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Four new series of bis-(1,3,4-oxadiazoles) 1a – c and tris-(1,3,4-oxadiazoles) 1d containing peripheral quinoxalines were prepared and their mesomorphic behavior was reported. Except for compound 1c ( n =12), all other compounds 1a – d formed columnar phases which were confirmed by powder X-ray diffractometer (XRD). Compounds 1d have the highest clearing temperatures and the widest temperature range of columnar phases than those of other compounds 1a – b . Compounds 1d exhibited a phase crossover between the rectangular and hexagonal columnar phases. A value of N cell =2.85 and 2.16 A within a column slice of 9.0 A thick was obtained for compound 1a ( n =12) and 1d ( n =12), indicating that two molecule was correlated within columns in columnar phases. All compounds 1a – d ( n =12) showed good stabilities at temperature below T dec =412.5–420.8 °C on thermogravimetric analysis. The PL spectra of all compounds 1a – d ( n =12) showed one intense peak at λ max =517–520 nm, and these photoluminescent emissions originated from peripheral quinoxaline moiety.

This study analyzes the role of corporate governance in the relationship among credit, interest rate, and liquidity risks encountered by banks. In particular, the study investigates how banks make the trade-offs among these risks under the maturity transformation business model. The sample consists of banks in 43 countries over the period of 2002–2010. Results show that credit, interest rate, and liquidity risks are related to one another, and that the interactions among them can be reduced by corporate governance and regulations. During the regular yield curve spread (YCS) period, management-controlled banks take less credit risk and even less liquidity risk whereas shareholder-controlled banks encounter more liquidity risk as they pursue more interest rate risk. During the inverted YCS period, management-controlled banks still opt for less credit risk-taking, but shareholder-controlled banks are greatly exposed to risks and should thus be monitored by concerned authorities.

Over the past decade, deep convolutional neural networks (CNN) have been widely embraced in various visual recognition applications owing to their extraordinary accuracy. However, their high computational complexity and excessive data storage present two challenges when designing CNN hardware. In this paper, we propose an energy-aware bit-serial streaming deep CNN accelerator to tackle these challenges. Using ring streaming dataflow and the output reuse strategy to decrease data access, the amount of external DRAM access for the convolutional layers is reduced by 357.26x when compared with that of no output reuse case on AlexNet. We optimize the hardware utilization and avoid unnecessary computations using the loop tiling technique and by mapping the strides of the convolutional layers to unit-ones for computational performance enhancement. In addition, the bit-serial processing element (PE) is designed to use fewer bits in weights, which can reduce both the amount of computation and external memory access. We evaluate our design using the well-known roofline model. The design space is explored to find the solution with the best computational performance and communication to computation (CTC) ratio. We can reach 1.36x speed and reduce energy consumption by 41% for external memory access compared with the design in [1]. The hardware implementation for our PE Array architecture design can reach an operating frequency of 119 MHz and consumes 68 k gates with a power consumption of 10.08 mW using TSMC 90-nm technology. Compared to the 15.4 MB external memory access for Eyeriss [2] on the convolutional layers of AlexNet, our method only requires 4.36 MB of external memory access to dramatically reduce the costliest portion of power consumption.

This paper demonstrates nanoscale infrared thermal imaging in electrically biased bilayer graphene (BLG) by using a scattering-type scanning near-field optical microscope (s-SNOM). s-SNOM provides a noncontact technique to detect the thermally excited electromagnetic evanescent fields (~21 THz) generated on the surface of a Joule-heated BLG. With increasing bias current, a strong near-field signal appears mainly in the sub-micrometer-sized constricted region. The temperature mapping of the graphene film can be derived from the infrared near-field signals, and shows good agreement with the finite-element simulation. Hence, we prove that s-SNOM is a potential infrared nano-thermography for the graphene device.

Molecular-dipole-induced surface-enhanced Raman scattering (SERS) has attracted a lot of attention due to its high sensitivity without the need for noble metals. However, its main mechanisms are still unclear. In this work, functional-group-rich graphene oxide (GO)/ZnO (GZ) films are fabricated as SERS platforms. A maximum enhancement factor of 70,000 is achieved by manipulating the chain reactions between the functional groups and ZnO under various annealing conditions. The electronic structures of the GZ composite films, characterized using ultraviolet photoelectron spectroscopy, indicate that the high sensitivity arises from molecular dipole interactions rather than photoinduced charge transfer. Electrostatic force microscopy images show that the amount and spatial uniformity of molecular dipoles on GZ are both significantly improved when appropriate heat treatment is employed, leading to a tremendous 43-fold sensitivity improvement compared to that of pristine GO. Stability tests demonstrate great retention of the dipole-induced enhancement, up to 87%, after more than six months of aging in the dark. The excellent sensitivity, uniformity, and stability make the GZ composite film an excellent SERS platform for practical applications in molecular identification and chemical sensing.

All material surfaces are covered with strong infrared/terahertz (IR/THz) evanescent waves since all materials contain positive and negative charges and the charge movement generates local electromagnetic waves at finite temperature. Previous theoretical analyses suggest that the thermal evanescent waves on metals and dielectrics are strongly localized within 100 nm from the surface, the energy density is more than 10000 times higher than the one of Planck’s radiation and their spectra lie in THz regions (wavelength: 8～20 μm). Probing such spontaneous evanescent waves with nanoscale spatial resolution can visualize the local dynamics of thermal equilibrium and non-equilibrium phenomena. Recently we have developed a passive scanning near-field optical microscope (SNOM), which probes surface evanescent waves without any external illumination. The microscope consists of a confocal infrared microscope, and an ultra-highly sensitive detector, named the charge-sensitive infrared phototransistor (CSIP, wavelength range is 14.5 ± 0.7 μm). In this presentation, we first describe the development of the passive SNOM. Then we show the results obtained with the SNOM; thermal evanescent waves on metals and dielectrics, and nanoscale distribution of evanescent waves derived from non-equilibrium phenomena in two dimensional electron gas. Our SNOM should open up a new way of investigating material surfaces in general and provide a novel technique of probing local temperature/electro-magnetic field distribution.

Two new series of mesogenic palladium complexes 1a–b derived from salicylaldimines containing phenyl or naphenyl moiety were prepared, characterized and their mesomorphic properties investigated. Two single crystallographic structures of mesogenic 1a (n=4) and nonmesogenic 1b (n=3) were determined by X-ray analysis; both crystals crystallize in a triclinic space group P1. The geometry at both palladium atoms was nearly square planar. All Schiff bases 2a–b and palladium complexes 1a–b exhibited mesomorphic properties. However, the formation of mesophases was sensitive to terminal naphthalyl and phenyl group. Compounds 2a formed N or/and SmC phases and compounds 2b exhibited N or/and SmC phases. In contrast, palladium complexes 1a formed N or N/SmC phases and complexes 1b exhibited N, N or/and SmC phases. Compounds 1b have a higher clearing temperature than those of 1a by a ΔTcl=35.4−14.8 °C. An improved mesomorphic behavior observed in compounds 1b was attributed to the H-bonds and π–π interaction.

Changes in fuel characteristics and design of diesel engines have been applied in the last decades to reduce pollutant emissions in the transportation sector. Characteristics of exhaust particles and their environmental impacts need to be brought up to date. In this study, diesel and rapeseed oil were used in modern internal combustion engines (BMW and John Deere) in order to simulate stationary and transient non-road driving conditions, with attention on fouling processes in the exhaust system and contributions to atmospheric pollution. Engine particulate exhaust samples were subjected to individual particle analysis and bulk physico-chemical characterization with respect to polycyclic aromatics, water-soluble organic carbon and inorganic ions. Functionalities of alkanes and oxygen-containing compounds were determined in the exhaust particles. The emitted particles with similar morphology and composition were separated in specific groups, revealing the exhaust microstructure. In-depth characterization of individual particle composition provided insights into the relationship of chemical composition and hygroscopicity, based on fractionation analysis. With improved characterization of diesel/biofuel combustion emissions we demonstrate that the multicomponent composition of modern internal combustion engine exhaust is impacted by both fuel properties and operation conditions.

Justicidin A (JA), a novel arylnaphthalide lignan, was previously found to reduce the growth of human hepatocellular carcinoma cells (HCC), Hep 3B cells, in NOD-SCID mice via induction of apoptosis. Here, using L1000 microarray profiling obtained from JA-treated HCC cells, the z-score signatures of JA exhibited positive connectivity to known autophagy inducers among 3122 compounds from the Library of Integrated Network-based Cellular Signatures database. JA-induced autophagy in HCC Hep 3B cells was confirmed by formation of acidic vesicular organelles and an increase in the expression of LC3-II and LAMP2a. JA-induced autophagic flux was demonstrated by accumulation of LC3-II and LAMP2a, as well as a decrease in colocalization of LC3 and LAMP2a puncta in the presence of autophagy inhibitor bafilomycin A1. Administration of bafilomycin A1 also demonstrated that JA-induced autophagy suppressed apoptosis. Activation of Ras/MEK/ERK pathway was observed. Following administration of apoptosis inhibitor zVAD, it was found that JA-induced apoptosis did not affect JA-induced autophagy. It is noteworthy that addition of JA promoted chemosensitivity of sorafenib, the only FDA-approved targeted therapy for advanced HCC. The results demonstrate the effectiveness of this novel strategy for rapid discovery of molecular actions of small molecules and suggest the applications of JA in HCC treatment.

Three new series of compounds 1a–c containing multiple heterocyclic 2,5-pyrazoles, 1,3,4-oxadiazole and thiophene exhibiting mesophases were reported. Crystallographic data showed that the crystal 1a (n=8) is a linear-shaped molecule with a molecular length of ca. 40.57 A. However, three heterocyclic rings were not coplanar. All compounds 1a formed smectic A/C phases, and all compounds 1c exhibited columnar phases, which were confirmed by powder X-ray diffractometer (XRD). A Ncell and Rar value equal to 3.91 and 18.29 A within a slice of 9.0 A thick were obtained for derivatives 1c (n=8), indicating that two molecule was correlated within columns in Colh phases. All derivatives showed good stabilities at temperature below T=383–426 °C on thermogravimetric analysis (TGA). The PL spectra of all compounds 1b–c (n=8) showed one intense peak at λmax=428–496 nm, and these photoluminescent emissions (PL) originated from 1,3,4-oxadiazole moiety.

// Hong-Jhih Jhuang 1, * , Wei-Hsiang Hsu 2, * , Kuan-Ting Lin 3 , Shih-Lan Hsu 4 , Feng-Sheng Wang 5 , Chen-Kung Chou 6 , Kuen-Haur Lee 8 , Ann-Ping Tsou 9 , Jin-Mei Lai 7 , Sheau-Farn Yeh 1 , Chi-Ying F. Huang 2, 3, 9 1 Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei, Taiwan 2 Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan 3 Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan 4 Department of Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan 5 Department of Chemical Engineering, National Chung Cheng University, Chiayi, Taiwan 6 Department of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan 7 Department of Life Science, Fu-Jen Catholic University, New Taipei City, Taiwan 8 Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan 9 Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan * These authors have contributed equally to this work Correspondence to: Jin-Mei Lai, e-mail: jmlai@mail.fju.edu.tw Sheau-Farn Yeh, e-mail: fyeh@ym.edu.tw Chi-Ying F. Huang, e-mail: cyhuang5@ym.edu.tw Keywords: Graptopetalum paraguayense, HBV, Gluconeogenesis, Lipogenesis, PGC-1α Received: November 04, 2014 Accepted: January 06, 2015 Published: February 03, 2015 ABSTRACT PGC-1α, a major metabolic regulator of gluconeogenesis and lipogenesis, is strongly induced to coactivate Hepatitis B virus (HBV) gene expression in the liver of fasting mice. We found that 8-Br-cAMP and glucocorticoids synergistically induce PGC-1α and its downstream targets, including PEPCK and G6Pase. Also, HBV core promoter activity was synergistically enhanced by 8-Br-cAMP and glucocorticoids. Graptopetalum paraguayense (GP), a herbal medicine, is commonly used in Taiwan to treat liver disorders. Partially purified fraction of GP (named HH-F3) suppressed 8-Br-cAMP/glucocorticoid-induced G6Pase, PEPCK and PGC-1α expression and suppressed HBV core promoter activity. HH-F3 blocked HBV core promoter activity via inhibition of PGC-1α expression. Ectopically expressed PGC-1α rescued HH-F3-inhibited HBV surface antigen expression, HBV mRNA production, core protein levels, and HBV replication. HH-F3 also inhibited fatty acid synthase (FASN) expression and decreased lipid accumulation by down-regulating PGC-1α. Thus, HH-F3 can inhibit HBV replication, gluconeogenesis and lipogenesis by down-regulating PGC-1α. Our study indicates that targeting PGC-1α may be a therapeutic strategy for treatment of HBV infections. HH-F3 may have potential use for the treatment of chronic hepatitis B patients with associated metabolic syndrome.

Pre-mRNA splicing can contribute to the switch of cell identity that occurs in carcinogenesis. Here, we analyze a large collection of RNA-seq data sets and report that splicing changes in hepatocyte-specific enzymes, such as AFMID and KHK, are associated with HCC patients’ survival and relapse. The switch of AFMID isoforms is an early event in HCC development and is associated with driver mutations in TP53 and ARID1A. The switch of AFMID isoforms is human-specific and not detectable in other species, including primates. Finally, we show that overexpression of the full-length AFMID isoform leads to a higher NAD+ level, lower DNA-damage response, and slower cell growth in HepG2 cells. The integrative analysis uncovered a mechanistic link between splicing switches, de novo NAD+ biosynthesis, driver mutations, and HCC recurrence.

Pre-mRNA splicing can contribute to the switch of cell identity that occurs in carcinogenesis. Here, we analyze a large collection of RNA-seq data sets and report that splicing changes in hepatocyte-specific enzymes, such as AFMID and KHK, are associated with HCC patients’ survival and relapse. The switch of AFMID isoforms is an early event in HCC development and is associated with driver mutations in TP53 and ARID1A. The switch of AFMID isoforms is human-specific and not detectable in other species, including primates. Finally, we show that overexpression of the full-length AFMID isoform leads to a higher NAD+ level, lower DNA-damage response, and slower cell growth in HepG2 cells. The integrative analysis uncovered a mechanistic link between splicing switches, de novo NAD+ biosynthesis, driver mutations, and HCC recurrence.

The nonreciprocal scattering of silicon nanoparticle on gold film is studied. The scattering cross section is simulated. When light oblique incidents from the air, it shows different spectra due to the different polarization of light. When light incidents from the gold film, the spectrum change less with the different polarization of light. In addition, a new peak appears because of the interference of the electric dipole and magnetic dipole.

Hypoxia signaling is an ancient pathway by which animals can respond to low oxygen. Malfunction of this pathway disturbs the hypoxic acclimation and results in various diseases, including cancers. The role of the hypoxia pathway in early embryogenesis remains unclear. Here, we show that in the sea urchin Strongylocentrotus purpuratus blastula, hypoxia-inducible factor α (HIFα), the downstream transcription factor of this pathway, is localized and transcriptionally active on the future dorsal side. This asymmetric distribution is attributable to its oxygen-sensing ability. Manipulations of the HIFα level entrained the dorsoventral axis, as the side with the higher level of HIFα tends to develop into the dorsal side. Gene expression analyses revealed that HIFα restricted the expression of nodal to the ventral side and activated several genes encoding transcription factors on the dorsal side. We also observed that intrinsic hypoxic signals in the early embryos formed a gradient, which was disrupted under hypoxic conditions. Our results present an unprecedented role of the hypoxia pathway in animal development.

Three new series of heterocyclic 1,3,4-oxa(thia)diazoles 1a – c were prepared and their mesomorphic behavior studied. All compounds 1a exhibited monotropic columnar phases, which were confirmed by powder XRD diffractometer. Compounds 1b were not mesogenic. The formation of columnar phases was sensitive to the substituent groups attached on the phenyl moiety; those with electron-donating groups (R=H, OCH 3 ) were not liquid crystals, in contrast, other derivatives with electron-withdrawing groups (R=F, NO 2 ) formed enantiotropic columnar phases. A N cell and R ar value equal to 4.73 and 20.20 A 2 of compound 1a ( n =16) within a slice of 9.0 A thick were obtained, indicating that two molecules was correlated to give a supplemental more disc-like molecule within columns. This is the first example, showing that the formation of columnar phases could be controlled by polar groups. The PL spectra of two compounds 1a – c showed one intense peak at λ max =505–511 nm, and these photoluminescent emissions originated from quinoxaline moiety.

Cancer is a complex disease that is strongly associated with defects in signal transduction pathways. A systematic understanding of signal transduction networks in cancer cells will make it possible to develop alternative therapeutic strategies. However, this understanding relies, at least in part, on the detection of endogenous protein–protein interactions (PPIs) that participate in these networks. The aim of this study is to find intervention strategies under the assumptions of inhibiting cell proliferation and activating cell apoptosis. We utilized 115 endogenous HeLa cell PPIs validated by in situ proximity ligation assay and information from on-line databases to reconstruct a cell-type specific signal transduction network. The CellNetAnalyzer were used to analyze the reconstructed network. The computational results from the minimal intervention set (MIS) showed that at least five proteins (AKT, DVL1, EGFR, IGF1R, and PDGFR) inhibited simultaneously in the reconstructed network were required for achieving the goals of drug interventions. By searching the IPA database, the proteins in the MIS, except DVL1, are single targets inhibited by clinic trial drugs to suppress cancer cells. The results suggest that a combination drug treatment may be more efficacious than a single-drug approach. Experiments should be carried out to validate the computational results in future research.

Three new series of catenar liquid crystals 1a – c derived from heterocyclic bisoxazoles and bisthiazoles exhibiting columnar phases were reported. All compounds 1a – c exhibited hexagonal columnar phases, which were confirmed by powder XRD diffractometer. Compounds 1a have a slightly wider temperature range of columnar phases than that of compounds 1b , which might be attributed to higher dipole polarized in 1a . A N cell and R ar value equal to 2.54–2.76 and 19.99–20.45 A 2 within a slice of 9.0 A thick were obtained for three derivatives 1a – c (all n s=12), indicating that a single molecule was packed within columns in Col h phases. All derivatives showed good stabilities at temperature below T =408 °C on TGA. The PL spectra of all compounds 1a – c showed one intense peak at λ max =505–510 nm, and these photoluminescent emissions originated from quinoxaline moiety.

In Taiwan, the hillside is about 70 % of total area. These areas also have steep topography and geological vulnerability. When an event of torrential rain comes during a typhoon, the landslide disasters usually occur at these areas due to the long duration and high intensity of rainfall. Therefore, a design which considers the potential landslide has become an important issue in Taiwan. In this study, a temporal characteristic of landslide fragility curve (LFC) was developed, based on the geomorphological and vegetation factors using landslides at the Chen-Yu-Lan watershed in Taiwan, during Typhoon Sinlaku (September 2008) and Typhoon Morakot (August 2009). This study addressed an effective landslide hazard assessment process, linking together the post-landslide damage and post-rainfall data for LFC model. The Kriging method was used to interpolate the rainfall indices (R 0, R, I) for numerical analysis. Remote sensing data from SPOT images were applied to analyze the landslide ratio and vegetation conditions. The 40-m digital elevation model was used for slope variation analysis in the watershed, and the maximum likelihood estimate was conducted to determine the mean and standard deviation parameters of the proposed empirical LFC model. This empirical model can express the probability of exceeding a damage state for a certain classification (or conditions) of landslides by considering a specific hazard index for a given event. Finally, the vulnerability functions can be used to assess the loss from landslides, and, in the future, to manage the risk of debris flow in the watershed.

Curcumin has been used as a traditional medicine and/or functional food in several cultures because of its health benefits including anticancer properties. However, poor oral bioavailability of curcumin has limited its oral usage as a food supplement and medical food. Here we formulated curcumin pellets using a solid dispersion technique. The pellets had the advantages of reduced particle size, improved water solubility, and particle porosity. This pellet form led to an improvement in curcumin&rsquo, s oral bioavailability. Additionally, we used the C-Map and Library of Integrated Network-Based Cellular Signatures (LINCS) Unified Environment (CLUE) gene expression database to determine the potential biological functions of formulated curcumin. The results indicated that, similar to conventional curcumin, the formulated curcumin acted as an NF-&kappa, B pathway inhibitor. Moreover, ConsensusPathDB database analysis was used to predict possible targets and it revealed that both forms of curcumin exhibit similar biological functions, including apoptosis. Biochemical characterization revealed that both the forms indeed induced apoptosis of hepatocellular carcinoma (HCC) cell lines. We concluded that the formulated curcumin increases the oral bioavailability in animals, and, as expected, retains characteristics similar to conventional curcumin at the cellular level. Our screening platform using big data not only confirms that both the forms of curcumin have similar mechanisms but also predicts the novel mechanism of the formulated curcumin.

Curcumin is a polyphenol derived from curcumin longa that exhibits anticancer and anti-inflammatory properties. The consumption of foods at supernutritional levels to obtain health benefits may paradoxically result in negative health outcomes. In the present study, multiple targeting characteristics of curcumin were analyzed using our gene expression screening system, which utilized the gene expression signatures of curcumin from human hepatocellular carcinoma and colorectal cancer cells to query gene expression databases and effectively identify the molecular actions of curcumin. In agreement with prediction, curcumin inhibited NF-&kappa, B and Aurora-A, and induced G2/M arrest and apoptosis. Curcumin-suppressed NF-&kappa, B was identified through inhibition of PLCG1, PIK3R1, and MALT1 in the CD4-T-cell-receptor-signaling NF-&kappa, B cascade pathway. The results suggest that our novel gene expression screening platform is an effective method of rapidly identifying unknown biological functions and side effects of compounds with potential nutraceutical benefits.

We systematically compare the active and the passive methods for infrared scattering-type scanning near-field optical microscopy (s-SNOM). The active SNOM makes use of IR lasers or incoherent thermal emitters to illuminate a sample, whereas the passive method directly measures extremely weak fluctuating electromagnetic evanescent fields spontaneously generated at the sample surface without any external illumination. For this reason, our specific version of the passive SNOM is called a scanning noise microscope (SNoiM). In thermal equilibrium, the two methods are shown to be similar, both mapping the nanoscale variation of the complex dielectric constant of the sample. We demonstrate that a significant difference between the two methods emerges when the sample is driven out of thermal equilibrium, viz., the active SNOM is insensitive whereas the SNoiM is extremely sensitive to the electron temperature in locally heated nanoregions.

Although alloying and heat treatments are common industrial practices to obtain ductile irons with desired mechanical properties, related information on how the two practices affect corrosion behavior is scarce. In this study, two ductile irons—with and without 1 wt pct copper addition—were austempered to obtain austempered ductile irons (ADIs). Polarization tests and salt spray tests were conducted to explore how both copper-alloying and austempering heat treatments influenced the corrosion behavior of ductile irons. The results showed that the corrosion resistance of 1 wt pct copper-alloyed ductile iron was better than that of the unalloyed one, while ADI had improved corrosion resistance compared with the as-cast. In particular, the ductile iron combined with the copper-alloying and austempering treatments increased the corrosion inhibition efficiency up to 84 pct as tested in 3.5 wt pct NaCl solution.

Two new series of unsymmetric 1,3,4-oxa(thia)diazoles 1a,b containing both quinoxaline and naphthalene moieties were prepared and their mesomorphic properties were investigated. The mesomorphic behavior of compounds 1a,b and 2 was studied by DSC analysis and polarized optical microscopy. All compounds 1a and 2 exhibited hexagonal columnar phases (Colh), which were also confirmed by powder XRD diffractometer. Ncell and Rar values equal to 5.23 and 22.73 A2 within a slice of 9.0 A thick were also obtained for 1a (n=16), indicating that a more disc-like structure constructed by two molecules lying side-by-side was correlated in Colh phases. In contrast, all compounds 1b were not mesogenic, and the lack of mesomorphic properties in 1b might be due to their unfavorable conformations. The PL spectra of all compounds 1a,b showed one intense peak at λmax=509–512 nm, and these photoluminescent emissions originated from quinoxaline moiety.

Deciphering the network of signaling pathways in cancer via protein-protein interactions (PPIs) at the cellular level is a promising approach but remains incomplete. We used an in situ proximity ligation assay to identify and quantify 67 endogenous PPIs among 21 interlinked pathways in two hepatocellular carcinoma (HCC) cells, Huh7 (minimally migratory cells) and Mahlavu (highly migratory cells). We then applied a differential network biology analysis and determined that the novel interaction, CRKL-FLT1, has a high centrality ranking, and the expression of this interaction is strongly correlated with the migratory ability of HCC and other cancer cell lines. Knockdown of CRKL and FLT1 in HCC cells leads to a decrease in cell migration via ERK signaling and the epithelial-mesenchymal transition process. Our immunohistochemical analysis shows high expression levels of the CRKL and CRKL-FLT1 pair that strongly correlate with reduced disease-free and overall survival in HCC patient samples, and a multivariate analysis further established CRKL and the CRKL-FLT1 as novel prognosis markers. This study demonstrated that functional exploration of a disease network with interlinked pathways via PPIs can be used to discover novel biomarkers.

The performance degradation of flattened heat pipes is studied experimentally under a horizontal orientation. The original cylindrical copper/water heat pipes are ϕ6 mm and 30 cm in length. Tested are the sintered-powder wick and the groove wick. The maximum heat load ( Q max ), the evaporator resistance ( R e ), the condenser resistance, the overall thermal resistance, and the longitudinal temperature distributions are measured under incremented heat loads. After flattening, R e is slightly reduced. Q max is hardly affected when only the evaporator is flattened; but it is greatly reduced for fully flattened heat pipes. Different mechanisms of performance degradation are observed for flattened powdered and grooved heat pipes. With a thicker wick and larger saturate charge, the main degradation mechanism of flattened powdered heat pipes is liquid clogging at the condenser end. This causes malfunction of a powdered heat pipe flattened to 2.5 mm. When flattened to 3 mm, the powdered heat pipe exhibits milder Q max degradation than a grooved heat pipe because the liquid flow is better protected against the vapor–liquid interfacial shear. In contrast, the serious Q max degradation of a flattened grooved heat pipe is mainly caused by the interfacial shear which leads to greatly prompted dryout at the evaporator.

A wideband (0.8–6 GHz) receiver front-end (RFE) utilizing a shunt resistive feedback low-noise amplifier (LNA) and a micromixer is realized in 90 nm CMOS technology for software-defined radio (SDR) applications. With the shunt resistive feedback and series inductive peaking, the proposed LNA is able to achieve a wideband frequency response in input matching, power gain and noise figure (NF). A micromixer down converts the radio signal and performs single-to-differential transition. Measurements show the conversion gain higher than 17 dB and input matching (S11) better than −7.3 dB from 0.8 to 6 GHz. The IIP3 ranges from −7 to −10 dBm, and the NF from 4.5 to 5.9 dB. This wideband receiver occupies 0.48 mm2 and consumes 13 mW.

Wu and Tsai proposed PVD (pixel-value differencing) data hiding method in 2003. PVD partitions a cover image into non-overlapping blocks of two consecutive pixels and calculated the difference value from the two pixels in each block. This method provides an easy way to produce a more imperceptible result. Afterwards, some scholars have proposed PVD-related improvements in image quality and embedding capacity. This paper classifies and discusses the recent PVD-based methods. We will compare each PVD related method in terms of the embedding capacity and PSNR.

Hypoxia signaling is an ancient pathway by which animals can respond to low oxygen. Malfunction of this pathway disturbs hypoxic acclimation and can result in various diseases, including cancers. The role of hypoxia signaling in early embryogenesis remains unclear. Here, we show that in the blastula of the sea urchin

The passive near-field microscope probes thermal evanescent waves derived from local dynamics on surfaces. Here we study dielectric samples, whose surface phonon resonances are close to the detection wavelength. GaAs and SiC show finite near-field signals due to thermal phonons, which decay rapidly from the surface. On the other hand, GaN and AlN show very unique characteristics, derived from phonon polaritons, with 14.2 and 11 μm, respectively. In this report, we show and discuss the results.

We have developed a passive THz s-SNOM (scattering-type scanning near-field optical microscope) equipped with a helium-free cryostat. The mechanical vibration from the compressor is reduced for accurately controlling the probe-sample distance. Besides, the confocal system with a solid immersion lens leads to gather higher signal-to-noise ratio. To demonstrate the capability of the s-SNOM, we measured the thermally excited surface evanescent wave on a Au/SiO 2 sample. Achieved SNR of the near-field signal on Au is 5.5 with a 0.1 s/pixel scan rate. These results show that the improved passive s-SNOM not only provides more convenient cooling process but also significantly speeds up the scan rate for the passive THz near-field image.

Electromagnetic (EM) evanescent waves generated on material surfaces without external illumination are of particular interest. If materials are in thermal equilibrium, thermal fluctuation of current and/or charge is induced by stochastic thermal motion of conduction electrons (in metals) or by thermally-activated lattice vibrations (in polar dielectrics), which generates intense thermal EM evanescent waves [1]. If materials are driven out of equilibrium, say, by electric-field-induced currents or by chemical reactions, even stronger EM evanescent waves are induced because the fluctuation of current and/or charge is promoted by activated motion of charge carriers or electric dipoles in non-equilibrium states. Hence, a sensitive passive microscopy of EM evanescent waves with nanometer resolution is expected to provide us with a unique and powerful probe to the local kinetics of material phenomena in equilibrium and non-equilibrium conditions. We have developed such microscopes as described in the above, by incorporating ultra-highly sensitive detectors, called CSIP [2], into passive terahertz (THz) scattering-type scanning near-field optical microscopes (s-SNOMs) [3]. Owing to the high sensitivity, detailed nature of the thermal EM evanescent waves has been clarified through quantitative analysis of imaging of both metals [4, 5] and dielectrics. The spatial resolution reaches a value about 20nm (λ/750) [6]. We also demonstrate the potentiality and powerfulness of our system for probing non-equilibrium kinetics: We show that current-induced hot-electron distribution in narrow metal wires at room temperature is clearly visualized with nanometer resolution. These results show that our systems will find broad application areas in the near future.

A compact low-power VCO in 0.18 μm CMOS technology is presented for V-band applications. Unlike conventional push-push VCOs using huge passive transmission-line-based frequency doublers to rise their output oscillation frequencies, the proposed VCO adopts a more compact transistor-based frequency doubler to reduce chip layout area. Under 1-V supply operation, experimental results show that the output power of VCO ranges from −13.5 dBm to −6.5 dBm over the V band of interest with low power dissipation from 6.3 mW to 16.1 mW excluding the output buffer. The measured phase noise is −93.12 dBc/Hz at 10MHz offset from 55 GHz carrier. This VCO only occupies a small chip layout area of 0.1 mm2 excluding pads and bypass capacitors.

Passive THz s-SNOM (scattering-type scanning near-field optical microscope) is a powerful tool, which can reveal the weak spontaneous radiation on a sample surface (e.g., Au, GaAs, or SiC) without external light source [1, 2]. In our passive s-SNOM, an extremely sensitive CSIP (charge-sensitive infrared phototransistor [3]) detector is necessary to be operated at low temperature less than 10 K. To cool down the CSIP more conveniently and to save the helium resource, we introduced a helium-free cryostat to the passive s-SNOM as shown in Fig. 1(a). Mechanical and helium gas dampers are used to attenuate the vibration from the cold head and the compressor [see Fig. 1(a)]. Furthermore, to get a better SNR for higher scan speed, we improved the confocal microscope as follows: (1) The solid immersion lens (SIL) is introduced to seal the CSIP. It can achieve smaller focusing spot on a sensing area of the CSIP to enlarge the number of the collected photon. (2) The metal-mirror type Cassegrain objective (N.A.: 0.4) whose thermal emission is almost zero. Fig. 1(b) shows that the smooth topography (upper panel) indicated that we have overcome the vibration problem. We have successfully observed the passive near-field signal on a Au stripe (lower panel). The SNR is derived to 5 with a scan speed of 100 ms per step.

Based on the exact non-Markovian master equation for two interacting two-level atoms coupled to a dissipative zero-temperature bonsonic environment, we extend the results of Tai [Phys. Rev. A 89, 062310 (2014)], in which optimal control approach is used to implement one-qubit gates within the same environment, to two-qubit gate implementations with the help of Krotov's iterative method for optimal control. Furthermore, for practical applications, the realization of a quantum circuit comprising cascaded quantum gates is considered.

A 2.4 GHz transmitter front-end with a wideband active balun is proposed.The wideband active balun is able to work ideally by adopting a resistive compensation technique, which balances the gain of the differential input. In addition, a variable-gain preamplifier driver with a dynamic range of 18 dB is utilized for the autogain loop control feature. The proposed wideband active balun only occupies 15 × 27 μm2, which is profoundly small compared with conventional baluns and is promising in the differential to single signal conversion in wideband applications. © 2012 Wiley Periodicals, Inc. Microwave Opt Technol Lett 54:2868–2871, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/mop.27190

In this study, ductile irons with and without 1 wt% copper alloy were austempered to become austempered ductile irons (ADIs). Microstructure, impact toughness, and fracture toughness were evaluated to determine how both the copper alloying and austempering treatments influenced the toughness properties of ductile irons. The results show that, because copper increases the retained austenite content in ADI, the Cu-alloyed ADI has better impact toughness and fracture toughness ( K IC value) than does the unalloyed one. In particular, the impact toughness and the fracture toughness of ADI could be efficiently improved by treating the Cu-alloyed ductile iron at a higher austempering temperature (360 °C) to obtain more retained austenite in its microstructure.

A gold plated carbon nanotube (CNT) bundle antenna, which is integrated with a voltage control oscillator (VCO) is reported. Gold plating reduces ohmic loss and improves radiation efficiency of the CNT antenna. Reflection measurements of the antenna show a return loss of 12 dB at 67 GHz and -6 dB impedance bandwidth at 53-87.5 GHz, 140-168 GHz, and 207-220 GHz, respectively. The VCO implemented in 65-nm CMOS technology is designed to be integrated with the antenna for the measurement of antenna gain. The measurement result of the antenna gain is -9.7 dBi at 50.7 GHz. These experimental results demonstrate that the proposed antenna is very promising for millimeter-wave applications.

RNA-binding proteins (RBPs) regulate many aspects of transcription and translation in a cell- and tissue-specific manner and are frequently dysregulated in malignancy. We systematically evaluated RBPs preferentially required in acute myeloid leukemia (AML) over other forms of cancer or normal hematopoietic precursors using a CRISPR/Cas9 domain-based, loss-of-function screen targeting 490 classical RBPs with 2,900 sgRNAs (Fig. A). This screen was performed in cells lines representing AML, T-cell acute lymphoblastic leukemia (T-ALL), and lung adenocarcinoma (LUAD) and revealed multiple RBPs preferentially required for AML survival, but not for T-ALL or LUAD survival. We identified genes encoding 21 RBPs that were >3-fold depleted in AML cells and significantly overexpressed in AML patient samples versus normal adult CD34+ precursors (p-value < 0.05; Fig. B). Amongst RBPs required and upregulated in AML was RBM39, an RBP described to be involved in a number of cellular processes and to interact with key splicing proteins SF3B1 and U2AF2. Genetic ablation of Rbm39 in mouse MLL-AF9 leukemia cells dramatically delayed AML development and progression (Fig. C). In parallel, it has recently been described that a class of clinically-validated anti-cancer sulfonamide compounds (including indisulam and E7820) mediate RBM39 degradation as their dominant cellular mechanism of action. This occurs via novel interactions with the DCAF15 adapter protein of the CUL4/Ddb1 ubiquitin ligase complex with RBM39 as a neo-substrate. Treatment of MOLM-13 cells xenografted into mice with indisulam conferred significant anti-leukemic effects and improved overall survival (Fig. D). To explore the mechanism of RBM39 dependence in AML, we performed proteomic analyses of RBM39 interacting proteins in MOLM-13 cells as well as transcriptome-wide analysis of RBM39 RNA binding by enhanced UV cross-linking and immunoprecipitation (eCLIP) in the same cells. RBM39 physically interacted with an entire network of RBPs identified by our CRISPR screen as crucial for AML cell survival in addition to interacting with the core SF3b splicing complex. Further, anti-RBM39 eCLIP revealed RBM39 binding to exonic regions and most enriched at exon/intron borders at 5' and 3' splice sites of pre-mRNA (Fig. E), suggesting a prominent role of RBM39 in regulating splicing. Consistent with this, RNA-sequencing of AML cells following RBM39 deletion revealed significant effects of RBM39 loss on RNA splicing, most prominently causing increased cassette exon skipping (Fig. F). Recent studies suggest that myeloid leukemias with mutations in RNA splicing factors are sensitized to pharmacologic perturbation of RNA splicing. Analysis of the effects of RBM39 degrading compounds over a panel of 18 AML cells revealed that leukemia cells bearing splicing factor mutations or with high DCAF15 expression were the most sensitive to treatment (Fig. G). Genetic introduction of SF3B1, SRSF2, or U2AF1 hotspot mutations in K562 or NALM6 cells resulted in a 20-50% reduction in IC50 in response to sulfonamides. We next performed RNA sequencing of isogenic K562 cells with or without knockin of SF3B1K700E and SRSF2P95H mutations into the endogenous loci, and treated at the IC50 of E7820 or E7107, a small molecule that inhibits the SF3b core spliceosome complex. Treatment with either drug dramatically increased cassette exon skipping events and intron retention relative to DMSO control, with greater effects in splicing mutant cells. However, at equipotent doses, E7820 markedly increased mis-splicing compared with E7107. Furthermore, E7820 treatment resulted in mis-splicing of a number of RBP targets identified in our CRISPR screen as being required for AML survival, including SUPT6H, hnRNPH, and SRSF10, as well as RBM3 and U2AF2, consistent with previous observations (Fig. H). Here through systematic evaluation of RBPs across several cancers, we identify RBPs specifically required in AML. In so doing we identify a network of functionally and physically interacting RBPs upregulated in AML over normal precursors. Genetic or pharmacologic elimination one such RBP, RBM39, led to aberrant splicing of multiple members of this RBP network as well as of transcriptional regulators required for AML survival. These data suggest important clinical potential for anti-cancer sulfonamide treatment in splicing mutant myeloid leukemias. Disclosures Uehara: Eisai: Employment. Owa:Eisai: Employment.

Angiogenesis is observed in many diseases, such as tumor progression, diabetes and rheumatoid arthritis; it is a process that involves proliferation, migration, differentiation and tube formation of endothelial cells. Vascular endothelial growth factor (VEGF) plays an important role in angiogenesis by induction of these endothelial functions. Thus, inhibition of these critical angiogenic steps is a practical therapeutic strategy for those diseases. NP-184 is a substituted benzimidazole analogue which exhibits a potent anti-thrombotic activity. In this report, NP-184 inhibited the viability of human umbilical vascular endothelial cells (HUVEC) in a concentration-dependent manner, and caused cell apoptosis as examined by cell-cycle analysis and Annexin V staining with flow cytometry. NP-184 also concentration-dependently inhibited the HUVEC migration, tube formation on Matrigel, and rat aortic ring sprouting stimulated by VEGF. Regarding the intracellular signal transduction, NP-184 concentration-dependently interfered with the activation of AKT, ERK and the nuclear translocation of NF-kappaB. In vivo study showed that NP-184 dose-dependently reduced angiogenesis in Matrigel plug assay. These results indicate that NP-184 is a potential candidate for developing the treatment of angiogenesis related-diseases.

Background and purpose: During the development of atherosclerotic plaques, vascular smooth muscle cells (VSMCs) migrate from the media to the intima through the basement membrane and interstitial collagenous matrix, and proliferate to form neointima. Here, we investigate the mechanism of VSMC migration and proliferation caused by aggretin, a snake venom integrin α2β1 agonist. Experimental approach: Cultures of rat and human VSMCs were treated with aggretin and the signal transduction pathways induced by this agonist were examined by Western blotting, immunoprecipitation and electrophoretic mobility shift assay techniques. Key results: Aggretin-induced VSMC proliferation was blocked by a monoclonal antibody (mAb) against integrin α2 (AII2E10) or against the platelet-derived growth factor receptor (PDGFR)-β. Proliferation was also blocked by inhibition of the tyrosine kinase Src with PP2, phospholipase C (PLC) with U73122, extracellular signal-regulated kinase (ERK) with PD98059 or nuclear factor-kappa B (NF-kB) activation with pyrrolidine dithiocarbamate (PDTC). VSMC migration towards immobilized aggretin was increased in a modified Boyden chamber and this effect was blocked by α2β1-Src-PLC-MAPK axis inhibitors, but not by PDTC, PDGFR-β mAb, or a phosphoinositide-3 kinase inhibitor, LY294002. Aggretin stimulated the phosphorylation of PDGFR-β, Src and ERK in a time-dependent manner. NF-kB translocation and platelet-derived growth factor (PDGF)-BB production were also observed. The ERK activation, NF-kB translocation and PDGF-BB production were blocked by PP2, U73122 and PD98059. Conclusions and implications: Aggretin induces VSMC proliferation and migration mainly through binding to integrin α2β1, and subsequently activates Src, PLC and ERK pathways, inducing NF-kB activation and PDGF production.

Our passive near-field microscope probes thermal evanescent waves due to local phenomena on material's surface. With the microscope, we study dielectric samples since they have surface phonon resonances whose resonance wavelengths are very close to our detection wavelength. From the results, GaAs, SiC, and AlN show reasonable signals due to thermal fluctuations, whereas GaN show very unique characteristics. In this report, we show and discuss the results.

Bioassay-guided fractionation led to the discovery of a novel neo-clerodane diterpenoid, scutebarbalactone VN (BalA: 8,13-epoxy-3-en-7-hydroxy-6,11- O-dibenzoyl-15,16-clerodanolide), from the methanol extract of the whole-plant of Vietnamese Scutellaria barbata D. Don. A microarray technique combined with bioinformatic analyses showed that BalA could inhibit cell cycle pathways by downregulating genes such as CDC25A and AURKA. BalA also showed the potential to reactivate downregulated genes in hepatocellular carcinoma cells and genes in antioxidant pathways such as HMOX1 and HSPA1A. Querying Connectivity map 2.0 resulted in a match of the BalA-modulated gene signature with that of 10 known compounds, most of which are currently marketed chemotherapy drugs. The highest matching scores belonged to lomustine, semustine, and withaferin A. Lomustine and semustine were found to alkylate DNA and RNA, while withaferin A inhibits nuclear factor kappa B (NF-κB) activity. A luciferase reporter assay was also conducted on 293/NF-κB human embryonic kidney cells that had been transfected with the NF-κB-luciferase plasmid to verify the anticancer activity of BalA. The assay showed that Ba1A effectively blocked NF-κB with an IC50 of 38.6 ± 0.05 μM.

We have developed a passive long-wavelength infrared (LWIR) scattering-type scanning near-field optical microscope (s-SNOM) installed in a helium-free mechanically cooled cryostat, which facilitates cooling of an LWIR detector and optical elements to 4.5 K. To reduce mechanical vibration propagation from a compressor unit, we have introduced a metal bellows damper and a helium gas damper. These dampers ensure the performance of the s-SNOM to be free from mechanical vibration. Furthermore, we have introduced a solid immersion lens to improve the confocal microscope performance. To demonstrate the passive s-SNOM capability, we measured thermally excited surface evanescent waves on Au/SiO2 gratings. A near-field signal-to-noise ratio is 4.5 times the improvement with an acquisition time of 1 s/pixel. These improvements have made the passive s-SNOM a more convenient and higher-performance experimental tool with a higher signal-to-noise ratio for a shorter acquisition time of 0.1 s.