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To characterize the findings of eyes with choroidal vascular hyperpermeability (CVH), a hallmark of central serous chorioretinopathy, using multimodal imaging and investigate the locational agreement between these findings and CVH.Among patients with central serous chorioretinopathy in either eye, eyes with CVH identified using indocyanine green angiography without exudative changes were included. All eyes were examined using funduscopy, fluorescein angiography, spectral-domain optical coherence tomography, and short-wavelength or near-infrared autofluorescence (SWAF or NIRAF). The locational agreement between CVH and imaging findings was evaluated for each modality. The relative index on how they overlapped was calculated as the overlapping index. Binarized images, particularly for NIRAF, were also evaluated.This study included 69 CVH sites in 33 eyes of 28 patients. Pachydrusen was detected in 36% of CVH sites. Fluorescein angiography revealed hyperfluorescent areas in 39% of CVH sites. Optical coherence tomography findings identified 65% of CVH sites, but the overlapping index was 5%. Short-wavelength or near-infrared autofluorescence imaging identified 89% of CVH sites, but they exhibited variable autofluorescence. NIRAF imaging revealed hypoautofluorescence findings in all CVH sites. When binarized, near-infrared autofluorescent dark dots were observed in all CVH sites. Overlapping indices before and after binarization were 78% and 98%, respectively. The near-infrared autofluorescent dark dots area corresponded well with that of CVH (intraclass correlation coefficient, 0.987 [95% confidence interval, 0.952-0.995]).Hypoautofluorescent findings revealed on NIRAF imaging, especially after binarization processing, corresponded well with CVH sites. These multimodal imaging results may help investigate the anatomical or locational characteristics of CVH in patients with central serous chorioretinopathy.

On January 26, 2023, Science issued an editorial announcing that its journal policy would be changed to restrict artificial intelligences (AIs), such as ChatGPT, from being used to write papers, in addition to disallowing authorship of AIs. Indeed, AIs are not eligible for authorship because they do not have free will and they cannot make decisions to be an author. However, several observations have been made that researchers can use ChatGPT as an English proofreader, rather than a writer of first drafts. Therefore, we discussed the usage of AIs and the way of authorship, particularly, in terms of English proofreading. Then, we wrote an eLetter for that editorial, but its eLetter section suddenly disappeared, so we released the eLetter as a preprint with additional discussion. Although AIs are a double-edged sword and they could exacerbate scholarly publishing and science, they also have potentialities to remove language barriers and improve science all over the world. The present article claimed the importance of continuous discussion about the use of AIs and the language barriers.

Scientists write research articles, process ethics reviews, evaluate proposals and research, and seek funding. Several strategies have been proposed to optimize these operations and to decentralize access to research resources and opportunities. For instance, we previously proposed the trinity review method, combining registered reports with financing and research ethics assessments. However, previously proposed systems have a number of shortcomings, including how to implement them, e.g., who manages them, how incentives for reviewers are paid, etc. Various solutions have been proposed to address these issues, employing decentralized science (DeSci) in an independent organization built on the blockchain. Decentralized approaches that exploit these developments offer potentially profound improvements to the troubled scientific ecosystem. Here, we propose a system that integrates ethics reviews, peer reviews, and funding in a decentralized manner, based on Web3 technology. This new method, named ABCDEF publishing, would enhance the speed, fairness, and transparency of scientific research and publishing.

Constant-pressure heat capacities (CPs) of crystalline benzoic acid (BAh) and its deuterated analogue (C6H5COOD, BAd) were measured by adiabatic calorimetry, and the phonon density (g(ω)) of states was determined from their CP data using a real-coded genetic algorithm (RCGA) with just generation gap + real-coded ensemble cross-over. The distribution of g(ω) was in reasonable agreement with the spectroscopic one observed for molecular vibration modes, indicating sufficient reliability of g(ω) determined by the RCGA. Based on the fact that CPs reveals an inverse-isotope effect in the temperature range 30-130 K, the determined g(ω)s were used to investigate the molecular mechanism of the effect: g(ω) of BAd revealed blue shifts in the ranges of ω = 80-100 and 150-230 K, as referred to that of BAh. It was suggested from the combined considerations on g(ω) and spectroscopic results that an anticooperative correlation exists between O-H···O hydrogen bonds and interdimer interactions in BA.

PurposeTo investigate retinal sensitivity of highly myopic eyes without choroidal neovascularisation (CNV) or patchy chorioretinal atrophy (PCA) and investigated its association with anatomical characteristics including melanin distribution at the retinal pigment epithelium (RPE), which was evaluated with polarisation-sensitive optical coherence tomography (PS-OCT).DesignRetrospective consecutive observational cohort study.MethodsWe included highly myopic eyes (refractive error ≤−8.0 dioptres or axial length of ≥26.5 mm) from patients at the University of Tokyo Hospital. Retinal sensitivity was measured by microperimetry at 25 sectors within 6 degrees from the fovea. Depolarisation value, which reflected melanin pigmentation, was measured by a clinical prototype of PS-OCT and was parameterised as polarimetric entropy. Retinal sensitivity or entropy at the RPE in high myopia was compared with emmetropic control subjects. The association of retinal sensitivity with age, axial length, entropy, or choroidal thickness was assessed in per-eye and per-sector analysis.ResultsTwenty-three highly myopic eyes (age, 66.6±12.3 years) were included. The average retinal sensitivity was 25.3±3.0 dB, which was significantly decreased compared with the control (pConclusionsDecreased depolarisation at the RPE measured with PS-OCT, which reflected altered melanin pigmentation, was independently associated with reduced retinal sensitivity in patients with early stages of myopic maculopathy without CNV or PCA.

Intermediate species formed on Ag(110) surfaces under the presence of ethylene and oxygen in the sub-Torr pressure range were studied by near-ambient-pressure X-ray photoelectron spectroscopy (XPS)...

One major source of exhaustion for researchers is the redundant paperwork of three different documents—research papers, ethics review applications, and research grant applications—for the same research plan. This is a wasteful and redundant process for researchers, and it has a more direct impact on the career development of early-career researchers. Here, we propose a trinity review system based on Registered Reports that integrates scientific, ethics, and research funding reviews. In our proposed trinity review system, scientific and ethics reviews are undertaken concurrently for a research protocol before running the study. After the protocol is approved in principle through these review processes, a funding review will take place, and the researchers will begin their research. Following the experiments or surveys, the scientific review will be conducted on a completed version of the paper again, including the results and discussions (i.e., the full paper), and the full paper will be published once it has passed the second review. This paper provides the brief process of the trinity review system and discusses the need for and benefits of the proposed system. Although the trinity review system only applies to a few appropriate disciplines, it helps improve reproducibility and integrity.

Background: The COVID-19 pandemic has led to instructions and suggestions from governments and experts to maintain social (physical) distance between people to prevent aerosol transmission of the virus, which is now becoming the norm. Thus, we examined whether the pandemic extended the distance between personal belongings. Methods: We recruited 68 university students and instructed them to place their belongings on a long table following another participant (i.e., confederate). We measured the physical distance between the two belongings (i.e., the participant’s and the confederate’s). We collected data between June 10, 2022 and January 23, 2023. Pre-pandemic data was from Ariga (2016). Analysis was completed with one-tailed t-tests. Results: Compared with the pre-pandemic results, via one-tailed t-test, the distance between the two belongings during the pandemic was significantly longer. Our results supported the hypothesis that the psychological framework for processing people’s belongings has dramatically changed during this pandemic. Conclusion: This change may have been driven by social distancing practices or an increase in perceived vulnerability to disease. Our results provide new implications for future public spatial design, in other words, not only the distance between people, but also the distance between their belongings.

This study was conducted to examine retinal sensitivity (RS) in eyes with pachychoroid diseases and to analyze its association with the presence or absence of quiescent choroidal neovascularization (CNV), that can be protective against retinal dysfunction or atrophy in other macular diseases such as age-related macular degeneration. A total of 12 eyes of 12 patients aged ≥45 years having the characteristic findings of central serous chorioretinopathy but not presenting any exudative changes were included in this study. Choroidal vascular hyper permeability (CVH) was identified by indocyanine green angiography, and the presence or absence of CNV was evaluated by optical coherence tomography angiography. RS at 68 points was examined by microperimetry. The average RS corresponding to within and outside CVH was compared. The association between the difference in RS and the presence or absence of CNV was also analyzed. CNV was detected in six eyes (50%). In eyes without CNV, the RS within CVH was similar compared with that outside CVH. However, in eyes with CNV, the RS within CVH was significantly decreased compared with that outside CVH. Multiple regression analysis revealed the presence of CNV as an independent factor associated with RS. In eyes with pachychoroid diseases, RS decreased within the CVH area under the coexistence of nonexudative CNV.

We study spin Hall magnetoresistance (SMR) in Pt/ferrimagnetic insulator Y3Fe5O12 (YIG) bilayers by focusing on crystallinity, magnetization, and interface roughness by controlling post-annealing temperatures. The SMR in the Pt/YIG grown on Si substrate is comparable to that grown on widely used Gd3Ga5O12 substrate, indicating that the large SMR can be achieved irrespective of the crystallinity. We deduced the spin mixing conductance from the Pt thickness dependence of the SMR to find the high interface quality of the optimized Pt/YIG grown on Si in terms of spin current. We also clarified that the SMR correlates well with the magnetization, the interface roughness, and carrier density. These findings highlight that optimizing YIG properties is a key to control of magnetization by spin current, leading to the development of the low power consumption spintronic device based on the magnetic insulator.

The 5d transition-metal oxides are an intriguing platform to demonstrate efficient charge-to-spin-current conversion due to a unique electronic structure dominated by strong spin-orbit coupling. Here, we report on the stacking-order effect of spin-orbit torque (SOT), spin-Hall magnetoresistance, and magnetic anisotropy in bilayer ${\mathrm{Ni}}_{81}{\mathrm{Fe}}_{19}$-5d iridium oxide, ${\mathrm{Ir}\mathrm{O}}_{2}$. While all ${\mathrm{Ir}\mathrm{O}}_{2}$ and $\mathrm{Pt}$ control samples exhibit large dampinglike SOT generation, stemming from the efficient charge-to-spin-current conversion, the magnitude of the SOT is larger in the ${\mathrm{Ir}\mathrm{O}}_{2}$($\mathrm{Pt})$ bottom sample than in the ${\mathrm{Ir}\mathrm{O}}_{2}$($\mathrm{Pt})$ top one. The fieldlike SOT has an even more significant stacking-order effect, resulting in an opposite sign in the ${\mathrm{Ir}\mathrm{O}}_{2}$ samples in contrast to the same sign in the $\mathrm{Pt}$ samples. Furthermore, we observe that the magnetic anisotropy energy density and the anomalous Hall effect are increased in the ${\mathrm{Ir}\mathrm{O}}_{2}$($\mathrm{Pt})$ bottom sample, suggesting enhanced interfacial perpendicular magnetic anisotropy. Our findings highlight the significant influence of the stacking order on spin transport and the magnetotransport properties of $\mathrm{Ir}$ oxide-ferromagnet systems, providing useful information for the design of SOT devices, including 5d transition-metal oxides.

Pre-painted hot-dip 55 mass% Al-Zn coated steel sheets are widely used as a building material due to their superior corrosion resistance. In consideration of its long-term service, a pre-painted hot-dip 55 mass% Al-Zn-2 mass% Mg coated steel sheet with enhanced corrosion resistance has been developed in recent years.1 It has been shown that the addition of 2 mass% Mg not only reduced the corrosion rate by 1/3 but also inhibited the delamination of organic paints from the cut-edge. As yet, however, the role of Mg in the cut-edge corrosion protection of the 55 mass% Al-Zn-2 mass% Mg coated steel has not been completely clear. In this study, we focused on the influence of Mg-containing corrosion products on the electrochemical properties of the coating layer and the steel substrate. Hot-dip 55 mass% Al-Zn-2 mass% Mg-1.6 mass% Si and 55 mass% Al-Zn-1.6 mass% Si coated steel sheets were used in this study. The Al-Zn-Mg coating layer is composed of Al-rich, Zn-rich, and Mg-Si phases. Our previous study has reported that for the Al-Zn-Mg coating layer, the Zn-rich phase preferentially dissolves during the initial process of cut-edge corrosion.2 In addition, Mg also preferentially dissolves from the Mg-Si phase in the Al-Zn-Mg coating layer. The wet and dry cyclic corrosion test showed that the formation of the Zn-based corrosion products at the cut-edge for the Al-Zn-Mg coated steel was more inhibited than that for the Al-Zn coated steel. In addition, the sacrificial corrosion protection ability of the Al-Zn-Mg coated steel was higher than the Al-Zn coated steel. It was found that the dense corrosion products including Mg were formed on the steel substrate at the cut-edge for the Al-Zn-Mg coated steel 1 hour after the onset of the corrosion test. The Mg-containing corrosion products slightly reduced the cathodic current for the oxygen reduction reaction, and this is thought to be one of the factors for the improved cut-edge corrosion resistance. 1) N. Shimoda, Y. Morimoto, Y. Kubo, S. Fujii, and S. Shiragaki, Galvatech 2015 Proceedings, 802 (2015). 2) S. Tokuda, I. Muto, Y. Sugawara, M. Takahashi, M Matsumoto, and N. Hara, Corros. Sci, 129, 126 (2017).

In order to reduce the decoding latency, the belief propagation (BP) decoder, which is generally used for decoding of the low-density parity-check (LDPC) codes, is effective. In general, the error rate performance of BP decoder is degraded. Therefore, this paper investigates the influence of design signal-to-noise ratio (SNR) on the bit error rate (BER) performance under BP decoder. We first generate the multiple polar codes by setting the multiple design-SNR. The BER performance is used to optimize the polar code for the BP decoder. The simulation results employing N = 1024 and the coding rate of 1/2 show that by setting slightly larger design-SNR compared to the SC decoder, the BER performance is slightly improved.

We have previously shown that podocyte injury increases the glomerular filtration of liver-derived angiotensinogen (Agt) and the generation of intrarenal angiotensin (Ang) II and that the filtered Agt is reabsorbed by proximal tubules in a manner dependent on megalin. In the present study, we aimed to study the role of megalin in the generation of renal Ang II and sodium handling during nephrotic syndrome. We generated proximal tubule-specific megalin knockout (KO) mice and crossed these animals with NEP25 mice, in which podocyte-specific injury can be induced by injection of the immunotoxin LMB2. Without podocyte injury, renal Agt staining was markedly diminished and urinary Agt increased in KO mice. However, renal Ang II was similar between KO and control mice on average: 117 (95% CI 101–134) vs. 101 (68–133) fmol/g tissue. We next tested the effect of megalin KO on intrarenal Ang II generation with podocyte injury. Control NEP25 mice showed markedly increased renal Agt staining and renal Ang II levels: 450 (336–565) fmol/g tissue. Megalin KO/NEP25 mice showed markedly diminished Agt reabsorption and attenuated renal Ang II: 199 (156–242) fmol/g tissue (p < 0.001). Compared with control NEP25 mice, megalin KO/NEP25 mice excreted 5-fold more sodium in the urine. Western blot analysis showed that megalin KO decreased NHE3 and the cleaved α and γ forms of ENaC. These data indicate that Agt reabsorbed by proximal tubules via megalin in nephrotic syndrome is converted to Ang II, which may contribute to sodium retention and edema formation by activating NHE3 and ENaC. SUMMARY: This study shows that in nephrotic syndrome, plasma angiotensinogen leaked into the renal tubular lumen is reabsorbed by proximal tubules via megalin and converted to angiotensin II, which may contribute to sodium retention and edema formation by activating NHE3 and ENaC.

The active oxygen species for ethylene epoxidation on Ag surfaces has been a long-standing issue. We conducted in situ observations of Ag(111) surfaces under exposure to ethylene and oxygen gases w...

This paper examines whether the economic crisis induced by the COVID-19 pandemic exhibits a Schumpeterian “cleansing” of less productive firms. Using firm-level data for 31 economies, the study finds that less productive firms have a higher probability of permanently closing during the crisis, suggesting that the process of cleansing out unproductive arrangements may be at work. The paper also uncovers a strong and negative relationship between firm exit and innovation and digital presence, especially for small firms, confirming the relevance of the ability to adapt to market conditions as a determinant of firm survival. Finally, the study finds evidence of a negative relationship between firm exit and a burdensome business environment, as well as between firm exit and age.

Purpose To investigate the three-dimensional distribution and associating demographic factors of depolarization, using polarization-sensitive optical coherence tomography (PS-OCT), to evaluate melanin pigmentation in the retinal pigment epithelium (RPE) and choroid in healthy eyes. Methods In total, 39 unaffected healthy eyes of 39 subjects were examined using a PS-OCT clinical prototype. The degree of depolarization, expressed as the polarimetric entropy, was assessed in the RPE, the superficial and the total choroid layer, especially in the center, the inner, or the outer areas centered at the fovea. The values and their association with the demographic data were analyzed. Near-infrared fundus autofluorescence (NIRAF) was also used, in the same manner, for the comparison. Twenty-eight of 39 eyes were measured twice to evaluate intrasession repeatability. Results Both the polarimetric entropy in the RPE and the gray level in NIRAF, decreased from the center to the periphery (P < 0.001). The polarimetric entropy in the RPE was significantly associated with age in each area (P ≤ 0.001). In the RPE and the superficial choroid, the polarimetric entropy was negatively associated with axial length in each area (P ≤ 0.002). The intraclass correlation coefficient of the polarimetric entropy in the same session was excellent in each area of the RPE, superficial choroid, or total choroid layer (0.94-0.98). Conclusions The distribution of fundus melanin pigment-related depolarization was evaluated using PS-OCT. The depolarization was associated with the subjects' demographic data, such as age or axial length. Translational Relevance The presented information in healthy eyes provides an essential basis for the investigation into a variety of chorioretinal pathologies.

A method was proposed to derive the phonon density [g(ω)] of states of materials from their heat capacity data by using Real-Coded Genetic Algorithm (RCGA) with Just Generation Gap + Real-Coded Ensemble Crossover. The performance of the method was confirmed by testing whether or not the RCGA reproduces a reasonable g(ω) by analyzing the set of heat capacity data evaluated from an initially assumed model g0(ω) composed of Debye and optical modes. As an example, constant-pressure heat capacities (CPs) were measured for soft molecular materials, diphenyl phosphate (DPP) and diphenylphosphinic acid, in the condensed state, and their g(ω)s were determined from the CP data by applying the RCGA. The unusual behavior that the CP value of glass was smaller than the one of the crystal in the temperature range from 10 to 70 K was observed in DPP; the behavior is contrary to that expected ordinarily for the glass as compared with the crystal. The g(ω)s determined by the RCGA demonstrated that the unusual behavior was attributed to the blue shift in g(ω) of ω = 30-240 K in the glass compared with the crystal. The blue shift and other effects were discussed reasonably as originating from the competitive concurrence of strong and weak intermolecular hydrogen bonds in DPP, with the help of determination of their intramolecular vibrations for the isolated molecule by the density functional theory calculation. It was concluded that the method using the RCGA is of value for obtaining the microscopic information of g(ω) from the precise heat capacity data and for investigating any difference between the details of g(ω)s in different phases of materials.

The $5d$ transition-metal oxides have a unique electronic structure dominated by strong spin-orbit coupling and hence they can be an intriguing platform to explore spin-current physics. Here, we report on room-temperature generation of spin-orbit torque (SOT) from a conductive $5d$ iridium oxide, $\mathrm{Ir}{\mathrm{O}}_{2}$. By measuring second-harmonic Hall resistance of ${\mathrm{Ni}}_{81}{\mathrm{Fe}}_{19}/\mathrm{Ir}{\mathrm{O}}_{2}$ bilayers, we find both dampinglike and fieldlike SOTs. The former is larger than the latter, enabling easier control of magnetization. We also observe that the dampinglike SOT efficiency has a significant dependence on $\mathrm{Ir}{\mathrm{O}}_{2}$ thickness, which is well described by the drift-diffusion model based on the bulk spin Hall effect. We deduce the effective spin Hall angle of +0.093 \ifmmode\pm\else\textpm\fi{} 0.003 and the spin-diffusion length of 1.7 \ifmmode\pm\else\textpm\fi{} 0.2 nm. By comparison with control samples Pt and Ir, we show that the effective spin Hall angle of $\mathrm{Ir}{\mathrm{O}}_{2}$ is comparable to that of Pt and seven times higher than that of Ir. The fieldlike SOT efficiency has a negative sign without appreciable dependence on the thickness, in contrast to the dampinglike SOT. This suggests that the fieldlike SOT likely stems from the interface. These experimental findings suggest that the uniqueness of the electronic structure of $5d$ transition-metal oxides is crucial for highly efficient charge to spin-current conversion.

Utilization of carbon dioxide (CO2) molecules leads to increased interest in the sustainable synthesis of methane (CH4) or methanol (CH3OH). The representative reaction intermediate consisting of a carbonyl or formate group determines yields of the fuel source during catalytic reactions. However, their selective initial surface reaction processes have been assumed without a fundamental understanding at the molecular level. Here, we report direct observations of spontaneous CO2 dissociation over the model rhodium (Rh) catalyst at 0.1 mbar CO2. The linear geometry of CO2 gas molecules turns into a chemically active bent-structure at the interface, which allows non-uniform charge transfers between chemisorbed CO2 and surface Rh atoms. By combining scanning tunneling microscopy, X-ray photoelectron spectroscopy at near-ambient pressure, and computational calculations, we reveal strong evidence for chemical bond cleavage of O‒CO* with ordered intermediates structure formation of (2 × 2)-CO on an atomically flat Rh(111) surface at room temperature., Direct observation of carbon dioxide dissociation provides an origin of catalytic conversion for industrial chemical reactions. Here, the authors reveal their molecular interactions on the rhodium catalyst at near-ambient pressure by interface science techniques and computational calculations.

Density functional theory calculations were applied to a study on ligand effects on a Pd surface oxide formed on RhPd(100) alloy surfaces. It was found that chemical composition of the topmost layer of alloy significantly influences on the electronic structure of the Pd surface oxide. Such interlayer ligand effects are originating from the Rh−O and Pd−O interactions between the topmost layer of alloy and the Pd surface oxide. These effects give rise to substantial changes in binding energies of adsorbates and could change catalytic activity depending on atomic fraction of the Rh−Pd alloy.

NO reduction by CO on Rh(111) was investigated by near-ambient pressure X-ray photoelectron spectroscopy, mass spectrometry, and kinetic analysis. Under exposure to NO + CO mixed gases and with heating the surface from room temperature to 450 °C, NO dissociation and NO reduction reaction start simultaneously independent of gas pressure ratio of NO/CO, which indicates that NO dissociation triggers this reaction. From kinetic analyses based on observed adsorbate coverages under reaction conditions, the following two points are suggested: (i) NOhollow is a reactive species for N2 and N2O formation via N + NO reaction. (ii) At low temperatures, the N + NO reaction is dominant for N2 production, whereas above around 400 °C, the N + N reaction becomes dominant, which leads to an increase in N2 selectivity at the higher temperatures. Compared with the NO + CO reaction on Ir(111) surfaces, which exhibits a high N2 selectivity, the adsorption site of reactive NO and the availability of vacant surface sites could b...

Genome-wide analysis of renal sodium-transporting system has identified specific variations of Mendelian hypertensive disorders, including HSD11B2 gene variants in apparent mineralocorticoid excess. However, these genetic variations in extrarenal tissue can be involved in developing hypertension, as demonstrated in former studies using global and brain-specific Hsd11b2 knockout rodents. To re-examine the importance of renal dysfunction on developing hypertension, we generated kidney-specific Hsd11b2 knockout mice. The knockout mice exhibited systemic hypertension, which was abolished by reducing salt intake, suggesting its salt-dependency. In addition, we detected an increase in renal membrane expressions of cleaved epithelial sodium channel-α and T53-phosphorylated Na + -Cl − cotransporter in the knockout mice. Acute intraperitoneal administration of amiloride-induced natriuresis and increased urinary sodium/potassium ratio more in the knockout mice compared with those in the wild-type control mice. Chronic administration of amiloride and high-KCl diet significantly decreased mean blood pressure in the knockout mice, which was accompanied with the correction of hypokalemia and the resultant decrease in Na + -Cl − cotransporter phosphorylation. Accordingly, a Na + -Cl − cotransporter blocker hydrochlorothiazide significantly decreased mean blood pressure in the knockout mice. Chronic administration of mineralocorticoid receptor antagonist spironolactone significantly decreased mean blood pressure of the knockout mice along with downregulation of cleaved epithelial sodium channel-α and phosphorylated Na + -Cl − cotransporter expression in the knockout kidney. Our data suggest that kidney-specific deficiency of 11β-HSD2 leads to salt-dependent hypertension, which is attributed to mineralocorticoid receptor–epithelial sodium channel–Na + -Cl − cotransporter activation in the kidney, and provides evidence that renal dysfunction is essential for developing the phenotype of apparent mineralocorticoid excess.

The constructional details and performance of a low-temperature ac calorimetric system for extremely small single crystal samples of molecule-based compounds of which sensing parts is consisting of commercially available micro-chip device of XEN-39390 are reported. We succeeded to detect the thermal anomaly related to the glass formation of the ethylene conformation in a charge transfer complex of κ-(BEDT-TTF) 2 Cu[N(CN) 2 ]Br, where BEDT-TTF is bisethylenedithiotetrathiafulvalene. From the analyses of temperature and frequency dependences of heat capacity, we suggest that XEN-39390 can give similar experimental resolution as that of TCG-3880 with much smaller single crystals less than 100 ng. We also observed a glass-like freezing of molecular dynamics in the large asymmetric cations in EtMe 3 Sb[Pd(dmit) 2 ] 2 which are known as a spin liquid compound by single piece of crystal where dmit is 1,3-dithiole-2-thione-4,5-dithiolate. The comparison with the relaxation calorimetry result with absolute precision is performed.

The nitric oxide (NO) reduction by carbon monoxide (CO) on Ir(111) surfaces under near ambient pressure conditions was studied by a combination of near-ambient-pressure X-ray photoelectron spectroscopy (NAP-XPS) and mass spectrometry (MS), particularly paying attention to the dominant reaction pathway to formation of molecular nitrogen (N2). Under a relatively low CO pressure condition (50 mTorr NO + 10 mTorr CO), two reaction pathways to form N2 are clearly observed at different ignition temperatures (280 and 400 °C) and attributed to a reaction of NO adsorbed at atop site (NOatop) with atomic nitrogen (Nad) and associative desorption of Nad, respectively. Since the adsorption of NOatop is inhibited by CO adsorbed at atop site (COatop), the ignition of the NOatop + Nad reaction strongly depends on the coverage of COatop; the ignition temperature shifts to higher temperature as increasing CO pressure. In contrast, for the Nad + Nad reaction the ignition temperature keeps almost constant (∼400 °C). The onl...

Aging is associated with a high prevalence of hypertension due to elevated susceptibility of BP to dietary salt, but its mechanism is unknown. Serum levels of Klotho, an anti-aging factor, decline with age. We found that high salt (HS) increased BP in aged mice and young heterozygous Klotho-knockout mice and was associated with increased vascular expression of Wnt5a and p-MYPT1, which indicate RhoA activity. Not only the Wnt inhibitor LGK974 and the Wnt5a antagonist Box5 but Klotho supplementation inhibits HS-induced BP elevation, similarly to the Rho kinase inhibitor fasudil, associated with reduced p-MYPT1 expression in both groups of mice. In cultured vascular smooth muscle cells, Wnt5a and angiotensin II (Ang II) increased p-MYPT1 expression but knockdown of Wnt5a with siRNA abolished Ang II–induced upregulation of p-MYPT1, indicating that Wnt5a is indispensable for Ang II–induced Rho/ROCK activation. Notably, Klotho inhibited Wnt5a- and Ang II–induced upregulation of p-MYPT1. Consistently, Klotho supplementation ameliorated HS-induced augmentation of reduced renal blood flow (RBF) response to intra-arterial infusion of Ang II and the thromboxane A(2) analog U46619, which activated RhoA in both groups of mice and were associated with the inhibition of BP elevation, suggesting that abnormal response of RBF to Ang II contributes to HS-induced BP elevation. Thus, Klotho deficiency underlies aging-associated salt-sensitive hypertension through vascular non-canonical Wnt5a/RhoA activation.

Background Regulation of sodium chloride transport in the aldosterone-sensitive distal nephron is essential for fluid homeostasis and BP control. The chloride-bicarbonate exchanger pendrin in β-intercalated cells, along with sodium chloride cotransporter (NCC) in distal convoluted tubules, complementarily regulate sodium chloride handling, which is controlled by the renin-angiotensin-aldosterone system. Methods Using mice with mineralocorticoid receptor deletion in intercalated cells, we examined the mechanism and roles of pendrin upregulation via mineralocorticoid receptor in two different models of renin-angiotensin-aldosterone system activation. We also used aldosterone-treated NCC knockout mice to examine the role of pendrin regulation in salt-sensitive hypertension. Results Deletion of mineralocorticoid receptor in intercalated cells suppressed the increase in renal pendrin expression induced by either exogenous angiotensin II infusion or endogenous angiotensin II upregulation via salt restriction. When fed a low-salt diet, intercalated cell-specific mineralocorticoid receptor knockout mice with suppression of pendrin upregulation showed BP reduction that was attenuated by compensatory activation of NCC. In contrast, upregulation of pendrin induced by aldosterone excess combined with a high-salt diet was scarcely affected by deletion of mineralocorticoid receptor in intercalated cells, but depended instead on hypokalemic alkalosis through the activated mineralocorticoid receptor-epithelial sodium channel cascade in principal cells. In aldosterone-treated NCC knockout mice showing upregulation of pendrin, potassium supplementation corrected alkalosis and inhibited the pendrin upregulation, thereby lowering BP. Conclusions In conjunction with NCC, the two pathways of pendrin upregulation, induced by angiotensin II through mineralocorticoid receptor activation in intercalated cells and by alkalosis through mineralocorticoid receptor activation in principal cells, play important roles in fluid homeostasis during salt depletion and salt-sensitive hypertension mediated by aldosterone excess.

International audience; The surface chemical states of Pd(100) during CO oxidation were investigated using ambient pressure x-ray photoelectron spectroscopy and mass spectroscopy. Under the reactant ratio of CO/O2 = 0.1, i.e. an oxygen-rich reaction condition, the formation of surface oxides was observed with the onset of CO oxidation reaction at T = 525 K. As the reactant ratio (CO/O2) increased from 0.1 to 1.0, ∼ 90 % surface oxides remains on surface during the reaction. Upon the formation of surface oxides, the core level shift of oxygen gas phase peak was observed, indicating that change of surface work function. As CO oxidation takes places, i.e. making a transition from CO covered surface to the oxidic surface, the work functions of surface oxide on Pd(100) and Pt(110) display opposite behavior.

High-intensity focused ultrasound (HIFU) treatment is a non-invasive method of cancer treatment. In a HIFU treatment, ultrasound is focused on a target tumor tissue leading to temperature rise that coagulates the tissue. The treatment has a problem of long treatment time because a tumor is usually larger than the focal spot of HIFU. To reduce the treatment time, cavitation bubbles can be used for accelerating ultrasonic heating. Additionally, the heat conducting away from a focal spot can be utilized by properly scanning the focus. In this study, three sequences of scanning the focus to form six foci were compared by observing cavitation bubbles and measuring temperature rise in an excised chicken breast tissue and an agarose gel as well as a thin slice of tissue sandwiched between agarose gels. The results showed that there were differences in the behavior of bubbles and the efficient sequence between the tissue and the gel.

Reduction of oxidized Rh catalysts under carbon monoxide (CO) exposure and reaction conditions were studied by using ambient-pressure x-ray photoelectron spectroscopy. First, Rh powders pressed into a pellet were deeply oxidized and the reduction process under 100 mTorr CO environment was monitored in situ at different temperatures. The oxidized Rh surfaces are composed of Rh2O3 and RhO2, the latter of which is more segregated near the surface. Both oxide species are reduced simultaneously to the metallic state; kinetic analyses indicate that the activation energy of the reduction of the Rh oxides is 1.68 eV, which is a little larger than those for Pd oxides, probably due to a stronger Rh–O interaction. Reduction of oxidized Rh nano-particles deposited on SiO2 under two reaction conditions (CO + O2 and CO + NO + O2) was observed with increasing temperature. It was found that the reduction temperature shifts to the higher temperature in the presence of NO, even though the S-factors are almost the same. The NO molecule more strongly prevents the reduction of oxidized Rh catalyst compared to O2.

Achondroplasia (ACH) is the most common short-limbed skeletal dysplasia caused by activating mutations in the fibroblast growth factor receptor 3 (FGFR3) gene. We identified that meclizine hydrochloride inhibited FGFR3 signaling in various chondrocytic cells and promoted longitudinal bone growth in mouse model of ACH. Meclizine has safely been used for more than 50 years, but it lacks the safety data for repeated administration and pharmacokinetics (PK) when administered to children. We performed a phase Ia study to evaluate the PK and safety of meclizine administered orally to ACH children. Twelve ACH children aged from 5 to younger than 11 years were recruited, and the first 6 subjects received once a day of meclizine in the fasted condition, subsequent 6 subjects received twice a day of meclizine in the fed condition. Meclizine was well tolerated in ACH children with no serious adverse events. The mean Cmax, Tmax, AUC0-24h, t1/2 during 24 hours in the fasted condition were 130 ng/mL, 1.7 hours, 761 ng·h/mL, and 8.5 hours respectively. The simulation of repeated administration of meclizine for 14 days demonstrated that plasma concentration apparently reached steady state around 10 days after the first dose both at once a day and twice a day administration. The AUC0-10h of the fasting and fed condition were 504 ng·h/mL and 813 ng·h/mL, respectively, indicating exposure of meclizine increased with the diet. Although higher drug exposure was confirmed in ACH children compared to adults, a single administration of meclizine seemed to be well tolerated.

Maternal malnutrition, which causes prenatal exposure to excessive glucocorticoid, induces adverse metabolic programming, leading to hypertension in offspring. In offspring of pregnant rats receiving a low-protein diet or dexamethasone, a synthetic glucocorticoid, mRNA expression of angiotensin receptor type 1a (Agtr1a) in the paraventricular nucleus (PVN) of the hypothalamus was upregulated, concurrent with reduced expression of DNA methyltransferase 3a (Dnmt3a), reduced binding of DNMT3a to the Agtr1a gene, and DNA demethylation. Salt loading increased BP in both types of offspring, suggesting that elevated hypothalamic Agtr1a expression is epigenetically modulated by excessive glucocorticoid and leads to adult-onset salt-sensitive hypertension. Consistent with this, dexamethasone treatment of PVN cells upregulated Agtr1a, while downregulating Dnmt3a, and decreased DNMT3a binding and DNA demethylation at the Agtr1a locus. In addition, Dnmt3a knockdown upregulated Agtr1a independently of dexamethasone. Hypothalamic neuron-specific Dnmt3a-deficient mice exhibited upregulation of Agtr1a in the PVN and salt-induced BP elevation without dexamethasone treatment. By contrast, dexamethasone-treated Agtr1a-deficient mice failed to show salt-induced BP elevation, despite reduced expression of Dnmt3a. Thus, epigenetic modulation of hypothalamic angiotensin signaling contributes to salt-sensitive hypertension induced by prenatal glucocorticoid excess in offspring of mothers that are malnourished during pregnancy.

Spin-related phenomena, such as the giant magnetoresistance and the spin-transfer torque, have led to a new era of nano-spintronics in last two decades. The discovery of these physical phenomena has contributed to a substantial increase in the data storage capacity of computers. Another revolutionary phenomenon, the interfacial Dzyaloshinskii-Moriya interaction (DMI), was recently discovered in ultra-thin ferromagnet/heavy-metal bilayers. The DMI stabilizes nanometre-sized chiral spin textures such as Neel domain walls and hedgehog skyrmions. These chiral objects find the potential for applications in ultra-high density, low-energy, and high-speed memory devices because they are stable due to topological protection and easy to move with high efficiency. As both stability and current-driven speed of chiral spin textures are proportional to the DMI strength [A. Thiaville et al., Europhys Lett. 100, 57002 (2012); A. Fert, V. Cros, and J. Sampiao, Nat. Nanotechnol. 8, 152 (2013)], tremendous efforts are being devoted to finding high-DMI materials. In this respect, understanding the microscopic origin of DMI is of critical importance. Here we discuss the microscopic origin of the interfacial DMI with experimental and theoretical studies as follows: First, we show the temperature dependence of the DMI for a Pt/Co/MgO trilayer; the DMI increases with decreasing temperature in a range from 300 to 100 K. To discuss this temperature dependence of the DMI, that of the spin and orbital magnetic moments of Co and Pt is studied by X-ray magnetic circular dichroism (XMCD) spectroscopy. We find that spin moment values of Co and Pt show temperature dependences due to change in Heisenberg exchange. Furthermore, the intra-atomic magnetic dipole moment, which is due to the asymmetric spin-density distribution, shows strong temperature dependence, suggesting a sizable modification of the charge distribution between the in-plane and the out-of-plane d-orbitals under temperature variation. We also find that the out-of-plane orbital moment shows large temperature dependence while in-plane orbital moment does not, revealing a close connection between the anisotropy of orbital moment and the DMI. The ab-initio and the tight-binding model calculations suggest that the ISB-dependent electron hopping, which gives rise to the asymmetric charge distribution at the interface of the FM/HM, is a possible microscopic origin of the correlation between the orbital anisotropy and the DMI.

Epigenetic abnormalities have been suggested to mediate metabolic memory observed in diabetic complications. We have shown that epigenetic alterations may induce persistent phenotypic changes in the proximal tubules of the diabetic kidneys. In this study, we show that pregnane X receptor (PXR), a xenobiotic nuclear receptor, is epigenetically altered and upregulated and may have a possible function in the diabetic kidney. PXR has been shown to play a critical role in metabolic changes in obesity and diabetes; however, its distribution and function in the kidney are unknown. In the normal kidney, Pxr was selectively expressed in the proximal tubular cells with demethylation in the promoter DNA. In db/db mice, significant increases in Pxr mRNA, further demethylation of DNA, and stimulatory histone marks in the promoter were observed. Epigenetic changes are likely to play a causative role in PXR induction, since a DNA methyltransferase inhibitor increased PXR mRNA in cultured human proximal tubular cells. Administration of a PXR agonist increased mRNA levels of solute carrier organic anion transporter family member 2B1 ( Slco2b1), a xenobiotic transporter; response gene to complement 32 ( Rgc32), a molecule known to exert fibrotic effects in the kidney; and phosphoenolpyruvate carboxykinase 1 ( Pck1), a gluconeogenic enzyme in the kidney. The expressions of these genes were inhibited by PXR small interfering RNA in cultured proximal tubular cells. Increased mRNA levels of Slco2b1, Rgc32, and Pck1 were also observed in the kidney of db/db mice. These data indicate that PXR is upregulated in the diabetic kidney with aberrant epigenetic modifications and may modulate the course of diabetic kidney disease through the activation of these genes.

Epigenetic modulation may underlie the progression of diabetic nephropathy (DN). Involvement of TGFB1 in mesangial fibrosis of DN led us to hypothesize that Tgfb1 DNA demethylation contributes to progression of DN. In primary mesangial cells from diabetic (db/db) mouse kidneys, demethylation of Tgfb1 DNA and upregulation of Tgfb1 mRNA progressed simultaneously. USF1 binding site in Tgfb1 promoter region were demethylated, and binding of USF1 increased, with decreased binding of DNMT1 in db/db compared with control. Given downregulation of Tgfb1 expression by folic acid, antioxidant Tempol reversed DNA demethylation, with increased and decreased recruitment of DNMT1 and USF1 to the promoter, resulting in decreased Tgfb1 expression in db/db mice. Addition of H2O2 to mesangial cells induced DNA demethylation and upregulated Tgfb1 expression. Finally, Tempol attenuated mesangial fibrosis in db/db mice. We conclude that aberrant DNA methylation of Tgfb1 due to ROS overproduction play a key to mesangial fibrosis during DN progression.

In a tens-of-nanometer-scale dynamic displacement measurement system based on a fiber interferometer using high-frequency phase modulation for the reference light, we introduce active change of operation point for the phase modulator. It is experimentally demonstrated that dynamic displacement measurement is possible independent of the initial operation point.