Nanosecond Random Telegraph Noise in In-Plane Magnetic Tunnel Junctions.

We study the timescale of random telegraph noise (RTN) of nanomagnets in stochastic magnetic tunnel junctions (MTJs). From analytical and numerical calculations based on the Landau-Lifshitz-Gilbert and the Fokker-Planck equations, we reveal mechanisms governing the relaxation time of perpendicular easy-axis MTJs (p-MTJs) and in-plane easy-axis MTJs (i-MTJs), showing that i-MTJs can be made to have faster RTN. Superparamagnetic i-MTJs with small in-plane anisotropy and sizable perpendicular effective anisotropy show relaxation times down to 8 ns at negligible bias current, which is more than 5 orders of magnitude shorter than that of typical stochastic p-MTJs and about 100 times faster than the shortest time of i-MTJs reported so far. The findings give a new insight and foundation in developing stochastic MTJs for high-performance probabilistic computers.

High-resolution three-dimensional imaging of topological textures in nanoscale single-diamond networks.

Topological defects-extended lattice deformations that are robust against local defects and annealing-have been exploited to engineer novel properties in both hard and soft materials. Yet, their formation kinetics and nanoscale three-dimensional structure are poorly understood, impeding their benefits for nanofabrication. We describe the fabrication of a pair of topological defects in the volume of a single-diamond network (space group Fd 3 ¯ m) templated into gold from a triblock terpolymer crystal. Using X-ray nanotomography, we resolve the three-dimensional structure of nearly 70,000 individual single-diamond unit cells with a spatial resolution of 11.2 nm, allowing analysis of the long-range order of the network. The defects observed morphologically resemble the comet and trefoil patterns of equal and opposite half-integer topological charges observed in liquid crystals. Yet our analysis of strain in the network suggests typical hard matter behaviour. Our analysis approach does not require a priori knowledge of the expected positions of the nodes in three-dimensional nanostructured systems, allowing the identification of distorted morphologies and defects in large samples.

Electrical control of the ferromagnetic phase transition in cobalt at room temperature.

Electrical control of magnetic properties is crucial for device applications in the field of spintronics. Although the magnetic coercivity or anisotropy has been successfully controlled electrically in metals as well as in semiconductors, the electrical control of Curie temperature has been realized only in semiconductors at low temperature. Here, we demonstrate the room-temperature electrical control of the ferromagnetic phase transition in cobalt, one of the most representative transition-metal ferromagnets. Solid-state field effect devices consisting of a ultrathin cobalt film covered by a dielectric layer and a gate electrode were fabricated. We prove that the Curie temperature of cobalt can be changed by up to 12 K by applying a gate electric field of about ±2 MV cm(-1). The two-dimensionality of the cobalt film may be relevant to our observations. The demonstrated electric field effect in the ferromagnetic metal at room temperature is a significant step towards realizing future low-power magnetic applications.

Observation of the intrinsic pinning of a magnetic domain wall in a ferromagnetic nanowire.

The spin transfer torque is essential for electrical magnetization switching. When a magnetic domain wall is driven by an electric current through an adiabatic spin torque, the theory predicts a threshold current even for a perfect wire without any extrinsic pinning. The experimental confirmation of this 'intrinsic pinning', however, has long been missing. Here, we give evidence that this intrinsic pinning determines the threshold, and thus that the adiabatic spin torque dominates the domain wall motion in a perpendicularly magnetized Co/Ni nanowire. The intrinsic nature manifests itself both in the field-independent threshold current and in the presence of its minimum on tuning the wire width. The demonstrated domain wall motion purely due to the adiabatic spin torque will serve to achieve robust operation and low energy consumption in spintronic devices.

Neuromorphic Spintronics.

Neuromorphic computing uses basic principles inspired by the brain to design circuits that perform artificial intelligence tasks with superior energy efficiency. Traditional approaches have been limited by the energy area of artificial neurons and synapses realized with conventional electronic devices. In recent years, multiple groups have demonstrated that spintronic nanodevices, which exploit the magnetic as well as electrical properties of electrons, can increase the energy efficiency and decrease the area of these circuits. Among the variety of spintronic devices that have been used, magnetic tunnel junctions play a prominent role because of their established compatibility with standard integrated circuits and their multifunctionality. Magnetic tunnel junctions can serve as synapses, storing connection weights, functioning as local, nonvolatile digital memory or as continuously varying resistances. As nano-oscillators, they can serve as neurons, emulating the oscillatory behavior of sets of biological neurons. As superparamagnets, they can do so by emulating the random spiking of biological neurons. Magnetic textures like domain walls or skyrmions can be configured to function as neurons through their non-linear dynamics. Several implementations of neuromorphic computing with spintronic devices demonstrate their promise in this context. Used as variable resistance synapses, magnetic tunnel junctions perform pattern recognition in an associative memory. As oscillators, they perform spoken digit recognition in reservoir computing and when coupled together, classification of signals. As superparamagnets, they perform population coding and probabilistic computing. Simulations demonstrate that arrays of nanomagnets and films of skyrmions can operate as components of neuromorphic computers. While these examples show the unique promise of spintronics in this field, there are several challenges to scaling up, including the efficiency of coupling between devices and the relatively low ratio of maximum to minimum resistances in the individual devices.

Spin-orbit torque switching of an antiferromagnetic metallic heterostructure.

The ability to represent information using an antiferromagnetic material is attractive for future antiferromagnetic spintronic devices. Previous studies have focussed on the utilization of antiferromagnetic materials with biaxial magnetic anisotropy for electrical manipulation. A practical realization of these antiferromagnetic devices is limited by the requirement of material-specific constraints. Here, we demonstrate current-induced switching in a polycrystalline PtMn/Pt metallic heterostructure. A comparison of electrical transport measurements in PtMn with and without the Pt layer, corroborated by x-ray imaging, reveals reversible switching of the thermally-stable antiferromagnetic Néel vector by spin-orbit torques. The presented results demonstrate the potential of polycrystalline metals for antiferromagnetic spintronics.

Shape anisotropy revisited in single-digit nanometer magnetic tunnel junctions.

Nanoscale magnetic tunnel junctions play a pivotal role in magnetoresistive random access memories. Successful implementation depends on a simultaneous achievement of low switching current for the magnetization switching by spin transfer torque and high thermal stability, along with a continuous reduction of junction size. Perpendicular easy-axis CoFeB/MgO stacks possessing interfacial anisotropy have paved the way down to 20-nm scale, below which a new approach needs to be explored. Here we show magnetic tunnel junctions that satisfy the requirements at ultrafine scale by revisiting shape anisotropy, which is a classical part of magnetic anisotropy but has not been fully utilized in the current perpendicular systems. Magnetization switching solely driven by current is achieved for junctions smaller than 10 nm where sufficient thermal stability is provided by shape anisotropy without adopting new material systems. This work is expected to push forward the development of magnetic tunnel junctions toward single-digit nm-scale nano-magnetics/spintronics.

Mouse suppressor of fused is a negative regulator of sonic hedgehog signaling and alters the subcellular distribution of Gli1.

The Hedgehog (Hh) signaling pathway has critical functions during embryogenesis of both invertebrate and vertebrate species [1]; defects in this pathway in humans can cause developmental disorders as well as neoplasia [2]. Although the Gli1, Gli2, and Gli3 zinc finger proteins are known to be effectors of Hh signaling in vertebrates, the mechanisms regulating activity of these transcription factors remain poorly understood [3] [4]. In Drosophila, activity of the Gli homolog Cubitus interruptus (Ci) is likely to be modulated by its interaction with a cytoplasmic complex containing several other proteins [5] [6], including Costal2, Fused (Fu), and Suppressor of fused (Su(fu)), the last of which has been shown to interact directly with Ci [7]. We have cloned mouse Suppressor of fused (mSu(fu)) and detected its 4.5 kb transcript throughout embryogenesis and in several adult tissues. In cultured cells, mSu(fu) overexpression inhibited transcriptional activation mediated by Sonic hedgehog (Shh), Gli1 and Gli2. Co-immunoprecipitation of epitope-tagged proteins indicated that mSu(fu) interacts with Gli1, Gli2, and Gli3, and that the inhibitory effects of mSu(fu) on Gli1's transcriptional activity were mediated through interactions with both amino- and carboxy-terminal regions of Gli1. Gli1 was localized primarily to the nucleus of both HeLa cells and the Shh-responsive cell line MNS-70; co-expression with mSu(fu) resulted in a striking increase in cytoplasmic Gli1 immunostaining. Our findings indicate that mSu(fu) can function as a negative regulator of Shh signaling and suggest that this effect is mediated by interaction with Gli transcription factors.

A spin-orbit torque switching scheme with collinear magnetic easy axis and current configuration.

Spin-orbit torque, a torque brought about by in-plane current via the spin-orbit interactions in heavy-metal/ferromagnet nanostructures, provides a new pathway to switch the magnetization direction. Although there are many recent studies, they all build on one of two structures that have the easy axis of a nanomagnet lying orthogonal to the current, that is, along the z or y axes. Here, we present a new structure with the third geometry, that is, with the easy axis collinear with the current (along the x axis). We fabricate a three-terminal device with a Ta/CoFeB/MgO-based stack and demonstrate the switching operation driven by the spin-orbit torque due to Ta with a negative spin Hall angle. Comparisons with different geometries highlight the previously unknown mechanisms of spin-orbit torque switching. Our work offers a new avenue for exploring the physics of spin-orbit torque switching and its application to spintronics devices.

Gamma subunit dependent modulation by nitric oxide (NO) in recombinant GABAA receptor.

The effect of nitric oxide (NO) on GABA induced Cl- current of recombinant GABAA receptors was studied. Either alpha 1 beta 2 gamma 2s or alpha 1 beta 2 subunit mRNAs synthesized from cDNA of mouse brain were injected into Xenopus oocytes and functional GABAA receptors were expressed. GABA-induced Cl- current was measured with the two electrode voltage clamp technique. The NO donor NOC-18 reduced the GABA-induced Cl- current in the alpha 1 beta 2 gamma 2s subunit receptor in a dose-dependent manner. In alpha 1,beta 2 subunit receptor, NOC-18 had no effects on GABA-induced currents at low concentrations but showed potentiation at high concentration. These effects were antagonized by the NO extinguisher, carboxy-PTIO. The cGMP analogue 8-Br-cGMP failed to induce NO-like effects. NO directly acts at the GABAA receptor and the gamma 2s subunit is involved in its action.

The effects of a point mutation of the beta2 subunit of GABA(A) receptor on direct and modulatory actions of general anesthetics.

The gamma-aminobutyric acid type A receptor (GABA(A) receptor) sites involved in the direct and modulatory actions of general anesthetics remain to be elucidated. The mutation of tyrosine at position 157 in the beta2 GABA(A) receptor subunit was reported to reduce sensitivity to activation by GABA, but not pentobarbital. We examined whether this mutation of the beta2 subunit (Tyr157-->Phe) affects the direct and modulatory actions of other general anesthetics such as propofol and etomidate. Using the two-electrode voltage clamp method, we recorded Cl- current in Xenopus oocytes expressing alpha1beta2gamma2s and alpha1-mutated beta2gamma2s subunits. The mutation of the beta2 subunit reduced the apparent affinity for propofol. However, the mutation had no effect on both the direct actions of pentobarbital and etomidate or on the modulatory actions of pentobarbital, propofol and etomidate. These results suggest that unique loci may exist for the direct action of propofol and that the GABA binding site may not mediate the modulatory actions of general anesthetics at GABA(A) receptors.

The alpha and gamma subunit-dependent effects of local anesthetics on recombinant GABA(A) receptors.

Although convulsions due to local anesthetic systemic toxicity are thought to be due to inhibition of GABA(A) receptor-linked currents in the central nervous system, the mechanism of action remains unclear. We therefore examined the effects of local anesthetics on gamma-aminobutyric acid (GABA)-induced currents using recombinant GABA(A) receptors with specific combinations of subunits. Murine GABA(A) receptors were expressed by injection of cRNAs encoding each subunit into Xenopus oocytes. The effects of local anesthetics (lidocaine, bupivacaine, procaine and tetracaine) on GABA-induced currents of receptors expressing different subunit combinations (alpha1beta2, alpha1beta2gamma2s, alpha4beta2gamma2s and beta2) were examined via the two electrode voltage clamp method. At alpha1beta2, alpha1beta2gamma2s and alpha4beta2gamma2s GABA(A) receptors, all local anesthetics inhibited GABA-induced currents in a dose-dependent manner. The presence of the gamma2s subunit resulted in a greater inhibition by all local anesthetics, but the presence of the alpha4 subunit resulted in less inhibition. At beta2 homomeric receptors, local anesthetics directly induced an outward current similar to that of picrotoxin. These data indicated that (1) the alpha and gamma subunits of GABA(A) receptors modulated the inhibitory effects of local anesthetics on GABA(A) function, and (2) local anesthetics can activate the beta2 subunit and may block the GABA(A) receptor channel pore.

Enhanced resistance of mice to Escherichia coli infection induced by administration of peptidoglycan derived from Bifidobacterium thermophilum.

Peptidoglycan (PG) of Bifidobacterium thermophilum (B. thermophilum) from swine were orally administered to SPF-ICR mice in order to confirm the enhancement of the defence activity of the mice against Escherichia coli (E. coli) infection. It was found that the survival rates of the PG-administered group were significantly higher than those of the non-treated control group after the single oral administration of PG. And the proper concentration at which PG enhanced defence activity most effectively was found to be 500 micrograms per mouse. The number of E. coli in the peripheral blood, liver and spleen of the PG-administered group at 24 hr after the inoculation was significantly smaller than that in the control group. Liver weight per body weight in the PG treated group significantly increased in comparison with that of the non-treated group. The number of blastoid plasmacytes in the spleen of the PG-administered mice was found to be greater than that in the control group. These results indicate that the defence activity of mice against E. coli infection was accelerated by PG treatment.

Enhancement of cytotoxic activity of lymphocytes in mice by oral administration of peptidoglycan (PG) derived from Bifidobacterium thermophilum.

A preparation of peptidoglycan (PG) of Bifidobacterium thermophilum (B. thermophilum) of swine was orally administered to SPF-C57BL/6CrSlc mice in order to confirm the enhancement of the cytotoxic activity of natural killer cells (NK), intraperitoneal cytotoxic T lymphocytes (CTL) and lymphocytes stimulated by concanavalin A (Con A-stimulated lymphocytes). The NK cells from the spleen and the mesenteric lymph node (MLN) of mice that were continuously fed with PG-mixed feed for three weeks showed a significantly higher rate of cytolysis than those from the control group. However, a single oral administration of PG had no significant effect on NK activity. The activity of peritoneally sensitized CTL of the mice that were continuously fed with PG-mixed feed was assayed. The PG-mixed feed administered group showed a higher CTL activity than that of the control group. The cytotoxic activity of Con A-stimulated lymphocytes in the PG-mixed feed administered group was higher than that of the control group. These results indicate that the cytotoxic activity of mice was enhanced by orally administered PG.

[Tetanus antitoxin levels in various Japanese age groups in 1989].

The nationwide DPT vaccine program was started in 1969 for infants under 12 months of age. In order to estimate the tetanus immune status among the general population of various age groups, we measured the serum tetanus antibody level in randomly selected outpatients from Metropolitan Tokyo (n = 211, 6 months-60 years) and Hamamatsu, a city of 510 thousand population (n = 128, 3 years-80 years) between January 1987 and June 1989. Among the 211 subjects from Tokyo, the antibody value exceeding effective level of 0.01 HAU/ml was observed in 102 subjects (48.3%). The antibody positive rate was 90.8% in subjects of 3 to 21 years and was 27.7% in subjects of 22 years or older. The positive rate was significantly higher in subjects of 21 years or younger (p less than 0.005). Among 128 subjects from Hamamatsu, 60 (46.1%) had a positive antibody and the antibody positive rare was 96.9% in subjects of 3 to 21 years and was 29.5% in subjects of 21 years or younger (p less than 0.005). The above findings indicate that our DPT vaccination program has been functioning well for the last 20 years and that the immunized population is adequately protected against tetanus.

[General anesthesia for patients with hypertrophic cardiomyopathy].

General anesthesia was given to six surgical patients with hypertrophic cardiomyopathy on eight occasions from 1990 to 1992. Anesthetic courses were uneventful in five patients diagnosed previously as hypertrophic cardiomyopathy. However, a patient without a diagnosis of hypertrophic cardiomyopathy had intractable cardiac arrest. A slight hypotension caused by epidural anesthesia had a devastating effect on the patient. The above experiences stress the importance of early diagnosis and careful observation in perioperative period.

[Benign infantile mitochondrial myopathy due to reversible cytochrome c oxidase deficiency: histological and biochemical analysis].

We reported a 3-week-old girl with profound generalized weakness, requiring assisted ventilation. There was no consanguinity or family history of any neuromuscular disorders. Serum levels of GOT, GPT and CK were slightly elevated. Although the clinical manifestations mimicked those of Werdning-Hoffmann disease, a lack of the respiratory muscle involvement and the presence of high serum lactate levels suggested an underlying metabolic disorder. During the observation over the months, she gradually improved clinically and assisted ventilation was discontinued at 19 months. Muscle biopsies were performed at 4 and 19 months of age. The first biopsy showed an excessive mitochondrial aggregation and numerous ragged-red fibers. The second biopsy revealed rare ragged-red fibers. However there were definite neurogenic changes including type grouping and angulated fibers. Cytochrome c oxidase (CCO) stain was positive in less than 5% of fibers in the first biopsy but in all fibers in the second biopsy. Biochemical analysis using muscle specimens showed a decreased CCO activity; 18.5% of the control level in the first biopsy and 53.3% in the second biopsy. Immunocytochemistry showed the presence of immunologically reactive enzyme protein in both biopsies. Clinical manifestations of our patient were almost identical to those of two cases reported by DiMauro, et al (1983). The enzyme defect in this case was reversible in contrast to that in the fatal infantile form of CCO deficiency. Histochemical and biochemical bases for these differences were discussed.

[HELP syndrome and anesthetic management].

From January 1990 to December 1994, 24 parturients were diagnosed as having HELLP syndrome alone or combined with preeclampsia/eclampsia among 8,224 patients who were delivered at our institution. They consisted of 14 primiparous and 10 multiparous patients. Mean maternal age was 28.9 +/- 3.3 and gestational age was 34.8 +/- 5.6 weeks. Of 24 parturients, 8 had vaginal delivery and the remaining 16 were delivered by caesarean section. Serious maternal morbidity included eclampsia (n = 3), preeclampsia (n = 18), renal failure (n = 5), hydrothorax (n = 4), and DIC (n = 1). There was no maternal death. There were 3 intrauterine fetal deaths and two neonatal deaths. Perinatal deaths were 2 (0.9%, 2/26). Three caesarean sections were performed under general anesthesia, and 13 under spinal anesthesia. In cases with apparent bleeding tendency, spinal and epidural anesthesia should be avoided. In providing general anesthesia, hypertension should be controlled, and the uterus is preferably dilated before the delivery and contracted there-after.

[Reration between symptom and counts of scattering Japanese cedar pollen--examination of clinical observation and repeated provocation].

We examined relation with the scattering number of Japanese cedar pollens in Mibu, Tochigi, Japan and a nasal allergy symptom expects from pollen observation at an appearance and symptom progress in detail. We investigated appearance day of nasal allergy symptom and relation with pollen number. High relation was admitted as accumulate rate of nasal allergy as accumulation pollen during a numerical square root. When it was long period of the first observation day of pollen to the first day of pollen scatterring, the rate of nasal allergy symptom became high. An equilateral correlation was admitted as symptom a score in symptom progress and relation with pollen number accumulation pollen during a numerical square root. ECP and tryptase value in nose juice washing liquid rose with progressive of symptom. Early phase reaction progresses in a continuation nose mucous membrane induction examination and ECP in nose juice washing and tryptase rose with it. Late phase reaction was halved with positive group by negative group, progress of reaction by repetition of induction was not accepted. In our conclusion, a symptom is caused by little pollen being exposed repeatedly and that a symptom will become worsen was observed by numerical accumulation pollen.

Development of virtual histology and virtual biopsy using laser-scanning confocal microscopy.

The aim of this project is to acquire a direct image of histology from in vivo gastrointestinal mucosa. In other words, the task of 'endo-microscope' is to observe the cellular architecture of tissue in vivo during routine endoscopic examination. As the first step to completing this study, resected fresh specimens from the oesophagus. stomach and colon were examined by laser-scanning confocal microscopy (LCM) (Fluoview, Olympus, Tokyo). Fresh untreated mucosal specimens obtained by endoscopic pinch biopsy, polypectomy or endoscopic mucosal resection were collected and placed in normal saline and examined by LCM, collecting the reflective light of a 488-nm wavelength argon laser beam. As the second step, a probe-type LCM 'endo-microscope' was designed and applied to observe the human oral-cavity mucosa. The probe has 4.5-mm outer diameter and 20-cm length, which enables easy access to oral cavity mucosa. The estimated special resolution of the probe is 1-5 microm. A real-time microscopic image directly from ex vivo fresh specimens was acquired. The acquired LCM images corresponded well with the conventional H-E light microscopic images. Cell wall, nucleus and cytoplasm were simultaneously visualized by LCM scanning. This novel method enables serial imaginary microscopic sections on fresh specimens. In addition, a probe-type LCM 'endo-microscope' was designed and was applied to observe human oral cavity mucosa. Virtual histological images from the living oral squamous cell were successfully obtained. LCM images from ex vivo fresh specimens demonstrated the features of the H-E staining histological image. In the next step to accomplish our project, we developed a LCM probe with 4.5-mm outer diameter to obtain a virtual image of human oral cavity mucosa.