Search

The therapeutic potential of monoacylglycerol lipase (MAGL) inhibitors in central nervous system-related diseases has attracted attention worldwide. However, the availability of reversible-type inhibitor is still limited to clarify the pharmacological effect. Herein, we report the discovery of novel spiro chemical series as potent and reversible MAGL inhibitors with a different binding mode to MAGL using Arg57 and His121. Starting from hit compound 1 and its co-crystal structure with MAGL, structure-based drug discovery (SBDD) approach enabled us to generate various spiro scaffolds like 2a (azetidine-lactam), 2b (cyclobutane-lactam), and 2d (cyclobutane-carbamate) as novel bioisosteres of 3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl moiety in 1 with higher lipophilic ligand efficiency (LLE). Optimization of the left hand side afforded 4f as a promising reversible MAGL inhibitor, which showed potent in vitro MAGL inhibitory activity (IC50 6.2 nM), good oral absorption, blood-brain barrier penetration, and significant pharmacodynamic changes (2-arachidonoylglycerol increase and arachidonic acid decrease) at 0.3-10 mg/kg, po. in mice.

Voltage-control spintronics memory (VoCSM) is a spintronics-based memory that uses the voltage-control-magnetic-anisotropy (VCMA) effect as a selection method and the spin-Hall effect as a write method, and is a candidate for future nonvolatile main memory because of its advantages such as high density, low energy consumption, and robustness against read disturbance. In this paper, we demonstrate VoCSM with a self-aligned heavy-metal electrode, which is the most desirable in mass production and can expect the lowest critical current ( $I_{C})$ due to its narrow electrode structure. We obtain the value of $I_{C}$ of around $400~\mu \text{A}$ for a magnetic tunnel junction of size $35~{\mathrm{ nm}} \times 245$ nm by using a self-aligned heavy-metal electrode. The value is lowered to one-third that of the conventional VoCSM structure and is comparable with that of spin-transfer torque writing. Moreover, $I_{C}$ decreased due to the VCMA effect and reached $260~\mu \text{A}$ for $\text{V}_{\mathrm {MTJ}} = -0.8$ V. We also found that the diffusion spin current from the lateral region, which is the concern matter of this structure, did not contribute very much to the switching due to the extremely short spin diffusion length of the heavy-metal electrode. It indicates that VoCSM with a self-aligned heavy-metal electrode may lead to the production of high-density and low-energy-consumption memory.

We successfully demonstrated write tests in voltage-control spintronics memory (VoCSM) in which in-plane magnetic tunnel junctions (MTJs) with aspect ratio of about 1 (AR1) were used. Retention energy as large as that in MTJs with an aspect ratio of 2.5 was stored in AR1-MTJs. We controlled the strain introduced into the AR1-MTJs to store retention energy owing to strain-induced anisotropy. Results in the write tests show the possibility of high-density VoCSM using in-plane MTJs whose cell area is as small as 4F2.

We report a novel convolutional neural network (CNN) accelerator utilizing “voltage control spintronics memory” (VoCSM). High throughput processing is achieved by high speed in-“nonvolatile memory”-computation using high density VoCSM array. Since VoCSM has largest endurance even in short write pulse of all nonvolatile memories, write access speed can be increased. Also, density of processing element is higher than conventional SRAM based one, throughput is further increased. These technique reduces latency of CNN by 46% (ternary) and 73% (binary) compared to conventional CMOS processor with 8bit integer (INT8) for CIFAR-10 classification task. Also, energy is reduced by 72% (ternary) and 86% (binary).

Magnetic random-access memory (MRAM) using spin-transfer torque for write operations has been intensively developed as a technology for saving energy. The authors' recently presented voltage-controlled spintronic memory (VoCSM), which instead employs the spin Hall effect for writing, is here refined. High writing efficiency in VoCSM is achieved by means of an $a$-TaB/$\ensuremath{\beta}$-Ta spin Hall electrode, which features reduced write-current density, low write-error rate, strong durability, and high breakdown voltage. This improved VoCSM is seen as a path to high-density, high-speed nonvolatile memory with low power consumption.

Monoacylglycerol lipase (MAGL) is a major serine hydrolase that hydrolyzes 2-arachidonoylglycerol (2-AG) to arachidonic acid (AA) and glycerol in the brain. Because 2-AG and AA are endogenous biologically active ligands in the brain, inhibition of MAGL is an attractive therapeutic target for CNS disorders, particularly neurodegenerative diseases. In this study, we report the structure-based drug design of novel piperazinyl pyrrolidin-2-ones starting from our hit compounds 2a and 2b. By enhancing the interaction of the piperazinyl pyrrolidin-2-one core and its substituents with the MAGL enzyme via design modifications, we identified a potent and reversible MAGL inhibitor, compound ( R)-3t. Oral administration of compound ( R)-3t to mice decreased AA levels and elevated 2-AG levels in the brain.

We investigated a voltage-control spintronics memory (VoCSM) with a shunt-free design process and W spin-Hall electrode. We successfully reduced the write current to 62 μA at a 5-ns write pulse (48 μA at a 20-ns write pulse), utilizing a high spin-Hall efficiency by developing the shunt-free design process and optimized W spin-Hall electrode. Moreover, the device was very reliable, exhibiting properties such as a low write error rate ( 1 × 1012 cycles). The spin-Hall MRAM and VoCSM with the shunt-free design process and W spin-Hall electrode could lead to high-speed nonvolatile memory with low power consumption and high durability.

Voltage Control Spintronics Memory (VoCSM) is a magnetic memory combining the spin Hall effect and Voltage Controlled Magnetic Anisotropy (VCMA). It has the potential to make MRAM work faster. In this paper, we described memory design of a write window and a read window of high-speed VoCSM from experimental data. The design windows of both writing and reading are large enough for gigabit memory.

The requirement of low power consumption, high speed, high endurance for emerging next generation universal memory, a three terminal (separate read/write terminals) spin-orbit-torque (SOT) based non-volatile memory (SOT-MRAM) devices have been gaining much interests than two-terminal spin-transfer-torque MRAM (STT-MRAM) due to its improved magnetization switching, exploiting the spin Hall effect (SHE) mechanism [1–6]. The free layer of SOT-MRAM devices, consists of heavy metal (HM)/ferromagnet metal (FM) bilayer structure, essentially rely on two factors, first the magnitude of SOT from HM which is proportional to spin Hall angle (SHA), and the second is the effective damping constant $( \alpha _{\mathrm{eff}})$ of FM in FM/HM bilayer structure. Since the switching current in SOT-MRAM using in-plane magnetization of magnetic tunnel junction (i-MTJ) is inversely proportional to HM’s SHA and directly proportional to FM’s $\alpha_{\mathrm{eff}}$, we need to search for HM materials with high SHA and at the same time with low $\alpha _{\mathrm{eff}}$ of FM for HM/FM bilayer structure combination. Previously, we have shown the excellent magnetization switching behavior of SOT-MRAM using Ta 50 B 50 (HM), and evaluated its SHA by spin Hall magnetoresistance (SMR) measurement [7]. However, analysis of SHA based on SMR assume a simple drift-diffusion model and as for estimation of the effective damping constant, SMR cannot be applied. In this study, the spin-transfer ferromagnetic resonance (ST-FMR) method was used to evaluate both SHA of Ta 50 B 50 (HM) and $\alpha _{\mathrm{eff}}$ of Co 40 Fe 40 B 20 (FM) for Ta 50 B 50 ($t$ nm)/Co 40 Fe 40 B 20 (4 nm) bilayer structure. The ST-FMR mixed-signal can be fitted by the combination of symmetrical and asymmetrical components by $\mathrm {V_{Total}} = \mathrm {V_{Sym}} + \mathrm {V_{Asym}}$, where $\mathrm {V_{Total}}$ is total mixed signal, $\mathrm {V_{Sym}}$ is total symmetrical signal due to spin current, and $\mathrm {V_{Asym}}$ is total asymmetrical component due to charge current. The ST-FMR signal, its fitting and extracted each individual components are shown in Fig. 1 (a). The SHA evaluation is not straightforward, since other parameters/mechanisms, which are taking place simultaneously, have to be taken into account. At ferromagnetic resonance two phenomenons are taking place concurrently, the SHE from HM to FM and spin pumping (SP) from FM to HM. The SP induced spin current is converted back to charge current in HM through the inverse spin Hall effect (ISHE) which is reflected in symmetrical ST-FMR voltage signal and can be represented by $\mathrm {V_{Sym}} = \mathrm {V_{ST-FMR}} + \mathrm {V_{ISHE}}$. In order to remove the SP influence or considering contribution only from SHE i.e. $\mathrm {V_{ST-FMR}}$, the ratio of $\mathrm {V_{ST-FMR}}$ to $\mathrm {V_{Sym}}$ defined by η, is crucial and can be expressed as $\eta = \mathrm{V_{ST-FMR}}/ \mathrm{V_{Sym}} = \mathrm{V_{ST-FMR}}/ (\mathrm{V_{ST-FMR}}+ \mathrm{V_{ISHE}})$. This ratio η is very important, since both SHE and ISHE have the same angle dependence (due to similar mechanism), it is very difficult to isolate them, as suggested by other groups too [8, 9]. In addition, the influence of transparency $T$ at Ta 50 B 50 /Co 40 Fe 40 B 20 interface has to be taken into account for reliable SHA estimation [9, 10]. The transparency, which controls the spin trasnmittance at interface, is related to spin mixing conductance at the HM/FM interface. The spin mixing conductance was calculated from the enhancement of damping constant $( \Delta \alpha )$ of FM due to spin pumping from its intrinsic value $( \alpha _{0})$. The real value of SHA can be calculated by incorporating interface transparency $T$ and isolating the ISHE $( \mathrm{V_{ISHE}})$ contribution from $\mathrm{V_{Sym}}$, that is η. These contributions are incorporated by mathematically multiplying $T$ and η to conventional SHA $\Theta _{\mathrm{SH(r)}} = \eta T \Theta _{\mathrm{SH(m)}}$, where $\Theta _{\mathrm{SH(r)}}$ is the real value of SHA while $\Theta _{\mathrm{SH(m)}}$ is the observed value of SHA estimated by typical approach. In the observed SHA value, neither SHE contributions were separated nor was interface transparency considered, which leads to the overestimation of SHA. The values η, $T$ and $\eta T$ are shown as a function of Ta 50 B 50 layer thickness in Fig. 1 (b). As it is clear that the ratio η decreases systematically with Ta 50 B 50 layer thickness, however the interface transparency $T$ increases steeply and then saturates at around 2.5 nm. Their product $\eta T$ shows initial enhancement and after peak, a systematic decrease is observed. It is obvious that at lower Ta 50 B 50 thickness, interface transparency controls whereas at higher thickness the $V_{ST-FMR}$ contribution dominates. In the Fig. 1 (c), each individual symmetrical components are shown, which is required for reliable SHA estimation. The dependency of $\Theta _{\mathrm{SH(r)}}$ on Ta 50 B 50 layer thickness is illustrated in Fig. 1(d). By considering only SHE contribution and interface transparency we are able to evaluate the real value of SHA. This SHA value is nearly consistent with the derived SHA from separately fabricated SMR devices [7]. In conclusion, we have successfully estimated the SHA (-0.18) of Ta 50 B 50 by isolating SHE contribution from total ST-FMR signal combined with transparency at Co 40 Fe 40 B 20 Ta 50 B 50 interface. Additionally, we were able to achieve desired low damping constant $( \alpha _{\mathrm{eff}}) \approx 0.008$ for Co 40 Fe 40 B 20 /Ta 50 B 50 bilayer which is also crucial factor for realizing low switching current for future SOT-MRAM applications.

In recent years, writing data in magnetic random access memory (MRAM) utilizing voltage controlled magnetic anisotropy (VCMA) has attracted much attention for its potential low power consumption [1]. We proposed voltage-control spintronics memory (VoCSM) which had high-efficient and deterministic writing properties [2]. In order to realize those memories, three features of a large VCMA, a large surface anisotropy Ks, and a large tunneling magnetoresistance (TMR) should coexist. In addition, a large spin-Hall angle is a must for VoCSM. Many challenges based on MgO tunneling barrier/ferromagnetic layer (FL) such as CoFeB thin films combined with various materials as an insertion layer at the MgO/FL interface or as an underlayer of FL showed improved VCMA but were concerned to fail in the coexistence of the feature because of very thin storage-layer or degraded lattice growth between MgO and CoFeB [3]–[5]. As a result, none of them have had a practical meaning as a memory cell so far. In this study, the experiments were conducted in which the insertion position of Ir was changed in MgO/CoFeB/Ta thin films. Each of the interface layer, the interlayer and the underlayer of Ir showed an increase in VCMA, and the largest VCMA was obtained in the case of inserting the Ir interlayer into the CoFeB layer. In addition, both the resistance-area product (RA) and TMR ratio decreased greatly when using the Ir interface layer, but clearly improved by employing the Ir interlayer. The base multilayer structure for VCMA measurement was Ta (5 nm)/MgO $(\sim 3$ nm)/CoFeB (1–2 nm)/Ta (5–8 nm), which was deposited on a thermally oxidized Si substrate. The CoFeB layer was set to in-plane magnetization, and the base stack of IrMn/ CoFe/Ru/CoFeB /MgO/CoFeB/Ta with a reference layer was prepared for RA and TMR measurement by using current in-plane tunneling (CIPT). The multilayers for VCMA were patterned and etched into the device size with one side of 3 to $50 \mu \mathrm {m}$ and their hysteresis curves were measured using the magneto-optical polar Kerr effect. The effective perpendicular magnetic anisotropy field Hk $_{eff}$ of the CoFeB layer was measured while bias voltage was applied to the device, and the variation of Ks depending on the electric field E was evaluated as the VCMA coefficient. Figure 1 shows the VCMA coefficients (–dKs/dE) of the MgO/CoFeB/Ta thin films as the “Base” sample, “Interface” sample in which Ir (0.2 or 0.3 nm) is layered at the MgO/ CoFeB interface, “Interlayer” sample in which Ir (0.3 nm) is inserted in the middle of the CoFeB layer, and “Underlayer” sample in which Ir (0.5 nm) is formed between the CoFeB and the Ta layer. All coefficients of the “Interface”, “Interlayer”, and “Underlayer” samples increased more than that of the “Base” sample in terms of each average value, although each coefficient had a certain degree of dispersion. The Ks in the “Interface” sample also increased more than in the “Base” sample at each average value, however, the largest Ks (maximum of 2.2 erg/cm $^{2})$ and VCMA (maximum of 190 fJ/ Vm) were obtained in the “Interlayer” sample. The relationship between RA and TMR ratio in the MTJ samples similar to Fig. 1 with the reference layer is plotted in Fig. 2. Both RA and the TMR ratio in the “Underlayer” sample were almost the same as those in the “Base” sample, but both decreased in the “Interface” sample and further decreased by increasing the Ir layer thickness from 0.2 to 0.3 nm. In the “Interlayer” sample, the deterioration of RA was not observed, and although the TMR ratio decreased, it still showed a high value of more than 120%. By comparison at the Ir thickness of 0.3 nm, it can be seen that both RA and TMR are clearly improved by changing from the Ir interface layer to the Ir interlayer. In summary, we successfully found the practical MTJ structure as a memory cell which realized coexistence of a large VCMA, a large Ks, and a large TMR for the first time. The structure is expected to have a large spin-Hall effect as well. This work was partly supported by the ImPACT Program of the Council for Science, Technology and Innovation (Cabinet Office, Government of Japan).

MRAM has been developed since 1980s until now with several ups and downs. The ultimate purpose is to realize non-volatile working memories to save energy consumption of conventional volatile working memories such as SRAM and DRAM. However all of non-volatile memories including MRAM have been facing a dilemma of non-volatility and high energy consumption in their active mode because non-volatility has led to large writing-energy consumption, $E_{w}$. As a result, they have been used as data storages and none of them overcame the historical dilemma for busy applications. This is the one of the reasons why MRAM has not had big markets so far. Recently, the possibilities of overcoming the dilemma were demonstrated by both STT-MRAM and VoCSM [1], [2]. STT has better maturity but less room for further improvement. On the other hands, VoCSM has poor maturity but better potentials in terms of higher writing efficiency and better endurance [3]. In this talk, STT technologies and VoCSM technologies is reviewed with respect to saving energy consumption and remaining issues for VoCSM will be discussed at the conference.

Our new proposal of voltage-control spintronics memory (VoCSM) in which spin-orbit torque in conjunction with the voltage-control-magnetic-anisotropy effect works as the writing principle showed small switching current of $37~\mu \text{A}$ for about 350 $K_{B}T$ switching energy. This indicates VoCSM’s writing efficiency is so high that VoCSM would be applicable for deep learning memories requiring ultra-low power consumption.

Low power consumption of high-speed memories such as cache memories will be realized by use of magnetic random access memory (MRAM). We have proposed the voltage-control spintronics memory (VoCSM) as a writing method. The VoCSM has a large operation margin because the current path in writing and the voltage path in reading are separated. The fabrication process we have employed is the two-step self-alignment (TSSA) process that is advantageous for reducing write current and thus addresses one of the MRAM issues. The electrical properties of the VoCSM indicate that the write error rate (WER) steeply decreases depending on write current. This shows the VoCSM is available for low write current. For highspeed operation, differential operation is demonstrated. In this operation, two magnetic tunnel junctions (MTJs) are simultaneously written at write current, and then either of them is in the high-resistance state and the other is in the low-resistance state. Furthermore, we propose and demonstrate that the write current during differential operation is reduced by the U-shape, since the write current beneath two MTJs absolutely flows to the opposite directions in this shape. The VoCSM is suitable for application to high-speed memories.

We propose a new spintronics-based memory architecture with 2 MTJs and 4 transistors as a unit cell for high-speed application. The architecture employs spin-Hall effect as a writing principle and voltage-control-magnetic-anisotropy (VCMA) effect as a write speed acceleration. We successfully demonstrated the unique complementary flash-writing scheme and proved a potential of ultrahigh speed writing with the prototype unit-cell and the test-element.

Spin-accumulation in Si for epitaxial CoFe/highly (100)-textured MgO/Si devices is investigated and compared to that for CoFe/polycrystalline or (110)-textured MgO/Si devices. We find that magnesium (Mg) insertion between MgO and Si leads to highly (100)-textured MgO and epitaxial CoFe films. Interface resistance dependence on magnitude of spin-accumulation signal by the three-terminal Hanle measurement is quantitatively evaluated. Devices with highly (100)-textured MgO show larger magnitude of spin-accumulation signal in the low-interface-resistance region, than that with polycrystalline or (110)-textured MgO. These results indicate that magnitude of spin-accumulation signal depends on the crystallinity or the texture of ferromagnet/tunnel barrier layers on Si.

Magnetization switching was observed in real time in voltage-control spintronics memory (VoCSM), which utilizes a hybrid writing method that combines spin–orbit torque and voltage-controlled magnetic anisotropy (VCMA). VCMA lowers the switching energy barrier between parallel and antiparallel states, leading to a reduction in the write current and acceleration of magnetization switching. Real-time observation revealed that this acceleration of magnetization switching was accomplished by reducing the incubation and switching times. Using this writing method, high write durability was realized over 1013 write cycles using 2-ns write pulses. These results indicate that VoCSM realizes high speed and highly reliable switching with low power consumption and has the potential to shape next-generation computing systems.Magnetization switching was observed in real time in voltage-control spintronics memory (VoCSM), which utilizes a hybrid writing method that combines spin–orbit torque and voltage-controlled magnetic anisotropy (VCMA). VCMA lowers the switching energy barrier between parallel and antiparallel states, leading to a reduction in the write current and acceleration of magnetization switching. Real-time observation revealed that this acceleration of magnetization switching was accomplished by reducing the incubation and switching times. Using this writing method, high write durability was realized over 1013 write cycles using 2-ns write pulses. These results indicate that VoCSM realizes high speed and highly reliable switching with low power consumption and has the potential to shape next-generation computing systems.

New innovative ferromagnetic source/drain technologies on Si for next-generation-transistor applications are researched and developed using CoFe/AlOxn+-Si and CoFe/MgO n+-Si junctions. As evidence of the spin accumulation in the n+-Si conduction channels, nonlocal spin signals and four-terminal nonlocal-Hanle signals are presented for CoFe/MgO/SOI devices. The spin diffusion times determined by four-terminal nonlocal-Hanle signals are consistent with those observed in three-terminal Hanle signals. The relatively long spin diffusion time of τs=1.4 nsec and relatively large spin polarization P=0.43 at room temperature for CoFe/MgO/SOI devices were observed, when fitting to the existing diffusion model for spin injection and accumulation. We have observed the marked enhancement of the absolute value of three-terminal voltage changes via Hanle-type spin precessions (|ΔV|) as a function of interface resistance in the temperature range between 20 K and 300 K. We also have observed the asymmetric bias voltage dependence on ΔV. In terms of the reason of marked enhancement of |ΔV| as a function of interface resistance, the spin absorption into ferromagnet would be most effective. For the explanation of the asymmetric bias voltage dependence, we should take into account two additional possible origins. Moreover, we succeed in decreasing the interface resistance for CoFe/MgO/ n+-Si junctions down to 36 Ωμm2 by using evaporation method for MgO deposition.

The synthesis and biological evaluation of a series of novel 3-phenylpiperidine-4-carboxamide derivatives are described. These compounds are generated by hybridization of the substructures from two types of tachykinin NK 1 receptor antagonists. Compound 42 showed high metabolic stability and excellent efficacy in the guinea-pig GR-73637-induced locomotive activity assay at 1 and 24 h after oral administration. It also exhibited good pharmacokinetic profiles in four animal species, and a low potential in a pregnane X receptor induction assay.

We proposed a novel spin-based MOSFET “Spin-Transfer-torque-Switching MOSFET (STS-MOSFET)” that offers non-volatile memory and transistor functions with complementary metal-oxide-semiconductor (CMOS) compatibility, high endurance and fast write time using STS. The STS-MOSFETs with Heusler alloy (Co2Fe1Al0.5Si0.5) were prepared and reconfigurability of a novel spintronics-based MOSFET, STS-MOSFET, was successfully realized for the transport properties owing to reduction of the contact resistance in ferromagnetic metal/thin insulator tunnel barrier/Si junctions. The device showed magnetocurrent (MC) and write characteristics with the endurance of over 105 cycles. It was also clarified that the read characteristic can be improved in terms of MC ratio, however, is deteriorated in terms of the mobility by choosing connection configurations of the source and the drain in the STS-MOSFETs.

We experimentally demonstrate a giant voltage-controlled magnetic anisotropy (VCMA) coefficient in a crystallographically strained CoFe layer (~15 monolayers in thickness) in a MgO/CoFe/Ir system. We observed a strong applied voltage dependence of saturation field and an asymmetric concave behavior with giant VCMA coefficients of −758 and 1043 fJ V−1 m−1. The result of structural analysis reveals epitaxial growth in MgO/CoFe/Ir layers and the orientation relationship MgO(001)[110] ∥ CoFe(001)[100] ∥ Ir(001)[110]. The CoFe layer has a bcc structure and a tetragonal distortion due to the lattice mismatch; therefore, the CoFe layer has a large perpendicular magnetic anisotropy.

We conducted a detailed study of hard axis magnetic field (Hhard) dependence on current-induced magnetization switching (CIMS) in MgO-based magnetic tunnel junctions (MTJs) with various junction sizes and various uniaxial anisotropy fields. The decreases in critical current density (Jc) and the intrinsic critical current density (Jc0) estimated from the pulse duration dependence on Jc in CIMS are observed when applying Hhard for all MTJs. The decrease in energy barrier of CIMS is also observed except for the largest sample. These results indicate that the reduction of Jc is attributable to both the increase of spin-transfer efficiency and the decrease in energy barrier in the case of applying Hhard. The Jc0 decreases with increase in the mutual angle between the direction of magnetization and the easy axis (θf), which is consistent with the theoretical prediction proposed by Slonczewski. The degree of the reduction of Jc0 for the same value of Hhard decreases with decreasing size of MTJs. This behavior is considered to be related to not only decrease in θf due to the increase in anisotropy field in MTJs, but also to the increase in the variance of the initial angle of magnetization due to the thermally activated magnon excitation. The stable switching endurance related to CIMS was observed in a wide range of MTJ sizes when applying Hhard. Moreover, we proposed a new architecture and a new switching method considering write disturbance. These results would be useful for application to spin memory and other spin-electronic devices.

Data on the water quality of about 500 effluent samples collected from septic tank (johkasou) systems being used at individual residences in Gunma prefecture were examined to determine the treatment performance of each system. The pollutant loads discharged from the johkasou systems were calculated using the water quality data. In addition, more effective means of wastewater management in an unsewered area where most of town's wastewater was mainly treated by tandoku-shori johkasou systems were discussed on the basis of the calculated pollutant load factor. The results of the water quality analysis showed that the treatment performance of the advanced gappei-shori johkasou (type 1-3) system was the highest of all the johkasou systems. Changing the tandoku-shori johkasou system to the type 1-3 system is recommended to prevent the eutrophication of a lake in the unsewered area.

As a novel class of IKKbeta inhibitors, a series of tricyclic furan derivatives was designed and synthesized based on the structure of known thiophene IKKbeta inhibitors. Among the various fused furan derivatives synthesized, a benzothieno[3,2-b]furan derivative 13a displayed potent inhibitory activity towards IKKbeta in enzymatic and cellular assays. The potent inhibitory activity originates from an intramolecular non-bonded S...O interaction which was confirmed by the X-ray structure of JNK3 with 16k. The introduction of further substituents on the core structure led to the discovery of the 6-alkoxy derivatives, which possessed a comparable IKKbeta inhibitory activity to 13a and an improved metabolic stability. Among these, appropriately lipophilic compounds 16a, h, i, and 13g (log D2) were found to possess good oral bioavailability.

Highly efficient electrical spin injection and detection between ferromagnetic electrodes and semiconductors are important technologies for semiconductor-based spintronic devices, such as spin-MOSFETs. In an ideal system, the efficiency of spin injection and detection in a ferromagnetic metal/tunnel barrier/semiconductor junction depends on the spin polarization of the ferromagnetic metal, the spin filtering efficiency of the tunnel barrier, and the conductivity matching condition. However, other complex mechanisms affect spin-dependent transport in real junctions. It has been pointed out that a sequential tunneling process through localized states at an interface of a junction affect an amplitude and a width of Hanle signal so that the calculated spin lifetime are affected by effects of localized states [1-4]. Recently, the effects of these localized states were directly investigated by inelastic electron tunneling spectroscopy (IETS) [5-7]. The purpose of this study is to reveal relationship between the localized states and the spin-dependent transport properties in more detail by means of dependence of the differential conductance and IET signals on the measurement frequency.

We conducted a detailed comparative study of thermal stability properties over a thermal excitation of switching of the free layer in a magnetic tunnel junction (MTJ) with Ni 81 Fe 19 , Co 90 Fe 10 , and synthetic antiferromagnetic (Syn-AF) free layers with several strengths of interlayer exchange coupling ( J EX ). The thermal stability properties were investigated using the junction magnetoresistance of current-perpendicular MTJ devices with a word line as probes. The observed sweep-rate-dependent coercivities were analyzed using the Sharrock formula. The results confirmed strong J EX dependence on thermal stability parameters ( K u V / kT ) in Syn-AF free layers. The values of K u V / k B T for MTJs with Syn-AF free layers decreased with a decrease in the strength of J EX , and the increase in the effective volume of the Syn-AF free layer disappeared at J EX ⩽ 0.52 erg / cm 2 . The Syn-AF free layer with J EX >0.52 erg/cm 2 is relevant for high-density spin electronic nanodevices with a low aspect ratio.

A general method for the construction of N-reverse-prenyl indoles was established using copper catalyzed N-propargylation, the Lindlar hydrogenation of the acetylenic bond. and dehydrogenation with chemical manganese dioxide as key steps. The antifungal indole alkaloids (1 and 2) and N-reverse-prenyl tryptophan (3) were efficiently synthesized by this method.

We examined the fabrication conditions to obtain high-quality ramp-edge Josephson junctions on a liquid-phase-epitaxy YBa2Cu3Oy (LPE-YBCO) ground plane, in particular, focusing on the fabrication of a suitable insulating layer on the ground plane and the post-annealing conditions to load oxygen to the ground plane. A (LaAlO3)0.3–(SrAl0.5Ta0.5O3)0.7 (LSAT) insulating film on the ground planes exhibited a conductance ranging from 10−4 to 10−8 S after deposition of an upper superconducting film, suggesting existence of some leak paths through the LSAT insulating layer. By introducing approximately 30 nm thick SrTiO3 (STO) buffer layers on both side of the LSAT insulating layer. We reproducibly obtained a conductance lower than 10−8 S. The dielectric constant of the STO/LSAT/STO layer was 32, which was slightly larger than that of the single LSAT layer. It was found that a very slow cooling rate of 1.0 °C/h in oxygen was needed to fully oxidize the ground plane through the STO/LSAT/STO insulating layers, while the oxidation time could be effectively reduced by introducing via holes in the insulating layer at an interval of 200 μm. Ramp-edge junctions on LPE-YBCO ground planes with STO/LSAT/STO insulating layers exhibited a 1σ-spread in Ic of 8% for 100-junction series-arrays and a sheet inductance of 0.7 pH/□ at 4.2 K.

An SFQ-dc converter and a voltage amplifier have been designed and fabricated for use in oxide RSFQ circuits. The SFQ-dc converter comprised a stack of SQUIDs and switches to voltage state by injection of the SFQ signal current. The voltage amplifier was formed by increasing the number of stacked SQUIDs more than three. Operations of these SFQ-dc converters and voltage amplifiers were experimentally verified. The output voltage was almost proportional to the number of stacked SQUIDs. The output voltage greater than 1 mV was obtained by increasing the number of stacked SQUIDs up to five.

For SFQ circuits using high-Tc Josephson junctions, it is very important to reduce the Ic spread of the junctions. We have studied several causes of the Ic spread in interface-modified ramp-edge junctions. First, the relation between the structure and the fabrication process of the barrier has been examined. Reflection high energy electron diffraction pattern observation in the recrystallization process of the interface-modified barrier and transmission electron microscopy observation indicate that several types of barrier structures appear by changing the electron cyclotron resonance ion-bombardment and subsequent annealing conditions. Ion bombardment at a high acceleration voltage of 700 V induces no cubic layer at the interface, while several types of cubic structure can be observed for lower acceleration voltages (300–500 V). Thus, distribution of ion beam energy is one of the important factors determining the Ic spread. We also report the importance of other factors including the uniformity of ion beam for making an amorphous layer, and the base-electrode film quality such as the density of outgrowth or particles and the roughness of the ramp surface. By improving these factors in the junction fabrication process, an Ic spread of 17% has been obtained for an array of 1000JJs with a relatively small average Ic of 0.1 mA, suggesting a possibility of further improvement for junctions with a higher Jc.

Evaluating system of the I c spread was developed for integrating the ramp–edge junctions. The system had functions of measuring I – V curves of the series junction array, converting the analog data to digital data and determining each I c value. The I c value was determined by detecting the local peak of the current in the I – V curve taking into account the RSJ model. The I c -spread evaluating system could successfully be applied to the series array of 1000 YBa 2 Cu 3 O 7− x ramp–edge junctions.

The stereoselective syntheses of four unusual amino acids, constituents of cyclomarin A, are described. The protected N -methylhydroxyleucine 2 was synthesized using Evans’ asymmetric azide-transfer reaction. The unusual amino acid 3 was prepared via diastereoselective methylation of the l -aspartic acid derived lactone 13 . The stereoselective formation of threo-β-methoxyphenylalanine 4 was performed via aldol reaction using Schollkopf's chiral glycine enolate. The synthesis of N -reverse prenylated tryptophane 5 was achieved by the AQN ligand-promoted Sharpless regioreversed asymmetric aminohydroxylation protocol.

A hybrid writing scheme that combines the spin Hall effect and voltage-controlled magnetic-anisotropy effect is investigated in Ta/CoFeB/MgO/CoFeB/Ru/CoFe/IrMn junctions. The write current and control voltage are applied to Ta and CoFeB/MgO/CoFeB junctions, respectively. The critical current density required for switching the magnetization in CoFeB was modulated 3.6-fold by changing the control voltage from −1.0 V to +1.0 V. This modulation of the write current density is explained by the change in the surface anisotropy of the free layer from 1.7 mJ/m2 to 1.6 mJ/m2, which is caused by the electric field applied to the junction. The read disturb rate and write error rate, which are important performance parameters for memory applications, are drastically improved, and no error was detected in 5 × 108 cycles by controlling read and write sequences.

Observation of the spin signals in devices with low interface resistance of ferromagnetic/semiconductor junctions is one of the most important issues from the application view point. We demonstrate spin transport and accumulation signals in highly doped ∼1×1020 cm-3 n+-Si by using CoFe/MgO/n+-Si (10 nm, 20 nm)/n-Si devices. The highly doped n+-Si was confined within a thin n+-Si layer (10 nm and 20 nm in thickness). In this confined structure, we observed the spin accumulation signals for the devices with impurity concentration of ∼1×1020 cm-3 and the spin transport signals for the devices with ∼1 kΩμm2 interface resistance. This indicates that the n+ confined structure is important for observing and increasing spin signals in the low-interface-resistance region.

The post annealing temperature dependence of room temperature spin signals in Co2FeSi/MgO/n+-Si on insulator fabricated on Si(2×1) surface was investigated. For the devices fabricated on the Si(2×1) surface, the large and reliable three- and four-terminals spin signals were obtained even at room temperature. The magnitude of three-terminal narrow Hanle signals has a peak around 325 °C with respect to post annealing temperature. The trend of increasing spin accumulation signal with decreasing bias voltage was observed for both as deposited and sample annealed at 325 °C in the bias voltage range 600–800 mV. The enhancement of three- and four-terminals non-local magnetoresistance (MR) for post annealed sample at 325 °C, indicates that the spin polarization increases due to the structural ordering of Heusler alloy Co2FeSi. As a result, we observed large spin injection efficiency into Si (P ~ 41.7%) even at room temperature. These results will pave a way to the future Si spintronics devices such a spin-MOSFET.

The efficient method for the synthesis of N-1,1-dimethyl-2-propenyl (reverse prenyl) indole was developed by the N-propargylation of the indoline, partial hydrogenation of the terminal alkyne, and oxidation to the indole using chemical manganese dioxide (CMD). This method was used for the synthesis of the antifungal indole alkaloids 2, 3, and N-reverse prenylated tryptophan.

The chemical synthesis of pentosidine (1), an advanced glycation end product, was achieved via the asymmetric alkylation of the chiral schiff base derived from (+)-2-hydroxy-3-pinanone ((+)-HyPN) and glycine tert-butyl ester, the mercury salt mediated intramolecular guanylation, and the regioselective alkylation of imidazo[4,5-b]pyridine ring. This reliable synthetic achievement will promise availability of pentosidine (1) in quantities.

[structure: see text] In this Letter we describe the first total synthesis of mycothiazole, a polyketide thiazole from a marine sponge. Key steps include our CMD oxidation for the conversion of thiazolidine 11 to thiazole 12 and the Nagao acetate aldol reaction of 5 with aldehyde 4 to construct the chiral secondary alcohol. The skipped diene was constructed by the standard Stille coupling, and the conjugated diene was synthesized by lithium(I)- and copper(I)-mediated Stille coupling.

We systematically investigated the characteristics of Nb/Al/AlO x /Al/AlO x /Nb junctions having a structure in which Al/AlO x films are placed in a Nb/Al/AlO x /Nb trilayer junction. The junction characteristics reflect superconductivity in the second Al film due to the proximi ty effect. As a result, the critical current density J c and the hysteresis on its current–voltage ( I – V ) curve strongly depend on the transparencies of the AlO x barriers. The hystereses of the junctions are smaller than t hose of Nb/Al/AlO x /Nb junctions at the same J c . Intrinsically overdamped junctions are also realized. The intrinsically overdamped junctions can considerably reduce an area occupied by a single gate. Furthermore, the spread of critical current I c for the junctions, which have hystereses, connected in series, is ±1.2%. This shows that the junctions with additional Al/AlO x have uniform enough characteristics to be used in integrated circuits.

The efficient total synthesis of pentosidine (1), an advanced glycation endproduct, was achieved using the asymmetric alkylation of a chiral schiff base (2), the intramolecular guanylation with mercury (II) chloride, and the quaternization accompanied by removal of the trityl group as key steps.

He ion yield XAFS measurements under He atmosphere at ambient pressure have been adopted for analyzing the local structure of several metal nitride thin films. XANES spectra and EXAFS parameters for zinc blend-type iron nitride, obtained by the yield XAFS, have coincided with those obtained using the conventional transmission XAFS. The yield XAFS measurements employing the grazing incidence technique have been presented for the determination of chemical species on the surface of Ti-Al-N films after the erosion experiment, showing the followings; the corrosion products on the film surface after heating at 600°C under O2 gas flow were Ti based oxides, either TiO2 or Al2TiO5. Al2TiO5 was slightly yielded not only on Al-rich Ti1-xAlxN but also on Ti-rich Ti1-xAlxN films after aging in a distilled water for 2 weeks. The local structure around Fe for Si-Fe-N films before and after annealing in an H2 atmosphere at several temperatures has been investigated. The as-deposited Si-Fe-N film contained Fe with local structure similar to that of FeNy (y>0.5) and such local structure was not broken against the annealing at 300°C. Annealing at 500°C changed the local structure around Fe, i.e., N bonded to Fe was almost eliminated and Fe formed a fine particle similar to α-Fe.

Amorphous Si-Fe-N thin films were prepared by reaction cosputtering of variable numbers of Si chips on a Fe target with nitrogen sputter gas. They were homogeneous amorphous having both local structures similar to zinc blende type γ′′′-FeN0.91 around Fe atoms and also to Si3N4 around Si atoms. Fine particles of α-Fe were precipitated to show ferromagnetism by thermal decomposition of γ′′′-FeN0.91 like local structure above 400°C in hydrogen atmosphere. Weaker ferromagnetic component such as Fe3Si was formed above 600°C. Thermal instability of iron nitride was slightly improved by forming the Si-Fe-N amorphous material.

Formation of iron nitrides, especially Fe 16 N 2 , was investigated by nitrogen ion implantation for both bulk and thin film of α-Fe. A part of the implanted nitrogen was lost during the process in the case of high energy implantation because of the thermal instability of iron nitrides. N + ion implantation with an ion beam voltage of less than 100 keV and a current of less than 5 μA was effective for the Fe 16 N 2 formation. Successive annealing in vacuum at 373 K improved its crystallinity. The formation was explicitly detected by an XRD method for a thin film with an incident X-ray beam angle of 1 °. It was also observed on a normal powder XRD pattern for the N + ion implanted α-Fe(211) preferred oriented thin film with a thickness of about 1 μm deposited on capton tape by rf-sputter deposition. The presence of Fe 16 N 2 was detected by XRD as small crystallite around 10 nm in diameter. Mossbauer spectroscopy at room temperature showed only a slight difference in the as-implanted product from that for α-Fe. Further annealing will be necessary to obtain a well ordering of nitrogen in Fe 16 N 2 .

We designed a quasi-one junction superconducting quantum interference device (QOS) based on single-flux-quantum technology using high-Tc superconductors. A circuit containing 10 interface-engineered ramp-edge Josephson junctions was fabricated on a La-substituted YBa2Cu3Oy ground plane. The output voltage as a function of the input current for the QOS indicated correct operation as a periodic comparator at clock frequency of 94 and 77 GHz at 35 and 40 K, respectively. A comparison of the observed maximum operating frequency with the product of the critical current and normal resistance for the junctions suggests that comparator operation above 100 GHz at 40 K is possible if one optimizes the junction parameters.

The post annealing temperature dependence of spin accumulation and transport signals in Co2FeSi/MgO/n+-Si on insulator were investigated. The spin signals were detected using 3- and 4-terminal Hanle, 2-terminal local and 4-terminal nonlocal magnetoresistance measurements. The post annealing temperature (TA) dependence of the magnitude in 3-terminal narrow Hanle signals is nearly constant up to TA < 400°C, however a slight decrease above TA ≥ 400°C is observed. This behavior is consistent with the TA dependence of the magnitude of 4-terminal nonlocal magnetoresistance (MR) signals. The spin polarization estimated from the 3-terminal narrow Hanle signals and the magnitude of 2-terminal local MR signals show a slight improvement with increasing post annealing temperature with a peak at around 325°C and then start reducing slowly. The slight increase in the spin signal would be due to high spin polarization of Co2FeSi as a result of structural ordering. The 2-terminal local MR signals do not vary significantl...