A crossbar array of magnetoresistive memory devices for in-memory computing.

Implementations of artificial neural networks that borrow analogue techniques could potentially offer low-power alternatives to fully digital approaches1-3. One notable example is in-memory computing based on crossbar arrays of non-volatile memories4-7 that execute, in an analogue manner, multiply-accumulate operations prevalent in artificial neural networks. Various non-volatile memories-including resistive memory8-13, phase-change memory14,15 and flash memory16-19-have been used for such approaches. However, it remains challenging to develop a crossbar array of spin-transfer-torque magnetoresistive random-access memory (MRAM)20-22,  despite the technology's practical advantages such as endurance and large-scale commercialization5. The difficulty stems from the low resistance of MRAM, which would result in large power consumption in a conventional crossbar array that uses current summation for analogue multiply-accumulate operations. Here we report a 64 × 64 crossbar array based on MRAM cells that overcomes the low-resistance issue with an architecture that uses resistance summation for analogue multiply-accumulate operations. The array is integrated with readout electronics in 28-nanometre complementary metal-oxide-semiconductor technology. Using this array, a two-layer perceptron is implemented to classify 10,000 Modified National Institute of Standards and Technology digits with an accuracy of 93.23 per cent (software baseline: 95.24 per cent). In an emulation of a deeper, eight-layer Visual Geometry Group-8 neural network with measured errors, the classification accuracy improves to 98.86 per cent (software baseline: 99.28 per cent). We also use the array to implement a single layer in a ten-layer neural network to realize face detection with an accuracy of 93.4 per cent.

Comparative Analysis of Ginsenoside Profiles: Antioxidant, Antiproliferative, and Antigenotoxic Activities of Ginseng Extracts of Fine and Main Roots.

The aim of this study was to compare ginsenosides profiles, and antioxidant, antiproliferative, and antigenotoxic activities of ginseng extract derived from fine and main roots. The result of the analysis showed a higher total content of ginsenoside in fine roots than in main roots; differences in levels between the different extracts were also confirmed. The oxygen radical absorbance capacity (ORAC) assay showed that H2O main root extract had a significantly higher activity than that from fine roots. MeOH and H2O extracts from the fine and main roots also exhibited stronger cellular antioxidant capacity 2,2'-azobis(2-amidinopropane) dihydrochloride-induced oxidative stress in HepG2 cells compared with the positive control. Through calculating the half-maximal inhibitory concentration values, the cytotoxicity of the main root extracts were ranked as follows: MeOH (6.1±1.2 µg/mL)> H2O (6.6±0.1 µg/mL)> ethanol (10.4±0.6 µg/mL); however, the cytotoxicity of all fine root extracts did not significantly differ. All the fine root extracts showed an inhibitory capacity against 4-hydroxynonenal-induced DNA damage, however only the MeOH extract of the main root showed a decrease in DNA damage. All three solvent extracts from the fine roots reduced DNA damage more in the H2O2-treated group, whereas only the MeOH and H2O extracts of the main roots produced a significant reduction. Levels of Rg3 ginsenoside were positively correlated with indices of the ORAC value, and total ginsenoside contents showed a negative correlation with DNA damage induced by H2O2. This study suggests that ginseng and the extraction solvent both affect levels of ginsenoside. Furthermore, the antioxidant potency of ginseng can be attributed to the content of some ginsenosides.

Two complete chloroplast genome sequences of Cannabis sativa varieties.

In this study, we determined the complete chloroplast (cp) genomes from two varieties of Cannabis sativa. The genome sizes were 153,848 bp (the Korean non-drug variety, Cheungsam) and 153,854 bp (the African variety, Yoruba Nigeria). The genome structures were identical with 131 individual genes [86 protein-coding genes (PCGs), eight rRNA, and 37 tRNA genes]. Further, except for the presence of an intron in the rps3 genes of two C. sativa varieties, the cp genomes of C. sativa had conservative features similar to that of all known species in the order Rosales. To verify the position of C. sativa within the order Rosales, we conducted phylogenetic analysis by using concatenated sequences of all PCGs from 17 complete cp genomes. The resulting tree strongly supported monophyly of Rosales. Further, the family Cannabaceae, represented by C. sativa, showed close relationship with the family Moraceae. The phylogenetic relationship outlined in our study is well congruent with those previously shown for the order Rosales.

The prognostic impact of mutations in spliceosomal genes for myelodysplastic syndrome patients without ring sideroblasts.

BACKGROUND: Mutations in genes that are part of the splicing machinery for myelodysplastic syndromes (MDS), including MDS without ring sideroblasts (RS), have been widely investigated. The effects of these mutations on clinical outcomes have been diverse and contrasting. METHODS: We examined a cohort of 129 de novo MDS patients, who did not harbor RS, for mutations affecting three spliceosomal genes (SF3B1, U2AF1, and SRSF2). RESULTS: The mutation rates of SF3B1, U2AF1, and SRSF2 were 7.0 %, 7.8 %, and 10.1 %, respectively. Compared with previously reported results, these rates were relatively infrequent. The SRSF2 mutation strongly correlated with old age (P < 0.001), while the mutation status of SF3B1 did not affect overall survival (OS), progression-free survival (PFS), or acute myeloid leukemia (AML) transformation. In contrast, MDS patients with mutations in U2AF1 or SRSF2 exhibited inferior PFS. The U2AF1 mutation was associated with inferior OS in low-risk MDS patients (P = 0.035). The SRSF2 mutation was somewhat associated with AML transformation (P = 0.083). CONCLUSION: Our findings suggest that the frequencies of the SF3B1, U2AF1, and SRSF2 splicing gene mutations in MDS without RS were relatively low. We also demonstrated that the U2AF1 and SRSF2 mutations were associated with an unfavorable prognostic impact in MDS patients without RS.

A missense mutation (c.1963A

Serum Ca(++) levels play important roles in the humoral immunity. The aim of this study was to detect quantitative trait loci and the associated positional candidate genes affecting baseline serum Ca(++) concentrations. A genome-wide association study was conducted in an F(2) intercross population between Landrace and Korean native pigs using the porcine single nucleotide polymorphism (SNP) 60 K beadchip and the PLINK program based on linear regression. Data used in the study included 410 F(2) pigs. All experimental animals were genotyped with 36,613 SNP markers located throughout the pig autosomes. We identified a strong association between a SNP marker on chromosome 7 and serum Ca(++) levels (DIAS0002191, genomic control-corrected P = 7.7 × 10(-5)). The position of DIAS0002191 was closely located to SLA class III region containing the C2 gene encoding the complementary component 2 protein, a protein which is important in the humoral immune responses. De novo sequencing of the porcine C2 gene revealed a missense mutation [c.1963A

Effects of puffer (Sphoeroides rubripes) supplementation on disruption of antioxidant defense systems in ethanol-treated rats.

We investigated the effects of puffer (Sphoeroides rubripes) supplementation on antioxidant metabolism in ethanol-treated rats. Sprague-Dawley rats were randomly assigned into 4 groups of 7 rats each and fed (1) an AIN-93G diet (NC), (2) 25% ethanol (E), (3) 25% ethanol and an AIN-93G diet containing 1% puffer flesh (E+F), or (4) 25% ethanol and an AIN-93G diet containing 1% puffer skin (E+S) for 5 wk. At the end of the experimental period, the rats were sacrificed and their blood and organs were collected. To evaluate the effect of puffer supplementation, lipid-soluble antioxidant vitamin and conjugated diene (CD) levels, DNA damage, and mRNA expression of heme oxygenase-1 (HO-1) were assessed. Animals that were fed ethanol showed reduced plasma levels of lipid-soluble antioxidant vitamin and significantly increased levels of lipid peroxides, DNA damage, and HO-1 expression. Dietary supplementation with puffer conferred an antioxidant effect by significantly increasing the levels of γ-tocopherol, a lipid-soluble antioxidant vitamin, and by significantly decreasing the plasma levels of CD, DNA damage, and HO-1 expression. These results suggest that consumption of puffer improves the antioxidant status of ethanol-treated rats.

An accurate method for quantifying and analyzing copy number variation in porcine KIT by an oligonucleotide ligation assay.

BACKGROUND: Aside from single nucleotide polymorphisms, copy number variations (CNVs) are the most important factors in susceptibility to genetic disorders because they affect expression levels of genes. In previous studies, pyrosequencing, mini-sequencing, real-time PCR, invader assays and other techniques have been used to detect CNVs. However, the higher the copy number in a genome, the more difficult it is to resolve the copies, so a more accurate method for measuring CNVs and assigning genotype is needed. RESULTS: PCR followed by a quantitative oligonucleotide ligation assay (qOLA) was developed for quantifying CNVs. The accuracy and precision of the assay were evaluated for porcine KIT, which was selected as a model locus. Overall, the root mean squares of bias and standard deviation of qOLA were 2.09 and 0.45, respectively. These values are less than half of those in the published pyrosequencing assay for analyzing CNV in porcine KIT. Using a combined method of qOLA and another pyrosequencing for quantitative analysis of KIT copies with spliced forms, we confirmed the segregation of KIT alleles in 145 F1 animals with pedigree information and verified the correct assignment of genotypes. In a diagnostic test on 100 randomly sampled commercial pigs, there was perfect agreement between the genotypes obtained by grouping observations on a scatter plot and by clustering using the nearest centroid sorting method implemented in PROC FASTCLUS of the SAS package. In a test on 159 Large White pigs, there were only two discrepancies between genotypes assigned by the two clustering methods (98.7% agreement), confirming that the quantitative ligation assay established here makes genotyping possible through the accurate measurement of high KIT copy numbers (>4 per diploid genome). Moreover, the assay is sensitive enough for use on DNA from hair follicles, indicating that DNA from various sources could be used. CONCLUSION: We have established a high resolution quantification method using an oligonucleotide ligation assay to measure CNVs, and verified the reliability of genotype assignment for random animal samples using the nearest centroid sorting method. This new method will make it more practical to determine KIT CNV and to genotype the complicated Dominant White/KIT locus in pigs. This procedure could have wide applications for studying gene or segment CNVs in other species.

Self-tuning of threshold for a two-state system.

A two-state system (TSS) under time-periodic perturbations (to be regarded as input signals) is studied in connection with self-tuning (ST) of threshold and stochastic resonance (SR). By ST, we observe an improvement of the signal-to-noise ratio (SNR) in a weak-noise region. An analytic approach to a tuning equation reveals that SNR improvement is possible also for the large-noise region and this is demonstrated by Monte Carlo simulations of hopping processes in a TSS. ST and SR are discussed from a little more physical point of view of the energy transfer (dissipation) rate, which behaves in a similar way as the SNR. Finally ST is considered briefly for a double-well potential system, which is closely related to the TSS.

Effects of simvastatin on plasma antioxidant status and vitamins in hypercholesterolemic patients.

BACKGROUND: Statins are known to possess antioxidant properties in addition to their cholesterol-lowering effects. However, recent studies have suggested that statins reduce the levels of antioxidant vitamins such as vitamin E and coenzyme Q(10), possibly resulting in impaired left ventricular function. We investigated the effects of simvastatin on the blood lipids, LDL oxidation and plasma antioxidant status, and whether these effects were associated with changes in plasma antioxidant vitamin levels. METHODS: Simvastatin (20-40 mg/day) was administered for 8 weeks in seventy-six hypercholesterolemic patients. We measured plasma lipids, oxidized LDL, total radical trapping antioxidant potential (TRAP) and plasma antioxidant vitamin levels at baseline and after 8 weeks of simvastatin administration. RESULTS: Simvastatin significantly lowered serum levels of total cholesterol and LDL-cholesterol by 30.1% and 41.9%, respectively. A significant reduction in oxidized LDL levels (p<0.0001) and improvement in plasma antioxidant status as measured by TRAP (p<0.05) after the 8-week simvastatin treatment were observed. Regarding the effects of simvastatin on plasma antioxidant vitamin levels, there were significant increases in the levels of lipid-corrected retinol (p<0.001), alpha-tocopherol (p<0.001) and gamma-tocopherol (p<0.005) after the 8-week simvastatin treatment. Lipid-corrected levels of coenzyme Q10 and carotenoids remained unchanged after simvastatin treatment. CONCLUSIONS: Our results show that simvastatin reduced blood lipids and circulating oxidized LDL, and improved plasma antioxidant status without altering the antioxidant vitamin system. These data indicate that simvastatin not only decreases blood lipids and circulating oxidized LDL but also increases lipid corrected levels of antioxidant vitamins and may improve plasma antioxidant status synergizing with the biological effects of antioxidants.

Ergodic-nonergodic transition in a threshold system with feedback.

A threshold system with feedback is studied from the viewpoint of an ergodic-nonergodic transition, a kind of nonequilibrium phase transition, as the rate of input signal variation is changed. By discussing the time evolution of the distribution function, instead of its lowest moment (an order parameter), we can determine the transition point and make clear the role and limitation of the self-consistent equation for the order parameter. Finally the feedback strength is related to an activation energy from a statistical mechanical viewpoint.