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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.

Gabexate (GB), a serine protease inhibitor that is widely used for the treatment of acute pancreatitis and disseminated intravascular coagulation, has been reported to be partly hydrolyzed by human serum albumin. However, other enzymes responsible for GB hydrolysis in human blood remain unclear. In this study, we examined in vitro metabolism of GB with human blood samples. The hydrolytic activities of the plasma and erythrocytes at 100µM of GB were 167 ± 26 and 151 ± 9n mol/min/ml blood fraction (mean ± S.D., n = 8), respectively. Kinetic analysis indicated that Vmax and Km values were 1.75µmol/min/ml blood fraction and 529µ Mf or the plasma and 10.6µmol/min/ml blood fraction and 7360µ Mf or the erythrocytes, respectively. The activity of human plasma wa si nhibited by ethopropazine, a butyrylcholinesterase inhibitor (27% inhibition at 100µM). Furthermore, the plasma activity was inhibited by 5,5 � -dithiobis(2-nitrobenzoic acid) (DTNB) (40% inhibition at 5000µM), suggesting the involvement of albumin in the plasma GB hydrolysis. The erythrocyte activity was also decreased by DTNB (56% inhibition at 5000µM), implying that this activity was dependent on the presence of sulfhydryl group(s), while little or no inhibition of the activity was seen with phenylmethylsulfonyl fluoride, diisopropyl fluorophosphate, and BW284C51. Butyrylcholinesterase from human serum showed GB hydrolytic activity with Vmax of 363 nmol/min/m gp rotein and Km of 263µM. These results suggest that, in addition to albumin, butyrylcholinesterase and erythrocyte sulfhydryl-dependent enzyme are responsible for GB hydrolysis in human blood.

Metabolism of nafamostat, a clinically used serine protease inhibitor, was investigated with human blood and liver enzyme sources. All the enzyme sources examined (whole blood, erythrocytes, plasma and liver microsomes) showed nafamostat hydrolytic activity. V(max) and K(m) values for the nafamostat hydrolysis in erythrocytes were 278 nmol/min/mL blood fraction and 628 microM; those in plasma were 160 nmol/min/mL blood fraction and 8890 microM, respectively. Human liver microsomes exhibited a V(max) value of 26.9 nmol/min/mg protein and a K(m) value of 1790 microM. Hydrolytic activity of the erythrocytes and plasma was inhibited by 5, 5'-dithiobis(2-nitrobenzoic acid), an arylesterase inhibitor, in a concentration-dependent manner. In contrast, little or no suppression of these activities was seen with phenylmethylsulfonyl fluoride (PMSF), diisopropyl fluorophosphate (DFP), bis(p-nitrophenyl)phosphate (BNPP), BW284C51 and ethopropazine. The liver microsomal activity was markedly inhibited by PMSF, DFP and BNPP, indicating that carboxylesterase was involved in the nafamostat hydrolysis. Human carboxylesterase 2 expressed in COS-1 cells was capable of hydrolyzing nafamostat at 10 and 100 microM, whereas recombinant carboxylesterase 1 showed significant activity only at a higher substrate concentration (100 microM). The nafamostat hydrolysis in 18 human liver microsomes correlated with aspirin hydrolytic activity specific for carboxylesterase 2 (r=0.815, p

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.

Triangular In0.53Ga0.47As-OI nMOSFETs with smooth (111)B side surfaces on Si have been successfully fabricated. Triangular shaped channels with bottom width down to 30 nm were formed by MOVPE growth on narrow InGaAs-OI fins. The formed (111)B surface was demonstrated to provide higher mobility compared with reference InGaAs-OI tri-gate (1.9×) as well as bulk (100) InGaAs nMOSFETs (1.6×), which is possibly due to reduced Dit in conduction band and resultant suppressed carrier trapping at the MOS interface. Lower noise and hysteresis in triangular device supported this model. High Ion value of 930 μA/μm at Lg = 300 nm indicates the potential of the triangular InGaAs-OI nMOSFETs for ultra-low power and high performance CMOS applications.

We compared current drivability between (001)/ and (001)/ strained Ge-on-insulator pMOSFETs under biaxial and uniaxial stress. Higher intrinsic transconductance (gm, int) was experimentally demonstrated for the first time in the (001)/ devices with a gate length (Lg) less than 100 nm under the both strain conditions, although this is not the case for the long-channel devices. This is possibly attributable to more significant non-parabolicity of the valence band (VB) dispersion, i.e., heavier effective mass at energy apart from the VB minimum, along than along . It is also found that the parasitic resistance (RSD) governed by the contact resistance between the NiGe-source and the strained-Ge channel is lower along direction than the counterpart. As a result, higher drive current was observed for a device with Lg of 55 nm under both the biaxial-(644 μA/μm) and uniaxial stress (536 μA/μm) at Vd = -0.5 V than for counterpart, although mobility was highest in the channel under the uniaxial stress.

InGaAs/Ge stacked 3D CMOS inverters have been successfully demonstrated down to Vdd = 0.2 V. The negligible degradation of the top and the bottom device characteristics indicates high technical feasibility of the InGaAs/Ge stacked 3D integration for ultra low-power and high performance CMOS.

We studied the adhesive and sealing effects of sheet style fibrin adhesive, TO-193 (TachoComb), on some tissues and organs, comparing them with those of sheet style collagen agent, collagen sponge, Novacol, and Avitene and liquid fibrin adhesive agent, Beriplast P. TO-193 showed more a potent adhesive effect on liver than the sheet style collagen agents and was more potent on bone and skin than the liquid fibrin adhesive agent. Furthermore, TO-193 had a potent sealing effect at the site of incomplete suture immediately after application on a motile organ such as lung and stomach. These effects may be partly attributable to rapid expression of the effect due to the presence of a high concentration of fibrinogen on coverage. Enhancement of fibrin penetrability to the tissues by compression and inhibition of cleavage of coverage by the collagen sponge also may be participating in the effects of TO-193. These results suggest that TO-193 will be a valuable adhesive and sealing agent.

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.

We have successfully fabricated InGaAs-OI tri-gate nMOSFETs, for the first time. The devices were depletion-type (p-n junction-less) nFETs with Fin-channel width (W fin ) down to 20 nm and had metal source/drain structures. It was experimentally demonstrated that W fin scaling effectively improved cut-off properties at N d up to 5 × 1018 cm−3 and the electron mobility in the narrowest channel (W fin = 20 nm) was about 3x higher than that of the inversion layer. It was also demonstrated that enhancement of In content from 53% to 70% leaded to 30% I on enhancement without I off degradation.

The effects of KBT-3022 and its metabolite desethyl KBT-3022 on platelet aggregation were determined in rat, guinea-pig, rabbit and human platelets in-vitro and ex-vivo. KBT-3022 and desethyl KBT-3022 inhibited platelet aggregation induced by arachidonic acid and collagen in-vitro more potently than aggregation induced by adenosine diphosphate, platelet-activating factor or thrombin, as well as by acetylsalicylic acid, and their effects were approximately 100 times more potent than those of acetylsalicylic acid. Desethyl KBT-3022, but not KBT-3022 or acetylsalicylic acid, inhibited thrombin-induced aggregation and 5-hydroxytryptamine release from platelets more potently than ticlopidine hydrochloride at higher concentrations. Oral administration of KBT-3022 inhibited both arachidonic acid- and collagen-induced platelet aggregation and reduced platelet retention in a glass-bead column approx. 100 times more potently than acetylsalicylic acid. KBT-3022 showed little or no anti-inflammatory effect on either ultraviolet-induced erythema or arachidonic acid induced ear oedema, and had lower gastro-ulcerogenicity than acetylsalicylic acid. These results suggest that KBT-3022 is a potent inhibitor of platelet activation with weak side-effects.

HfAlO/GeOx/Ge p-MISFETs with EOT of 0.84nm are demonstrated. Low interface trap density of GeOx/Ge interface enable us to high mobility. Careful control of high-k fixed charges will allow achieving low EOT and high mobility of Ge p-MISFETs.

Thin-body GeOI substrates with thin Al2O3/SiO2 BOX layers are successfully fabricated for the first time. It is found that the bonding interface was robust enough for Mechanical Polishing and CMP even after bonding at a room temperature in atmosphere. The GeOI surfaces etched with ozone water are atomically flat. Moreover, Dit of as low as 3.9e+11 eV-1cm-2 at the GeOI/BOX is obtained. These results suggest that negligible negative impact on carrier mobility and sub-threshold characteristics can be realized by using the GeOI substrates with thin Al2O3/SiO2 BOX layers.

Hole-mobility and carrier-velocity characteristics of Ge-rich SGOI-nanowire were comprehensively investigated. The Ge-rich SGOI-nanowire channel devices were found to have higher hole-mobility and velocity than that of the unstrained-Ge and SOI devices. The ideal performance assessment revealed that a significant increase (over 2.6 times) in drive current is expected. These indicate that the Ge-rich uniaxially strained SGOI-nanowire channel device has potential to paves the way to future low-power consumption and high-performance CMOS technology.

By developing 6-amidino-2-naphthyl 4-guanidinobenzoate (I, FUT-175) as a basic structure, its various derivatives were synthesized and their inhibitory activities on trypsin, plasmin, kallikrein, thrombin, C1r and C1s as well as on complement-mediated hemolysis were examined. The protective effect of these compounds on complement-mediated Forssman shock was also examined in guinea pigs. 6-Amidino-2-naphthyl 4-[(4,5-dihydro-1H-imidazol-2-yl)amino]-benzoate (41, FUT-187) was found to be a suitable compound for oral administration with anti-complement activity superior to that of compound I.

Although the authors recently reported that nafamostat, a clinically used serine protease inhibitor, was mainly hydrolysed by carboxylesterase in human liver microsomes, the involvement of human liver cytosol has not been elucidated. The current study examined the in vitro metabolism of nafamostat with human liver cytosols. Kinetic analysis indicated that the Vmax and Km values in the liver cytosols were 9.82 nmolmin(-1) mg(-1) protein and 197 microM for a liver sample HL-1, and 15.1 nmolmin(-1) mg(-1) protein and 157 microM for HL-2, respectively. The Vmax/Km values in both cytosols were at least threefold higher than those in the corresponding microsomes. The liver cytosolic activity for nafamostat hydrolysis was inhibited by phenylmethylsulfonyl fluoride (PMSF) (43% inhibition at 100 microM), whereas diisopropyl fluorophosphate (DFP) and bis(p-nitrophenyl)phosphate (BNPP) failed to inhibit the activity. Furthermore, the hydrolytic activity was also reduced by palmitoyl-CoA (67% inhibition at 100 microM) but not by acetyl-CoA. Effects of PMSF, DFP and BNPP on cytosolic palmitoyl-CoA hydrolytic activity were comparable with those of the cytosolic nafamostat hydrolytic activity. In addition, the palmitoyl-CoA hydrolytic activity was competitively inhibited by nafamostat with the apparent Ki value of 164 microM for the liver cytosol from HL-2. These results suggest that an isoform of long-chain acyl-CoA hydrolase may be responsible for the nafamostat hydrolysis in human liver cytosol.

Introduction High mobility channel materials are extensively explored to replace strained-Si in MOSFET devices to reduce power consumption by lowering supply voltages, V dd, without degrading circuit performance. Among the various high mobility channel materials, compressively strained-Ge[1-4] is recognized as the most promising option for p-channel FETs due to its significantly high hole-mobility and compatibility with Si-CMOS process. In this paper, Ge nanowire MOSFETs with a uniaxial compressive strain as high as 3.9% were demonstrated by 2-step Ge-condensation technique. Record-high hole mobility (μ eff = 1922 cm2/Vs) and record-low off-current (2.7x10-9A/μm at V d = -0.5V) were achieved among scaled (sub-100nm L g) Ge MOSFET for the device with the L gof 45nm. Device fabrication Uniaxially strained-Ge nanowire channel was formed by the two-step Ge condensation technique, which induced uniaxial stress along the channel direction[3]. As a gate insulator, 5 nm thick Al2O3 was grown by using ALD. Partly, in order to improve the interface characteristics and hole mobility, MMT-plasma oxidized GeOx / 3.2 nm-Al2O3 stacked gate insulator were adopted[4,5]. Ni(Si)Ge-metal S/D structures were formed by SALICIDE-like process. Detailed device fabrication process was shown in [4]. The Relationship between the wire width, W wire and strain applied to the channel was measured by an immersion high-NA Raman spectroscopy[6] and a NBD measurement. The dependence of strain along the channel direction, ε xx on wire width is shown in Fig.1. Extremely high (-3.8%) strain was evaluated for W wire= 20 nm device, which was almost identical with the value obtained from the NBD measurement. Moreover, extremely high (over -3.9%) strain, which is almost identical with the misfit strain between Ge and Si, was evaluated by strained-Ge nanowire channel formed by improved two-step Ge condensation technique[4]. Mobility enhancement by uniaxial compressive strain In order to estimate the mobility enhancement factors in uniaxially strained-Ge and Si1-x Ge x inversion channels, Poisson-Schrodinger self-consistent solver[7] was used to calculate the effective mass (m eff) values. Here, 6x6 k*p method was used. Figure 2 shows the calculated Ge concentration dependence of inversion layer effective hole mass along [110] channel direction. For Ge (x=1), m eff was calculated to be 0.055m 0 at fully strained condition, i.e., the lattice constant is identical with that of Si in [110] directions. Considering the ratio of m eff, 12 times higher mobility that for unstrained Si can be expected on uniaxially strained-Ge. At these highly strained condition, orientation dependence among (001), (112) and (110) is diminished due to the band deformation. Device characterization Hole mobility was extracted by a split CV method for long-channel and multi-wire devices. Figure 3(a) shows hole-mobility of the fabricated multi-wire MOSFETs. The W wire = 40nm device, which has 95% Ge channel and GeOx / Al2O3 stacked gate insulator, showed a peak hole mobility of 1922 cm2/Vs at N s = 1.7x1012cm-2, which exceeds that of -3.8% strained-Ge nanowire MOSFET with Al2O3 gate stack. Moreover, the obtained mobility at N s = 5x1012cm-2 is corresponding to 5.8 times of the counterpart of a state-of-the-art strained-Si pMOSFETs[1]. Figure 3(b) shows that mobility values for fixed N s increased with Ge concentration, x. The tendency is consistent with the m eff calculation in Fig.2. Figure 4 shows I d-V g characteristics of fabricated strained-Ge nanowire pMOSFET with GeOx / Al2O3 stacked gate insulator. Ion/Ioff ~ 105 has also been attained. And a minimum drain leakage current (I d,off), as low as current 2.7x10-9A/μm at V d = -0.5V, were achieved with L g = 45 nm. This I d,off value is the lowest minimum drain leakage among the previously reported sub-100nm L g strained-Ge devices even though that has a shortest L g. Conclusion s Ge nanowire MOSFETs with a uniaxial compressive strain as high as 3.9% were demonstrated by 2-step Ge-condensation technique. Record high hole mobility (μ eff = 1922 cm2/Vs) and record-low off-current (2.7x10-9A/μm at V d = -0.5V) were achieved among scaled (sub-100nm L g) Ge MOSFET for the device with the L gof 45nm. These results indicate that strained-Ge channels have a potential to serve as pFET channel of scaled future CMOS. References [1] R. Pillarisetty et al., IEDM p.150 (2010). [2] W. Chern et al., IEDM p.387 (2012). [3] K. Ikeda et al., VLSI Symp. p.165 (2012). [4] K. Ikeda et al., VLSI Symp. p.T31 (2013). [5] Y. Kamimuta et al., ISTDM. p.34 (2012). [6] D. Kosemura et al., SSDM p.931(2011). [7] S. Birner et al., IEEE TED 54(2007)2137. Acknowledgements This work was granted by JSPS through FIRST Program initiated by the Council for Science and Technology Policy (CSTP).

Introduction High mobility channel materials are extensively investigated to replace strained-Si in MOSFET devices to reduce power consumption by lowering supply voltages, V dd, without degrading circuit performance. Among the various high mobility channel materials, strained-Ge[1-4] is recognized as the most promising option for p-channel FETs due to its significantly high hole-mobility and compatibility with Si-CMOS process. This paper presents metal S/D nanowire pFETs having a high-mobility strained Ge channel formed by doping-free processes for channels and S/D. The large compressive strain as high as -3.9% resulted in a record high hole mobility (μ eff = 1992 cm2/Vs @ N s = 1.7x1012 cm-2) and a low contact resistivity (ρ c ~ 3.8x10-8 Ω cm2). Device fabrication Uniaxially strained-Ge nanowire channel was formed by the two-step Ge condensation technique, which induced uniaxial stress along the channel direction. As a gate insulator, GeOx interlayer and 3.2 nm- Al2O3 were grown by using MMT-plasma[4,5] and ALD, respectively. NiGe-metal S/D structures were formed by SALICIDE-like process on the unintentionally doped Ge nanowire. Detailed device fabrication process was shown in [3,4]. Figure 1(a) shows a XTEM of the narrowest channel with a wire width (W wire) of 15 nm. The Relationship between the W wire and strain applied to the channel was measured by a Raman spectroscopy. The dependence of strain along the channel direction ε xx on W wire is shown in Fig. 1(b). Extremely high (over -3.9%) strain, which is almost identical with the misfit strain between Ge and Si, was evaluated for sub W wire=40 nm devices. Device characterization Hole mobility was extracted by a split CV method for long-channel and multi-wire devices. Figure 2(a) shows hole-mobility of the fabricated multi-wire MOSFETs. The W wire = 40nm device, which has 95% Ge channel, showed a peak hole mobility of 1922 cm2/Vs at N s = 1.7x1012cm-2, which exceeds that of -3.8% strained-Ge nanowire MOSFET with Al2O3 gate stack[3]. Moreover, the obtained mobility at N s = 5x1012cm-2 is corresponding to 5.8 times of the counterpart of a state-of-the-art strained-Si pMOSFETs[1]. Ion / Ioff ~ 105 has also been attained for the strained-Ge nanowire pMOSFET with a gate length (Lg ) of 40 nm (Fig. 2(b)). A metal S/D MOSFET is an attractive candidate because of its low extension sheet resistance properties without a heavy doping in extension regions. However, parasitic resistance (R para) which is dominated by contact resistance (R c) between the extension metal and the inversion layer in this device, have been still an issue because of the decreasing contact area. Here, we demonstrate low R c characteristic due to low Schottky barrier height (SBH) for NiGe/ strained-Ge interface. The W wire dependence of parasitic resistance (R SD) were evaluated as shown in Fig. 3. Reduced R SD as low as 490 Ωμm for W wire = 54 nm device is achieved by using undoped Ge nanowire formed by two-step Ge condensation. The specific contact resistivity, ρ c of NiGe / strained-Ge interface was estimated by using previously proposed model[3]. Extremely low ρ c, that is as low as ~ 3.8x10-8 Ω cm2 has been achieved in spite of doping-free Schottky contact presumably due to the strong Fermi-level pinning to the valence band edge of the strained-Ge and reduction of SBH at Ni(Si)Ge/(Si)Ge interface by rising valence subband top energy for higher Ge concentration and strain. Conclusion Record high hole mobility (μ eff = 1922 cm2/Vs) and extremely low S/D contact resistivity (ρ c ~ 3.8x10-8 Ω cm2) were achieved for the highly strained-Ge nanowire pMOSFET. These results indicate that strained-Ge channels have a potential to serve as pFET channel of ultimately-scaled future CMOS. References [1] R. Pillarisetty et al., IEDM p.150 (2010). [2] W. Chern et al., IEDM p.387 (2012). [3] K. Ikeda et al., VLSI Symp. p.165 (2012). [4] K. Ikeda et al., VLSI Symp. p.T31 (2013). [5] Y. Kamimuta et al., ISTDM. p.34(2012). Acknowledgements This work was granted by JSPS through FIRST Program initiated by the Council for Science and Technology Policy (CSTP).

Ga2O3 film growth on InGaAs substrates was investigated using an atomic layer deposition system with trimethylgallium (TMGa) and H2O as precursors. Self-limiting growth of Ga2O3 was confirmed on InGaAs substrates as well as on Si and GaAs. During initial formation of the Ga2O3 film on an InGaAs substrate, the selective self-cleaning effect of TMGa on AsOx and GaOx was observed. The insertion of ultrathin Ga2O3 into an Al2O3/InGaAs gate stack as an interfacial passivation layer proved quite effective to reduce Dit around the midgap. The Al2O3/InGaAs MISFET performance also revealed improvement of the effective mobility for both NH4OH- and (NH4)2S-treated devices.

TO-193 (TachoComb) is a new fibrin adhesive agent that consists of a collagen sheet coated with fibrin glue. We compared the hemostatic effect of TO-193 in several experimental models with Beriplast P as a fibrin adhesive agent, Avitene and Novacol as a microfibrillar collagen hemostat, and a sponge-like collagen sheet as the constitutional parts of TO-193. In the in vitro bleeding model in which blood leaks out through cotton cloth, the pressure of TO-193 when blood leakage was observed was higher than those of Beriplast P, Avitene, Novacol and the collagen sheet, indicating that TO-193 possessed a strong adhesive effect on the bleeding surface. On the kidney resection surface, TO-193 showed a more potent adhesive effect than those of Beriplast P and the collagen sheet, suggesting that TO-193 has a potent hemostatic effect. In the liver resection, TO-193 significantly reduced the bleeding volume compared with that of Novacol in normal rats. Furthermore, the bleeding volume of TO-193 was about half that of Beriplast P and equivalent to that of Novacol even in anticoagulant-treated rats. From these data, it is expected that TO-193 would be a valuable hemostatic agent for clinical use since TO-193 possesses a potent adhesive ability on the bleeding resection surface and would certainly stop bleeding in both patients with normal coagulation and those with a low blood coagulation condition.

We devised a method for evaluating polymorphonuclear leukocyte (PMN) infiltration in vivo employing an air bleb technique combined with measurement of myeloperoxidase (MPO) activity, and the effects of some anti-platelet agents were evaluated. KBT-3022 (ethyl 2-[4,5-bis (4-methoxyphenyl)thiazol-2-yl] pyrrol-1-ylacet ate) and cilostazol inhibited the increase in MPO activity in the connective tissue around the air bleb induced by leukotriene B4 (LTB4) and formyl-methionyl-leucyl-phenylalanine (fMLP). Indomethacin inhibited only the fMLP-induced increase in MPO activity, but ticlopidine hydrochloride and acetylsalicylic acid had no effect. Histologic observation confirmed the inhibition of PMN infiltration by KBT-3022. These results indicate that KBT-3022 may be a potent inhibitor of both LTB4- and fMLP-induced infiltration of PMNs.

Inhibitory activities of FUT-187 on trypsin-like serine proteases were compared using camostat mesilate (camostat), and 4-(4-guanidino benzoyloxy)-phenyl acetic acid methanesulfonate (GBPA) known as an active metabolite of camostat in the blood. Ki values of FUT-187 on the competitive inhibition mechanism were 0.097 microM for trypsin, 0.029 microM for pancreatic kallikrein, 0.61 microM for plasma kallikrein, 0.57 microM for plasmin, 2.5 microM for thrombin, 20.4 microM for factor Xa and 6.4 microM for C1r. However, FUT-187 acted as a noncompetitive inhibitor for factor XIIa and an uncompetitive inhibitor for C1s, and Ki values for these proteases were 0.021 and 0.18 microM, respectively. Ki values of camostat for these proteases were in the range of 0.037 to 96.4 microM, and those of GBPA for the above proteases except trypsin and plasma kallikrein were higher than those of FUT-187. The inhibitory activity of FUT-187 on trypsin was not reduced by the addition of the serum at 10%, whereas, that of GBPA was reduced (4.3 fold) in terms of IC50 values. The concentration of FUT-187 required to double APTT (activated partial thromboplastin time) was 1.09 microM, while GBPA, by concentrations up to 1 mM failed to double APTT. The kinin formation by glandular kallikrein in the rat plasma was inhibited by FUT-187 with IC50 value of 0.024 microM, while camostat revealed no inhibition by concentrations up to 1 microM. The complement-mediated hemolyses in the classical and alternative pathways were also inhibited by FUT-187 with IC50 values of 0.17 and 3.5 microM, respectively, the corresponding values for camostat being 350 and 150 microM, respectively. It is concluded that FUT-187 is a potent and selective inhibitor of trypsin-like serine proteases, and its inhibitory activities are stronger than those of camostat on glandular kallikrein, factor XIIa and C1s in complement pathway.

on such Ge-rich non-planar channels. 9) In this letter, we demonstrate a fabrication process and high hole mobility characteristic of uniaxially strained SiGe-on-insulator (SGOI) channel tri-gate MOSFET with Ge fraction x of 0.65 formed by two-step Ge condensation. The current drive of a uniaxially strained SGOI channel tri-gate MOSFET, which has a nickel-germanosilicide (NiSiGe) metal S/D structure with gate length (Lg) of 50 nm and wire width (Wwire) of 25 nm, was also investigated and compared with that of SOI channel tri-gate MOSFETs. Sufficiently high mobility and higher current drive were obtained in the SGOI channel tri-gate FETs than those of the SOI channel tri-gate MOSFET, as well as high immunity to the short-channel effects.

Antigenicity study of 6-amidino-2-naphthyl 4-[(4, 5-dihydro-1H-imidazol-2-yl) amino] benzoate dimethanesulfonate (FUT-187), a new protease inhibitor, was investigated in guinea pigs and mice and the following results were obtained. 1. In guinea pigs immunized with FUT-187 plus adjuvant by intramuscular / subcutaneous routes, ASA, ACA and PCA reactions challenged intraveneously or intradermally were positive. 2. In guinea pigs immunized with FUT-187 plus adjuvant by intramuscular / subcutaneous routes, ASA and PCA reactions challenged orally were negative. 3. In guinea pigs immunized with FUT-187 by the oral route, ASA, ACA and PCA reactions were negative. 4. In guinea pigs immunized with IABA and AN plus adjuvant by intramuscular / subcutaneous routes, ASA and PCA reactions were negative. 5. 48-hr PCA reactions were elicited with sera obtained from BALB / c and C3H / He mice immunized with FUT-187 plus adjuvant by the intraperitoneal route, responses were negative. 6. From the results of hapten inhibition tests using anti-FUT-187 guinea pig serum, it is suggested that the antigenicity of FUT-187 is attributable to the its benzoic acid.

Effect of nafamostat mesilate (FUT-175), a serine protease inhibitor, having anti-inflammatory effects was studied on superoxide (O2-) production in rat polymorphonuclear leucocytes (PMN) and compared with those of other serine protease inhibitors and typical anti-inflammatory agents. 1) O2- productions in rat PMN stimulated with concanavalin A (Con A) and cytochalasin B (Cyt B) were too weak to observe. With NADH, however, strong O2- production was induced by Con A and Cyt B. 2) FUT-175 at 10(-6) and 10(-5) M inhibited O2- production in rat PMN induced by Con A and Cyt B with NADH in a concentration-dependent manner. 3) The serine protease inhibitor L-tosylamido-2-phenylethyl-chloromethyl ketone (TPCK) and soybean trypsin inhibitor (SBTI) inhibited O2- production at 10(-5) M and 10(-4) M, respectively, while aprotinin, chymostatin and leupeptin did not. 4) Neither indomethacin nor dexamethasone, typical anti-inflammatory agents, inhibited O2- production. Mepacrine, a phospholipase A2 inhibitor, strongly inhibited it. 5) O2- production in PMN prepared from the rat administered FUT-175, 200 mg/kg, p.o., was significantly decreased in comparison with that of the control rat. 6) FUT-175 had no effect on O2- production by hypoxanthine-xanthine oxidase. These results showed FUT-175 had a strong inhibitory effect on O2- production in rat PMN which other typical anti-inflammatory agents did not have.

Stable hydraulic pressure pulse series can be generated by an appropriate valve operation at a pipe end. The pressure of the pulse series is amplified by a booster piston, consequently the pressure pulse series with a pressure higher than 400 MPa is obtained for a frequency of 15.2 Hz. By a pressure intensifier applying the amplified pressure pulse series, a continuous oil flow with an amplified pressure higher than 300 MPa is obtained for a source pressure of 6.6 MPa, Using this pressure pulse series generator as a lateral pressure cutting device of a ductile material, an aluminum column of 20 mm in diameter with a notch is cut after 580 cycles of the repeating pressure of 204 MPa. Hydraulic pressure pulse series generator discussed in this paper is practical enough to be used as a pressure intensifier and a lateral pressure cutting device.

繊維の密度-水分率曲線から,(p+c) を求める式を導いた。ここにpは繊維内部 (有機媒質の浸入しない部分) の吸着水と全吸着水との質量比で, cは繊維1gあたりの外部 (有機媒質の浸入する部分) 吸着水の容積収縮に自由水の密度をかけたものである。木綿, レーヨン, 羊毛, 絹および合成繊維について,(p+c) と水分率との関係を求め, これらの繊維の吸湿性について論じた。さらに, 水中で測定した密度について論じ, cはpに比してかなり小さいことを結論した。

酢酸繊維素繊維および皮膜の吸湿による密度の変化を有機媒質を用いて浮沈法で測定し, さらに水中の密度も測定した。他の繊維の場合と同じように, 密度は数%の吸湿量で極犬を示す。これらの結果から, 試料内部 (有機媒質の入れない部分) の吸湿量pと全吸湿量xの関係を求めた。三酢酸繊維素繊維 (酢化度61.8%) は二酢酸繊維素繊維 (酢化度54%) よりpが少ない。これは前者の結晶化度が高いためであろう。未処理の三酢酸繊維素皮膜 (酢化度60.5%) は二酢酸繊維素皮膜 (酢化度54.7%) とほとんど同じpの値をもつ。これは両皮膜が似た結晶化度をもつためであろう。また, 繊維, 皮膜とも, p-x曲線は徐々に飽和値まで増大する。

The apparent molal volume of amino acids in aqueous solutions increases with the ionic strength of other simple ions. The relation between molal volume and ionic strength was explained according to Kirkwood's theory. From the fact that this relation is equal for various α-amino acid, it was concluded that the hydration of hydrocarbon part was not accompanied with the electrostriction. Thus the two kinds of hydration are epxected for amino acids, or, more generally, for all water-soluble organic substances.

ビニロン製造工程中の3種類のポリビニルアルコール繊維 (D. P. 1600, 3d), すなわち未処理のもの (A), 熱処理したもの (B), およびさらにホルマール化したもの (C) について, 吸湿による密度の変化を浮沈法により測定した。吸湿量0のA, B, Cの密度は25℃でそれぞれ1.298, 1327, 1, 2789/ccであった。密度一吸湿量の関係でA, Bは吸湿量約2%のところに密度の極大があり, 吸湿量の増えるに従って徐々に密度が減少する。しかしCには極大がないようで, また密度の減少する勾配がA, Bより急である。これらの挙動はポリビニルアルコール繊維の吸着水について若干の示唆を与える。

1. The effects of FUT-175 on the development of adjuvant arthritis in rats were studied and compared with those of indomethacin. FUT-175 inhibited both primary and secondary paw lesions in the adjuvant arthritic rats when it was administered orally on a daily basis from the day before through 18th day after adjuvant injection. 2. In addition, FUT-175 inhibited the increase in hemolytic complement in adjuvant arthritic rats in a dose-dependent manner. 3. Indomethacin also showed an inhibitory effect on the development of arthritic lesion, but had no effect on the increase in hemolytic complement in the adjuvant arthritis in rats. 4. Furthermore, FUT-175 inhibited the activities of various proteases in vitro , and then strongly inhibited complement-mediated hemolysis via the classical and alternative pathways, while indomethacin had no effect on them. 5. These results suggest that the anti-inflammatory activity of FUT-175 may differ from indomethacin in the mechanisms of action and, at least in part, due to the anti-complement activity.

FUT-175 inhibited the zymosan-induced rat paw edema in a dose-dependent manner, while indomethacin exhibited no significant activites in this model. FUT-175 also inhibited the decrease in hemolytic complement (CH50) induced by zymosan in vitro, and indomethacin was inactive. These results suggest that FUT-175 has potent in vitro and in vivo nhibitory activity against the activation of the complement system induced by zymosan.

FUT-175, 6-amidino-2-naphthyl p-guanidinobenzoate dimethanesulfonate (nafamstat mesilate), a novel synthetic protease-inhibiting agent, was studied to determine its in vitro effects against various proteases and other enzymes, as well as to determine its in vivo protease inhibitory effects. FUT-175 was found to inhibit, in an intense, specific and reversible way, the enzyme activities of trypsin, C1r, C1s, thrombin, kallikrein and plasmin with IC50 values of the order of 10(-6)-10(-8) M. FUT-175 also inhibited complement-mediated hemolysis, including both classical and alternative pathways, sites of inhibition being on C1r and C1s as evidenced by the intermediate-cell technique. In animal model reactions in which the complement system is known to be involved as pathogenetic factors, e.g., Forssman shock, Forssman cutaneous vasculitis, zymosan-induced paw edema, endotoxin shock and local Shwartzman reaction, FUT-175 was highly effective in that, for example, intravenous dosing at 3 mg/kg could completely protect guinea pigs from the lethal Forssman shock. FUT-175 was also found to be effective in trypsin-induced shock in mice, in lethality due to thrombin-thrombosis in mice and in kinin formation in the inflammatory process in rats.

Angiotensin converting enzyme (ACE) inhibitory activity of MK-0521 in dogs and the effects of its single oral administration on blood pressure and the renin-angiotensin system in 2-kidney Goldblatt hypertensive dogs were compared with those of captopril and MK-421. MK-0521 at 0.001-0.1 mg/kg, i.v., or 0.01-1 mg/kg, p.o., attenuated the pressor effect of angiotensin I without affecting that of angiotensin II and augmented the depressor effect of bradykinin. The potency of MK-0521 to reduce the pressor effect of angiotensin I was 9.8 times that of captopril by intravenous administration, and by oral administration, it was 15.9-32.1 times that of captopril and approximately 3 times that of MK-421. When administered orally, the onset of action and the time to peak effectiveness were more rapid than those of MK-421, but slower than those of captopril. Duration of the action of MK-0521 was longer than that of captopril and equal or longer than that of MK-421. The inhibition of ACE was well correlated with serum MK-0521 levels. MK-0521 produced a dose-dependent antihypertensive effect in 2-kidney Goldblatt hypertensive dogs at over 0.3 mg/kg, p.o., without affecting the heart rate. The antihypertensive effect of MK-0521 was persistent and approximately 3 times more potent than that of captopril. MK-0521 inhibited the serum ACE activity and increased the plasma renin activity, while it had a tendency to decrease plasma aldosterone level. These changes were parallel to the time course of the antihypertensive effect. These results suggest that the main mechanism of the antihypertensive effect of MK-0521 is the suppression of angiotensin II production due to the inhibition of the ACE.

N-alpha-[(S)-1-carboxy-3-phenylpropyl]-L-lysyl-L-proline (MK-0521) is a new non-sulfhydryl-containing angiotensin converting enzyme (ACE) inhibitor. The present investigation describes its ACE and other enzymes inhibitory properties and compares it to those of captopril, MK-421 and MK-422 in vitro. MK-0521 inhibited rat pulmonary ACE by 50% (IC50) at a concentration of 3 nM and was 6.13 times more potent than captopril. The IC50 values of MK-421 and MK-422 against ACE were 2,000 nM and 3.5 nM, respectively. MK-0521 had practically no inhibitory activities against carboxypeptidase A, carboxypeptidase B, leucine aminopeptidase, papain, pepsin and trypsin. The kinetic study on the inhibitory activity of M-0521 against ACE using Lineweaver-Burk plots indicated that MK-0521 exerted competitive ACE inhibition. The dialysis study conducted on the ACE-MK-0521 complex revealed that the inhibitory effect of MK-0521 against ACE was reversible. In the guinea pig ileum, MK-0521 potentiated the contractile effect of bradykinin and depressed the contractile effect of angiotensin I. These effects on bradykinin and angiotensin I were 33.11 and 2.63 times more potent than that of captopril, respectively. The present results suggest that MK-0521 may show a potent hypotensive effect in vivo.

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..