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the paper summarizes both analytical and numerical considerations as well as experimental data of low voltage (50 V) trench MOSFET in unclamped (UIS) and self-clamped (SCIS) inductive switching applications. The herein presented data summarize failure mechanisms that ultimately limit UIS / SCIS rating of a device once all other design factors are exploited.

Electrostatic discharge (ESD) robustness improvement of ultra-high-voltage devices is a challenging task. This paper presents an ESD robustness enhancement study of an 800 V junction field-effect transistor (JFET) including a silicon-controlled rectifier (SCR) structure. During a human body model (HBM) event, the fabricated SCR-JFET showed a deep voltage snapback and an unexpectedly high current peak, resulting in an ESD failure due to current filamentation. 3-D TCAD analysis is effectively utilized for ESD enhancement study. First, 3-D HBM simulation reproduces the current filamentation phenomenon and the observed ESD failure. Then, a drain modified SCR-JFET, which includes a p+ ballast region, is studied. TCAD simulations demonstrate ESD robustness improvement with the ballast device and make clear its performance enhancement mechanism. Based on the TCAD study results, the ballast device is fabricated. Photo-emission microscope measurement results clearly show an alleviation of the current filamentation. As a result of HBM tests, we successfully improve HBM robustness from 1.93 kV to 2.63 kV with the ballast structure.

The cardiac sarco/endoplasmic reticulum Ca2+-dependent ATPase 2a (SERCA2a) plays a central role in Ca2+ handling within cardiomyocytes and is negatively regulated by phospholamban (PLN), a sarcoplasmic reticulum (SR) membrane protein. The activation of SERCA2a, which has been reported to improve cardiac dysfunction in heart failure, is a potential therapeutic approach for heart failure. Therefore, we developed a novel small molecule, compound A and characterized it both in vitro and in vivo. Compound A activated the Ca2+-dependent ATPase activity of cardiac SR vesicles but not that of skeletal muscle SR vesicles that lack PLN. The surface plasmon resonance assay revealed a direct interaction between compound A and PLN, suggesting that the binding of compound A to PLN attenuates its inhibition of SERCA2a, resulting in SERCA2a activation. This was substantiated by inhibition of the compound A-mediated increase in Ca2+ levels within the SR of HL-1 cells by thapsigargin, a SERCA inhibitor. Compound A also increased the Ca2+ transients and contraction and relaxation of isolated adult rat cardiomyocytes. In isolated perfused rat hearts, the compound A enhanced systolic and diastolic functions. Further, an infusion of compound A (30mg/kg, i.v. bolus followed by 2mg/kg/min, i.v. infusion) significantly enhanced the diastolic function in anesthetized normal rats. These results indicate that compound A is a novel SERCA2a activator, which attenuates PLN inhibition and enhances the systolic and diastolic functions of the heart in vitro and in vivo. Therefore, compound A might be a novel therapeutic lead for heart failure.

ESD robustness enhancement study of an 800V JFET including the SCR structure is conducted. A p+ ballast structure is introduced in the device and ESD robustness improvement is demonstrated with 3D TCAD simulations. Based on the TCAD study results, a ballasted device is fabricated and improved ESD performance is successfully obtained.

Our study measured circulating microRNA (miRNA) levels in the plasma of calsequestrin (CSQ)-tg mouse, a severe heart failure model, and evaluated whether treatment with angiotensin II type 1 receptor blocker, azilsartan medoxomil (AZL-M) influenced their levels using miRNA array analysis. MiR-146a, miR-149, miR-150, and miR-342-3p were reproducibly reduced in the plasma of CSQ-tg mice. Among them, miR-146a and miR-342-3p were significantly restored by AZL-M, which were associated with improvement of survival rate and reduction of congestion. These results suggest that miRNA, especially miR-146a and miR-342-3p, could be used as potential biomarkers for evaluating the efficacy of anti-heart failure drugs.

The antihypertensive and cardiovascular properties of a new potassium channel opener, TCV-295, were studied in rats and dogs. In conscious, spontaneously hypertensive rats (SHR), TCV-295 (0.03-1 mg/kg orally, p.o.) reduced blood pressure (BP) dose dependently with slow onset of action. The antihypertensive effects induced by TCV-295 lasted much longer than those of levcromakalim and nisoldipine, and the reflex tachycardia it evoked was less marked than that evoked by these drugs as compared at doses showing similar maximal hypotensive effects. Glibenclamide (30 mg/kg intravenously, i.v.) inhibited the TCV-295-induced BP decrease in anesthetized rats. In a 4-week chronic dosing study in SHR, TCV-295 (0.3 mg/kg/day p.o.) produced neither potentiation nor tolerance to its antihypertensive action and no rebound hypertension occurred when drug treatment was discontinued. In anesthetized normotensive dogs, TCV-295 (4.5 micrograms/kg/min i.v.) induced BP reductions accompanied by reductions in systemic vascular resistance. TCV-295 also reduced resistances of the coronary, vertebral, mesenteric, and renal vascular beds, and the most marked effect was observed in the coronary vasculature. Myocardial O2 consumption was reduced by TCV-295, possibly owing to afterload decrease. These results suggest that TCV-295 has a desirable profile for an antihypertensive agent.

The pattern replication characteristics in X-ray proximity lithography were investigated. Replication accuracy was evaluated as a function of proximity gap, pattern size and pattern density. It is found that 0.15μm lines and spaces can be delineated in the wide proximity gap range of 40 μm and that 0.2-μm-level pattern replication minimally depends on the pattern density. The 0.25-μm-level critical dimension (CD) of the resist pattern was measured over a 6" wafer and the CD variation (3σ) was 0.0134μm or ±5.4% for the linewidth. The resolution limit of X-ray proximity printing is discussed. Calculation results demonstrate that X-ray lithography has a high resolution of less than 0.1μm. Resolution of 0.1μm is confirmed by experimental results.

The replicated pattern distortion for feature sizes down to 0.15 μm, characterized by pattern linearity, pattern density dependence, and corner rounding, is investigated in synchrotron radiation (SR) lithography. In the investigation, a highly accurate X-ray mask delineated by a focused ion beam, a chemically amplified resist, and a Fresnel diffraction model simulator are used. At a 15 μm mask-to-wafer gap, no pattern proximity effect is observed. The corner rounding radius due to Fresnel diffraction is approximately 0.04 μm.

The replicated pattern distortion for feature sizes down to 0.15 μm, characterized by pattern linearity, pattern density dependence, and corner rounding, is investigated in synchrotron radiation (SR) lithography, using a highly accurate x-ray mask delineated by a focused ion beam. At a 15 μm mask-to-wafer gap, no proximity effect is observed. The corner rounding due to Fresnel diffraction is approximately 0.04 μm.

The role of endogenous endothelin-1 (ET-1) in myocardial infarction was investigated in a rabbit ischemia-reperfusion model and in rabbit Langendorff hearts. AwETN40, a monoclonal antibody against ET-1, at 10 mg/kg i.v. inhibited hypertension and hypotension induced by ET-1 (0.3 nmol/kg i.v.): about 70-100% inhibition lasted for 24 h. In a coronary occlusion (30 min)-reperfusion (24 h) model, AwETN40 (10 mg/kg i.v.) reduced the infarct size from 60.9 +/- 4.6% (infarct region/ischemic region in weight, IgG1 kappa control; n = 5) to 37.1 +/- 5.2% (n = 5, p0.05). Plasma ET-1 levels were increased significantly by coronary occlusion-reperfusion and returned to control level 24 h after reperfusion. Effects of ET-1 on the coronary vessels and cardiac contractility were studied in the Langendorff heart. ET-1 increased the perfusion pressure from concentrations as low as 10 pM, whereas the developed left ventricular pressure was not altered. These results suggest that ET-1 decreases oxygen supply to the cardiac muscles by constricting coronary vessels and that this, in turn, worsens the ischemic condition of the heart to extend the infarct size.

In the course of our research into new types of non-acylguanidine Na(+)/H(+) exchanger (NHE) inhibitors, we designed and synthesized aryl-fused tetrahydropyranylidene and cyclohexylidene aminoguanidine derivatives I (X = O, CH(2)), which were tested for their inhibitory effects on rat platelet NHEs. After optimization, we found that the S isomer of tetrahydroquinoline derivatives that possess a methyl group in the 4-position and a halogen or methyl group in the o-position of Ar(2) exhibited high inhibitory activity. In these compounds, (5E,7S)-[[7-(5-fluoro-2-methylphenyl)-4-methyl-7,8-dihydro-5(6H)-quinolinylidene]amino]guanidine dimethanesulfonate (18, T-162559) was found to be a potent inhibitor of both rat and human platelet NHEs, with IC(50) values of 14 and 13 nM, respectively. Furthermore, in a rat myocardial infarction model in vivo (1 h ischemia-24 h reperfusion), 18 (0.1 mg/kg, intravenously administered 5 min or 2 h before coronary occlusion) showed significant activity (33% or 23% inhibition, respectively). These results suggested that 18 may exhibit a potent and long-lasting protective activity against cardiac injuries induced by ischemia-reperfusion.

1. The aims of the present study were to characterize the pharmacological profile of a new endothelin (ET) receptor antagonist, TAK-044 and to consider whether it limits the extension of myocardial infarct size in rats. 2. Binding of [125I]-ET-1 to ET receptors on rabbit ventricular and cerebellar membrane fractions was inhibited by TAK-044 with IC50 values of 3.8 nM and 130 nM, respectively. 3. It inhibited ET-1, ET-2 and ET-3-induced vasoconstriction of porcine isolated coronary arteries in a competitive (ET-1, ET-2) and a non-competitive (ET-3) manner. 4. In the rat in vivo, the ET-1-induced blood pressure changes including transient hypotension followed by sustained hypertension, were inhibited by TAK-044 (0.1-10 mg kg-1, i.v.) in a dose-dependent manner. 5. Acute myocardial infarction induced by 1 h coronary occlusion followed by 24 h reperfusion in rats caused an infarct size of 60 +/- 2% (n = 12) of the area-at-risk by weight. 6. Intravenous injection of TAK-044 10 min before coronary occlusion reduced the infarct size in a dose-dependent manner: 32% and 54% reductions at 1 and 3 mg kg-1, respectively. 7. TAK-044 administered 10 min before or 1 h after reperfusion (1 mg kg-1, i.v.) showed similar inhibitory effects: 34% and 23% reductions, respectively. 8. We conclude that TAK-044 is an ETA/ETB receptor antagonist which shows strong inhibitory effects on the extension of myocardial infarct size after coronary artery occlusion-reperfusion in rats.

The effects of TAK-044 on the extension of ischemia/reperfusion-induced myocardial infarction were studied in rats. Acute myocardial infarction was induced by occlusion of the left coronary artery for 1 h followed by reperfusion for 24 h. Infarct size and the area at risk were determined histochemically. Infarct size as a percentage of the area at risk (IS) was significantly reduced in a dose-dependent manner by TAK-044 administered 30 min before reperfusion (0.3-3.0 mg/kg, i.v.). Size-limiting effects similar to those in rats were also obtained in rabbits and dogs. In addition, TAK-044 administered 3 h after reperfusion also reduced the IS significantly. Preconditioning (5 min of LAD occlusion preceding 1 h of coronary occlusion) inhibited the extension of the IS. These effects of preconditioning and TAK-044 were inhibited by glibenclamide (0.1 mg/kg, i.v.; an inhibitor of the ATP-sensitive K channel) but not by DPCPX (1 mg/kg, i.v.; an adenosine A1 receptor antagonist). These results indicate that endogenous endothelin plays an important role in the extension of myocardial infarction and that the cardioprotective effects of TAK-044 can be partially explained by a mechanism similar to that of preconditioning in rats.

Replicated pattern accuracy was investigated in synchrotron radiation (SR) lithography, using a chemically amplified (CA) negative-type resist and a highly accurate x-ray mask delineated by focused ion beams (FIB). The size of the hole resist pattern which is arranged in a lattice is affected by the proximity gap and the pattern pitch, but that of the dot resist pattern is hardly dependent on these variables. The dot resist pattern, which was replicated with the 0.25- micrometers -square hole mask pattern, became circular with a proximity gap of over 20 micrometers . In order to obtain highly accurate pattern shape as well as pattern size, the proximity gap should be less than 20 micrometers . The resist pattern size and shape depend on the exposure dose. This was confirmed through the simulation of Fresnel diffraction. The resist pattern was influenced considerably by the post-exposure baking (PEB) conditions, temperature and time. The PEB condition dependence of a replicated pattern was investigated. It is effective to extend the PEB time to improve the sensitivity without deforming the pattern shape.

A highly accurate focused ion beam (FIB) lithography and its application to the x-ray mask fabrication are discussed. The pattern delineation accuracy in FIB lithography was investigated by drawing various two-dimensional (2-D) test patterns. We could obtain 0.15 ii m feature resist patterns on the heavy-metal layers of the x-ray mask substrate.FIB lithography suffers little proximity effect and thus various 2-D test patterns wereobtained with small distortion. The FIB drawn patterns were precisely transferred into the W absorber layer by the time modulated etching technique. X-ray masks used for the evaluation of the pattern replication accuracy in synchrotron radiation lithography were successfully fabricated. 1. INTRODUCTIONA highly accurate pattern delineation technique must be developed for thefabrication of x-ray masks. Electron beam (EB) ' 2 or focused ion beam (FIB)lithography is expected to be promising for this purpose. One of the problems in EBlithography is the proximity effect due to the backscattering from the substrate. This

Ion bombardment enhanced etching using Br2 solution, previously applied to BiSrCaCuO films, has also been successfully applied to YBaCuO high-Tc superconducting thin films. It was found that the etch rate of the damaged region which was formed by the ion irradiation with a 200 keV Si++ focused ion beam was enhanced with the Br2 treatment. Bridge structures with a width of 0.3 µm were successfully fabricated with little degradation in Tc and Jc. The 0.3-µm bridge had a Jc value of about 106 A/cm2 at 15 K.

We present measurements of the characteristics of superconducting weak links prepared in epitaxial bilayer structures of Bi2Sr2CuO6 (BSCO)/Bi2Sr2CaCu2O8 (BSCCO) by focused ion beam lithography. The bilayer films with each layer thickness of 150 nm have been grown in situ by atomic-layer- by-layer molecular beam epitaxy and then patterned by implanting Si+ ions to destroy the superconductivity of the BSCCO top layer. We find S-N-S-like I-V characteristics for junctions in which the separation between the two superconducting BSCCO banks is about 300–400 nm. Shapiro steps in the nonhysteretic I-V curves appear in response to microwave radiation. We further find that the critical currents I c for all the weak links fit well with the form given by the Ginzburg-Landau theory, (1-T/T c’)3/2, where T c’ is estimated to be 26–33 K. We conclude that our junctions are not proximity-effect-type but microbridge-type S-S’-S weak links. This characteristics can be interpreted as the formation of filamentary superconducting paths in BSCO.

The parallel and perpendicular superconducting transport properties of epitaxial superlattices that consist of alternating Bi2Sr2CaCu2O8 (BSCCO) and Bi2Sr2CuO6 (BSCO) layers are reported. The interlayer coupling of Cu-O planes within a cell and in adjacent cells is studied by varying the superlattice sequence of different c-axis half-unit cells. All of our superlattices show superconductivity in the plane of the layer, including superlattices containing isolated Cu-O double planes of BSCCO in a semiconducting BSCO matrix. The overall shapes of superconducting transitions are found to be quite similar independent of the separation of the BSCCO layer. In the perpendicular direction, the transition width increases with the number of BSCO half-unit cells, but a residual resistivity appears for five half-unit cells. We conclude that superconductivity is essentially independent of the BSCCO and BSCO half-unit-cell sequence, and proximity-effect coupling along the c-axis direction cannot occur through the BSCO layer more than two unit cells (49 A) thick.

Focused ion beam (FIB) processes have been used for the patterning of Bi-Ca- Sr-Cu-O high-Tc superconducting thin films. Maskless sputter etching was carried out using Bi+ FIB to minimize the effect of impurity. V-shaped fine grooves with the 0.2 μm width near the surface of the film and the depth of 2 μm were obtained by the FIB processes. Bridge structures with the width of 0.7 μm were fabricated with little degradation in Tc. Planer S-N-S Josephson junctions were made by depositing Au into the grooves. Superconducting current flowing across the junctions was clearly observed.

Ion bombardment enhanced etching (IBEE) has been successfully applied to BiSrCaCuO high-T c superconducting thin films using nonaqueous Br2 solution. It was found that the etch rate of the damaged region which was formed by the ion irradiation with a 200 keV Si++ focused ion beam was enhanced with the Br2 treatment. The critical dose of the IBEE process was about 1×1014 ions/cm2, which is roughly the same as the dose which destroys the superconductivity of the film. Bridge structures with a width of 0.2 µm were successfully fabricated with little degradation in T c and J c. The 0.2-µm bridge had a J c value of more than 105 A/cm2 below 20 K.

We report resistive measurements on epitaxial superlattices consisting of alternating Bi2Sr2CaCu2O8 (2212) and Bi2Sr2CuO6 (2201) layers grown by atomic-layer-by-layer molecular beam epitaxy (MBE) using oxygen radical beams. The influence of interplane coupling between Cu-O planes was studied by varying the superlattice sequence of different c-axis half-unit cells. A single-half-unit-cell-thick 2212 layer was found to be superconducting in a 2201 matrix, independent of the conductivity and the thickness of neighboring 2201 layers. The fact that all of our superlattices showed superconductivity essentially equal to that of a 2212 single-phase film suggests that this cuprate is a two-dimensional superconductor due to its Cu-O double planes.

Ion bombardment enhanced etching (IBEE) has been first applied to Bi–Ca–Sr–Cu–O (BCSCO) high-T c superconducting thin films. It was found out that the damaged region formed by the ion irradiation with a 200 keV Si++ focused ion beam was selectively dissolved in 1 normal KOH solution. The IBEE process resolves 0.1 µm patterns in the BCSCO films. Other strong alkaline solutions such as NaOH solution were also effective for the selective etching of the BCSCO films, but acid solutions did not give an enhanced etch rate at the irradiated region. The KOH treatment gave no effect on T c of the BCSCO film. Bridge structures with the width of 1.5 µm were successfully fabricated with little degradation in T c.

Attempts were made to demonstrate release of vasoactive substances from the heart during coronary occlusion (for 60 min) and reperfusion (for 60 min), and to clarify the pathophysiological significance of them. Vasoactive substances were detected by superfusion of rabbit aortic and dog coronary arterial strips with great coronary venous blood. Plasma thromboxane (TX) B2 was radioimmunologically assayed. Gradually developing, sustained contraction of both vascular strips was noted during coronary occlusion and reperfusion, while a transient contraction in rabbit aortic and relaxation in dog coronary arterial strips were seen immediately after reperfusion. The TXB2 released into the great coronary venous blood significantly increased during occlusion and reperfusion. Indomethacin treatment of the dog abolished the sustained contraction of both vascular strips and TXB2 release. The transient contraction of rabbit aorta after reperfusion was inhibited by phenoxybenzamine. Reactive hyperaemia following a 60 min occlusion was significantly depressed, as compared with that following 30 s to 30 min occlusion, and the depression was alleviated by indomethacin and imidazole. These results suggest that catecholamine(s) and TXA2 are released during coronary occlusion and reperfusion, and that the latter might be responsible for the coronary circulatory failure during reperfusion of irreversibly damaged myocardium.

A new method for pattern reduction in the x‐ray region is proposed. In its principle was used the asymmetric Bragg reflection giving the different beamwidth in the reflected beam from the incident one. Light from an undulator line (BL‐2) at the Photon Factory was used to obtain highly spatially resolved replication in reasonably short exposure time. Performed was one‐dimensional demagnification of a pattern with a ratio of 1/4 in the following condition: Si 111 reflection was used where the offset angle α from the surface is 22° and the wavelength λ was 3.5 λ, which is available from the 7th harmonic of the undulator radiation. The submicron scale resist pattern was resolved.

The effect of 2-phenylaminoadenosine (CV-1808) against myocardial ischemia was studied in anesthetized dogs. During intravenous infusion of CV-1808 (0.25 and 0.5 microgram/kg/min for 10 min) the ST-segment elevation in the epicardial ECG induced by a 5-min occlusion of a coronary arterial branch was occasionally enhanced in association with cardiac acceleration. In a dose of 0.5 microgram/kg/min, the agent inhibited the ST elevation 30 and 60 min after administration. The same dose did not change myocardial blood flow in the ischemic area despite significant systemic hypotension. In hearts with continuous coronary occlusion, CV-1808 (0.3 and 1.0 microgram/kg, i.v. bolus) increased the retrograde blood flow from the ischemic area immediately after administration, suggesting a collateral vasodilating action. Nifedipine (0.5 and 2.5 microgram/kg/min, i.v. for 10 min) and nitroglycerin (0.5 and 5.0 microgram/kg/min, i.v. for 10 min) had no influence on the ischemic ST-segment elevation, while a significant inhibition was seen with propranolol (0.5 mg/kg, i.v.). A moderate hypotension was induced by CV-1808, nifedipine, and nitroglycerin, while a significant reduction in cardiac function was seen after dosing with propranolol.

Age-related changes in the myocardial energy metabolism were studied in spontaneously hypertensive (SHR) rats of 5–25 weeks of age. Systolic blood pressure increased rapidly during 5 to 10 weeks of age (developing phase) and attained a plateau level at 10 to 15 weeks (sustained phase). Even during the developing phase, the heart was hypertrophic, as assessed by an increase in the ratio of the ventricular weight to body weight. However, myocardial contents of glycolytic intermediates and high energy phosphate compounds and thus, the myocardial energy state (phosphorylation potential) in SHR rats did not differ from those in age-matched normotensive Wistar-Kyoto (WKY) rats. The lactate/pyruvate ratio was significantly lower in SHR rats. On the other hand, during the sustained phase, cardiac hypertrophy progressed only gradually, and myocardial contents of creatine phosphate and ATP were lower, while the lactate content was higher than in WKY rats. The lactate/pyruvate ratio was elevated, while phosphorylation potential was lowered. These findings suggest that the energy state is normal during the developing phase of hypertension despite the presence of cardiac hypertrophy and the increased pressure load, whereas the energy state is at a lower level during the sustained phase of hypertension.

The significance of pre-existing coronary collaterals for preservation of the myocardium during coronary occlusion and reperfusion was studied in anaesthetised open-chest dogs. The extent of myocardial ischaemic damage was assessed by the accumulation of calcium in the central zone of the ischaemic area and the size of myocardial infarct by the p-nitroblue tetrazolium staining method. Myocardial creatine kinase release was considered as an index reflecting both the extent of ischaemic myocardial damage and the size of the infarct. Reperfusion with the arterial blood of a main branch of the left coronary artery following the 60 min occlusion aggravated the ischaemic myocardial damage, as evidenced by exaggerated cardiac irregularity, myocardial calcium accumulation, and creatine kinase release. The myocardial calcium content and the logarithm of the creatine kinase release during reperfusion were linearly related to the infarct size. These parameters of myocardial damage were inversely related to the retrograde blood flow through the peripheral end of the occluded artery or the ratio of the retrograde-to-orthograde flow, indicating that the pre-existing collaterals influence preservation of the ischaemic myocardium. Thus, it is suggested that the collateral flow available during an ischaemic episode determines the viability of the myocardial cells during ischaemia, and in turn during reperfusion.

A novolac resin resist (ONPR-800) is exposed to 50 keV Ga focused ion beam (FIB) to create a fine line pattern by a self-development process. A dose dependence of the self-developed depth shows a rapid increase at some critical dose of about 3x10 -2 C/cm 2 . Furthermore, it is found out that the shape of the groove is considerably affected by the tensile force in the resist film. We can obtain grooves with the width of 40 nm and the aspect ratio of 40 by eliminating the stress. Gold line pattern of a 0.1 μm width is successfully produced by electroplating into the self-developed resist pattern.

Fresnel lenses were fabricated by the patterned proton-exchange technique in titanium-diffused lithium niobate waveguides. The large change in refractive index available with the proton exchange allows fabrication of a high-efficiency thin Fresnel lens. Lens characteristics of nearly diffraction-limited focus spot size and efficiency up to 70% were obtained. The use of the lens to construct an integrated-optic rf spectrum analyzer of 1-GHz bandwidth and 2-MHz resolution is also demonstrated.