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In this paper, we discover an operation method that can effectively decrease the forming voltage in resistance random access memory (RRAM). Forming voltage can be reduced by either increasing the rising time of the forming-waveform or by increasing the temperature in the forming process. However, the resulting electronic RRAM characteristics after each of these methods differ. While increasing the rising time causes greater damage to the switching layer due to longer accumulation of charge, increasing temperature in the forming process does not. The high temperature-formed RRAM excels in retention and endurance tests, proving an effective means to decrease forming voltage.

Understanding its resistance switching (RS) properties is beneficial to the development of resistance random access memory (RRAM). In this work, a RRAM device with a Cu/GeSO/TiN structure (from top to bottom) is investigated. Before forming, the device can operate with a small ratio (

Simple Summary Inhibition of cyclin-dependent kinase 9 (CDK9) can impact multiple survival pathways in cancers and may be a promising therapeutic approach for glioblastoma, which is known to be highly resistant to treatments and thus challenging to treat. This review assesses the mechanisms by which CDK9 inhibition impacts cancer cell survival pathways in glioblastoma and other cancer types and presents results from clinical trials involving CDK9 inhibitors. A more thorough understanding of these mechanisms may lead to novel combination treatment strategies involving CDK9 inhibitors that can ultimately improve clinical outcomes for glioblastoma patients. Abstract Glioblastoma is the most common and aggressive primary malignant brain tumor, and more than two-thirds of patients with glioblastoma die within two years of diagnosis. The challenges of treating this disease mainly include genetic and microenvironmental features that often render the tumor resistant to treatments. Despite extensive research efforts, only a small number of drugs tested in clinical trials have become therapies for patients. Targeting cyclin-dependent kinase 9 (CDK9) is an emerging therapeutic approach that has the potential to overcome the challenges in glioblastoma management. Here, we discuss how CDK9 inhibition can impact transcription, metabolism, DNA damage repair, epigenetics, and the immune response to facilitate an anti-tumor response. Moreover, we discuss small-molecule inhibitors of CDK9 in clinical trials and future perspectives on the use of CDK9 inhibitors in treating patients with glioblastoma.

Neuronal damage in primary auditory cortex (A1) underlies complex manifestations of noise exposure, prevention of which is critical for health maintenance. Acid sphingomyelinase (ASM) catalyzes generation of ceramide (Cer) which if over-activated mediates neuronal disorders in various diseases. Tricyclic antidepressants (TCAs), by restraining ASM/Cer, benefits multiple neuronal anomalies, so we aimed to elucidate the effect of TCA on noise induced hearing loss and auditory cortex derangement, unraveling mechanism involved. The mice were exposed to noise with frequencies of 20-20k Hz and intensity of 95 dB. Doxepin hydrochloride (DOX), a kind of TCAs, was given intragastrically by 5 mg/kg/d. Morphology of neurons was examined using hematoxylin-eosin (HE) and Nissl staining. Apoptosis was assayed through transferase-mediated dUTP nick end labeling (TUNEL). The content of ASM, Cer or acid ceramidase (AC) was detected by western blot and immunohistochemistry analysis. We demonstrated intense, broad band noise caused upward shift of auditory brainstem response (ABR) threshold to sound over frequencies 4k-32k Hz, with prominent morphologic changes and enhanced apoptosis in neurons of primary auditory cortex (A1) (P

Background Glioma-associated macrophages and microglia (GAMs) are components of the glioblastoma (GBM) microenvironment that express MerTK, a receptor tyrosine kinase that triggers efferocytosis and can suppress innate immune responses. The aim of the study was to define MerTK as a therapeutic target using an orally bioavailable inhibitor, UNC2025. Methods We examined MerTK expression in tumor cells and macrophages in matched patient GBM samples by double-label immunohistochemistry. UNC2025-induced MerTK inhibition was studied in vitro and in vivo. Results MerTK/CD68+ macrophages increased in recurrent tumors while MerTK/glial fibrillary acidic protein-positive tumor cells did not. Pharmacokinetic studies showed high tumor exposures of UNC2025 in a syngeneic orthotopic allograft mouse GBM model. The same model mice were randomized to receive vehicle, daily UNC2025, fractionated external beam radiotherapy (XRT), or UNC2025/XRT. Although median survival (21, 22, 35, and 35 days, respectively) was equivalent with or without UNC2025, bioluminescence imaging (BLI) showed significant growth delay with XRT/UNC2025 treatment and complete responses in 19%. The responders remained alive for 60 days and showed regression to 1%-10% of pretreatment BLI tumor burden; 5 of 6 were tumor free by histology. In contrast, only 2% of 98 GBM mice of the same model treated with XRT survived 50 days and none survived 60 days. UNC2025 also reduced CD206+ macrophages in mouse tumor samples. Conclusions These results suggest that MerTK inhibition combined with XRT has a therapeutic effect in a subset of GBM. Further mechanistic studies are warranted.

This letter investigates the influence of ammonia on amorphous carbon resistance random access memory by sputtering the carbon target with argon and ammonia mixed gas. The device fabricated with ammonia (C (NH3)-RRAM) showed remarkable improvement in memory window and high resistance state as compared to the device deposited without ammonia. Material analysis confirmed the absorption signal of amine. Current fitting indicated the conduction mechanism changes from hopping conduction to Schottky conduction with the addition of ammonia. Finally, we propose a model to explain the influence of ammonia on the resistive switching behaviors of the amorphous carbon RRAM.

Structural adaptation of arteries to weightlessness might lower the working ability or even threaten the physical health of astronauts, but the underlying mechanism is unclear. Acid sphingomyelinase (ASM) catalyzes ceramide (Cer) generation controlling arterial remodeling through multiple signaling pathways. In the present study, we aimed to investigate the contribution of ASM/Cer to the changes of common carotid artery intima-media thickness (CIMT) induced by simulated weightlessness. Hindlimb-unloaded tail-suspended (HU) rats were used to simulate the effect of weightlessness. Morphology of the carotid artery (CA) was examined by hematoxylin-eosin staining. Protein content of ASM or proliferating cell nuclear antigen (PCNA) was detected by Western blot. Cer level was measured by immunohistochemistry analysis. Apoptosis events were observed by transferase-mediated dUTP nick end labeling (TUNEL) staining. During 4 weeks of tail suspension, CIMT was increased gradually in HU but not in their synchronous control rats (P

Nonvolatile stateful logic through RRAM is a promising route to build in-memory computing architecture. In this letter, a logic methodology based on 1T1R structure has been proposed to implement functionally complete Boolean logics. Arbitrary logic functions could be realized in two steps: initialization and writing. An additional read step is required to read out the logic result, which is in situ stored in the nonvolatile resistive state of the memory. Cascade problem in building larger logic circuits is also discussed. Our 1T1R logic device and operation method could be beneficial for massive integration and practical application of RRAM-based logic.

In this study, an O2 inductively coupled plasma (ICP) treatment was developed in order to modify the characteristics of indium tin oxide (ITO) film for use as an insulator in resistive random access memory (RRAM). After the O2 plasma treatment, the previously conductive ITO film is oxidized and becomes less conductive. In addition, after capping the same ITO material for use as a top electrode, we found that the ITO/ITO(O2 plasma)/TiN device exhibits very stable and robust resistive switching characteristics. On the contrary, the nontreated ITO film for use as an insulator in the ITO/ITO/TiN device cannot perform resistance switching behaviors. The material analysis initially investigated the ITO film characteristics with and without O2 plasma treatment. The surface was less rough after O2 plasma treatment. However, the molar concentration of each element and measured sheet resistance results for the O2-plasma-treated ITO film were dramatically modified. Next, electrical measurements were carried out to e...

Resistive random access memory (RRAM) based reconfigurable logic provides a temporal programmable dimension to realize Boolean logic functions and is regarded as a promising route to build non-von Neumann computing architecture. In this work, a reconfigurable operation method is proposed to perform nonvolatile sequential logic in a HfO2-based RRAM array. Eight kinds of Boolean logic functions can be implemented within the same hardware fabrics. During the logic computing processes, the RRAM devices in an array are flexibly configured in a bipolar or complementary structure. The validity was demonstrated by experimentally implemented NAND and XOR logic functions and a theoretically designed 1-bit full adder. With the trade-off between temporal and spatial computing complexity, our method makes better use of limited computing resources, thus provides an attractive scheme for the construction of logic-in-memory systems.

Virtual goods are usually classified as services. The popular instant messenger LINE, with its stickers, is one of the most successful business models for virtual goods. Our study explores the intention to purchase virtual goods and examines the critical successful factors in LINE stickers. We propose a theoretical model based on perceived value, satisfaction, personal innovativeness, and reference group acceptance. Our key findings reveal (1) the significant influence of individual perception, personal characteristics, and social influence and (2) the key role of personal innovativeness in in-app purchases using mobile social media.

This study proposes a method for a HfO2-based device to exhibit both resistive switching (RS) characteristics as resistive random access memory (RRAM) and selector characteristics by introducing vanadium (V) as the top electrode. This simple V/HfO2/TiN structure can demonstrate these two different properties depending on forming polarities. The RS mechanism is activated by a positive forming bias. In contrast, the selector property is induced by a negative forming bias. The material analyses firstly confirm the existence of V in the top electrode. Then the electrical measurements for the same V/HfO2/TiN structures but with different forming polarities were carried out to further investigate their DC sweeping characteristics to act as either a selector or RRAM device. Furthermore, reliability tests for both selector and RRAM devices were also conducted to confirm their switching stabilities. Finally, current fitting methods and temperature influence experiments were performed to investigate the carrier transport mechanisms. Finally, physical models were proposed to illustrate the selector property and RS mechanism for selector and RRAM devices, respectively. This simple device structure with its easy operating method accomplishes a significant advancement of devices combining both selector properties and RRAM for remarkable real applications in the near future.

Background/Aims: High concentration of bile acids (BAs) induces hydrophobicity-dependent vasorelaxtant effects with hydrophobic BAs showing greater responses than hydrophilic BAs, of which the underlying mechanisms are still unclear. Caveolae are invaginations on membranes of endothelial cells (ECs) entraping endothelial nitric oxide synthase (eNOS) to prevent its activation, which plays a critical role in regulation of vascular function. The purpose of the present study was to investigate the role of caveolae in vasorelaxant effects of BAs. Methods: Chenodeoxycholic acid (CDCA) and cholic acid (CA) were used to represent hydrophobic and hydrophilic BA, respectively. Vascular responses of abdominal aorta were measured by isometric force recording. Morphology of caveolae was examined by transmission electron microscopy. Protein expression of total eNOS (t-eNOS) or phosphorylated eNOS (p-eNOS) was determined by Western blot. Nitric oxide (NO) content was observed by fluorometric assay. Results: We demonstrated that CDCA as well as Methyl-β-cyclodextrin (MCD), a commonly used reagent for cholesterol depletion, reduced potassium chloride (KCl)- or phenylephrine (PE)-elicited vasoconstriction (P < 0.05), and enhanced acetylcholine (Ach)-elicited vasodilatation (P < 0.05) in endothelium-intact abdominal aorta but not in endothelium-denuded or CA-treated vessels. CDCA and MCD, but not CA significantly disrupted caveolae structure on ECs of abdominal aorta which was recovered by cholesterol incubation (P < 0.05). Protein expression of t-eNOS was significantly decreased (P < 0.05), and that of p-eNOS together with NO content was significantly increased in CDCA- and MCD- but not CA-treated vessels (P < 0.05) as compared with vehicle. The effect was reversed by either endothelium-denudation or cholesterol replenishment. Moreover, with cholesterol incubation, no significant differences were found in vascular responses among CDCA-, CA- or vehicle-treated vessels. Conclusion: These results indicate that CDCA diminishes caveolae on ECs of abdominal aorta promoting eNOS phosphorylation and NO production which contributes to its vasorelaxtant effect.

This paper investigates the characteristics of applying indium–tin oxide (ITO) with and without nitride gas (N2) as the insulator in resistive random access memory (RRAM). After cosputtering an ITO target with N2 as the insulator and capping the same ITO material as the top electrode, the device exhibits rectifier and resistance switching characteristics before and after the forming process, respectively. The Schottky diodelike rectifier mechanism was also verified by various temperature measurements. Furthermore, robust resistance switching at a positive forming voltage, smaller than that required during negative bias forming, can be achieved. Both positive and negative forming processes are examined with current fitting results, which show different dominant mechanisms when using positive or negative biases. All these mechanisms have also been verified by temperature effect experiments, which confirmed the dominant conduction mechanisms. This, in combination with the fact that the positive forming voltage itself is smaller than the negative forming voltage, and decreases with device scale down, provides two highly beneficial results. This good performance achieved by using ITO with N2 suggests significant progress of RRAM and remarkable potential applications.

Isocitrate dehydrogenase (IDH) mutations are biomarkers to classify diffuse gliomas into biologically similar subgroups. Tremendous efforts have been made to understand the biology of IDH-mutant gliomas at the genetic, epigenetic, transcriptional, and protein levels. Preclinical models that recapitulate human tumor biology are crucial not only to our understanding of IDH mutations in gliomagenesis, but also in testing of novel therapeutic agents that may lead to more effective therapies for IDH-mutant glioma patients.

This paper proposes an improved social spider algorithm to enable the particles of the original algorithm to move intelligently in the evolving process for almost all benchmark functions. In order to enhance the convergence rate and searching capability of the original social spider algorithm, the tent map control is adopted for the neighbor search of male spiders and the mating operator is presented to obtain better search capability and convergence rate. The experimental results show that the method proposed in this paper can uplift the algorithm performance and avoid falling into locally optimal solution in comparison with other algorithms. Finally, the improved algorithm has been applied to a nonlinear system to design a best fuzzy PID controller.

BACKGROUND Glioblastoma is known for its aggressive behavior and resistance to most available treatments. Topoisomerase 1 (Top1) functions by relaxing DNA supercoiling to facilitate replication. The novel Top1 inhibitor, LMP400, traps the enzyme and prevents its normal function, particularly in highly proliferative cells, resulting in DNA damage. Poly(ADP-ribose) polymerase (PARP) is involved in DNA repair responses triggered by Top1 inhibition. Phosphatase and tensin homolog (PTEN) loss, a frequent occurrence in glioblastoma, promotes DNA damage repair deficiency. We hypothesize that PTEN loss presents a vulnerability to combined induction of DNA damage and inhibition of repair mechanisms. METHODS Human glioblastoma cells were treated with LMP400 and/or Olaparib, a PARP inhibitor. Effects on cell proliferation and cell death were determined using a Beckman Coulter cell viability analyzer and colony formation assays. Synergism was calculated using COMPUSYN software. Cell cycle analysis was performed by FACS with EdU/DAPI staining, and Western blotting of lysate from drug-treated cells was performed to explore mechanisms of cytotoxicity. RESULTS LMP400 inhibited cell proliferation with an EC50 of 8.0 nM in U251 cells, and combination of LMP400 and Olaparib had a synergistic cytotoxic effect. Combination treatment enhanced activation of ATM-Chk2 and ATR-Chk1 pathways involved in DNA damage response signaling and increased S phase arrest. Increased protein expression of gamma-H2AX, cleaved caspase 3, and cleaved PARP was observed in combination-treated cells compared to single agents. Cell viability assays using isogenic glioblastoma cell lines with and without PTEN indicate that PTEN loss increases sensitivity to combination treatment. CONCLUSION Our results suggest that LMP400 and Olaparib combined treatment synergistically induces glioblastoma cell death, partially through inducing DNA damage, cell cycle arrest, and apoptosis. Mechanistic studies to investigate this vulnerability in glioblastoma with PTEN loss are ongoing. These results may lead to an effective personalized therapy for a molecularly defined subset of glioblastoma patients.

Weightlessness exposure conduces to substantial vascular remodeling, mechanisms behind which remain unclear. Acid sphingomyelinase (ASM) catalyzed ceramide (Cer) generation accounts for multiple vascular disorders, so the role of it in adjustment of cerebral artery (CA) and small mesenteric artery (MA) was investigated in simulated weightless rats.Rats were hindlimb unloaded tail suspended (HU) to simulate the effect of weightlessness. Arterial morphology was examined by hematoxylin-eosin staining. Cer abundance was measured by immunohistochemistry. Western blotting was used to detect protein content. Apoptosis was detected by transferase-mediated dUTP nick end labeling.During 4 weeks of tail suspension, intima-media thickness (IMT) and media cross section area (CSA) were increased gradually in CA but decreased gradually in MA (P 0.05). Correspondingly, the apoptosis and proliferation of vascular smooth muscle cells were reduced and enhanced respectively in CA (P 0.05), while promoted and restrained in MA (P 0.05). As compared to control, both ASM protein expression and Cer content were lowered in CA and elevated in MA of HU rats (P 0.05). Permeable Cer incubation reversed the change of apoptosis and proliferation in CA of HU rats, while ASM inhibition recapitulated it in control rats. On the contrary, ASM inhibitors restored the alteration of apoptosis and proliferation in MA of HU.The results suggest that by controlling the balance between apoptosis and proliferation, ASM/Cer exerts an important role in structural adaptation of CA and MA to simulated weightlessness.

Inspired by the self-exploring learning approach, this paper proposes an object-learning system in which a robot interacts with objects to obtain their features and construct object concepts. The system consists of three kinds of features: interaction features, visual features, and intrinsic features. When the robot interacts with an object, it observes the changes in the object to obtain its interaction features. At the same time, the robot learns the visual features of the object. The intrinsic features are the properties of the object. Models of the relationships among the three kinds of features are constructed through an Artificial Bee Colony based Random Forest algorithm and a Convolutional Neural Network. The established models help the robot to predict the properties of new objects and to make decisions. Two experiments are constructed in this paper: the service-providing task and the stacking task. In the former, the robot decides on an appropriate object, using the object concept models, to accomplish an appointed task. In the second experiment, the robot uses a Gated Recurrent Neural Network to learn the stacking sequence of various objects. All the experimental results demonstrate that the robot can build object concept models by interacting with objects, and can utilize these models to accomplish various tasks.

Background This study aims to investigate the antimicrobial ability and mechanism analysis of Lactobacillus species against carbapenemase-producing Enterobacteriaceae (CPE). Methods Five Lactobacillus spp. strains and 18 CPE clinical isolates were collected. Their anti-CPE effects were assessed by agar well diffusion and broth microdilution assay, as well as time-kill test. Finally, the specific anti-CPE mechanism, especially for the effect of organic acids was determined using broth microdilution method. Results All of five Lactobacilli isolates displayed the potent activity against most CPE isolates with mean zones of inhibition ranging 10.2 to 21.1 mm. The anti-CPE activity was not affected by heating, catalase, and proteinase treatment. Under the concentration of 50% LUC0180 cell-free supernatant (CFS), lactic acid, and mix acid could totally inhibit the growth of carbapenem-resistant Klebsiella pneumoniae (CPE0011), and acetic acid could inhibit 67.8%. In contrast, succinic acid and citric acid could not inhibit the growth of CPE0011. While we decreased the concentration to 25%, only lactic acid and mix acid displayed 100% inhibition. In contrast, succinic acid, citric acid and acetic acid did not show any inhibitory effect. Conclusions Lactobacillus strains exhibit potent anti-CPE activity, and lactic acid produced by Lactobacillus strains is the major antimicrobial mechanism.

The presence of only morphologically poor embryos (MPEs) on day3 is common in autologous in vitro fertilization (IVF), particularly among p Tel: 886-7-7317123 Ext. 8916. Fax: 886-7-7322915.atients who have advanced maternal age or are poor responders. However, there are limited data regarding the disposition of embryos from patients who only produced MPEs on day3. The present study was designed to investigate the possible benefits of extended culturing MPEs. Try to detect whether the extended culture (day4 or day5 culture) can improve the live birth rate per cycle?This retrospective, observational, single-center, cohort study examined 224 IVF/intracytoplasmic sperm injection (ICSI) cycles between January 2010 and June 2015, in which women only produced MPEs on day3. A total of 544 MPEs were analyzed. The defines a day3 embryo as an MPE if it fails to develop to eight cells, blastomeres of equal size, and less than 20% cytoplasmic fragments. Of the 224 cycles, 89 (39.7%) underwent fresh embryo transfer on day3, and 135 (60.3%) underwent extended culture. Of the 135 extended cultures, 54 cycles (40.0%) experienced day4, or day5 embryo transfer, 16 cycles (11.9%) had all embryos frozen, and 65 cycles (48.1%) had total embryo arrest.Analysis of patient baseline demographic data, cycle characteristics, and cycle outcomes for day3 transfer group and extended culture group indicated that a higher body mass index in the day3 transfer group was the only significant difference (p = 0.006). Both fresh transfer groups had low live birth rates (LBRs) (4.5% vs. 7.4% p = 0.46). After extended culture, 65 cycles (48.1%) were cancelled because the embryos exhibited developmental arrest and 70 cycles (51.9%) grew to day4 or day5. Thirteen frozen embryo transfer (FET) cycles and 22 frozen blastocysts derived from MPEs were thawed. There were more high-quality embryos (p 0.001), higher implantation rates (IRs) (p = 0.038), and higher LBRs (p = 0.042) for embryos that underwent FET cycles. MPES in extended culture transfer have favorable survival than MPES in day3 transfer.The extended culture of MPEs in fresh transfer cycles did not increase the LBR. However, younger females with the extended culture of MPEs followed by FET resulted in significantly higher LBRs and may be a feasible strategy to improve outcomes for patients with poor embryo quality. However, day3 embryo transfer may be a better choice if a fresh transfer is unrestricted and avoid the cycle cancellation. Extended culture may decrease to the transfer of developmental potential arrest embryos to patients.

Noise-induced hearing loss (NIHL) relates closely to auditory cortex (AC) injury, so countermeasures aiming at the AC recovery would be of benefit. In this work, the effect of hyperbaric oxygen treatment on NIHL was elucidated, which was imposed on mice before (HBOP), during (HBOD) or after (HBOA) noise exposure. Morphology of neurons was assayed by hematoxylin-eosin or Nissl staining. Ceramide (Cer) level was measured through immunohistochemistry analysis. Apoptotic neurons were counted using transferase-mediated dUTP nick end labeling (TUNEL) staining. We demonstrated that the intense, broad band noise raised the threshold of auditory brainstem response, evoked neuronal degeneration or apoptosis and triggered the Cer accumulation in AC, all of which were restored significantly by HBOP, but not HBOD or HBOA. Cer over-generation reversed the advantages of HBOP significantly, while its curtailment recapitulated the effect. Next, noise exposure raised the superoxide or malondialdehyde (MDA) production which was blocked by HBOP or Cer repression. Oxidative control not only attenuated the hearing loss or neurodegeneration but, in turn, reduced the Cer formation significantly. In summary, mutual regulation between Cer and oxidative stress underlies the HBOP&rsquo, s curative effect on hearing loss and neuronal damage in noise-exposed mice.

BACKGROUND Pooled human platelet lysate (HPL) can replace fetal bovine serum (FBS) as xeno-free supplement for ex vivo expansion of mesenchymal stromal cells (MSCs). We evaluate here whether a double-virally-inactivated HPL (DVI-HPL) prepared from expired Intercept-treated platelet concentrates (PCs) and treated by solvent/detergent (S/D) can be used for MSC expansion. STUDY DESIGN AND METHODS Expired Intercept-treated PCs in 65% platelet (PLT) additive solution were pooled and subjected to a 1% tri-n-butyl phosphate/1% Triton X-45 treatment followed by soybean oil, hydrophobic interaction chromatography purification, and sterile filtration. Bone marrow-derived MSCs (BM-MSCs) were expanded for four passages in growth medium containing 10% DVI-HPL, I-HPL (from Intercept-PC only), untreated HPL, and FBS. MSC morphology, doubling time, immunophenotype, immunosuppressive activity, and differentiation capacity were compared. RESULTS Expanded cells had typical spindle morphology and showed higher viability in all HPL conditions than in FBS. The DVI-HPL and FBS-expanded cells were morphologically larger than in I-HPL and HPL supplements. The cumulative population doubling was lower using DVI-HPL than with HPL and I-HPL, but significantly higher than using FBS. Immunophenotype was not affected by the supplements used. Immunosuppressive activity was maintained with all supplements. Differentiation capacity into chondrocytes and osteocytes was more effective in DVI-HPL but less toward adipocytes compared to other supplements. CONCLUSIONS Human PLT lysate made from Intercept-PCs subjected to S/D treatment may be an alternative to untreated HPL and to I-HPL for BM-MSC expansion. This finding reinforces the potential of HPL as a virally safe alternative to FBS for clinical grade MSC expansion protocols.

In this paper, indium-tin-oxide (ITO) was used to act as both insulator and top electrode in resistive random access memory (RRAM) on identical bottom substrates. This is achieved by cosputtering an ITO target with nitride (N2) or oxygen (O2) gas as the insulator; then capping by an ITO electrode, such that both the rectifier and RRAM characteristics can be achieved before and after a forming process, respectively. In contrast, using pure ITO as an insulator does not exhibit RRAM behavior. To verify the rectifier and RRAM characteristics, material analyses and electrical measurements at various temperatures were conducted. Reliability tests including retention and endurance were also applied to verify the resistance switching stability. Finally, the rectifier and RRAM conduction models were proposed to examine the resistance switching behaviors. By applying the ITO material as both electrode and insulator, the resistance switching characteristic with high reliability is thus obtained.

Solution processing enables organic devices to be fabricated cost-effectively, while deep-red emitters enable displays with high color saturation and lighting with high light quality. However, limited deep-red emitters were reported with solution-process feasibility and high efficiency. We demonstrate here a high-efficiency, solution-process-feasible deep-red emitter by coupling the highly efficient phosphorescent complex with a highly thermally stable fluorescent compound. The device exhibits a maximum external quantum efficiency of 11.2% at 10 cd m–2 and 8.4% at 100 cd m–2. The latter is coupled with an ultradeep red emission (0.70, 0.27) and a potential color saturation of 108%. Besides the intrinsically high-efficiency nature of the phosphorescent complex, the record high efficiency may be attributable to the spirally configured fluorene moiety in the fluorescent compound to prevent concentration-quenching effect, a proper host to enable an effective host-to-guest energy transfer, and the employed coh...

Sphingolipids (SLs) are compounds containing a long-chain fatty alcohol amine called sphingosine which exists in cellular membranes, cytoplasm, nucleus, interstitial fluid, blood and lymphatic circulation. SLs act as essential constituents of membranes of eukaryotic cells, so the seesaw of SLs will lead to structural alteration of membranes instigating cellular functional change. SLs also act as crucial signaling molecules taking effect intracellularly or extracellularly which regulates activity of downstream molecules determining cellular adaptation to numerous stimulus. This review aims to highlight the contribution of SLs to physiological and pathophysiological remodeling of vasculature. We will first provide a short overview on metabolism, trafficking and compartmentalization of SLs. Then the regulation of SLs on reactive oxygen species (ROS) formation, vascular tone modulation, endothelial barrier integrity, apoptosis and autophagy are summarized. Finally, we will discuss how the SLs are modulated contributing to vascular development, angiogenesis and vascular remodeling in pathological situations as hypertension, atherosclerosis, and aging. The compellingly regulative actions of SLs bring about copious therapeutic targets for potential pharmacological intervention on the diseases involving vascular maladaptation.

Robust image hashing, which maps the perceptual contents of image to a short digest, is a key technique for tackling the challenges of content-based indexing, searching and copyright protection. In this letter, we propose a quaternion invariance based hashing algorithm that can fuse complementary visual features to compact hash. The proposed algorithm leverages quaternion polar cosine transform to holistically capture the spatial and chromatic characteristics of digital image, and rotation-invariant features are derived from the phase information in the quaternion frequency domain. In addition, we also propose an information theoretic based metric for feature quality assessment and a greedy strategy to select the optimal subset of features for hash computation. Extensive experiments over a large database demonstrate that the proposed work shows higher content identification accuracy than most competing algorithms, and the resulting hash is compact and easy to compute.

Organic light-emitting diodes (OLEDs) have attracted increasing attention due to their superiority as high quality displays and energy-saving lighting. However, improving the efficiency of solution-processed devices especially based on blue emitter remains a challenge. Excitation of surface plasmons on metallic nanoparticles has potential for increasing the absorption and emission from optoelectronic devices. We demonstrate here that the incorporation of gold nano particles (GNPs) in the hole injection layer of poly(3,4-ethylene dioxythiophene):polystyrene sulfonic acid with an appropriate size and doping concentration can greatly enhance the efficiency OLED device especially at higher voltage. Apparently, the spectral of the multiple plasmon resonances of the GNPs and the luminescence of the emitting materials significantly overlap with each other. At 1000 cd m-2 for example, the power efficiency of a studied green device is increased from 29.0 to 36.2 lm W-1, an increment of 24.8%, and the maximum brightness improved from 21 550 to 27 810 cd m-2, an increment of 29.1%, as 2 wt% of a 12 nm GNP is incorporated. Remarkably, designed blue OLED also exhibited an increment of 50% and 35% in power efficacy at 100 and 1000 cd m-2, respectively, for same device structure. The reason why the enhancement is marked may be attributed to a strong absorption of the short-wavelength emission from the device by the gold nano particles, which in turn initiates a strong surface plasmon resonance effect, leading to a high device efficiency.

With the potential to act as the next generation of non-volatile memory, resistive random access memory (RRAM) not only has stable and excellent electrical characteristics, but can also be used in such versatile applications as neuron computing and logic circuit design. However, material selection for RRAM devices to accomplish the metal-insulator-metal structure which initiates the resistance switching (RS) mechanism is incomplete because of the many different material characteristics between the metal and insulator. In this work, we demonstrate a via-hole structure, full transparent RRAM (TRRAM) with indium-tin-oxide (ITO) acting as both electrode and middle insulator in the ITO/ITOX/ITO structure. The originally conductive ITO thin film successfully acts as an insulator after a supercritical fluid (SCF) oxidation treatment. This all-ITO RRAM device exhibits superb electrical performance and excellent environmental stability to high temperature without significant degradation in its RS characteristics. In addition, the ITO-based TRRAM also displays stable performance under different light illumination conditions. Another ITO-based TRRAM constructed on soft polyimide (PI) substrate has also been demonstrated. The present all-ITO TRRAM is not only of great interest for future stable transparent electron applications, but it also provides a guideline for the simplification of material selection for transparent electron devices.

Candles were invented 5000 years ago and are still widely adopted in numberless occasions to illuminate the buildings and to create a romantic environment due to their warm and pleasant sensation giving emission, which helps people relax. Nevertheless, some myths remain unsolved regarding their color, color temperature, power efficiency, their effects on human health, and fire hazard. We have hence investigated these based on a paraffin wax candle. As learned experimentally, the flickering candle flame shows on average an orange-red color with Commission Internationale de l'Eclairage 1931 coordinates of (0.55, 0.41) and a 1819 K color temperature through observation behind a tracing paper. Although the luminous intensity may vary from 1.0 to 2.2 cd, the luminous efficacies of studied candles fall around 0.27 l m/W. From a retina protection perspective, candlelight is presumably 2 times safer than the typical incandescent bulb or warm-white compact fluorescent lamp (CFL), and 3 times safer than the warm-white light-emitting diode (LED). Correspondingly, if used at night, it is about 2 times better for melatonin secretion than the incandescent bulb or warm-white LED, and 3 times better than the warm-white CFL. However, surprisingly, candlelight-style organic light-emitting diode (OLED) is healthier than real candlelight: from retina protection and melatonin secretion perspective, the candlelight style OLED is about 3 times safer and 2 times better than candlelight, respectively. While the luminous intensity may sensitively vary with the variation of wax as well as wick material and size, the candle color and color temperature barely alter with different compositions.

BACKGROUND: Glioblastoma is aggressive with poor prognosis. Nicotinamide phosphoribosyltransferase (NAMPT) is essential to maintain nicotinamide adenine dinucleotide metabolism during rapid proliferation and regulates poly (ADP-ribose) polymerase (PARP), which is crucial for DNA repair. Targeting both NAMPT and PARP may represent a treatment strategy in glioblastoma. We hypothesize that the combined inhibition of NAMPT and PARP can induce synergistic cell death in tumor, while sparing significant cytotoxicity in normal astrocytes. METHODS: NAMPT expression was determined in a group of six human glioblastoma cell lines and normal human astrocytes (NHA) by Western blotting. To analyze the cytotoxic effects of the treatments in tumor and normal cells, U251 and NHA cells were selected to receive FK866 (NAMPT inhibitor), Olaparib (PARP inhibitor), or both drugs for 72 hours prior to the cell viability test. RESULTS: Various levels of NAMPT expression were demonstrated in a group of glioblastoma cell lines and NHA, where U251 showed the strongest expression. We demonstrated a significant decrease of cell viability in U251 cells that were treated with FK866 in a dose-dependent manner. A 32% reduction of cell viability was demonstrated at a dose as low as 10 nM. However, a 28% reduction of cell viability was found in NHA at the EC(50) concentration for U251 cells. When tumor cells were treated with a combination of FK866 and Olaparib at their EC(50) concentrations (28nM and 406nM), 72% and 50% reductions of cell viability occurred in tumor cells and NHA, respectively. CONCLUSION: The combined treatment with FK866 and Olaparib enhances cytotoxicity in glioblastoma cells compared to the single-agent therapy, representing a promising therapeutic strategy. However, the toxic effects on NHA are concerning and warrant further investigations to determine a precise therapeutic window in preclinical models before the treatment is considered for clinical trials.

RRAM is a promising candidate to construct in-memory computing architecture which can break through the von Neumann bottleneck. Taking advantage of the CMOS compatible 1T1R RRAM, functionally complete Boolean logics can be realized within two steps in a single unit that can suppress sneak pass problem and avoid cascading problem partially. In addition, an 8-bit pre- calculation adder with low computation complexity is designed and demonstrated experimentally to verify the feasibility and efficiency of 1T1R based in-memory computing architecture, which is applicable to future energy-efficient information processing systems.

Objective We investigate the clinical effectiveness of a novel deep learning-based noise reduction (NR) approach under noisy conditions with challenging noise types at low signal to noise ratio (SNR) levels for Mandarin-speaking cochlear implant (CI) recipients. Design The deep learning-based NR approach used in this study consists of two modules: noise classifier (NC) and deep denoising autoencoder (DDAE), thus termed (NC + DDAE). In a series of comprehensive experiments, we conduct qualitative and quantitative analyses on the NC module and the overall NC + DDAE approach. Moreover, we evaluate the speech recognition performance of the NC + DDAE NR and classical single-microphone NR approaches for Mandarin-speaking CI recipients under different noisy conditions. The testing set contains Mandarin sentences corrupted by two types of maskers, two-talker babble noise, and a construction jackhammer noise, at 0 and 5 dB SNR levels. Two conventional NR techniques and the proposed deep learning-based approach are used to process the noisy utterances. We qualitatively compare the NR approaches by the amplitude envelope and spectrogram plots of the processed utterances. Quantitative objective measures include (1) normalized covariance measure to test the intelligibility of the utterances processed by each of the NR approaches; and (2) speech recognition tests conducted by nine Mandarin-speaking CI recipients. These nine CI recipients use their own clinical speech processors during testing. Results The experimental results of objective evaluation and listening test indicate that under challenging listening conditions, the proposed NC + DDAE NR approach yields higher intelligibility scores than the two compared classical NR techniques, under both matched and mismatched training-testing conditions. Conclusions When compared to the two well-known conventional NR techniques under challenging listening condition, the proposed NC + DDAE NR approach has superior noise suppression capabilities and gives less distortion for the key speech envelope information, thus, improving speech recognition more effectively for Mandarin CI recipients. The results suggest that the proposed deep learning-based NR approach can potentially be integrated into existing CI signal processors to overcome the degradation of speech perception caused by noise.

BACKGROUND Therapies targeting multiple survival pathways are desirable for high-grade gliomas. TG02 (Zotiraciclib), a CDK9 inhibitor, regulates transcription and metabolism of tumor cells and synergizes with temozolomide. A phase I/II trial was launched to test the TG02/temozolomide combined treatment in recurrent high-grade astrocytomas. Phase I results are reported here. METHODS Adults with recurrent high-grade astrocytoma, KPS≥60, adequate organ function, < 2 prior relapses were enrolled. Primary endpoint was dose limiting toxicity (DLT) in cycle1 in each arm. Bayesian optimal interval design was employed to determine the maximum tolerated dose (MTD) with the target DLT rate of 35% and the toxicity profile of the combination of TG02 (starting dose 200mg orally on days1,12,15, and 26) and temozolomide, either as a dose-dense (DD; 125mg/m2/d, 7on/7off, Arm1) or metronomic (MN; 50mg/m2/d, Arm2) dosing schedule on a 28-day cycle. RESULTS Thirty-eight patients were evaluable; median age 50.7, KPS 90. Of 18 evaluable patients in Arm1, at TG02 dose-level 200mg, 1/6 had a DLT: Gr3 diarrhea; at dose-level 250mg, 3/12 had DLTs: Gr4 neutropenia for over 5 days, Gr3 elevated ALT, and Gr3 fatigue. Of 20 evaluable patients in Arm2, at TG02 dose-level 200mg, 1/6 had a DLT: recurrent Gr3 neutropenia; at dose-level 250mg, 5/12 had a DLT: Gr3 elevated ALT, Gr3 fatigue, and Gr4 neutropenia; at dose-level 300mg,1 of 2 had a DLT: Gr4 febrile neutropenia, Gr4 elevated ALT, Gr4 elevated AST. TG02 dose-level of 250mg was declared as the MTD in both Arms. Using the MDASI-BT, patients with high symptom burden had increased symptoms during cycle1 but became stable as they continued treatment. CONCLUSION The combination of TG02 at the MTD of 250mg with DD or MN temozolomide was tolerated. Cohort expansion continues at the MTD in both arms. Objective responses have been observed, suggesting activity of this regimen and supporting continued investigation.

Purpose: Glioblastoma (GBM) is highly resistant to treatment, largely due to disease heterogeneity and resistance mechanisms. We sought to investigate a promising drug that can inhibit multiple aspects of cancer cell survival mechanisms and become an effective therapeutic for GBM patients. Experimental Design: To investigate TG02, an agent with known penetration of the blood–brain barrier, we examined the effects as single agent and in combination with temozolomide, a commonly used chemotherapy in GBM. We used human GBM cells and a syngeneic mouse orthotopic GBM model, evaluating survival and the pharmacodynamics of TG02. Mechanistic studies included TG02-induced transcriptional regulation, apoptosis, and RNA sequencing in treated GBM cells as well as the investigation of mitochondrial and glycolytic function assays. Results: We demonstrated that TG02 inhibited cell proliferation, induced cell death, and synergized with temozolomide in GBM cells with different genetic background but not in astrocytes. TG02-induced cytotoxicity was blocked by the overexpression of phosphorylated CDK9, suggesting a CDK9-dependent cell killing. TG02 suppressed transcriptional progression of antiapoptotic proteins and induced apoptosis in GBM cells. We further demonstrated that TG02 caused mitochondrial dysfunction and glycolytic suppression and ultimately ATP depletion in GBM. A prolonged survival was observed in GBM mice receiving combined treatment of TG02 and temozolomide. The TG02-induced decrease of CDK9 phosphorylation was confirmed in the brain tumor tissue. Conclusions: TG02 inhibits multiple survival mechanisms and synergistically decreases energy production with temozolomide, representing a promising therapeutic strategy in GBM, currently under investigation in an ongoing clinical trial. Clin Cancer Res; 24(5); 1124–37. ©2017 AACR.

This study proposes a method for a HfO

A candlelight-style organic light emitting diode (OLED) is a human-friendly type of lighting because it is blue-hazard-free and has a low correlated color temperature (CCT) illumination. The low CCT lighting is deprived of high-energy blue radiation, and it can be used for a longer duration before causing retinal damage. This work presents the comprehensive protocols for the fabrication of blue-hazard-free candlelight OLEDs. The emission spectrum of the OLED was characterized by the maximum exposure time limit of the retina and the melatonin suppression sensitivity. The devices can be fabricated using dry and wet processes. The dry-processed OLED resulted in a CCT of 1,940 K and exhibited a maximum retinal exposure limit of 1,287 s at a brightness of 500 lx. It showed 2.61% melatonin suppression sensitivity relative to 480 nm blue light. The wet-processed OLED, where the spin coating is used to deposit hole injection, hole transport, and emissive layers, making fabrication fast and economical, produced a CCT of 1,922 K and showed a maximum retinal exposure limit of 7,092 at a brightness of 500 lx. The achieved relative melatonin suppression sensitivity of 1.05% is 86% and 96% less than that of the light emitting diode (LED) and compact fluorescent lamp (CFL), respectively. Wet-processed blue-hazard-free candlelight OLED exhibited a power efficiency of 30 lm/W, which is 2 times that of the incandescent bulb and 300 times that of the candle.

Resistive random access memory (RRAM) based reconfigurable logic provides a temporal programmable dimension to realize Boolean logic functions and is regarded as a promising route to build non-von Neumann computing architecture. In this work, a reconfigurable operation method is proposed to perform nonvolatile sequential logic in a HfO

In this study, an O

Background and Purpose Oxidative stress is an important pathogenic factor in the development of hypertension. Resveratrol, the main antioxidant in red wine, improves NO bioavailability and prevents cardiovascular disease. The aim of this study was to examine whether resveratrol decreases the generation of reactive oxygen species (ROS), thereby reducing BP in rats with fructose-induced hypertension. Experimental Approach Rats were fed 10% fructose with or without resveratrol (10 mg·kg−1·day−1) for 1 week or for 4 weeks with resveratrol treatment beginning at week 2; systolic BP (SBP) was measured by tail-cuff method. Endogenous in vivo O2− production in the nucleus tractus solitarii (NTS) was determined with dihydroethidium. Real-time PCR and immunoblotting analyses were used to quantify RNA and protein expression levels. Key Results In fructose-fed rats, ROS levels in the NTS were higher, whereas the NO level was significantly decreased. Also, RNA and protein levels of NADPH oxidase subunits (p67, p22-phox) were elevated, superoxide dismutase 2 (SOD2) reduced and AMP-activated PK (AMPK) T172 phosphorylation levels in the NTS were lower in fructose-fed rats. Treatment with the AMPK activator resveratrol decreased levels of NADPH oxidase subunits and ROS, and increased NO and SOD2 levels in the NTS of fructose-fed rats. Administration of resveratrol, in combination with fructose at week 0 and later at week 2, significantly reduced the SBP of fructose-fed rats. Conclusions and Implications Collectively, resveratrol decreased BP through the phosphorylation of AMPK, Akt and neuronal NOS in fructose-fed rats. These novel findings suggest that resveratrol may be a potential pharmacological candidate for the treatment of hypertension.