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In this article, for the first time, self-rectifying memristors are exploited for logic-in-memory computation. We report a Pt/TaO x /Ta memristor with salient self-rectifying bipolar features (104 ON-/ OFF-ratio, 105 rectification ratio, 105 nonlinearity, and ~1 pA leakage current), which could support a large passive crossbar array up to 160 Mb with the premise of 10% read margin. Moreover, we propose and experimentally validate a controlled majority-inverter graph logic method based on the self-rectifying switching behaviors, with advantages in computation complexity. Our work is a step forward toward in-memory computing in high-density or even 3-D memristor architectures.

We propose an AgGeSe/Al2O3/Pt selector with great potential in a dense memory array. In terms of on-current drive, selectivity, and uniformity, devices with the mixed AgGeSe layer outperform the Ag/Al2O3/Pt device. The introduction of GeSe not only blocks the diffusion of Ag, but also facilitates the backflow of Ag to the active electrode, therefore increasing the on-current. The ultra-high on-current drive (3 mA and 12.7 MA/cm2), high selectivity (1010), small variation, high thermal stability, and steep switching slope (0.27 mV/dec) realized in our AgGeSe/Al2O3/Pt device render it a promising candidate for selector application.

Similarity search, that is, finding similar items in massive data, is a fundamental computing problem in many fields such as data mining, and information retrieval. However, for large-scale and high-dimension data, it suffers from high computational complexity, requiring tremendous computation resources. Here, based on the one-selector-one-resistor memristors, for the first time, we propose an in-memory search (IMS) system with two innovative designs. First, by exploiting the natural distribution law of the devices resistance, a hardware local sensitive hash encoder has been designed to transform the real-valued vectors into more efficient binary codes. Second, a compact memristive ternary content addressable memory is developed to calculate the Hamming distances between the binary codes in parallel. Our IMS system demonstrated a 168× energy efficiency improvement over all-transistors counterparts in clustering and classification tasks, while achieving a software-comparable accuracy, thus providing a low-complexity and low-power solution for in-memory data mining applications.

In-memory computing based on memristor is a promising solution to accelerate on-chip deep neural networks. Concerning the nonideal factors of the device analog behaviors, binary neural network (BNN) with ±1 weight and 0/+1 neuron is an alternative route to better employ the binary memristors with high technical maturity. In this article, we demonstrate a select column scheme for the BNN inference accelerator. By incorporating the performance of a W/AlO x /Al2O3/Pt memristor, the BNN shows high robustness and achieves a high recognition accuracy of 98.31% on the MNIST data set. We further propose a bit error model to investigate the impact of device error on recognition accuracy. The effects of device variation and nonideal input are also considered. The results show that the accuracy keeps satisfying (more than 90%) even under a high invalid rate, high input swing (0.21 standard deviation), and 7% salt noise in binary input, respectively, whereas the device variation has a trivial effect on the network.

Threshold switching (TS) devices are promising candidates to build highly compact and energy efficient artificial neurons. Here, we present a Pt/Ag/TiN/HfAlOx/Pt (PATHP) device with excellent TS characteristics, including a large selectivity(1010), a wide range of operation current from 10 nA to 1 mA, an extremely steep slope (0.63 mV/dec) and fast turn-on speed (50 ns). The stable TS performance can be ascribed to the introduction of TiN buffer layer and the alternate atomic layer deposited HfAlOx layer. Further, we experimentally demonstrate the functions of leaky-integrate-and-fire neurons with low power feature based on a RC circuit and a single device, respectively, which are essential for constructing spiking neuromorphic systems.

Through oxygen profile engineering, we fabricated W/AlO $_{\mathbf {x}}$ /Al $_{\mathbf {{2}}}~\text{O}_{\mathbf {{3}}}$ /Pt bilayer memristors with a 250-nm feature size. The AlO $_{{\mathbf {x}}}$ fabricated by sputtering serves as an oxygen vacancy source, whereas the Al $_{{\mathbf {{2}}}}~\text{O}_{{\mathbf {{3}}}}$ deposited by atomic layer deposition acts as a dominant resistive switching (RS) layer. Our devices show forming-free RS behaviors with high speed (28 ns), uniform resistance distribution, large on/off ratio ( $\sim 10^{{\mathbf {{3}}}}$ @100K, $\sim 10^{{\mathbf {{3}}}}$ @298K, and $\sim 80$ @400K), and good retention. Besides, temperature stability with record high endurance from cryogenic to high-temperature ( $10^{{\mathbf {{8}}}}$ @100K, $10^{{\mathbf {{10}}}}$ @298K, and $10^{{\mathbf {{7}}}}$ @400K) is demonstrated, to the best of our knowledge.

Background: The FK506-binding protein 4 ( FKBP4 ), a tumor-related gene, plays a vital role in tumorigenesis and cancer progression. The study is aimed to clarify the effect of FKBP4 in lung adenocarcinoma (LUAD). Methods: Relying on The Cancer Genome Atlas (TCGA) cohort, the FKBP4 expression difference between LUAD tissues and non-tumor tissues was first detected, and verified with public tissue microarrays (TMAs), clinical LUAD specimen cohort and Gene Expression Omnibus (GEO) cohort. Then, logistic regression analysis and chi-square test were applied to detect the correlation between FKBP4 expression and clinicopathological parameters. Kaplan-Meier survival analysis and Cox regression model were utilized to evaluate the effect of FKBP4 expression on survival. Signaling pathways related to LUAD were obtained via employing Gene Set Enrichment Analysis (GSEA). Results: The FKBP4 expression level in LUAD samples was dramatically higher than that in non-tumor samples. High FKBP4 expression in LUAD is associated with gender, pathological stage, T classification, lymph node metastasis and distant metastasis. The Kaplan-Meier curve indicated a poor prognosis for LUAD patients with high FKBP4 expression. Multivariate analysis suggested that the high FKBP4 expression was a vital independent predictor of poor overall survival (OS). GSEA showed that a total of 15 signaling pathways were enriched in samples with high FKBP4 expression phenotype. Conclusions: FKBP4 may be an oncogene in LUAD, and is promised to become a prognostic indicator and therapeutic target for LUAD.

Memristive convolutional neural network accelerator has attracted intensive interest in reducing time and energy consumption. In this article, we analysis the viability of the quantization method using LeNet-5 model on MNIST dataset. Low bit-precision quantization is achieved with slight accuracy loss. The fabricated bilayer AlO x memristor with 3-bit states is used to emulate the synapse, and an accuracy of 97.93% is accomplished within the device nonideality. Furthermore, the device requirements of variation and reliability on inference application are evaluated and proposed.

Sensitive biological analysis requires optical labels have good water solubility and relative longer excitation wavelength. Herein, two water-soluble lanthanide (Ln) organic complexes, Na3Ln(DIEDPA)3 (Ln=Eu, Tb) have been synthesized with a new tridentate ligand, 4-[2-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-ethoxy]-pyridine-2,6-dicarboxylic acid (H2DIEDPA). The two lanthanide complexes showed characteristic emissions of Eu3+ and Tb3+ ions with high quantum yields of 11±1.1% and 13±1.5% respectively. Moreover, compared with those for the europium and terbium complexes with pyridine-2,6-dicarboxy acid as a ligand, the effective excitation wavelengths for the two complexes shifted more than 60 nm to longer wavelengths by decoration of the molecular structure of the organic ligand. The results might provide reference for design and synthesis of organic luminescent lanthanide bioprobes with longer excitation wavelengths.

High-performance memristor is greatly desired to develop memcomputing. Here, we report a W/AlO x /Al 2 O 3 /Pt memristor based on oxygen vacancy filament engineering. The oxygen-rich AlO x film fabricated by sputtering (RF) severs as oxygen vacancy (Vo) reservoir with low oxygen chemical potential and high mobility, whereas the denser AI 2 O 3 film deposited by atomic layer deposition (ALD) acts as a dominant resistive switching (RS) layer. Our device, which satisfies promising characteristics for data storage and memcomputing, displays low-power, high-uniformity, large on/off ratio, high-speed and high-temperature stability at 125 °C.

Memristive logic device is a promising unit for beyond von Neumann computing systems and 2D materials are widely used because of their controllable interfacial properties. Most of these 2D memristive devices, however, are made from semiconducting chalcogenides which fail to gate the off‐state current. To this end, a crossbar device using 2D HfSe2 is fabricated, and then the top layers are oxidized into “high‐k” dielectric HfSe x O y via oxygen plasma treatment, so that the cell resistance can be remarkably increased. This two‐terminal Ti/HfSe x O y /HfSe2/Au device exhibits excellent forming‐free resistive switching performance with high switching speed (, An energy‐efficient memristive device based on 2D HfSe2 oxides is fabricated, which is able to implement functionally complete Boolean logic with operation current down to 100 pA. The low‐power switching is realized by the formation and rupture of cone‐shaped O‐vacancy filaments in the ultrathin Hf−Se−O layer.

In this work, we enhance the DC/AC resistive switching performance in AlOx memristors by using a two-technique bilayer approach. Compared to the single-layer memristors (W/AlOx or Al2O3/Pt), the dual-layer memristor (W/AlOx/AlOy/Pt) shows high uniformity in DC cycling (σ/μ 100), fast switching speed (20 ns), high endurance (107 cycles), and high-temperature stability (104 s at 125 °C). These performance enhancements are attributed to the localization of the conductive region after using a dual layer with different defect concentrations. Moreover, the W/AlOx/AlOy/Pt memristor exhibits stable III-bit multilevel storage capability by varying the amplitude of negative pulses. Our results provide an effective strategy to develop high-performance memristors for future memory and computing applications.

Ir(ppy)2(VPHD) (ppy=2-phenyl pyridine, VPHD=6-(4-vinylphenyl)-2,4-hexanedione) was copolymerized with methyl methacrylate (MMA). The copolymer had high quantum yield of 52.3±0.5% in dilute ethyl acetate solution, and the yield increased around 45% than that of the iridium monomer. The maximum emission peaks for the copolymers shifted from 515 to 489 nm while the iridium complex content was less than 0.005 mol% in the feed. The blue emission at 489 nm and the green emission at 520 nm were analyzed by Lorenz function. They are attributed to 1MLCT and 3MLCT emissions, respectively.

Sensitive method for chemical analysis of free cholesterol (FC) and cholesterol esters (CE) was developed. Mouse arteries were dissected and placed in chloroform-methanol without tissue grinding. Extracts underwent hydrolysis of cholesteryl esters and derivatization of cholesterol followed by liquid chromatography/mass spectrometry (LC/MS/MS) analysis. We demonstrated that FC and CE could be quantitatively extracted without tissue grinding and that lipid extraction simultaneously worked for tissue fixation. Delipidated tissues can be embedded in paraffin, sectioned, and stained. Microscopic images obtained from delipidated arteries have not revealed any structural alterations. Delipidation was associated with excellent antigen preservation compatible with traditional immunohistochemical procedures. In ApoE(-/-) mice, LC/MS/MS revealed early antiatherosclerotic effects of dual PPARalpha,gamma agonist LY465606 in brachiocephalic arteries of mice treated for 4 weeks and in ligated carotid arteries of animals treated for 2 weeks. Reduction in CE and FC accumulation in atherosclerotic lesions was associated with the reduction of lesion size. Thus, a combination of LC/MS/MS measurements of CE and FC followed by histology and immunohistochemistry of the same tissue provides novel methodology for sensitive and comprehensive analysis of experimental atherosclerotic lesions.

Inflammation is critically involved in atherogenesis. Signaling from innate immunity receptors TLR2 and 4, IL-1 and IL-18 is mediated by MyD88 and further by interleukin-1 receptor activated kinases (IRAK) 4 and 1. We hypothesized that IRAK4 kinase activity is critical for development of atherosclerosis. IRAK4 kinase-inactive knock-in mouse was crossed with the ApoE-/- mouse. Lesion development was stimulated by carotid ligation. IRAK4 functional deficiency was associated with down-regulation of several pro-inflammatory genes, inhibition of macrophage infiltration, smooth muscle cell and lipid accumulation in vascular lesions. Reduction of plaque size and inhibition of outward remodeling were also observed. Similar effects were observed when ApoE-/- mice subjected to carotid ligation were treated with recombinant IL-1 receptor antagonist thereby validating the model in the relevant pathway context. Thus, IRAK4 functional deficiency inhibits vascular lesion formation in ApoE-/- mice, which further unravels mechanisms of vascular inflammation and identifies IRAK4 as a potential therapeutic target.

Stearoyl-CoA desaturase (SCD) is an integral membrane protein of the endoplasmic reticulum (ER) that catalyzes the formation of monounsaturated fatty acids from saturated fatty acids. Recent studies suggest that SCD is a key regulator of energy metabolism and has implications in dislipidemia and obesity. Four SCD isoforms (SCD1–4) have been identified in mouse. In human, only one SCD isoform has been characterized so far. Here we report that the previously reported human ACOD4 gene encodes a distinct stearoyl-CoA desaturase, hSCD5. GenBank database mining revealed orthologues of hSCD5 in the primates, but not in the rodents. In transiently transfected 293 cells, hSCD5 co-localized with calnexin on ER membrane. Microsome fractions prepared from hSCD1 and hSCD5 transfected cells displayed similar delta 9 desaturase activity. Quantitative real-time RT-PCR analysis suggested that hSCD5 was abundantly expressed in adult brain and pancreas. These data suggested that hSCD5 plays a role distinct from that of hSCD1 during development and in normal physiological conditions.

We have previously demonstrated that protein kinase C (PKC)- alpha expression is significantly elevated in failing human left ventricle, with immunostaining showing increased PKC- alpha localization at the intercalated disks of cardiomyocytes. In the present study we sought to determine, in the failing heart, if PKC- alpha interacted with connexin-43 (Cx-43) both spatially and functionally, and to compare the association of PKC- alpha/Cx-43 with that of PKC- epsilon, a PKC isozyme that does not significantly increase in failing hearts. The possibility of a PKC- alpha or PKC- epsilon/Cx-43 association in non-failing hearts was also investigated. Co-immunoprecipitation of PKC- alpha or PKC- epsilon and Cx-43 in non-failing and failing left ventricle was achieved using antibodies to PKC- alpha or Cx-43. Confocal microscopy confirmed that PKC- alpha distribution within the cardiomyocyte included co-localization with connexin-43 in both failing and non-failing myocardium. In a similar manner, confocal imaging of PKC- epsilon showed cardiomyocyte distribution in both cytosol and membrane, and colocalization of PKC- epsilon with Cx-43. Recombinant PKC- alpha or - epsilon increased PKC activity significantly above endogenous levels in the co-immunoprecipitated Cx-43 complexes (P

In the present study, we have investigated the changes in the expression and distribution of the principal gap-junction channel protein in ventricular muscle, connexin 43 (Cx43), during the first 2 weeks of culturing adult guinea pig cardiomyocytes at low density to prevent formation of cellular contacts. In freshly isolated cardiomyocytes, immunoreactive Cx43 occupied 6.5 +/- 0.4% of the pixel area of the cell, with 85% being localized to dense particles at the step-like end projections of the myocytes (intercalated disk regions) and 15% being within the sarcoplasm or along the lateral surface of the myocytes ("nondisk" distribution). During the myocytes' first 48 h in culture, immunoreactive Cx43 decreased by 27.5% from control values, to 4.7 +/- 0.5% of the cells' pixel area (P < 0.01). Cx43 particles also redistributed: after 48 h in culture approximately 90% of the immunoreactive Cx43 was localized in the sarcoplasm and nondisk regions of the myocyte. After 7 days, immunoreactive Cx43 only occupied 50% of the cells' control pixel area (P < 0.01) and was nearly uniform in its punctate pattern throughout the sarcoplasm. This distribution remained the same during the 2nd week in culture. Changes in myosin light chain staining during 8 days in culture largely paralleled those in Cx43 staining. Laser confocal microscopic analysis of double-immunolabeled myocytes that had been in culture for 24-48 h showed colocalization of Cx43 with clathrin in approximately 30% of the sarcoplasmic Cx43 particles. Thus it is demonstrated that the expression of Cx43 decreases significantly during the first 48 h in culture after myocyte isolation and that Cx43 also undergoes substantial redistribution but for the next 2 weeks remains more or less unchanged and at relatively high levels (approximately 50%). These data indicate that cardiomyocytes in isolation maintain their ability to reconnect with each other for up to at least 2 weeks. This is the first time that this property has been investigated in cultured adult ventricular cardiomyocytes.

The phase generated carrier (PGC) modulation-demodulation technique is the main demodulation technique for fiber interferometric sensors. There are two methods to realize PGC modulation. One method is inner modulation, and the other is external modulation. However, there is less study on the PGC external modulation than the PGC inner modulation. In this paper, we focus on the PGC external modulation to analyze its characteristics. The experiment results indicate that the external demodulation performs well. Furthermore, its cost is much lower than that of inner modulation.

The pleiotropic antiatherosclerotic effects of statins are believed to be associated with the inhibition of Rho-kinase. However, a systematic analysis of Rho-kinase activation in atherosclerotic lesions is missing.To analyze the distribution and phosphorylation of target proteins of Rho-kinase, such as myosin light chain (MLC) and ezrin-radixin-moesin (ERM) proteins, in the apolipoprotein E (ApoE) knockout model of accelerated atherosclerosis, as well as the effects of treatment with the Rho-kinase inhibitor Y-27632.Western diet-fed ApoE-deficient mice underwent carotid ligation and were sacrificed 14 days after surgery. One group of ligated mice was treated with the Rho-kinase inhibitor Y-27632. Nonligated C57Bl6/J mice on normal chow and ApoE-deficient mice on Western diet were used as controls. Lesion structure and size were analyzed using Masson-elastic stained cross-sections. The distribution and phosphorylation of Rho-kinase target proteins were studied immunohistochemically.Two weeks after surgery, atherosclerotic plaque-like lesions developed in ligated carotids. Lesion development was inhibited by Y-27632. ERM was expressed ubiquitously, but in the intact arteries, it was phosphorylated exclusively in the endothelium and periadventitial adipocytes. In the atherosclerotic lesions, foamy macrophages also exhibited a strong phospho-ERM signal. Y-27632 inhibited ERM phosphorylation in the plaques. MLC and phospho-MLC were associated with smooth muscle cells and did not respond to the Y-27632 treatment.A cell type-selective distribution and phosphorylation of target proteins of Rho-kinase were demonstrated in the carotid artery of the normal mouse model, as well as in the ApoE-knockout model of accelerated atherosclerosis. Various downstream targets of the same enzyme may be differentially involved in specific pathological processes in a cell type-specific manner.

Heterogeneous Loss of Connexin43 Protein in Ischemic Dog Hearts. Introduction: Ischemia causes cell decoupling in the myocardium. Prolonged ischemia activates proteases and causes degradation of structural proteins as well as gap junctions. There is little information about the degradation of gap junction protein during the early time period after acute ischemia. The purpose of the present study was to investigate connexin43 (Cx43) protein degradation and distribution patterns in (he canine left ventricular wall during 1 to 6 hours of ischemia. Methods and Results: Ischemia of canine left ventricular myocardium was induced by ligation of the left anterior descending coronary artery. Following a period of in situ ischemia of up to 6 hours, samples were harvested, and standard paraffin slides were prepared for Cx43 and wheat germ agglutinin double labeling. Cx43 distribution was visualized by confocal microscopy. In controls, homogeneous distribution of Cx43 staining was determined. Ischemia caused a loss of Cx43 with a heterogeneous pattern by mixing foci of infarcted cells among normal cardiac myocytes. To determine if the changes were induced by heterogeneous reduction in the blood supply, an in vitro ischemic model was studied to induce more homogeneous ischemia. Western blot analysis of these in vitro ischemic tissue samples revealed a reduction of Cx43 protein concentration with a 50% decay time of 4.8 hours. Cx43 dephosphorylation was detected after 1 hour of in vitro ischemia. Heterogeneous loss of Cx43 was found in the in vitro ischemic tissue. There were no. significant changes in Cx43 staining density during the first hour of ischemia at a time when dephospharylation of the protein was observed. After 1 hour of ischemia, Cx43 was reduced at intercalated disk areas, and. after 6 hours, most Cx43 disappeared at intercalated disk areas, while small amounts of Cx43 remained at side-to-side junctions. Conclusion: Cx43 undergoes both distribution and concentration changes following acute cardiac Ischemia. The loss of Cx43 protein is heterogeneous. Cx43 dephosphorylation occurred within 1 hour following ischemia.

Background We assessed the effects of radiofrequency catheter ablation (RFCA) of the atrial epicardium on pacing-induced sustained atrial fibrillation (AF) and the expression and distribution of the intercellular gap junction protein connexin 43 (Cx43) in dogs. Methods and Results In 12 mongrel dogs, after creation of complete AV block and implantation of a ventricular inhibited pacemaker, a high-rate pulse generator (20 to 30 Hz to induce AF) was implanted in the neck, connected to a right atrial endocardial pacing lead, and used to pace the atrium for 10 to 14 weeks. In group 1 (n=9 dogs), corrected sinus node recovery time (CSNRT), P-wave duration, 24-hour Holter ECG, maximal heart rate (MHR) in response to isoproterenol, and intrinsic heart rate (IHR) after atropine (0.04 mg/kg) and propranolol were measured before and after atrial pacing and RFCA. Group 2 dogs were used to assess the effect of chronic AF alone on Cx43 expression and distribution. All group 1 dogs developed sustained (>24 hours) AF. Right-sided RFCA of the atria eliminated the sustained AF in 5 dogs, but both right and left atrial RFCA was required to abolish sustained AF in the other 4 dogs. After RFCA restored sinus rhythm, CSNRT and P-wave duration were prolonged and MHR and IHR were decreased. Chronic rapid atrial pacing (group 2) increased the expression of Cx43, which was absent in ablated areas and markedly depressed in viable atrial myocytes near the ablation zones (group 1). Conclusions Rapid atrial pacing for long time periods induced sustained AF that can be eliminated by linear right and left atrial lesions created with RFCA, with preservation of sinus rhythm and atrial contractile function. Chronic AF increased the expression and distribution of gap junction protein Cx43, which became reduced in ablated and nearby nonablated areas.

Background Current drug therapy of atherosclerosis is focused on treatment of major risk factors, e.g. hypercholesterolemia while in the future direct disease modification might provide additional benefits. However, development of medicines targeting vascular wall disease is complicated by the lack of reliable biomarkers. In this study, we took a novel approach to identify circulating biomarkers indicative of drug efficacy by reducing the complexity of the in vivo system to the level where neither disease progression nor drug treatment was associated with the changes in plasma cholesterol. Results ApoE-/- mice were treated with an ACE inhibitor ramipril and HMG-CoA reductase inhibitor simvastatin. Ramipril significantly reduced the size of atherosclerotic plaques in brachiocephalic arteries, however simvastatin paradoxically stimulated atherogenesis. Both effects occurred without changes in plasma cholesterol. Blood and vascular samples were obtained from the same animals. In the whole blood RNA samples, expression of MMP9, CD14 and IL-1RN reflected pro-and anti-atherogenic drug effects. In the plasma, several proteins, e.g. IL-1β, IL-18 and MMP9 followed similar trends while protein readout was less sensitive than RNA analysis. Conclusion In this study, we have identified inflammation-related whole blood RNA and plasma protein markers reflecting anti-atherogenic effects of ramipril and pro-atherogenic effects of simwastatin in a mouse model of atherosclerosis. This opens an opportunity for early, non-invasive detection of direct drug effects on atherosclerotic plaques in complex in vivo systems.