wall boundaries. Very recently, we have developed an innovative wall boundary model in the DEM-CFD simulations, where the signed distance function (SDF) and the immersed boundary method (IBM) are used for the wall boundary in the DEM and CFD. The SDF makes it possible to create an arbitrary shape wall boundary based on the scalar field. The IBM can be used for the wall boundary model by reflecting the number of the SDF points on the local volume fraction in CFD grid. Thus, the arbitrary shape wall boundary can be easily created in the DEM-CFD method by combining the SDF with the IBM. On the other hand, the authors' group has pointed out the necessity of the density scale technique in CFD. In the density scale technique, the density scale coefficient is considered in the calculation of the pressure Poisson equation. When the SDF/IBM is applied to CFD without density scaling technique, an unnatural fluid flow might occur through the wall boundary object. The effect of the density scaling coefficient on a gas-solid flow has not been examined so far. From this background, the influence of the density scale coefficient on a gas-solid flow is investigated in the present study. Through this study, introduction of the density scaling technique is designated to be crucial when the IBM is used for the wall boundary in the DEM-CFD simulation. The density scaling coefficient is shown to be decided not by theory but by experience, and the value should become 100 to 1000 in a typical gas-solid flow system. Besides, it is illustrated that the calculation cost is not influenced by the value of the density scale coefficient in the DEM-CFD simulations.

Diabetic macular edema (DME) refractory to anti-VEGF drugs is a socioeconomic burden. In this retrospective study, we investigated the relationship between DME remission and hyperreflective walls in foveal cystoid spaces, a novel finding on spectral domain optical coherence tomography (SD-OCT) images in DME. In a cross-sectional study, we assessed the relationship between hyperreflective walls in foveal cystoid spaces and other OCT findings in 110 eyes of 110 DME patients. Hyperreflective walls were delineated in 27 of 171 foveal cystoid spaces. Eyes with hyperreflective walls in foveal cystoid spaces had poorer visual acuity and more severe photoreceptor disruption than did those without such findings (P = 0.008 and P P = 0.025). We characterized hyperreflective walls in foveal cystoid spaces and designated them as a predictor of no DME remission under ranibizumab injections.

The discrete element method (DEM) and the moving particle semi-implicit (MPS) method are the most popular mesh-free particle methods in the discontinuum and continuum. This paper describes a state-of-the-art modeling on multi-phase flows using these mesh-free particle methods. Herein, a combinational model of the signed distance function (SDF) and immersed boundary method (IBM) is introduced for an arbitrary-shaped wall boundary in the DEM simulation. Practically, this model uses a simple operation to create the wall boundary. Although the SDF is a scalar field for the wall boundary of the DEM, it is useful for the wall boundary of the CFD through combination with the IBM. Validation tests are carried out to demonstrate the adequacy of the SDF/IBM wall boundary model. Regarding the mesh-free particle method for continuum, the phase change problem is one of the challenging topics, as the solid state is usually modeled by extremely high viscous fluid in the phase change simulation. The phase change simulation is shown to be efficiently performed through an implicit algorithm and a heat flux model in the MPS method. The adequacy of these models is verified by the numerical examples.

Skeletal muscle atrophy is associated with mortality and poor prognosis in patients with chronic kidney disease (CKD). However, underlying mechanism by which CKD causes muscle atrophy has not been completely understood. The quality of lipids (lipoquality), which is defined as the functional features of diverse lipid species, has recently been recognized as the pathology of various diseases. In this study, we investigated the roles of the stearoyl-CoA desaturase (SCD), which catalyzes the conversion of saturated fatty acids into monounsaturated fatty acids, in skeletal muscle on muscle atrophy in CKD model animals. In comparison to control rats, CKD rats decreased the SCD activity and its gene expression in atrophic gastrocnemius muscle. Next, oleic acid blocked the reduction of the thickness of C2C12 myotubes and the increase of the endoplasmic reticulum stress induced by SCD inhibitor. Furthermore, endoplasmic reticulum stress inhibitor ameliorated CKD-induced muscle atrophy (the weakness of grip strength and the decrease of muscle fiber size of gastrocnemius muscle) in mice and the reduction of the thickness of C2C12 myotubes by SCD inhibitor. These results suggest that the repression of SCD activity causes muscle atrophy through excessive endoplasmic reticulum stress in CKD.

In the electroluminescence from chiral liquid crystals comprising a bis(fluorophenyl)terthiophene unit with macroscopic polarization, two characteristic phenomena were observed. Firstly, linearly polarized light was emitted from the polarized liquid crystal phase under a DC bias, and the polarized plane of the electroluminescence was rotated by 90° owing to the inversion of the polarity of the DC bias applied during the phase transition from the chiral smectic A phase to the chiral crystal smectic phase. This resulted in a low threshold voltage in 2 μm thick samples having a symmetric structure. Secondly, the hole and electron injection barriers at the electrodes were significantly reduced by the internal electric field produced by the macroscopic polarization of the liquid crystal. This is the first report on linearly polarized electroluminescence with a polarized plane that can be rotated.

We present a novel fuel cell heterogeneous catalyst based on rhodium, nickel and sulfur with power densities 5–28% that of platinum. The NiRhS heterogeneous catalyst was developed via a homogeneous model complex of the [NiFe]hydrogenases (H2ases) and can act as both the cathode and anode of a fuel cell.

Bioamination methods using microorganisms have attracted much attention because of the increasing demand for environmentally friendly bioprocesses. n-Butylamine production from glucose in Escherichia coli was demonstrated in this study, which has never been reported because of the absence of n-butylamine-producing pathway in nature. We focused on a transaminase-mediated cascade for bioamination from an alcohol or aldehyde. The cascade can convert an alcohol or an aldehyde to the corresponding amine with l -alanine as an amine donor. Here, n-butyraldehyde, which is a metabolic intermediate in the n-butanol producing pathway, is a potential intermediate for producing n-butylamine using this cascade. Hence, the n-butanol-producing pathway and the transaminase-mediated cascade were combined into a synthetic metabolic pathway for producing n-butylamine from glucose. Firstly, we demonstrated the conversion of n-butanol to n-butylamine using a three enzyme-mediated cascade. n-Butanol was successfully converted to n-butylamine in 92% yield in the presence of l -alanine and ammonium chloride. Then, the n-butanol-producing pathway and transaminase-mediated cascade were introduced into E. coli. Using this system, n-butylamine was successfully produced from glucose as a carbon source at a concentration of 53.2 mg L−1 after 96 h cultivation using a ppc (phosphoenolpyruvate carboxylase)-deficient strain. To the best of our knowledge, this is the first report of the direct production of n-butylamine from glucose, and may provide a starting point for the development of microbial methods to produce other bioamines.

A 51-year-old woman had an incidental finding of a tracheal tumor during oesophagogastroduodenoscopy following the diagnosis of asthma for 2 months. A computed tomography scan revealed a 15-mm tumor in the subglottis. Endoscopic resection was performed safely, and pleomorphic adenoma was diagnosed histologically. The patient’s condition was satisfactory 30 months after the procedure. Tracheal pleomorphic adenoma is rare and may be misdiagnosed as asthma. If the tumor is large, surgery may be required; however, endoscopic polypectomy may be effective if the tumor is small. Therefore, early diagnosis of tracheal pleomorphic adenoma is important. At the first visit, the flow–volume curve suggested upper airway obstruction, which should have raised the suspicion of an upper airway obstruction. In patients with suspected asthma, early pulmonary function testing is needed to substantiate asthma diagnosis and prevent an alternative diagnosis being missed.

Objective Rapid on-site cytological evaluation (ROSE) in bronchoscopy is a useful ancillary technique. ROSE is usually performed by a cytopathologist or cytotechnologist. However, because of staff shortages and reduced availability, ROSE cannot be performed in every hospital. We aimed to evaluate the accuracy of ROSE when performed by a trained pulmonologist, comparing the diagnosis results with the final diagnosis of cytopathologists. Methods We performed a retrospective cohort study on 125 patients who underwent bronchoscopy with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and endobronchial ultrasonography with a guide sheath (EBUS-GS) for peripheral pulmonary lesions by conventional bronchoscopy at Sapporo Medical University Hospital between March 2012 and September 2018. ROSE was performed by a pulmonologist who was trained by a cytotechnologist for a total of 1 month. DiffQuik® staining for ROSE was used to prepare cytology slides. The results of ROSE were compared with the final diagnosis obtained using Papanicolaou staining by cytopathologists. Results In all procedures, the sensitivity, specificity and diagnostic accuracy of ROSE were 88.5%, 83.0% and 86.4%, respectively. There was no significant difference in the sensitivity, specificity, positive predictive value, negative predictive value or accuracy between EBUS-TBNA and EBUS-GS. Conclusions ROSE of lung cancer by a trained pulmonologist can be highly accurate and deemed as feasible and useful for not only EBUS-TBNA but also EBUS-GS.

In this paper, we present a method for controlling incoherent light through scattering media based on machine learning and its potential application to multiview stereo displays. The inverse function between input and output light intensity patterns through a scattering medium is regressed with a machine learning algorithm. The inverse function is used for calculating an input pattern for generating a target output pattern through a scattering medium. We demonstrate the proposed method by assuming a potential application to multiview stereo displays. This concept enables us to use a diffuser as a parallax barrier, a cylindrical lens array, or a lens array on a conventional multiview stereo display, which will contribute to a low-cost, highly functional display. A neural network is trained with a large number of pairs of displayed random patterns and their parallax images at different observation points, and then a displayed image is calculated from arbitrary parallax images using the trained neural network. In the experimental demonstration, the scattering-based multiview stereo display was composed of a diffuser and a conventional liquid crystal display, and it reproduced different handwritten characters, which were captured by a stereo camera.

To identify susceptibility genes for macular neovascularization (MNV) development in central serous chorioretinopathy (CSC).Genome-wide survival analysis using a longitudinal cohort study.We included 402 and 137 patients with CSC but without MNV at their first visit from the Kyoto CSC Cohort and Kobe CSC dataset, respectively. All patients underwent detailed ophthalmic examinations, including multimodal imaging, such as fundus autofluorescence, spectral-domain OCT, and fluorescein angiography/indocyanine green angiography or OCT angiography.We conducted a genome-wide survival analysis using the Kyoto CSC Cohort. We applied the Cox proportional hazard model to adjust for age, sex, and the first principal component. Single nucleotide polymorphisms (SNPs) with P values1.0 × 10The association between SNPs and MNV development in patients with CSC.Rs370974631 near ARMS2 displayed a genome-wide significant association in the meta-analysis of discovery and replication result (hazard ratio [HR]ARMS2, CFH, COL4A3, and B3GALTL were identified as susceptibility genes for MNV development in CSC. These 4 genes are known as susceptibility genes for AMD, whereas COL4A3 and B3GALTL were previously reported to be polypoidal choroidal vasculopathy (PCV)-specific susceptibility genes. Our findings revealed the shared genetic susceptibility between PCV and MNV secondary to CSC.

In this Letter we report a discovery of a prominent flash of a peculiar overluminous Type Ia supernova, SN 2020hvf, in about 5 hours of the supernova explosion by the first wide-field mosaic CMOS sensor imager, the Tomo-e Gozen Camera. The fast evolution of the early flash was captured by intensive intranight observations via the Tomo-e Gozen high-cadence survey. Numerical simulations show that such a prominent and fast early emission is most likely generated from an interaction between $0.01~M_{\odot}$ circumstellar material (CSM) extending to a distance of $\sim$$10^{13}~\text{cm}$ and supernova ejecta soon after the explosion, indicating a confined dense CSM formation at the final evolution stage of the progenitor of SN 2020hvf. Based on the CSM-ejecta interaction-induced early flash, the overluminous light curve, and the high ejecta velocity of SN 2020hvf, we suggest that the SN 2020hvf may originate from a thermonuclear explosion of a super-Chandrasekhar-mass white dwarf ("super-$M\rm_{Ch}$ WD"). Systematical investigations on explosion mechanisms and hydrodynamic simulations of the super-$M\rm_{Ch}$ WD explosion are required to further test the suggested scenario and understand the progenitor of this peculiar supernova., 20pages, 6 figures, accepted for publication in the Astrophysical Journal Letters

All-trans retinoic acid (ATRA) increases the sensitivity to unfolded protein response (UPR) in differentiating leukemic blasts. The downstream transcriptional factors of PERK, a major arm of UPR, regulates muscle differentiation. However, the role of growth arrest and DNA damage-inducible protein 34 (GADD34), one of the downstream factors of PERK, and the effects of ATRA on GADD34 expression in muscle remain unclear. In this study, we identified ATRA increased the GADD34 expression independent of the PERK signal in the gastrocnemius muscle of mice. ATRA up-regulated GADD34 expression through the transcriptional activation of it via inhibiting the interaction of homeobox Six1 and transcription co-repressor TLE3 with the MEF3-binding site on the GADD34 gene promoter in myoblasts. ATRA also inhibited the interaction of TTP, which induces mRNA degradation, with AU-rich element on GADD34 mRNA via p38 MAPK, resulting in the instability of GADD34 mRNA. Overexpressed GADD34 in myoblasts changes the type of myosin heavy chain in myotubes. These results suggest ATRA increases GADD34 expression via transcriptional and post-transcriptional regulation in myoblasts, which changes muscle fiber type in myotubes.

All-Solid-State Battery (ASSB), which is nonflammable, safe, and high capacity, is expected to be commercialized for electric vehicle applications in the near future. However, the correlation between the electrode structure and the stress on the solid-solid contact surface is unknown, and no design theory has been established. However, the design theory has not been established because the correlation between the stresses on the electrode structure and the solid-solid contact surface is unknown. In this study, a stress distribution estimation method for complex electrode structures using machine learning was investigated. The stress estimation was performed using the discrete element method (DEM)¹⁾ . The average particle size of LCO was given as 9-12 ㎛, standard deviation as 0-2, and Young's modulus was given as 264 GPa²⁾. The LGPS particles were fixed at 1 ㎛ in diameter, with Young's modulus of 26.7 GPa, Poisson's ratio of 0.32, and density of 1.988 g/cm³. The distribution of the stresses on each particle was calculated from the DEM calculation results and confirmed to be approximately Gaussian. A convolutional neural network (CNN)³⁾ was used as the model for machine learning, and various structural parameters, including the stress on each particle calculated by DEM, were identified to create a dataset. Five hundred images were used for training, 320 of which were used for training, 80 for validation, and 100 for testing. The coefficient of determination (R²) of the standard deviation of the stress on each particle was AM_0.861, SE_0.936, and SE_0.936, confirming that the stress distribution can be predicted by the machine learning model. The contact area of the electrochemical reaction interface, AM-SE, was calculated from the stress on the contact surface calculated by DEM and Hertzian contact theory⁴⁾. The total interfacial area was also predicted well with a coefficient of determination of 0.921. Thus, it was possible to predict the stress distribution and effective contact area in the electrode layer of the all-solid-state battery. Next, we will verify the validity of the electrode structure and stress distribution by simultaneously measuring the in-situ stress distribution and Li concentration distribution during charging and discharging using X-ray spectroscopy and atomic force microscopy. In addition, a machine learning model of crack formation during charging and discharging will be developed. By linking machine learning and measurement, we will connect to the structural design of electrode layers to improve charge-discharge and cycle characteristics, and aim to establish fundamental technology that will contribute to the early commercialization of all-solid-state batteries. References [1] M. So et al., J. Power Sources, 508, 230344 (2021). [2] F. Hao et al., J. Electrochem. Soc.,165, 9, A1857 (2018). [3] Y. LeCun et al., Lect. Notes Comput. Sci., 1681, 319 (1999). [4] B.N.J.Persson, Surf. Sci. Reports, 61, 4, 201 (2006).

Even normally shipped batteries may contain disturbing factors such as very small amounts of foreign matter or structural inhomogeneity, which can cause serious accidents such as thermal runaway or explosions. Since dismantling and identifying the cause is time-consuming and costly, nondestructive techniques for identifying the cause are required. A method for detecting abnormal current distribution by magnetic field inverse analysis has been proposed as one such method, but it is difficult to directly elucidate the factors that cause the abnormal current distribution itself. In this study, we first focused on the effect of different separator structures and analyzed the in-plane directional current distribution using machine learning in order to construct a non-destructive model for estimating the causes. A one-dimensional model based on porous electrode theory [1] was used. Constant current charging, homogeneous electrode layer structure, uniform Li concentration in active material particles, and isothermal conditions were assumed. The electrode layer was assumed to be a porous body consisting of active material, electrolyte, and auxiliary materials (conductivity assistant and binder). Using the previously reported structural information and physical properties [2], [3], Case 1 was a coin cell using LiNi1/3Co1/3Mn1/3O2 as the cathode active material, and Case 2 was a laminated cell using LiCoO2 as the cathode active material. The anode active material was graphite and the electrolyte was 1.0 M LiPF6 solution in EC・DEC solvent for both Case 1 and 2. The degree of flexure of the cathode and anode was determined using the formulas from previous studies [4]. Cross-sectional images of the actual biaxially oriented separator were obtained using a focused ion beam scanning electron microscope, and the three-dimensional simulated structure was reproduced based on these images (Sep. A). Similarly, a nonwoven fabric structure (Sep. B) and a foam structure (Sep. C) were also reproduced. Since the collector foils are connected in-plane, the potentials at both ends of the cell must be uniform. Under this constraint, the ion current distribution can be estimated depending on the in-plane structure distribution of the separator. In this study, the correlation between the local porosity (ε) of the separator and the local ion current (denoted as C-rate) was determined using a nonlinear regression method called Support Vector Regression (SVR) [5]. 100 points were taken randomly from 0.4~1.0 and 5~10 for ε and C-rate, respectively, and used as explanatory variables. Each charging curve was compared with the charging curve at the in-plane mean value of (ε, C) = (0.545, 7.5), and the RMSE (root mean square error) of the voltage was calculated as the objective variable. The in-plane reaction distribution was obtained from the voltage error predicted from ε and C-rate by SVR and the porosity distribution of the separator. The mesh size was 40 nm/pixel. For each separator, the difference between high and low reaction profiles was more clearly observed in Case 2. The reaction overvoltage distribution at a certain point in Case 2 was acquired, and it was confirmed that the reaction was concentrated near the separator of the negative electrode. This also made it possible to estimate the Li deposition point, which is the starting point of degradation. Using machine learning to analyze the in-plane current distribution, it was found that the current distribution differs depending on the electrode conditions even for the same separator. We will use this technology to develop a technique for identifying factors based on the current distribution obtained by nondestructive measurement. References [1] G. M. Goldin et al., Electrochim. Acta., 64 118 (2012). [2] G. Inoue et al., J. Chem. Eng. Japan., 54 (5) 207-212 (2021). [3] K. Ikeshita et al., ECS Trans., 75 (20) 165-172 (2017). [4] G. Inoue et al., J. Pow. Sour., 342, 476 (2017). [5] C. Cortes et al., Mach. Learn., 20 (3) 273-297 (1995).

BackgroundAntifibrotic therapies are available to treat chronic fibrosing interstitial lung diseases (CF-ILDs), including idiopathic pulmonary fibrosis. Early use of these treatments is recommended to slow deterioration of respiratory function and to prevent acute exacerbation. However, identifying patients in the early stages of CF-ILD using chest radiographs is challenging. In this study, we developed and tested a deep-learning algorithm to detect CF-ILD using chest radiograph images.MethodFrom the image archive of Sapporo Medical University Hospital, 653 chest radiographs from 263 patients with CF-ILDs and 506 from 506 patients without CF-ILD were identified; 921 were used for deep learning and 238 were used for algorithm testing. The algorithm was designed to output a numerical score ranging from 0 to 1, representing the probability of CF-ILD. Using the testing dataset, the algorithm's capability to identify CF-ILD was compared with that of doctors. A second dataset, in which CF-ILD was confirmed using computed tomography images, was used to further evaluate the algorithm's performance.ResultsThe area under the receiver operating characteristic curve, which indicates the algorithm's detection capability, was 0.979. Using a score cut-off of 0.267, the sensitivity and specificity of detection were 0.896 and 1.000, respectively. These data showed that the algorithm's performance was noninferior to that of doctors, including pulmonologists and radiologists; performance was verified using the second dataset.ConclusionsWe developed a deep-learning algorithm to detect CF-ILDs using chest radiograph images. The algorithm's detection capability was noninferior to that of doctors.

To investigate the 2-year effectiveness of reduced-fluence photodynamic therapy (rf-PDT) for chronic central serous chorioretinopathy (cCSC).Retrospective cohort study.A total of 223 consecutive patients with newly diagnosed cCSC with active serous retinal detachment (SRD) were included from May 2007 to June 2017 and followed up for at least 2 years. Patients who underwent ocular treatment other than cataract surgery before the beginning of recruitment and those who had macular neovascularization at baseline were excluded.All patients underwent a comprehensive ophthalmic evaluation, including measurements of best-corrected visual acuity (BCVA), slit-lamp examination, dilated fundus examination, color fundus photography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, and spectral-domain OCT. An inverse probability of treatment weighting (IPTW) methodology was applied to balance 18 baseline characteristics between patients who received rf-PDT (rf-PDT group) and those who did not receive treatment (controls). Inverse probability of treatment weighting survival analysis and regression were performed.The proportion of patients whose BCVA at 24 months was the same or improved compared with the baseline visual acuity (VA) (VA maintenance rate).A total of 155 eyes (rf-PDT group: 74; controls: 81) were analyzed. The patients' backgrounds were well balanced after IPTW with standardized differences of0.10. An IPTW regression analysis revealed that the VA maintenance rate was significantly higher in the rf-PDT group than in the controls (93.6% vs. 70.9%,The study suggests the beneficial effect of rf-PDT for cCSC for both VA maintenance and higher proportion of complete SRD remission in the clinical setting.

PURPOSE To investigate whether the efficacy of anti-vascular endothelial growth factor (VEGF) monotherapy for polypoidal choroidal vasculopathy (PCV) differs between pachychoroid and non-pachychoroid phenotypes in the long term. METHODS This retrospective longitudinal study included 115 treatment-naive eyes in 115 consecutive patients with symptomatic PCV who were treated with anti-VEGF monotherapy and were followed up for 5 years. Eligible eyes were assigned to either a pachy-PCV group, with a pachychoroid phenotype, or a non-pachy-PCV group, without a pachychoroid phenotype. Best-corrected visual acuity (BCVA) and other parameters over a 5-year period were compared between the groups. RESULTS Forty-eight eyes and 67 eyes were classified into the pachy-PCV and non-pachy-PCV groups respectively. Baseline and 5-year BCVA (logarithm of the minimum angle of resolution) were 0.19 ± 0.20 and 0.16 ± 0.28 in the pachy-PCV group, respectively, and 0.25 ± 0.26 and 0.26 ± 0.36 in the non-pachy-PCV group respectively. BCVA did not change significantly in either group (p = 0.18 and 0.08 respectively). BCVA did not differ between the groups at any observation time-point. Subfoveal choroidal thickness (SFCT) at baseline and at 5 years was significantly higher in the pachy-PCV group than in the non-pachy-PCV group (both p

It is still a controversial issue how the electron transport reaction is carried out around photosystem I (PSI) in the photosynthetic electron transport chain. The measurable component in PSI is the oxidized P700, the reaction center chlorophyll in PSI, as the absorbance changes at 820-830 nm. Previously, the quantum yield at PSI [Y(I)] has been estimated as the existence probability of the photo-oxidizable P700 by applying the saturated-pulse illumination (SP; 10,000-20,000 µmol photons m

Image captioning is a task to generate a sentence explaining an input image. In autonomous driving, image captioning is expected for providing linguistic explanations of autonomous driving control decision-making because it can reduce the psychological burden on passengers and prevent accidents. Current image-captioning methods are limited to generating a caption for an input image and not generating captions for events in the near future. It is important to generate captions for any event that will happen in the near future to prevent accidents and alert passengers. Therefore, we created a task to generate an explanatory sentence of near-future events using images observed from past to present. For this task, we propose a near-future image-captioning method suitable for in-vehicle camera images. Our experiments using the Berkeley Deep Drive eXplanation Dataset showed that the proposed method can appropriately generate captions for near-future events.

An n-channel 4H-SiC insulated-gate bipolar transistor (IGBT) with an extremely low switching loss was demonstrated by making 70 μm thin drift layers designed for 6.5 kV blocking voltage, without substrates. A conductivity-modulated bipolar operation was successfully performed as a on-voltage of 4.96 V at a 100 A cm−2 collector current. The turn-off losses under 3.6 kV/32 A operation were 8.8 (at room temperature) and 22.7 mJ (at 150 °C), which were much lower than the estimated losses of SiC IGBTs with thick drift layers. A detailed investigation on turn-off transition of SiC IGBTs specifically focused on a voltage-slope increase was also conducted. This phenomenon can cause ringing in switching characteristics. A device structure has been proposed to eliminate it by controlling the expansion of a depletion layer. Voltage-slope control and ringing reduction without noticeable degradation in static characteristics and switching loss were demonstrated with the SiC IGBT with the proposed device structure.

We developed a novel scotoma detection system using time required for fixation to the random targets, or the” eye-guided scotoma detection method “. In order to verify the” eye-guided scotoma detection method “, we measured 78 eyes of 40 subjects, and examined the measurement results in comparison with the results of measurement by Humphrey perimetry. The results were as follows: (1) Mariotte scotomas were detected in 100% of the eyes tested; (2) The false-negative rate (the percentage of cases where a scotoma was evaluated as a non-scotoma) was less than 10%; (3) The positive point distribution in the low-sensitivity eyes was well matched. These findings suggested that the novel scotoma detection method in the current study will pave the way for the realization of mass screening to detect pathological scotoma earlier.Author summaryConventional perimeters, such as the Goldmann perimeter and Humphrey perimeter, require experienced examiners and space occupying. With either perimeter, subjects’ eye movements need to be strictly fixed to the fixation target of the device. Other perimeters can monitor fixation and automatically measure the visual field. With the eye-guided scotoma detection method proposed in the current study, subjects feel less burdened since they do not have to fixate on the fixation target of the device and can move their eyes freely. Subjects simply respond to visual targets on the display; then, scotomas can be automatically detected. The novel method yields highly accurate scotoma detection through an algorithm that separates scotomas from non-scotomas.

The trade-off between low on-resistance and high short-circuit (SC) capability crucial for silicon carbide metal-oxide-semiconductor (MOS) field-effect transistors. To break this trade-off, we clarified the design parameters that are key in improving SC capability and confirmed that our trench-etched double-diffused MOS (TED-MOS) can be suitably designed using its unique parameters to achieve low on-resistance while maintaining high SC capability.

To evaluate ethnic variations, ocular and systemic determinants of retinal nerve fiber layer (RNFL) thickness, and neuroretinal rim area among Asians using a large consortium of population-based eye studies.Cross-sectional pooled analysis.Twenty-two thousand four hundred thirty-six participants (22 436 eyes) from 10 population-based studies (in China, Hong Kong, India, Japan, Russia, and Singapore) of the Asian Eye Epidemiology Consortium.Participants 40 years of age or older without glaucoma were included. All participants underwent spectral-domain OCT imaging and systemic and ocular examinations. Data were pooled from each study. Multivariable regression was performed to evaluate interethnic differences, intermachine variations, and ocular and systemic factors associated with RNFL thickness and rim area, adjusting for age, gender, diabetes, intraocular pressure (IOP), spherical equivalent (SE), ethnicity, OCT model, and study group. When evaluating body mass index, smoking, and hypertension as exposures, these factors were additionally adjusted for in the model.Average RNFL thickness (in micrometers) and rim area (in square millimeters).Indian and Japanese eyes have thinner RNFLs than those of other Asian ethnicities (β values range, 7.31-12.76 μm; P0.001 for all pairwise comparisons). Compared with measurements by Cirrus HD-OCT (Carl Zeiss Meditec, Inc), RNFL on average was 7.29 μm thicker when measured by Spectralis (Heidelberg Engineering), 12.85 μm thicker when measured by RS-3000 (NIDEK Co, Ltd), and 17.48 μm thicker when measured by iVue/RTVue (Optovue, Inc) devices (all P0.001). Additionally, older age (per decade, β = -2.70), diabetes (β = -0.72), higher IOP (per 1 mmHg, β = -0.07), more myopic SE (per diopter, β = -1.13), cardiovascular disease (β = -0.94), and hypertension (β = -0.68) were associated with thinner RNFL (all P ≤ 0.003). Similarly, older age (β = -0.019), higher IOP (β = -0.010), and more myopic SE (β = -0.025) were associated with smaller rim area (all P0.001).In this large pooled analysis of Asian population studies, Indian and Japanese eyes were observed to have thinner RNFL profiles. These findings suggest the need for an ethnic-specific normative database to improve glaucoma detection.

Colored compounds formed by the Maillard reaction of carnosine with xylose or glucose were investigated in this study. Yellow pigments showing an absorption maximum at 450 nm were found in a heated solution of carnosine with xylose at pH 5.0. These pigments were then isolated and identified as dicarnosyl-dipyrrolones A and B. The generation of dipyrrolones in the absence of lysine suggests that dipyrrolone pigments can be formed by pentose as well as every amino compound such as amino acids, peptides and proteins possessing a free amino group. Analysis of α-dicarbonyls using LC-MS/MS showed that pentosone, 1-deoxypentosone, 3-deoxypentosone (3-DP), and methylglyoxal were predominantly generated via degradation of Amadori compounds. Also, a potential formation pathway of dypyrrolones was established, indicating that an Amadori compound that could form 3-DP is likely to play a role as a main precursor for dipyrrolones.

The entorhinal cortex (EC) is the spatial processing center of the brain and structurally is an interface between the three layered paleocortex and six layered neocortex, known as the periarchicortex. Limited studies indicate peculiarities in the formation of the EC such as early emergence of cells in layers (L) II and late deposition of LIII, as well as divergence in the timing of maturation of cell types in the superficial layers. In this study, we examine developmental events in the entorhinal cortex using an understudied model in neuroanatomy and development, the pig and supplement the research with BrdU labeling in the developing mouse EC. We determine the pig serves as an excellent anatomical model for studying human neurogenesis, given its long gestational length, presence of a moderate sized outer subventricular zone and early cessation of neurogenesis during gestation. Immunohistochemistry identified prominent clusters of OLIG2+ oligoprogenitor-like cells in the superficial layers of the lateral EC (LEC) that are sparser in the medial EC (MEC). These are first detected in the subplate during the early second semester. MRI analyses reveal an acceleration of EC growth at the end of the second trimester. BrdU labeling of the developing MEC, shows the deeper layers form first and prior to the superficial layers, but the LV/VI emerges in parallel and the LII/III emerges later, but also in parallel. We coin this lamination pattern parallel lamination. The early-born Reln+ stellate cells in the superficial layers express the classic LV marker, Bcl11b (Ctip2) and arise from a common progenitor that forms the late deep layer LV neurons. In summary, we characterize the developing EC in a novel animal model and outline in detail the formation of the EC. We further provide insight into how the periarchicortex forms in the brain, which differs remarkably to the inside-out lamination of the neocortex.Competing Interest StatementThe authors have declared no competing interest. The entorhinal cortex (EC) is the spatial processing center of the brain and structurally is an interface between the three layered paleocortex and six layered neocortex, known as the periarchicortex. Limited studies indicate peculiarities in the formation of the EC such as early emergence of cells in layers (L) II and late deposition of LIII, as well as divergence in the timing of maturation of cell types in the superficial layers. In this study, we examine developmental events in the entorhinal cortex using an understudied model in neuroanatomy and development, the pig and supplement the research with BrdU labeling in the developing mouse EC. We determine the pig serves as an excellent anatomical model for studying human neurogenesis, given its long gestational length, presence of a moderate sized outer subventricular zone and early cessation of neurogenesis during gestation. Immunohistochemistry identified prominent clusters of OLIG2+ oligoprogenitor-like cells in the superficial layers of the lateral EC (LEC) that are sparser in the medial EC (MEC). These are first detected in the subplate during the early second semester. MRI analyses reveal an acceleration of EC growth at the end of the second trimester. BrdU labeling of the developing MEC, shows the deeper layers form first and prior to the superficial layers, but the LV/VI emerges in parallel and the LII/III emerges later, but also in parallel. We coin this lamination pattern parallel lamination. The early-born Reln+ stellate cells in the superficial layers express the classic LV marker, Bcl11b (Ctip2) and arise from a common progenitor that forms the late deep layer LV neurons. In summary, we characterize the developing EC in a novel animal model and outline in detail the formation of the EC. We further provide insight into how the periarchicortex forms in the brain, which differs remarkably to the inside-out lamination of the neocortex.

Ribozymes with modular architecture constitute an attractive class of structural platforms for design and construction of nucleic acid nanostructures with biological functions. Through modular engineering of the Tetrahymena ribozyme, we have designed unit RNAs (L-RNAs), assembly of which formed ribozyme-based closed trimers and closed tetramers. Their catalytic activity was dependent on oligomer formation. In this study, the structural variety of L-RNA oligomers was extended by tuning their structural elements, yielding closed pentamers and closed hexamers. Their assembly properties were analyzed by electrophoretic mobility shift assay (EMSA) and atomic force microscopy (AFM).

Designing effective and safe tuberculosis (TB) subunit vaccines for inhalation requires identification of appropriate antigens and adjuvants and definition of the specific areas to target in the lungs. Magnetic resonance imaging (MRI) enables high spatial resolution, but real-time anatomical and functional MRI of lungs is challenging. Here, we describe the design of a novel gadoteridol-loaded cationic adjuvant formulation 01 (CAF01) for MRI-guided vaccine delivery of the clinically tested TB subunit vaccine candidate H56/CAF01. Gadoteridol-loaded CAF01 liposomes were engineered by using a quality-by-design approach to (i) increase the mechanistic understanding of formulation factors governing the loading of gadoteridol and (ii) maximize the loading of gadoteridol in CAF01, which was confirmed by cryotransmission electron microscopy. The encapsulation efficiency and loading of gadoteridol were highly dependent on the buffer pH due to strong attractive electrostatic interactions between gadoteridol and the cationic lipid component. Optimal gadoteridol loading of CAF01 liposomes showed good in vivo stability and safety upon intrapulmonary administration into mice while generating 1.5-fold MRI signal enhancement associated with approximately 30% T1 relaxation change. This formulation principle and imaging approach can potentially be used for other mucosal nanoparticle-based formulations, species, and lung pathologies, which can readily be translated for clinical use.

Purpose CD81 is a member of the tetraspanin family of membrane proteins. Recently, it has been shown that CD81 may be involved in cancer cell proliferation and metastasis. As yet, however, there have been few reports on the expression and role of CD81 in osteosarcoma. Methods The expression of CD81 was investigated in human osteoblast cell line hFOB1.19 and in human osteosarcoma cell lines Saos2, MG63 and 143B. The expression of CD81 was inhibited in osteosarcoma cells using siRNA after which cell proliferation, migration and invasion were assessed. We also used Western blotting to investigate the phosphorylation status of Akt, Erk, JNK and p38, and measured the expression of MMP-2, MMP-9 and MT1-MMP. In addition, we used a CRISPR/Cas9 system to stably knock out CD81 expression in 143B cells, transplanted the cells into mice, and assessed tumor formation and lung metastasis in these mice compared to those in the control group. Results We found that CD81 was expressed in the human osteoblast cell line and in all osteosarcoma cell lines tested. The osteosarcoma cell line 143B exhibited a particularly high level of expression. In addition, we found that osteosarcoma cell proliferation, migration and invasion were decreased after CD81 inhibition, and that the phosphorylation of Akt and Erk was suppressed. Also, the expression levels of MMP-2, MMP-9 and MT1-MMP were found to be suppressed, with MMP-9 showing the greatest suppression. In vivo, we found that mice transplanted with CD81 knockout 143B cells exhibited significantly less tumor formation and lung metastasis than mice in the control group. Conclusion Based on our findings we conclude that inhibition of CD81 suppresses intracellular signaling and reduces tumorigenesis and lung metastasis in osteosarcoma cells.

We report the physical and electrical characterization of the inversion layer carrier and the shallow interface trap sites with n-and p-channel SiC-MOSFET in terms of high temperature electronics. This work proposes a physical model that explains the difference between Id-Vg measurement result and calculation result supposing the ideal condition with Pao and Sah double ideal in room temperature. The measurement at 500°C confirmed our model so that inversion carrier were thermally excided, they could not be easily trapped by shallow trap sites, and Id-Vg measurement result approached the ideal condition.

6.5-kV SiC IGBT with novel drift layer structure is developed to eliminate collector voltage steepening during turn-off and thus to suppress a ringing noise. The proposed IGBT has a depletion-controlled structure (DCS) of a two-step drift layer to suppress the increase of a depletion layer during the turn-off. We fabricated n-channel SiC IGBTs with DCS designed for a blocking voltage of 6.5 kV. Also, we applied our original backside-grinding-last (BG-last) process that enables low switching loss. The DCS device successfully reduced a riging of the gate voltage and had a turn-off loss of 17.6 mJ with 3.6-kV and 32-A switching operation. Although this value is larger than that of the conventional devices (8.8 mJ) due to a tail current, it is still quite low compared with the reported switching loss of SiC IGBTs with the proper switching curves, which is estimated to be 46.1 mJ with the same rated voltage and current.

A novel structure, trench-eched double-diffused MOS (TED-MOS), were proposed. In this study, we demonstrate compatibility of reliability and small loss for applications to electric vehicle. To suppress the dielectric breakdown of gate insulator, a field relaxation layer (FRL) are formed above JFET region. Device simulation shows an effective decrease of electric field on gate dioxide, and furthure improvement of switching-and conduction-loss were expected. The fabricated TED-MOS chip doesn’t show gate leakage current even over 1600 V. We confirmed stable normally-off characteristic of the chip at 175 °C, and its Ron was 66 mΩ under Vg = 20 V and 175 °C condition. As an uniqueness to FRL TED-MOS, capacitance shows a steep decline with several step, which may attributed to depletion between FRL and p-Body and should contributed to the reduction of switching loss.

Visual Abstract, Highlights • Intravenously injected ONO-1301–containing nanoparticles selectively accumulated in the ischemic border area of the myocardium. • Prominent up-regulation occurred of proangiogenic cytokines such as vascular endothelial growth factor and angiopoietin-1 in the ischemic myocardium, which may have contributed to the preservation of the native vascular and capillary networks, thus preserving regional myocardial blood flow. • Down-regulation of the proinflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α in the ischemic myocardium might have led to the attenuation of myocyte swelling and the suppression of the endothelial bleb formation, also contributing to the preservation of myocardial blood flow or the reduced infarct size., Summary Intravenously injected ONO-1301–containing nanoparticles (ONO-1301NPs), unlike an ONO-1301 solution, selectively accumulated in the ischemia/reperfusion (I/R)-injured myocardium of rats and contributed to the prolonged retention of ONO-1301 in the targeted myocardial tissue. In the ischemic area, proangiogenic cytokines were up-regulated and inflammatory cytokines were down-regulated upon ONO-1301NP administration. Consequently, ONO-1301NP–injected rats exhibited a smaller infarct size, better-preserved capillary networks, and a better-preserved myocardial blood flow at 24 h after I/R injury, compared with those in vehicle-injected or ONO-1301 solution–injected rats. ONO-1301NPs attenuate the myocardial I/R injury via proangiogenic and anti-inflammatory effects of the drug.

We herein report a case of autoimmune pulmonary alveolar proteinosis (PAP) diagnosed after one-time exposure to silica powder. Owing to the misuse of a silica-containing fire extinguisher and the inhalation of large amounts of its powder, the patient experienced prolonged cough and visited our hospital. The findings of chest computed tomography and surgical lung biopsy specimens led to the diagnosis of PAP. Interestingly, the presence of anti-GM-CSF antibody was detected; therefore, both autoimmune characteristics and exposure to large amounts of silica may have caused the development of PAP in this patient. This case provides important insight into the mechanisms leading to the onset of PAP.

We conduct 24.4~fps optical observations of repeating Fast Radio Burst (FRB) 20190520B using Tomo-e Gozen, a high-speed CMOS camera mounted on the Kiso 105-cm Schmidt telescope, simultaneously with radio observations carried out using the Five-hundred-meter Aperture Spherical radio Telescope (FAST). We succeeded in the simultaneous optical observations of 11 radio bursts that FAST detected. However, no corresponding optical emission was found. The optical fluence limits as deep as 0.068 Jy ms are obtained for the individual bursts (0.029 Jy ms on the stacked data) corrected for the dust extinction in the Milky Way. The fluence limit is deeper than those obtained in the previous simultaneous observations for an optical emission with a duration $\gtrsim 0.1$ ms. Although the current limits on radio--optical spectral energy distribution (SED) of FRBs are not constraining, we show that SED models based on observed SEDs of radio variable objects such as optically detected pulsars, and a part of parameter spaces of theoretical models in which FRB optical emission is produced by inverse-Compton scattering in a pulsar magnetosphere or a strike of a magnetar blastwave into a hot wind bubble, can be ruled out once a similar fluence limit as in our observation is obtained for a bright FRB with a radio fluence $\gtrsim 5$ Jy ms., Comment: Accepted for publication in ApJ, metadata corrected

Lipophagy, a form of selective autophagy, degrades lipid droplet (LD) in adipose tissue and the liver. The chemotherapeutic isothiocyanate sulforaphane (SFN) contributes to lipolysis through the activation of hormone-sensitive lipase and the browning of white adipocytes. However, the details concerning the regulation of lipolysis in adipocytes by SFN-mediated autophagy remain unclear. In this study, we investigated the effects of SFN on autophagy in the epididymal fat of mice fed a high-fat diet (HFD) or control-fat diet (CFD) and on the molecular mechanisms of autophagy in differentiated 3T3-L1 cells. Western blotting revealed that the protein expression of lipidated LC3 (LC3-II), an autophagic substrate, was induced after 3T3-L1 adipocytes treatment with SFN. In addition, SFN increased the LC3-II protein expression in the epididymal fat of mice fed an HFD. Immunofluorescence showed that the SFN-induced LC3 expression was co-localized with LDs in 3T3-L1 adipocytes and with perilipin, the most abundant adipocyte-specific protein, in adipocytes of mice fed an HFD. Next, we confirmed that SFN activates autophagy flux in differentiated 3T3-L1 cells using the mCherry-EGFP-LC3 and GFP-LC3-RFP-LC3ΔG probe. Furthermore, we examined the induction mechanisms of autophagy by SFN in 3T3-L1 adipocytes using western blotting. ATG5 knockdown partially blocked the SFN-induced release of fatty acids from LDs in mature 3T3-L1 adipocytes. SFN time-dependently elicited the phosphorylation of AMPK, the dephosphorylation of mTOR, and the phosphorylation of ULK1 in differentiated 3T3-L1 cells. Taken together, these results suggest that SFN may provoke lipophagy through AMPK-mTOR-ULK1 pathway signaling, resulting in partial lipolysis of adipocytes.

The development of hydrogen fuel cells is greatly hindered by the unwanted generation of H2 O2 at the cathode. A non-Pt cathode catalyst is now shown to be capable of simultaneously reducing both O2 and H2 O2 , thus rendering H2 O2 a useful part of the feed stream. The applicability of this unique catalyst is demonstrated by employing it in a fuel cell running on H2 /CO and O2 /H2 O2 .

MicroRNAs are potential targets for drug development. Small molecules that can inhibit or promote a specific miRNA's biogenesis would be useful for regulating its target genes. Various types of small molecules have been investigated so far for their potential application in modulating miRNA biogenesis. They bind to the target primary or precursor miRNAs and inhibit the processing of these precursors by Drosha or Dicer. However, the binding site that effectively interferes with the Dicer cleavage reaction is still undetermined. Here we report that our designed small molecule restricted naphthyridine dimer (RND) binds to the hairpin loop of a hairpin RNA and induces its dimerization. This study shows that the binding of the RND to the hairpin loop was not effective in interfering with the Dicer cleavage reaction, but dimerization of the hairpin RNA by RND binding effectively interfered with the Dicer cleavage reaction.

The glymphatic system is network of perivascular spaces through which cerebrospinal fluid and interstitial fluid can move through the brain, clearing metabolic waste, such as amyloid beta, lactate and more, from the parenchyma. This cleaning system is regulated by sleep and norepinephrine, with increased levels of norepinephrine during wakefulness inhibiting fluid movement. Norepinephrine is also essential for transition from acute to chronic pain, and sufferers of chronic neuropathic pain frequently present with sleep disruption. These connections among glymphatic clearance, sleep, and pain are very intriguing, and might lead to nonpharmaceutical interventions for pain treatment. This short perspective provides a rationale for the hypothesis that mind-body interventions-such as acupuncture-can reduce norepinephrine and increase glymphatic function, ultimately relieving chronic neuropathic pain.

A 49-year-old male with untreated diabetes mellitus type 2 experienced eyesight deterioration and general malaise, and was treated for uveitis and orbital cellulitis. Later, he was taken to a local hospital via ambulance for a consciousness disorder and was diagnosed with bilateral infectious endophthalmitis, a right ureteral stone, and emphysematous pyelonephritis. He was then referred to our hospital for further examination and treatment. We immediately initiated intravenous antibiotic therapy with meropenem and glycemic control with continuous subcutaneous insulin infusion, and placed a ureteral and percutaneous drain tube into the right ureter and the emphysema, respectively. We performed a diagnostic and therapeutic vitrectomy on the patient's left eye. Urinary, blood, and vitreous cultures were positive for Klebsiella aerogenes. Abdominal contrast-enhanced computed tomography showed bilaterally comparable renal contrast enhancement. On the 60th hospital day, we performed endoscopic combined intrarenal surgery (ECIRS) and completely removed the urinary stone. Although he lost light sensitivity in his right eye, his left eyesight improved, and his blood glucose level was adequately managed by oral medication. Three months after the surgery, he was discharged from our hospital and he showed no sign of recurrence of the infection at ten months after surgery.