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The emerging disease of rabies was confirmed in Taiwan ferret badgers (FBs) and reported to the World Organization for Animal Health (OIE) on July 17, 2013. The spread of wildlife rabies can be related to neighborhood countries in Asia. The phylogenetic analysis was conducted by maximum likelihood (ML) methods and the Bayesian coalescent approach based on the glycoprotein (G) and nucleoprotein (N) genes. The phylogeographic and spatial temporal dynamics of viral transmission were determined by using SPREAD, QGIS. Therefore, the origin and the change with time of the viruses can be identified. Results showed the rabies virus of FB strains in Taiwan is a unique clade among other strains in Asia. According to the phylogeographic coalescent tree, three major genotypes of the FB rabies virus have circulated in three different geographical areas in Taiwan. Two genotypes have distributed into central and southern Taiwan between two ecological river barriers. The third genotype has been limited in southeastern Taiwan by the natural mountain barrier. The diversity of FB rabies viruses indicates that the biological profile of FBs could vary in different geographical areas in Taiwan. An enhanced surveillance system needs to be established near the currently identified natural barriers for early warnings of the rabies virus outbreak in Taiwan. [ABSTRACT FROM AUTHOR]

Methylobacterium extorquens AM1 (AM1) has shown promise for use in industry due to its ability to use methanol as a sole carbon and energy source. Mevalonic acid (MEV) is an important platform chemical for the biosynthesis of isoprenoids, and a building block in the synthesis of polymers. In our previous study, the growth and MEV production of AM1-dcel-mvt strain were found to be unstable in the culture media tested (CHOI, MP, MC and HP), which contained ammonium salts, magnesium, calcium, buffers, methanol and trace elements. In this study, we developed a novel MC medium based on MP and CHOI, which improved the growth rate and the reproducibility and replicability of culture process considerably. AM1-dcel-mvt cells cultivated in MC displayed a more homogenous doubling time than cells in other media, which could explain their more stable growth. The optimized MO medium containing a higher phosphate buffer concentration and lower trace elements was developed, which enhanced MEV production by 0.61-fold to 340 mg/L. In fed-batch fermentation in a 5 L fermenter, a MEV titre of 2.59 g/Land a dry cell weight (DCW) of 9.03 g/L were obtained, representing the highest MEV production reported to date for the AM1-dcel-mvt strain. The MO medium facilitate the stable growth of AM1, and improve the industrial-scale production of MEV. [ABSTRACT FROM AUTHOR]

Background: Recurrence and metastasis are the usual manifestations of treatment failure of epithelial ovarian carcinoma (EOC). Vasculogenic mimicry (VM; blood supply development often seen in highly aggressive cancers), aldehyde dehydrogenase 1 (ALDH1, cancer stem cell biomarker), KiSS-1 (suppressor of tumor metastasis), and metastasis associated in colon cancer-1 (MACC1) are all useful predictive factors for metastasis and prognosis in various cancers. In this study, we analyzed associations among VM, ALDH1, KiSS-1, and MACC1 in EOC, and their respective correlations with clinicopathological characteristics and survival in EOC. Methods: Positive rates of VM, ALDH1, KiSS-1, and MACC1 in 207 whole EOC tissue samples were detected by immunohistochemistry. Patients' clinical data were also collected. Results: Levels of VM, ALDH1, and MACC1 were significantly higher, and levels of KiSS-1 significantly lower, in EOC tissues than in benign ovary tumors. Levels of VM, ALDH1, KiSS-1, and MACC1 were associated significantly with tumor/lymph node/metastasis (LNM) grade, implantation, and International Federation of Gynecology and Obstetrics (FIGO) stage, and with patients' overall survival (OS); whereas the KiSS-1+ subgroup had significantly longer OS than did the KiSS-1- subgroup. In multivariate analysis, high VM, ALDH1 or MACC1 levels, FIGO stage, implantation and low KiSS-1 levels were independently associated with shorter OS in patients with EOC. Conclusions: VM and expressions of ALDH1, KiSS-1, and MACC1 represent promising markers for metastasis and prognosis, and potential therapeutic targets for EOC. [ABSTRACT FROM AUTHOR]

Acetyl-CoA is not only an important intermediate metabolite for cells but also a significant precursor for production of industrially interesting metabolites. Methylobacterium extorquens AM1, a model strain of methylotrophic cell factories using methanol as carbon source, is of interest because it produces abundant coenzyme A compounds capable of directing to synthesis of different useful compounds from methanol. However, acetyl-CoA is not always efficiently accumulated in M. extorquens AM1, as it is located in the center of three cyclic central metabolic pathways. Here we successfully demonstrated a strategy for sensor-assisted transcriptional regulator engineering (SATRE) to control metabolic flux re-distribution to increase acetyl-CoA flux from methanol for mevalonate production in M. extorquens AM1 with introduction of mevalonate synthesis pathway. A mevalonate biosensor was constructed and we succeeded in isolating a mutated strain (Q49) with a 60% increase in mevalonate concentration (an acetyl-CoA–derived product) following sensor-based high-throughput screening of a QscR transcriptional regulator library. The mutated QscR-49 regulator (Q8*,T61S,N72Y,E160V) lost an N-terminal α-helix and underwent a change in the secondary structure of the RD-I domain at the C terminus, two regions that are related to its interaction with DNA. 13 C labeling analysis revealed that acetyl-CoA flux was improved by 7% and transcriptional analysis revealed that QscR had global effects and that two key points, NADPH generation and fumC overexpression, might contribute to the carbon flux re-distribution. A fed-batch fermentation in a 5-L bioreactor for QscR-49 mutant yielded a mevalonate concentration of 2.67 g/L, which was equivalent to an overall yield of 0.055 mol acetyl-CoA/mol methanol, the highest yield among engineered strains of M. extorquens AM1. This work was the first attempt to regulate M. extorquens AM1 on transcriptional level and provided molecular insights into the mechanism of carbon flux regulation. [ABSTRACT FROM AUTHOR]

The modern commercial optoelectronic infrastructure rests on a foundation of only a few, select semiconductor materials, capable of serving as viable substrates for devices. Any new active device, to have any hope of moving past the laboratory setting, must demonstrate compatibility with these substrate materials. Across much of the electromagnetic spectrum, this simple fact has guided the development of lasers, photodetectors, and other optoelectronic devices. In this work, we propose and demonstrate the concept of a multi-functional metamorphic buffer (MFMB) layer that not only allows for growth of highly lattice-mismatched active regions on InP substrates but also serves as a bottom cladding layer for optical confinement in a laser waveguide. Using the MFMB concept in conjunction with a strain-balanced multiple quantum well active region, we demonstrate laser diodes operating at room temperature in the technologically vital, and currently underserved, 2.5-3.0 lm wavelength range. [ABSTRACT FROM AUTHOR]

Background: Tumor recurrence and metastasis are the most common reason for treatment failure. Metastasis-associate in colon cancer-1 (MACC1) has been identified as a metastatic and prognostic biomarker for colorectal cancer and other solid tumors. Aldehyde dehydrogenase 1 (ALDH1), a marker of cancer stem cells, is also associated with metastasis and poor prognosis in many tumors. However, the prognostic value of either MACC1 or ALDH1 in non-small cell lung cancer (NSCLC) is unclear. In this study, we explored the relationship between MACC1 and ALDH1 expression, as well as their respective associations with clinicopathological features, to determine if either could be useful for improvement of survival prognosis in NSCLC. Methods: The expression levels of both MACC1 and ALDH1 in 240 whole tissue sections of NSCLC were examined by immunohistochemistry. Clinical data were also collected. Results: MACC1 and ALDH1 were significantly overexpressed in NSCLC tissues when compared to levels in normal lung tissues. Investigation of associations between MACC1 or ALDH1 protein levels with clinicopathological parameters of NSCLC revealed correlations between the expression of each with tumor grade, lymph node metastasis, and tumor node metastasis. The overall survival of patients with MACC1- or ALDH1-positive NSCLC tumors was significantly lower than that of those who were negative. Importantly, multivariate analysis suggested that positive expression of either MACC1 or ALDH1, as well as TNM stage, could be independent prognostic factors for overall survival in patients with NSCLC. Conclusions: MACC1 and ALDH1 may represent promising metastatic and prognostic biomarkers, as well as potential therapeutic targets, for NSCLC. [ABSTRACT FROM AUTHOR]

The aim of the study was to examine changes in left atrial appendage volume (LAA-V) in patients with non-valvular atrial fibrillation (AF) using real-time threedimensional transesophageal echocardiography (RT3D-TEE) and evaluate the prediction value on the high risk of thrombosis of LAA. Using RT3D-TEE we measured: i) LAA peak empty velocity (LAA-PEV), ii) LAA-V including LAA end-diastolic volume (LAA-EDV) and end-systolic volume (LAA-ESV). We also calculated LAA ejection fraction (LAA-EF). RT3D-TEE was applied in 20 control cases and 74 patients with non-valvular AF. According to the presence of thrombosis, 74 patients were divided into the no thrombosis group (NTH group, n=52) and thrombosis group (TH group, n=22). Our results showed that there were significant differences in LAA-V and LAA-EF values in different groups (P<0.05). LAA-EDV moderately correlated with LAA-PEV (r=-0.531, P<0.001) while LAA-ESV demonstrated a strong correlation with LAA-PEV (r=-0.741, P<0.001). LAA-EF also showed a strong correlation with LAA-PEV (r=0.693, P<0.001). Through receiver operating characteristic (ROC) curves, the cut-off values of LAA-EDV and LAA-ESV in thrombosis of LAA were 18.45 and 9.69 ml, respectively. RT3D-TEE effectively evaluated the LAA-V, LAA-PEV and LAA-EF parameters, and proved to be valuable in the process of evaluation of thrombosis of LAA. [ABSTRACT FROM AUTHOR]

PTEN plays an essential role in tumorigenesis and both its mutation and inactivation can influence proliferation, apoptosis, and cell cycle progression in tumor cells. However, the precise role of PTEN in lung cancer cells has not been well studied. To address this, we have generated lung adenocarcinoma A549 cells overexpressing wild-type or mutant PTEN as well as A549 cells expressing a siRNA directed toward endogenous PTEN. Overexpression of wild-type PTEN profoundly inhibited cell proliferation, promoted cell apoptosis, caused cell cycle arrest at G1, downregulated p-AKT, and decreased expression of the telomerase protein hTERT. In contrast, in cells expressing a PTEN directed siRNA, the opposite effects on cell proliferation, apoptosis, cell cycle arrest, p-AKT levels, and hTERT protein expression were observed. A549 cells transfected with a PTEN mutant lacking phosphatase activity (PTEN-C124A) or an empty vector (null) did not show any effect. Furthermore, using the PI3K/AKT pathway blocker LY294002, we confirmed that the PI3K/AKT pathway was involved in mediating these effects of PTEN. Taken together, we have demonstrated that PTEN downregulates the PI3K/AKT/hTERT pathway, thereby suppressing the growth of lung adenocarcinoma cells. Our study may provide evidence for a promising therapeutic target for the treatment of lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

We investigate the atomic current in optical lattices under the presence of both constant and periodic external field with Landau–Zener tunneling considered. By simplifying the system to a two-band model, the atomic current is obtained based on the Boltzmann equations. We focus on three situations to discuss the influence of the Landau–Zener tunneling and periodic field on the atomic current. Numerical calculations show the atomic transient current would finally become the stable oscillation, whose amplitude and average value can be further adjusted by the periodic external field. It is concluded that the periodic external field could provide an effective modulation on the atomic current even when the Landau–Zener tunneling probability has almostly become a constant. [ABSTRACT FROM AUTHOR]

Biochar has been applied as a bulk agent or an additive to compost. The mixture of biochar and compost has been considered to exert synergistic effect as a soil amendment. In a composting system, the macro-porous sites of biochar may act as a novel niche that selects and cultures the microorganisms from the bulk compost. A variety of volatile organic carbons (VOCs) such as aromatic hydrocarbons and aliphatics were detected in biochar pellets (BC) pyrolyzed at 100 °C. In the mesosphilic phase, the water-soluble carbon (WSC) and water-soluble phenols (WSP) in biochar increased from 2.1 to 26 mg kg −1 and 5.9 to 101 μg kg −1 , respectively. These labile carbons however, were subjected to a rapid metabolism over the composting course. We further compared the responses of microbial community in BC to those in the bulk organic matter. Both Shannon-Wiener and Richness indexes of bacterial communities were higher in BC than in the adjacent compost (ADJ) and the bulk organic matter (control). As for fungal communities, the two indexes were higher in BC than ADJ and control only in the mature phase. During the composting course, the bacterial activity was higher than the fungal counterpart in terms of the changes of corresponding biomarkers, glucosamine and muramic acids. The results suggested that the diversified labile carbons sources including VOCs and WSC in BC could influence the structure of microbial community and resulted in an enhanced carbon catabolic capacity. [ABSTRACT FROM AUTHOR]

Dye wastewater in production process of the textile industry will cause serious environmental problems. Hydrodynamic cavitation includes many structures, such as a venturi tube, orifice, and pulsed jet. Self-excited oscillation cavitation is a kind of pulsed jet. In this paper, hydrodynamic cavitation is realized by self-excited oscillation cavitation. In this research, to study the hydrodynamic cavitation (HC) characteristics of the self-excited oscillation cavity and the degradation effect of dye wastewater, several experimental studies were carried out by selecting methylene blue as the colorant pollutant. During the experiment, the effects of experimental operating condition (including system pressure and initial solution concentration) on the degradation of methylene blue were studied, and its optimal operating conditions were obtained. And then the effects of the combination method of HC and oxidizing additives (hydrogen peroxide and ozone) on methylene blue degradation were analyzed. The results show that under the optimal system pressure of 1.4 MPa and solution concentration of 5.6 mg/L, the maximum extent of degradation is 24.90%, and the degradation rate is 2.3 × 10−3 min−1. The degradation effects of the combination methods of HC + Hydrogen peroxide and HC + Ozone can be greatly improved compared to only HC. The extent of methylene blue degradation of HC + Hydrogen peroxide is 83.70%, the degradation rate is 14.9 × 10−3 min−1, and the synergy index is 3.63; the extent of degradation of HC + Ozone is 92.62%, the degradation rate is 37.7 × 10−3 min−1, and the synergy index is 5.80. The lowest cost of the HC + Ozone combination method is 9.797 USD/m3, thereby the comparison of cavitation yield and energy consumption cost shows that HC + Ozone is the preferential combination treatment method. This study will not only play a significantly guiding role on the optimization of process parameters of SEOC for AOPs to obtain the preferable cavitation effect, but also provide support for the development of hybrid AOPs for wastewater treatment in the direction of large-scale application. • Hybrid advanced oxidation processes for treatment of MB dye wastewater. • Optimizations of various parameters for degradation of MB dye in hybrid system. • Self-excited oscillation cavity exhibits a significant synergistic effect for MB degradation. • Comparison of cavitation yield and energy cost shows the HC + O 3 method is optimal. [ABSTRACT FROM AUTHOR]

Dye wastewater in production process of the textile industry will cause serious environmental problems. Hydrodynamic cavitation includes many structures, such as a venturi tube, orifice, and pulsed jet. Self-excited oscillation cavitation is a kind of pulsed jet. In this paper, hydrodynamic cavitation is realized by self-excited oscillation cavitation. In this research, to study the hydrodynamic cavitation (HC) characteristics of the self-excited oscillation cavity and the degradation effect of dye wastewater, several experimental studies were carried out by selecting methylene blue as the colorant pollutant. During the experiment, the effects of experimental operating condition (including system pressure and initial solution concentration) on the degradation of methylene blue were studied, and its optimal operating conditions were obtained. And then the effects of the combination method of HC and oxidizing additives (hydrogen peroxide and ozone) on methylene blue degradation were analyzed. The results show that under the optimal system pressure of 1.4 MPa and solution concentration of 5.6 mg/L, the maximum extent of degradation is 24.90%, and the degradation rate is 2.3 × 10−3 min−1. The degradation effects of the combination methods of HC + Hydrogen peroxide and HC + Ozone can be greatly improved compared to only HC. The extent of methylene blue degradation of HC + Hydrogen peroxide is 83.70%, the degradation rate is 14.9 × 10−3 min−1, and the synergy index is 3.63; the extent of degradation of HC + Ozone is 92.62%, the degradation rate is 37.7 × 10−3 min−1, and the synergy index is 5.80. The lowest cost of the HC + Ozone combination method is 9.797 USD/m3, thereby the comparison of cavitation yield and energy consumption cost shows that HC + Ozone is the preferential combination treatment method. This study will not only play a significantly guiding role on the optimization of process parameters of SEOC for AOPs to obtain the preferable cavitation effect, but also provide support for the development of hybrid AOPs for wastewater treatment in the direction of large-scale application. • Hybrid advanced oxidation processes for treatment of MB dye wastewater. • Optimizations of various parameters for degradation of MB dye in hybrid system. • Self-excited oscillation cavity exhibits a significant synergistic effect for MB degradation. • Comparison of cavitation yield and energy cost shows the HC + O 3 method is optimal. [ABSTRACT FROM AUTHOR]

• The torso reflections in head-related transfer functions (HRTFs) of various simplified model were compared and analyzed. • To further evaluate the effect of torso reflections, we conducted the psychoacoustic experiment. • The human-like torso shape can provide enough torso reflection, improving low-frequency lateral elevation localization performance. The effect of torso reflection on head-related transfer functions (HRTFs) is considered a suitable elevation localization cue for lateral sound sources below 3.0 kHz, and various torso models have been hitherto adopted in HRTF simulation. However, their torso reflection effects have not been compared in detail. This work analyzes the torso reflection effects of the representative torso models on HRTFs, and further evaluates their elevation localization performance via psychoacoustic experiments. The results show that the semi-ellipsoidal torso and truncated Knowles Electronics Mannequin for Acoustic Research (KEMAR) torso, both of which have considerable advantages over the spherical torso, can achieve better elevation localization performance, which validates the torso with human-like shape provide enough torso reflection and have a better ability in low-frequency lateral elevation perception. [ABSTRACT FROM AUTHOR]

Left. Top view and side view of the optimized lattice structure of Ti 2 CO 2 /Ti 2 CF 2. The parallelogram with dashed line denotes the 2D unit cell. Right. The Schottky barrier height of the Ti 2 CO 2 /Ti 2 CF 2 heterostructure as a function of the external electric field. [Display omitted] • A novel Ti 2 CO 2 /Ti 2 CF 2 van der Waals heterostructure is designed and the band structures of each layer are well preserved. • The Schottky barrier height of the Ti 2 CO 2 /Ti 2 CF 2 heterostructure is robust under external electric field. • The robust Schottky barrier opens the possibility of MXenes device designs for nanoelectronics. Transition metal carbides, nitrides and carbonitrides (MXenes) are considered as multifunctional materials due to their various elemental composition possibilities, surface functional tunability, various magnetic orders, and large spin–orbit coupling. Herein, a novel Ti 2 CO 2 /Ti 2 CF 2 heterostructure is designed and its electronic and interfacial properties are investigated based on first-principles calculations. Our results reveal that the band structures of Ti 2 CO 2 and Ti 2 CF 2 layers are well preserved in the heterostructure due to the van der Waals interaction between the two layers, and a n -type Schottky contact forms due to the band bending at the interface. The most striking and much novel property is that the Schottky barrier height is nearly independent of the intensity of external electric field which is kept along the direction perpendicular to the Ti 2 CO 2 or Ti 2 CF 2 plane. The result denotes that a Fermi level pinning behavior occurs upon varying the intensity of electric field, which can change the doping concentration of electrons in the Ti 2 CO 2 layer. This robust Schottky barrier opens the possibility of MXenes device designs for nanoelectronics. [ABSTRACT FROM AUTHOR]

[Display omitted] • A novel surface cleaning and passivation method is demonstrated for semiconductor devices with AlGaAs-containing facet structure. • The removal of surface states was implemented by Ar-plasma cleaning and passivated by ZnO films. • The method is applied to semiconductor lasers with comprehensive optimization, material characterization, device testing, and reliability results. • We demonstrated 21 W laser output power and reliable operation by utilizing this method. Passivation of dangling bonds at the cleaved mirror facet and its durability are fundamental features of semiconductor lasers to obtain reliable operation with a long device lifetime. The high non-radiative recombination activity of the surface states needs to be controlled to prevent the Fermi level pinning before the deposition of mirror coating materials. Here, we report the incorporation of plasma cleaning of the facet and ZnO film as a passivation layer for the fabrication of high-power semiconductor lasers. The Argon plasma cleaning process was investigated to eliminate surface contamination without damaging the cavity surface. The ZnO passivation films were systematically studied by varying the chamber pressure and sputtering power of the radio frequency (RF) sputter coating process. We obtained homogeneous and dense ZnO films with high surface quality and optical absorption coefficient of zero. By incorporating the optimum plasma cleaning and passivation layer parameters, GaAs-based laser devices with significantly improved catastrophic optical mirror damage (COMD) power were achieved. COMD threshold was increased from 11.9 W to 20.7 W. The life test results demonstrate no failure for facet cleaned and passivated devices for more than 500 h, confirming the long-term effectiveness of the process for actual device integration. [ABSTRACT FROM AUTHOR]

In this research, single phase -MoSi2 was prepared by solid state hybrid microwave heating within 90 min at relatively low temperature 1273 K. Such precursor powders were then ball milled and sintered by microwave heating at different temperatures. The thermoelectric (TE) properties of MoSi2 bulks were investigated in the temperature range of 300-673 K. When the sintering temperature increases from 973 K to 1273 K, the electrical resistivity decreases significantly and the Seebeck coefficients increase obviously, leading to the maximum TE powder factor of at 673 K. These results demonstrate the feasibility of high efficient and economical synthesis of MoSi2 by microwave heating technique, with the final products having comparable TE performance in comparison to those from typical methods with long duration and energy-extensive consumption. [ABSTRACT FROM AUTHOR]

Citrus pectin is widely used as a gelling/thickening agent and stabilizer in the food and pharmaceutical industries. The usefulness of citrus pectin, however, has been limited due to its large size, an obstacle that can be partially overcome with pH-modified citrus pectin (MCP). In the present study, we fractionated MCP into four fractions (MCP-1, −2, −3, and −4) and then sub-fractions of type-I rhamnogalacturonan-rich pectins (RG-I: MCP-1a, MCP-2a, MCP-3Sa and MCP-4a) and homogalacturonan-rich pectins (HG: MCP-2b, MCP-3Sb, MCP-3P, MCP-4b). Upon analysis of their chemical structures, we found that the RG-I sub-fractions contain (1 → 4)-linked β- D -galactan and (1 → 5)-linked α- L -arabinans or type-I arabinogalactan side-chains. Because parent MCP is known to inhibit hemagglutination mediated by galectin-3 (a lectin associated with cancer progression and metastasis), we used this assay to define which MCP fraction best promotes anti-galectin-3 activity. Our results demonstrate that MCP-2 was the most inhibitory with a MIC of 0.06 μg/ml (ten-fold more potent than parent MCP), and that RG-I-rich pectins with (1 → 4)-linked β- D -galactan side-chains were more active than the other RG-I-rich and HG-rich pectins. These findings provide new insight into structure-activity relationships of MCP and provide impetus towards the development of MCP-based food stabilizers and galectin-3 targeted therapeutics for use in the clinical setting. [ABSTRACT FROM AUTHOR]

The synthesis and biological evaluation of new series of 6,7-dihydro-5 H -cyclopenta[ d ]pyrimidine and 5,6,7,8-tetrahydroquinazoline derivatives as selective sigma-1 receptor ( σ 1 R) antagonists are reported. The receptor affinities of new compounds were evaluated in vitro in σ 1 and σ 2 receptor binding assays. The structure-active relationship study leads us to the most promising compound: 2-(4-chlorophenyl)-4-(3-(4-methylpiperidin-1-yl)propoxy)-5,6,7,8-tetra-hydroquinazoline ( 33 ). Compound 33 has exerted nanomolar affinity for σ 1 R ( K i σ 1 = 15.6 nM) and high σ 1 / σ 2 selectivity ( K i σ 2 >2000 nM), and identified to be a σ 1 R antagonist. In animal model, compound 33 exhibited dose dependent anti-nociceptive effects in the formalin test. These results suggest that compound 33 could be a potent analgesic for pain treatment. [ABSTRACT FROM AUTHOR]

Within the framework of the fermion-spin theory, the charge transport in the doped Mott insulators on a honeycomb lattice is studied by taking into account the pseudogap effect. It is shown that the conductivity spectrum in the low-doped regime is separated by the pseudogap into a low-energy non-Drude peak followed by a broad mid-infrared band. However, the decrease of the pseudogap with the increase of doping leads to a shift of the position of the mid-infrared band towards the low-energy non-Drude peak, and then the low-energy Drude behavior recovers in the high-doped regime. The combined results of both the doped honeycomb-lattice and square-lattice Mott insulators indicate that the two-component conductivity induced by the pseudogap is a universal feature in the doped Mott insulators. [ABSTRACT FROM AUTHOR]

The rising climatic concerns force the conventional power system to minimise the gas emissions. Microgrid integrating with renewable energy plays a key role in utilising power systems in a more environment friendly way. Compared with single renewable energy system, the microgrid with multi‐energy systems is more attractive in practice. The schedule problem is considered to schedule wind power, combined heating and power generation (CHP), battery, and power grid in order to satisfy the electricity load and heat loads in the microgrid with the minimal cost in real time. Owing to the stochastic nature of wind power generation, it is a challenge to solve the multi‐energy scheduling problem when using the obtained real‐time information. In this study, the joint scheduling of the microgrid with multi‐energy systems is formulated as a rolling horizon Markov decision process (MDP). Moreover, then the rollout algorithm is applied to solve the problem in order to deal with the large state and decision space of MDP, which is caused by the increase of the number of CHPs. The feasible base policy needed in the rollout algorithm is constructed using a greedy algorithm. Numerical results demonstrate that the algorithm can achieve the requirement of real‐time scheduling effectively. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is characterized by memory loss and cognitive dysfunction. Aquaporin-4 (AQP4), which is primarily expressed in astrocytes, is the major water channel expressed in the central nervous system (CNS). This protein plays an important role in water and ion homeostasis in the normal brain and in various brain pathological conditions. Emerging evidence suggests that AQP4 deficiency impairs learning and memory and that this may be related to the expression of glutamate transporter-1 (GLT-1). Moreover, the colocalization of AQP4 and GLT-1 has long been studied in brain tissue; however, far less is known about the potential influence that the AQP4/GLT-1 complex may have on AD. Research on the functional interaction of AQP4 and GLT-1 has been demonstrated to be of great significance in the study of AD. Here, we review the interaction of AQP4 and GLT-1 in astrocytes, which might play a pivotal role in the regulation of distinct cellular responses that involve neuroprotection against AD. The association of AQP4 and GLT-1 could greatly supplement previous research regarding neuroprotection against AD. [ABSTRACT FROM AUTHOR]

Molecular forces involved in corn germ proteins (CGP) gelation were investigated using a rheometer. With the inclusion of urea and guanidine hydrochloride (GuHCl), the storage moduli (G′) of CGP gels tends to decrease. This is an indication that hydrophobic interactions and hydrogen bonds are present. The involvement of propylene glycol (PG) provides evidence that hydrogen bonds and electrostatic interactions are present. The impact of thiocyanate (NaSCN) and sodium sulfate (Na 2 SO 4 ) further proves the involvement of hydrogen bonds. The effects of 2-mercaptoethanol (2-ME) and N-ethylmaleimide (NEM) reveal that involvement of disulfide bonds contribute to CGP gel stiffness. Reheating and recooling tests revealed that during the initial cooling phase the gel is thermally reversible and higher levels of G′ suggested more hydrogen bonds are formed when recooled. It can be deduced that hydrogen bonds play a greater role than hydrophobic interactions from the increasing G′ during cooling and recooling. [ABSTRACT FROM AUTHOR]

Background: Cancer metastasis is a multi-step event including epithelial-to-mesenchymal transition (EMT). Breast cancer metastasis suppressor 1 (BRMS1) is a novel metastasis suppressor protein without anti-proliferating activity. However, a detailed underlying mechanism by which BRMS1 attenuates cancer cell EMT and invasion remained to be answered. In the present study, we report an additional mechanism by which BRMS1 attenuates Transforming growth factor-beta1 (TGF-β1)-induced breast cancer cell EMT and invasion.Methods: Experimental analysis involving chromosome immunoprecipitation (ChIP) and luciferase reporter assays were used to validate hypoxia inducible factor-1alpha (HIF-1α) as a transcriptional regulator of TWIST1 and Snail. Quantitative RT-PCR was used to analyze transcript expression. Immunoblotting and immunofluorescence were used to analyze protein expression. Matrigel-coated in vitro invasion insert was used to analyze cancer cell invasion.Results: BRMS1 strongly inhibited TGF-β1-induced breast cancer cell EMT and invasion. Unexpectedly, we observed that BRMS1 downregulates not only TWIST1 but also Snail expression, thereby inhibiting breast cancer cell invasion. In addition, we provide evidence that HIF-1α is required for Snail and TWIST1 expression. Further, BRMS1 reduced TGF-β1-induced HIF-1α transcript expression through inactivation of nuclear factor kappaB (NF-κB).Conclusion: Collectively, the present study demonstrates a mechanical cascade of BRMS1 suppressing cancer cell invasion through downregulating HIF-1α transcript and consequently reducing Snail and TWIST1 expression. [ABSTRACT FROM AUTHOR]

In this paper, the high-energy magnetic excitations in cuprate superconductors are studied based on the kinetic energy driven superconducting mechanism. The spin self-energy is evaluated explicitly in terms of the collective charge carrier modes in the particle-hole and particle-particle channels, and employed to calculate the dynamical spin structure factor. Our results show the existence of damped but well-defined dispersive spin excitations in the whole doping phase diagram. In particular, the charge carrier doping has a more modest effect on the high-energy spin excitations, and then the high-energy magnetic excitations retain roughly constant energy as a function of doping, with spectral weights and dispersion relations comparable to those found in the parent compound. [ABSTRACT FROM AUTHOR]

In an increasingly multilingual world, it is important to examine methods that may lead to more efficient second language learning, as well as to analyze the mechanisms by which successful learning occurs. The purpose of the current study was to investigate how different learning contexts can impact the learning of Mandarin Chinese as a second language. Two contexts [virtual environment (VE) vs. traditional learning environment] were compared and examined from cognitive and linguistic perspectives. Thirty-one monolingual English speakers participated in a training study consisting of seven learning and testing sessions, followed by one additional sessions of delayed post-testing. The participants' behavioral performances with regard to accuracy, reaction time, and exposure were collected and analyzed. Through analyses of variance and mixed-effects modeling, the current study shows that the learning trajectory of the participants in the VE showed a larger acceleration than that of those in the traditional learning context, which suggests that simulated embodied experience in the VE may have aided in the processing of a second language, especially with regard to enhancing the learning trajectory in short-term second language training. [ABSTRACT FROM AUTHOR]

An introduction is presented which discusses topics within the issue including the effects of using collaborative models on learners' French performance, learning contexts for learners of Chinese as a foreign language and the relationship between virtual embodiment and language learning.

Background: KAI1 and epithelial-mesenchymal transition (EMT) is related to both angiogenesis and lymphangiogenesis and is an important target in new cancer treatment strategies. We aimed to investigate the KAI1 and marker of EMT expression and correlation with lymph node metastasis (LNM) and explore their prognostic impact in non-small cell lung cancer (NSCLC). Methods: Tumor tissue specimens from 312 resected patients with stage I-IIIA NSCLC were obtained. Immunohistochemistry was used to assess the expression of the molecular markers KAI1, E-cadherin (E-cad), vimentin, CD34, and D2-40. Results: There were 153 N0 and 159 N+ patients. Tumor cell expression of KAI1and the marker of EMT, lymphatic vessel density (LVD), and microvessel density (MVD) were related to LNM. In multivariate analyses, the ages of patients, high tumor cell KAI1 expression, EMT, and the scores of MVD were independent factor of prognosis. Conclusions: Tumor cell KAI1 expression, EMT, LVD, and MVD correlate with LNM. Thus, the detection of KAI1, expression of markers of EMT, and the scores of MVD may be used as a potential indicator of NSCLC prognosis. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma is the most common of all the bone malignancies and accounts for 30-80 % of the primary skeletal sarcomas. The overall survival rate of patients with osteosarcoma is < 20 % suggesting poor prognosis. Methods: The present study demonstrates the effect of retinoic acid chlorochalcone (RACC) incorporated glycol chitosan (GC) nanoparticle transfection in osteosarcoma cells. MG-63 and Saos-2 osteosarcoma cells were transfected with various concentrations of RACC-incorporated GC nanoparticle for 24 h. The effect on cell proliferation, Ezh2 expression, apoptosis, cell cycle arrest, cell migration and invasiveness, Akt phosphorylation and local tumour growth and metastases were studied. Results: MG-63 and Saos-2 osteosarcoma cells on RACC-incorporated GC nanoparticle transfection for 24 h showed a concentration-dependent inhibition of cell proliferation. Of the various concentrations of RACC tested, the effective concentration started from 5 μM with an IC50 of 20 μM. Wound healing assay also showed that RACC-incorporated GC nanoparticles inhibited migration of tumor cells more effectively compared to the parent RA. RACC transfection resulted in inhibition of cell proliferation, Ezh2 expression inhibition, apoptosis through mitochondrial pathway by decrease in membrane potential and release of cytochrome c and cell cycle arrest in the G0/G1 phase. The invasiveness of cells treated with 5 and 20 μM RACC was decreased by 49 and 76 % respectively, compared to the control. RACC-treated mice showed significantly lower number of metastases compared to that in the control mice. Conclusions: Thus, RACC-incorporated glycol chitosan nanoparticle strategy can be promising for the treatment of osteosarcoma. [ABSTRACT FROM AUTHOR]

Superconductivity in cuprate superconductors occurs upon charge-carrier doping Mott insulators, where a central question is what mechanism causes the loss of electrical resistance below the superconducting (SC) transition temperature? In this paper, we attempt to summarize the basic idea of the kinetic-energy-driven SC mechanism in the description of superconductivity in cuprate superconductors. The mechanism of the kinetic-energy-driven superconductivity is purely electronic without phonons, where the charge-carrier pairing interaction in the particle-particle channel arises directly from the kinetic energy by the exchange of spin excitations in the higher powers of the doping concentration. This kinetic-energy-driven d-wave SC-state is controlled by both the SC gap and quasiparticle coherence, which leads to that the maximal SC transition temperature occurs around the optimal doping, and then decreases in both the underdoped and overdoped regimes. In particular, the same charge-carrier interaction mediated by spin excitations that induces the SC-state in the particle-particle channel also generates the normal-state pseudogap state in the particle-hole channel. The normal-state pseudogap crossover temperature is much larger than the SC transition temperature in the underdoped and optimally doped regimes, and then monotonically decreases upon the increase of doping, eventually disappearing together with superconductivity at the end of the SC dome. This kinetic-energy-driven SC mechanism also indicates that the strong electron correlation favors superconductivity, since the main ingredient is identified into a charge-carrier pairing mechanism not from the external degree of freedom such as the phonon but rather solely from the internal spin degree of freedom of the electron. The typical properties of cuprate superconductors discussed within the framework of the kinetic-energy-driven SC mechanism are also reviewed. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma is the most common of all the bone malignancies and accounts for 30-80 % of the primary skeletal sarcomas. The overall survival rate of patients with osteosarcoma is < 20 % suggesting poor prognosis. Methods: The present study demonstrates the effect of retinoic acid chlorochalcone (RACC) incorporated glycol chitosan (GC) nanoparticle transfection in osteosarcoma cells. MG-63 and Saos-2 osteosarcoma cells were transfected with various concentrations of RACC-incorporated GC nanoparticle for 24 h. The effect on cell proliferation, Ezh2 expression, apoptosis, cell cycle arrest, cell migration and invasiveness, Akt phosphorylation and local tumour growth and metastases were studied. Results: MG-63 and Saos-2 osteosarcoma cells on RACC-incorporated GC nanoparticle transfection for 24 h showed a concentration-dependent inhibition of cell proliferation. Of the various concentrations of RACC tested, the effective concentration started from 5 μM with an IC50 of 20 μM. Wound healing assay also showed that RACC-incorporated GC nanoparticles inhibited migration of tumor cells more effectively compared to the parent RA. RACC transfection resulted in inhibition of cell proliferation, Ezh2 expression inhibition, apoptosis through mitochondrial pathway by decrease in membrane potential and release of cytochrome c and cell cycle arrest in the G0/G1 phase. The invasiveness of cells treated with 5 and 20 μM RACC was decreased by 49 and 76 % respectively, compared to the control. RACC-treated mice showed significantly lower number of metastases compared to that in the control mice. Conclusions: Thus, RACC-incorporated glycol chitosan nanoparticle strategy can be promising for the treatment of osteosarcoma. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by memory loss and disordered cognition. Women have a higher AD incidence than men, indicating that the declining estrogen levels during menopause may influence AD pathogenesis. However, the mechanism underlying estrogen's neuroprotective effect is not fully clarified and is complicated by the presence of several distinct estrogen receptor (ER) types and the identification of a growing number of ER splice variants. Thus, a deeper analysis of ERs could elucidate the role of estrogen in age-related cognitive changes. Intracellular calcium signaling cascades play a pivotal role in ERα neuroprotection against AD. The ERα-mediated inhibition of Death domain-associated protein (Daxx) translocation and the combination of membrane ERα and caveolin in caveolae may protect against AD. Moreover, the voltage-dependent anion channel (VDAC)/ERα association may be important for maintaining channel inactivation and may be relevant in neuronal preservation against Aβ injury. Additionally, ERα may prevent glutamate excitotoxic injury by Aβ through estrogen signaling mechanisms. ERα and IGF-IR co-activation may mediate neuroprotection, and many other growth factors and intracellular signaling responses triggered by ERα may also play important roles in this process. Furthermore, details regarding the genes and mRNA variants of ERα that are expressed in different parts of the human organs have been clarified recently. Therefore, here we review the literature to clarify the neuroprotective role of ERα. This review focuses on the potential mechanisms mediated by ERα in the intracellular signaling events in nervous system cells, thereby clarifying ERα-mediated protection against AD. [ABSTRACT FROM AUTHOR]

Within the framework of the kinetic energy driven superconducting mechanism, the dynamical spin response of cuprate superconductors is studied from low-energy to high-energy. The spin self-energy is evaluated explicitly in terms of the collective charge carrier modes in the particle–hole and particle–particle channels, and employed to calculate the dynamical spin structure factor. Our results show the existence of damped but well-defined dispersive spin excitations in the whole doping phase diagram. In particular, the low-energy spin excitations in the superconducting-state have an hour-glass-shaped dispersion, with commensurate resonance that appears in the superconducting-state only , while the low-energy incommensurate spin fluctuations can persist into the normal-state. The high-energy spin excitations in the superconducting-state on the other hand retain roughly constant energy as a function of doping, with spectral weights and dispersion relations comparable to those in the corresponding normal-state. The theory also shows that the unusual magnetic correlations in cuprate superconductors can be ascribed purely to the spin self-energy effects which arise directly from the charge carrier–spin interaction in the kinetic energy of the system. [ABSTRACT FROM AUTHOR]

Aims To explore the risk of subsequent ischemic events in type 2 diabetes mellitus (DM) patients who had lower extremity amputations (LEAs) were compared with DM patients without LEAs. Methods A population-based cohort study was conducted utilizing the data of 2011 patients with newly diagnosed DM with and without LEAs sourced from the Longitudinal Health Insurance Database 2000 (LHID 2000) of the Taiwan National Health Insurance (NHI) program between 1996 and 2008. Main outcome measures Relative risks (RRs), hazard ratios (HRs), and disease-free rates for various ischemic events. Results In contrast with the comparison group, subjects with LEAs were more likely to reside in less urbanized areas, be white collar workers, and have higher DM-related costs ( p < 0.05). Subjects with LEAs also had significantly higher risks of developing ischemic diseases, except intestinal ischemia. In the multivariate Cox proportional hazards regression model analysis, the HR of end-stage renal disease (ESRD) was highest (HR = 3.91, 95% CI = 2.38–6.42), followed by embolism and thrombosis (HR = 3.47, 95% CI = 2.12–5.67), other peripheral vascular diseases (HR = 3.11, 95% CI = 2.11–4.57), atherosclerosis (HR = 2.64, 95% CI = 1.60–4.35), retinopathy (HR = 2.24, 95% CI = 1.79–2.80), cerebral ischemia (HR = 1.61, 95% CI = 1.25–2.06), and coronary artery disease (HR = 1.44, 95% CI = 1.18–1.74). Conclusions DM patients with LEAs had significantly higher risks for subsequent ischemic events, particularly among men. The greatest risk detected among DM patients with LEA's was for end-stage renal disease. Disease free survival rates also indicated that the course of generalized DM ischemia proceeded despite treatment. [ABSTRACT FROM AUTHOR]

Thediscovery and synthesis of a new series of pyrimidines as potentsigma-1 receptor (σ1R) antagonists, associated withpharmacological antineuropathic pain activity, are the focus of thisarticle. The new compounds were evaluated in vitro in σ-1 andσ-2 receptor binding assays. The nature of the pyrimidine scaffoldwas crucial for activity, and a basic amine was shown to be necessaryaccording to the known pharmacophoric model. The most promising derivativewas 5-chloro-2-(4-chlorophenyl)-4-methyl-6-(3-(piperidin-1-yl)propoxy)pyrimidine(137), which exhibited a high binding affinity to σ1R receptor (Kiσ1= 1.06 nM) and good σ-1/2 selectivity (1344-fold). In in vivotests, compound 137exerted dose-dependent antinociceptiveeffects in mice formalin model and rats CCI models of neuropathicpain. In addition, no motor impairments were found in rotarod tests;acceptable pharmacokinetic properties were also noted. These datasuggest compound 137may constitute a novel class ofdrugs for the treatment of neuropathic pain. [ABSTRACT FROM AUTHOR]

Glutamate is the most abundant excitatory brain neurotransmitter that has important functional significance with respect to neurodegenerative conditions. Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer's disease (AD) has been gradually becoming elucidated recently. Excessive release of glutamate induces an increase in intracellular Ca levels, thus triggers a cascade of cellular responses, ultimately leading to neuronal cell death. This type of neuronal damage induced by over-excitation has been proposed to be involved in a number of neuropathological conditions, ranging from acute insults to chronic neurodegenerative disorders. Estrogen could be effective in modulating glutamate-induced neurotoxicity and the protective responsivenesses are mostly estrogen receptors (ERs)-dependent. However, the mechanism underlying estrogen's neuroprotective effect is not fully clarified and is complicated by the presence of several distinct ER types. So a deeper research into the neuroprotection of ERs might be informative about the positive effect that estrogen might have on ageing-related cognitive changes. Extensive studies have indicated the neuroprotective effects of ERs against glutamate-induced neurotoxicity. The purpose of this review is to elucidate ERs' neuroprotective effects against glutamate-induced cytotoxicity and explore new ways to prevent and cure neurotoxicity-associated neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

The Patient-Reported Outcomes Measurement Information System (PROMIS®) is an NIH Roadmap initiative devoted to developing better measurement tools for assessing constructs relevant to the clinical investigation and treatment of all diseases—constructs such as pain, fatigue, emotional distress, sleep, physical functioning, and social participation. Following creation of item banks for these constructs, our priority has been to validate them, most often in short-term observational studies. We report here on a three-month prospective observational study with depressed outpatients in the early stages of a new treatment episode (with assessments at intake, one-month follow-up, and three-month follow-up). The protocol was designed to compare the psychometric properties of the PROMIS depression item bank (administered as a computerized adaptive test, CAT) with two legacy self-report instruments: the Center for Epidemiological Studies Depression scale (CESD; Radloff, 1977) and the Patient Health Questionnaire (PHQ-9; Spitzer et al., 1999). PROMIS depression demonstrated strong convergent validity with the CESD and the PHQ-9 (with correlations in a range from .72 to .84 across all time points), as well as responsiveness to change when characterizing symptom severity in a clinical outpatient sample. Identification of patients as "recovered" varied across the measures, with the PHQ-9 being the most conservative. The use of calibrations based on models from item response theory (IRT) provides advantages for PROMIS depression both psychometrically (creating the possibility of adaptive testing, providing a broader effective range of measurement, and generating greater precision) and practically (these psychometric advantages can be achieved with fewer items—a median of 4 items administered by CAT—resulting in less patient burden). [ABSTRACT FROM AUTHOR]

Estrogens contribute to the development and growth of the prostate and are implicated in prostate tumorigenesis. In their target tissues, estrogens mediate their effects via estrogen receptor ɑ (ERɑ (ESR1)) and β (ERβ (ESR2)). Hyperplasia and decreased differentiation of epithelial cells in the prostate have been reported in ERβ knockout (BERKO) mice. Herein, we studied the effect of ERβ deficiency on prostate tumorigenesis by crossing BERKOFVB mice with prostate-targeted human fibroblast growth factor 8b transgenic (FGF8b-Tg) mice. Consistent with results described in our previous report, the prostates of 1-year-old FGF8b-Tg mice displayed stromal aberrations, prostatic intraepithelial neoplasia (mPIN) lesions, inflammation, and occasionally cancer. The prostates of BERKOFVB mice exhibited mild epithelial hypercellularity and inflammation. The prostate phenotypes of FGF8b-Tg-BERKOFVB mice closely resembled those of FGF8b-Tg mice. However, mucinous metaplasia, indicated by Goblet-like cells in the epithelium, was significantly more frequent in the prostates of FGF8b-Tg-BERKOFVB mice when compared with FGF8b-Tg mice. Furthermore, compared with FGF8b-Tg mice, there was a tendency for increased frequency of inflammation but milder hyperplasias in the prostate stroma of FGF8b-Tg-BERKOFVB mice. The expression levels of mRNAs for FGF8b-regulated genes including osteopontin (Spp1), connective tissue growth factor (Ctgf), fibroblast growth factor receptors (Fgfrs), and steroid hormone receptors and cytokines were similar in the prostates of FGF8b-Tg and FGF8b-Tg-BERKOFVB mice. Our results indicate that ERβ plays a role in the differentiation of the prostatic epithelium and, potentially, in the defensive mechanism required for protection against inflammation but do not support a direct tumor-suppressive function of ERβ in the prostate of FGF8b-Tg mice. [ABSTRACT FROM AUTHOR]

Thermosensitive cationic magnetic liposomes (TCMLs), prepared from dipalmitoylphosphatidylcholine (DPPC), cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)]-2000, and didodecyldimethylammonium bromide (DDAB) were used in this study for the controlled release of drug/gene for cancer treatment. After co-entrapping citric-acid-coated magnetic nanoparticles (MNPs) and the chemotherapeutic drug irinotecan (CPT-11) in the core of TCML (TCML@CPT-11), SLP2 shRNA plasmids were complexed with DDAB in the lipid bilayer to prepare TCML@CPT-11/shRNA with a 135.6 ± 2.1 nm diameter. As DPPC has a melting temperature slightly above the physiological temperature, drug release from the liposomes can be triggered by an increase in solution temperature or by magneto-heating induced with an alternating magnetic field (AMF). The MNPs in the liposomes also endow the TCMLs with magnetically targeted drug delivery with guidance by a magnetic field. The successful preparation of drug-loaded liposomes was confirmed by various physical and chemical methods. Enhanced drug release, from 18% to 59%, at pH 7.4 was observed when raising the temperature from 37 to 43 °C, as well as during induction with an AMF. The in vitro cell culture experiments endorse the biocompatibility of TCMLs, whereas TCML@CPT-11 shows some enhancement of cytotoxicity toward U87 human glioblastoma cells when compared with free CPT-11. The U87 cells can be transfected with the SLP2 shRNA plasmids with very high efficiency (~100%), leading to silencing of the SLP2 gene and reducing the migration ability of U87 from 63% to 24% in a wound-healing assay. Finally, an in vivo study, using subcutaneously implanted U87 xenografts in nude mice, demonstrates that the intravenous injection of TCML@CPT11-shRNA, plus magnetic guidance and AMF treatment, can provide a safe and promising therapeutic modality for glioblastoma treatment. [ABSTRACT FROM AUTHOR]

Vanadium pentoxide can undergo a reversible phase transition by heating above 260 °C; its non-thermal phase transition, as well as ultrafast dynamical processes, is still not known. Here, femtosecond laser-induced phase transition properties in V2O5 thin films were first explored using femtosecond time-resolved pump–probe spectroscopy. The results show that the phase transient processes occur on a 10−15–10−13 temporal scale. The phase transition and recovery properties are dependent on both the substrates and pump laser energy densities. We propose the oxygen vacancies theory to explain the results, and we provide valuable insights into V2O5 films for potential applications. [ABSTRACT FROM AUTHOR]

Abstract: The synthesis and sigma-1 receptor (σ 1R) antagonist activity of a new series of 3,4-dihydro-2(1H)-quinolinone derivatives are reported. The new compounds were evaluated in vitro in sigma-1 and sigma-2 receptor-binding assays in guinea pig brain membranes. The structure–activity relationship led us to the promising derivative 7-(3-(piperidin-1-yl)propoxy)-1-(4-fluorobenzyl)-3,4-dihydro-2(1H)-quinolinone (35). The compounds with highest affinity and greatest selectivity were further profiled, and compound 35 had a high binding constant for sigma-1 receptor (K i σ 1 = 1.22 nM) and high sigma-1/2 selectivity (1066-fold). Thus, compound 35, which proved to be an antagonist of sigma-1 receptor, emerged as the most interesting candidate. In addition, compound 35 exerted dose-dependent anti-nociceptive effects in the formalin test. These characteristics suggested that the potent and selective compound 35 could be a potent candidate for pain treatment. [Copyright &y& Elsevier]

Background Microtubule-associated protein tau (MAPT) is a neuronal protein involved in the pathogenesis of several neurodegenerative diseases including Parkinson's Disease (PD). Glycogen synthase kinase 3 beta (GSK3B) catalyzes phosphorylation in multiple sites of tau protein. However, whether or not there is any association between the GSK3B gene alteration, MAPT haplotype and PD remains unexplored in Chinese population, especially in central Chinese population. Results Here, we aimed at studying the effect of MAPT rs242562 and GSK3B rs334558 on the risk of PD by performing a case-control association study in central China. Our data showed that all PD patients and controls were of MAPT H1/H1 diplotype in our study, thus confirming that the distribution of the MAPT H1 haplotype is common in China. GG genotype of MAPT rs242562 serves protection effect on PD risk in central Chinese population, while genotype of GSK3B rs334558 showed no difference between PD patients and controls. Conclusions We conclude that the MAPT rs242562 is associated with PD in central China in the background of MAPT H1/H1 diplotype. The GG genotype of rs242562 displays protection against PD in subgroup with GSK3B rs334558 T carrier. [ABSTRACT FROM AUTHOR]

Background Presently, CD133 is one of the hottest markers to characterize cancer stem cells and KAI1/CD82 is reported as an important marker for the metastasis and prognosis of many cancers. The purpose of our study is to explore the relationship between cancer stem cells (CSCs) marked by CD133 and KAI1/CD82 expression and the clinicopathological characteristics of patients with laryngeal squamous cell carcinoma (LSCC). Methods Immunohistochemical analysis was used to detect the expression of CD133 and KAI1/CD82 in 83 archival surgical specimens of human LSCC and 83 cases of normal laryngeal tissues. Results In LSCC, positive rates of 49.4% and 41.0% were obtained for CD133 and KAI1/CD82, respectively. The expression of CD133 in LSCC tissues was significantly higher than that in normal tissues (P < 0.001), and the expression of CD133 was positively associated with pTNM stage (P = 0.005), pathological grade (P = 0.001), and lymph node metastasis (P < 0.001). The reduced expression of KAI1/CD82 was present in LSCC tissues. The positive rate of KAI1/CD82 expression was negatively correlated with pTNM stage (P = 0.014), pathological grade (P < 0.001), and lymph node metastasis (P = 0.007). A correlation analysis showed that there was a negative relationship between the expression of CD133 and KAI1/CD82 protein in LSCC tissues (P < 0.001). By Kaplan-Meier analysis, the expression of CD133 was negatively correlated with overall survival (OS) (log-rank = 40.949, P < 0.001) and disease-free survival (DFS) (log-rank = 39.307, P < 0.001) time of LSCC. The expression of KAI1/CD82 was positively correlated with OS (log-rank = 40.279, P < 0.001) and DFS (log-rank = 39.271, P < 0.001) time of LSCC. Cox regression analysis: the expression of CD133 and KAI1/CD82, and pTNM stages were independent prognostic factors of LSCC (P < 0.05). Conclusions Thus the detection of CD133 and KAI1/CD82 proteins may be used as a potential indicator of LSCC prognosis. [ABSTRACT FROM AUTHOR]

Abstract: In this paper, we report the synthesis of novel, potential antipsychotic coumarin derivatives combining potent dopamine D2, D3 and serotonin 5-HT1A, 5-HT2A receptors properties. We describe the structure activity relationship that leads us to the promising derivative: 7-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)butoxy)-6-methyl-2,3-dihydrocyclopenta[c]chromen-4(1H)-one 27. The unique pharmacological features of compound 27 are a high affinity for dopamine D2, D3 and serotonin 5-HT1A, 5-HT2A receptors, together with a low affinity for H1 receptor (to reduce the risk of obesity under chronic treatment). In animal models, compound 27 inhibited apomorphine-induced climbing and MK-801-induced hyperactivity without observable catalepsy at the highest dose tested. In particular, compound 27 was more potent than clozapine. [Copyright &y& Elsevier]

Highlights: [•] Integrated networks of Bmp, Fgf, Shh, and Wnt pathways regulate tooth organogenesis. [•] Increased activity of Fgf, Shh, or Wnt signaling revitalizes mouse vestigial teeth. [•] Bmp4–Msx1 positive feedback loop drives expansion of tooth developmental field. [•] Osr2 patterns odontogenic mesenchyme along buccolingual and anteroposterior axes. [•] The Wnt–Shh and Bmp–Sostdc1 negative feedback loops regulate spatial tooth patterning. [ABSTRACT FROM AUTHOR]

With the continuous development of cloud computing, the virtual desktop solution becomes increasingly mature and the desktop virtualization becomes a typical cloud computing application. Virtual desktop technology can effectively solve those problems when using traditional personal computers and also reduce maintenance costs, which draws industries' attentions. As an open source desktop delivery protocol, SPICE has its own unique architecture and characteristics. Using SPICE protocol, virtual desktops can be deployed between servers and remote terminal clients with good quality of user experiences. However, SPICE protocol has its own drawbacks, and it is not suitable for low-bandwidth networks. Virtual desktop technology is introduced and the theories of virtual desktop delivery protocols as well as factors that affect virtual desktop performances are analyzed. Based on the analysis, the architecture of SPICE virtual desktop solution and its core technology are further analyzed. Finally the drawbacks of SPICE protocol are pointed out and some improvements methods without affecting QoE are proposed, which will play a guide role for the development of virtual desktop technology. [ABSTRACT FROM AUTHOR]

We investigate the phase relationship between grouped solar flares (GSFs) and sunspot numbers (SNs) during the time interval from 1965 January to 2008 June. It is found that, (1) from a global point of view, GSFs lead SNs in phase during solar cycles 20, 22 & 23, while the former lags behind the latter in solar cycle 21; (2) the phase relationship between them is not only time-dependent but also frequency-dependent. This implies that their relationship is a complex nonlinear relationship, although they are highly correlated with each other [ABSTRACT FROM AUTHOR]

Abstract: The interplay between the superconducting gap and normal-state pseudogap in the bilayer cuprate superconductors is studied based on the kinetic energy driven superconducting mechanism. It is shown that the charge carrier interaction directly from the interlayer coherent hopping in the kinetic energy by exchanging spin excitations does not provide the contribution to the normal-state pseudogap in the particle–hole channel and superconducting gap in the particle–particle channel, while only the charge carrier interaction directly from the intralayer hopping in the kinetic energy by exchanging spin excitations induces the normal-state pseudogap in the particle–hole channel and superconducting gap in the particle–particle channel, and then the two-gap behavior is a universal feature for the single layer and bilayer cuprate superconductors. [Copyright &y& Elsevier]

Background: Hantaviruses cause acute hemorrhagic fever with renal syndrome (HFRS). Currently, several types of inactivated HFRS vaccines are widely used, however the limited ability of these immunogen to elicit neutralizing antibodies restricts vaccine efficacy. Development of an effective vaccine to overcome this weakness is must. Methods: In the present study, a recombinant pseudotyped lentivirus bearing the hantaan virus (HTNV) envelope glycoproteins (GP), rLV-M, was constructed. C57BL/6 mice were immunized with the rLV-M and a series of immunological assays were conducted to determine the immunogenicity of the recombinant pseudotyped lentivirus. The humoral and cell-mediated immune responses induced by rLV-M were compared with those of the inactivated HFRS vaccine. Results: Indirect immunofluorescence assay (IFA) showed the rLV-M expressed target proteins in HEK-293cells. In mice, the rLV-M efficiently induced GP-specific humoral responses and protection against HTNV infection. Furthermore, the rLV-M induced higher neutralizing antibody titers than the inactivated HFRS vaccine control. Conclusions: The results indicated the potential of using a pseudotyped lentivirus as a delivery vector for a hantavirus vaccine immunogen. [ABSTRACT FROM AUTHOR]

Highlights: [•] Influenza A/pdmH1N1 virus prevalence peak occurred in November 2009, but sharply dropped in February 2010 in Taiwan. [•] NJ and ML phylogenetic trees showed 11 unique clusters of influenza A/pdmH1N1, A/H3N2 and B viruses in Taiwan. [•] Phylogenetic evidence indicated multiple independent clades of co-circulating influenza A and B strains in Taiwan. [ABSTRACT FROM AUTHOR]