Formation of Cluster-Structured Metallic Filaments in Organic Memristors for Wearable Neuromorphic Systems with Bio-Mimetic Synaptic Weight Distributions.

With increasing demand for wearable electronics capable of computing huge data, flexible neuromorphic systems mimicking brain functions have been receiving much attention. Despite considerable efforts in developing practical neural networks utilizing several types of flexible artificial synapses, it is still challenging to develop wearable systems for complex computations due to the difficulties in emulating continuous memory states in a synaptic component. In this study, polymer conductivity is analyzed as a crucial factor in determining the growth dynamics of metallic filaments in organic memristors. Moreover, flexible memristors with bio-mimetic synaptic functions such as linearly tunable weights are demonstrated by engineering the polymer conductivity. In the organic memristor, the cluster-structured filaments are grown within the polymer medium in response to electric stimuli, resulting in gradual resistive switching and stable synaptic plasticity. Additionally, the device exhibits the continuous and numerous non-volatile memory states due to its low leakage current. Furthermore, complex hardware neural networks including ternary logic operators and a noisy image recognitions system are successfully implemented utilizing the developed memristor arrays. This promising concept of creating flexible neural networks with bio-mimetic weight distributions will contribute to the development of a new computing architecture for energy-efficient wearable smart electronics.

Organic Memristor-Based Flexible Neural Networks with Bio-Realistic Synaptic Plasticity for Complex Combinatorial Optimization.

Hardware neural networks with mechanical flexibility are promising next-generation computing systems for smart wearable electronics. Several studies have been conducted on flexible neural networks for practical applications; however, developing systems with complete synaptic plasticity for combinatorial optimization remains challenging. In this study, the metal-ion injection density is explored as a diffusive parameter of the conductive filament in organic memristors. Additionally, a flexible artificial synapse with bio-realistic synaptic plasticity is developed using organic memristors that have systematically engineered metal-ion injections, for the first time. In the proposed artificial synapse, short-term plasticity (STP), long-term plasticity, and homeostatic plasticity are independently achieved and are analogous to their biological counterparts. The time windows of the STP and homeostatic plasticity are controlled by the ion-injection density and electric-signal conditions, respectively. Moreover, stable capabilities for complex combinatorial optimization in the developed synapse arrays are demonstrated under spike-dependent operations. This effective concept for realizing flexible neuromorphic systems for complex combinatorial optimization is an essential building block for achieving a new paradigm of wearable smart electronics associated with artificial intelligent systems.

Molecular Effects of Elongation Factor Ts and Trigger Factor on the Unfolding and Aggregation of Elongation Factor Tu Induced by the Prokaryotic Molecular Chaperone Hsp33.

Hsp33, a prokaryotic redox-regulated holding chaperone, has been recently identified to be able to exhibit an unfoldase and aggregase activity against elongation factor Tu (EF-Tu) in its reduced state. In this study, we investigated the effect of elongation factor Ts (EF-Ts) and trigger factor (TF) on Hsp33-mediated EF-Tu unfolding and aggregation using gel filtration, light scattering, circular dichroism, and isothermal titration calorimetry. We found that EF-Tu unfolding and subsequent aggregation induced by Hsp33 were evident even in its complex state with EF-Ts, which enhanced EF-Tu stability. In addition, although TF alone had no substantial effect on the stability of EF-Tu, it markedly amplified the Hsp33-mediated EF-Tu unfolding and aggregation. Collectively, the present results constitute the first example of synergistic unfoldase/aggregase activity of molecular chaperones and suggest that the stability of EF-Tu is modulated by a sophisticated network of molecular chaperones to regulate protein biosynthesis in cells under stress conditions.

Tourism Destination Management Strategy for Young Children: Willingness to Pay for Child-Friendly Tourism Facilities and Services at a Heritage Site.

The present study seeks to establish tourism destination management centered on young children for accessible tourism from a public perspective. Preferences for services and facilities for young children were identified using a choice experiment (CE). The present study was conducted at Hwaseong Fortress, a UNESCO World Heritage Site, located in Suwon City, which leads the clean restroom culture. Overall, 1870 experiments were conducted with 374 participants to estimate their willingness to pay for child-friendly tourism facilities and services. As a result, willingness to pay was found in the order of specialized courses for young children, rest areas, restrooms, and rides. In conclusion, the importance of health/hygiene and amenities has implications for tourism destination management for young children. This study contributes to a better understanding of families with young children by evaluating preferences for levels of services and facilities for young children.

Effects of Banxia Xiexin Decoction () on Cisplatin-Induced Apoptosis of Human A549 Lung Cancer Cells.

OBJECTIVE: To examinie the synergistic effects of Banxia Xiexin Decoction (, Known as Banhasasim-tang in Korean) extract (BXDE) on cisplatin-induced cytotoxicity in the A549 human lung cancer cell lines. METHODS: A549 cells were treated with varying concentrations (50-200 µg/mL) of cisplatin and BXDE alone or in combination for 96 h. We used 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan assay and flow cytometry to analyze cell viability and apoptosis, respectively. RESULTS: The exposure of cells to cisplatin and BXDE alone or in combination decreased cell viability dose- and time-dependently (P<0.05), which was found to be mediated by the apoptotic pathway as confirmed by the increase in the annexin V+/propidium iodide- stained cell population and a ladder pattern of discontinuous DNA fragments. Furthermore, the apoptosis was inhibited by the pan-caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (z-VAD-FMK). CONCLUSIONS: BXDE significantly potentiated apoptotic effects of cisplatin in A549 cells. Moreover, apoptosis induced by BXDE might be the pivotal mechanism mediating its chemopreventative action against cancer.

Suppression of TPA-induced cancer cell invasion by Peucedanum japonicum Thunb. extract through the inhibition of PKCα/NF-κB-dependent MMP-9 expression in MCF-7 cells.

Metastatic cancers spread from their site of origin (the primary site) to other parts of the body. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix, is important in metastatic cancers as it plays a major role in cancer cell invasion. The present study examined the inhibitory effect of an ethanol extract of Peucedanum japonicum Thunb. (PJT) on MMP-9 expression and the invasion of MCF-7 breast cancer cells induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Western blot analysis, gelatin zymography, and reverse transcription-quantitative PCR revealed that PJT significantly suppressed MMP-9 expression and activation in a dose-dependent manner. Furthermore, PJT attenuated TPA-induced nuclear translocation and the transcriptional activation of nuclear factor (NF)-κB. The results indicated that the PJT-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involved the suppression of the PKCα/NF-κB pathway in MCF-7 cells. Thus, the inhibition of MMP-9 expression by PJT may have potential value as a therapy for restricting the invasiveness of breast cancer.

Fisetin regulates TPA-induced breast cell invasion by suppressing matrix metalloproteinase-9 activation via the PKC/ROS/MAPK pathways.

Invasion and metastasis are among the main causes of death in patients with malignant tumors. Fisetin (3,3',4',7-tetrahydroxyflavone), a natural flavonoid found in the smoke tree (Cotinus coggygria), is known to have antimetastatic effects on prostate and lung cancers; however, the effect of fisetin on breast cancer metastasis is unknown. The aim of this study was to determine the anti-invasive activity of fisetin in human breast cancer cells. Matrix metalloproteinase (MMP)-9 is a major component facilitating the invasion of many cancer tumor cell types, and thus the inhibitory effect of fisetin on MMP-9 expression in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated human breast cancer cells was investigated in this study. Fisetin significantly attenuated TPA-induced cell invasion in MCF-7 human breast cancer cells, and was found to inhibit the activation of the PKCα/ROS/ERK1/2 and p38 MAPK signaling pathways. This effect was furthermore associated with reduced NF-κB activation, suggesting that the anti-invasive effect of fisetin on MCF-7 cells may result from inhibited TPA activation of NF-κB and reduced TPA activation of PKCα/ROS/ERK1/2 and p38 MAPK signals, ultimately leading to the downregulation of MMP-9 expression. Our findings indicate the role of fisetin in MCF-7 cell invasion, and clarify the underlying molecular mechanisms of this role, suggesting fisetin as a potential chemopreventive agent for breast cancer metastasis.

Crotonis Fructus and Its Constituent, Croton Oil, Stimulate Lipolysis in OP9 Adipocytes.

Introduction. Crotonis fructus (CF) is the mature fruit of Croton tiglium L. and has been used for the treatment of gastrointestinal disturbance in Asia. It is well known that the main component of CF is croton oil (CO). The present study is to investigate the effects of CF extracts (CFE) and CO on lipolysis in OP9 adipocytes. Methods. Glycerol release to the culture supernatants was used as a marker of adipocyte lipolysis. Results. Treatment with various concentrations of CFE and CO stimulates glycerol release in a dose-dependent manner. The increase in glycerol release by CFE is more potent than isoproterenol, which is a ß-adrenergic agonist as a positive control in our system. The increased lipolysis by CFE and CO was accompanied by an increase of phosphorylated hormone sensitive lipase (pHSL) but not nonphosphorylated HSL protein and mRNA. Pretreatment with H89, which is a protein kinase A inhibitor, significantly abolished the CFE- and CO-induced glycerol release in OP9 adipocytes. These results suggest that CFE and CO may be a candidate for the development of a lipolysis-stimulating agent in adipocytes.

Ethanol Extract of Alismatis rhizome Inhibits Adipocyte Differentiation of OP9 Cells.

The rhizome of Alisma orientale (Alismatis rhizome) has been used in Asia for promoting diuresis to eliminate dampness from the lower-jiao and to expel heat. In this study, an ethanol extract of the rhizome of Alisma orientale (AOE) was prepared and its effects on adipocyte differentiation of OP9 cells were investigated. Treatment with AOE in a differentiation medium for 5 days resulted in dose-dependent inhibition of lipid droplet formation in OP9 cells. Furthermore, AOE significantly inhibited adipocyte differentiation by downregulating the expression of the master transcription factor of adipogenesis, peroxisome proliferation-activity receptor γ (PPAR γ ), and related genes, including CCAAT/enhancer binding protein ß (C/EBP ß ), fatty acid-binding protein (aP2), and fatty acid synthase (FAS). AOE exerted its inhibitory effects primarily during the early adipogenesis stage (days 1-2), at which time it also exerted dose-dependent inhibition of the expression of C/EBP ß , a protein related to the inhibition of mitotic clonal expansion. Additionally, AOE decreased the expression of autophagy-related proteins, including beclin 1, and the autophagy-related genes, (Atg) 7 and Atg12. Our results indicate that AOE's inhibitory effects on adipocyte differentiation of OP9 cells are mediated by reduced C/EBP ß expression, causing inhibition of mitotic clonal expansion and autophagy.

Saussurea lappa extract suppresses TPA-induced cell invasion via inhibition of NF-κB-dependent MMP-9 expression in MCF-7 breast cancer cells.

BACKGROUND: Saussurea lappa (SL) has been used as a traditional herbal medicine to treat abdominal pain and tenesmus, and has been suggested to possess various biological activities, including anti-tumor, anti-ulcer, anti-inflammatory, anti-viral, and cardiotonic activities. The effect of SL on breast cancer metastasis, however, is unknown. Cell migration and invasion are crucial in neoplastic metastasis. Matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix, is a major component in cancer cell invasion. METHODS: Cell viability was examined by MTT assay, whereas cell motility was measured by invasion assay. Western blot, Real-time PCR, and Zymography assays were used to investigate the inhibitory effects of ESL on matrix metalloproteinase-9 (MMP-9) expression level in MCF-7 cells. EMSA confirmed the inhibitory effects of ESL on DNA binding of NF- κB in MCF-7 cells. RESULTS: Cells threated with various concentrations of Saussurea lappa (ESL) for 24 h. Concentrations of 2 or 4 µM did not lead to a significant change in cell viability or morphology. Therefore, subsequent experiments utilized the optimal non-toxic concentration (2 or 4 µM) of ESL. In this study, we investigated the inhibitory effect of ethanol extract of ESL on MMP-9 expression and cell invasion in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MCF-7 cells. ESL inhibited the TPA-induced transcriptional activation of nuclear factor-kappa B (NF-κB). However, this result obtained that ESL did not block the TPA-induced phosphorylation of the kinases: p38, ERK, and JNK. Therefore, ELS-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-kB pathway in MCF-7 cells. CONCLUSIONS: These results indicate that ELS-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of NF-kB pathway in MCF-7 cells. Thus, ESL has potential for controlling breast cancer invasiveness in vitro.

Decursin prevents TPA-induced invasion through suppression of PKCα/p38/NF-κB-dependent MMP-9 expression in MCF-7 human breast carcinoma cells.

Decursin, a coumarin compound, was first isolated from the roots of Angelica gigas almost four decades ago. It was found to exhibit cytotoxicity against various human cancer cells and to possess anti-amnesic activity in vivo through the inhibition of AChE activity. However, the effect of decursin on breast cancer invasion is unknown. Matrix metalloproteinase-9 (MMP-9) is known to be an important factor for cancer cell invasion. Therefore, in this study, we investigated the inhibitory effect of decursin on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 expression and cell invasion, as well as the molecular mechanisms involved in MCF-7 cells. Our results showed that decursin inhibits TPA-induced MMP-9 expression and cell invasion through the suppression of NF-κB. Furthermore, decursin repressed the TPA-induced phosphorylation of p38 MAPK and inhibited TPA-induced translocation of PKCα from the cytosol to the membrane, but did not affect the translocation of PKCδ. These results indicate that decursin-mediated inhibition of TPA-induced MMP-9 expression and cell invasion involves the suppression of the PKCα, MAPK and NF-κB pathways in MCF-7 cells. Thus, decursin may have potential value in restricting breast cancer metastasis.

Inhibitory effects of Pericarpium zanthoxyli extract on adipocyte differentiation.

Obesity is a risk factor associated with numerous disorders, such as type 2 diabetes, hypertension, dyslipidemia and coronary heart disease. In this study, we investigated the inhibitory effects of Pericarpium zanthoxyli extract (PZE) on the adipocytic differentiation of OP9 cells. During adipocyte differentiation, the OP9 cells were treated with 0, 10 and 20 µg/ml of PZE at various time intervals, followed by the examination of lipid droplet formation and the mRNA expression of adipogenesis-related genes. The cells treated with PZE during the early period (days 0-2) showed a significant reduction in the accumulation of lipid droplets, which were induced by a standard adipogenic cocktail, as well as a decrease in the expression of the adipogenesis-related transcription factor, peroxisome proliferator-activated receptor γ (PPARγ) and PPARγ-target genes, such as adipocyte protein 2 (aP2), fatty acid synthase (FAS) and other adipocyte markers. Adipocyte differentiation was not inhibited by treatment with PZE during the late stage of differentiation (days 3-5). Thus, the inhibitory effects of PZE on adipocyte differentiation occurred during the early stages of adipogenesis, which was confirmed by the decrease in the levels of CCAAT/enhancer-binding protein ß (C/EBPß) in a dose-dependent manner when the OP9 cells were exposed to PZE. Taken together, our results indicate that PZE inhibit the early stages of adipogenic differentiation by inhibiting C/EBPß expression.

Tunable catalytic alloying eliminates stacking faults in compound semiconductor nanowires.

Planar defects in compound (III-V and II-VI) semiconductor nanowires (NWs), such as twin and stacking faults, are universally formed during the catalytic NW growth, and they detrimentally act as static disorders against coherent electron transport and light emissions. Here we report a simple synthetic route for planar-defect free II-VI NWs by tunable alloying, i.e. Cd(1-x)Zn(x)Te NWs (0 ≤ x ≤ 1). It is discovered that the eutectic alloying of Cd and Zn in Au catalysts immediately alleviates interfacial instability during the catalytic growth by the surface energy minimization and forms homogeneous zinc blende crystals as opposed to unwanted zinc blende/wurtzite mixtures. As a direct consequence of the tunable alloying, we demonstrated that intrinsic energy band gap modulation in Cd(1-x)Zn(x)Te NWs can exploit the tunable spectral and temporal responses in light detection and emission in the full visible range.

Choline and osmotic-stress tolerance induced in Arabidopsis by the soil microbe Bacillus subtilis (GB03).

Choline (Cho) is an essential nutrient for humans as well as the precursor of glycine betaine (GlyBet), an important compatible solute in eukaryotes that protects cells from osmotic stress caused by dehydrating conditions. The key enzyme for plant Cho synthesis is phosphoethanolamine N-methyltransferase (PEAMT), which catalyzes all three methylation steps, including the rate-limiting N-methylation of phosphoethanolamine. Herein, we report that the beneficial soil bacterium Bacillus subtilis (strain GB03) enhances Arabidopsis Cho and GlyBet synthesis associated with enhanced plant tolerance to osmotic stress. When stressed with 100 mM exogenous mannitol, GB03-exposed plants exhibit increased transcript level of PEAMT compared with stressed plants without bacterial exposure. Endogenous Cho and GlyBet metabolite pools were elevated by more than two- and fivefold, respectively, by GB03 treatment, consistent with increased stress tolerance. Moreover, in the xipotl mutant line with reduced Cho production, a loss of GB03-induced drought tolerance is observed. Osmotic-stressed plants with or without GB03 exposure show similar levels of abscsisic acid (ABA) accumulation in both shoots and roots, suggesting that GB03-induced osmoprotection is ABA independent. GB03 treatment also improves drought tolerance in soil-grown plants as characterized by phenotypic comparisons, supported by an elevated accumulation of osmoprotectants. These results provide a biological strategy to enhance Cho biosynthesis in plants and, in turn, increase plant tolerance to osmotic stress by elevating osmoprotectant accumulation.

A soil bacterium regulates plant acquisition of iron via deficiency-inducible mechanisms.

Despite the abundance of iron in nature, it is the third most limiting nutrient for plants due to its minimal solubility in most soils. While certain soil microbes produce chelating agents that enhance the solubility of iron, the effectiveness of such siderophores in the assimilation of iron by plants is debated. With an increasing understanding that select soil microbes play a signaling role in activating growth and stress responses in plants, the question arises as to whether such symbionts regulate iron assimilation. Here we report a previously unidentified mechanism in which the growth-promoting bacterium Bacillus subtilis GB03 activates the plant's own iron acquisition machinery to increase assimilation of metal ions in Arabidopsis. Mechanistic studies reveal that GB03 transcriptionally up-regulates the Fe-deficiency-induced transcription factor 1 (FIT1), which is necessary for GB03-induction of ferric reductase FRO2 and the iron transporter IRT1. In addition, GB03 causes acidification of the rhizosphere by enhancing root proton release and by direct bacterial acidification, thereby facilitating iron mobility. As a result, GB03-exposed plants have elevated endogenous iron levels as well as increased photosynthetic capacity compared with water-treated controls. In contrast, loss-of-function fit1-2 mutants are compromised in terms of enhanced iron assimilation and photosynthetic efficiency triggered by GB03. In all studies reported herein, a physical partition separating roots from bacterial media precludes non-volatile microbial siderophores from contributing to GB03-stimulated iron acquisition. These results demonstrate the potential of microbes to control iron acquisition in plants and emphasize the sophisticated integration of microbial signaling in photosynthetic regulation.

Mutual partner violence: mental health symptoms among female and male victims in four racial/ethnic groups.

This study examines racial/ethnic and sex differences in the prevalence of mutual intimate partner violence (IPV) and mental health symptoms. The authors asked 676 university students in heterosexual relationships if they had experienced IPV, coercive victimization, and/or perpetration as well as symptoms of depression, anxiety, hostility, and somatization. Analyses were conducted separately for female and male respondents in four racial/ethnic groups, totaling eight groups (female and male groups each for African Americans, Asian Americans, Latinos, and European Americans). Men, as compared to women, reported stronger correlations between IPV perpetration and IPV victimization, with Asian American men reporting the highest associations of any group. Additionally, experiencing higher partner and coercive violence was significantly related to increased mental health symptoms for all groups except Asian American men. Taken together, these findings suggest that the majority of couples experience mutual violence that elicits mental health problems for both members of the couple.

Soil bacteria confer plant salt tolerance by tissue-specific regulation of the sodium transporter HKT1.

Elevated sodium (Na(+)) decreases plant growth and, thereby, agricultural productivity. The ion transporter high-affinity K(+) transporter (HKT)1 controls Na(+) import in roots, yet dysfunction or overexpression of HKT1 fails to increase salt tolerance, raising questions as to HKT1's role in regulating Na(+) homeostasis. Here, we report that tissue-specific regulation of HKT1 by the soil bacterium Bacillus subtilis GB03 confers salt tolerance in Arabidopsis thaliana. Under salt stress (100 mM NaCl), GB03 concurrently down- and upregulates HKT1 expression in roots and shoots, respectively, resulting in lower Na(+) accumulation throughout the plant compared with controls. Consistent with HKT1 participation in GB03-induced salt tolerance, GB03 fails to rescue salt-stressed athkt1 mutants from stunted foliar growth and elevated total Na(+) whereas salt-stressed Na(+) export mutants sos3 show GB03-induced salt tolerance with enhanced shoot and root growth as well as reduced total Na(+). These results demonstrate that tissue-specific regulation of HKT1 is critical for managing Na(+) homeostasis in salt-stressed plants, as well as underscore the breadth and sophistication of plant-microbe interactions.

Soil bacteria augment Arabidopsis photosynthesis by decreasing glucose sensing and abscisic acid levels in planta.

Photosynthesis is regulated by environmental factors as well as endogenous sugar signals. Whereas light-driven sugar biosynthesis is essential for terrestrial organisms, as well as belowground microflora, whether and how soil symbionts regulate photosynthesis has yet to be reported. Here, we show that the plant growth-promoting soil bacterium Bacillus subtilis GB03 augments photosynthetic capacity by increasing photosynthetic efficiency and chlorophyll content in Arabidopsis. Mechanistic studies reveal an elevation of sugar accumulation as well as the suppression of classic glucose signaling responses, including hypocotyl elongation and seed germination, with exposure to GB03. Compared with wild-type plants, two Arabidopsis mutants defective in hexokinase-dependent sugar signaling exhibit increased photosynthetic capacity, which is not further enhanced with GB03 exposure. Overlap in sugar/ABA sensing is observed in GB03-exposed plants, with a reduction of ABA-biosynthetic transcripts as well as downstream metabolite levels in leaves. Moreover, exogenous ABA abrogates GB03-triggered increases in photosynthetic efficiency and chlorophyll content. These results demonstrate that certain rhizobacteria elevate photosynthesis through the modulation of endogenous sugar/ABA signaling, and establish a regulatory role for soil symbionts in plant acquisition of energy.

Rhizobacterial volatile emissions regulate auxin homeostasis and cell expansion in Arabidopsis.

Certain plant growth-promoting rhizobacteria (PGPR), in the absence of physical contact with a plant stimulate growth via volatile organic compound (VOC) emissions, through largely unknown mechanisms. To probe how PGPR VOCs trigger growth in plants, RNA transcript levels of Arabidopsis seedlings exposed to Bacillus subtilus (strain GB03) were examined using oligonucleotide microarrays. In screening over 26,000 protein-coded transcripts, a group of approximately 600 differentially expressed genes related to cell wall modifications, primary and secondary metabolism, stress responses, hormone regulation and other expressed proteins were identified. Transcriptional and histochemical data indicate that VOCs from the PGPR strain GB03 trigger growth promotion in Arabidopsis by regulating auxin homeostasis. Specifically, gene expression for auxin synthesis was up regulated in aerial regions of GB03-exposed plants; auxin accumulation decreased in leaves and increased in roots with GB03 exposure as revealed in a transgenic DR5::GUS Arabidopsis line, suggesting activation of basipetal auxin transport. Application of the auxin transport inhibitor 1-naphthylphthalamic acid (NPA) restricted auxin accumulation to sites of synthesis thereby preventing GB03-mediated decreases in shoot auxin levels as well as thwarting GB03-mediated growth promotion. In addition, microarray data revealed coordinated regulation of cell wall loosening enzymes that implicated cell expansion with GB03 exposure, which was confirmed by comparative cytological measurements. The discovery that bacterial VOCs, devoid of auxin or other known plant hormones regulate auxin homeostasis and cell expansion provides a new paradigm as to how rhizobacteria promote plant growth.