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Sodium dehydroacetate (DHA-S) is used as a food additive, preservative and antimicrobial agent. Repeated oral administration of DHA-S in rats induced severe hemorrhage in multiple organs and prolongation of blood coagulation factors. To determine the mechanism of hemorrhage, the protective effect of vitamin K (VK) was investigated. Increased VK-dependent blood coagulation parameters, a prolonged prothrombin time (PT) and an activated partial thromboplastin time (APTT) were observed in rats when DHA-S alone was administered, while only a slight change was observed in animals that received a single injection of vitamin K2 following the DHA-S dosing. These results suggest that DHA-S-induced hemorrhage is caused by a deficiency of vitamin K. In addition, the inhibitory effect of DHA-S on vitamin K1 epoxide reductase (VKOR) activity was measured with an in vitro system using liver microsomes of normal male rats. DHA-S concentration-dependently inhibited VKOR activity similar to warfarin, but the inhibitory concentration was high. Therefore, it was concluded that the DHA-S-induced hemorrhage was caused by a depletion of blood VK, associated with any factors including VKOR inhibition.

This paper proposes a method to improve the power efficiency in the half-bridge LLC resonant DC-DC converter. The optimum design of a transformer is discussed to improve power efficiency. The interlinkage magnetic flux in the primary and secondary wires causes eddy currents, which results in a power loss. This study demonstrates that power loss can be reduced through optimum design of the strand diameter of the Ritz wire. A maximum efficiency of 98% was achieved using a Ritz wire diameter of 0.03 φ.

Topological defects such as magnetic solitons, vortices, Bloch lines, and skyrmions have started to play an important role in modern magnetism because of their extraordinary stability, which can be exploited in the production of memory devices. Recently, a novel type of antisymmetric exchange interaction, namely the Dzyaloshinskii-Moriya interaction (DMI), has been uncovered and found to influence the formation of topological defects. Exploring how the DMI affects the dynamics of topological defects is therefore an important task. Here we investigate the dynamic domain wall (DW) under a strong DMI and find that the DMI induces an annihilation of topological vertical Bloch lines (VBLs) by lifting the four-fold degeneracy of the VBL. As a result, velocity reduction originating from the Walker breakdown is completely suppressed, leading to a soliton-like constant velocity of the DW. Furthermore, the strength of the DMI, which is the key factor for soliton-like DW motion, can be quantified without any side effects possibly arising from current-induced torques or extrinsic pinnings in magnetic films. Our results therefore shed light on the physics of dynamic topological defects, which paves the way for future work in topology-based memory applications.

Postsurgical peritoneal adhesion is a serious surgical complication. In situ hydrogel formation on the surface of tissues, which will develop adhesions, is a recent feasible approach to prevent peritoneal adhesion. Here, we report on-tissue surface formation of a hyaluronic acid-based hydrogel by administration of a pre-hydrogel aqueous solution. The hydrogelation was initiated by contact with body fluid containing glucose on tissue surfaces. During the hydrogelation, a hyaluronic acid derivative possessing phenolic hydroxyl moieties (HA-Ph) was cross-linked by a cascade reaction of glucose oxidase (GOx) and horseradish peroxidase (HRP). About 5 s of hydrogelation was accomplished using a solution containing 1.5% (w/v) HA-Ph, 5 U/mL HRP, and 2.5 U/mL GOx in 1 mg/mL glucose that is equivalent to the normal blood glucose concentration. The hydrogel was degradable by hyaluronidase and much softer than rat peritoneal sidewalls. We confirmed the efficiency of the hydrogel to prevent post-operative peritoneal adhesions by applying the solution containing HA-Ph, GOx, and HRP to animals with bowel abrasion-abdominal sidewall defects. A significant reduction in the development of peritoneal adhesions was found compared with animals applied with phosphate-buffered saline or saline containing HA-Ph alone. Statement of Significance Postsurgical peritoneal adhesion is a serious surgical complication. In this paper, we report a novel system for preventing it through an on-tissue surface formation of a biodegradable and biocompatible hyaluronic acid-based hydrogel by administration of a pre-hydrogel aqueous solution. The in situ hydrogelation is mediated by a cascade enzyme reaction of glucose oxidase (GOx) and horseradish peroxidase (HRP) initiated by contacting with body fluid containing glucose. The efficiency of the system was confirmed by applying the system to animals with bowel abrasion-abdominal sidewall defects.

We investigate the in-plane field dependence of current-induced magnetic domain wall motion in asymmetric Co/Ni nanowires. The application of an in-plane field changed the direction of domain wall motion. In a systematic study, by varying the magnetic layer thickness, we show that the in-plane field induces a crossover from spin Hall torque to adiabatic spin-transfer torque for the magnetic domain wall motion. Furthermore, the dependence of the threshold current density on the in-plane longitudinal field provides a way for determining the strength of the Dzyaloshinskii-Moriya interaction.

Pulmonary fibrosis is the result of abnormal processes of repair that occur after lung injury. Transforming growth factor (TGF)-beta is a key molecule in the progression of pulmonary fibrosis. Although clinical use of interferon (IFN)-beta did not improve survival in patients with idiopathic pulmonary fibrosis, because some preclinical studies have suggested that IFN-beta is a potent inhibitor of fibrogenesis, beneficial effects of IFN-beta have been expected. We therefore attempted to determine effects of IFN-beta and investigated the mechanism of action of IFN-beta in bleomycin-induced pulmonary fibrosis. Bleomycin at Day 0 and IFN-beta for 4 wk were administered intravenously to ICR mice. At 28 d after bleomycin injection, histologic and chemical analysis was performed for evaluation of effects of IFN-beta. Tissue distribution and amounts of TGF-beta1 and thrombospondin (TSP)-1/2 were analyzed. IFN-beta attenuated prolylhydroxylase activity, resulting in inhibition of pulmonary fibrosis. Bleomycin-induced increase in TGF-beta1 in epithelial cells and extracellular matrix was attenuated by IFN-beta. TSP-1/2 was limited in platelets of control mice, but was present in foamy cells in fibrotic regions induced by bleomycin. These findings suggest that the antifibrotic effect of IFN-beta is inhibition of TGF-beta and its activation via decrease in TSP-1/2 in lung tissue and change in location of TSP-1/2 from platelets to foamy cells.

In recent years, many studies have been reported on remote sensing techniques in agricultural production to utilize the advantage of simultaneous and wider monitoring capability of satellite data. Several studies have been conducted to develop links between spectral reflectance and temperature for traditional paddy rice cultivation. In our study to characterize the spectral reflectance of paddy rice (Oryza sativa L., cv. Hinohikari) with the lengthening growing days, the spectral reflectance of rice leaves from 400 nm to 1, 100 nm wavelength range was acquired with a handheld spectroradiometer. A wide range of nitrogen (N) was applied in experimentally field-grown paddy rice. To develop a growth model for paddy rice we analyzed physical parameters, spectral reflectance and fractional photosynthetically active radiation (fPAR). The following conclusions were drawn: (1) Different spectral characteristics were observed during the growth stages for different N-treatments; (2) Detection of significant differences between N-treatments was realized with the ratio vegetation index (RVI) at full heading stage; (3) Red edge points poorly correlated with leaf area index (LAI), dry weight (DW) and fPAR; (4) The R830/R550 ratio highly correlated with LAI and DW during the entire growing season. The prediction accuracy of fPAR was also very high using the R830/R550 ratio. Though our study accounts for only limited factors, it was concluded that growth models for monitoring paddy rice could be based on RVI and the R830/R550 ratio.

The authors have investigated wire width dependence of threshold current density for current-induced magnetic domain wall (DW) motion in perpendicularly magnetized Co/Ni nanowires. Threshold current density decreased with reducing the wire width, and the lowest threshold value of 1.6×1011 A/m2 was observed at the narrowest width of 36 nm. The micromagnetic simulation shows that the observed width dependence of threshold current density can be understood by the adiabatic spin transfer model.

Epigenetic mechanisms may underlie the progression of diabetic kidney disease. Because the kidney is a heterogeneous organ with different cell types, we investigated DNA methylation status of the kidney in a cell type-specific manner. We first identified genes specifically demethylated in the normal proximal tubules obtained from control db/m mice, and next delineated the candidate disease-modifying genes bearing aberrant DNA methylation induced by diabetes using db/db mice. Genes involved in glucose metabolism, including Sglt2, Pck1, and G6pc, were selectively hypomethylated in the proximal tubules in control mice. Hnf4a, a transcription factor regulating transporters for reabsorption, was also selectively demethylated. In diabetic mice, aberrant hypomethylation of Agt, Abcc4, Cyp4a10, Glut5, and Met and hypermethylation of Kif20b, Cldn18, and Slco1a1 were observed. Time-dependent demethylation of Agt, a marker of diabetic kidney disease, was accompanied by histone modification changes. Furthermore, inhibition of DNA methyltransferase or histone deacetylase increased Agt mRNA in cultured human proximal tubular cells. Aberrant DNA methylation and concomitant changes in histone modifications and mRNA expression in the diabetic kidney were resistant to antidiabetic treatment with pioglitazone. These results suggest that an epigenetic switch involving aberrant DNA methylation causes persistent mRNA expression of select genes that may lead to phenotype changes of the proximal tubules in diabetic kidney disease.

The acute onset of idiopathic nephrotic syndrome (NS) is often accompanied by acute kidney injury, which can lead to congestive heart failure and lung edema. In this report, we present two cases of NS-induced acute kidney injury successfully treated with a low dose of carperitide, a human atrial natriuretic peptide. In combination with standard diuretic therapy and immunotherapy, carperitide retained the renal function and spared the need for renal replacement therapy, including hemodialysis. Although further investigation in clinical trials is required to validate these findings, carperitide may be useful for maintaining the renal function in cases of NS-induced acute kidney injury.

Conservation payments lead to improvement in environmental quality only if farmers and ranchers who receive them adopt conservation practices that would not have been adopted without the payment. When a voluntary payment causes a change in practice(s) that lead(s) to improved environmental quality, these changes are “additional.” We estimate this “additionality” for a number of common conservation practices that are frequently supported by existing conservation programs. We find that the level of additionality varies by practice and that additionality is high for structural and vegetative practices while the risk of nonadditionality appears to be higher for management practices. While the risk of nonadditionality cannot be completely eliminated, it can be reduced. We discuss a number of approaches to managing nonadditionality in both conservation programs and environmental offset programs.

We quantified the bulk perpendicular magnetic anisotropy (PMA) and spin-orbit torques (SOTs) in bilayer Ta/TbxCo100-x ferrimagnetic alloy films with varying Tb concentration. The coercivity increases dramatically with increasing TbxCo100-x thickness and is enhanced by the presence of a Ta underlayer. The Ta underlayer simultaneously serves as a source of SOT due to the spin Hall effect, which we show provides an efficient means to manipulate the magnetization in bulk PMA materials. It is further shown that the sign of the anomalous Hall voltage is different for rare-earth (RE) and transition-metal (TM) dominated alloy compositions, whereas the sign of the SOT effective field remains the same, suggesting that the former is related to the TM sublattice magnetization whereas the latter is related to the net magnetization. Our results suggest that Ta/TbxCo100-x is a potential candidate for spin-orbitronic device applications and give insight into spin transport and SOTs in rare-earth/transition-metal alloys.

Parameters of ethinylestradiol-induced testicular toxicity were evaluated with organ weight determination, histopathological examination and quantitative morphometry. Male Sprague-Dawley rats were administered ethinylestradiol orally at 3 or 10 mg/kg/day for 2 weeks and 3 mg/kg/day for 4 weeks. Final body weights in all treated groups were lower than in the respective control group. Decreased absolute and/or relative organ weights of epididymides, prostate, seminal vesicles and testes were observed in all treated groups. In the testes, apoptosis of round spermatids, atrophy of seminiferous tubules, exfoliation of spermatids or spermatocytes, and vacuolar degeneration of Sertoli cells were only observed with 4 weeks treatment. Apoptosis of pachytene spermatocytes and atrophy of Leydig cells were also more marked in the 4 week treated group than after 2 weeks. Therefore, degenerative histopathological changes in testes were more remarkable after 4 weeks treatment than in the 2 weeks treatment groups. However, retention of spermatids was less after 4 weeks treatment and the TUNEL index, calculated as the number of TUNEL-positive spermatocytes or spermatids, was increased in all treated groups. These results suggest that ethinylestradiol-induced testicular toxicity can be detected in male rats administered the compound for 2 weeks and that the TUNEL method for in situ detection of apoptosis is effective for evaluation of testicular toxicity.

Energy barriers in magnetization reversal dynamics have long been of interest because the barrier height determines the thermal stability of devices as well as the threshold force triggering their dynamics. Especially in memory and logic applications, there is a dilemma between the thermal stability of bit data and the operation power of devices, because larger energy barriers for higher thermal stability inevitably lead to larger magnetic fields (or currents) for operation. Here we show that this is not the case for current-induced magnetic domain-wall motion induced by adiabatic spin-transfer torque. By quantifying domain-wall depinning energy barriers by magnetic field and current, we find that there exist two different pinning barriers, extrinsic and intrinsic energy barriers, which govern the thermal stability and threshold current, respectively. This unique two-barrier system allows low-power operation with high thermal stability, which is impossible in conventional single-barrier systems.

The renin-angiotensin-aldosterone system (RAAS) plays pivotal roles in the pathogenesis of chronic kidney disease (CKD) progression. Aliskiren, a direct renin inhibitor, inhibits the rate-limiting step of the RAAS without any alternative pathway. It is proven to reduce albuminuria in CKD patients treated with angiotensin blockade. However, there are few reports which evaluate the advantage of aliskiren as the first-line drug against CKD progression in RAAS-activated hypertensive patients.Tsukuba hypertensive mice (THM), double transgenic mice carrying both the human renin and human angiotensinogen genes, were fed a high-salt diet and treated with hydraladine, ramipril and aliskiren for 10 weeks. Blood pressure and urinary albumin excretion were measured every 2 weeks during the experimental period. We evaluated renal histological changes and gene expression. Plasma angiotensin concentration was measured to evaluate the RAAS inhibitory effect.High-salt-loaded THM showed severe hypertension and renal injury. All antihypertensive drugs suppressed blood pressure and prevented renal disease progression. RAAS blockade showed a higher renoprotective effect than hydraladine despite an equivalent blood pressure lowering effect. Aliskiren exhibited even stronger renoprotection than ramipril. Plasma angiotensin concentration was increased in THM fed both normal salt and high salt. Hydraladine did not alter the plasma angiotensin concentration. Ramipril significantly decreased angiotensin II concentration. Aliskiren treatment almost completely suppressed angiotensin I and resulted in lower angiotensin II concentration than ramipril treatment.Aliskiren prevents renal disease progression by suppressing both angiotensin I and II in RAAS-activated pathology. Our data suggest the application of a renin inhibitor for preventing kidney disease progression in CKD patients.

The mineralocorticoid receptor (MR) is a member of the steroid-responsive nuclear receptor family. Currently, in addition to its classical role in fluid homeostasis, attention has been focused on the pro-proteinuric and pro-inflammatory effects of MR in renal and cardiovascular diseases. Since proteinuria has been shown to be an important factor in the prognosis of patients with chronic kidney disease (CKD) [according to the newest Japanese Society of Nephrology and Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for the treatment of CKD], it is worth discussing the role of MR in the progression of proteinuric CKD and the possible association with podocyte injury. Rac1, a Rho-GTPase family protein, is known for its role in the regulation of the cytoskeleton. We discovered the role of active Rac1 in amplifying MR activation in one of our studies and then continued to study how the Rac1−MR pathway contributes to the progression of kidney diseases. We then discovered the harmful effects of the activation of the Rac1−MR pathway in response to salt loading in the kidney for proteinuric kidney diseases of various animal models with salt-sensitive hypertension, such as Dahl salt-sensitive rats, RhoGDIα-knockout mice, angiotensin II-overproducing mice, and aldosterone-infused rats. In this review, we have introduced recent findings that suggest the contribution of MR activation to kidney diseases and the role of the Rac1−MR pathway in kidney injury associated with salt-sensitive hypertension and proteinuria. Thus, the Rac1−MR pathway is a potential therapeutic target in patients with proteinuric CKD.

We report the effect of the rare earth metal Gd on current-induced spin-orbit torques (SOTs) in perpendicularly magnetized Pt/Co/Gd heterostructures, characterized using harmonic measurements and spin-torque ferromagnetic resonance (ST-FMR). By varying the Gd metal layer thickness from 0 nm to 8 nm, harmonic measurements reveal a significant enhancement of the effective fields generated from the Slonczewski-like and field-like torques. ST-FMR measurements confirm an enhanced effective spin Hall angle and show a corresponding increase in the magnetic damping constant with increasing Gd thickness. These results suggest that Gd plays an active role in generating SOTs in these heterostructures. Our finding may lead to spin-orbitronics device application such as non-volatile magnetic random access memory, based on rare earth metals.

A 62-year-old man was hospitalized for acute rheumatic fever. He had previously suffered from rheumatic fever at 15 years of age. The rheumatic fever was complicated by carditis, which caused valve disease that required surgical treatment. The incidence of rheumatic fever has decreased in most developed countries with improvements in sanitary conditions. The low incidence of this disease makes a timely and accurate diagnosis difficult. Due to the fact that both the first occurrence and recurrence of acute rheumatic fever can occur in the elderly and adults, this potential disease should not be overlooked when making a differential diagnosis.

A Rho family GTPase, Rac1, has emerged as an important molecule involved in cardiac remodeling. Some studies demonstrated the requirement of Rac1 in angiotensin II-induced cardiac hypertrophy and diabetic cardiomyopathy in association with generation of reactive oxygen species (ROS). However its role in pressure overload-induced cardiac remodeling is still unclear. On the other hand, we previously reported that Rac1 can activate mineralocorticoid receptor (MR) in cultured cardiomyocytes. Here we demonstrate the requirement of Rac1 in pressure-overload cardiac remodeling, and putative role of MR as a downstream pathway of Rac1. First, we performed sham or transverse aortic constriction (TAC) surgery in C57BL/6 mice, and examined the effect of Rac1 inhibitor ( NSC23766 ) and MR blocker (eplerenone). After 7 weeks, TAC caused severe hypertrophy and dysfunction of left ventricle with significant increase in active form of Rac1. In addition, the amount of MR protein in nuclear fraction, and the expression of some target genes of MR (including serpina3n and serpine-1) in left ventricle were also increased by TAC. NSC23766 significantly reduced the TAC-induced activation of Rac1, and both NSC23766 and eplerenone attenuated cardiac hypertrophy and dysfunction, along with inhibition of MR signaling. Furthermore, TAC significantly increased ROS production in left ventricle, which was also attenuated by both of the pharmacological interventions. We next generated cardiomyocyte-specific heterozygous Rac1-deficient mice (Rac1 CM +/− ) and littermate wild-type mice (WT), and performed Sham or TAC surgery. The TAC-induced hypertrophy and dysfunction of left ventricle were significantly suppressed in Rac1 CM +/− compared with WT (heart/body weight ratio: 6.4 ± 0.86 vs 10.8 ± 0.81 mg/g, ejection fraction 54.1 ± 6.5 vs 33.3 ± 7.3 %, p < 0.05), with inhibition of Rac1 activation. Nuclear translocation of MR protein and increases in expression of the target genes of MR were also significantly attenuated in Rac1 CM +/− compared with WT. These results indicate that Rac1 plays an essential role in the maladaptive cardiac hypertrophy induced by pressure overload, and that MR is an important downstream pathway of Rac1 in heart.

High-speed capability and excellent reliability of a magnetic domain wall (DW) motion device required for embedded memory and logic-in-memory applications were achieved by optimizing the film stack structure of Co/Ni wire. Low-current with high-speed writing, high heat resistance, low error rate, wide operation range for temperature and magnetic field, high retention, and high endurance features were confirmed.

Experiments with hyperaldosteronemic animals suggest that, despite lowering plasma aldosterone, salt worsens renal injury by paradoxical activation of the mineralocorticoid receptor (MR). Salt and aldosterone synergistically contribute to renal impairment through Rac1-mediated activation of the MR, but whether angiotensin II also promotes renal injury through this mechanism is unknown. Here, we placed angiotensin II-overproducing double transgenic Tsukuba hypertensive mice on a low- or high-salt intake for 6 weeks and treated some animals with adrenalectomy, the MR antagonist eplerenone, the Rac inhibitor EHT1864, or hydralazine. High-salt intake, but not low-salt intake, led to hypertension and prominent kidney injury. Adrenalectomy prevented angiotensin II/salt-induced nephropathy in mice receiving high-salt intake, which was recapitulated by aldosterone supplementation, suggesting the involvement of aldosterone/MR signaling. Plasma aldosterone levels, however, were lower in high- than low-salt conditions. Instead, angiotensin II/salt-evoked MR activation associated with Rac1 activation and was not dependent on plasma aldosterone level. Both EHT1864 and eplerenone repressed the augmented MR signaling and mitigated kidney injury with partial but significant reduction in BP with high-salt intake. Hydralazine similarly reduced BP, but it neither suppressed the Rac1-MR pathway nor ameliorated the nephropathy. Taken together, these results show that angiotensin II and salt accelerate kidney injury through Rac1-mediated MR activation. Rac inhibition may be a promising strategy for the treatment of CKD.

The spin transfer torque is essential for electrical magnetization switching. When a magnetic domain wall is driven by an electric current through an adiabatic spin torque, the theory predicts a threshold current even for a perfect wire without any extrinsic pinning. The experimental confirmation of this 'intrinsic pinning', however, has long been missing. Here, we give evidence that this intrinsic pinning determines the threshold, and thus that the adiabatic spin torque dominates the domain wall motion in a perpendicularly magnetized Co/Ni nanowire. The intrinsic nature manifests itself both in the field-independent threshold current and in the presence of its minimum on tuning the wire width. The demonstrated domain wall motion purely due to the adiabatic spin torque will serve to achieve robust operation and low energy consumption in spintronic devices.

Heparin is a polysulfated glycosaminoglycan that has been shown to have antiproliferative and apoptotic effects in addition to its anticoagulant effects.The present work investigated the effects of unfractioned heparin (UFH) on cell growth and apoptosis in four oral squamous cell carcinoma (SCC) cell lines and the mechanism(s) underlying its actions using MTT assay, Annexin-V-FITC and Western blotting.Treatment with UFH resulted in significant reduction in cell viability and increase in apoptosis in three of the four tested cell lines. Further, such treatment resulted in a significant decrease in phosphorylated AKt, and consequently led to activation of the mitochondrial pathway in heparin-sensitive cells. Moreover, pretreatment with UFH significantly increased the apoptosis induced by cisplatin.These findings indicate that heparin induces apoptosis through suppression of AKt, and suggest a potential utility of heparin for development of less toxic chemotherapy in treatment of oral SCC.

Deep tissue injury (DTI) is difficult to detect in the early phase. Creatine phosphokinase (CPK) as a muscle enzyme could represent a promising indicator of DTI. However, serum CPK levels reflect the systemic condition rather than the local wound environment. Wound exudates can be indicative of the local wound environment. This study aimed to investigate the usefulness of CPK levels in wound exudates as an indicator of DTI. Rats were divided into control, 6 hours 10-kg and 6 hours 20-kg loading groups. Serum samples were obtained before wounding, and at 8 and 12 hours, and 1, 2 and 3 days after wounding, while exudate samples were obtained on days 2 and 3. Serum CPK levels were markedly increased in the 10-kg and 20-kg groups at 8 and 12 hours after loading compared with the baseline value and control group, but decreased to the normal level on day 1. In both loading groups, exudate CPK levels were high on day 2 and decreased on day 3. Muscle necrosis was more severe in the 20-kg group than in the 10-kg group by histological examination. This is the first study to indicate the potential of CPK in wound exudates as an indicator of DTI.

Tritium labelled gaseous hydrogen was used to clarify the role of gaseous hydrogen in coal liquefaction. Datong coal was hydrogenated under 5.9 MPa (initial pressure) of tritium-labelled hydrogen in tetralin at 400°C in the presence or absence of NiMoAl2O3 catalyst. The catalyst accelerates both the hydrogen transfer from gaseous hydrogen and the hydrocracking of coal products. At the initial stage of the liquefaction without catalyst, the amount of hydrogen transferred from tetralin to coal was twice as large as that from gaseous hydrogen. In the presence of the catalyst, the hydrogen exchange between coal and molecular hydrogen was very rapid even at the initial stage of the liquefaction. In the absence of the catalyst, hydrogen transfer from gas phase to coal remarkably increased for rise from 300 to 350°C in temperature while that from solvent to coal suddenly increased at 400°C.

We have investigated the temperature dependence of current-induced magnetic domain wall (DW) motion in a Co/Ni nanowire, where the spin Hall torque is responsible for the DW motion. The threshold current density (Jth) for DW motion is found to be dependent on the temperature T and the depinning magnetic field Hdep, which is different from the symmetric Co/Ni system where Jth is insensitive to T and Hdep. This result indicates that an extrinsic pinning governs the DW motion when it is driven by the spin Hall torque. Our work therefore suggests that reducing the extrinsic pinning is a key for achieving a low-power-consumption device.

Objective: TheWFS1gene encodes an endoplasmic reticulum (ER) membrane-embedded protein. HomozygousWFS1gene mutations cause Wolfram syndrome, characterized by insulin-deficient diabetes mellitus and optic atropy. Pancreatic β-cells are selectively lost from the patient’s islets. ER localization suggests that WFS1 protein has physiological functions in membrane trafficking, secretion, processing and/or regulation of ER calcium homeostasis. Disturbances or overloading of these functions induces ER stress responses, including apoptosis. We speculated that WFS1 protein might be involved in these ER stress responses.Design and methods: Islet expression of the Wfs1 protein was analyzed immunohistochemically. Induction of Wfs1 upon ER stress was examined by Northern and Western blot analyses using three different models: human skin fibroblasts, mouse pancreatic β-cell-derived MIN6 cells, and Akita mouse-derivedIns296Y/Yinsulinoma cells. The humanWFS1gene promoter-luciferase reporter analysis was also conducted.Result: Islet β-cells were the major site ofWfs1expression. This expression was also found in δ-cells, but not in α-cells.WFS1expression was transcriptionally up-regulated by ER stress-inducing chemical insults. Treatment of fibroblasts and MIN6 cells with thapsigargin or tunicamycin increasedWFS1mRNA. WFS1 protein also increased in response to thapsigargin treatment in these cells.WFS1gene expression was also increased inIns296Y/Yinsulinoma cells. In these cells, ER stress was intrinsically induced by mutant insulin expression. TheWFS1gene promoter-luciferase reporter system revealed that the humanWFS1promoter was activated by chemically induced ER stress in MIN6 cells, and that the promoter was more active inIns296Y/Ycells thanIns2wild/wildcells.Conclusion:Wfs1expression, which is localized to β- and δ-cells in pancreatic islets, increases in response to ER stress, suggesting a functional link betweenWfs1and ER stress.

We have studied the nucleation and growth processes of silicon nanowires (SiNWs) by means of transmission electron microscopy and scanning tunneling microscopy. SiNWs are grown on hydrogen-terminated Si surface via the VLS (Vapor-Liquid-Solid) mechanism using silane (SiH4) as source gas. We have classified the growth process of SiNWs into three stages: the formation of nanocatalysts on a substrate, the nucleation of SiNWs in nanocatalysts, followed by the growth of SiNWs. We have shown that the structures of SiNWs are varied in several ways in each stage, and accordingly the structural properties of grown SiNWs can be modified to great extents. At the present moment, the phenomena at the each stage are not fully controlled, and this prevents us utilizing silicon nanowires more effectively.

Glutamate dehydrogenase (GDH) catalyzes reversible oxidative deamination of l-glutamate to α-ketoglutarate. Enzyme activity is regulated by several allosteric effectors. Recognition of a new form of hyperinsulinemic hypoglycemia, hyperinsulinism/hyperammonemia (HI/HA) syndrome, which is caused by gain-of-function mutations in GDH, highlighted the importance of GDH in glucose homeostasis. GDH266C is a constitutively activated mutant enzyme we identified in a patient with HI/HA syndrome. By overexpressing GDH266C in MIN6 mouse insulinoma cells, we previously demonstrated unregulated elevation of GDH activity to render the cells responsive to glutamine in insulin secretion. Interestingly, at low glucose concentrations, basal insulin secretion was exaggerated in such cells. Herein, to clarify the role of GDH in the regulation of insulin secretion, we studied cellular glutamate metabolism using MIN6 cells overexpressing GDH266C (MIN6-GDH266C). Glutamine-stimulated insulin secretion was associated with increased glutamine oxidation and decreased intracellular glutamate content. Similarly, at 5 mmol/l glucose without glutamine, glutamine oxidation also increased, and glutamate content decreased with exaggerated insulin secretion. Glucose oxidation was not altered. Insulin secretion profiles from GDH266C-overexpressing isolated rat pancreatic islets were similar to those from MIN6-GDH266C, suggesting observation in MIN6 cells to be relevant in native β-cells. These results demonstrate that, upon activation, GDH oxidizes glutamate to α-ketoglutarate, thereby stimulating insulin secretion by providing the TCA cycle with a substrate. No evidence was obtained supporting the hypothesis that activated GDH produced glutamate, a recently proposed second messenger of insulin secretion, by the reverse reaction, to stimulate insulin secretion.

The behavior of a three-terminal domain wall (DW) device with a perpendicularly magnetized CoFeB free layer and underlying hard magnets was investigated. In a Ta/CoFeB/MgO free layer without hard magnets, a current-induced DW motion in the direction of electron flow was observed. In a device having a hard magnet under each end of the free layer, we found that a DW nucleated by injecting current played an important role in the switching of magnetization. We concluded that the switching of magnetization in our device is due to the displacement in the direction of electron flow of the DW created by current. After deriving the principle of operation through experiments, we describe a way to reduce the current required for writing by increasing the thickness of the hard magnets.

We report a systematic study of the DW motion in perpendicularly magnetized Co/Ni nanowires having different thicknesses with structure inversion asymmetry. The transition from bulk to interfacial effects is confirmed as a change in the DW motion direction at a reduced layer thickness. The bias field dependence reveals that the adiabatic spin transfer torque (STT) dominates the DW motion in the thick regime, whereas the interfacial torque originating from the spin Hall effect (SHE) is responsible for the DW motion with a fixed DW chirality induced by the Dzyaloshinskii–Moriya interaction (DMI) in the thin regime.

Prompted by the recent findings that a tryptophan to arginine (Trp64Arg) mutation in the beta3-adrenergic receptor gene was associated with an earlier onset of non-insulin-dependent diabetes mellitus (NIDDM) in Pima Indians, with abdominal obesity and insulin resistance in Finns, and with an increased capacity to gain weight in French whites, we studied the prevalence of this mutation in 231 diabetic and 95 nondiabetic Japanese subjects and assessed its contribution to the development of obesity and NIDDM. The allelic frequencies of the mutation were 0.18 in diabetic and 0.23 in nondiabetic subjects, showing no significant difference between the two groups (P = .067). In nondiabetic subjects, body mass index (BMI) did not differ between those with and without the mutation (22.2 +/- 3.5 v 21.4 +/- 3.2 kg/m2, P = .252). In NIDDM subjects, BMI at the time of study and maximal BMI before the start of treatment did not differ between those with and without the mutation (22.8 +/- 2.6 v 23.2 +/- 3.7 kg/m2, P = .678, and 24.7 +/- 2.6 v 24.9 +/- 3.1 kg/m2, P = .277). Homozygotes for the mutation did not have trends to have increased BMI in either diabetic or nondiabetic subjects. The age at diagnosis of NIDDM also did not differ between the two groups (48.8 +/- 9.9 v 47.8 +/- 12.5 years, P = .796). Fasting serum cholesterol and triglyceride levels and systolic and diastolic blood pressure before the start of treatment did not differ between NIDDM subjects with and without the mutation. In conclusion, although the Trp64Arg mutation is not uncommon in Japanese, it does not appear to be associated with obesity, NIDDM, age at diagnosis of NIDDM, or dyslipidemia. Our results suggest that the mutation has minor effects, if any, on the development of obesity and NIDDM in Japanese.

We have investigated the temperature dependence of the current-induced magnetic domain wall (DW) motion in a perpendicularly magnetized Co/Ni nanowire at various temperatures and with various applied currents. The carrier spin polarization was estimated from the measured domain wall velocity. We found that it decreased more with increasing temperature from 100 K to 530 K than the saturation magnetization did.

Magnetic domain wall (DW) motion induced by currents in a perpendicularly magnetized Co/Ni nanowire has been investigated both at room temperature and low temperature. The threshold current density was almost independent of temperature, although the external magnetic field to depin a DW was doubled at low temperature. The result is consistent with the theory based on the adiabatic spin transfer model.

We have investigated the velocity of magnetic domain wall (DW) motion induced by electric currents in a Co/Ni nanowire with a perpendicular magnetic anisotropy. The DW velocity increased as current density increased and the maximum velocity of 60 m/s was observed. Furthermore, the DW velocity was found to be almost independent of external perpendicular magnetic fields in the range of −50 to +50 Oe. The mechanism of the observed field insensitivity of the current induced DW motion is also discussed.

The authors have investigated magnetic domain wall motion induced by electric currents in ferromagnetic nano-wires made of Co/Ni multilayers. The thicknesses of Co and Ni layers were changed, whereas the numbers of layer stacks of Co and Ni were the same in all samples. The sample with thinner total Co/Ni thickness showed the lower threshold current density for the domain wall motion as an overall trend, which is qualitatively in agreement with the expectation by the theory based on the adiabatic spin-transfer model. The lowest threshold current density was 2.9×1011 A/m2 obtained in the sample with the total Co/Ni thickness of 3.4 nm and the wire width of 110 nm.

All-electrical control and local detection of multiple magnetic domain walls in perpendicularly magnetized Co/Ni nano-wires were demonstrated. A series of domain walls was reproducibly shifted in the same direction by the current, keeping the distance between the walls almost the same. Furthermore, the walls can be shifted back and forth depending on the direction of the pulsed currents.