Neuromorphic Computing through Time-Multiplexing with a Spin-Torque Nano-Oscillator.

Fabricating powerful neuromorphic chips the size of a thumb requires miniaturizing their basic units: synapses and neurons. The challenge for neurons is to scale them down to submicrometer diameters while maintaining the properties that allow for reliable information processing: high signal to noise ratio, endurance, stability, reproducibility. In this work, we show that compact spin-torque nano-oscillators can naturally implement such neurons, and quantify their ability to realize an actual cognitive task. In particular, we show that they can naturally implement reservoir computing with high performance and detail the recipes for this capability.

Highly sensitive nanoscale spin-torque diode.

Highly sensitive microwave devices that are operational at room temperature are important for high-speed multiplex telecommunications. Quantum devices such as superconducting bolometers possess high performance but work only at low temperature. On the other hand, semiconductor devices, although enabling high-speed operation at room temperature, have poor signal-to-noise ratios. In this regard, the demonstration of a diode based on spin-torque-induced ferromagnetic resonance between nanomagnets represented a promising development, even though the rectification output was too small for applications (1.4 mV mW(-1)). Here we show that by applying d.c. bias currents to nanomagnets while precisely controlling their magnetization-potential profiles, a much greater radiofrequency detection sensitivity of 12,000 mV mW(-1) is achievable at room temperature, exceeding that of semiconductor diode detectors (3,800 mV mW(-1)). Theoretical analysis reveals essential roles for nonlinear ferromagnetic resonance, which enhances the signal-to-noise ratio even at room temperature as the size of the magnets decreases.

Understanding of Phase Noise Squeezing Under Fractional Synchronization of a Nonlinear Spin Transfer Vortex Oscillator.

We investigate experimentally the synchronization of vortex based spin transfer nano-oscillators to an external rf current whose frequency is at multiple integers, as well as at an integer fraction, of the oscillator frequency. Through a theoretical study of the locking mechanism, we highlight the crucial role of both the symmetries of the spin torques and the nonlinear properties of the oscillator in understanding the phase locking mechanism. In the locking regime, we report a phase noise reduction down to -90 dBc/Hz at 1 kHz offset frequency. Our demonstration that the phase noise of these nanoscale nonlinear oscillators can be tuned and eventually lessened, represents a key achievement for targeted radio frequency applications using spin torque devices.

Large scale cDNA sequencing for analysis of quantitative and qualitative aspects of gene expression.

Large scale sequencing of cDNAs provides a complementary approach to structural analysis of the human genome by generating expressed sequence tags (ESTs). We have initiated the large-scale sequencing of a 3'-directed cDNA library from the human liver cell line HepG2, that is a non-biased representation of the mRNA population. 982 random cDNA clones were sequenced yielding more than 270 kilobases. A significant portion of the identified genes encoded secretable proteins and components for protein-synthesis. The abundance of cDNA species varied from 2.2% to less than 0.004%. Fifty two percent of the mRNA were abundant species consisting of 173 genes and the rest were non-abundant, consisting of about 6,600 genes.

Functional transplant of megabase human immunoglobulin loci recapitulates human antibody response in mice.

We constructed two megabase-sized YACs containing large contiguous fragments of the human heavy and kappa (kappa) light chain immunoglobulin (Ig) loci in nearly germline configuration, including approximately 66 VH and 32 V kappa genes. We introduced these YACs into Ig-inactivated mice and observed human antibody production which closely resembled that seen in humans in all respects, including gene rearrangement, assembly, and repertoire. Diverse Ig gene usage together with somatic hypermutation enables the mice to generate high affinity fully human antibodies to multiple antigens, including human proteins. Our results underscore the importance of the large Ig fragments with multiple V genes for restoration of a normal humoral immune response. These mice are likely to be a valuable tool for the generation of therapeutic antibodies.

Spin-torque diode effect in magnetic tunnel junctions.

There is currently much interest in the development of 'spintronic' devices, in which harnessing the spins of electrons (rather than just their charges) is anticipated to provide new functionalities that go beyond those possible with conventional electronic devices. One widely studied example of an effect that has its roots in the electron's spin degree of freedom is the torque exerted by a spin-polarized electric current on the spin moment of a nanometre-scale magnet. This torque causes the magnetic moment to rotate at potentially useful frequencies. Here we report a very different phenomenon that is also based on the interplay between spin dynamics and spin-dependent transport, and which arises from unusual diode behaviour. We show that the application of a small radio-frequency alternating current to a nanometre-scale magnetic tunnel junction can generate a measurable direct-current (d.c.) voltage across the device when the frequency is resonant with the spin oscillations that arise from the spin-torque effect: at resonance (which can be tuned by an external magnetic field), the structure exhibits different resistance states depending on the direction of the current. This behaviour is markedly different from that of a conventional semiconductor diode, and could form the basis of a nanometre-scale radio-frequency detector in telecommunication circuits.

Cholinergic Stimulation by Pyridostigmine Bromide Before Myocardial Infarction Prevent Cardiac and Autonomic Dysfunction.

Inflammatory processes and cardiovascular autonomic imbalance are very relevant characteristic of the enormous dynamic process that is a myocardial infarction (MI). In this sense, some studies are investigating pharmacological therapies using acetylcholinesterase inhibitors, such as pyridostigmine bromide (PYR), aiming to increase parasympathetic tone after MI. Here we hypothesized that the use of PYR before the MI might bring an additional positive effect to the autonomic function, and consequently, in the inflammatory response and cardiac function. The present study aimed to evaluate left ventricular function, baroreflex sensitivity, autonomic modulation, and inflammatory profile in PYR-treated rats previously to MI. METHODS: Male Wistar rats (250-300 g) were treated for 60 days with PYR. After treatment, they were submitted to the MI. After the MI, the autonomic and ventricular function were evaluated, as well as the systemic, left ventricle, and adipose tissue inflammatory profile. RESULTS: PYR, performed before MI, prevented HR increase, systolic function impairment, baroreflex sensitivity drop, as well as pulse interval variance, RMSSD, blood pressure and parasympathetic modulation reduction in treated rats compared to untreated rats. Also, this positive functional changes may have been a result of the reduced inflammatory parameters in the left ventricle (IFN-γ, IL-6, and IL-1ß), as well as increased IL-10 expression and IL-10/TNF-α ratio in treated animals before MI. CONCLUSION: Prior treatment with PYR prevents impairment of the autonomic nervous system after MI, which may be associated with the attenuated expression of inflammatory factors and heart dysfunction.

Temporal pattern recognition with delayed feedback spin-torque nano-oscillators.

The recent demonstration of neuromorphic computing with spin-torque nano-oscillators has opened a path to energy efficient data processing. The success of this demonstration hinged on the intrinsic short-term memory of the oscillators. In this study, we extend the memory of the spin-torque nano-oscillators through time-delayed feedback. We leverage this extrinsic memory to increase the efficiency of solving pattern recognition tasks that require memory to discriminate different inputs. The large tunability of these non-linear oscillators allows us to control and optimize the delayed feedback memory using different operating conditions of applied current and magnetic field.

The gene for the embryonic stem cell coactivator UTF1 carries a regulatory element which selectively interacts with a complex composed of Oct-3/4 and Sox-2.

UTF1 is a transcriptional coactivator which has recently been isolated and found to be expressed mainly in pluripotent embryonic stem (ES) cells (A. Okuda, A. Fukushima, M. Nishimoto, et al., EMBO J. 17:2019-2032, 1998). To gain insight into the regulatory network of gene expression in ES cells, we have characterized the regulatory elements governing UTF1 gene expression. The results indicate that the UTF1 gene is one of the target genes of an embryonic octamer binding transcription factor, Oct-3/4. UTF1 expression is, like the FGF-4 gene, regulated by the synergistic action of Oct-3/4 and another embryonic factor, Sox-2, implying that the requirement for Sox-2 by Oct-3/4 is not limited to the FGF-4 enhancer but is rather a general mechanism of activation for Oct-3/4. Our biochemical analyses, however, also reveal one distinct difference between these two regulatory elements: unlike the FGF-4 enhancer, the UTF1 regulatory element can, by its one-base difference from the canonical octamer-binding sequence, selectively recruit the complex comprising Oct-3/4 and Sox-2 and preclude the binding of the transcriptionally inactive complex containing Oct-1 or Oct-6. Furthermore, our analyses reveal that these properties are dictated by the unique ability of the Oct-3/4 POU-homeodomain that recognizes a variant of the Octamer motif in the UTF1 regulatory element.

Mutual synchronization of spin torque nano-oscillators through a long-range and tunable electrical coupling scheme.

The concept of spin-torque-driven high-frequency magnetization dynamics, allows the potential construction of complex networks of non-linear dynamical nanoscale systems, combining the field of spintronics and the study of non-linear systems. In the few previous demonstrations of synchronization of several spin-torque oscillators, the short-range nature of the magnetic coupling that was used has largely hampered a complete control of the synchronization process. Here we demonstrate the successful mutual synchronization of two spin-torque oscillators with a large separation distance through their long range self-emitted microwave currents. This leads to a strong improvement of both the emitted power and the linewidth. The full control of the synchronized state is achieved at the nanoscale through two active spin transfer torques, but also externally through an electrical delay line. These additional levels of control of the synchronization capability provide a new approach to develop spin-torque oscillator-based nanoscale microwave-devices going from microwave-sources to bio-inspired networks.

Involvement of programmed death-ligand 2 (PD-L2) in the development of experimental allergic conjunctivitis in mice.

BACKGROUND/AIM: Involvement of programmed death-1 (PD-1) and its ligands has been demonstrated in experimental allergic airway disease. Here, the authors aimed to examine whether PD-1 and its ligands are involved in the development of experimental allergic conjunctivitis (EC) in mice. METHODS: EC was induced in Balb/c mice by active immunisation with short ragweed pollen (RW) in alum. 10 days later (day 10), the mice were challenged with eye drops containing RW. 24 hours after the challenge, conjunctivas, spleens, and sera were harvested for histological analysis, cytokine assays, and measurement of RW specific Ig levels. The actively immunised mice were treated with anti-PD-1, anti-PD-L1, anti-PD-L2 antibodies (Abs), or normal rat immunoglobulin G (nrIgG) during either the induction (day 0, 2, 4, 6, and 8) or the effector (2 hours before RW challenge on day 10) phase. RESULTS: Ab treatment during the induction phase did not affect eosinophil infiltration although immune responses were modulated. In contrast, treatment with anti-PD-L2 Ab, but not anti-PD-1 or anti-PD-L1 Ab, during the effector phase significantly increased eosinophil infiltration into the conjunctiva without affecting systemic immune responses. CONCLUSIONS: Similar to allergic airway inflammation, PD-L2 is involved in the development of EC during the effector phase but not the induction phase.

Interleukin 10 and transforming growth factor beta contribute to the development of experimentally induced allergic conjunctivitis in mice during the effector phase.

AIM: To investigate the involvement of interleukin (IL)10 and transforming growth factor (TGF) beta in the development of experimentally induced allergic conjunctivitis in mice. METHODS: Balb/c mice were actively sensitised with ragweed in alum, and then challenged with ragweed in eye drops after 10 days. 24 h later, the conjunctivas, spleens and blood were collected for histological and cytokine expression analyses, proliferation and cytokine production assays and measurement of immunoglobulin (Ig) levels. Mice developing experimentally induced allergic conjunctivitis were injected intraperitoneally with 200 microg of anti-IL10 or anti-TGF beta antibodies at 0, 2, 4, 6 and 8 days (induction phase treatment) or 500 microg of antibodies 2 h before ragweed challenge (effector phase treatment). Normal rat IgG was used for control injections. RESULTS: Treatment with either anti-IL10 or anti-TGF beta antibodies during the induction phase did not affect eosinophil infiltration into the conjunctiva. By contrast, treatment with either antibody during the effector phase suppressed infiltration. During the effector phase, treatment with anti-TGF beta antibody, but not the anti-IL10 antibody, markedly up regulated proliferation and Th2 cytokine production by splenocytes. IL1alpha levels in the conjunctiva were reduced after treatment with either antibody; in addition, eotaxin and tumour necrosis factor alpha levels were reduced after treatment with antibody to TGF beta. CONCLUSIONS: IL10 and TGF beta do not have immunosuppressive roles in the development of experimentally induced allergic conjunctivitis. Rather, they augment the infiltration of eosinophils into the conjunctiva during the effector phase of experimentally induced allergic conjunctivitis.

Coherent microwave generation by spintronic feedback oscillator.

The transfer of spin angular momentum to a nanomagnet from a spin polarized current provides an efficient means of controlling the magnetization direction in nanomagnets. A unique consequence of this spin torque is that the spontaneous oscillations of the magnetization can be induced by applying a combination of a dc bias current and a magnetic field. Here we experimentally demonstrate a different effect, which can drive a nanomagnet into spontaneous oscillations without any need of spin torque. For the demonstration of this effect, we use a nano-pillar of magnetic tunnel junction (MTJ) powered by a dc current and connected to a coplanar waveguide (CPW) lying above the free layer of the MTJ. Any fluctuation of the free layer magnetization is converted into oscillating voltage via the tunneling magneto-resistance effect and is fed back into the MTJ by the CPW through inductive coupling. As a result of this feedback, the magnetization of the free layer can be driven into a continual precession. The combination of MTJ and CPW behaves similar to a laser system and outputs a stable rf power with quality factor exceeding 10,000.

Spin-torque resonant expulsion of the vortex core for an efficient radiofrequency detection scheme.

It has been proposed that high-frequency detectors based on the so-called spin-torque diode effect in spin transfer oscillators could eventually replace conventional Schottky diodes due to their nanoscale size, frequency tunability and large output sensitivity. Although a promising candidate for information and communications technology applications, the output voltage generated from this effect has still to be improved and, more pertinently, reduces drastically with decreasing radiofrequency (RF) current. Here we present a scheme for a new type of spintronics-based high-frequency detector based on the expulsion of the vortex core in a magnetic tunnel junction (MTJ). The resonant expulsion of the core leads to a large and sharp change in resistance associated with the difference in magnetoresistance between the vortex ground state and the final C-state configuration. Interestingly, this reversible effect is independent of the incoming RF current amplitude, offering a fast real-time RF threshold detector.

Isolation of a cDNA encoding a widely expressed novel zinc finger protein with the LeR and KRAB-A domains.

We have isolated a human cDNA clone representing a novel human gene. The predicted 683-amino-acid protein, designated FPM315, contains nine C2H2-type zinc finger motifs and two regions homologous to the LeR domain, a finger-associated structural domain, and the A element of the Kruppel-associated box (KRAB) domain involved in transcriptional repression. The FPM315 mRNAs were expressed in all human tissues so far examined. A cross-species genomic hybridization indicates that the FPM315 gene is highly conserved among eukaryotes. These data suggest that FPM315 might play an important role in basic cellular processes.

Enhanced secretion of insulin plays a role in the development of atherosclerosis and restenosis of coronary arteries: elective percutaneous transluminal coronary angioplasty in patients with effort angina.

OBJECTIVES: We investigated the relation between insulin and coronary atherosclerosis and restenosis of the coronary arteries, by performing elective percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Insulin is known to promote atherosclerosis of the arteries and has been implicated in the development of restenosis after PTCA. METHODS: Of 210 angina patients who underwent PTCA, newly detected lesions in 35 consecutive nondiabetic subjects without previous intervention on the same main coronary arteries were analyzed after a 75-g oral glucose tolerance test (OGTT) and follow-up coronary angiography. Atherosclerotic lesions were evaluated by pattern, severity and extent. Restenosis was defined as loss of gain, the percentage of loss of the initial gain in the coronary diameter achieved by PTCA > or = 50%. RESULTS: Patients with restenosis had a significantly higher extent index (a marker of atherosclerosis), insulin area, ratio of insulin area to glucose area, insulinogenic index and minimal lumen diameter after PTCA than those without restenosis (p=0.001, 0.011, 0.002, 0.016 and 0.041, respectively). Simple regression analysis revealed that only the ratio of insulin area to glucose area (a relative marker of enhanced insulin secretion) significantly correlated with the extent index (p=0.035). Extent index, insulin area, the ratio of insulin area to glucose area and insulinogenic index significantly correlated with loss of gain (p=0.001, 0.010, 0.002 and 0.032, respectively). Stepwise multiple regression analyses revealed that extent index and the ratio of insulin area to glucose area significantly correlated with loss of gain. CONCLUSIONS: Enhanced secretion of insulin during the OGTT might be useful as a predictor of coronary atherosclerosis and of restenosis after elective PTCA in nondiabetic patients with effort angina.

Cardiovascular effects of leukotoxin (9, 10-epoxy-12-octadecenoate) and free fatty acids in dogs.

Leukotoxin (9,10-epoxy-12-octadecenoate) biosynthesised from linoleate by neutrophils is highly toxic to cellular function. Its cardiovascular effects were studied in dogs together with the effects of various fatty acids. Aortic flow, left ventricular peak dP.dt-1, and aortic pressure were measured in 60 anaesthetised dogs, which were divided into 10 groups of six animals each--namely, control group (10 ml of physiological saline), three leukotoxin groups (5, 10, and 50 mg.kg-1), two linoleic acid groups (10 and 50 mg.kg-1), two oleic acid groups (10 and 50 mg.kg-1), and two stearic acid groups (10 and 50 mg.kg-1). Leukotoxin injected intravenously depressed cardiac function in a dose dependent manner. Administration of leukotoxin 5 mg.kg-1 showed no significant cardiotoxic effect. However, 10 mg.kg-1 of leukotoxin significantly decreased aortic flow from 0.74(0.04) to 0.40(0.07) litre.min-1 (mean(SEM], left ventricular peak dP.dt-1 from 2040(205) to 1140(217) mmHg.s-1, and aortic pressure from 106(7.1)/67(6.3) to 75(9.2)/48(6.5) mmHg 5 min after injection. Dogs given leukotoxin 50 mg.kg-1 showed more pronounced cardiodepressive effects; aortic flow was decreased to 0.19(0.06), left ventricular dP.dt-1 to 560(134), and aortic pressure to 72(15.1)/41(10.6) 5 min after injection. All dogs in this group were dead within 45 min. Administration of 10 mg.kg-1 of linoleic acid, oleic acid, or stearic acid caused no significant haemodynamic changes. Administration of linoleic acid 50 mg.kg-1 had cardiotoxic effects, but the effect was less than that of leukotoxin. Since leukotoxin appears to be a potent cardiodepressive agent it may be an important factor in the development of heart failure observed in patients with severe burns.

Effect of laser suture lysis on filtration openings: a prospective three-dimensional anterior segment optical coherence tomography study.

PURPOSE: To investigate the effects of laser suture lysis (LSL) on filtration openings after trabeculectomy. METHODS: Prospective study analyzing the changes in the location and width of filtration openings, fluid cavity height, total bleb height, bleb wall thickness, and bleb wall intensity before and after LSL using three-dimensional anterior segment optical coherence tomography (3D AS-OCT). RESULTS: Fourteen patients had clear scleral flap image analysis. As five patients underwent LSL twice and two patients underwent LSL thrice, 23 comparison studies were possible. After LSL the intraocular pressure (IOP) decreased (P = 0.0015) from 20.5 ± 5.3 to 14.9 ± 6.4 mm Hg, and the fluid cavity height increased significantly from 0.2 ± 0.2 mm to 0.3 ± 0.1 mm (P = 0.0094). Other bleb parameters were not significantly different when comparing before and after LSL. When the IOP reduction ratio was > 25% following LSL, the width of the filtration openings on the LSL side, the total bleb height, and the fluid cavity height increased (P = 0.0273, 0.0342, and 0.0024, respectively). In multiple regression analysis the changes in fluid cavity height, the wall thickness, the wall intensity, and the width of the filtration opening were positively associated with the IOP reduction rate (P = 0.0428, 0.0226, 0.0420, and 0.0356, respectively). CONCLUSIONS: 3D AS-OCT allowed a detailed examination of the internal morphology of filtration blebs and openings before and after LSL. The changes in the internal morphology were closely associated with the success of LSL to decrease IOP.

Chromosomal assignments of novel genes expressed in HL60 granulocytes.

By collecting 3'-directed cDNA sequences called gene signatures (GSs) on a large scale, it is possible to make an expression profile of genes in a particular tissue, as well as discovering a number of novel genes. A total of 305 novel GSs collected from granulocytoid cells derived from HL60, a human promyelocytic leukemia cell line, by exposure to dimethyl sulfoxide were radiolabeled and used for Southern blot analyses to determine the copy number of the corresponding genes. Of these, 198 GSs identified as representing single-copy genes were then used as probes for hybridization analyses using a monochromosomal hybrid cell DNA panel. Sixty-nine of them were assigned to individual chromosomes. These results demonstrate that the chromosomal distribution of the GSs seems not to be proportional to the cytogenetic length of each chromosome.