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Find video protocols related to scientific articles indexed in Pubmed.
Rectangular Ion Funnel (RIF): A New Ion Funnel Interface for Structures for Lossless Ion Manipulations (SLIM).
Anal. Chem.
PUBLISHED: 11-20-2014
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Structures for Lossless Ion Manipulations (SLIM) have recently demonstrated the ability for near lossless ion focusing, transfer, and trapping in sub-atmospheric pressure regions. While lossless ion manipulations are advantageously applied to the applications of ion mobility separations and gas phase reactions, ion introduction through ring electrode ion funnels or more conventional ion optics to SLIM can involve discontinuities in electric fields or other perturbations that result in ion losses. In this work, we developed and investigated a new funnel design that aims to seamlessly couple to SLIM at the funnel exit. This rectangular ion funnel (RIF) was initially evaluated by ion simulations, fabricated utilizing printed circuit board technology and tested experimentally. The RIF was integrated to a SLIM-TOF MS system, and the operating parameters, including RF, DC bias of the RIF electrodes, and electric fields for effectively interfacing with a SLIM were characterized. The RIF provided a 2-fold sensitivity increase without significant discrimination over a wide m/z range along with greatly improved SLIM operational stability.
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In situ observation of facet-dependent oxidation of graphene on platinum in an environmental TEM.
Chem. Commun. (Camb.)
PUBLISHED: 11-20-2014
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We performed a direct observation of a crystal facet-dependent oxidation of graphene layers on platinum nanocrystals at atomic resolution in an environmental transmission electron microscope. Combined with density functional theory calculations, our work provides a novel approach for the dynamical exploration of the facet-dependent reactions at the atomic level.
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Distinct aetiopathogenesis in subgroups of functional dyspepsia according to the Rome III criteria.
Gut
PUBLISHED: 11-20-2014
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Whether there is distinct pathogenesis in subgroups of functional dyspepsia (FD), the postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS) remains controversial. We aimed to identify the risk factors of FD and its subgroups in the Chinese population.
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A microring resonator photodetector for enhancement in L-band performance.
Opt Express
PUBLISHED: 11-18-2014
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We proposed a microring resonator (MRR) enhanced photodetector (PD) structure. Resonance wavelength enhanced by the MRR amplifies the PD response. At L-band wavelengths, responsivity was doubled for an ultra-short germanium PD of 4 µm employing the MRR structure. Data rates of up to 40 Gb/s were also demonstrated at 1600 nm.
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Novel integration technique for silicon/III-V hybrid laser.
Opt Express
PUBLISHED: 11-18-2014
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Integrated semiconductor lasers on silicon are one of the most crucial devices to enable low-cost silicon photonic integrated circuits for high-bandwidth optic communications and interconnects. While optical amplifiers and lasers are typically realized in III-V waveguide structures, it is beneficial to have an integration approach which allows flexible and efficient coupling of light between III-V gain media and silicon waveguides. In this paper, we propose and demonstrate a novel fabrication technique and associated transition structure to realize integrated lasers without the constraints of other critical processing parameters such as the starting silicon layer thicknesses. This technique employs epitaxial growth of silicon in a pre-defined trench with taper structures. We fabricate and demonstrate a long-cavity hybrid laser with a narrow linewidth of 130 kHz and an output power of 1.5 mW using the proposed technique.
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dbSNO 2.0: a resource for exploring structural environment, functional and disease association and regulatory network of protein S-nitrosylation.
Nucleic Acids Res.
PUBLISHED: 11-17-2014
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Given the increasing number of proteins reported to be regulated by S-nitrosylation (SNO), it is considered to act, in a manner analogous to phosphorylation, as a pleiotropic regulator that elicits dual effects to regulate diverse pathophysiological processes by altering protein function, stability, and conformation change in various cancers and human disorders. Due to its importance in regulating protein functions and cell signaling, dbSNO (http://dbSNO.mbc.nctu.edu.tw) is extended as a resource for exploring structural environment of SNO substrate sites and regulatory networks of S-nitrosylated proteins. An increasing interest in the structural environment of PTM substrate sites motivated us to map all manually curated SNO peptides (4165 SNO sites within 2277 proteins) to PDB protein entries by sequence identity, which provides the information of spatial amino acid composition, solvent-accessible surface area, spatially neighboring amino acids, and side chain orientation for 298 substrate cysteine residues. Additionally, the annotations of protein molecular functions, biological processes, functional domains and human diseases are integrated to explore the functional and disease associations for S-nitrosoproteome. In this update, users are allowed to search a group of interested proteins/genes and the system reconstructs the SNO regulatory network based on the information of metabolic pathways and protein-protein interactions. Most importantly, an endogenous yet pathophysiological S-nitrosoproteomic dataset from colorectal cancer patients was adopted to demonstrate that dbSNO could discover potential SNO proteins involving in the regulation of NO signaling for cancer pathways.
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Association between antiviral treatment and extrahepatic outcomes in patients with hepatitis C virus infection.
Gut
PUBLISHED: 11-16-2014
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To elucidate the association between antiviral therapy and extrahepatic outcomes in individuals infected with HCV.
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Using acrylic resin tooth veneers in patients with an abnormal jaw relationship: a case report.
Int J Prosthodont
PUBLISHED: 11-13-2014
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This case report describes and evaluates a method of arranging artificial teeth in patients with an abnormal jaw relationship in which a wider maxillary arch opposes a narrower mandibular arch. First, the fossa of mandibular posterior teeth was positioned on the crest of the mandibular edentulous ridge. The maxillary posterior teeth were then placed palatally to maximize occlusal contacts with the opposing mandibular teeth. Finally, acrylic resin tooth veneers were attached on the buccal surface of posterior maxillary teeth to improve the arch discrepancy. This method addresses functional considerations with the inner aspect of teeth and esthetic considerations with acrylic resin tooth veneers.
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Low cord blood vitamin D levels are associated with increased milk sensitization in early childhood.
Pediatr Allergy Immunol
PUBLISHED: 11-13-2014
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The association between vitamin D status at birth and allergen sensitizations is uncertain. The aim of this study was to investigate the relationship of cord blood vitamin D status with allergen sensitizations and the development of atopic diseases in early childhood.
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Shared Molecular Pathways and Gene Networks for Cardiovascular Disease and Type 2 Diabetes in Women across Diverse Ethnicities.
Circ Cardiovasc Genet
PUBLISHED: 11-06-2014
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-While cardiovascular disease (CVD) and type 2 diabetes (T2D) share many common risk factors, potential molecular mechanisms that may also be shared for these two disorders remain unknown.
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Clinical significance of pathological complete response in patients with metastatic gastrointestinal stromal tumors after imatinib mesylate treatment - lessons learned.
Anticancer Res.
PUBLISHED: 11-05-2014
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Imatinib mesylate (IM) has substantial efficacy in patients with metastatic gastrointestinal stromal tumors (GISTs), and pathological complete response (pCR) following IM treatment has been sporadically reported; however, its clinical significance for GIST needs to be clarified.
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Silicon optical modulator with shield coplanar waveguide electrodes.
Opt Express
PUBLISHED: 10-17-2014
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A silicon Mach-Zehnder Interferometer (MZI) optical modulator with a shield coplanar waveguide (CPW) transmission line electrode design was demonstrated. This shield-CPW electrode suppresses the signal distortion caused by the parasitic slot-line (SL) mode and improves the electrical bandwidth and the electro-optical (EO) bandwidth. With the shield-CPW electrodes and 5.5 mm-long phase shifters, the silicon MZI optical modulator delivered an EO bandwidth of above 24 GHz and a V ? = 3.0 V was achieved at ? = 1310nm. When modulated at 28-Gb/s data rate, it achieved an extinction ratio of 5.66 dB under a driving voltage of V pp = 1.3 V, corresponding to a power consumption of 0.8 pJ/bit.
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Mode size converter between high-index-contrast waveguide and cleaved single mode fiber using SiON as intermediate material.
Opt Express
PUBLISHED: 10-17-2014
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High-index-contrast (HIC) waveguide such as Si and Si3N4 has small mode size enabling compact integration. However, the coupling loss with single mode fiber is also remarkable owning to the mode mismatching. Therefore, mode size converter, as the interface between HIC waveguide and optical fiber, takes an important role in the field of integrated optics. The material with refractive index (RI) between HIC waveguide and optical fiber can be used as a bridge to reduce the mode mismatching loss. In this letter, we employ silicon oxynitride (SiON) with RI about 1.50 as the intermediate material and optimize the structure of the SiON waveguide to match with cleaved single mode fiber and HIC waveguide separately. Combined with inverse taper and suspended structure, the mismatching loss is reduced and the dependence to the dimension of the structure is also released. The coupling loss is 1.2 and 1.4 dB/facet for TE and TM mode, respectively, with 3dB alignment tolerance of ± 3.5 µm for Si3N4 waveguide with just 200nm-wide tip. While for Si waveguide, a critical dimension of 150nm is applied due to the higher index contrast than Si3N4 waveguide. Similar alignment tolerance is realized with coupling loss about 1.8 and 2.1 dB/facet for TE and TM mode. The polarization dependence loss (PDL) for both platforms is within 0.5 dB.
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CMOS compatible monolithic multi-layer Si3N4-on-SOI platform for low-loss high performance silicon photonics dense integration.
Opt Express
PUBLISHED: 10-17-2014
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We demonstrated a low-loss CMOS-compatible multi-layer platform using monolithic back-end-of-line (BEOL) integration. 0.8dB/cm propagation loss is measured for the PECVD Si3N4 waveguide at 1580nm wavelength. The loss is further reduced to 0.24dB/cm at 1270nm wavelength, justifying the platform's feasibility for O-band operation. An inter-layer transition coupler is designed, achieving less than 0.2dB/transition loss across 70nm bandwidth. This is the lowest inter-layer transition loss ever reported. A thermally tuned micro-ring filter is also integrated on the platform, with performance comparable to similar device on SOI platform.
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Silicon-based traveling-wave photodetector array (Si-TWPDA) with parallel optical feeding.
Opt Express
PUBLISHED: 10-17-2014
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We demonstrate silicon-based traveling-wave photodetector arrays (Si-TWPDAs) with parallel optical feeding by integrating multiple Germanium photodetectors. Such Si-TWPDAs feature the merit of high optical saturation power with remaining the large operation bandwidth. The impedance-matched traveling-wave electrode design takes into account the individual Ge photodetector loading effect. Optical waveguide delay lines are designed in order to balance the electrical phase delay of the traveling-wave electrode. The maximum linear photocurrent at -4V biased voltage are respectively 16 mA, 38 mA, and 65 mA with integrating 1, 2, and 4 photodetectors, upon the saturation power of 40 mW, 100 mW, and 160 mW. This corresponds to a normalized photocurrent generation of >0.32 mA/µm3 and a normalized saturation power of 0.8 mW/µm3. The extracted fiber access responsivity is ~0.42 A/W and the intrinsic responsivity of ~0.82 A/W. The measured 3-dB bandwidth for 4-channel TWPDA is ~20 GHz.
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Three-dimensional (3D) monolithically integrated photodetector and WDM receiver based on bulk silicon wafer.
Opt Express
PUBLISHED: 10-17-2014
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We propose a novel three-dimensional (3D) monolithic optoelectronic integration platform. Such platform integrates both electrical and photonic devices in a bulk silicon wafer, which eliminates the high-cost silicon-on-insulator (SOI) wafer and is more suitable for process requirements of electronic and photonic integrated circuits (ICs). For proof-of-concept, we demonstrate a three-dimensional photodetector and WDM receiver system. The Ge is grown on a 8-inch bulk silicon wafer while the optical waveguide is defined in a SiN layer which is deposited on top of it, with ~4 µm oxide sandwiched in between. The light is directed to the Ge photodetector from the SiN waveguide vertically by using grating coupler with a Aluminum mirror on top of it. The measured photodetector responsivity is ~0.2 A/W and the 3-dB bandwidth is ~2 GHz. Using such vertical-coupled photodetector, we demonstrated an 8-channel receiver by integrating a 1 × 8 arrayed waveguide grating (AWG). High-quality optical signal detection with up to 10 Gbit/s data rate is demonstrated, suggesting a 80 Gbit/s throughput. Such receiver can be applied to on-chip optical interconnect, DRAM interface, and telecommunication systems.
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Chaotic Extension Neural Network Theory-Based XXY Stage Collision Fault Detection Using a Single Accelerometer Sensor.
Sensors (Basel)
PUBLISHED: 10-06-2014
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The collision fault detection of a XXY stage is proposed for the first time in this paper. The stage characteristic signals are extracted and imported into the master and slave chaos error systems by signal filtering from the vibratory magnitude of the stage. The trajectory diagram is made from the chaos synchronization dynamic error signals E1 and E2. The distance between characteristic positive and negative centers of gravity, as well as the maximum and minimum distances of trajectory diagram, are captured as the characteristics of fault recognition by observing the variation in various signal trajectory diagrams. The matter-element model of normal status and collision status is built by an extension neural network. The correlation grade of various fault statuses of the XXY stage was calculated for diagnosis. The dSPACE is used for real-time analysis of stage fault status with an accelerometer sensor. Three stage fault statuses are detected in this study, including normal status, Y collision fault and X collision fault. It is shown that the scheme can have at least 75% diagnosis rate for collision faults of the XXY stage. As a result, the fault diagnosis system can be implemented using just one sensor, and consequently the hardware cost is significantly reduced.
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Fractioned dose regimen of sunitinib for patients with gastrointestinal stromal tumor: a pharmacokinetic and treatment efficacy study.
Transl Oncol
PUBLISHED: 10-01-2014
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Sunitinib has shown benefit in patients with imatinib (IM)-resistant gastrointestinal stromal tumor (GIST). However, its advantages are somewhat diminished because of associated toxicities. Herein, we clarify the efficacy and safety of fractioned dose regimen of sunitinib by a pharmacokinetic and efficacy study.
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Mobility-resolved ion selection in uniform drift field ion mobility spectrometry/mass spectrometry: dynamic switching in structures for lossless ion manipulations.
Anal. Chem.
PUBLISHED: 09-26-2014
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A Structures for Lossless Ion Manipulations (SLIM) module that allows ion mobility separations and the switching of ions between alternative drift paths is described. The SLIM switch component has a "Tee" configuration and allows the efficient switching of ions between a linear path and a 90-degree bend. By controlling switching times, ions can be efficiently directed to an alternative channel as a function of their mobilities. In the initial evaluation the switch is used in a static mode and shown compatible with high performance ion mobility separations at 4 Torr. In the dynamic mode, we show that mobility-selected ions can be switched into the alternative channel, and that various ion species can be independently selected based on their mobilities for time-of-flight mass spectrometer (TOF MS) IMS detection and mass analysis. This development also provides the basis of, for example, the selection of specific mobilities for storage and accumulation, and the key component of modules for the assembly of SLIM devices enabling much more complex sequences of ion manipulations.
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The Contribution of Class 1 Integron to Antimicrobial Resistance in Stenotrophomonas maltophilia.
Microb. Drug Resist.
PUBLISHED: 09-23-2014
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Two hundred clinical isolates of Stenotrophomonas maltophilia were examined for the presence of class 1 integron and for the susceptibility to 12 different antimicrobials and detergents. The prevalence of class 1 integron in S. maltophilia isolates was 11%. The class 1 integron-positive isolates exhibited a higher resistance to kanamycin, tobramycin, and trimethoprim-sulfamethoxazole (SXT) than the class 1 integron-negative ones. Polymerase chain reaction (PCR), amplifying the variable region of the class 1 integron, showed the existence of six different amplicon sizes, indicating that there are at least six different class 1 integrons distributed in the 23 class 1 integron-positive isolates. Sequence analysis of six representative PCR amplicons revealed that qacK, aac(6')-Ib', qacK-aac(6')-Ib, qacK-aac(6')-Ib-aac(6')-Ib, and qacL-aadB-cmlA-aadA2 were identified in the 550-, 800-, 1,200-, 1,800, and 3,600-bp amplicons, respectively. The sequence analysis of the 150-bp PCR amplicon demonstrated no additional resistance-associated genes except the basic genetic elements of class 1 integron. The impact of class 1 integron acquisition on the antimicrobials susceptibility was assayed by isogenic integron deletion mutant construction and the susceptibility test. The most significant contribution of the class 1 integron acquisition to S. maltophilia is the increased resistance to SXT.
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Imatinib escalation or sunitinib treatment after first-line imatinib in metastatic gastrointestinal stromal tumor patients.
Anticancer Res.
PUBLISHED: 09-10-2014
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Imatinib mesylate (IM) is effective in metastatic gastrointestinal stromal tumor (GIST) patients; however, disease progression eventually occurs due to IM resistance or intolerance. Treatment options include IM escalation or a direct shift to sunitinib, but comparison of these strategies is required.
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Electrochemically induced surface metal migration in well-defined core-shell nanoparticles and its general influence on electrocatalytic reactions.
ACS Nano
PUBLISHED: 09-05-2014
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Bimetallic nanoparticle catalysts provide enhanced activity, as combining metals allows tuning of electronic and geometric structure, but the enhancement may vary during the reaction because the nanoparticles can undergo metal migration under catalytic reaction conditions. Using cyclic voltammetry to track the surface composition over time, we carried out a detailed study of metal migration in a well-defined model Au-Pd core-shell nanocatalyst. When subjected to electrochemical conditions, Au migration from the core to the shell was observed. The effect of Pd shell thickness and electrolyte identity on the extent of migration was studied. Migration of metals during catalytic ethanol oxidation was found to alter the particle's surface composition and electronic structure, enhancing the core-shell particles' activity. We show that metal migration in core-shell nanoparticles is a phenomenon common to numerous electrochemical systems and must be considered when studying electrochemical catalysis.
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Experimental evaluation and optimization of structures for lossless ion manipulations for ion mobility spectrometry with time-of-flight mass spectrometry.
Anal. Chem.
PUBLISHED: 09-05-2014
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We report on the performance of structures for lossless ion manipulation (SLIM) as a means for transmitting ions and performing ion mobility separations (IMS). Ions were successfully transferred from an electrospray ionization (ESI) source to the TOF MS analyzer by means of a linear SLIM, demonstrating lossless ion transmission and an alternative arrangement including a 90° turn. First, the linear geometry was optimized for radial confinement by tuning RF on the central "rung" electrodes and potentials on the DC-only guard electrodes. Selecting an appropriate DC guard bias (2-6 V) and RF amplitude (?160 V(p-p) at 750 kHz) resulted in the greatest ion intensities. Close to ideal IMS resolving power was maintained over a significant range of applied voltages. Second, the 90° turn was optimized for radial confinement by tuning RF on the rung electrodes and DC on the guard electrodes. However, both resolving power and ion transmission showed a dependence on these voltages, and the best conditions for both were >300 V(p-p) RF (685 kHz) and 7-11 V guard DC bias. Both geometries provide IMS resolving powers at the theoretical limit (R ~ 58), showing that degraded resolution from a "racetrack" effect from turning around a corner can be successfully avoided, and the capability also was maintained for essentially lossless ion transmission.
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Molecular encapsulation beyond the aperture size limit through dissociative linker exchange in metal-organic framework crystals.
J. Am. Chem. Soc.
PUBLISHED: 08-29-2014
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Under linker exchange conditions, large guests with molecular diameters 3-4 times the framework aperture size have been encapsulated into preformed nanocrystals of the metal-organic framework ZIF-8. Guest encapsulation is facilitated by the formation of short-lived "open" states of the pores upon linker dissociation. Kinetic studies suggested that linker exchange reactions in ZIF-8 proceed via a competition between dissociative and associative exchange mechanisms, and guest encapsulation was enhanced under conditions where the dissociative pathway predominates.
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Persistent improper upregulation of Th17 and TReg cells in patients with juvenile idiopathic arthritis.
J Microbiol Immunol Infect
PUBLISHED: 08-28-2014
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Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease. A break in the balance between Th17 and TReg cells has been reported as an important factor in the development of autoimmune diseases. This study aimed to analyze peripheral Th17 and TReg cell levels in patients with JIA.
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Design of Portable Mass Spectrometers with Handheld Probes: Aspects of the Sampling and Miniature Pumping Systems.
J. Am. Soc. Mass Spectrom.
PUBLISHED: 08-26-2014
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Miniature mass spectrometry analytical systems of backpack configuration fitted with sampling probes could potentially be of significant interest for in-field, real-time chemical analysis. In this study, various configurations were explored in which a long narrow tube was used to connect the turbo and backing pumps used to create and maintain vacuum. Also, for the first time we introduced two new types of pumps for miniature mass spectrometers, the Creare 130 g drag pump and Creare 350 g scroll backing pump. These pumps, along with another Creare 550 turbo pump and the commercially available Pfeiffer HiPace 10 turbo and KnF diaphragm backing pumps, were tested with the backpack configurations. The system performance, especially the scan time, was characterized when used with a discontinuous atmospheric pressure interface (DAPI) for ion introduction. The pumping performance in the pressure region above 1 mtorr is critical for DAPI operation. The 550 g turbo pump was shown to have a relatively higher pumping speed above 1 mtorr and gave a scan time of 300 ms, almost half the value obtained with the larger, heavier HiPace 10 often used with miniature mass spectrometers. The 350 g scroll pump was also found to be an improvement over the diaphragm pumps generally used as backing pumps. With a coaxial low temperature plasma ion source, direct analysis of low volatility compounds glass slides was demonstrated, including 1 ng DNP (2,4-Dinitrophenol) and 10 ng TNT (2,4,6-trinitrotoluene) with Creare 550 g turbo pump as well as 10 ng cocaine and 20 ng DNP with Creare 130 g drag pump.
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MacABCsm, an ABC-type tripartite efflux pump of Stenotrophomonas maltophilia involved in drug resistance, oxidative and envelope stress tolerances and biofilm formation.
J. Antimicrob. Chemother.
PUBLISHED: 08-19-2014
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To characterize a five gene cluster, macRS-macABCsm, in Stenotrophomonas maltophilia.
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NK cells kill mycobacteria directly by releasing perforin and granulysin.
J. Leukoc. Biol.
PUBLISHED: 08-19-2014
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Although the mechanisms underlying the cytotoxic effect of NK cells on tumor cells and intracellular bacteria have been studied extensively, it remains unclear how these cells kill extracellular bacterial pathogens. In this study, we examine how human NK cells kill Mycobacterium kansasii and M.tb. The underlying mechanism is contact dependent and requires two cytolytic proteins: perforin and granulysin. Mycobacteria induce enhanced expression of the cytolytic proteins via activation of the NKG2D/NCR cell-surface receptors and intracellular signaling pathways involving ERK, JNK, and p38 MAPKs. These results suggest that NK cells use similar cellular mechanisms to kill both bacterial pathogens and target host cells. This report reveals a novel role for NK cells, perforin, and granulysin in killing mycobacteria and highlights a potential alternative defense mechanism that the immune system can use against mycobacterial infection.
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Applying T-cell receptor excision circles and immunoglobulin ?-deleting recombination excision circles to patients with primary immunodeficiency diseases.
Ann. Med.
PUBLISHED: 08-11-2014
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Abstract Background. Biomarkers of T-cell receptor excision circles (TRECs) and immunoglobulin ?-deleting recombination excision circles (KRECs) reflect naïve T and B cell emigrants. This study assessed the biomarkers in patients with primary immunodeficiency diseases (PIDs) to determine the lymphocyte output disturbance and the correlation to lymphocytes. Methods. A standard plasmid was constructed to calculate TRECs and KRECs in 250 ng genomic DNA from whole blood of PIDs patients. These were correlated to naïve and memory lymphocytes for further classification and adequate treatment. Results. In 69 studied patients, the low TRECs mainly included those with severe combined T and B immunodeficiency (SCID, 7/8), combined immunodeficiency (CID, 4/4), and common variable immunodeficiency (CVID, 6/7). The diminished KRECs was in SCID (4/8), CID (4/4), CVID (7/7), Bruton's tyrosine kinase mutation (Btk, 3/4), anti-B cell deletion (by anti-CD20 antibody in 1), and Behçet syndrome under steroid treatment (1). The TRECs and KRECs positively correlated to absolute naïve T (CD4 + CD45RA+) and naïve B (CD19 + CD27-), and to memory B (CD19 + CD27+) numbers, respectively. Conclusion. This study validates that low TRECs and KRECs values reflect low naïve T and B lymphocytes in 'combined immunodeficiencies' and in some CVID patients with the potential to develop the CID phenotype.
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Decoding the s-nitrosoproteomic atlas in individualized human colorectal cancer tissues using a label-free quantitation strategy.
J. Proteome Res.
PUBLISHED: 08-04-2014
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The abnormal S-nitrosylation induced by the overexpression and activation of inducible nitric oxide synthase (iNOS) modulates many human diseases, such as inflammation and cancer. To delineate the pathophysiological S-nitrosoproteome in cancer patients, we report an individualized S-nitrosoproteomic strategy with a label-free method for the site-specific quantification of S-nitrosylation in paired tumor and adjacent normal tissues from 11 patients with colorectal cancer (CRC). This study provides not only the first endogenous human S-nitrosoproteomic atlas but also the first individualized human tissue analysis, identifying 174 S-nitrosylation sites in 94 proteins. Fourteen novel S-nitrosylation sites with a high frequency of elevated levels in 11 individual patients were identified. An individualized S-nitrosylation quantitation analysis revealed that the detected changes in S-nitrosylation were regulated by both the expression level and the more dramatic post-translational S-nitrosylation of the targeted proteins, such as thioredoxin, annexin A4, and peroxiredoxin-4. These endogenous S-nitrosylated proteins illustrate the network of inflammation/cancer-related and redox reactions mediated by various S-nitrosylation sources, including iNOS, transnitrosylase, or iron-sulfur centers. Given the demonstrated sensitivity of individualized tissue analysis, this label-free approach may facilitate the study of the vastly under-represented S-nitrosoproteome and enable a better understanding of the effect of endogenous S-nitrosylation in cancer.
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An intelligent system for identifying acetylated lysine on histones and nonhistone proteins.
Biomed Res Int
PUBLISHED: 07-24-2014
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Lysine acetylation is an important and ubiquitous posttranslational modification conserved in prokaryotes and eukaryotes. This process, which is dynamically and temporally regulated by histone acetyltransferases and deacetylases, is crucial for numerous essential biological processes such as transcriptional regulation, cellular signaling, and stress response. Since the experimental identification of lysine acetylation sites within proteins is time-consuming and laboratory-intensive, several computational approaches have been developed to identify candidates for experimental validation. In this work, acetylated protein data collected from UniProtKB were categorized into histone or nonhistone proteins. Support vector machines (SVMs) were applied to build predictive models by using amino acid pair composition (AAPC) as a feature in a histone model. We combined BLOSUM62 and AAPC features in a nonhistone model. Furthermore, using maximal dependence decomposition (MDD) clustering can enhance the performance of the model on a fivefold cross-validation evaluation to yield a sensitivity of 0.863, specificity of 0.885, accuracy of 0.880, and MCC of 0.706. Additionally, the proposed method is evaluated using independent test sets resulting in a predictive accuracy of 74%. This indicates that the performance of our method is comparable with that of other acetylation prediction methods.
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Surfactant-directed atomic to mesoscale alignment: metal nanocrystals encased individually in single-crystalline porous nanostructures.
J. Am. Chem. Soc.
PUBLISHED: 07-23-2014
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Composite nanomaterials are attractive for a diverse range of applications in catalysis, plasmonics, sensing, imaging, and biology. In such composite nanomaterials, it is desired, yet still challenging to create a controlled alignment between components with lattices in disparate scales. To address this challenge, we report a new concept of colloidal synthesis, in which self-assembled molecular layers control the alignment between materials during the synthesis. To illustrate this concept, self-assembled cetyltrimethylammonium bromide (CTAB) molecules are used to control interfaces in a core-shell nanocomposite with a well-defined metal nanocrystal core and a metal-organic-framework (MOF) shell, which differ in structural dimensions by orders of magnitude. We show that single metal nanocrystals are captured individually in single-crystalline MOFs, and an alignment between the {100} planes of the metal and {110} planes of the MOFs is observed. By utilizing the same concept, a layer of mesostructured silica is formed over MOF crystals. These multilayered core-shell structures demonstrate a controlled alignment across a wide range of materials, from the metal nanocrystals, extending to nanoporous MOFs and mesostructured silica.
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Wnt5A regulates ABCB1 expression in multidrug-resistant cancer cells through activation of the non-canonical PKA/?-catenin pathway.
Oncotarget
PUBLISHED: 06-17-2014
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Multidrug resistance in cancer cells arises from altered drug permeability of the cell. We previously reported activation of the Wnt pathway in ABCB1-overexpressed human uterus sarcoma drug-resistant MES-SA/Dx5 cells through active ?-catenin and associated transactivation activities, and upregulation of Wnt-targeting genes. In this study, Wnt5A was found to be significantly upregulated in MES-SA/Dx5 and MCF7/ADR2 cells, suggesting an important role for the Wnt5A signaling pathway in cancer drug resistance. Higher cAMP response elements and Tcf/Lef transcription activities were shown in the drug-resistant cancer cells. However, expression of Wnt target genes and CRE activities was downregulated in Wnt5A shRNA stably-transfected MES-SA/Dx5 cells. Cell viability of the drug-resistant cancer cells was also reduced by doxorubicin treatment and Wnt5A shRNA transfection, or by Wnt5A depletion. The in vitro data were supported by immunohistochemical analysis of 24 paired breast cancer biopsies obtained pre- and post-chemotherapeutic treatment. Wnt5A, VEGF and/or ABCB1 were significantly overexpressed after treatment, consistent with clinical chemoresistance. Taken together, the Wnt5A signaling pathway was shown to contribute to regulating the drug-resistance protein ABCB1 and ?-catenin-related genes in antagonizing the toxic effects of doxorubicin in the MDR cell lines and in clinical breast cancer samples.
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Selective deposition of Ru nanoparticles on TiSi? nanonet and its utilization for Li?O? formation and decomposition.
J. Am. Chem. Soc.
PUBLISHED: 06-16-2014
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The Li-O2 battery promises high capacity to meet the need for electrochemical energy storage applications. Successful development of the technology hinges on the availability of stable cathodes. The reactivity exhibited by a carbon support compromises the cyclability of Li-O2 operation. A noncarbon cathode support has therefore become a necessity. Using a TiSi2 nanonet as a high surface area, conductive support, we obtained a new noncarbon cathode material that corrects the deficiency. To enable oxygen reduction and evolution, Ru nanoparticles were deposited by atomic layer deposition onto TiSi2 nanonets. A surprising site-selective growth whereupon Ru nanoparticles only deposit onto the b planes of TiSi2 was observed. DFT calculations show that the selectivity is a result of different interface energetics. The resulting heteronanostructure proves to be a highly effective cathode material. It enables Li-O2 test cells that can be recharged more than 100 cycles with average round-trip efficiencies >70%.
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Low-loss high-speed silicon IQ modulator for QPSK/DQPSK in C and L bands.
Opt Express
PUBLISHED: 06-13-2014
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A low-loss high-speed silicon in-phase (I) quadrature (Q) modulator is designed, fabricated and characterized. The fabricated IQ modulator has a low passive optical loss of 9 dB in C and L bands. Using the modulator, differential quadrature phase-shift keying (DQPSK) transmission at 44.6 Gb/s with differential detection is confirmed with an optical signal-to-noise ratio (OSNR) of 16.3 dB for a bit error rate (BER) of 10(-3) and a dispersion tolerance of -96 to 107 ps/nm. Moreover, in digital coherent detection, quadrature phase-shift keying (QPSK) up to 64 Gb/s are achieved with an OSNR of 11.6-11.8 dB for a BER of 10(-2) at 1530, 1550, and 1610 nm.
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Shaped Pd-Ni-Pt core-sandwich-shell nanoparticles: influence of Ni sandwich layers on catalytic electrooxidations.
ACS Nano
PUBLISHED: 06-11-2014
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Shape-controlled metal nanoparticles (NPs) interfacing Pt and nonprecious metals (M) are highly active energy conversion electrocatalysts; however, there are still few routes to shaped M-Pt core-shell NPs and fewer studies on the geometric effects of shape and strain on catalysis by such structures. Here, well-defined cubic multilayered Pd-Ni-Pt sandwich NPs are synthesized as a model platform to study the effects of the nonprecious metal below the shaped Pt surface. The combination of shaped Pd substrates and mild reduction conditions directs the Ni and Pt overgrowth in an oriented, layer-by-layer fashion. Exposing a majority of Pt(100) facets, the catalytic performance in formic acid and methanol electro-oxidations (FOR and MOR) is assessed for two different Ni layer thicknesses and two different particle sizes of the ternary sandwich NPs. The strain imparted to the Pt shell layer by the introduction of the Ni sandwich layer (Ni-Pt lattice mismatch of ?11%) results in higher specific initial activities compared to core-shell Pd-Pt bimetallic NPs in alkaline MOR. The trends in activity are the same for FOR and MOR electrocatalysis in acidic electrolyte. However, restructuring in acidic conditions suggests a more complex catalytic behavior from changes in composition. Notably, we also show that cubic quaternary Au-Pd-Ni-Pt multishelled NPs, and Pd-Ni-Pt nanooctahedra can be generated by the method, the latter of which hold promise as potentially highly active oxygen reduction catalysts.
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Cognitive inference device for activity supervision in the elderly.
ScientificWorldJournal
PUBLISHED: 06-10-2014
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Human activity, life span, and quality of life are enhanced by innovations in science and technology. Aging individual needs to take advantage of these developments to lead a self-regulated life. However, maintaining a self-regulated life at old age involves a high degree of risk, and the elderly often fail at this goal. Thus, the objective of our study is to investigate the feasibility of implementing a cognitive inference device (CI-device) for effective activity supervision in the elderly. To frame the CI-device, we propose a device design framework along with an inference algorithm and implement the designs through an artificial neural model with different configurations, mapping the CI-device's functions to minimise the device's prediction error. An analysis and discussion are then provided to validate the feasibility of CI-device implementation for activity supervision in the elderly.
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Life-threatening pneumonitis complicating low-dose methotrexate treatment for juvenile idiopathic arthritis in a child.
Pediatr Emerg Care
PUBLISHED: 06-04-2014
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Methotrexate, a drug commonly used to treat juvenile idiopathic arthritis (JIA), has been reported to cause interstitial pneumonitis as a rare complication in adults with rheumatoid arthritis. Only 1 suspicious case of methotrexate pneumonitis in a child with JIA has been reported in 1998, though with no histopathologic proof. Given its rarity and nonspecific presenting symptoms, diagnosis may be challenging, and a life-threatening illness can occur without a high index of suspicion, as illustrated by this report of a 13-year-old girl with JIA who developed fever, nonproductive cough, and dyspnea as presenting features of interstitial pneumonitis after 1 year of methotrexate therapy. Chest high-resolution computed tomography revealed patchy ground-glass opacities and interlobular septal thickening without pleural effusion. Lung biopsy showed interstitial pneumonitis with diffuse alveolar damage. The symptoms and radiographs improved dramatically after withdrawal of methotrexate and administration of corticosteroids. A restrictive ventilatory defect with decreased diffusion capacity on pulmonary function testing persisted until 20 months after methotrexate withdrawal. There is no single pathognomic feature for methotrexate pneumonitis; rather, diagnosis relies on a constellation of clinical, radiologic, and pathologic findings. This report highlights the necessity for pediatricians to be continuously vigilant for interstitial pneumonitis in children receiving methotrexate who develop new unexplained pulmonary symptoms.
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Serum 25-Hydroxyvitamin D Levels in Relation to Lung Function and Exhaled Nitric Oxide in Children.
J. Pediatr.
PUBLISHED: 05-09-2014
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To investigate the relationship of vitamin D status with lung function and fraction of exhaled nitric oxide (FeNO) in a population sample of children.
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Antitumor activity of the combination of an HSP90 inhibitor and a PI3K/mTOR dual inhibitor against cholangiocarcinoma.
Oncotarget
PUBLISHED: 05-07-2014
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The PI3K/Akt/mTOR pathway is overactivated and heat shock protein (HSP) 90 is overexpressed in common cancers. We hypothesized that targeting both pathways can kill intrahepatic cholangiocarcinoma (CCA) cells. HSP90 and PTEN protein expression was evaluated by immunohistochemical staining of samples from 78 patients with intrahepatic CCA. CCA cell lines and a thioacetamide (TAA)-induced CCA animal model were treated with NVP-AUY922 (an HSP90 inhibitor) and NVP-BEZ235 (a PI3K/mTOR inhibitor) alone or in combination. Both HSP90 overexpression and loss of PTEN were poor prognostic factors in patients with intrahepatic CCA. The combination of the HSP90 inhibitor NVP-AUY922 and the PI3K/mTOR inhibitor NVP-BEZ235 was synergistic in inducing cell death in CCA cells. A combination of NVP-AUY922 and NVP-BEZ235 caused tumor regression in CCA rat animal model. This combination not only inhibited the PI3K/Akt/mTOR pathway but also induced ROS, which may exacerbate the vicious cycle of ER stress. Our data suggest simultaneous targeting of the PI3K/mTOR and HSP pathways for CCA treatment.
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dbGSH: a database of S-glutathionylation.
Bioinformatics
PUBLISHED: 04-29-2014
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S-glutathionylation, the reversible protein posttranslational modification (PTM) that generates a mixed disulfide bond between glutathione and cysteine residue, critically regulates protein activity, stability and redox regulation. Due to its importance in regulating oxidative/nitrosative stress and balance in cellular response, a number of methods have been rapidly developed to study S-glutathionylation, thus expanding the dataset of experimentally determined glutathionylation sites. However, there is currently no database dedicated to the integration of all experimentally verified S-glutathionylation sites along with their characteristics or structural or functional information. Thus, the dbGSH database has been created to integrate all available datasets and to provide the relevant structural analysis. As of January 31, 2014, dbGSH has manually collected >2200 experimentally verified S-glutathionylated peptides from 169 research articles using a text-mining approach. To solve the problem of heterogeneity of the data collected from different sources, the sequence identity of the reported S-glutathionylated peptides is mapped to UniProtKB protein entries. To delineate the structural correlations and consensus motifs of these S-glutathionylation sites, the dbGSH database also provides structural and functional analyses, including the motifs of substrate sites, solvent accessibility, protein secondary and tertiary structures, protein domains and gene ontology.
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Exclusive breastfeeding is associated with reduced cow's milk sensitization in early childhood.
Pediatr Allergy Immunol
PUBLISHED: 04-22-2014
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Although breastfed infants have consistently been reported as having fewer infections and respiratory morbidity during infancy, none have reached a definitive conclusion as to whether breastfeeding is an effective strategy to prevent allergic diseases. This study aims to investigate the relationship between exclusive breastfeeding and sequential changes of several biomarkers of allergy, such as absolute eosinophil count, total IgE level, and specific IgE level during the first 3 yrs of life.
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JOINT ANALYSIS OF SNP AND GENE EXPRESSION DATA IN GENETIC ASSOCIATION STUDIES OF COMPLEX DISEASES.
Ann Appl Stat
PUBLISHED: 04-15-2014
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Genetic association studies have been a popular approach for assessing the association between common Single Nucleotide Polymorphisms (SNPs) and complex diseases. However, other genomic data involved in the mechanism from SNPs to disease, e.g., gene expressions, are usually neglected in these association studies. In this paper, we propose to exploit gene expression information to more powerfully test the association between SNPs and diseases by jointly modeling the relations among SNPs, gene expressions and diseases. We propose a variance component test for the total effect of SNPs and a gene expression on disease risk. We cast the test within the causal mediation analysis framework with the gene expression as a potential mediator. For eQTL SNPs, the use of gene expression information can enhance power to test for the total effect of a SNP-set, which are the combined direct and indirect effects of the SNPs mediated through the gene expression, on disease risk. We show that the test statistic under the null hypothesis follows a mixture of ? (2) distributions, which can be evaluated analytically or empirically using the resampling-based perturbation method. We construct tests for each of three disease models that is determined by SNPs only, SNPs and gene expression, or includes also their interactions. As the true disease model is unknown in practice, we further propose an omnibus test to accommodate different underlying disease models. We evaluate the finite sample performance of the proposed methods using simulation studies, and show that our proposed test performs well and the omnibus test can almost reach the optimal power where the disease model is known and correctly specified. We apply our method to re-analyze the overall effect of the SNP-set and expression of the ORMDL3 gene on the risk of asthma.
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Integrative modeling of multiple genomic data from different types of genetic association studies.
Biostatistics
PUBLISHED: 04-04-2014
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Genome-wide association studies (GWASs) and expression-/methylation-quantitative trait loci (eQTL/mQTL) studies constitute popular approaches for investigating the association of single nucleotide polymorphisms (SNPs) with disease and expression/methylation, respectively. Here, we propose to integrate QTL studies to more powerfully test the SNP effect on disease in GWASs when they are conducted among different subjects. We propose a model for the joint effect of SNPs, methylation, and gene expression on disease risk and obtain the marginal model for SNPs by integrating out methylation and expression. We characterize all possible causal relations among SNPs, methylation, and expression and study the corresponding null hypotheses of no SNP effect in terms of the regression coefficients in the joint model. We develop a score test for variance components of regression coefficients to evaluate the genetic effect. We further propose an omnibus test to accommodate different models. We illustrate the utility of the proposed method in an asthma GWAS study, a brain tumor study, and numerical simulations.
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A novel approach to the discovery of survival biomarkers in glioblastoma using a joint analysis of DNA methylation and gene expression.
Epigenetics
PUBLISHED: 03-26-2014
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Glioblastoma multiforme (GBM) is the most aggressive of all brain tumors, with a median survival of less than 1.5 years. Recently, epigenetic alterations were found to play key roles in both glioma genesis and clinical outcome, demonstrating the need to integrate genetic and epigenetic data in predictive models. To enhance current models through discovery of novel predictive biomarkers, we employed a genome-wide, agnostic strategy to specifically capture both methylation-directed changes in gene expression and alternative associations of DNA methylation with disease survival in glioma. Human GBM-associated DNA methylation, gene expression, IDH1 mutation status, and survival data were obtained from The Cancer Genome Atlas. DNA methylation loci and expression probes were paired by gene, and their subsequent association with survival was determined by applying an accelerated failure time model to previously published alternative and expression-based association equations. Significant associations were seen in 27 unique methylation/expression pairs with expression-based, alternative, and combinatorial associations observed (10, 13, and 4 pairs, respectively). The majority of the predictive DNA methylation loci were located within CpG islands, and all but three of the locus pairs were negatively correlated with survival. This finding suggests that for most loci, methylation/expression pairs are inversely related, consistent with methylation-associated gene regulatory action. Our results indicate that changes in DNA methylation are associated with altered survival outcome through both coordinated changes in gene expression and alternative mechanisms. Furthermore, our approach offers an alternative method of biomarker discovery using a priori gene pairing and precise targeting to identify novel sites for locus-specific therapeutic intervention.
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Fas/Fas ligand mediates keratinocyte death in sunitinib-induced hand-foot skin reaction.
J. Invest. Dermatol.
PUBLISHED: 03-24-2014
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Sunitinib, a multitargeted receptor Y kinase inhibitor (TKI) used for the treatment of renal cell carcinoma and gastrointestinal stromal tumor (GIST), is notorious for cutaneous adverse effects, such as hand-foot skin reaction (HFSR). To explore the underlying mechanism of HFSR, we enrolled 53 sunitinib-treated GIST patients, including 23 HFSR cases, and 30 tolerant controls. Among the 29 biomarkers examined, soluble FasL (sFasL) showed significant increase in the plasma, blister fluids, and skin lesions of HFSR patients. The plasma levels of sFasL were significantly correlated with those of sunitinib in HFSR patients. In addition to FasL, augmented expression of Fas and active caspase 3 was also detected in the epidermis of HFSR patients. The increased FasL caused keratinocyte death, as the use of anti-FasL antibody specifically blocked cell apoptosis. Oral administration of sunitinib to mice increased skin susceptibility to mechanical injuries in a dose/time-dependent manner. The administration of sunitinib (40?mg?kg(-1) per day) for 4 weeks to mice caused the maximally affected skin area with an erosion-to-ulceration response to tape-stripping. The skin biopsies of mice administered sunitinib exhibited increased expression of Fas and FasL in the apoptotic keratinocytes in the epidermis. Our data revealed that Fas/FasL interaction mediates keratinocyte death in sunitinib-induced HFSR.
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Good-Turing frequency estimation in a finite population.
Biom J
PUBLISHED: 03-13-2014
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Good-Turing frequency estimation (Good, ) is a simple, effective method for predicting detection probabilities of objects of both observed and unobserved classes based on observed frequencies of classes in a sample. The method has been used widely in several disciplines, such as information retrieval, computational linguistics, text recognition, and ecological diversity estimation. Nevertheless, existing studies assume sampling with replacement or sampling from an infinite population, which might be inappropriate for many practical applications. In light of this limitation, this article presents a modification of the Good-Turing estimation method to account for finite population sampling. We provide three practical extensions of the modified method, and we examine performance of the modified method and its extensions in simulation experiments.
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The medicinal fungus Antrodia cinnamomea suppresses inflammation by inhibiting the NLRP3 inflammasome.
J Ethnopharmacol
PUBLISHED: 03-09-2014
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Antrodia cinnamomea--a medicinal fungus that is indigenous to Taiwan--has been used as a health tonic by aboriginal tribes and the Asian population. Recent studies indicate that Antrodia cinnamomea extracts exhibit hepato-protective, anti-hypertensive, anti-oxidative, anti-inflammatory, immuno-modulatory, and anti-cancer effects on cultured cells and laboratory animals. This study aims to explore the anti-inflammatory activity of an Antrodia cinnamomea ethanol extract (ACEE) and elucidate its underlying mechanisms of action using lipopolysaccharide (LPS)-primed, ATP-stimulated human THP-1 macrophages.
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Frequency of relining procedures during the maintenance period of removable prostheses: an experiential report.
Int J Prosthodont
PUBLISHED: 03-06-2014
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This retrospective report describes an individual prosthodontist's views regarding clinical factors that presumably influence the frequency of relining procedures (FRP) during the maintenance period of removable prostheses. Patient selection was composed of 60 removable prosthesis-wearing individuals who had been clinically monitored and maintained at 3-month intervals for periods ranging from 5 to 25 years. The FRP was designated as the dependent value, and the number of occlusal supporting areas, number of remaining teeth, sex, and age were designated as independent values using linear regression analysis (P < .05). Factors influencing the FRP were the number of occlusal supporting areas and patient age; the period between relining procedures increased as occlusal supporting areas and age increased.
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Delimitation of a continuous morphological character with unknown prior membership: application of a finite mixture model to classify scapular setae of Abacarus panticis.
Exp. Appl. Acarol.
PUBLISHED: 02-28-2014
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Unambiguous classification is a prerequisite for the study of polymorphism, but accurate delimitation of continuous morphological characters can be challenging. Finite mixture modeling is a rigorous and flexible approach for delimiting continuous variables with unknown prior membership, but its application to morphological studies remains limited. In this study, the lengths of scapular setae of the eriophyoid mite Abacarus panticis Keifer collected from 18 sites in Taiwan were used as an example to evaluate the eligibility of finite mixture models. We then tested the hypothesis that longer scapular setae can facilitate dispersal. Lastly, we investigate morphological variation in various seta morphs by geometric morphometric techniques. Finite mixture models can satisfactorily classify scapular setae of A. panticis into long and short seta morphs. Abacarus panticis of the long morph only occurred in five sites whereas the short seta morph existed in all study sites. Geometric morphometric analyses revealed a more elongated coxal area in individuals of long morph than in those of short morph. Because the short morph is more widespread in geographical distribution than the long morph, longer scapular setae seem unlikely a specialized adaptation for dispersal. Further studies should capitalize on the finite mixture model in the delimitation of continuous morphological characters.
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Autonomous in situ analysis and real-time chemical detection using a backpack miniature mass spectrometer: concept, instrumentation development, and performance.
Anal. Chem.
PUBLISHED: 02-24-2014
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A major design objective of portable mass spectrometers is the ability to perform in situ chemical analysis on target samples in their native states in the undisturbed environment. The miniature instrument described here is fully contained in a wearable backpack (10 kg) with a geometry-independent low-temperature plasma (LTP) ion source integrated into a hand-held head unit (2 kg) to allow direct surface sampling and analysis. Detection of chemical warfare agent (CWA) simulants, illicit drugs, and explosives is demonstrated at nanogram levels directly from surfaces in near real time including those that have complex geometries, those that are heat-sensitive, and those bearing complex sample matrices. The instrument consumes an average of 65 W of power and can be operated autonomously under battery power for ca. 1.5 h, including the initial pump-down of the manifold. The maximum mass-to-charge ratio is 925 Th with mass resolution of 1-2 amu full width at half-maximun (fwhm) across the mass range. Multiple stages of tandem analysis can be performed to identify individual compounds in complex mixtures. Both positive and negative ion modes are available. A graphical user interface (GUI) is available for novice users to facilitate data acquisition and real-time spectral matching.
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Mini 12, miniature mass spectrometer for clinical and other applications--introduction and characterization.
Anal. Chem.
PUBLISHED: 02-24-2014
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A benchtop miniature mass spectrometer system, Mini 12, with ambient ionization source and tandem mass spectrometry capabilities has been developed and characterized. This instrument was developed as a self-contained system to produce quantitative results for unprocessed samples of small volumes including nonvolatile analytes. The ion processing system, vacuum system, and control system are detailed. An integrated sample loading system facilitates automated operation. A user interface has been developed to acquire and to interpret analytical results for personnel who have limited mass spectrometry knowledge. Peak widths of ?m/z 0.6 Th (full width at half-maximum) and a mass range of up to m/z 900 are demonstrated with the rectilinear ion trap mass analyzer. Multistage experiments up to MS(5) are accomplished. Consumable cartridges have been designed for use in ambient paper spray ionization, and the recently developed extraction spray ionization method has been employed to improve the quantitative performance. Monitoring of trace-levels of chemicals in therapeutic drugs, as well as in food safety and environmental protection operations is demonstrated. Dual MS/MS scans are implemented to obtain the intensities of the fragment ions from the analyte and its internal standard, and the ratio is used in quantitative analysis of complex samples. Limits of quantitation (LOQ) of 7.5 ng/mL, with relative standard deviations below 10%, have been obtained for selected therapeutic drugs in whole blood throughout their individual therapeutic ranges.
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Optimized metal-organic-framework nanospheres for drug delivery: evaluation of small-molecule encapsulation.
ACS Nano
PUBLISHED: 02-14-2014
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We have developed a general synthetic route to encapsulate small molecules in monodisperse zeolitic imid-azolate framework-8 (ZIF-8) nanospheres for drug delivery. Electron microscopy, powder X-ray diffraction, and elemental analysis show that the small-molecule-encapsulated ZIF-8 nanospheres are uniform 70 nm particles with single-crystalline structure. Several small molecules, including fluorescein and the anticancer drug camptothecin, were encapsulated inside of the ZIF-8 framework. Evaluation of fluorescein-encapsulated ZIF-8 nanospheres in the MCF-7 breast cancer cell line demonstrated cell internalization and minimal cytotoxicity. The 70 nm particle size facilitates cellular uptake, and the pH-responsive dissociation of the ZIF-8 framework likely results in endosomal release of the small-molecule cargo, thereby rendering the ZIF-8 scaffold an ideal drug delivery vehicle. To confirm this, we demonstrate that camptothecin encapsulated ZIF-8 particles show enhanced cell death, indicative of internalization and intracellular release of the drug. To demonstrate the versatility of this ZIF-8 system, iron oxide nanoparticles were also encapsulated into the ZIF-8 nanospheres, thereby endowing magnetic features to these nanospheres.
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Integrative modeling of multi-platform genomic data under the framework of mediation analysis.
Stat Med
PUBLISHED: 02-05-2014
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Given the availability of genomic data, there have been emerging interests in integrating multi-platform data. Here, we propose to model genetics (single nucleotide polymorphism (SNP)), epigenetics (DNA methylation), and gene expression data as a biological process to delineate phenotypic traits under the framework of causal mediation modeling. We propose a regression model for the joint effect of SNPs, methylation, gene expression, and their nonlinear interactions on the outcome and develop a variance component score test for any arbitrary set of regression coefficients. The test statistic under the null follows a mixture of chi-square distributions, which can be approximated using a characteristic function inversion method or a perturbation procedure. We construct tests for candidate models determined by different combinations of SNPs, DNA methylation, gene expression, and interactions and further propose an omnibus test to accommodate different models. We then study three path-specific effects: the direct effect of SNPs on the outcome, the effect mediated through expression, and the effect through methylation. We characterize correspondences between the three path-specific effects and coefficients in the regression model, which are influenced by causal relations among SNPs, DNA methylation, and gene expression. We illustrate the utility of our method in two genomic studies and numerical simulation studies. Copyright © 2014 John Wiley & Sons, Ltd.
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Implementation of dipolar resonant excitation for collision induced dissociation with ion mobility/time-of-flight MS.
J. Am. Soc. Mass Spectrom.
PUBLISHED: 01-28-2014
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An ion mobility/time-of-flight mass spectrometer (IMS/TOF MS) platform that allows for resonant excitation collision induced dissociation (CID) is presented. Highly efficient, mass-resolved fragmentation without additional excitation of product ions was accomplished and over-fragmentation common in beam-type CID experiments was alleviated. A quadrupole ion guide was modified to apply a dipolar AC signal across a pair of rods for resonant excitation. The method was characterized with singly protonated methionine enkephalin and triply protonated peptide angiotensin I, yielding maximum CID efficiencies of 44% and 84%, respectively. The Mathieu q(x,y) parameter was set at 0.707 for these experiments to maximize pseudopotential well depths and CID efficiencies. Resonant excitation CID was compared with beam-type CID for the peptide mixture. The ability to apply resonant waveforms in mobility-resolved windows is demonstrated with a peptide mixture yielding fragmentation over a range of mass-to-charge (m/z) ratios within a single IMS-MS analysis.
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Clinical features of patients with carbapenem nonsusceptible Klebsiella pneumoniae and Escherichia coli in intensive care units: A nationwide multicenter study in Taiwan.
J Microbiol Immunol Infect
PUBLISHED: 01-16-2014
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Patients in intensive care units (ICUs) are especially prone to colonization and infection by carbapenem-resistant Enterobacteriaceae. We conducted a multicenter investigation to study the clinical and microbiological characteristics of patients with carbapenem nonsusceptible Klebsiella pneumoniae and Escherichia coli in ICUs of Taiwanese hospitals.
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TREM-1 promotes survival during Klebsiella pneumoniae liver abscess in mice.
Infect. Immun.
PUBLISHED: 01-06-2014
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Klebsiella pneumoniae liver abscess (KPLA) is prevalent in East Asia. Liver abscess can develop after translocation of K. pneumoniae from a patient's bowel into the liver via the portal circulation. TREM-1 (triggering receptor expressed on myeloid cells 1) amplifies inflammatory signaling during infection, but its role in KPLA is poorly understood. We used an animal study to characterize the role of TREM-1 in KPLA. We compared survival rates, bacterial burdens in tissues, inflammatory cytokine levels, and histology findings between wild-type and Trem-1 knockout (KO) mice after oral inoculation of capsular type K1 K. pneumoniae. Translocation of K. pneumoniae to mesenteric lymph nodes and liver was examined, and intestinal permeability, antimicrobial peptide expression, and the clearance of K. pneumoniae in the small intestine were determined. In the absence of TREM-1, KPLA model mice showed increased K. pneumoniae dissemination, enhanced liver and systemic inflammation, and reduced survival. Impaired bacterial clearance in the small intestine causes enhanced K. pneumoniae translocation, which renders Trem-1 KO mice more susceptible to K. pneumoniae oral infection. In conclusion, TREM-1-mediated bacterial clearance in the small intestine is an important immune response against K. pneumoniae. TREM-1 deficiency enhances K. pneumoniae translocation in the small intestine and increases mortality rates in mice with KPLA.
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A Linkage between SmeIJK Efflux Pump, Cell Envelope Integrity, and ?E-Mediated Envelope Stress Response in Stenotrophomonas maltophilia.
PLoS ONE
PUBLISHED: 01-01-2014
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Resistance nodulation division (RND) efflux pumps, such as the SmeIJK pump of Stenotrophomonas maltophilia, are known to contribute to the multidrug resistance in Gram-negative bacteria. However, some RND pumps are constitutively expressed even though no antimicrobial stresses occur, implying that there should be some physical implications for these RND pumps. In this study, the role of SmeIJK in antimicrobials resistance, envelope integrity, and ?E-mediated envelope stress response (ESR) of S. maltophilia was assessed. SmeIJK was involved in the intrinsic resistance of S. maltophilia KJ to aminoglycosides and leucomycin. Compared with the wild-type KJ, the smeIJK deletion mutant exhibited growth retardation in the MH medium, an increased sensitivity to membrane-damaging agents (MDAs), as well as activation of an ?E-mediated ESR. Moreover, the expression of smeIJK was further induced by sub-lethal concentrations of MDAs or surfactants in an ?E-dependent manner. These data collectively suggested an alternative physiological role of smeIJK in cell envelope integrity maintenance and ?E-mediated ESR beyond the efflux of antibiotics. Because of the necessity of the physiological role of SmeIJK in protecting S. maltophilia from the envelope stress, smeIJK is constitutively expressed, which, in turn, contributes the intrinsic resistance to aminoglycoside and leucomycin. This is the first demonstration of the linkage among RND-type efflux pump, cell envelope integrity, and ?E-mediated ESR in S. maltophilia.
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Sensitization to food and inhalant allergens in relation to atopic diseases in early childhood: a birth cohort study.
PLoS ONE
PUBLISHED: 01-01-2014
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A correct interpretation of sensitization to common allergens is critical in determining susceptibility to allergic diseases. The aim of this study was to investigate the patterns of sensitization to food and inhalant allergens, and their relation to the development of atopic diseases in early childhood.
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Identification of CD24 as a cancer stem cell marker in human nasopharyngeal carcinoma.
PLoS ONE
PUBLISHED: 01-01-2014
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Cancer stem cells (CSCs) represent a unique sub-population of tumor cells with the ability to initiate tumor growth and sustain self-renewal. Although CSC biomarkers have been described for various tumors, only a few markers have been identified for nasopharyngeal carcinoma (NPC). In this study, we show that CD24+ cells isolated from human NPC cell lines express stem cell genes (Sox2, Oct4, Nanog, Bmi-1, and Rex-1), and show activation of the Wnt/?-catenin signaling pathway. CD24+ cells possess typical CSC characteristics that include enhanced cell proliferation, increased colony and sphere formation, maintenance of cell differentiation potential in prolonged culture, and enhanced resistance to chemotherapeutic drugs. Notably, CD24+ cells produce tumors following inoculation of as few as 500 cells in immunodeficient NOD/SCID mice. CD24+ cells further show increased invasion ability in vitro, which correlates with enhanced expression of matrix metalloproteinase 2 and 9. In summary, our results suggest that CD24 represents a novel CSC biomarker in NPC.
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Suboptimal vitamin D status in a population-based study of Asian children: prevalence and relation to allergic diseases and atopy.
PLoS ONE
PUBLISHED: 01-01-2014
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New evidence shows high prevalence of vitamin D deficiency in many countries and some studies suggest a possible link between vitamin D status and allergic diseases. The objectives of this study were to determine the prevalence of suboptimal vitamin D status in a population sample of Asian children and to investigate the relationship of vitamin D status with allergic diseases and atopy.
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Broad-spectrum transgenic resistance against distinct tospovirus species at the genus level.
PLoS ONE
PUBLISHED: 01-01-2014
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Thrips-borne tospoviruses cause severe damage to crops worldwide. In this investigation, tobacco lines transgenic for individual WLm constructs containing the conserved motifs of the L RNA-encoded RNA-dependent RNA polymerase (L) gene of Watermelon silver mottle virus (WSMoV) were generated by Agrobacterium-mediated transformation. The WLm constructs included: (i) translatable WLm in a sense orientation; (ii) untranslatable WLmt with two stop codons; (iii) untranslatable WLmts with stop codons and a frame-shift; (iv) untranslatable antisense WLmA; and (v) WLmhp with an untranslatable inverted repeat of WLm containing the tospoviral S RNA 3'-terminal consensus sequence (5'-ATTGCTCT-3') and an NcoI site as a linker to generate a double-stranded hairpin transcript. A total of 46.7-70.0% transgenic tobacco lines derived from individual constructs showed resistance to the homologous WSMoV; 35.7-100% plants of these different WSMoV-resistant lines exhibited broad-spectrum resistance against four other serologically unrelated tospoviruses Tomato spotted wilt virus, Groundnut yellow spot virus, Impatiens necrotic spot virus and Groundnut chlorotic fan-spot virus. The selected transgenic tobacco lines also exhibited broad-spectrum resistance against five additional tospoviruses from WSMoV and Iris yellow spot virus clades, but not against RNA viruses from other genera. Northern analyses indicated that the broad-spectrum resistance is mediated by RNA silencing. To validate the L conserved region resistance in vegetable crops, the constructs were also used to generate transgenic tomato lines, which also showed effective resistance against WSMoV and other tospoviruses. Thus, our approach of using the conserved motifs of tospoviral L gene as a transgene generates broad-spectrum resistance against tospoviruses at the genus level.
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RegPhos 2.0: an updated resource to explore protein kinase-substrate phosphorylation networks in mammals.
Database (Oxford)
PUBLISHED: 01-01-2014
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Protein phosphorylation catalyzed by kinases plays crucial roles in regulating a variety of intracellular processes. Owing to an increasing number of in vivo phosphorylation sites that have been identified by mass spectrometry (MS)-based proteomics, the RegPhos, available online at http://csb.cse.yzu.edu.tw/RegPhos2/, was developed to explore protein phosphorylation networks in human. In this update, we not only enhance the data content in human but also investigate kinase-substrate phosphorylation networks in mouse and rat. The experimentally validated phosphorylation sites as well as their catalytic kinases were extracted from public resources, and MS/MS phosphopeptides were manually curated from research articles. RegPhos 2.0 aims to provide a more comprehensive view of intracellular signaling networks by integrating the information of metabolic pathways and protein-protein interactions. A case study shows that analyzing the phosphoproteome profile of time-dependent cell activation obtained from Liquid chromatography-mass spectrometry (LC-MS/MS) analysis, the RegPhos deciphered not only the consistent scheme in B cell receptor (BCR) signaling pathway but also novel regulatory molecules that may involve in it. With an attempt to help users efficiently identify the candidate biomarkers in cancers, 30 microarray experiments, including 39 cancerous versus normal cells, were analyzed for detecting cancer-specific expressed genes coding for kinases and their substrates. Furthermore, this update features an improved web interface to facilitate convenient access to the exploration of phosphorylation networks for a group of genes/proteins. Database URL: http://csb.cse.yzu.edu.tw/RegPhos2/
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Clinical and microbiological characteristics of tigecycline non-susceptible Klebsiella pneumoniae bacteremia in Taiwan.
BMC Infect. Dis.
PUBLISHED: 01-01-2014
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Resistance among Klebsiella pneumoniae to most antibiotics is on the rise. Tigecycline has been considered as one of the few therapeutic options available to treat multidrug-resistant bacteria. We investigated the clinical and microbiological characteristics of tigecycline non-susceptible K. pneumoniae bacteremia.
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topPTM: a new module of dbPTM for identifying functional post-translational modifications in transmembrane proteins.
Nucleic Acids Res.
PUBLISHED: 12-02-2013
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Transmembrane (TM) proteins have crucial roles in various cellular processes. The location of post-translational modifications (PTMs) on TM proteins is associated with their functional roles in various cellular processes. Given the importance of PTMs in the functioning of TM proteins, this study developed topPTM (available online at http://topPTM.cse.yzu.edu.tw), a new dbPTM module that provides a public resource for identifying the functional PTM sites on TM proteins with structural topology. Experimentally verified TM topology data were integrated from TMPad, TOPDB, PDBTM and OPM. In addition to the PTMs obtained from dbPTM, experimentally verified PTM sites were manually extracted from research articles by text mining. In an attempt to provide a full investigation of PTM sites on TM proteins, all UniProtKB protein entries containing annotations related to membrane localization and TM topology were considered potential TM proteins. Two effective tools were then used to annotate the structural topology of the potential TM proteins. The TM topology of TM proteins is represented by graphical visualization, as well as by the PTM sites. To delineate the structural correlation between the PTM sites and TM topologies, the tertiary structure of PTM sites on TM proteins was visualized by Jmol program. Given the support of research articles by manual curation and the investigation of domain-domain interactions in Protein Data Bank, 1347 PTM substrate sites are associated with protein-protein interactions for 773 TM proteins. The database content is regularly updated on publication of new data by continuous surveys of research articles and available resources.
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Clinical performance and satisfaction of removable prostheses with self-adjusting magnetic attachments.
J Prosthet Dent
PUBLISHED: 11-07-2013
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Conventional magnetic attachments have rigid assemblies and are unable to compensate for the movement of the prosthesis under function, which may result in the deepening of periodontal pockets and an increase in the mobility of abutment teeth.
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Magnetic attachment for implant overdentures: influence of contact relationship with the denture base on stability and bending strain.
Int J Prosthodont
PUBLISHED: 11-02-2013
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This study evaluated how the contact height between the magnetic attachment and denture base influences stability and bending strain. An implant modified with strain gauges and a magnetic attachment mounted in an acrylic resin block were used to characterize systems with varying degrees or heights of contact with the abutment. Bending strain under lateral loading increased significantly as the contact height decreased. In the no contact and resilient contact groups, magnetic assemblies separated at reduced bending strain in all loading conditions. The contact height of the magnetic attachment influenced the stability and the amount of bending strain on the implant.
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cis-Resveratrol produces anti-inflammatory effects by inhibiting canonical and non-canonical inflammasomes in macrophages.
Innate Immun
PUBLISHED: 10-22-2013
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Resveratrol, a natural phenolic compound found in red grapes and wine, exists as cis and trans isomers. Recent studies have shown that trans-resveratrol possesses anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-tumor and immunomodulatory properties. However, it remains unclear whether cis-resveratrol may exhibit similar activities. The objective of the present study was to examine the effects of cis- and trans-resveratrol on the production of pro-inflammatory cytokines and mediators in human macrophages. We examined the possibility that cis- and trans-resveratrol may affect cytokine secretion by modulating inflammasomes, intracellular multi-protein complexes, the assembly of which leads to caspase-1 activation and secretion of active IL-1? by macrophages. Our results show that pre-treatment of macrophages with cis-resveratrol not only reduces pro-IL-1? production and IL-1? secretion, but also suppresses ATP-induced transcription and activation of caspase-1 and caspase-4. Notably, cis-resveratrol inhibits the expression of the purinergic receptor, P2X7R, and the endoplasmic reticulum stress marker, Glc-regulated protein 78, but also reduces reactive oxygen species production. Moreover, cis-resveratrol attenuates cyclooxygenase-2 expression and prostaglandin E2 production. cis-Resveratrol also decreases the phosphorylation of p38 MAPK and expression of the c-Jun protein. These results indicate that cis-resveratrol produces anti-inflammatory effects by inhibiting both the canonical and non-canonical inflammasomes, and associated pathways in human macrophages.
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Design and characterization of low loss 50 picoseconds delay line on SOI platform.
Opt Express
PUBLISHED: 10-10-2013
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We design and experimentally demonstrate 50 picoseconds (ps) low loss delay line on 300 nm SOI platform. The delay line unit consists of straight rib waveguide and strip bend section linked by a transition taper waveguide. Low propagation loss of ~0.1 dB/cm is achieved on the straight rib waveguide. With taking into account both low loss and desirable delay, a complete design and characterization process for passive delay line is presented. Our measurement results show that about 0.7 dB excess loss is achievable for 50 ps delay. The loss can be further reduced by adjusting the layout parameters.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.