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While the use of oral beta (2)-agonists by athletes is prohibited because of their anabolic effects, some inhaled beta (2)-agonists can be used in accordance with the World Anti-Doping Agency regulations. We examined the dose disparity between the bronchodilating effect and anabolic effect of inhaled procaterol, a selective beta (2)-agonist, to determine if the drug might be effective for athletes with asthma. Intact rats were given nebulized procaterol at 0.001, 0.01, 0.1 and 1 mg/mL by inhalation, and its inhibitory effect on carbachol-induced bronchoconstriction was evaluated. Castrated rats were given nebulized procaterol at 0.03, 0.1, 0.3 and 1 mg/mL by inhalation 3 times a day for 14 days, and anabolic markers (body weight gain, weight of the levator ani muscle and gastrocnemius muscle) were measured. At 0.01 mg/mL and higher, procaterol dose-dependently inhibited carbachol-induced bronchoconstriction with a significant effect. At doses of up to 0.3 mg/mL, there were no signs indicating an anabolic effect of procaterol. At 1 mg/mL, however, a slight but statistically significant increase in the weight of the levator ani muscle was observed with no significant changes in other anabolic markers. It was suggested that inhaled procaterol might be useful for athletes with asthma because of the big dose disparity between its bronchodilating effect and anabolic effect in rats.

Calcium salts of long-chain fatty acids from palm fatty acid distillate (CaPFAD) and soybean oil (CaSOFA) were compared using 14 first lactation and 26 multiparous Holstein cows housed in a free-stall barn. It was hypothesized that if replacing CaPFAD with CaSOFA, a rich source of linoleic acid, could result in increased conjugated linoleic acid (CLA) content in milk without losing the lactational and reproductive benefits of feeding CaPFAD, this would be beneficial to the dairy industry and public health, as well as potentially enhance the consumption of dairy products. Cows were group-fed one of two total mixed rations (TMR) containing 1.7% CaPFAD or CaSOFA (DM basis) for ad libitum intake following recommendations from the manufacturer of the fat supplements. Fatty acid profiles (g/100 g of fatty acid) of CaPFAD and CaSOFA, respectively, were 16:0: 48.1, 12.1; 18:0: 4.27, 5.34; 18:1: 35.7, 23.9; and 18:2: 8.9, 51.2. Cows spent about 45 days in the fresh group, after which they were moved to high producing group where they stayed up to 10 weeks post-partum within their treatment assignments. The TMR (DM basis) were 50:50 forage:concentrate for both the fresh group and high producing group cows and contained (DM) 28% NDF and 18% CP. There were no treatment differences in milk yield, milk fat percentage, milk CLA content, milk true protein percentage, milk lactose percentage, milk urea N, linear somatic cell count and change in body condition score. Cows fed CaSOFA produced milk containing a higher content of 18:1(t) (P

CdS/CdTe solar cells have attracted attention recently for their potential as low-cost, high-efficiency solar cells of the future. It is because the CdTe layer (used for photoelectric conversion) has a bandgap energy of 1. 51 eV, which corresponds well to sunlight spectra, and the direct transition type energy band structure enables formation of thinner films. We have already industrialized CdS/CdTe solar cells in mass production stage using a printing-sintering process, as large-area modules for electric power generation(Higuchi et al. , 1993, Omura et al. , 1991), and as cells for indoor applications (primarily in calculators. Suyama et al. , 1986). However, this solar cell has a conversion efficiency of approximately 6%. Recently, there has been considerable research into thin-film CdS/CdTe solar cells which have a thinner CdS film formed by CVD or CBD (Britt et al. , 1993) process, and thus are photosensitive to light with wavelengths of 500 nm or less. At present stage of our art, in solar cells formed by the CSS with a CdTe film on CVD CdS, a conversion efficiency of 15. 05% has been obtained in cells with an area of 1 cm2 (verified at JQA).

Since a fuzzy linear regression model was proposed in 1987, its possibilistic model is employed to analyze data in various fields. From viewpoints of fuzzy linear regression, data are interpreted to express the possibilities of a latent system. Therefore, when data have error or samples are irregular, the obtained regression model has unnaturally too wide possibility range. In this paper we propose a fuzzy robust linear regression model which is not influenced by data with error. Especially a hyperelliptic function is employed to select focal samples which may have a large error or be irregular so that the number of combinatorial calculations can be reduced to a great extent. The model is built to minimize the total error between the model and the data. The robustness of the model is shown using numerical examples. >

The antibacterial activity of OPC-17116, a new fluoroquinolone antibacterial agent, against important pathogens that cause respiratory tract infections was evaluated in vitro and in vivo and compared with those of ciprofloxacin, ofloxacin, and norfloxacin. The pharmacokinetic profiles of OPC-17116 were studied in both mice and rats given the drug orally at doses of 50 and 40 mg/kg of body weight, respectively. OPC-17116 showed a high degree of distribution in the lung tissues of both species, with maximum concentrations of 29.6 and 32.0 micrograms/g, respectively. Furthermore, the drug concentrations in lung tissue were about 10 to 15 times greater than the concentrations in plasma. OPC-17116 showed potent antibacterial activity against such pathogens as Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, Pseudomonas aeruginosa, Haemophilus influenzae, and Moraxella catarrhalis. The MICs of this compound for 90% of these organisms except methicillin-resistant S. aureus and P. aeruginosa ranged from < or = 0.006 to 0.78 microgram/ml. The in vitro antibacterial activity of OPC-17116 was reflected by the efficacy of a single oral dose against systemic bacterial infections in mice. OPC-17116 showed a superior effect against gram-positive bacteria, H. influenzae, and M. catarrhalis. In comparison with the other reference compounds, the efficacy of OPC-17116 was less than that of ciprofloxacin against K. pneumoniae and P. aeruginosa. OPC-17116 showed a greater therapeutic effect than the other drugs against experimental acute pneumonia caused by these organisms in mice or rats. This excellent therapeutic effect against respiratory tract infections may be a result of its high level of distribution in lung tissue.

Solute-free water diuretics (aquaretics) by antagonizing hydrosmotic vasopressin receptors (V2) may be useful in treating water-retaining diseases. The effects of intravenous administration of a newly developed nonpeptide, selective V2 antagonist, OPC-31260, at doses ranging from 0.017 to 1.0 mg/kg to groups of healthy, normally hydrated men were compared with those of 0.33 mg/kg furosemide and placebo. OPC-31260 increased the hypotonic urine volume dose dependently for the first 4 h, while furosemide induced sodium diuresis for 2 h. The absolute increase in the cumulative response in the urine to the highest doses of OPC-31260 was not significantly different from that to furosemide. The higher doses of OPC-31260 rapidly lowered urine osmolality for 2 h, particularly between minutes 15 and 45 (e.g., 1.0-mg/kg dose: 63 +/- 2 mOsm/kg in urine collected between minutes 30 and 45). In a marked hypotonic diuresis, mean free water clearance of the 4-h urine increased dose proportionally into the positive range, reaching 1.80 +/- 0.21 ml/min at 1.0 mg/kg. Whereas furosemide induced marked Na and K diuresis, OPC-31260 increased urinary Na excretion only slightly. At 4 h, 0.75 and 1.0 mg/kg of OPC-31260 almost doubled the plasma arginine vasopressin; and the higher doses increased plasma osmolality and plasma Na slightly, but did not alter plasma K, blood pressure, or heart rate. OPC-31260 thus safely induced a potent aquaretic effect in men.

Tungsten disulphide crystals used as lubricants have been studied by high resolution transmission electron microscopy (HRTEM). Theoretical calculation of the HRTEM image using the multislice method shows that the WS2 [2 1 1 0] images can distinguish between the W and S columns along the incident electron beam and enable one to determine not only the crystal structure but also the fault structure. Observation of a WS2 [2 1 1 0] crystal, prepared by grinding, discloses stacking faults and an array of edge dislocations whose extra planes are single S-W-S layers, revealing the stacking sequence of W and S layers, and also the stepwise structure of its (0001) surfaces as a result of the shear strain. The lubrication mechanism for solid lubricants such as WS2 and MoS2 is interpreted microscopically in terms of the crystallography on the basis of the observation.

Catecholamines can overcome myocardial stunning. However, a previous report on energy metabolism in stunned myocardium during catecholamine infusion was based on the conventional biochemical methods which might affect contractile function. Twenty farm pigs were anesthetized and underwent 15 min coronary artery occlusion and 2 h reperfusion. Ten pigs were given 10 micrograms/kg/min dobutamine from immediately after and throughout the reperfusion (dobutamine group). The other ten pigs were given saline (control group). Phosphorus-31 magnetic resonance spectroscopy and sonomicrometry were done alternately. Dobutamine improved percent segment shortening after reperfusion (control/dobutamine = 3.8%-5.7%/11.7%-13.4%; P0.01). At 15 min ischemia, adenosine triphosphate (ATP) decreased (control/dobutamine = 72 +/- 8%/73 +/- 10%, n.s.), and remained depressed after reperfusion in both groups. After reperfusion, phosphocreatine (PCr) returned to and maintained the preischemic value in the dobutamine group, while in the control group, PCr overshoot (112 +/- 5%) was observed. Except for the presence and absence of PCr overshoot, there was no significant difference of ATP and PCr between the two groups, although rate pressure product was significantly higher in the dobutamine group than in the control group. Regional myocardial blood flow after reperfusion was significantly higher in the dobutamine group. Dobutamine may improve "stunning" through effective improvement of energy utilization and production, indicated by the disappearance of PCr overshoot and maintained ATP level.

BACKGROUND It has been reported that a brief period of coronary occlusion and reperfusion slows the rate of ATP depletion during subsequent sustained ischemia as well as limiting infarct size. However, it has not yet been determined whether ischemic preconditioning also has an effect on the functional and metabolic recovery of stunned myocardium. Our study was designed to address this problem. METHODS AND RESULTS Farm pigs were anesthetized with fluothane and randomly assigned to either a control group or a preconditioned group. The control group (n = 15) underwent 15 minutes of coronary occlusion followed by 120 minutes of reperfusion. The preconditioned group (n = 14) underwent two episodes of 5-minute occlusion and 5-minute reperfusion followed by 15 minutes of occlusion and 120 minutes of reperfusion. This protocol was designed to exclude the stunning effect of the preconditioning procedure itself as much as possible besides preconditioning the heart. A pair of ultrasonic crystals was implanted in the area at risk perfused by the left anterior descending coronary artery. 31P-nuclear magnetic resonance spectroscopy and sonomicrometry were performed alternately. Regional myocardial blood flow (RMBF) was determined with colored microspheres. At 15 minutes of sustained ischemia, phosphocreatine (Pcr), ATP, and intracellular pH were significantly better preserved in the preconditioned group (Pcr: control/preconditioned, 1 +/- 1%/14 +/- 1%; ATP:control/preconditioned, 66 +/- 2%/74 +/- 2%; pH:control/preconditioned, 6.32 +/- 0.07/6.52 +/- 0.05; P < .05). After reperfusion, ATP increased progressively and was almost normalized at 120 minutes of reperfusion in the preconditioned group (control/preconditioned, 73 +/- 4%/95 +/- 3%; P < .05). Overshoot of Pcr (which indicates that the energy generating system is operating better than energy utilizing system) persisted in preconditioned hearts but disappeared rapidly in controls (control/preconditioned, 104 +/- 3%/130 +/- 3% after 120 minutes of reperfusion). There was no significant difference in percent segment shortening (%SS), RMBF, and hemodynamics between the two groups throughout the experiment (%SS: control/preconditioned, 29.8 +/- 5.9%/28.8 +/- 6.3% of baseline after 120 minutes of reperfusion). CONCLUSIONS Preconditioning improves energy metabolism during reperfusion, although it does not attenuate myocardial stunning for at least 2 hours after reperfusion.

BACKGROUND Ischemic preconditioning slows ATP depletion and ultrastructural damage during the final episode of ischemia. To define the influence of creatine phosphate (CP) and intracellular pH (pHi) on this effect, CP and pHi were serially measured in porcine hearts without collateral circulation by using 31P-NMR spectroscopy and ultrastructural examination. METHODS AND RESULTS Farm pigs weighing 12-15 kg were anesthetized with Fluothane. The control group underwent a single occlusion (20 minutes or 60 minutes); the preconditioned group underwent four episodes of 5-minute occlusion and 5-minute reperfusion followed by a sustained occlusion (20 minutes or 60 minutes). After ischemic preconditioning, CP increased to 115 +/- 11% (p less than 0.05) of preischemic value and ATP decreased to 84 +/- 8% (p less than 0.05) of preischemic value, but pHi returned to preischemic value. At 5 and 10 minutes of sustained ischemia, CP was significantly preserved in the preconditioned group (control group, 19 +/- 3% versus preconditioned group, 29 +/- 4% at 5 minutes; control group, 5 +/- 3% versus preconditioned group, 11 +/- 3% at 10 minutes; p less than 0.05). At 15 and 20 minutes of sustained ischemia, ATP was significantly preserved in the preconditioned group (control group, 64 +/- 3% versus preconditioned group, 73 +/- 3% at 15 minutes; control group, 51 +/- 7% versus preconditioned group, 62 +/- 2% at 20 minutes; p less than 0.05). At 10, 15, 20, and 25 minutes of sustained ischemia, pHi was significantly higher in the preconditioned group (control group, 6.5 +/- 0.05 versus preconditioned group, 6.7 +/- 0.1 at 10 minutes; control group, 6.3 +/- 0.05 versus preconditioned group, 6.6 +/- 0.06 at 15 minutes; control group, 6.1 +/- 0.1 versus preconditioned group, 6.4 +/- 0.1 at 20 minutes; control group, 6.0 +/- 0.2 versus preconditioned group, 6.3 +/- 0.1 at 25 minutes; p less than 0.05). Ultrastructural changes were milder in the preconditioned group at 20 minutes of sustained ischemia. CONCLUSIONS In addition to ATP and ultrastructure, preconditioning preserved CP and pHi during sustained ischemia. These protective effects might be due to overshoot phenomenon of CP and/or reduced ATP consumption. The relatively longer period of preservation of pHi, which probably is the result of reduced ATP consumption, indicates its greater contribution to reducing infarct size than that of CP and ATP.

Cilostazol, an antiplatelet drug, and probucol, a cholesterol-lowering drug, are reported to ameliorate atherosclerosis in animal models. However, their combined effect on atherosclerosis is unclear. We therefore evaluated their combined effect on atherosclerotic lesions in LDL receptor-deficient mice. Male LDL receptor-deficient mice were fed a high fat diet with or without cilostazol alone, probucol alone, or with cilostazol and probucol in combination, for 8 weeks. Body weight and plasma lipid levels were measured before and during treatment. At the end of treatment, the size distribution of plasma lipoproteins was analyzed by HPLC and then plasma HDL cholesterol levels and en face aortic atherosclerotic lesion areas were measured. Probucol alone significantly decreased both total cholesterol and HDL cholesterol, while cilostazol alone did not decrease total cholesterol, but significantly increased HDL cholesterol. Both cilostazol alone and probucol alone significantly decreased atherosclerotic lesion areas, and their combined administration showed more significant decreases than when each drug was administered singly. The combination of cilostazol and probucol was more effective in preventing atherosclerotic lesion formation than the administration of each drug alone; this may provide us with a new strategy for treating atherosclerosis.

To assess the protective effect of verapamil on ischemic myocardium, the changes in high energy phosphates, inorganic phosphate, and intracellular pH were serially and quantitatively measured in ischemic porcine hearts without collateral circulation using 31 P-NMR spectroscopy, together with ultrastructural examination. Twenty-six farm pigs weighing 11 to 14 kg were anesthetized with fluothane and were divided into control (C) group and verapamil pretreatment (V) group. In V group 0.2 mg/kg of verapamil was administered for 20 mins before occlusion of the anterior descending cornary artery. 31 P-NMR spectra were serially obtained throughout the experiment, and ultrastructural examination was done at 20-min occlusion and at 120-minute occlusion in each group. At 10-min ischemia, creatin phosphate was significantly preserved in V group ( C V = 11 ± 4% 16 ± 5% P ). At 20 min ischemia, ATP was significantly preserved ( C V = 60 ± 9% 73 ± 8% P ), and intracellular pH was significantly higher in V group ( C V = 6.4 ± 0.2 6.6 ± 0.1 P ). Morphologically, clumping of the nuclear chromatin, mitochondrial swelling and decrease in glycogen were milder in V group at 20 min ischemia. However, these beneficial effects disappeared at 120 min ischemia. Thus pretreatment with verapamil attenuated depletion of high energy phosphates, progression of acidosis, and ultrastructural changes. There was no significant difference of rate pressure product and regional blood flow between hearts with and without pretreatment of verapamil. Therefore, this protective effect may be due to the energy sparing effect or other direct subcellular effect of verapamil on ischemic myocyte.

Project management is one of central issues in management of technology and engineering. Kathy Schwalbe summarized recent statistics that average time overrun is 163% in 2001 and 227% in 1995, and average cost overrun is 145% in 2001 and 189% in 1995. The project management is not so much successful. A software development company is expected to provide high quality and functional software to the world. It is difficult to control software quality because software is invisible and cannot be felt with our finger. In addition, it is hard to make its productivity efficient because software is created as a result of brainwork. Generally speaking, a project team is organized to create software. Human relationships and work environment affect software qualities. Therefore, it is very important to study the project management of software development for the cost of management and the quality control. The objective of this paper is to illustrate the influential features of software development projects by analyzing questionnaires collected from several software development companies. In the analysis, a multivariate model is employed to quantitatively evaluate the influential features of software development projects.

We have studied a cylindrical moving coil linear DC motor to ink jet shuttle printer that make it possible to print with high speed, high resolution and low power consumption. The actuator is supposed to be driven using resonance of spring plates which are placed at the end of the permanent magnet and the armature respectively. However, the permanent magnet and armature of the actuator did not resonated at the same frequency and the spring coefficient changed because these were fixed to the supports by screws. At present, a new support mechanism is being made.

The effect of an interface dipole layer on the energy level alignment at organic-conductor interfaces is studied on a copper phthalocyanine (CuPc) monolayer/electric dipole layer/graphite system via ultraviolet photoemission spectroscopy (UPS) and metastable atom electron spectroscopy. An oriented monolayer of the OTi-phthalocyanine molecule, which has an electric dipole moment, is grown on graphite to yield a well-defined dipole layer with the vacuum side negatively charged. The CuPc monolayer is sequentially deposited on the dipole layer kept at $123\phantom{\rule{0.3em}{0ex}}\mathrm{K}$. This weakly interacting system made of a very thin organic layer on top of a very thin dipole layer is in thermodynamic equilibrium. The UPS data from the system grown with and without the interface dipole layer show that the binding energy of the highest occupied state of the CuPc monolayer decreases when the dipole layer is inserted. The binding energy shift is in excellent agreement with the increase in vacuum level energy of the graphite substrate upon deposition of the dipole layer. The results show that the Fermi level of the CuPc shifts toward the valence states when the interface dipole layer is inserted.

Since a fuzzy linear regression model was proposed in 1987, its possibilistic model was employed to analyze data. From viewpoints of fuzzy linear regression, data are understood to express the possibilities of a latent system. When data have error or data are very irregular, the obtained regression model has an unnaturally wide possibility range. We propose a fuzzy robust linear regression which is not influenced by data with error. The model is built as rigid a model as possible to minimize the total error between the model and the data. The robustness of the proposed model is shown using numerical examples. >

The structure and crystallinity of a segregation on a borophosphosilicate glass (BPSG) film have been clarified by scanning electron microscopy (SEM), transmission electron microscopy (TEM), transmission electron diffraction (TED), and electron energy loss spectroscopy (EELS). The segregation arises on the BPSG film surface after annealing in nitrogen ambient. Its size is below 0.5 μm. The segregation is identified as crystalline BPO4 from the results of TED and EELS. In this letter, TED pattern of crystalline BPO4 is indicated in detail. The growth mechanism of crystalline BPO4 is proposed on the basis of a series of the results.

We investigated if blockade of ATP-sensitive K+ channels (KATP) abolishes the protective effect of ischemic preconditioning (IP) on myocardial metabolism and ischemia-induced reactive hyperemia (RH) in pigs.IP was elicited by a single cycle of 5 min occlusion and 5 min reperfusion of coronary artery, followed by 15 min of test ischemia and 120 min of reperfusion. Vehicle or the ATP-sensitive K+ channels (KATP) blocker, glibenclamide (3 or 6 mg/kg; G3 or G6) was administered before IP (groups; IP, G3+IP, G6+IP). As respective controls, the same treatment was performed in groups without IP (groups; C, G3, G6). Tissue levels of ATP, creatine phosphate (CP) and intracellular pH (pHi) in the area at risk were measured by 31P-nuclear magnetic resonance spectroscopy. RH after 5 min of preconditioning ischemia was assessed by regional myocardial blood flow.ATP and pHi were preserved after 15 min of ischemia in the IP group [C/IP; ATP=57+/-4/76+/-10% of baseline, pHi=6.18+/-0.08/6.66+/-0.03, P0.05, C vs. IP]. Both doses of glibenclamide completely abolished the ATP sparing effect of IP. The high dose completely abolished pHi preservation (G6+IP=6.33+/-0.06), while the low dose showed only a partial effect (G3+IP=6.48+/-0.03). Glibenclamide did not adversely affect myocardial metabolism in groups without IP. Glibenclamide attenuated RH after 5 min of ischemia by 30% in both subendocardium and subepicardium.Blockade of KATP abolished the preconditioning effect on myocardial metabolism, and partially attenuated post-ischemic reactive hyperemia in pigs. These results indicate that KATP activation might be involved in the mechanisms of these phenomena, reactive hyperemia is not sufficient to induce IP protection.

Cadmium Telluride is the most promising photovoltaic material as low cost, high efficiency solar cells. In this work, two types of CdS/CdTe solar cells are investigated. One is fabricated by screen printing and sintering CdS and CdTe formation process. The other type is fabricated using CdS films deposited by chemical vapor deposition (CVD) and p-CdTe film deposited by close-spaced sublimation (CSS) method. By the analysis of the X-ray diffraction patterns, the orientation of the sintered CdS film and the sintered CdTe film is almost random, whereas the crystal structure of the CVD-CdS film is hexagonal, and strongly oriented. The CSS-CdTe film strongly oriented, too. Solar cells of 1 cm/sup 2/ with an efficiency of 15.05% under AM 1.5, have been prepared from CVD-CdS/CSS-CdTe films.

To elucidate the mechanisms of the potent and long-lasting antihypertensive action of pranidipine (CAS 99522-79-9, OPC-13340), a wash-out experiment in isolated rat aorta preparations and a displacement binding experiment of (+)[3H]PN200-110 (isradipine) with pranidipine and other dihydropyridines to porcine skeletal T-tubules was conducted. It was revealed that the inhibition of KCl-induced contraction by pranidipine remained complete even after washing out the drug 9 times. Also, pranidipine had the lowest Ki value for (+)[3H]PN200-110 binding in skeletal T-tubules. The lipophilicity of pranidipine measured by octanol-buffer partition coefficient was the highest among the tested compounds, and the order of lipophilicity coincided with the order of potency in the displacement binding experiments. These results suggest that pranidipine has a very high affinity to Ca channels or to T-tubule membranes, and strongly support the "membrane-bilayer pathway hypothesis" which assumes the partitioning of the drug into the lipid bilayer before drug binding to Ca channels as an explanation of the potent and long-lasting action of pranidipine compared with other dihydropyridines.

We investigated whether transient adenosine (Ado) infusion before ischemia had the same effect on myocardial metabolism and function as ischemic preconditioning (IP). The control (C) group underwent 15 min of coronary artery occlusion followed by 120 min of reperfusion. The Ado group received a 15-min infusion of Ado (200 micrograms.kg-1.min-1) into the left atrium starting 20 min before ischemia. IP was elicited by two cycles of 5-min ischemia and 5-min reperfusion. In the area at risk, tissue levels of ATP, creatine phosphate (CP), and intracellular pH (pHi) were serially measured by 31P-nuclear magnetic resonance spectroscopy in 10 pigs from each group, and percent segment shortening (%SS) was measured in 7 pigs from each group. ATP and pHi were preserved after 15 min of ischemia in both Ado and IP groups [ATP = 64 +/- 7, 76 +/- 6, and 74 +/- 9% of baseline; pHi = 6.35 +/- 0.19, 6.54 +/- 0.11, and 6.64 +/- 0.11 in C, Ado, and IP groups, respectively (P < 0.05, Ado and IP vs. C)]. During reperfusion, ATP was restored progressively in both groups [71 +/- 7, 90 +/- 8, and 91 +/- 9% of baseline at 120 min of reperfusion in C, Ado, and IP groups, respectively (P < 0.05, Ado and IP vs. C)]. However, in contrast to the IP group, CP was not preserved during 15-min ischemia nor did it show persistent overshoot during reperfusion in the Ado group. There were no significant differences in %SS during ischemia and reperfusion among the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Fin field-effect transistors are promising next-generation electronic devices, and the identification of dopant positions is important for their accurate characterization. We report atom probe tomography (APT) of silicon fin structures prepared by a recently developed self-regulatory plasma doping (SRPD) technique. Trenches between fin-arrays were filled using a low-energy focused ion beam to directly deposit silicon, which allowed the analysis of dopant distribution by APT near the surface of an actual fin transistor exposed to air. We directly demonstrate that SRPD can achieve a boron concentration above 1 × 1020 atoms/cm3 at the fin sidewall.

To obtain a highly spin polarized positron beam, 68Ge isotope have been produced using a nuclear reaction of 69Ga(p,2n)68Ge. As target materials, we examined a metal form 69Ga stable isotope and a GaN substrate. By 20 MeV proton irradiation, the production of 68Ge source was confirmed in both targets. The production rates of 68Ge were 0.16 and 0.53 MBq/μA/h for the metal Ga and GaN target, respectively. The spin polarizations of positrons emitted from 68Ge was estimated to be approximately 50 to 70%.

The action of methyl 3-phenyl-2 (E)-propenyl 1,4-dihydro-2,6-dimethyl- 4-(3-nitrophenyl)-3,5-pyridinedicarboxylate (pranidipine, OPC-13340, CAS 99522-79-9) on the endothelium-dependent relaxation in the isolated aorta in vitro was examined in comparison with other calcium antagonists (nifedipine, nitrendipine, nicardipine, diltiazem and verapamil). In the isolated aortic preparation of Wistar rats, acetylcholine (10(-5) mol/l), ATP (10(-5) mol/l or histamine (10(-5)-10(-4) mol/l) caused endothelium-dependent relaxation when the strips were previously contracted with prostaglandin F2 alpha. This endothelium-dependent relaxation recovered within a few minutes, although the mechanisms of this contraction after relaxation were not clear. The pretreatment with pranidipine for 20 min extended the duration of the endothelium-dependent relaxation, however, there was no potentiation in magnitude of the relaxation. This effect on the duration of endothelium-dependent relaxation was prominent in pranidipine, namely, other calcium antagonists tested had not this action at clinical concentrations. This phenomenon was also observed when the strips were pre-contracted with norepinephrine. This action of pranidipine might be some beneficial feature for therapeutic use of the compound.

The cardiovascular effects of OPC-13340, a newly developed 1,4-dihydropyridine calcium channel blocker, were examined in several canine preparations. In conscious normotensive and DOCA-salt hypertensive dogs, OPC-13340, at doses of 10 to 30 micrograms/kg, i.v., and 0.3 to 3 mg/kg, p.o., exerted an hypotensive action in a dose-dependent manner. The hypotensive action of OPC-13340 was longer lasting and more potent than that of nicardipine and nifedipine. In conscious, normotensive instrumented dogs, OPC-13340, at doses of 1 and 3 mg/kg, p.o., dose-dependently decreased total peripheral resistance and mean blood pressure and increased heart rate, cardiac output and left ventricular contractility. In anesthetized open-chest dogs, OPC-13340, at doses of 1 to 30 micrograms/kg, i.v., increased coronary blood flow and decreased mean blood pressure, heart rate, coronary vascular resistance, arteriovenous oxygen difference and myocardial oxygen consumption. In contrast to OPC-13340, nicardipine did not change the myocardial oxygen consumption. From these results it was concluded that OPC-13340 lowered blood pressure and improved coronary circulation in dogs and that the duration of these actions was longer lasting than that of nifedipine and nicardipine. These actions of OPC-13340 may be useful in the treatment of hypertension and angina pectoris.

The effect of the molecular orientation on the molecular electronic structure is studied on the Cu-phthalocyanine∕graphite system via film thickness dependences of metastable-atom electron spectra and ultraviolet photoelectron spectra. We observed a decrease in the vacuum-level position and a corresponding band-bending-like shift in the highest occupied state only for thick films where the molecular tilt angle increases gradually with the film thickness. These shifts are explained by electric dipoles produced in the film by a gradient of the intermolecular electronic interaction along the surface normal due to the continuous increase in the molecular tilt angle. The result indicates that the change in the molecular orientation is an important origin of the band-bending-like shift in the molecular electronic states even if the molecule has no permanent electric dipole.

SUMMARY 1. The antiarrhythmic properties of 5–(3-tert-butylarnino-2-hydroxy)propoxy-3,4-dihydrocarbostyril hydrochloride (OPC-1085) were compared with those of propranolol and pindolol using various kinds of preparations for experimental arrhythmia in dogs. 2. Although OPC-1085 was the most potent drug to antagonize adrenaline-induced arrhythmia in animals anaesthetized with either pentobarbitone sodium or halothane, it was scarcely effective on ouabain-induced arrhythmia in pentobarbitone sodium anaesthetized animals. 3. When these compounds were administered intravenously to conscious dogs 24 h after two-stage ligation of the anterior descending artery, ectopic ventricular beats of coronary ligation-induced arrhythmia were reduced while regular sinus beats were simultaneously increased. 4. OPC-1085 was very effective on aconitine-induced arrhythmia in dogs anaesthetized with pentobarbitone sodium. The effective dose was similar to that of propranolol but about fifteen times less than that of pindolol. 5. It is concluded that different potencies among these β-adrenoreceptor antagonists against various kinds of experimental arrhythmias cannot be simply deduced from any one of the following properties; β-adrenoreceptor antagonism, intrinsic myocardial stimulation, local anaesthetic and so-called quinidine-like effects.

Effects of procaterol (PRO) on the CNS were investigated in comparison with those of salbutamol (SAL) and isoproterenol (ISO). PRO, 15 to 50 mg/kg given subcutaneously suppressed spontaneous movement in mice, rats and rabbits and with a large dose, 1000 mg/kg, the animals became quiet and immobile. In dogs, PRO produced similar symptoms and in addition, there was nausea and vomiting. The animals recovered within 3--8 hours. ID50's in depressing spontaneous movement were 20.2 and 245 mg/kg for PRO, 51.1 and 133 mg/kg for SAL and 2.37 and 143 mg/kg for ISO, respectively, both by the subcutaneous and oral routes of administration. Methamphetamine induced increase in motility and fighting behavior was also suppressed by PRO when similar doses were given. PRO had no effect on coordinating movement, halothane anesthesia, drug and electric stimulation induced convulsions and body temperature, and there was no muscle relaxant action. However, PRO in large doses prolonged sleeping time with hexobarbital. The analgesic effect of PRO was not observed with Haffner's and Landall Selitto's methods but acetic acid induced writhing was suppressed by PRO. PRO had little effect on spontaneous EEGs either cortical or from deep structures, and EEG arousal responses. The effects of PRO on the CNS were slight and nonspecific, and similar to those of SAL and ISO.

The cardiovascular effects of 3,4-dihydro-6-[4-(3,4- dimethoxybenzoyl )-1-piperazinyl]-2(1H)- qu inolinone ( OPC -8212) were investigated in isolated ventricular muscles of various mammalian species, anaesthetized dogs and conscious dogs. In the isolated ventricular muscles of the dog, cat, rabbit and guinea pig, OPC -8212 (3 X 10(-6)-3 X 10(-4) mol/l) increased the developed tension in a concentration-related manner and these positive inotropic effects of OPC -8212 were 1/140-1/120 those of dobutamine but 5-17 times and 8-25 times those of amrinone and theophylline, respectively. The positive inotropic effect of OPC -8212 was not modified by pindolol or phentolamine. In the isolated rat ventricular muscle, OPC -8212, amrinone and theophylline exerted no positive inotropic effect, although dobutamine did. In anaesthetized dogs, OPC -8212 (0.1-3 mg/kg i.v.) was nearly as active as amrinone in producing an increase in left ventricular contractile force. However, OPC -8212 was much less active than amrinone in increasing heart rate and decreasing blood pressure. In conscious dogs OPC -8212 at doses of 1 and 3 mg/kg i.v. increased peak LV dP/dt by 27% and 59%, respectively, without significant changes in heart rate and blood pressure. OPC -8212 did not affect the dog heart Na+,K+-ATPase activity. These results suggest the following: (1) OPC -8212 has a mechanism of action different from those of catecholamines and cardiac glycosides, (2) it has a useful profile in the treatment of heart failure because it caused a selective positive inotropic effect with no obvious positive chronotropic and vascular effects.

The antiulcer effects of OPC-12759, a novel antiulcer agent were compared with those of cetraxate in various experimental ulcer models and on gastric secretion in rats. OPC-12759 (0.3-30 mg/kg, b.i.d., p.o.) significantly accelerated the healing rate of acetic acid-induced gastric ulcer in a dose-dependent manner, while cetraxate did not. When administered orally at 0.3-30 mg/kg, b.i.d., for 7 days, pretreatment with OPC-12759 (0.3-30 mg/kg, b.i.d., p.o.) prevented the formation of acute gastric ulcers, induced by: restraint water immersion stress, aspirin, indomethacin, histamine, serotonin, platelet activating factor (PAF) and DDC. Cetraxate showed antiulcer activity against a part of the OPC-12759-positive gastric ulcer models. Given intraperitoneally at the single dosing range of 10-100 mg/kg, OPC-12759 inhibited the formation of these acute gastric ulcer models. OPC-12759 administered orally at 0.3-30 mg/kg, b.i.d., for 7 days did not inhibit basal gastric secretion in pylorus ligated rats. The results indicated that OPC-12759 possesses wide spectrum antiulcer activity as compared with cetraxate.

Pharmacological properties of procaterol (PRO) in the peripheral organs were examined in comparison with those of sulbutamol (SAL) and isoproterenol (ISO). PRO slightly enhanced twitch tension of the tibialis anterior muscle but affected little the mono- and poly-synaptic spinal reflexes and ganglionic transmission. PRO depressed spontaneous contractions of the isolated ileum, non-pregnant and pregnant uterus and also the gastrointestinal and uterine movements in vivo. PRO prolonged the time of peroral charcoal transport in the intestine. Potencies of PRO in producing these effects were between those of ISO and SAL except those on the uterus in which PRO was more potent than ISO and SAL. Pro depressed gastric and bile secretion but had no effect on pancreatic secretion. ISO, PRO and SAL reduced resistance of the common carotid, femoral and renal arteries and the relative potencies of PRO and SAL to ISO were significantly less in the renal artery than in the other arteries. In accelerating heart rate in conscious rats and dogs, PRO (p.o. or s.c.) was almost equipotent to SAL. Urine flow, GFR, RPF, free water and osmolar clearance and also excretion of electrolytes were reduced by PRO with the concomitant fall of systemic blood pressure. PRO has no effect on blood coagulation and hemolysis but inhibited carrageenin edema and an increase in permeability of blood vessels induced by acetic acid. PRO had no alpha-adrenolytic, cholinolytic and anti-histaminic effects.

The effect of diltiazem on the contractile and vascular responses to 2 min of total occlusion and reperfusion was investigated in isolated blood-perfused canine papillary muscle preparations. Diltiazem, in doses (3 and 10 micrograms/min) that increased coronary blood flow but did not change developed tension and maximum rate of tension development (dT/dt) in papillary muscle before occlusion, attenuated tension development between 40 and 120 sec of ischemia. At-60 sec postocclusion, developed tension was at 36 +/- 4, 37 +/- 5 and 44 +/- 4% below preocclusion levels for 3, 10 and 100 micrograms/min of diltiazem, respectively (nondiltiazem treated = 24 +/- 3%). The dT/dt increased to 22 +/- 6% above preocclusion value during ischemia in nondiltiazem-treated preparations. This was blocked by diltiazem in a dose-dependent fashion. Propranolol and nitroprusside did not modify the developed tension and the increase in dT/dt of the papillary muscle during occlusion. On reperfusion, an overshoot in developed tension to 22 +/- 4% above preocclusion level was observed. This was significantly reduced by diltiazem and propranolol but not by nitroprusside. Diltiazem inhibited the maximal peak reactive hyperemia response after 2 min of occlusion by 30 to 38%. Both propranolol and nitroprusside did not change this response. The results show that diltiazem selectively depresses the inotropic state of the ischemic myocardium and suggest that a diltiazem-induced reduction in myocardial oxygen consumption during ischemia may contribute to the protection of ischemic myocardium and the reduction in reactive hypermia response in the ischemic heart.

1. The beta-adrenoceptor stimulant properties of 5-(1-hydroxy-2-isopropylaminobutyl)-8-hydroxy-carbostyril hydrochloride hemihydrate (OPC-2009) were compared with those of isoprenaline and salbutamol on guinea-pig isolated tissues. 2. In producing tracheal relaxation, OPC-2009 was approximately 7 times more potent and salbutamol 5 times less potent than isoprenaline. Both compounds were less potent than isoprenaline in increasing either the rate of beating of isolated right atria or the contractile force of left atria, OPC-2009 being 4 and 127 times and salbutamol being 100 and 700 times less potent on the respective preparations. 3. Selectivity calculated from EC50 ratio indicates that OPC-2009 was approximately 26 times and salbutamol approximately 21 times more selective than isoprenaline for tracheal smooth muscle as compared to right atrial muscle, whereas OPC-2009 was approximately 850 times and salbutamol 140 times more selective than isoprenaline for tracheal smooth muscle as compared to left atria. 4. The responses to OPC-2009 on trachea and right atria were not altered by treatment of animals with reserpine 24 h previously. Propranolol was a competitive antagonist of OPC-2009 on these tissues. 5. OPC-2009 at high concentrations competitively antagonized the positive chronotropic and inotropic responses to isoprenaline, indicating that OPC-2009 like salbutamol, may be classified as a partial agonist. 6. The results indicate that the action of OPC-2009 is more selective for tracheal smooth muscle than cardiac muscle and are interpreted in the light of subdivisions of beta-adrenoceptors.

1. The homogeneity of beta-adrenoceptors in femoral, superior mesenteric and renal vascular beds was investigated by the use of the regional perfusion technique in dogs. 2. Isoprenaline and salbutamol produced dose-related increases in femoral and superior mesenteric blood flow. The dose-response curves for the two agonists were parallel, but salbutamol was approximately 1/15 as potent as isoprenaline on a weight basis. 3. Isoprenaline and salbutamol increased renal blood flow in a dose-related manner. However, salbutamol was approximately 1/240 as potent as isoprenaline on a weight basis, and the slope of the dose-response curve for salbutamol was less steep than that for isoprenaline. 4. The dose-response curves to isoprenaline for increase in femoral and superior mesenteric blood flow were shifted to the right by intravenous pindolol but not by intravenous or intra-arterial practolol. 5. The dose-response curves to isoprenaline for increase in renal blood flow were shifted to the right more markedly by intravenous pindolol than by intravenous or intra-arterial practolol. 6. The results indicate that beta-adrenoceptors of the renal vascular bed consist of beta1-type and beta2-type whereas the femoral and superior mesenteric vascular beds contain only beta2-adrenoceptors.

The efficacy of orally active 3, 4-dihydro-6-[4-(3,4- dimethoxybenzoyl )-1-piperazinyl]-2(1H)- quin olinone ( OPC -8212) as a positive inotropic agent was examined using model right-sided heart failure dogs and compared with those of dobutamine and amrinone. Heart failure was produced in beagle dogs by a combination of tricuspid insufficiency and pulmonary stenosis, and then drugs were administered intravenously or orally. Intravenous OPC -8212, 1 and 3 mg/kg, amrinone, 1 and 3 mg/kg, and dobutamine, 0.01 and 0.03 mg/kg, increased the dP/dt of the right ventricular pressure for 5 to 10 min. These positive inotropic effects were accompanied by simultaneous increase in the heart rate in the cases of amrinone and dobutamine, and was accompanied by hypotension in the case of amrinone. However, OPC -8212 did not show such effects. This indicates that OPC -8212 has a relatively selective positive effect on cardiac contractility. Oral administration of OPC -8212, 10 to 100 mg/kg, and amrinone, 10 and 30 mg/kg, also showed a positive inotropic effect, appearing 1 h after administration and lasting up to the 5th h. Amrinone had about a 3 times stronger effect, but for similar positive inotropic effects, only amrinone showed positive chronotropic effect. The hypotensive effect of amrinone was also observed after oral administration, while such an effect was scarcely observed when using OPC -8212.

Peptides with both a tyrosyl-tyrosine and a cystine or S -benzylcysteine residue in the molecule (six peptides of cystinyltyrosyl-tyrosine derivatives and five peptides of S -benzylcysteinyl-tyrosyl-tyrosine derivatives) were synthesized, purified, and evaluated for antagonistic properties of oxytocin. Almost all the peptides exhibited antagonistic activities to the action of oxytocin on isolated rat uterus. The most active peptide was N -dicarbobenzoxy-L-cystinyl-di-(L-tyrosyl-L-tyrosine) with pA 2 of 6.06. This peptide also showed the inhibition of the responses to oxytocin on rat uterus in situ and on avian blood pressure. N -Carbobenzoxy- S -benzyl-L-cysteinyl-L-tyrosyl-L-tyrosine with pA 2 of 5.78 did not have the inhibitory actions of oxytocin in situ .