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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.

Purpose To report the clinical findings of the patients with retinal pigment epithelium (RPE) aperture secondary to age-related macular degeneration (AMD). Methods A retrospective data analysis was conducted of patients at the University of Tokyo Hospital eye clinic, from the year September 1st, 2012 to 2019. Review of the medical records of patients with RPE aperture accompanied by AMD was performed. We investigated age, best-corrected visual acuity (BCVA), images of spectral domain optical coherence tomography, short-wave fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography, and retinal sensitivity measured with microperimetry. The change in visual acuity or the area of the aperture during the follow-up period was analyzed. Results Five eyes of 5 patients (4 men, one woman) were included in the analysis. The mean age at presentation was 78.6 ± 9.1 years. The average length of follow-up was 23.6 ± 17.9 months. The RPE apertures appeared as round, either at the apex or at the base of PED, with no evidence of accompanying CNV but subretinal detachment (SRD) above the aperture. On FAF, the apertures appeared as sharply demarcated round areas of hypoautofluorescence. The FA revealed sharply demarcated round areas of window defects in the early and mid-phase with leakage in the late phase corresponding to SRD. The area of apertures enlarged during the follow-up period. Mean BCVA got worse from 0.20 logMAR at the initial presentation to 0.39 logMAR at the last visit. The retinal sensitivity was reduced but partly preserved above the area of aperture. Conclusions and importance RPE aperture was found in some patients with drusenoid PED secondary to AMD. It enlarged during follow-up. Visual acuity was declined. Retinal sensitivity was decreased but partly preserved.

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.

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.

In an isostructural series of anion radical salts β′-(Me4-xEtxZ)[Pd(dmit)2]2 (Z = P, As, Sb; x = 0, 1, 2), [Pd(dmit)2]2− units form a two-dimensional Mott insulator layer with a quasi-isosceles triangular lattice. The anisotropy of the triangular lattice is characterized by a ratio of interdimer transfer integrals, t′/t. The crystal structures of EtMe3Sb, Me4Sb, Me4As, and Et2Me2As salts were determined in the range of 5–295 K by the single crystal X-ray diffraction technique. Interdimer transfer integrals, Fermi surface, and band structures at low temperatures were calculated by the tight binding method and the first-principles density-functional theory (DFT) method based on experimentally obtained crystal structures. Interdimer transfer integrals increased with lowering temperature. At 5 K, the ratio t′/t decreased by about 15% from the room temperature value in every salt. The relationship between the transfer integrals and interdimer S⋯S distances indicated that the change of the t′/t value with temperature was due to a thermal contraction, rather than the arch-shaped molecular distortion of the Pd(dmit)2 molecule associated with the cation dependence of t′/t.

Spintronics is a research field that aims to understand and control spins on the nanoscale and should enable next-generation data storage and manipulation. One technological and scientific key challenge is to stabilize small spin textures and to move them efficiently with high velocities. For a long time, research focused on ferromagnetic materials, but ferromagnets show fundamental limits for speed and size. Here, we circumvent these limits using compensated ferrimagnets. Using ferrimagnetic Pt/Gd44Co56/TaOx films with a sizeable Dzyaloshinskii–Moriya interaction, we realize a current-driven domain wall motion with a speed of 1.3 km s–1 near the angular momentum compensation temperature (TA) and room-temperature-stable skyrmions with minimum diameters close to 10 nm near the magnetic compensation temperature (TM). Both the size and dynamics of the ferrimagnet are in excellent agreement with a simplified effective ferromagnet theory. Our work shows that high-speed, high-density spintronics devices based on current-driven spin textures can be realized using materials in which TA and TM are close together. Ferrimagnetic Gd44Co56 near the compensation temperature enables domain wall motion with a speed of 1.3 km s–1 and room temperature skyrmions with diameters close to 10 nm.

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.

The study of CO oxidation on Pt(1 1 0) surface is revisited using ambient pressure x-ray photoemission spectroscopy. When the surface temperature reaches the activation temperature for CO oxidation under elevated pressure conditions, both the α-phase of PtO2 oxide and chemisorbed oxygen are formed simultaneously on the surface. Due to the exothermic nature of CO oxidation, the temperature of the Pt surface increases as CO oxidation takes place. As the CO/O2 ratio increases, the production of CO2 increases continuously and the surface temperature also increases. Interestingly, within the diffusion limited regions, the amount of surface oxide changes little while the chemisorbed oxygen is reduced.

The renin-angiotensin-aldosterone system has an important role in the control of fluid homeostasis and BP during volume depletion. Dietary salt restriction elevates circulating angiotensin II (AngII) and aldosterone levels, increasing levels of the Cl-/HCO3- exchanger pendrin in β-intercalated cells and the Na+-Cl- cotransporter (NCC) in distal convoluted tubules. However, the independent roles of AngII and aldosterone in regulating these levels remain unclear. In C57BL/6J mice receiving a low-salt diet or AngII infusion, we evaluated the membrane protein abundance of pendrin and NCC; assessed the phosphorylation of the mineralocorticoid receptor, which selectively inhibits aldosterone binding in intercalated cells; and measured BP by radiotelemetry in pendrin-knockout and wild-type mice. A low-salt diet or AngII infusion upregulated NCC and pendrin levels, decreased the phosphorylation of mineralocorticoid receptor in β-intercalated cells, and increased plasma aldosterone levels. Notably, a low-salt diet did not alter BP in wild-type mice, but significantly decreased BP in pendrin-knockout mice. To dissect the roles of AngII and aldosterone, we performed adrenalectomies in mice to remove aldosterone from the circulation. In adrenalectomized mice, AngII infusion again upregulated NCC expression, but did not affect pendrin expression despite the decreased phosphorylation of mineralocorticoid receptor. By contrast, AngII and aldosterone coadministration markedly elevated pendrin levels in adrenalectomized mice. Our results indicate that aldosterone is necessary for AngII-induced pendrin upregulation, and suggest that pendrin contributes to the maintenance of normal BP in cooperation with NCC during activation of the renin-angiotensin-aldosterone system by dietary salt restriction.

Background: Renal mechanism of 11β-HSD2 deficiency for developing hypertension is to be evaluated because vascular mechanism associated with sympathetic nervous activity was prevailing in global Hsd11b2 knockout (KO) mice although brain-specific KO mice needed high salt intake to develop hypertension. We have demonstrated the importance of renal 11β-HSD2 deficiency on developing hypertension by using kidney-specific Hsd11b2 knockout ( Hsd11b2 Ksp-/- ; KS-KO) mice ( Hypertension , in press) and have continued the analysis of the systemic effect of renal 11β-HSD2 deficiency. Method: Blood pressure (BP) and heart rate (HR) was measured by using 24h telemetry. Amiloride (25 mg/L) and hydrochlorothiazide (HCTZ, 300 mg/L) were administered through drinking water. Pellet containing MR antagonist spironolactone (MRA; 50 mg/KgBW/day) was administered subcutaneously. Corticosterone concentration was determined by ELISA. Data are presented as mean±SE. Result: Systolic and diastolic BPs of KS-KO mice were significantly higher, although the HR was lower, than those of WT mice: SBP, 142.4±1.0 vs 122.4±0.8 mmHg; DBP, 103.9±0.8 vs 94.4±0.8 mmHg; HR, 492.5±2.7 vs 555.4±2.4 (n=7). Mean BP was decreased to the level of WT mice by reducing dietary sodium content from 0.3 % to 0.01 %. Plasma [K + ] was significantly lower in KS-KO mice: 2.9±0.2 vs 4.2±0.2 mEq/L (n=5). Renal membrane expressions of NCC, T53-phosphorylated NCC (pNCC), cleaved ENaCα and full-length ENaCα were upregulated in KS-KO mice. Correction of plasma [K + ] of KS-KO mice by using high KCl diet or amiloride downregulated the renal membrane expression of pNCC and decreased the MBP to the level of WT mice as well as chronic HCTZ-treated KS-KO mice. Subcutaneous administration of MRA decreased MBP of KS-KO mice and the renal membrane expressions of pNCC and cleaved ENaCα. Diurnal variation of plasma corticosterone concentration was diminished in KS-KO mice and the urinary excretion of corticosterone was higher compared to that in WT mice. Conclusion: Renal 11β-HSD2 deficiency is sufficient in developing hypertension via MR activation induced by excessive corticosterone, the systemic effect of which are also suggested.

The temperature dependence of spin-orbit torques (SOTs) and spin-dependent transport parameters is measured in bilayer Ta/TbCo ferrimagnetic alloy films with bulk perpendicular magnetic anisotropy. We find that the dampinglike (DL)-SOT effective field diverges as temperature is swept through the magnetic compensation temperature (${T}_{\mathrm{M}}$), where the net magnetization vanishes due to the opposing contributions from the Tb and Co sublattices. We show that DL-SOT scales with the inverse of the saturation magnetization (${M}_{\mathrm{s}}$), whereas the spin-torque efficiency is independent of the temperature-dependent ${M}_{\mathrm{s}}$. Our findings provide insight into spin transport mechanisms in ferrimagnets and highlight low-${M}_{\mathrm{s}}$ rare-earth/transition-metal alloys as promising candidates for SOT device applications.

A cytocompatible inkjet bioprinting approach that enables the use of a variety of bioinks to produce hydrogels with a wide range of characteristics is developed. Stabilization of bioinks is caused by horseradish peroxidase (HRP)-catalyzed cross-linking consuming hydrogen peroxide (H2 O2 ). 3D cell-laden hydrogels are fabricated by the sequential dropping of a bioink containing polymer(s) cross-linkable through the enzymatic reaction and H2 O2 onto droplets of another bioink containing the polymer, HRP, and cells. The ≈95% viability of enclosed mouse fibroblasts and subsequent elongation of the cells in a bioprinted hydrogel consisting of gelatin and hyaluronic acid derivatives suggest the high cytocompatibility of the developed printing approach. The existence of numerous polymers, including derivatives of polysaccharides, proteins, and synthetic polymers, cross-linkable through the HRP-catalyzed reaction, means the current approach shows great promise for biofabrication of functional and structurally complex tissues.

Chiral spin textures of a ferromagnetic layer in contact to a heavy non-magnetic metal, such as Néel-type domain walls and skyrmions, have been studied intensively because of their potential for future nanomagnetic devices. The Dyzaloshinskii–Moriya interaction (DMI) is an essential phenomenon for the formation of such chiral spin textures. In spite of recent theoretical progress aiming at understanding the microscopic origin of the DMI, an experimental investigation unravelling the physics at stake is still required. Here we experimentally demonstrate the close correlation of the DMI with the anisotropy of the orbital magnetic moment and with the magnetic dipole moment of the ferromagnetic metal in addition to Heisenberg exchange. The density functional theory and the tight-binding model calculations reveal that inversion symmetry breaking with spin–orbit coupling gives rise to the orbital-related correlation. Our study provides the experimental connection between the orbital physics and the spin–orbit-related phenomena, such as DMI., 原子磁石どうしが捻れて並ぶ現象のミクロな起源を解明 --新原理の情報記録技術をめざして--. 京都大学プレスリリース. 2018-05-01.

Genome-wide analysis of renal sodium-transporting system has identified specific variations of Mendelian hypertensive disorders, including

Background and objective Mineralocorticoid receptor (MR) is a member of nuclear receptor family proteins and contributes to fluid homeostasis in the kidney. Although aldosterone-MR pathway induces several gene expressions in the kidney, it is often unclear whether the gene expressions are accompanied by direct regulations of MR through its binding to the regulatory region of each gene. The purpose of this study is to identify the direct target genes of MR in a murine distal convoluted tubular epithelial cell-line (mDCT). Methods We analyzed the DNA samples of mDCT cells overexpressing 3xFLAG-hMR after treatment with 10−7 M aldosterone for 1 h by chromatin immunoprecipitation with deep-sequence (ChIP-seq) and mRNA of the cell-line with treatment of 10−7 M aldosterone for 3 h by microarray. Results 3xFLAG-hMR overexpressed in mDCT cells accumulated in the nucleus in response to 10−9 M aldosterone. Twenty-five genes were indicated as the candidate target genes of MR by ChIP-seq and microarray analyses. Five genes, Sgk1, Fkbp5, Rasl12, Tns1 and Tsc22d3 (Gilz), were validated as the direct target genes of MR by quantitative RT-qPCR and ChIP-qPCR. MR binding regions adjacent to Ctgf and Serpine1 were also validated. Conclusions We, for the first time, captured the genome-wide distribution of MR in mDCT cells and, furthermore, identified five MR target genes in the cell-line. These results will contribute to further studies on the mechanisms of kidney diseases.

Due to the high cation exchange capacity and large potential of swelling when wet, bentonite is the promising material for use in the disposal of the high-level radioactive waste. However, its swelling ability is affected by cations leached from both concrete barrier container and groundwater. This paper describes the phenominetic model of bentonite swelling in electrolyte solution, forcing on that for montmorillonite that is the main component in bentonite, to elucidate the effect of kind of cation on its swelling ability. It was assumed that swelling of montmorillonite caused according to two different steps：First step was the swelling of tactoids that were the assembles of basic layered element, so-called clay lamella, of montmorillonite and then second step, which was the rearrangement of structure in solution, was occurred. Swelling tactoids can be calculated from slit like pore model between two parallel plates considering the intermolecular forces between plates. As for rearrangement of aggregate structure of tactoid, it was assumed the actoides were aggregated and formed diamond-shaped structure, and to chemical potential in bulk solution that was equilibriumed to the solution in the slit pore. The later assumption required the when the slit distance was small, the chemical potential of bulk solution was influenced by the intermolecular forces between plates. The deformation due to rearrangement of structure could be calculated from difference between the experimental volume and the swelling volume of tactoids. It could be found that there was a good relationship between chemical potential and deformation due to rearrangement of structure despite the kind of cation. This enable the authors to estimate the effect of kind of cation on swelling of montmorillonite in electrolyte solutions.本研究では陽イオンによるモンモリロナイト（Mo）の膨潤モデルの構築を行った。Moの体積変化は（1）Moの基本構造の単位層の集合体であるTactoid（Ta）の膨潤による体積変化と、（2）Taが形成する粗大構造の膨潤による体積変化の総和と考えた。前者は2平板の分子間力を考慮したモデルより算出し、後者の粗大構造の変化は実測した体積変化とTaの膨張による体積変化の差から算出した。粗大構造中の溶液とTa中の単位層間の溶液は一様であると考え、その化学ポテンシャルを2平板間の分子間力により決定した。その結果、粗大構造と化学ポテンシャルにはイオン種によらず関係性が見られ、化学ポテンシャルに基づくMoの膨潤予測モデルの構築ができた。

Magnetic properties in ferrimagnetic GdCo alloy films with bulk perpendicular magnetic anisotropy (PMA) are investigated as a function of annealing temperature (Tanneal) and annealing time for several capping layers. Magnetic properties in films capped by TaOx vary markedly with Tanneal; the saturation magnetization and coercivity vary progressively with increasing Tanneal up to 300°C, and above that temperature, PMA is lost abruptly. By comparing the annealing temperature dependence for Co-dominated and Gd-dominated compositions close to the magnetization compensation point, the data are readily explained by preferential oxidation of Gd during annealing. When films are capped by a Ta/Pt bilayer, the film properties are stable up Tanneal = 300 °C, indicating that oxidation at high temperatures is effectively blocked, but the abrupt loss of PMA for Tanneal > 300 °C is still observed. X-ray diffraction measurement reveals that the amorphous structure of the films remains the same after high-temperature annealing that is sufficient to remove PMA, indicating that crystallization from the amorphous phase is not responsible for the lack of PMA. Instead, our results suggest that high annealing temperatures may cause segregation of Co and Gd atoms in the films, which reduces anisotropic pair-pair correlations responsible for the observed bulk PMA in the as-grown state.Magnetic properties in ferrimagnetic GdCo alloy films with bulk perpendicular magnetic anisotropy (PMA) are investigated as a function of annealing temperature (Tanneal) and annealing time for several capping layers. Magnetic properties in films capped by TaOx vary markedly with Tanneal; the saturation magnetization and coercivity vary progressively with increasing Tanneal up to 300°C, and above that temperature, PMA is lost abruptly. By comparing the annealing temperature dependence for Co-dominated and Gd-dominated compositions close to the magnetization compensation point, the data are readily explained by preferential oxidation of Gd during annealing. When films are capped by a Ta/Pt bilayer, the film properties are stable up Tanneal = 300 °C, indicating that oxidation at high temperatures is effectively blocked, but the abrupt loss of PMA for Tanneal > 300 °C is still observed. X-ray diffraction measurement reveals that the amorphous structure of the films remains the same after high-temperature anne...

Shigeto Fujimura,1,2 Kohei Ueda,1 Yoko Nomura,1 Yasuo Yanagi3,4 1Department of Ophthalmology, University of Tokyo School of Medicine, Tokyo, 2Department of Ophthalmology, Kanazawa University School of Medicine, Ishikawa, Japan; 3Singapore Eye Research Institute, 4Medical Retina Department, Singapore National Eye Centre, Singapore Purpose: To assess the relationship between combined serum lutein and zeaxanthin (L+Z) concentration and macular pigment optical density (MPOD), and to investigate the effect of L+Z+docosahexaenoic acid (DHA) dietary supplementation on the spatial distribution of MPOD.Methods: Twenty healthy fellow eyes with unilateral wet age-related macular degeneration or chronic central serous chorioretinopathy were included. All participants received a dietary supplement for 6 months that contained 20 mg L, 1 mg Z, and 200 mg DHA. The best-corrected visual acuity and contrast sensitivity (CS) were measured at baseline and at 1, 3, and 6 months. Serum L+Z concentrations were measured at baseline and at 3 months. MPOD was calculated at each time point using fundus autofluorescent images.Results: Serum L+Z concentration was correlated with MPOD at 1°–2° eccentricity at baseline (r=0.63, P=0.003) and 3 months (r=0.53, P=0.015). Serum L+Z concentration increased by a factor of 2.3±1.0 (P

Emergency Rescue Information Sharing System supports rescue operations in early stage by gathering information about victims in need of help at the time of disaster. In this system, in-vehicle relays are used to gather extensive information. In-vehicle relays transmit information sent by mobile terminals to a database server via gateway switches. There are several wireless connections between relays and gateway switches to make the transmission redundant. However, information loss occurs when all links are disconnected. In addition, mobile terminals cannot send information without available wireless connections. In this paper, we propose a disaster information gathering mechanism that adopts Web-based offline operation and OpenFlow-based routing control. Offline operation of the system is realized by information caching and synchronization. Wireless links between in-vehicle relays and gateway switches are controlled by OpenFlow. Our mechanism selects a link for transmission dynamically in response to the status and priority changes of the wireless links. In order to prevent information loss while relays isolated from networks, information from mobile terminals is temporarily stored in in-vehicle servers. Prototype demonstration shows that the proposed mechanism can achieve high information gathering rate at the database server.

Controlling the position of a magnetic domain wall with electric current may allow for new types of non-volatile memory and logic devices. To be practical, however, the threshold current density necessary for domain wall motion must be reduced below present values. Intrinsic pinning due to magnetic anisotropy, as recently observed in perpendicularly magnetized Co/Ni nanowires, has been shown to give rise to an intrinsic current threshold J(th)(0). Here, we show that domain wall motion can be induced at current densities 40% below J(th)(0) when an external magnetic field of the order of the domain wall pinning field is applied. We observe that the velocity of the domain wall motion is the vector sum of current- and field-induced velocities, and that the domain wall can be driven against the direction of a magnetic field as large as 2,000 Oe, even at currents below J(th)(0). We show that this counterintuitive phenomenon is triggered by Walker breakdown, and that the additive velocities provide a unique way of simultaneously determining the spin polarization of current and the Gilbert damping constant.

Overactivation of the mineralocorticoid receptor signaling is implicated in cardiovascular disease, including hypertensive heart disease. Oxidative stress is suggested to augment mineralocorticoid receptor signal transduction, but the precise mechanisms remain unclear. Mineralocorticoid receptor activity is regulated by multiple factors, in addition to plasma ligand levels. We previously identified Rac1 GTPase as a modulator of mineralocorticoid receptor activity. Here we show that oxidative stress induces mineralocorticoid receptor activation in a ligand-independent, Rac1-depenent manner in cardiomyocytes. Oxidant stress was induced in rat cultured cardiomyocytes (H9c2) by l -buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis. BSO depleted intracellular glutathione and concomitantly increased reactive oxygen species (199%; P P N -acetylcysteine. The ligand independency of BSO action was indicated using a mutant mineralocorticoid receptor that does not bind ligands. With this mutant mineralocorticoid receptor, BSO-evoked mineralocorticoid receptor activation remained intact, whereas ligand-induced mineralocorticoid receptor activation was abolished. We next examined the involvement of Rac1. BSO increased active Rac1 in a redox-dependent fashion, and Rac inhibition suppressed the enhancing effect of BSO. Constitutively active Rac1, indeed, potentiated mineralocorticoid receptor transactivation. Furthermore, mineralocorticoid receptor transactivation by BSO was accompanied by enhanced nuclear accumulation of mineralocorticoid receptor. We conclude that alteration of redox state modulates mineralocorticoid receptor–dependent transcriptional activity via Rac1 in the heart. This redox-sensitive, ligand-independent mineralocorticoid receptor activation may contribute to the processes by which oxidant stress promotes cardiac injury.

Gitelman's syndrome (GS), an inherited disorder due to loss of function of ion channels and transporters such as Na-Cl co-transporter (NCCT) in distal convoluted tubules, is characterized by hypokalemia, hypomagnesemia, hypocalciuria, metabolic alkalosis and hyperreninemic-hyperaldosteronism. A 39-year-old man was admitted to our hospital because of muscle weakness with such intractable disorders. We performed a thiazide-loading test, which revealed a poor response of the fractional excretion rate of chloride compared to healthy subjects. Based on these data, the clinical diagnosis of GS was made. Gene-sequencing analysis revealed compound heterozygous mutations of c.539C > A and c.1844C > T in SLC12A3, which is newly reported in Japanese GS.