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Background Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes.Methods We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18-85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR) 25-75 mL/min per 1.73 m(2) of body surface area, and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g who had received maximum labelled or tolerated renin-angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0.75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders) were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0.75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for >= 30 days) or end-stage kidney disease (eGFR = 90 days, chronic dialysis for >= 90 days, kidney transplantation, or death from kidney failure) in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials. gov, number NCT01858532.Findings Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325) or placebo group (n=1323). Median follow-up was 2.2 years (IQR 1.4-2.9). 79 (6.0%) of 1325 patients in the atrasentan group and 105 (7.9%) of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR] 0.65 [95% CI 0.49-0.88]; p=0.0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3.5%) of 1325 patients in the atrasentan group and 34 (2.6%) of 1323 patients in the placebo group (HR 1.33 [95% CI 0.85-2.07]; p=0.208). 58 (4.4%) patients in the atrasentan group and 52 (3.9%) in the placebo group died (HR 1.09 [95% CI 0.75-1.59]; p=0.65).Interpretation Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

A key challenge in processing carbon nanotubes and their composites for large-scale applications is aggregation. Cation-π stacking interactions have been discovered to disperse heavily entangled single-walled carbon nanotube (SWNT) bundles in ionic liquids (ILs). In this work, we found that a dispersible, silky single-layer graphene (SLG) can be readily gathered together to form a crosslinked gel after entrapping sufficient IL molecular via the likely noncovalent interaction. By incorporating the dispersed SWNTs into the gathered SLG gel synchronously, we prepared solid, finely crosslinked SWNTs-SLG films, assisted by an avenue of 2-step extraction to remove the IL completely. The gel-derived SWNTs-SLG complex film was applied as a support material of oxygen cathodes for Li-O2 batteries. It exhibited a remarkable improved cycleability in comparison to made of SWNTs and SLG alone due to the finely crosslinked feature. Decorated SWNTs and SLG can also form gel-derived complexes via the same process to construct support-catalyst complexes. A SWNTs-SLG film loaded with Ru nanoparticles exhibited not only catalytic effects, but also the ability to suppress the side reactions, and hence stabilized the whole Li-O2 battery. Our research introduces a gel-derived, high-dispersed processing of carbon nanotube-graphene complexes and demonstrates their favorable applications on Li-O2 batteries.

The remote voltage generation was successfully realized by the sono-electrochemical process. It was resulted from the formation of surface oxygen species and subsequent oxidation of adsorbed poisoning species over the platinum surface under the irradiation of ultrasound. The irradiation of ultrasound effectively oxidized the carbon monoxide on the platinum, which could be a new option for the removal of carbon monoxide. Under the irradiation of ultrasound (frequency = 100 kHz), we obtained the static voltage of 50 mV in the methanol solution, 40 mV in the ethanol solution, and 100 mV in the glucose solution. The voltage could be controlled by the selection of organics, change of frequency and time of application. Our results bring out a unique application of the ultrasound as the removal of carbon monoxide and remote voltage generation devices, and sensors. This may also have an immense potential in biomedical applications. Keywords: Voltage generation, Sonochemical process, Ultrasound, CO oxidation

Thin, semiconducting BaTiO 3 ceramic wires prepared in the present study exhibited reversible stress-induced, nonlinear current-voltage characteristics across several grain boundaries. A remarkable change in resistance with the application (by the three-point bending method) of only ∼1% tensile deformation indicated that the BaTiO 3 wires may have potential as stress-sensing devices. Resistance in the BaTiO 3 wires both increased and decreased with increasing tensile stress parallel to the electric fields, far below the ferroelectric transition temperature, T c ; in Sr-substituted wires near T c , on the other hand, resistance only increased. Detailed studies of the patterns and fluctuation of polarization at grain boundaries could be meaningful, because stress-sensing characteristics may be induced by changes in the relative angle between polarization vectors of adjacent grains.

Definite increases in the Curie point (TC) of undoped and lanthanum- (La-) doped (

Nd-substituted Bi4Ti3O12 (BNT) polycrystalline thin films with preferred a-/b-axes orientations were grown on sputter-grown IrO2(101) layers by chemical solution deposition method. After optimizing the heat treatment conditions, insulating characters and ferroelectric properties in 250-nm-thick BNT thin films with a-/b-axes orientations were investigated at room temperature. Low leakage current density of J=10-7~10-8 A/cm2 at 100 kV/cm and fair value of remnant polarization (2Pr=31 μC/cm2 at 400 kV/cm) were measured even though the Bi2O2 blocking layer aligned parallel to the film normal.

Thin films of calcium-strontium bismuth titanate (Ca1-xSrx)Bi4Ti4O15 solid solution were fabricated on (111)Pt/Ti/SiO2/(100)Si substrates by a chemical-solution deposition (CSD) technique. These films had x = 0–1.00 and consisted of a polycrystalline structure with random orientation of the bismuth layer-structured ferroelectric (BLSF) crystal (m = 4). The relative dielectric constants of (Ca1-xSrx)Bi4Ti4O15 films were enhanced from 40 to 220 with increasing x; these values did not vary significantly with changes in the measuring frequency and the bias field. The temperature coefficient of the relative dielectric constant at around room temperature became larger with increasing x from 0 to 1.00; the change in the dielectric constant of these film between 30–100°C increased from 2% to 15%.

Ferroelectric properties of ion-cosubstituted BIT thin films, (Bi4.00 − yLny)4-δ (Ti3.00-xXx)3O12 (BLnTX), with various lanthanoid (Ln: e.g., La3+, Nd3+, Pr3+, Sm3+) and higher-valent ions (X: e.g., V5+, Nb5+, Ta5+, W6+) were investigated to determine the optimum condition of the ion-cosubstitution. Ion-substituted BIT films were fabricated on (111)Pt/Ti/SiO2/(100)Si substrates using a chemical solution deposition (CSD) technique. In the case of Bi-site substitution, Pr3+, Nd3+ and Sm3+-substituted BIT films (BPT, BNT and BST) had larger remanent polarization (P r ) values than that of conventional La3+-substituted BIT film (BLT). Especially, P r and E c values of (Bi3.50Nd0.50)Ti3.00O12 film were measured to be 32 μC/cm2 and 126 kV/ cm, respectively. On the other hand, Ti-site substitution by higher-valent cations degraded the large leakage current density of the BIT film from ∼10−6 down to ∼10−7 A/cm2. V-substituted (Bi3.50Nd0.50)Ti3.00O12 films, i.e., Nd3+/V5+-cosubstituted BIT films (BNTV), had larger...

An atomic force microscope (AFM) probing system was connected with a ferroelectric test system to measure the polarization hysteresis (P–E) curve and longitudinal displacement properties simultaneously with a large AC drive signal at 5 Hz, since this measurement system has the advantages of enabling dynamic evaluation of longitudinal displacement and direct comparison of the ferroelectric and piezoelectric properties. With decreasing the top electrode diameter from 500 to 30 µm, the longitudinal displacement direction changes from negative to positive since the longitudinal piezoelectric effect becomes dominant. The longitudinal piezoelectric constant calculated with a unipolar signal (+5 V, 5 Hz) was d33 =108 pm/V for a 30-µm-dia top electrode. This value is lower than that of bulk PZT but higher than that of reported data measured using the double-beam laser interferometer or the AFM with a small AC signal of about 1 kHz.

Lanthanoid (M3+=La3+, Pr3+, Nd3+ and Sm3+)-substituted and lanthanoid/vanadium (V5+)-cosubstituted bismuth titanate thin films were fabricated on (111)Pt/Ti/SiO2/(100)Si substrates by a chemical solution deposition (CSD) technique. All the films consisted of a polycrystalline structure with random crystal orientation. Pr3+, Nd3+ and Sm3+-substituted BIT films [BPT, BNT and BST] had larger remanent polarization (Pr) values than that of conventional La3+-substituted BIT film [BLT]; furthermore, the Pr value of the BNT film was higher than those of the BPT and BST films. On the other hand, no significant difference in the coercive field (Ec) value was found among those films. Pr and Ec values of the BNT film with y=0.50 in (Bi4.00-y, Ndy)Ti3.00O12 were measured to be 32 µC/cm2 and 126 kV/cm, respectively. V5+-substitution varied the Pr value of the lanthanoid-substituted BIT films without changing the in Ec value. The Pr value of the BNT film with y=0.50 was improved up to 37 µC/cm2 by V5+-substitution of x=0.02 in (Bi4.00-y, Ndy)1-(x/12)(Ti3.00-x, Vx)O12 [BNTV]. Ferroelectric properties of the Pb-free polycrystalline BNT and BNTV films are comparable to those of conventional Pb-based ferroelectric films such as lead zirconate titanate [PZT] films.

Macrophage-derived foam cells are known to play an essential role in the development and progression of atherosclerotic lesions. Probucol prevents oxidative modification of low-density lipoprotein (LDL) and lowers plasma contents of LDL and high-density lipoprotein (HDL). A recent report using apoE : mice demonstrated that probucol treatment enhanced atherosclerosis in apoE : mice more rapidly than that in untreated apoE : mice, and a reduction in plasma cholesterol by probucol was not the cause of enhancement of atherosclerotic lesions in probucol-treated apoE : mice. Moreover, probucol was reported to inhibit apoA-I mediated cholesterol efflux from mouse macrophages. These reports suggested that probucol might directly affect cholesterol metabolism in mouse macrophages. Thus, we investigated the effects of probucol on cholesterol metabolism in mouse resident peritoneal macrophages. Probucol did not affect degradation of acetylated LDL (Ac-LDL), degradation of LDL and endogenous cholesterol synthesis in mouse macrophages. However, it significantly inhibited HDL-mediated cholesterol efflux. Moreover, probucol partially (30%) inhibited the binding of HDL to mouse macrophages, and significantly activated acyl-coenzyme A:cholesterol acyltransferase (ACAT). Our results suggested that probucol inhibited HDL-mediated cholesterol efflux by inhibiting the binding of HDL to mouse macrophages and reducing HDL-accessible free cholesterol content by ACAT activation, thereby worsening atherosclerotic lesions in apoE : mice. However, it remains unclear whether probucol inhibits HDL-mediated cholesterol efflux from human macrophages. © 2000 Elsevier Science Ireland Ltd. All rights reserved.

We have succeeded in single-step synthesis of polycrystalline BaTiO3 thin film on glass substrate with the thickness of 500 nm at 50°C by newly established sol–gel method starting from high-concentration Ba- and Ti-alkoxide precursor solutions. The film was in good quality with a crack-free, smooth surface. The key process of crystallization of BaTiO3 at low temperature was the aging of gel film in a mist of water and alcohol in a sealed cell. The water mist may slow hydrolysis and the alcohol mist may stabilize the reactive Ti-alkoxide to associate the reaction rate with that of Ba-alkoxide. Both effects may lead the alkoxides to crystallize into BaTiO3 perovskite instead of being hydrolyzed separately. The dried and fired films showed optical transmission spectra in the wavelength range of 350–2600 nm with sharp absorption edge at 350 nm and the refractive index n=2.0 in the visible light region was estimated from the interference fringes.

Extremely large piezoresistive effects with a gage factor (elastoresistance) of > 1 × 106 in single grain boundaries of thin ceramic bars of semiconducting barium titanate have been observed at room temperature. Thin barium titanate ceramic bars with a diameter in the range of 10 to 20 μm were prepared to consist of single grains joined together in series. Large piezoresistive effects were observed for some of the single grain boundaries in the present samples under compressive stresses, but no distinct piezoresistance was observed in the grain bulk. A giant piezoresistive effect with a gage factor of 3 × 107 was observed for a single grain boundary which exhibited a saw-tooth type PTCR (positive temperature coefficient of resistivity) characteristic with a significantly large bias dependence of it. This demonstrates that the piezoresistive phenomenon may be interpreted in terms of the change of the potential barrier height due to the change of ferroelectric domain morphologies in the vicinity of grain boundaries under mechanical and electric stresses.

Transparent barium titanate (BaTiO3) wet gels synthesized by sol-gel processing using high-concentration Ba,Ti-alkoxide solution (1.0 mol/l) were subjected to optical measurements, X-ray diffraction analysis and transmission electron microscope observations. A systematic shift of the optical absorption edge was observed for the transparent BaTiO3 wet gels shrinking during aging at 30 and 50°C, while no shift was observed for the wet gels aged at 5°C. The crystallinity and crystallite size of the gels increased with increasing aging time and temperature. The shift of the optical absorption edge of the BaTiO3 gels during aging was found to have a close relation to an increase in the crystallite size of the gels.

We have investigated on the synthesis of Ba1 − xSrxTiO3 (BST, x = 0.0–1.0) solid solution at low temperature by a sol-gel method using precursor solutions of Ba(OC2H5)2, Sr(OC2H5)2, and Ti(OCH(CH3)2)4 dissolved in 2-methoxyethanol. Crystalline BST solid solution monolithic gels were obtained as dried at 90°C. Crystalline fraction of BST gels increased with increasing concentration of the precursor solution and increasing amount of the hydrolysis water used. Ba0.4Sr0.6TiO3 (x = 0.6) gels from a precursor solution of 0.5 mol/l with hydrolysis water of H2O/Ti = 50 crystallized during aging at 30°C.

This paper deals with donor, acceptor-codoped (Ba0.4Sr.6)TiO3 ceramics with distinct varistor characteristics at room temperature, which were prepared by single-step firing in air. The materials, with the Curie point at around −90 °C, exhibited a large PTCR (positive temperature coefficient of resistivity) effect of more than seven orders of magnitude in the temperature range −90 °C (the resistivity ρ ≈ 103 Ω · cm) to room temperature (ρ > 1010 Ω · cm). An apparent dielectric constant of >20000 and tan δ < 0.05 (at 100 kHz) were observed for the present materials at room temperature, and moreover, the materials exhibited nonlinear current-voltage characteristics with the nonlinear coefficient, α, in the range 7–12 and the varistor field, Ev, in the range 0.3–1.0 kV/cm. The value of α in the present materials increased systematically with increasing ρ in their PTCR temperature range. It has been found that there exists a close correlation between α and the grain-boundary potential barrier height, eφ, obtained from the ρ-T characteristic of the materials. An almost linear relationship was also found to exist between α and log Ev for the present materials.

Serotonin enhances the production of type IV collagen by human mesangial cells. Background The plasma concentration of 5-hydroxytryptamine (5-HT) in diabetic patients is higher than that in normal subjects. Since recent reports have demonstrated the presence of 5-HT 2A receptor in glomerular mesangial cells, it is possible that 5-HT may be involved in the development of diabetic nephropathy through the 5-HT 2A receptor in mesangial cells. Because expansion of the glomerular mesangial lesion is a characteristic feature of diabetic nephropathy, we examined the effect of 5-HT on the production of type IV collagen by human mesangial cells. Methods Human mesangial cells were incubated with 5-HT with or without 5-HT receptor antagonists, protein kinase C (PKC) inhibitor or transforming growth factor- β (TGF- β ) antibody. Type IV collagen mRNA and protein concentration in medium were measured by Northern blot analysis and enzyme-linked immunosorbent assay (ELISA), respectively. TGF- β mRNA and bioactivity in the medium were measured by Northern blot analysis and bioassay using mink lung epithelial cells, respectively. Results 5-HT stimulated the production of type IV collagen by human mesangial cells, which was inhibited by ketanserin and sarpogrelate hydrochloride, 5-HT 2A receptor antagonists, but not by ondansetron, a 5-HT 3 receptor antagonist. 5-HT increased the bioactivities of both active and total TGF- β . However, the 5-HT-enhanced production of type IV collagen was completely inhibited by an anti-TGF- β antibody. Furthermore, a PKC inhibitor, calphostin C, inhibited the 5-HT-induced increase in type IV collagen secretion, and the activity of membrane PKC was increased by 5-HT. Phorbol ester activated type IV collagen production as well as active and total TGF- β . Calphostin C completely inhibited the 5-HT-enhanced activity of active TGF- β , but did not inhibit exogenous TGF- β -induced increase in type IV collagen secretion. Conclusions Our results suggest that 5-HT-enhanced production of type IV collagen by human mesangial cells is mediated by activation of PKC and subsequent increase in active TGF- β activity.

A high concentration of oxidized low density lipo- protein (Ox-LDL) showed a cytotoxic effect on mouse mac- rophage-derived J774 cells. Mutant cells were selected from these cells that were resistant to the cytotoxic effect of Ox- LDL. One mutant form, named JO21b cells, was character- ized in the present study. In spite of a marked resistance to the cytotoxic effect of Ox-LDL, JO21b cells were apparently as sensitive as the parent cells not only to toxic moieties of Ox- LDL, such as 7-ketocholesterol and lysophosphatidylcholine, but also to t -butyl hydroperoxide, an artificial lipid hydroper- oxide analog. However, the cellular association of 125 I-labeled Ox-LDL with, and subsequent endocytic degradation by JO21b cells was reduced by 70-80% compared with J774 cells. Similarly, accumulation of cholesteryl esters in JO21b cell by Ox-LDL was also reduced by 70%. Northern blot analyses of type I and type II macrophage scavenger receptors (type I and type II MSR) demonstrated that the mRNA levels of JO21b cells were lower than those of J774 cells. Moreover, peritoneal macrophages obtained from MSR-knockout mice showed a higher resistance to the cytotoxic effect of Ox-LDL than those from their wild-type littermates. Our results suggest, there- fore, that macrophage scavenger receptor-mediated en- docytic uptake of oxidized low density lipoproteins (Ox-LDL) may play an enhancing role in Ox-LDL cytotoxicity to mac- rophages or macrophage-derived cells.— Hakamata, H., A. Miyazaki, M. Sakai, H. Matsuda, H. Suzuki, T. Kodama, and S. Horiuchi. Isolation of macrophage-like cell mutants resistant to the cytotoxic effect of oxidized low density lipoproteins. J. Lipid Res. 1998. 39: 482-494.

Pure, translucent, and highly crystallized barium titanate (BaTiO3) monolithic gels were synthesized via a sol-gel technique at temperatures down to 90°C by using a high-concentration solution of barium alkoxide and titanium alkoxide. The gels consisted of fine particles with an average diameter of ~10 nm and showed the X-ray diffraction patterns of a pseudo-cubic BaTiO3 system at room temperature; however, in bulk crystal, the tetragonal structure was more stable. The optical transmission spectra of the polycrystalline gels were similar to those for single-crystalline BaTiO3. From the excitation energy dependence of the absorption-edge structures, the optical-gap energies for the gels were estimated to have values that were ~0.1 eV higher than those for the single crystal; these higher optical-gap energies may be attributed to size effects.

Development of Al-stabilized Li7La3Zr2O12 (LLZO) fast Li ion conducting thin films was attempted by chemical solution deposition (CSD) method with the nominal composition of Li5.95Al0.35La3Zr2O12. The films were crystallized at 600°C on Pt-coated Si substrates in almost single phase without a preferred orientation to any crystallographic axis. Subsequent thermal annealing at 760°C improved packing of LLZO grains with the film thickness of 1.1μm. AC impedance measurements were conducted both with Li reversible and Au blocking microelectrodes deposited on the films annealed at 760°C. Total Li ion conductivity σtotal comprised of bulk and grain boundary contribution was studied. The temperature dependence of σtotal was described with single thermal activation process and σtotal∼2x10-5 S/cm and activation energy of Ea=0.58eV were estimated. These values may be attributed to tetragonal modification of LLZO crystal.

Many studies have shown that sterols can stimulate acyl-coenzyme A:cholesterol acyltransferase (ACAT) activity in cells. To elucidate this mechanism, effects of sterol-mediated induction on both the enzyme activity of ACAT and its mRNA levels were studied in human hepatoblastoma cell line, HepG2 cells. When HepG2 cells were loaded with cholesterol and 25-hydroxycholesterol, both the whole-cell ACAT activity and the microsomal ACAT activity were increased by 85.1% and 41.3%. In contrast, cholesterol depletion of HepG2 cells with compactin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, resulted in a decrease in both the whole-cell and the microsomal ACAT activity by 46.4% and 58.3%. Under identical conditions, RT-PCR and Northern blotting analyses revealed that neither cholesterol loading nor cholesterol depletion of HepG2 cells altered the amounts of ACAT mRNA. Moreover, these treatments had no effect on the enzymatic ACAT activity determined by the reconstituted assay in which HepG2 cell homogenate had been supplemented in vitro with a saturating level of exogenous cholesterol. These results indicate that cholesterol-induced up-regulation of ACAT activity in HepG2 cells does not occur at the level of transcription, but rather at a posttranscriptional level.

A combination of the preparation techniques for the ferroelectric films and the micro machining of Si is considered to be an effective way to fabricate microelectromechanical systems (MEMS), such as piezoelectric micro-transducer devices for the electrical and medical fields. In this study, disk shape lead zirconate titanate (PZT) thick films were successfully fabricated. 10-mm-thick PZT films were deposited onto Pt/Ti/ SiO2/Si substrate using a chemical solution deposition (CSD) process. Pt top electrode and PZT layer were etched by reactive ion etching (RIE) process, and 100 to 500-mm-diameter PZT thick film disks were fabricated. The relative dielectric constant, dissipation factor, remnant polarization and coercive field were "r ¼ 1130, tan � ¼ 0:02, Pr ¼ 0:14 C/m 2 and Ec ¼ 2:5 MV/m, respectively. This means that the ferroelectric and dielectric properties of the PZT thick film disks were comparable with that of the bulk PZT ceramics. Moreover, the prepared PZT thick film disks showed the butterfly-shaped displacement curve, related with piezoelectric response, in the case of bipolar measurement. The PZT thick film disks could be poled with 80 V at room temperature, which is easier than the poling condition of bulk PZT. The piezoelectric constant of the poled PZT thick film disks was estimated to be AFM d33 ¼ 221 pm/V. Therefore, the micro fabricated 10-mm-thick PZT disks is considered to be applicable for piezoelectric micro devices.

The effect of methimazole on N- ethyl-N-hydroxyethylnitrosamine (EHEN)-induced renal lesions was investigated in a medium-term initiation/promotion bioassay in male Wistar rats. EHEN-initiated rats underwent unilateral nephrectomy of the left kidney and subsequent addition of the renal tumor promoters trisodium nitrilotriacetate (NTA), potassium dibasic phosphate (PDP), or hydroquinone (HQ), alone or in combination with methimazole, to the diet for 20 wk. The addition of methimazole reduced the severity of simple and adenomatous renal hyperplasias induced by NTA, PDP, and HQ, but had no effect on the number of renal cell tumors that arose in EHEN + NTA groups. Methimazole also decreased the bromodeoxyuridine (BrdU) labeling indices, but had little effect on the expression of α 2u-globulin in treated kidneys as compared to controls. It appears that methimazole exhibits antagonistic properties to nongenotoxic nephrotoxins, protecting against renal damage but not against tumorigenesis, probably arising from genotoxic insult.

Thin films of Nd3+-substituted bismuth titanate, (Bi4.00−y,Ndy)Ti3.00O12 (BNT), Nd3+/V5+-cosubstituted bismuth titanate, (Bi4.00−y,Ndy)(Ti3.00−xVx)O12 (BNTV), and La3+-substituted bismuth titanate, (Bi3.25,La0.75)Ti3.00O12 (BLT) were fabricated on the (111)Pt/Ti/SiO2/(100)Si substrates by a chemical solution deposition technique. These films possessed random-oriented polycrystalline structure. The BNT film had larger remnant polarization (Pr) than the BLT film; Pr and coercive field (Ec) of the BNT film with y=0.50 were 32 μC/cm2 and 126 kV/cm, respectively. Furthermore, V5+ substitution improved the Pr value of the BNT film up to 37 μC/cm2 (BNTV film; y=0.50, x=0.02), while the BNTV film had an Ec value of approximately 119 kV/cm which was similar to that of the BNT film. Ferroelectric properties of the Pb-free polycrystalline BNT and BNTV films are comparable with those of conventional Pb-based ferroelectric films like a lead zirconate titanate.

Thin, semiconducting barium titanate (BaTiO 3 ) ceramic bars, with a diameter of 10 to 20 μm, consisting of single grains joined together in series have been prepared to investigate the piezoresistivity in the materials, which was evaluated from their current (I)-voltage (V) characteristics under the loading condition of various bending stresses. I-V characteristics of single grain boundaries in some of the materials were found to exhibit distinct differential negative resistance (DNR) at room temperature with its feature changing with stress. The DNR appeared on the I-V curves at an electric field of several volts per one grain, and has been confirmed to be connected with the transition of current between two conduction states in the grain boundary region. The obtained results indicate that this phenomenon cannot be interpreted by a rise in the temperature of the materials up to their positive temperature coefficient of resistivity (PTCR) region above the Curie point by Joule heating due to current flow, that is their self-heating effect. This newly observed DNR phenomenon has thus been tentatively interpreted by the morphological change in the ferroelectric domain structure in the vicinity of grain boundaries under mechanical and electric stresses, on an assumption that different configurations of ferroelectric domains yield different conduction states in the grain boundary due to a difference in the degree of surface acceptor charge compensation or the anisotropic carrier mobilities in the crystal.

Pure, translucent, and highly crystallized barium titanate (BaTiO3) monolithic gels were synthesized via a sol-gel technique at temperatures down to 90°C by using a high-concentration solution of barium alkoxide and titanium alkoxide. The gels consisted of fine particles with an average diameter of ~10 nm and showed the X-ray diffraction patterns of a pseudo-cubic BaTiO3 system at room temperature; however, in bulk crystal, the tetragonal structure was more stable. The optical transmission spectra of the polycrystalline gels were similar to those for single-crystalline BaTiO3. From the excitation energy dependence of the absorption-edge structures, the optical-gap energies for the gels were estimated to have values that were ~0.1 eV higher than those for the single crystal; these higher optical-gap energies may be attributed to size effects.

Semiconducting donor (La)-doped barium titanate (BaTiO3) ceramics were synthesized at 1100°C in air by firing fine-grained crystalline gel powders of Ba-, La-, and Ti-alkoxides prepared by the sol-gel method. The ceramics showed resistivity of

A combination of the preparation technique for ferroelectric films such as lead zirconate titanate (PZT) and the micromachining of Si is considered to be an effective way to fabricate piezoelectric microdevices like microactuators called a microelectromechanical system (MEMS). However, the amount of the displacement and force of PZT thin films is not sufficient in some applications of microactuators. To achieve the property of large displacement, increase of the film thickness or improvement of the piezoelectric property is required. One of the techniques to improve the ferroelectric and piezoelectric properties is assumed to be the arrangement of the polarization direction using a texture control process. We successfully preparaed the (100) and (111) dominant oriented Pb(Zr 1-x Ti x )O 3 thin films using a chemical solution deposition (CSD) process. On the other hand, an arc-discharged reactive ion-plating (ADRIP) method is one of the candidates to fabricate the thick PZT films because of high deposition rate such as 3 μm/h. In this work, the texture-controlled PZT thin and thick films deposited onto Pt/Ti/SiO 2 /Si substrates were prepared using CSD or ADRIP process for actuator applications. In the case of ADRIP process, (100) and (111) dominant oriented PZT thick films was formed onto CSD derived and texture controlled PZT thin film layer.

Ti-site substitution using the higher-valent cation was performed on ferroelectric thin films of neodymium-substituted bismuth titanate, (Bi,Nd)4Ti3O12(BNT), in order to improve its ferroelectric properties by compensating the space charge in BIT-based crystal. Ti-site-substituted BNT films, (Bi3.50Nd0.50)1-(x/12)(Ti3.00-xVx)O15(x= 0 ∼ 0.09), were fabricated on (111)Pt/Ti/ SiO2/(100)Si substrates using a chemical solution deposition (CSD) technique. V5+-substitution enhanced the remanent polarization of BNT film without change in the coercive field. V5+-substitution also exhibited the possibilities for improving the endurance against leakage current and fatigue degradation.

A combination of the preparation techniques for the ferroelectric films and the micro machining of Si is considered to be an effective way to fabricate microelectromechanical systems (MEMS), such as piezoelectric micro-transducer devices for the electrical and medical fields. In this study, 10-μm-thick disk shape lead zirconate titanate (PZT) thick films were successfully fabricated using a chemical solution deposition (CSD) process. Pt top electrode and PZT layer were etched by reactive ion etching (RIE) process, and 100 to 500-μm-diameter PZT micro disks were fabricated on Pt/SiO2/Si substrate. The relative dielectric constant, dissipation factor, remnant polarization and coercive field were εr = 1130, tanδ = 0.02, Pr = 14 μC/cm2 and Ec = 25 kV/cm, respectively. This means that the ferroelectric and dielectric properties of the PZT micro disks were comparable with that of the bulk PZT ceramics. The PZT micro disk showed the butterfly-shaped displacement curve, related with piezoelectric response, in the case of bipolar measurement. The piezoelectric constant of the PZT disks poled at 80Vfor 10 min was estimated to be AFM d33 = 221 pm/V. A resonance frequency of the radial oscillation was evaluated to apply for micro transducer devices.

Abstract —Glucocorticoid, an anti-inflammatory agent, inhibits the development of atherosclerosis in various experimental animal models. This is partially explained by its ability to inhibit smooth muscle cell migration and proliferation in the intima and to reduce chemotaxis of circulating monocytes and leukocytes into the subendothelial spaces. We have recently demonstrated that oxidized LDL (Ox-LDL) has a mitogenic activity for macrophages in vitro in which Ox-LDL–induced granulocyte/macrophage colony-stimulating factor (GM-CSF) production plays an important role. Proliferation of cellular components is one of the characteristic events in the development and progression of atherosclerotic lesions. In the present study, we investigated the effects of glucocorticoids on Ox-LDL–induced macrophage growth. Dexamethasone, prednisolone, and cortisol inhibited Ox-LDL–induced thymidine incorporation into macrophages by 85%, 70%, and 50%, respectively. Ox-LDL induced a significant production of GM-CSF by macrophages, which was effectively inhibited by dexamethasone, prednisolone, and cortisol by 80%, 65%, and 50%, respectively. Dexamethasone-mediated inhibition of Ox-LDL–induced GM-CSF mRNA expression and macrophage growth was significantly abrogated by RU-486, a glucocorticoid receptor antagonist. Our results suggest that the inhibitory effects of glucocorticoids on macrophage growth may be due to the inhibition of Ox-LDL–induced GM-CSF production through transactivation of the glucocorticoid receptor.

Brefeldin A (BFA)-resistant mutants, JB15, JB23 and JB33, were isolated from mutagenized murine macrophage-like (J774) cells and their modified low density lipoprotein (LDL) metabolism was studied. When JB23 cells, the most resistant clone, were incubated with acetylated LDL, intracellular accumulation of cholesteryl esters (CE) was reduced by 31% as compared with J774 cells. The cell-association of 125 I-acetyl-LDL with, and subsequent endocytic degradation by JB23 cells were reduced by 40–60% compared with J774 cells. Western and Northern blot analyses showed that the protein and mRNA levels of the macrophage scavenger receptors (MSR) were reduced by 68% and 55% respectively in JB23 cells as compared with those in J774 cells. These results indicate that a putative BFA-target molecule(s) might regulate MSR gene expression as well as macrophage-derived foam cell formation.

Abstract Recent studies demonstrated that oxidized LDL (Ox-LDL) induces macrophage growth in vitro. The present study was undertaken to elucidate the intracellular signaling pathways for macrophage growth. Ox-LDL initiated a rapid and transient rise in intracellular free calcium ion and induced activation of membrane protein kinase C (PKC). Pertussis toxin completely inhibited the Ox-LDL–induced rise in free calcium ion and significantly inhibited macrophage growth by 50%. Moreover, PKC inhibitors calphostin C and H-7 significantly inhibited Ox-LDL–induced macrophage growth by 80%. On the other hand, phospholipase A2–treated acetylated LDL did not induce a rise in calcium but significantly activated PKC and led to significant macrophage growth that was significantly inhibited by calphostin C by 90%. These results suggest the presence of two intracellular signaling pathways for activation of PKC, a rise in calcium that was mediated by pertussis toxin–sensitive G protein and the internalization of lysophosphatidylcholine through the scavenger receptors. These two pathways may play an important role in Ox-LDL–induced macrophage growth.

To elucidate the mechanism of triglyceride (TG) accumulation in adipocytes induced by TG-rich lipoproteins, we examined the effect of β -very low density lipoprotein ( β -VLDL) on TG accumulation in 3T3-L1 adipocytes. β -VLDL did not induce TG accumulation in 3T3-L1 preadipocytes but in 3T3-L1 adipocytes. TG accumulation was significantly inhibited by cytochalasin B, an inhibitor of receptor mediated endocytosis. In contrast, cytochalasin B did not inhibit free fatty acid induced TG accumulation in adipocytes. The binding of [ 125 I] β -VLDL to preadipocytes was inhibited completely by both β -VLDL and LDL. In sharp contrast, the binding of [ 125 I] β -VLDL to adipocytes was inhibited completely by β -VLDL, but partially by LDL. The VLDL receptor mRNA was only expressed in adipocytes. These results suggest that β -VLDL induced TG accumulation in adipocytes may be mediated through the VLDL receptor pathway.

Ferroelectric properties of La3+-substituted bismuth titanate (BLT) films were modified by Ti-site substitution using higher-valence ions than the Ti4+ ion. Thin films of V5+-, W6+-, Zr4+- and nonsubstituted BLT, i.e., (Bi3.24La0.75)(Ti2.97V0.03)O12 (BLTV), (Bi3.23La0.75)(Ti2.97W0.03)O12 (BLTW), (Bi3.25La0.75)(Ti2.97Zr0.03)O12 (BLTZ) and (Bi3.25La0.75)Ti3.00O12, respectively, were fabricated on (111)Pt/Ti/SiO2/(100)Si substrates by chemical solution deposition. These films consisted of isotropic granular structures without a preferred crystal orientation. Remanent polarizations (P r) of the BLTV and BLTW films (13 and 12 µC/cm2, respectively) were larger than those of the BLT and BLTZ films (8 and 9 µC/cm2, respectively), while those films had similar coercive fields (E c) of approximately 120 kV/cm. BLTV and BLTW films also had lower leakage current densities (approximately 10-8 A/cm2 at 100 kV/cm) than that of BLT film (approximately 10-6 A/cm2 at 100 kV/cm). As no obvious difference was found in the crystal orientation or the microstructure, the enhancement of the P r value and suppression of the leakage current density could be achieved on a BLT film by the charge compensation using higher-valence ions than the Ti4+ ion.

Bismuth titanate (Bi4Ti3O12; BIT) -based ferroelectric thin films fabricated from a view point of “the site-engineering technique” have been expected to improve the fatal disadvantage of a ferroelectric BIT film, i.e., its low spontaneous polarization; here, Bi- and Ti-site ions in the BIT crystal are cosubstituted by lanthanoid ions and cations with a higher charge valence, respectively, In the present study, we have mainly focused on Ti-site substitution of bismuth titanate (Bi4Ti3O12; BIT)-based thin films using some ions with higher charge valences (V5+, Nb5+, Ta 5+ and W6+; in this study) to enhance the ferroelectric properties of those materials. The BIT-based films with various chemical compositions were fabricated on a (111)Pt/Ti/SiO2/(100)Si substrate by a chemical solution deposition method.Ti-site substitution of BIT films by the higher-valent ions, Bi3.99(Ti2.97V0.03)O12, Bi3.99(Ti2.97Nb0.03)O12, Bi3.99(Ti2.97Ta0.03)O12 and Bi3.98(Ti2.97W0.03)O12, reduced the leakage current density of BIT films from ∼ 10-6 down to ∼ 10-7 A/cm2 at an applied field of 50 kV/cm, while the substitution by the same-valent cation, e.g., Bi4.00(Ti2.97Zr0.03)O12, did not affect the behavior of leakage current. Whereas polarization (P) - electrical field (E) hysteresis loops of non-substituted and Zr-substituted BIT films were distorted due to the leakage current, non-distorted P-E loops were obtained at V5+-, Nb5+-, Ta5+- and W6+-substituted BIT films.Also, Ti-site substitution was effective for improving the ferroelectric properties in lanthanoid-substituted BIT films. In the case of La3+-substituted BIT film (BLT), remanent polarization (Pr) of V5+- and W6+-substituted BLT films, (Bi3.24La0.75)(Ti2.97V0.03)O12 and (Bi3.23La0.75)(Ti2.97W0.03)O12 (13 and 12 μC/cm2, respectively), were larger than those of Zr4+- and non-substituted BLT films, (Bi3.25La0.75)(Ti2.97Zr0.03)O12 and (Bi3.25La0.75)(Ti3.00)O12 (8 and 9 μC/cm2, respectively), while those films had similar coercive field (Ec) of approximately 120 kV/cm. Also in the case of Nd3+-substituted BIT film (BNT), Pr and Ec values of V5+-substituted BNT film, (Bi3.24Nd0.75)(Ti2.98V0.02)O12, were 37 μC/cm2 and 119 kV/cm, respectively, which were comparable with those of conventional Pb-based ferroelectrics such as lead zirconate titanate, Pb(Zr,Ti)O3. We concluded that enhancement of the Pr value was achieved by the charge compensation of oxygen vacancies in BIT-based ferroelectrics using higher-valent cations than Ti4+ ion whereas no obvious differences were found in the crystal orientation and or microstructure of these films.

Effects on ferroelectric and piezoelectric properties of top-electrode diameter variance from 80 to 8 μm were investigated using an AFM probing system connected with a ferroelectric test system with bipolar and unipolar signals at 5 Hz. The Pt and 1.2-μm-thick PZT layers were etched off to prepare Pt top electrode etched samples or Pt/PZT stack etched samples. In the case of bipolar measurement, the top electrode diameter did not affect ferroelectric properties, while the maximum displacement of the butterfly-shaped hysteresis curve, related with piezoelectric response, increased with decreasing top-electrode diameter. On the other hand, the longitudinal piezoelectric constant, AFM d33, calculated from the strain curve slope at 5 Hz, +5 V, increased with decreasing top-electrode diameter. The average value of the Pt/PZT stack-etched AFM d33 almost equals that of Pt-etched AFM d33. Average AFM d33 of the 8-μm-diameter Pt-etched and Pt/PZT stack-etched samples are 129 and 135 pm/V, respectively.

Thin, semiconducting barium titanate (BaTiO 3 ) ceramic bars, with a diameter of 10 to 20 μm, consisting of single grains joined together in series have been prepared to investigate the piezoresistivity in the materials, which was evaluated from their current (I)-voltage (V) characteristics under the loading condition of various bending stresses. I-V characteristics of single grain boundaries in some of the materials were found to exhibit distinct differential negative resistance (DNR) at room temperature with its feature changing with stress. The DNR appeared on the I-V curves at an electric field of several volts per one grain, and has been confirmed to be connected with the transition of current between two conduction states in the grain boundary region. The obtained results indicate that this phenomenon cannot be interpreted by a rise in the temperature of the materials up to their positive temperature coefficient of resistivity (PTCR) region above the Curie point by Joule heating due to current flow, that is their self-heating effect. This newly observed DNR phenomenon has thus been tentatively interpreted by the morphological change in the ferroelectric domain structure in the vicinity of grain boundaries under mechanical and electric stresses, on an assumption that different configurations of ferroelectric domains yield different conduction states in the grain boundary due to a difference in the degree of surface acceptor charge compensation or the anisotropic carrier mobilities in the crystal.