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Fabrication of bonded Germanium on insulator (GeOI) substrates with thin Al 2 O 3 /SiO 2 buried oxide layers was demonstrated for the first time. Thin Al 2 O 3 layers grown by an atomic-layer deposition method, which have hydroxyl groups on their surfaces, were inserted to Ge/SiO 2 interfaces to strengthen the adhesion between them. The interface bonded in the atmosphere at room temperature without post-anneal processes is flat and exhibits no additional interface. After the wafer bonding, thick GeOI layers were thinned by mechanical polishing, chemical mechanical polishing and O 3 water etching. The flatness of the surface is equivalent to that of commercially available Ge substrates. The interface state density ( D it ) of the Ge/Al 2 O 3 interface is estimated with low-temperature conductance technique and the D it of as low as 3.9 × 10 11 eV −1 cm −2 at the interface is obtained. This value is almost one order of magnitude lower than previously reported D it of Ge/SiO 2 interfaces. These results suggest that negligible negative impact on carrier mobility and sub-threshold characteristics is expected for the back-side interface in the GeOI substrate with thin Al 2 O 3 /SiO 2 BOX layers.

Effect of β2-microglobulin adsorption column on dialysis-related amyloidosis.Backgroundβ2-microglobulin (β2-m) is considered a major pathogenic factor in dialysis-related amyloidosis (DRA), often seen in long-term dialysis patients. No effective therapy for this severely debilitating disease is currently available. Lixelle™, an adsorption column, has been developed for the elimination of β2-m; the efficacy of this column has been evaluated in this study.MethodsSeventeen hemodialysis patients with DRA were first treated with high-flux dialysis for a minimum of 1 year. This was followed by 1-year treatment with Lixelle™ column connected in series to the high-flux dialyzer. Treatments were used three times a week for both phases of this study. During the study period, β2-m, pinch strength, motor terminal latency, and activities of daily living were evaluated.ResultsAfter 1-year treatment with high-flux dialysis the β2-m level remained unchanged; however, after 1-year treatment with the addition of the Lixelle™ column, β2-m level decreased significantly from 34.5 ± 8.4mg/L to 28.8 ± 7.3mg/L (P < 0.05). After 1 year of Lixelle™ column use, the pinch strength increased from 6.8 ± 4.7 pounds to 9.1 ± 5.5 pounds (P < 0.01), and the median motor terminal latency was significantly reduced from 5.1 ± 1.0 mseconds to 4.5 ± 1.1 mseconds. A significant improvement was also observed in the activities of daily living score of the upper extremities.ConclusionThese results suggest that the addition of Lixelle™ to the high-flux dialyzer is associated with a significant clinical improvement in DRA patients.

1. 1. The mechanism of action of a new antiplatelet agent, KBT-3022 (ethyl 2-[4,5-bis(4-methoxyphenyl)thiazol-2-yl]pyrrol-1-ylacetate) and its active main metabolite, desethyl KBT-3022, was investigated. 2. 2. KBT-3022 and desethyl KBT-3022 inhibited cyclooxygenase from ovine seminal gland with IC 50 values of 0.69 and 0.43 μM, respectively. 3. 3. At concentrations higher than those required for cyclooxygenase inhibition, desethyl KBT-3022 inhibited cAMP-phosphodiesterase, specific binding of U46619, and release of phosphatidic acid from thrombin-stimulated platelets. 4. 4. Oral administration of KBT-3022 inhibited the production of thromboxane B 2 during blood coagulation more potently than the production of 6-keto-prostaglandin F 1α from aortic strips in guinea pigs. 5. 5. These findings suggest that KBT-3022 may inhibit platelet activation principally via the inhibition of cyclooxygenase by desethyl KBT-3022.

The effect of KBT-3022 (ethyl 2-[4,5-bis(4-methoxyphenyl)thiazol-2-yl]pyrrol-1-ylacetate), a new cyclooxygenase inhibitor, on experimental brain edema was studied. In vitro, KBT-3022 (100 microM) and its metabolite desethyl KBT-3022 (10 and 100 microM), but neither acetylsalicylic acid nor indomethacin, inhibited arachidonic acid-induced swelling of guinea pig cortical slices. KBT-3022 (3-100 microM) and desethyl KBT-3022 (3-30 microM), but neither acetylsalicylic acid nor indomethacin, inhibited lipid peroxidation in guinea pig brain homogenate. In vivo, oral administration of KBT-3022 (1, 3 and 10 mg/kg) and indomethacin (10 and 30 mg/kg), but not acetylsalicylic acid, prevented brain edema induced by bilateral carotid occlusion and recirculation in gerbils. Indomethacin then prevented postischemic hyperthermia, but not KBT-3022. KBT-3022 (10 mg/kg) and indomethacin (30 mg/kg) inhibited lactate accumulation in gerbil brain after ischemia and recirculation. These results suggest that KBT-3022 prevents development of both cytotoxic edema in vitro and vasogenic edema in vivo.

The effects of the new anti-platelet agent KBT-3022, ethyl 2-[4,5-bis(4-methoxyphenyl)-thiazol-2-yl]pyrrol-1-ylacetate, and its metabolite desethyl KBT-3022 on rabbit neutrophil function were investigated in comparison with the effects of acetylsalicylic acid (ASA), ticlopidine hydrochloride (TP), cilostazol (CIL) and indomethacin (IM). The adhesion and migration of neutrophils induced by formyl-methionyl-leucyl-phenylalanine (fMLP) were inhibited by all the compounds tested, their rank order of potency being KBT-3022 = desethyl KBT-3022 > TP = CIL = IM > ASA. KBT-3022, desethyl KBT-3022, CIL and IM all suppressed fMLP-induced increases in the intracellular free Ca2+ concentration ([Ca2+]i) in neutrophils, their potencies correlating with their inhibitory effects on fMLP-induced adhesion and migration. KBT-3022 (1 microM), desethyl KBT-3022 (1-10 microM) and CIL (10 microM) but not IM significantly inhibited both neutrophil migration and the increase in [Ca2+]i induced by leukotriene B4 (LTB4). KBT-3022 (1 microM) and desethyl KBT-3022 (1 microM) suppressed the increase in [Ca2+]i induced by complement C5a. Although KBT-3022 and desethyl KBT-3022 did not influence [3H]LTB4 and [125I]C5a specific binding, [3H]fMLP specific binding was inhibited by desethyl KBT-3022 (IC50: 1.9 microM). Neutrophil adhesion and superoxide anion production stimulated by phorbol 12-myristate 13-acetate were partially inhibited by KBT-3022 (1 microM) and desethyl KBT-3022 (1-10 microM). These results suggest that KBT-3022 and desethyl KBT-3022 have a wider spectrum of action and are more potent inhibitors of neutrophil activation than ASA, TP, CIL and IM.

The protective effect of KBT-3022 (ethyl 2-[4,5-bis-(4-methoxyphenyl)thiazol-2-yl]pyrrol-1-ylacetate), a new cyclooxygenase inhibitor, in cerebral hypoxia and ischemia was studied and compared with those of indomethacin and acetylsalicylic acid (ASA). Oral administration of KBT-3022 (3-100 mg/kg) and indomethacin (3 and 10 mg/kg) significantly prevented KCN-induced death in mice, while ASA (100mg/kg) had no effect. KBT-3022 (3 and 10 mg/kg, p.o.) and indomethacin (10 mg/kg, p.o.) significantly prolonged the survival time of mice subjected to normobaric hypoxia, while ASA (100 mg/kg, p.o.) had no effect. KBT-3022 (3-30 mg/kg, p.o.) and indomethacin (3 mg/kg, i.p.) significantly ameliorated delayed neuronal death in the gerbil hippocampal CA1 sector after occlusion of bilateral carotid arteries for 5 min, while ASA (300 mg/kg, p.o.) had no effect. KBT-3022 (10 mg/kg, p.o.) significantly inhibited ATP depletion in the gerbil hippocampus after a 1-min occlusion of bilateral carotid arteries, but had no effect on ATP depletion after a 5-min occlusion and the recovery during recirculation. These results show that KBT-3022 exerts protective effects against cerebral anoxia and hypoxia and ameliorates delayed neuronal death in the hippocampus. KBT-3022 may therefore be useful for prophylaxis of ischemic cerebrovascular disorders.

In this study, we investigated the effects of KBT-3022 (ethyl 2-[4,5-bis(4-methoxyphenyl)-thiazol-2-yl]pyrrol-1-ylacetate), a potent and long-lasting anti-platelet agent, in several experimental thrombosis models and compared them with those of other anti-platelet drugs. Oral administration of KBT-3022 prevented arachidonic acid-induced death due to pulmonary embolism in mice and rabbits with respective ED50 values of 0.29 and 0.12 mg/kg. The protective effect of acetylsalicylic acid (ASA) against mortality was weaker than that of KBT-3022, and ticlopidine hydrochloride (TP) showed no such effect in these models. In a guinea pig arterio-venous shunt model, the inhibition by KBT-3022 of thrombus formation on a silk thread inserted into the shunt was dose-dependent and 300 and 30 times more potent than the inhibition obtained with ASA and indomethacin, respectively. In a model of aortic thrombosis induced by perivascular application of 20% silver nitrate solution, KBT-3022 (1 mg/kg, p.o.) inhibited thrombus formation significantly, ASA (100 mg/kg, p.o.) tended to inhibit it, and TP had no effect. However, in a stasis-induced venous thrombosis model in guinea pigs, TP inhibited thrombus formation significantly, but KBT-3022 and ASA were ineffective. These results suggest that KBT-3022 may be a useful drug for the treatment and/or prophylaxis of thrombus formation in shunts and aortic thrombosis.

A scientific satellite, dedicated to X-ray astronomy, was launched into orbit from Kagoshima Space Center, University of Tokyo on 21 February 1979. “Hakucho” (CORSA-b) is a spin-stabilized satellite which watches for appearance of X-ray burst in a sky region around the direction of the spin-axis, and scans and surveys a large part of the sky for X-ray sources. The direction of the spin-axis can be maneuvered to selected celestial locations. The outline of the mission, some technical details of the instrumentation, and the operational performance of the spacecraft are described. A short summary of the observational results is also presented.

FUT-175 has been reported by S.Fujii et al.1) to inhibit strongly Clr, Cls, trypsin and thrombin as well as kallikrein and plasmin. In the present study, effects of FUT-175 on the complement and kallikrein system were investigated in vitro and in vivo. The in vitro complement-mediated hemolysis via classical pathway activation was performed as described by Mayer et al., and the systemic Forssman shock in guinea pigs was induced by the method of Glovsky et al. The in vitro kinin formation was performed with glass powder in rat plasma. The anti-inflammatory effects of FUT-175 were also studied on kaolin- and scald-induced edema of rat paws. FUT-175 markedly inhibited the complement-mediated hemolysis, the IC50 being 4.5 × 10−8 M, and protected the guinea pig from the systemic Forssman shock at doses of 0.3 - 3 mg/kg, i.v., in a dose-dependent manner. FUT-175 also inhibited the in vitro kinin formation with the IC50 of 1.1 × 10−7 M (glass powder) and reduced the kaolin- and scald-induced edema formation at doses of 30 - 300 mg/kg, p.o..