WorldWideScience

Sample records for small signal amplification

  1. Small sample whole-genome amplification

    Science.gov (United States)

    Hara, Christine; Nguyen, Christine; Wheeler, Elizabeth; Sorensen, Karen; Arroyo, Erin; Vrankovich, Greg; Christian, Allen

    2005-11-01

    Many challenges arise when trying to amplify and analyze human samples collected in the field due to limitations in sample quantity, and contamination of the starting material. Tests such as DNA fingerprinting and mitochondrial typing require a certain sample size and are carried out in large volume reactions; in cases where insufficient sample is present whole genome amplification (WGA) can be used. WGA allows very small quantities of DNA to be amplified in a way that enables subsequent DNA-based tests to be performed. A limiting step to WGA is sample preparation. To minimize the necessary sample size, we have developed two modifications of WGA: the first allows for an increase in amplified product from small, nanoscale, purified samples with the use of carrier DNA while the second is a single-step method for cleaning and amplifying samples all in one column. Conventional DNA cleanup involves binding the DNA to silica, washing away impurities, and then releasing the DNA for subsequent testing. We have eliminated losses associated with incomplete sample release, thereby decreasing the required amount of starting template for DNA testing. Both techniques address the limitations of sample size by providing ample copies of genomic samples. Carrier DNA, included in our WGA reactions, can be used when amplifying samples with the standard purification method, or can be used in conjunction with our single-step DNA purification technique to potentially further decrease the amount of starting sample necessary for future forensic DNA-based assays.

  2. An enzymatic signal amplification system for calorimetric studies of cellobiohydrolases

    DEFF Research Database (Denmark)

    Murphy, Leigh; Baumann, Martin Johannes; Borch, Kim

    2010-01-01

    amplification method has been developed to measure even slow hydrolytically active enzymes such as cellobiohydrolases. This method is explained in detail for the amplification of the heat signal by more than 130 times by using glucose oxidase and catalase. The kinetics of this complex coupled reaction system...

  3. A mechanism of gene amplification driven by small DNA fragments.

    Directory of Open Access Journals (Sweden)

    Kuntal Mukherjee

    Full Text Available DNA amplification is a molecular process that increases the copy number of a chromosomal tract and often causes elevated expression of the amplified gene(s. Although gene amplification is frequently observed in cancer and other degenerative disorders, the molecular mechanisms involved in the process of DNA copy number increase remain largely unknown. We hypothesized that small DNA fragments could be the trigger of DNA amplification events. Following our findings that small fragments of DNA in the form of DNA oligonucleotides can be highly recombinogenic, we have developed a system in the yeast Saccharomyces cerevisiae to capture events of chromosomal DNA amplification initiated by small DNA fragments. Here we demonstrate that small DNAs can amplify a chromosomal region, generating either tandem duplications or acentric extrachromosomal DNA circles. Small fragment-driven DNA amplification (SFDA occurs with a frequency that increases with the length of homology between the small DNAs and the target chromosomal regions. SFDA events are triggered even by small single-stranded molecules with as little as 20-nt homology with the genomic target. A double-strand break (DSB external to the chromosomal amplicon region stimulates the amplification event up to a factor of 20 and favors formation of extrachromosomal circles. SFDA is dependent on Rad52 and Rad59, partially dependent on Rad1, Rad10, and Pol32, and independent of Rad51, suggesting a single-strand annealing mechanism. Our results reveal a novel molecular model for gene amplification, in which small DNA fragments drive DNA amplification and define the boundaries of the amplicon region. As DNA fragments are frequently found both inside cells and in the extracellular environment, such as the serum of patients with cancer or other degenerative disorders, we propose that SFDA may be a common mechanism for DNA amplification in cancer cells, as well as a more general cause of DNA copy number variation

  4. Signal amplification and Pierce's instability in convergent particle beams

    International Nuclear Information System (INIS)

    Gnavi, G.; Gratton, F.T.

    1988-01-01

    Relativistic electron beams flowing between cylindrical and spherical electrodes (or solid angles sections of electrodes with these geometries) are studied. The beams are focused through the axis in the cylindrical case or through the center when spherical electrodes are considered. It is assumed that the external electrode is part of a device which accelerates the particles, the inner electrode is passive and removes the beams from the system. Electrons move by inertia in the interelectrode space, neutralized by an ion background. Properties of radial, small amplitude, perturbations are analyzed theoretically. Previous analyses of counterstreaming beams indicated that convergence modifies considerably the oscillations spectrum. Here, results on the amplification of signals when a beam is modulated at the external electrode are reported. Then, conditions for the instability of a beam when it flows through grounded electrodes (Pierce's instability of only one beam) are examined

  5. Photoacoustic signal amplification through plasmonic nanoparticle aggregation

    OpenAIRE

    Bayer, Carolyn L.; Nam, Seung Yun; Chen, Yun-Sheng; Emelianov, Stanislav Y.

    2013-01-01

    Photoacoustic imaging, using targeted plasmonic metallic nanoparticles, is a promising noninvasive molecular imaging method. Analysis of the photoacoustic signal generated by plasmonic metallic nanoparticles is complex because of the dependence upon physical properties of both the nanoparticle and the surrounding environment. We studied the effect of the aggregation of gold nanoparticles on the photoacoustic signal amplitude. We found that the photoacoustic signal from aggregated silica-coate...

  6. Development of an electronic system for signals amplification

    International Nuclear Information System (INIS)

    Santos, Italo S.; Tobias, Carmen C.B.

    2009-01-01

    This paper presents the obtained results with a spectrometer for electromagnetic radiation whose detector, a Si PIN type diode, was directly coupled to a signal amplification system developed in this project for scientific initiation. The linearity conditions and the gain operational limits, constituted of two stages of amplification based on the employment of devices from AMTEK A225 and A206, were determined using a precision pulse generator. The obtained results shown that the developed system is stable and linear in the gain range of 50-150. The spectrometric response of the electronic system coupled to the Siemens SFH-00206 type diode, were studied in view of the register of the 59.5 keV gamma ray spectra proceeding from 241 Am as function of the reversal polarization voltage. The influence pf the voltage and the electronic contribution in the energy resolution of the registered spectra under room temperature (22 degree Celsius) had also investigated considering the more adequate value of the coupling capacitance of the amplification system diode. Up to the present. the best energy resolution (FWHM = 4.85 keV) of the 59.5 keV line was obtained for the condition of the detector polarization at 16 V. This result proves that the signal amplification system developed coupled to the SFH00206 diode, besides the low cost, excellent operational condition for the detection and spectrometry or low energy electromagnetic radiation

  7. PARAMETRIC AMPLIFICATION OF THE SIGNALS IN THE ELECTROSTATIC GRAVIINERTIAL SENSOR

    Directory of Open Access Journals (Sweden)

    I. Z. Gilavdary

    2017-01-01

    Full Text Available The challenges of designing simple, reliable, and high sensitivity graviinertial sensors are investigated. The sensor comprises a proof mass (PM and is fixed with the housing by the elastic torsion suspension. PM makes small rotations under the action of gravitational forces or inertial forces.The distinctive features of the sensor are that the differential electrostatic system provides simultaneous reading of the desired signal and a control the torsional rigidity of suspension. In addition, the PM's rotational angular velocity transforms in the alternating current flowing through the capacitors. The presence of аlternating current (AC voltage sources allows to get the parametric amplification of AC and significantly to improve the sensitivity of the sensor. In the simplest case, the sensor does not contain any feedback circuits.As an example, calculations of the micromechanical linear accelerations confirm that the periodic modulation of the coefficient of elastic stiffness of the suspension can significantly increase the sensitivity in the low frequency range, even in the absence of parametric resonance.Conditions for suppressions of background current participating in the output signal from a parametric pumping due to the asymmetry of the differential circuits are set. The frequency characteristics calculations of the sensor were carried out. It is expected, that the proposed sensor design ensures minimum noise level, which can be achievable in the graviinertial sensors. This design and the constructed theory can serve as a basis for creating a wide range of graviinertial devices operating on a movable base, for example, linear and angular accelerometer, gravity gradiometer, gravimeters, and inclinometers, which can be realized in the hybrid and in the micromechanical versions.

  8. Two-phase xenon detector with gas amplification and electroluminescent signal detection

    International Nuclear Information System (INIS)

    Akimov, D.Yu.; Burenkov, A.A.; Grishkin, Yu.L.; Kovalenko, A.G.; Lebedenko, V.N.; Stekhanov, V.N.

    2008-01-01

    An optical technique for detecting ionization electrons produced during ionization of the liquid phase has been experimentally tested in two-phase (liquid-gas) xenon. The effects of gas and electroluminescent amplifications at the wire anode are simultaneously used for detection. This method allows construction of a supersensitive detector of small ionization signals-down to those corresponding to the detection of single electrons [ru

  9. Electrochemical DNA biosensor based on MNAzyme-mediated signal amplification

    International Nuclear Information System (INIS)

    Diao, Wei; Tang, Min; Ding, Xiaojuan; Zhang, Ye; Yang, Jianru; Cheng, Wenbin; Mo, Fei; Wen, Bo; Xu, Lulu; Yan, Yurong

    2016-01-01

    The authors describe an electrochemical sensing strategy for highly sensitive and specific detection of target (analyte) DNA based on an amplification scheme mediated by a multicomponent nucleic acid enzyme (MNAzyme). MNAzymes were formed by multicomponent complexes which produce amplified “output” signals in response to specific “input” signal. In the presence of target nucleic acid, multiple partial enzymes (partzymes) oligonucleotides are assembled to form active MNAzymes. These can cleave H0 substrate into two pieces, thereby releasing the activated MNAzyme to undergo an additional cycle of amplification. Here, the two pieces contain a biotin-tagged sequence and a byproduct. The biotin-tagged sequences are specifically captured by the detection probes immobilized on the gold electrode. By employing streptavidinylated alkaline phosphatase as an enzyme label, an electrochemical signal is obtained. The electrode, if operated at a working potential of 0.25 V (vs. Ag/AgCl) in solution of pH 7.5, covers the 100 pM to 0.25 μM DNA concentration range, with a 79 pM detection limit. In our perception, the strategy introduced here has a wider potential in that it may be applied to molecular diagnostics and pathogen detection. (author)

  10. Signal amplification for impedimetric genosensing using gold-streptavidin nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Bonanni, A.; Esplandiu, M.J. [Sensors and Biosensors Group, Department of Chemistry, Universitat Autonoma de Barcelona, Edifici Cn, 08193 Bellaterra, Barcelona (Spain); Valle, M. del [Sensors and Biosensors Group, Department of Chemistry, Universitat Autonoma de Barcelona, Edifici Cn, 08193 Bellaterra, Barcelona (Spain)], E-mail: manel.delvalle@uab.es

    2008-04-20

    Streptavidin-coated gold nanoparticles (strept-AuNPs) were used in this work to amplify the impedimetric signal generated in a biosensor detecting the DNA hybridization event. Probe oligomer was adsorbed onto a graphite epoxy composite (GEC) electrode surface and the impedance measurement was performed in a solution containing the redox marker ferrocyanide/ferricyanide. The biotinylated complementary oligomer was used as target. The change of interfacial charge transfer resistance (R{sub ct}), experimented by the redox marker, was recorded to confirm the hybrid formation. The addition of strept-AuNPs, binding to the target due to the strong streptavidin-biotin interaction, led to a further increment of R{sub ct} thus obtaining significant signal amplification. Strept-AuNPs on the electrode surface were observed by scanning electron microscopy (SEM) after silver enhancement treatment. A competitive binding assay was also performed using unlabelled DNA target to demonstrate its applicability to real sample analysis.

  11. Current Technologies of Electrochemical Immunosensors: Perspective on Signal Amplification

    Directory of Open Access Journals (Sweden)

    Il-Hoon Cho

    2018-01-01

    Full Text Available An electrochemical immunosensor employs antibodies as capture and detection means to produce electrical charges for the quantitative analysis of target molecules. This sensor type can be utilized as a miniaturized device for the detection of point-of-care testing (POCT. Achieving high-performance analysis regarding sensitivity has been one of the key issues with developing this type of biosensor system. Many modern nanotechnology efforts allowed for the development of innovative electrochemical biosensors with high sensitivity by employing various nanomaterials that facilitate the electron transfer and carrying capacity of signal tracers in combination with surface modification and bioconjugation techniques. In this review, we introduce novel nanomaterials (e.g., carbon nanotube, graphene, indium tin oxide, nanowire and metallic nanoparticles in order to construct a high-performance electrode. Also, we describe how to increase the number of signal tracers by employing nanomaterials as carriers and making the polymeric enzyme complex associated with redox cycling for signal amplification. The pros and cons of each method are considered throughout this review. We expect that these reviewed strategies for signal enhancement will be applied to the next versions of lateral-flow paper chromatography and microfluidic immunosensor, which are considered the most practical POCT biosensor platforms.

  12. Signal Amplification Technique (SAT): an approach for improving resolution and reducing image noise in computed tomography

    International Nuclear Information System (INIS)

    Phelps, M.E.; Huang, S.C.; Hoffman, E.J.; Plummer, D.; Carson, R.

    1981-01-01

    Spatial resolution improvements in computed tomography (CT) have been limited by the large and unique error propagation properties of this technique. The desire to provide maximum image resolution has resulted in the use of reconstruction filter functions designed to produce tomographic images with resolution as close as possible to the intrinsic detector resolution. Thus, many CT systems produce images with excessive noise with the system resolution determined by the detector resolution rather than the reconstruction algorithm. CT is a rigorous mathematical technique which applies an increasing amplification to increasing spatial frequencies in the measured data. This mathematical approach to spatial frequency amplification cannot distinguish between signal and noise and therefore both are amplified equally. We report here a method in which tomographic resolution is improved by using very small detectors to selectively amplify the signal and not noise. Thus, this approach is referred to as the signal amplification technique (SAT). SAT can provide dramatic improvements in image resolution without increases in statistical noise or dose because increases in the cutoff frequency of the reconstruction algorithm are not required to improve image resolution. Alternatively, in cases where image counts are low, such as in rapid dynamic or receptor studies, statistical noise can be reduced by lowering the cutoff frequency while still maintaining the best possible image resolution. A possible system design for a positron CT system with SAT is described

  13. An ultrasensitive colorimeter assay strategy for p53 mutation assisted by nicking endonuclease signal amplification.

    Science.gov (United States)

    Lin, Zhenyu; Yang, Weiqiang; Zhang, Guiyun; Liu, Qida; Qiu, Bin; Cai, Zongwei; Chen, Guonan

    2011-08-28

    A novel catalytic colorimetric assay assisted by nicking endonuclease signal amplification (NESA) was developed. With the signal amplification, the detection limit of the p53 target gene can be as low as 1 pM, which is nearly 5 orders of magnitude lower than that of other previously reported colorimetric DNA detection strategies based on catalytic DNAzyme.

  14. Signal amplification of microRNAs with modified strand displacement-based cycling probe technology.

    Science.gov (United States)

    Jia, Huning; Bu, Ying; Zou, Bingjie; Wang, Jianping; Kumar, Shalen; Pitman, Janet L; Zhou, Guohua; Song, Qinxin

    2016-10-24

    Micro ribose nucleic acids (miRNAs) play an important role in biological processes such as cell differentiation, proliferation and apoptosis. Therefore, miRNAs are potentially a powerful marker for monitoring cancer and diagnosis. Here, we present sensitive signal amplification for miRNAs based on modified cycling probe technology with strand displacement amplification. miRNA was captured by the template coupled with beads, and then the first cycle based on SDA was repeatedly extended to the nicking end, which was produced by the extension reaction of miRNA. The products generated by SDA are captured by a molecular beacon (MB), which is designed to initiate the second amplification cycle, with a similar principle to the cycling probe technology (CPT), which is based on repeated digestion of the DNA-RNA hybrid by the RNase H. After one sample enrichment and two steps of signal amplification, 0.1 pM of let-7a can be detected. The miRNA assay exhibits a great dynamic range of over 100 orders of magnitude and high specificity to clearly discriminate a single base difference in miRNA sequences. This isothermal amplification does not require any special temperature control instrument. The assay is also about signal amplification rather than template amplification, therefore minimising contamination issues. In addition, there is no need for the reverse transcription (RT) process. Thus the amplification is suitable for miRNA detection.

  15. Simultaneous electrical and mechanical resonance drive for large signal amplification of micro resonators

    KAUST Repository

    Hasan, M. H.

    2018-01-12

    Achieving large signal-noise ratio using low levels of excitation signal is key requirement for practical applications of micro and nano electromechanical resonators. In this work, we introduce the double electromechanical resonance drive concept to achieve an order-of-magnitude dynamic signal amplification in micro resonators. The concept relies on simultaneously activating the micro-resonator mechanical and electrical resonance frequencies. We report an input voltage amplification up to 15 times for a micro-resonator when its electrical resonance is tuned to match the mechanical resonance that leads to dynamic signal amplification in air (Quality factor enhancement). Furthermore, using a multi-frequency excitation technique, input voltage and vibrational amplification of up to 30 times were shown for the same micro-resonator while relaxing the need to match its mechanical and electrical resonances.

  16. Simultaneous electrical and mechanical resonance drive for large signal amplification of micro resonators

    KAUST Repository

    Hasan, M. H.; Alsaleem, F. M.; Jaber, Nizar; Hafiz, Md Abdullah Al; Younis, Mohammad I.

    2018-01-01

    Achieving large signal-noise ratio using low levels of excitation signal is key requirement for practical applications of micro and nano electromechanical resonators. In this work, we introduce the double electromechanical resonance drive concept to achieve an order-of-magnitude dynamic signal amplification in micro resonators. The concept relies on simultaneously activating the micro-resonator mechanical and electrical resonance frequencies. We report an input voltage amplification up to 15 times for a micro-resonator when its electrical resonance is tuned to match the mechanical resonance that leads to dynamic signal amplification in air (Quality factor enhancement). Furthermore, using a multi-frequency excitation technique, input voltage and vibrational amplification of up to 30 times were shown for the same micro-resonator while relaxing the need to match its mechanical and electrical resonances.

  17. All-optical WDM Regeneration of DPSK Signals using Optical Fourier Transformation and Phase Sensitive Amplification

    DEFF Research Database (Denmark)

    Guan, Pengyu; Røge, Kasper Meldgaard; Kjøller, Niels-Kristian

    2015-01-01

    We propose a novel all-optical WDM regeneration scheme for DPSK signals based on optical Fourier transformation and phase sensitive amplification. Phase regeneration of a WDM signal consisting of 4x10-Gbit/s phase noise degraded DPSK channels is demonstrated for the first time.......We propose a novel all-optical WDM regeneration scheme for DPSK signals based on optical Fourier transformation and phase sensitive amplification. Phase regeneration of a WDM signal consisting of 4x10-Gbit/s phase noise degraded DPSK channels is demonstrated for the first time....

  18. Small signal microwave amplifier design

    CERN Document Server

    Grosch, Theodore

    2000-01-01

    This book explains techniques and examples for designing stable amplifiers for high-frequency applications in which the signal is small and the amplifier circuit is linear. An in-depth discussion of linear network theory provides the foundation needed to develop actual designs. Examples throughout the book will show you how to apply the knowledge gained in each chapter leading to the complex design of low noise amplifiers. Many exercises at the end of each chapter will help students to practice their skills. The solutions to these design problems are available in an accompanying solutions book

  19. Small Signal Loudspeaker Impedance Emulator

    DEFF Research Database (Denmark)

    Iversen, Niels Elkjær; Knott, Arnold

    2014-01-01

    Specifying the performance of audio amplifiers is typically done by playing sine waves into a pure ohmic load. However real loudspeaker impedances are not purely ohmic but characterized by the mechanical resonance between the mass of the diaphragm and the compliance of its suspension which vary...... from driver to driver. Therefore, a loudspeaker emulator capable of adjusting its impedance to that of a given driver is desired for measurement purposes. This paper proposes a loudspeaker emulator circuit for small signals. Simulations and experimental results are compared and show that it is possible...... to emulate the loudspeaker impedance with an electric circuit and that its resonance frequency can be changed by tuning two resistors....

  20. Tiny Grains Give Huge Gains: Nanocrystal–Based Signal Amplification for Biomolecule Detection

    Science.gov (United States)

    Tong, Sheng; Ren, Binbin; Zheng, Zhilan; Shen, Han; Bao, Gang

    2013-01-01

    Nanocrystals, despite their tiny sizes, contain thousands to millions of atoms. Here we show that the large number of atoms packed in each metallic nanocrystal can provide a huge gain in signal amplification for biomolecule detection. We have devised a highly sensitive, linear amplification scheme by integrating the dissolution of bound nanocrystals and metal-induced stoichiometric chromogenesis, and demonstrated that signal amplification is fully defined by the size and atom density of nanocrystals, which can be optimized through well-controlled nanocrystal synthesis. Further, the rich library of chromogenic reactions allows implementation of this scheme in various assay formats, as demonstrated by the iron oxide nanoparticle linked immunosorbent assay (ILISA) and blotting assay developed in this study. Our results indicate that, owing to the inherent simplicity, high sensitivity and repeatability, the nanocrystal based amplification scheme can significantly improve biomolecule quantification in both laboratory research and clinical diagnostics. This novel method adds a new dimension to current nanoparticle-based bioassays. PMID:23659350

  1. Method for signal conditioning and data acquisition system, based on variable amplification and feedback technique

    Energy Technology Data Exchange (ETDEWEB)

    Conti, Livio, E-mail: livio.conti@uninettunouniversity.net [Facoltà di Ingegneria, Università Telematica Internazionale Uninettuno, Corso Vittorio Emanuele II 39, 00186 Rome, Italy INFN Sezione Roma Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome (Italy); Sgrigna, Vittorio [Dipartimento di Matematica e Fisica, Università Roma Tre, 84 Via della Vasca Navale, I-00146 Rome (Italy); Zilpimiani, David [National Institute of Geophysics, Georgian Academy of Sciences, 1 M. Alexidze St., 009 Tbilisi, Georgia (United States); Assante, Dario [Facoltà di Ingegneria, Università Telematica Internazionale Uninettuno, Corso Vittorio Emanuele II 39, 00186 Rome, Italy INFN Sezione Roma Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome (Italy)

    2014-08-21

    An original method of signal conditioning and adaptive amplification is proposed for data acquisition systems of analog signals, conceived to obtain a high resolution spectrum of any input signal. The procedure is based on a feedback scheme of the signal amplification with aim at maximizing the dynamic range and resolution of the data acquisition system. The paper describes the signal conditioning, digitization, and data processing procedures applied to an a priori unknown signal in order to enucleate its amplitude and frequency content for applications in different environments: on the ground, in space, or in the laboratory. An electronic board of the conditioning module has also been constructed and described. In the paper are also discussed the main fields of application and advantages of the method with respect to those known today.

  2. Method for signal conditioning and data acquisition system, based on variable amplification and feedback technique

    International Nuclear Information System (INIS)

    Conti, Livio; Sgrigna, Vittorio; Zilpimiani, David; Assante, Dario

    2014-01-01

    An original method of signal conditioning and adaptive amplification is proposed for data acquisition systems of analog signals, conceived to obtain a high resolution spectrum of any input signal. The procedure is based on a feedback scheme of the signal amplification with aim at maximizing the dynamic range and resolution of the data acquisition system. The paper describes the signal conditioning, digitization, and data processing procedures applied to an a priori unknown signal in order to enucleate its amplitude and frequency content for applications in different environments: on the ground, in space, or in the laboratory. An electronic board of the conditioning module has also been constructed and described. In the paper are also discussed the main fields of application and advantages of the method with respect to those known today

  3. A new ultrasonic signal amplification method for detection of bacteria

    Science.gov (United States)

    Kant Shukla, Shiva; Resa López, Pablo; Sierra Sánchez, Carlos; Urréjola, José; Segura, Luis Elvira

    2012-10-01

    A new method is presented that increases the sensitivity of ultrasound-based techniques for detection of bacteria. The technique was developed for the detection of catalase-positive microorganisms. It uses a bubble trapping medium containing hydrogen peroxide that is mixed with the sample for microbiological evaluation. The enzyme catalase is present in catalase-positive bacteria, which induces a rapid hydrolysis of hydrogen peroxide, forming bubbles which remain in the medium. This reaction results in the amplification of the mechanical changes that the microorganisms produce in the medium. The effect can be detected by means of ultrasonic wave amplitude continuous measurement since the bubbles increase the ultrasonic attenuation significantly. It is shown that microorganism concentrations of the order of 105 cells ml-1 can be detected using this method. This allows an improvement of three orders of magnitude in the ultrasonic detection threshold of microorganisms in conventional culture media, and is competitive with modern rapid microbiological methods. It can also be used for the characterization of the enzymatic activity.

  4. A new ultrasonic signal amplification method for detection of bacteria

    International Nuclear Information System (INIS)

    Shukla, Shiva Kant; López, Pablo Resa; Sánchez, Carlos Sierra; Segura, Luis Elvira; Urréjola, José

    2012-01-01

    A new method is presented that increases the sensitivity of ultrasound-based techniques for detection of bacteria. The technique was developed for the detection of catalase-positive microorganisms. It uses a bubble trapping medium containing hydrogen peroxide that is mixed with the sample for microbiological evaluation. The enzyme catalase is present in catalase-positive bacteria, which induces a rapid hydrolysis of hydrogen peroxide, forming bubbles which remain in the medium. This reaction results in the amplification of the mechanical changes that the microorganisms produce in the medium. The effect can be detected by means of ultrasonic wave amplitude continuous measurement since the bubbles increase the ultrasonic attenuation significantly. It is shown that microorganism concentrations of the order of 10 5 cells ml −1 can be detected using this method. This allows an improvement of three orders of magnitude in the ultrasonic detection threshold of microorganisms in conventional culture media, and is competitive with modern rapid microbiological methods. It can also be used for the characterization of the enzymatic activity. (paper)

  5. Dual-signal amplification strategy for ultrasensitive chemiluminescence detection of PDGF-BB in capillary electrophoresis.

    Science.gov (United States)

    Cao, Jun-Tao; Wang, Hui; Ren, Shu-Wei; Chen, Yong-Hong; Liu, Yan-Ming

    2015-12-01

    Many efforts have been made toward the achievement of high sensitivity in capillary electrophoresis coupled with chemiluminescence detection (CE-CL). This work describes a novel dual-signal amplification strategy for highly specific and ultrasensitive CL detection of human platelet-derived growth factor-BB (PDGF-BB) using both aptamer and horseradish peroxidase (HRP) modified gold nanoparticles (HRP-AuNPs-aptamer) as nanoprobes in CE. Both AuNPs and HRP in the nanoprobes could amplify the CL signals in the luminol-H2 O2 CL system, owing to the excellent catalytic behavior of AuNPs and HRP in the CL system. Meanwhile, the high affinity of aptamer modified on the AuNPs allows detection with high specificity. As proof-of-concept, the proposed method was employed to quantify the concentration of PDGF-BB from 0.50 to 250 fm with a detection limit of 0.21 fm. The applicability of the assay was further demonstrated in the analysis of PDGF-BB in human serum samples with acceptable accuracy and reliability. The result of this study exhibits distinct advantages, such as high sensitivity, good specificity, simplicity, and very small sample consumption. The good performances of the proposed strategy provide a powerful avenue for ultrasensitive detection of rare proteins in biological sample, showing great promise in biochemical analysis. Copyright © 2015 John Wiley & Sons, Ltd.

  6. Performance evaluation of radiation sensors with internal signal amplification based on the BJT effect

    International Nuclear Information System (INIS)

    Bosisio, Luciano; Batignani, Giovanni; Bettarini, Stefano; Boscardin, Maurizio; Dalla Betta, Gian-Franco; Giacomini, Gabriele; Piemonte, Claudio; Verzellesi, Giovanni; Zorzi, Nicola

    2006-01-01

    Prototypes of ionizing radiation detectors with internal signal amplification based on the bipolar transistor effect have been fabricated at ITC-irst (Trento, Italy). Results from the electrical characterization and preliminary functional tests of the devices have been previously reported. Here, we present a more detailed investigation of the performance of this type of detector, with particular attention to their noise and rate limits. Measurements of the signal waveform and of the gain versus frequency dependence are performed by illuminating the devices with, respectively, pulsed or sinusoidally modulated IR light. Pulse height spectra of X-rays from an Am241 source have been taken with very simple front-end electronics (an LF351 operational amplifier) or by directly reading with an oscilloscope the voltage drop across a load resistor connected to the emitter. An equivalent noise charge (referred to input) of 380 electrons r.m.s. has been obtained with the first setup for a small device, with an active area of 0.5x0.5mm 2 and a depleted thickness of 0.6mm. The corresponding power dissipation in the BJT was 17μW. The performance limitations of the devices are discussed

  7. A sensitive electrochemical aptasensor for ATP detection based on exonuclease III-assisted signal amplification strategy.

    Science.gov (United States)

    Bao, Ting; Shu, Huawei; Wen, Wei; Zhang, Xiuhua; Wang, Shengfu

    2015-03-03

    A target-induced structure-switching electrochemical aptasensor for sensitive detection of ATP was successfully constructed which was based on exonuclease III-catalyzed target recycling for signal amplification. With the existence of ATP, methylene blue (MB) labeled hairpin DNA formed G-quadruplex with ATP, which led to conformational changes of the hairpin DNA and created catalytic cleavage sites for exonuclease III (Exo III). Then the structure-switching DNA hybridized with capture DNA which made MB close to electrode surface. Meanwhile, Exo III selectively digested aptamer from its 3'-end, thus G-quadruplex structure was destroyed and ATP was released for target recycling. The Exo III-assisted target recycling amplified electrochemical signal significantly. Fluorescence experiment was performed to confirm the structure-switching process of the hairpin DNA. In fluorescence experiment, AuNPs-aptamer conjugates were synthesized, AuNPs quenched fluorescence of MB, the target-induced structure-switching made Exo III digested aptamer, which restored fluorescence. Under optimized conditions, the proposed aptasensor showed a linear range of 0.1-20 nM with a detection limit of 34 pM. In addition, the proposed aptasensor had good stability and selectivity, offered promising choice for the detection of other small molecules. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Amplification and discrimination of signals from proportional multiwire chambers

    International Nuclear Information System (INIS)

    Papadopoulos, L.; Bosio, C.; Cordelli, M.

    1976-03-01

    A circuit is described which detects signals from proportional multiwire chambers. The threshold is about 3μ A and the time jitter of the pulse obtained is better than 2.5 ns. The circuit has one negative input and two complementary outputs. The realized module includes 8 channels with common trigger level control and was built as NIM standard unit

  9. Dual-signal heterodyne lock-in amplification with lasers

    NARCIS (Netherlands)

    Witteman, W.J.

    2006-01-01

    High-sensitivity heterodyne detection with lasers applied to radar and satellite communication is seriously hampered by the large electronic bandwidth due to Doppler shift and frequency instability. These drawbacks can be circumvented by dual-signal heterodyne detection. The system consists of

  10. New frontiers of molecular beacons: signal amplification and nanomachines

    DEFF Research Database (Denmark)

    Della Vedova, Paolo

    2013-01-01

    by two complementary strands (stem), conjugated respectively with a fluorophore and a quencher. Upon hybridization with complementary target, the stem bonds break, parting the fluorophore from the quencher and resulting in a detectable signal. This thesis is divided in two major sections. The first...

  11. Thousand-fold fluorescent signal amplification for mHealth diagnostics

    Science.gov (United States)

    The low sensitivity of Mobile Health (mHealth) optical detectors, such as those found on mobile phones, is a limiting factor for many mHealth clinical applications. To improve sensitivity, we have combined two approaches for optical signal amplification: (1) a computational approach based on an imag...

  12. Homogeneous electrochemical aptamer-based ATP assay with signal amplification by exonuclease III assisted target recycling.

    Science.gov (United States)

    Liu, Shufeng; Wang, Ying; Zhang, Chengxin; Lin, Ying; Li, Feng

    2013-03-21

    A novel and homogeneous electrochemical aptamer-based adenosine triphosphate (ATP) assay was demonstrated with signal amplification by exonuclease III-assisted target recycling. A superior detection limit of 1 nM toward ATP with an excellent selectivity could be achieved.

  13. Simulations of signal amplification and oscillations using a SNS junction

    International Nuclear Information System (INIS)

    Luiz, A.M.; Soares, V.; Nicolsky, R.

    1998-01-01

    A superconducting - normal metal - superconducting junction (SNS junction) may exhibit a low voltage negative differential resistance (LVNDR) effect over part of its current voltage characteristic (CVC). As the LVNDR effect is stable against a bias voltage at this CVC range, it should be possible to combine a SNS junction with conventional electronic circuits to obtain electronic devices such as mixers, amplifiers and oscillators. Making use of this remarkable effect, we show that an amplifier may be feasible by assembling a simple voltage divider made up of a SNS junction in series with a resistor. The amplifier circuit includes an adjustable DC voltage supply (the bias voltage) and an AC signal source with a given voltage. The SNS junction is connected in series with a resistor R. Choosing values of the load resistance R approximately equal to the module of the negative differential resistance (dV/dI), at the bias voltage, we may obtain large gains in this amplifier device. In order to get an oscillator, the SNS junction should be connected to a RLC tank circuit with a bias voltage adjusted in the range of the LVNDR region of its CVC. A power output of the order of one microwatt may be easily obtained. (orig.)

  14. Directionality and signal amplification in cryogenic dark matter detection

    International Nuclear Information System (INIS)

    More, T.

    1996-05-01

    A mounting body of evidence suggests that most of the mass in our universe is not contained in stars, but rather exists in some non- luminous form. The evidence comes independently from astronomical observation, cosmological theory, and particle physics. All of this missing mass is collectively referred to as dark matter. In this thesis we discuss two ways to improve the performance of dark matter detectors based on the measurement of ballistic phonons. First, we address the issue of signal identification through solitons. Secondly, we discuss a method for lowering the detection threshold and improving the energy sensitivity: amplifying phonons through the evaporation of helium atoms from a superfluid film coating the target and the adsorption of the evaporated atoms onto a helium-free substrate. A phonon amplifier would also be of use in many other applications in which a few phonons are to be measured at low temperatures. Factors contributing to the low amplifier gains achieved thus far are described and proposals for avoiding them are analyzed and discussed. 101 refs., 30 figs., 2 tabs

  15. Ultrafast Capillary Electrophoresis Isolation of DNA Aptamer for the PCR Amplification-Based Small Analyte Sensing

    Directory of Open Access Journals (Sweden)

    Emmanuelle eFiore

    2015-08-01

    Full Text Available Here, we report a new homogeneous DNA amplification-based aptamer assay for small analyte sensing. The aptamer of adenosine chosen as the model analyte was split into two fragments able to assemble in the presence of target. Primers were introduced at extremities of one fragment in order to generate the amplifiable DNA component. The amount of amplifiable fragment was quantifiable by Real-Time Polymerase Chain Reaction (RT-PCR amplification and directly reliable on adenosine concentration. This approach combines the very high separation efficiency and the homogeneous format (without immobilization of capillary electrophoresis and the sensitivity of real time PCR amplification. An ultrafast isolation of target-bound split aptamer (60 s was developed by designing a capillary electrophoresis input/ouput scheme. Such method was successfully applied to the determination of adenosine with a LOD of 1 µM.

  16. Comparison of calculated, simulated and measured signal amplification in variable pressure SEM

    Czech Academy of Sciences Publication Activity Database

    Neděla, Vilém; Konvalina, Ivo; Lencová, Bohumila; Zlámal, J.

    2011-01-01

    Roč. 645, č. 1 (2011), s. 79-83 ISSN 0168-9002 R&D Projects: GA ČR GAP102/10/1410; GA MPO FR-TI1/118; GA MPO FR-TI1/305 Institutional research plan: CEZ:AV0Z20650511 Keywords : electron-gas interactions * Monte Carlo simulation s * signal amplification * analytical models Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 1.207, year: 2011

  17. Isothermal multiple displacement amplification: a methodical approach enhancing molecular routine diagnostics of microcarcinomas and small biopsies

    Directory of Open Access Journals (Sweden)

    Mairinger FD

    2014-08-01

    Full Text Available Fabian D Mairinger,1 Robert FH Walter,2 Claudia Vollbrecht,3 Thomas Hager,1 Karl Worm,1 Saskia Ting,1 Jeremias Wohlschläger,1 Paul Zarogoulidis,4 Konstantinos Zarogoulidis,4 Kurt W Schmid1 1Institute of Pathology, 2Ruhrlandklinik, West German Lung Center, University Hospital Essen, Essen, 3Institute of Pathology, University Hospital Cologne, Cologne, Germany; 4Pulmonary Department, Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece Background and methods: Isothermal multiple displacement amplification (IMDA can be a powerful tool in molecular routine diagnostics for homogeneous and sequence-independent whole-genome amplification of notably small tumor samples, eg, microcarcinomas and biopsies containing a small amount of tumor. Currently, this method is not well established in pathology laboratories. We designed a study to confirm the feasibility and convenience of this method for routine diagnostics with formalin-fixed, paraffin-embedded samples prepared by laser-capture microdissection. Results: A total of 250 µg DNA (concentration 5 µg/µL was generated by amplification over a period of 8 hours with a material input of approximately 25 cells, approximately equivalent to 175 pg of genomic DNA. In the generated DNA, a representation of all chromosomes could be shown and the presence of elected genes relevant for diagnosis in clinical samples could be proven. Mutational analysis of clinical samples could be performed without any difficulty and showed concordance with earlier diagnostic findings. Conclusion: We established the feasibility and convenience of IMDA for routine diagnostics. We also showed that small amounts of DNA, which were not analyzable with current molecular methods, could be sufficient for a wide field of applications in molecular routine diagnostics when they are preamplified with IMDA. Keywords: isothermal multiple displacement amplification, isothermal, whole

  18. Three different signal amplification strategies for the impedimetric sandwich detection of thrombin

    Energy Technology Data Exchange (ETDEWEB)

    Ocaña, Cristina; Valle, Manel del, E-mail: manel.delvalle@uab.cat

    2016-03-17

    In this work, we report a comparative study on three highly specific amplification strategies for the ultrasensitive detection of thrombin with the use of aptamer sandwich protocol. The protocol consisted on the use of a first thrombin aptamer immobilized on the electrode surface, the recognition of thrombin protein, and the reaction with a second biotinylated thrombin aptamer forming the sandwich. Through the exposed biotin end, three variants have been tested to amplify the electrochemical impedance signal. The strategies included (a) silver enhancement treatment, (b) gold enhancement treatment and (c) insoluble product produced by the combination of the enzyme horseradish peroxidase (HRP) and 3-amino-9-ethylcarbazole (AEC). The properties of the sensing surface were probed by electrochemical impedance measurements in the presence of the ferrocyanide/ferricyanide redox marker. Insoluble product strategy and silver enhancement treatment resulted in the lowest detection limit (0.3 pM), while gold enhancement method resulted in the highest reproducibility, 8.8% RSD at the pM thrombin concentration levels. Results of silver and gold enhancement treatment also permitted direct inspection by scanning electron microscopy (SEM). - Highlights: • Aptasensor to detect thrombin reaching the femtomolar level. • Biosensing protocol employs two thrombin aptamers in a sandwich capture scheme. • Use of second biotinylated aptamer allows many amplification and detection variants. • Precipitation reaction provides the highest signal amplification of ca. 3 times. • Double recognition event improves remarkably selectivity for thrombin detection.

  19. Three different signal amplification strategies for the impedimetric sandwich detection of thrombin

    International Nuclear Information System (INIS)

    Ocaña, Cristina; Valle, Manel del

    2016-01-01

    In this work, we report a comparative study on three highly specific amplification strategies for the ultrasensitive detection of thrombin with the use of aptamer sandwich protocol. The protocol consisted on the use of a first thrombin aptamer immobilized on the electrode surface, the recognition of thrombin protein, and the reaction with a second biotinylated thrombin aptamer forming the sandwich. Through the exposed biotin end, three variants have been tested to amplify the electrochemical impedance signal. The strategies included (a) silver enhancement treatment, (b) gold enhancement treatment and (c) insoluble product produced by the combination of the enzyme horseradish peroxidase (HRP) and 3-amino-9-ethylcarbazole (AEC). The properties of the sensing surface were probed by electrochemical impedance measurements in the presence of the ferrocyanide/ferricyanide redox marker. Insoluble product strategy and silver enhancement treatment resulted in the lowest detection limit (0.3 pM), while gold enhancement method resulted in the highest reproducibility, 8.8% RSD at the pM thrombin concentration levels. Results of silver and gold enhancement treatment also permitted direct inspection by scanning electron microscopy (SEM). - Highlights: • Aptasensor to detect thrombin reaching the femtomolar level. • Biosensing protocol employs two thrombin aptamers in a sandwich capture scheme. • Use of second biotinylated aptamer allows many amplification and detection variants. • Precipitation reaction provides the highest signal amplification of ca. 3 times. • Double recognition event improves remarkably selectivity for thrombin detection.

  20. Light-Triggered Soft Artificial Muscles: Molecular-Level Amplification of Actuation Control Signals.

    Science.gov (United States)

    Dicker, Michael P M; Baker, Anna B; Iredale, Robert J; Naficy, Sina; Bond, Ian P; Faul, Charl F J; Rossiter, Jonathan M; Spinks, Geoffrey M; Weaver, Paul M

    2017-08-23

    The principle of control signal amplification is found in all actuation systems, from engineered devices through to the operation of biological muscles. However, current engineering approaches require the use of hard and bulky external switches or valves, incompatible with both the properties of emerging soft artificial muscle technology and those of the bioinspired robotic systems they enable. To address this deficiency a biomimetic molecular-level approach is developed that employs light, with its excellent spatial and temporal control properties, to actuate soft, pH-responsive hydrogel artificial muscles. Although this actuation is triggered by light, it is largely powered by the resulting excitation and runaway chemical reaction of a light-sensitive acid autocatalytic solution in which the actuator is immersed. This process produces actuation strains of up to 45% and a three-fold chemical amplification of the controlling light-trigger, realising a new strategy for the creation of highly functional soft actuating systems.

  1. Isothermal multiple displacement amplification: a methodical approach enhancing molecular routine diagnostics of microcarcinomas and small biopsies.

    Science.gov (United States)

    Mairinger, Fabian D; Walter, Robert Fh; Vollbrecht, Claudia; Hager, Thomas; Worm, Karl; Ting, Saskia; Wohlschläger, Jeremias; Zarogoulidis, Paul; Zarogoulidis, Konstantinos; Schmid, Kurt W

    2014-01-01

    Isothermal multiple displacement amplification (IMDA) can be a powerful tool in molecular routine diagnostics for homogeneous and sequence-independent whole-genome amplification of notably small tumor samples, eg, microcarcinomas and biopsies containing a small amount of tumor. Currently, this method is not well established in pathology laboratories. We designed a study to confirm the feasibility and convenience of this method for routine diagnostics with formalin-fixed, paraffin-embedded samples prepared by laser-capture microdissection. A total of 250 μg DNA (concentration 5 μg/μL) was generated by amplification over a period of 8 hours with a material input of approximately 25 cells, approximately equivalent to 175 pg of genomic DNA. In the generated DNA, a representation of all chromosomes could be shown and the presence of elected genes relevant for diagnosis in clinical samples could be proven. Mutational analysis of clinical samples could be performed without any difficulty and showed concordance with earlier diagnostic findings. We established the feasibility and convenience of IMDA for routine diagnostics. We also showed that small amounts of DNA, which were not analyzable with current molecular methods, could be sufficient for a wide field of applications in molecular routine diagnostics when they are preamplified with IMDA.

  2. Evolution and Design Governing Signal Precision and Amplification in a Bacterial Chemosensory Pathway.

    Directory of Open Access Journals (Sweden)

    Mathilde Guzzo

    2015-08-01

    Full Text Available Understanding the principles underlying the plasticity of signal transduction networks is fundamental to decipher the functioning of living cells. In Myxococcus xanthus, a particular chemosensory system (Frz coordinates the activity of two separate motility systems (the A- and S-motility systems, promoting multicellular development. This unusual structure asks how signal is transduced in a branched signal transduction pathway. Using combined evolution-guided and single cell approaches, we successfully uncoupled the regulations and showed that the A-motility regulation system branched-off an existing signaling system that initially only controlled S-motility. Pathway branching emerged in part following a gene duplication event and changes in the circuit structure increasing the signaling efficiency. In the evolved pathway, the Frz histidine kinase generates a steep biphasic response to increasing external stimulations, which is essential for signal partitioning to the motility systems. We further show that this behavior results from the action of two accessory response regulator proteins that act independently to filter and amplify signals from the upstream kinase. Thus, signal amplification loops may underlie the emergence of new connectivity in signal transduction pathways.

  3. Use of the squeezed (sub-Poisson) state of light in small-signal detection with preamplification upon four-wave mixing

    International Nuclear Information System (INIS)

    Kozlovskii, Andrei V

    2007-01-01

    The scheme of an active interferometer for amplification of small optical signals for their subsequent photodetection is proposed. The scheme provides a considerable amplification of signals by preserving their quantum-statistical properties (ideal amplification) and also can improve these properties under certain conditions. The two-mode squeezed state of light produced upon four-wave mixing, which is used for signal amplification, can be transformed to the non-classical state of the output field squeezed in the number of photons. The scheme is phase-sensitive upon amplification of the input coherent signal. It is shown that in the case of the incoherent input signal with the average number of photons (n s )∼1, the amplification process introduces no additional quantum noise at signal amplification as large as is wished. A scheme is also proposed for the cascade small-signal amplification ((n s )∼1) in the coherent state producing the amplified signal in the squeezed sub-Poisson state, which can be used for the high-resolution detection of weak and ultraweak optical signals. (quantum optics)

  4. Persistent Amplification of DNA Damage Signal Involved in Replicative Senescence of Normal Human Diploid Fibroblasts

    Directory of Open Access Journals (Sweden)

    Masatoshi Suzuki

    2012-01-01

    Full Text Available Foci of phosphorylated histone H2AX and ATM are the surrogate markers of DNA double strand breaks. We previously reported that the residual foci increased their size after irradiation, which amplifies DNA damage signals. Here, we addressed whether amplification of DNA damage signal is involved in replicative senescence of normal human diploid fibroblasts. Large phosphorylated H2AX foci (>1.5 μm diameter were specifically detected in presenescent cells. The frequency of cells with large foci was well correlated with that of cells positive for senescence-associated β-galactosidase staining. Hypoxic cell culture condition extended replicative life span of normal human fibroblast, and we found that the formation of large foci delayed in those cells. Our immuno-FISH analysis revealed that large foci partially localized at telomeres in senescent cells. Importantly, large foci of phosphorylated H2AX were always colocalized with phosphorylated ATM foci. Furthermore, Ser15-phosphorylated p53 showed colocalization with the large foci. Since the treatment of senescent cells with phosphoinositide 3-kinase inhibitor, wortmannin, suppressed p53 phosphorylation, it is suggested that amplification of DNA damage signaling sustains persistent activation of ATM-p53 pathway, which is essential for replicative senescence.

  5. Human small-cell lung cancers show amplification and expression of the N-myc gene

    International Nuclear Information System (INIS)

    Nau, M.M.; Brooks, B.J. Jr.; Carney, D.N.; Gazdar, A.F.; Battey, J.F.; Sausville, E.A.; Minna, J.D.

    1986-01-01

    The authors have found that 6 of 31 independently derived human small-cell lung cancer (SCLC) cell lines have 5- to 170-fold amplified N-myc gene sequences. The amplification is seen with probes from two separate exons of N-myc, which are homologous to either the second or the third exon of the c-myc gene. Amplified N-myc sequences were found in a tumor cell line started prior to chemotherapy, in SCLC tumor samples harvested directly from tumor metastases at autopsy, and from a resected primary lung cancer. Several N-myc-amplified tumor cell lines also exhibited N-myc hybridizing fragments not in the germ-line position. In one patient's tumor, an additional amplitifed N-myc DNA fragment was observed and this fragment was heterogeneously distributed in liver metastases. In contrast to SCLC with neuroendocrine properties, no non-small-cell lung cancer lines examined were found to have N-myc amplification. Fragments encoding two N-myc exons also detect increased amounts of a 3.1-kilobase N-myc mRNA in N-myc-amplified SCLC lines and in one cell line that does not show N-myc gene amplification. Both DNA and RNA hybridization experiments, using a 32 P-labelled restriction probe, show that in any one SCLC cell line, only one myc-related gene is amplified and expressed. They conclude that N-myc amplification is both common and potentially significant in the tumorigenesis or tumor progression of SCLC

  6. Parametric Amplification Protocol for Frequency-Modulated Magnetic Resonance Force Microscopy Signals

    Science.gov (United States)

    Harrell, Lee; Moore, Eric; Lee, Sanggap; Hickman, Steven; Marohn, John

    2011-03-01

    We present data and theoretical signal and noise calculations for a protocol using parametric amplification to evade the inherent tradeoff between signal and detector frequency noise in force-gradient magnetic resonance force microscopy signals, which are manifested as a modulated frequency shift of a high- Q microcantilever. Substrate-induced frequency noise has a 1 / f frequency dependence, while detector noise exhibits an f2 dependence on modulation frequency f . Modulation of sample spins at a frequency that minimizes these two contributions typically results in a surface frequency noise power an order of magnitude or more above the thermal limit and may prove incompatible with sample spin relaxation times as well. We show that the frequency modulated force-gradient signal can be used to excite the fundamental resonant mode of the cantilever, resulting in an audio frequency amplitude signal that is readily detected with a low-noise fiber optic interferometer. This technique allows us to modulate the force-gradient signal at a sufficiently high frequency so that substrate-induced frequency noise is evaded without subjecting the signal to the normal f2 detector noise of conventional demodulation.

  7. Ternary Surface Monolayers for Ultrasensitive (Zeptomole) Amperometric Detection of Nucleic-Acid Hybridization without Signal Amplification

    Science.gov (United States)

    Wu, Jie; Campuzano, Susana; Halford, Colin; Haake, David A.; Wang, Joseph

    2010-01-01

    A ternary surface monolayer, consisting of co-assembled thiolated capture probe (SHCP) mercaptohexanol (MCH) and dithiothreitol (DTT), is shown to offer dramatic improvements in the signal-to-noise characteristics of electrochemical DNA hybridization biosensors based on common self-assembled monolayers (SAMs). Remarkably low detection limits down to 40 zmole (in 4 μL samples) as well as only 1 CFU E. coli per sensor are thus obtained without any additional amplification step in connection to the commonly used horseradish peroxidase/3,3′,5,5′-tetramethylbenzidine (HRP/TMB) system. Such dramatic improvements in the detection limits (compared to common binary alkanethiol interfaces and to most electrochemical DNA sensing strategies without target or signal amplification) are attributed primarily to the remarkably higher resistance to non-specific adsorption. This reflects the highly compact layer (with lower pinhole density) produced by the coupling of the cyclic- and linear-configuration ‘backfillers’ that leads to a remarkably low background noise even in the presence of complex sample matrices. A wide range of surface compositions have been investigated and the ternary mixed monolayer has been systematically optimized. Detailed impedance spectroscopy and cyclic voltammetric studies shed useful insights into the surface coverage. The impressive sensitivity and high specificity of the simple developed methodology indicate great promise for a wide range of nucleic acid testing, including clinical diagnostics, biothreat detection, food safety and forensic analysis. PMID:20883023

  8. Ternary surface monolayers for ultrasensitive (zeptomole) amperometric detection of nucleic acid hybridization without signal amplification.

    Science.gov (United States)

    Wu, Jie; Campuzano, Susana; Halford, Colin; Haake, David A; Wang, Joseph

    2010-11-01

    A ternary surface monolayer, consisting of coassembled thiolated capture probe, mercaptohexanol and dithiothreitol, is shown to offer dramatic improvements in the signal-to-noise characteristics of electrochemical DNA hybridization biosensors based on common self-assembled monolayers. Remarkably low detection limits down to 40 zmol (in 4 μL samples) as well as only 1 CFU Escherichia coli per sensor are thus obtained without any additional amplification step in connection to the commonly used horseradish peroxidase/3,3',5,5'-tetramethylbenzidine system. Such dramatic improvements in the detection limits (compared to those of common binary alkanethiol interfaces and to those of most electrochemical DNA sensing strategies without target or signal amplification) are attributed primarily to the remarkably higher resistance to nonspecific adsorption. This reflects the highly compact layer (with lower pinhole density) produced by the coupling of the cyclic- and linear-configuration "backfillers" that leads to a remarkably low background noise even in the presence of complex sample matrixes. A wide range of surface compositions have been investigated, and the ternary mixed monolayer has been systematically optimized. Detailed impedance spectroscopy and cyclic voltammetric studies shed useful insights into the surface coverage. The impressive sensitivity and high specificity of the simple developed methodology indicate great promise for a wide range of nucleic acid testing, including clinical diagnostics, biothreat detection, food safety, and forensic analysis.

  9. Targeting and localized signalling by small GTPases

    NARCIS (Netherlands)

    ten Klooster, Jean Paul; Hordijk, Peter L.

    2007-01-01

    Polarized cellular responses, for example, cell migration, require the co-ordinated assembly of signalling complexes at a particular subcellular location, such as the leading edge of cells. Small GTPases of the Ras superfamily play central roles in many (polarized) responses to growth factors,

  10. Small-signal analysis of granular semiconductors

    Energy Technology Data Exchange (ETDEWEB)

    Varpula, Aapo; Sinkkonen, Juha; Novikov, Sergey, E-mail: aapo.varpula@tkk.f [Department of Micro and Nanosciences, Aalto University, PO Box 13500, FI-00076 Aalto, Espoo (Finland)

    2010-11-01

    The small-signal ac response of granular n-type semiconductors is calculated analytically using the drift-diffusion theory when electronic trapping at grain boundaries is present. An electrical equivalent circuit (EEC) model of a granular n-type semiconductor is presented. The analytical model is verified with numerical simulation performed by SILVACO ATLAS. The agreement between the analytical and numerical results is very good in a broad frequency range at low dc bias voltages.

  11. Small-signal analysis of granular semiconductors

    International Nuclear Information System (INIS)

    Varpula, Aapo; Sinkkonen, Juha; Novikov, Sergey

    2010-01-01

    The small-signal ac response of granular n-type semiconductors is calculated analytically using the drift-diffusion theory when electronic trapping at grain boundaries is present. An electrical equivalent circuit (EEC) model of a granular n-type semiconductor is presented. The analytical model is verified with numerical simulation performed by SILVACO ATLAS. The agreement between the analytical and numerical results is very good in a broad frequency range at low dc bias voltages.

  12. Biosensors for breast cancer diagnosis: A review of bioreceptors, biotransducers and signal amplification strategies.

    Science.gov (United States)

    Mittal, Sunil; Kaur, Hardeep; Gautam, Nandini; Mantha, Anil K

    2017-02-15

    Breast cancer is highly prevalent in females and accounts for second highest number of deaths, worldwide. Cumbersome, expensive and time consuming detection techniques presently available for detection of breast cancer potentiates the need for development of novel, specific and ultrasensitive devices. Biosensors are the promising and selective detection devices which hold immense potential as point of care (POC) tools. Present review comprehensively scrutinizes various breast cancer biosensors developed so far and their technical evaluation with respect to efficiency and potency of selected bioreceptors and biotransducers. Use of glycoproteins, DNA biomarkers, micro-RNA, circulatory tumor cells (CTC) and some potential biomarkers are introduced briefly. The review also discusses various strategies used in signal amplification such as nanomaterials, redox mediators, p19 protein, duplex specific nucleases (DSN) and redox cycling. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. A sensitive detection assay based on signal amplification technology for Alzheimer's disease's early biomarker in exosome.

    Science.gov (United States)

    Zhou, Jie; Meng, Lingchang; Ye, Weiran; Wang, Qiaolei; Geng, Shizhen; Sun, Chong

    2018-08-31

    Alzheimer's disease (AD) considered as the third health "killer" has seriously threatened the health of the elderly. However, the modern diagnostic strategies of AD present several disadvantages: the low accuracy and specificity resulting in some false-negative diagnoses, and the poor sensitivity leading to a delayed treatment. In view of this situation, a enzyme-free and target-triggered signal amplification strategy, based on graphene oxide (GO) and entropy-driven strand displacement reaction (ESDR) principle, was proposed. In this strategy, when the hairpin structure probes (H)specially binds with beta-amyloid-(1-42) oligomers (Aβ42 oligomers), it's structure will be opened, causing the bases complementary to FAM-labeled replacement probes R (R1 and R2) exposed. At this time, R1 and R2 will hybridize with H, resulting in the bound Aβ42 oligomers released. The released Aβ42 oligomers would participate in the next cycle reaction, making the signal amplified. As a quencher, GO could absorb the free single-stranded DNA R1 and R2 and quench their fluorescence; however, the DNA duplex still exists free and keeps its signal-on. Through the detection of Aβ42 oligomers in exosomes, this ultrasensitive detection method with the advantages of low limit of detection (LOD, 20 pM), great accuracy, excellent precision and convenience provides an excellent prospect for AD's early diagnosis. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Parametric Amplification, Wavelength Conversion, and Phase Conjugation of a 2.048-Tbit/s WDM PDM 16-QAM Signal

    DEFF Research Database (Denmark)

    Hu, Hao; Jopson, R. M.; Gnauck, A. H.

    2015-01-01

    We demonstrate polarization-independent parametric amplification of a 2.048-Tbit/s 8-WDM PDM 16-QAM signal and simultaneous wavelength conversion and phase conjugation in a highly nonlinear fiber. Two high-power continuous-wave pumps with orthogonal polarizations and counter-phase modulation are ...

  15. Parametric amplification and wavelength conversion of a 2.048-Tbit/s WDM PDM 16-QAM signal

    DEFF Research Database (Denmark)

    Hu, Hao; Jopson, R. M.; Gnauck, A. H.

    2014-01-01

    We demonstrate polarisation-insensitive parametric amplification in highly nonlinear fibre of a 2.048-Tbit/s dense WDM PDM 16-QAM signal with ∼10 dB on-off gain and simultaneous wavelength conversion and phase conjugation, with mean Q2 penalties of only 0.6 dB and 0.4 dB....

  16. Small-signal Loudspeaker Impedance Emulator

    DEFF Research Database (Denmark)

    Knott, Arnold; Iversen, Niels Elkjær

    2014-01-01

    Specifying the performance of audio ampliers is typically done by playing sine waves into a pure ohmic load. However real loudspeaker impedances are not purely ohmic but characterised by the mechanical resonance between the mass of the diaphragm and the compliance of its' suspension which vary from...... driver to driver. Therefore a loudspeaker emulator capable of adjusting its' impedance to a given driver is in need for measurement purposes. This paper proposes a loudspeaker emulator circuit for small signals. Simulations and experimental results are compared and show that it is possible to emulate...... the loudspeaker impedance with an electric circuit and that its' resonance frequency can be changed by tuning two resistors....

  17. Stochastic amplification and signaling in enzymatic futile cycles through noise-induced bistability with oscillations

    Science.gov (United States)

    Samoilov, Michael; Plyasunov, Sergey; Arkin, Adam P.

    2005-02-01

    Stochastic effects in biomolecular systems have now been recognized as a major physiologically and evolutionarily important factor in the development and function of many living organisms. Nevertheless, they are often thought of as providing only moderate refinements to the behaviors otherwise predicted by the classical deterministic system description. In this work we show by using both analytical and numerical investigation that at least in one ubiquitous class of (bio)chemical-reaction mechanisms, enzymatic futile cycles, the external noise may induce a bistable oscillatory (dynamic switching) behavior that is both quantitatively and qualitatively different from what is predicted or possible deterministically. We further demonstrate that the noise required to produce these distinct properties can itself be caused by a set of auxiliary chemical reactions, making it feasible for biological systems of sufficient complexity to generate such behavior internally. This new stochastic dynamics then serves to confer additional functional modalities on the enzymatic futile cycle mechanism that include stochastic amplification and signaling, the characteristics of which could be controlled by both the type and parameters of the driving noise. Hence, such noise-induced phenomena may, among other roles, potentially offer a novel type of control mechanism in pathways that contain these cycles and the like units. In particular, observations of endogenous or externally driven noise-induced dynamics in regulatory networks may thus provide additional insight into their topology, structure, and kinetics. network motif | signal transduction | chemical reaction | synthetic biology | systems biology

  18. Modified beacon probe assisted dual signal amplification for visual detection of microRNA.

    Science.gov (United States)

    Sun, Xiuwei; Ying, Na; Ju, Chuanjing; Li, Zhongyi; Xu, Na; Qu, Guijuan; Liu, Wensen; Wan, Jiayu

    2018-04-21

    In a recent study, we reported a novel assay for the detection of microRNA-21 based on duplex-specific nuclease (DSN)-assisted isothermal cleavage and hybridization chain reaction (HCR) dual signal amplification. The Fam modified double-stranded DNA products were generated after the HCR, another biotin modified probe was digested by DSN and released from the magnetic beads after the addition of the target miRNA. The released sequence was then combined with HCR products to form a double-tagging dsDNA, which can be recognized by the lateral flow strips. In this study, we introduced a 2-OMethyl-RNA modified beacon probe (2-OMe-MB) to make some improvements based on the previous study. Firstly, the substitution of modified probe combined on magnetic beads avoids the fussy washing steps for the separation of un-reacted probes. Furthermore, the modification of 2-OMe on the stem of the probe avoided the unnecessary cleavage by DSN, which greatly reduce the background signal. Compared to the previous work, these improvements save us a lot of steps but possess the comparable sensitivity and selectivity. Copyright © 2018 Elsevier Inc. All rights reserved.

  19. Development and significance of a fetal electrocardiogram recorded by signal-averaged high-amplification electrocardiography.

    Science.gov (United States)

    Hayashi, Risa; Nakai, Kenji; Fukushima, Akimune; Itoh, Manabu; Sugiyama, Toru

    2009-03-01

    Although ultrasonic diagnostic imaging and fetal heart monitors have undergone great technological improvements, the development and use of fetal electrocardiograms to evaluate fetal arrhythmias and autonomic nervous activity have not been fully established. We verified the clinical significance of the novel signal-averaged vector-projected high amplification ECG (SAVP-ECG) method in fetuses from 48 gravidas at 32-41 weeks of gestation and in 34 neonates. SAVP-ECGs from fetuses and newborns were recorded using a modified XYZ-leads system. Once noise and maternal QRS waves were removed, the P, QRS, and T wave intervals were measured from the signal-averaged fetal ECGs. We also compared fetal and neonatal heart rates (HRs), coefficients of variation of heart rate variability (CV) as a parasympathetic nervous activity, and the ratio of low to high frequency (LF/HF ratio) as a sympathetic nervous activity. The rate of detection of a fetal ECG by SAVP-ECG was 72.9%, and the fetal and neonatal QRS and QTc intervals were not significantly different. The neonatal CVs and LF/HF ratios were significantly increased compared with those in the fetus. In conclusion, we have developed a fetal ECG recording method using the SAVP-ECG system, which we used to evaluate autonomic nervous system development.

  20. Efficient Sub-Bandgap Light Absorption and Signal Amplification in Silicon Photodetectors

    Science.gov (United States)

    Liu, Yu-Hsin

    This thesis focuses on two areas in silicon photodetectors, the first being enhancing the sub-bandgap light absorption of IR wavelenghts in silicon, and the second being intrinsic signal amplification in silicon photodetectors. Both of these are achieved using heavily doped p-n junction devices which create localized states that relax the k-selection rule of indirect bandgap material. The probability of transitions between impurity band and the conduction/valence band would be much more efficient than the one between band-to-band transition. The waveguide-coupled epitaxial p-n photodetector was demonstrated for 1310 nm wavelength detection. Incorporated with the Franz-Keldysh effect and the quasi-confined epitaxial layer design, an absorption coefficient around 10 cm-1 has been measured and internal quantum efficiency nearly 100% at -2.5V. The absorption coefficient is calculated from the wave function of the electron and hole in p-n diode. The heavily doped impurity wave function can be formulated as a delta function, and the quasi-confined conduction band energy states, and the wave function on each level can be obtained from the Silvaco software. The calculated theoretical absorption coefficient increases with the increasing applied bias and the doping concentration, which matches the experimental results. To solve the issues of large excess noise and high operation bias for avalanche photodiodes based on impact ionization, I presented a detector using the Cycling Excitation Process (CEP) for signal amplification. This can be realized in a heavily doped and highly compensated Si p-n junction, showing ultra high gain about 3000 at very low bias (<4 V), and possessing an intrinsic, phonon-mediated regulation process to keep the device stable without any quenching device required in today's Geiger-mode avalanche detectors. The CEP can be formulated with the rate equations in conduction bands and impurity states. The gain expression, which is a function of the

  1. Signal processing for high granularity calorimeter: amplification, filtering, memorization and digitalization

    Energy Technology Data Exchange (ETDEWEB)

    Royer, L; Manen, S; Gay, P, E-mail: royer@clermont.in2p3.f [Clermont Universite, Universite Blaise Pascal, CNRS/IN2P3, LPC, BP 10448, F-63000 Clermont-Ferrand (France)

    2010-12-15

    A very-front-end electronics dedicated to high granularity calorimeters has been designed and its performance measured. This electronics performs the amplification of the charge delivered by the detector thanks to a low-noise Charge Sensitive Amplifier. The dynamic range is improved using a bandpass filter based on a Gated Integrator. Studying its weighting function, we show that this filter is more efficient than standard CRRC shaper, thanks to the integration time which can be expand near the bunch interval time, whereas the peaking time of the CRRC shaper is limited to pile-up consideration. Moreover, the Gated Integrator performs intrinsically the analog memorization of the signal before its delayed digital conversion. The analog-to-digital conversion is performed through a 12-bit cyclic ADC specifically developed for this application. The very-front-end channel has been fabricated using a 0.35 {mu}m CMOS technology. Measurements show a global non-linearity better than 0.1%. The Equivalent Noise Charge at the input of the channel is evaluated to 1.8 fC, compare to the maximum input charge of 10 pC. The power consumption of the complete channel is limited to 6.5 mW.

  2. Amplification factor variable amplifier

    NARCIS (Netherlands)

    Akitsugu, Oshita; Nauta, Bram

    2007-01-01

    PROBLEM TO BE SOLVED: To provide an amplification factor variable amplifier capable of achieving temperature compensation of an amplification factor over a wide variable amplification factor range. ; SOLUTION: A Gilbert type amplification factor variable amplifier 11 amplifies an input signal and

  3. Amplification factor variable amplifier

    NARCIS (Netherlands)

    Akitsugu, Oshita; Nauta, Bram

    2010-01-01

    PROBLEM TO BE SOLVED: To provide an amplification factor variable amplifier capable of achieving temperature compensation of an amplification factor over a wide variable amplification factor range. ;SOLUTION: A Gilbert type amplification factor variable amplifier 11 amplifies an input signal and can

  4. Asymmetric double Langmuir probe: Small signal application

    International Nuclear Information System (INIS)

    Uckan, T.

    1987-11-01

    We discuss the asymmetric double Langmuir probe (ADLP) and demonstrate the possibility of using it to measure plasma temperature T/sub e/ and density n when it is operated in the region of small signal response. The area of one of the ADLP collectors is considerably larger than the other. This probe can be operated at a relatively low applied voltage, eV/sub a/T/sub e/ < 1, and still provides sufficient information to determine the plasma T/sub e/ and n. There is no need for a direct measurement of the ion saturation current, which can be on the order of a few amperes in large fusion devices. This reduces the requirements on the probe power supply. 6 refs., 6 figs

  5. Transistor Small Signal Analysis under Radiation Effects

    International Nuclear Information System (INIS)

    Sharshar, K.A.A.

    2004-01-01

    A Small signal transistor parameters dedicate the operation of bipolar transistor before and after exposed to gamma radiation (1 Mrad up to 5 Mrads) and electron beam(1 MeV, 25 mA) with the same doses as a radiation sources, the electrical parameters of the device are changed. The circuit Model has been discussed.Parameters, such as internal emitter resistance (re), internal base resistance, internal collector resistance (re), emitter base photocurrent (Ippe) and base collector photocurrent (Ippe). These parameters affect on the operation of the device in its applications, which work as an effective element, such as current gain (hFE≡β)degradation it's and effective parameter in the device operation. Also the leakage currents (IcBO) and (IEBO) are most important parameters, Which increased with radiation doses. Theoretical representation of the change in the equivalent circuit for NPN and PNP bipolar transistor were discussed, the input and output parameters of the two types were discussed due to the change in small signal input resistance of the two types. The emitter resistance(re) were changed by the effect of gamma and electron beam irradiation, which makes a change in the role of matching impedances between transistor stages. Also the transistor stability factors S(Ico), S(VBE) and S(β are detected to indicate the transistor operations after exposed to radiation fields. In low doses the gain stability is modified due to recombination of induced charge generated during device fabrication. Also the load resistance values are connected to compensate the effect

  6. Highly frequent promoter methylation and PIK3CA amplification in non-small cell lung cancer (NSCLC)

    International Nuclear Information System (INIS)

    Ji, Meiju; Guan, Haixia; Gao, Cuixia; Shi, Bingyin; Hou, Peng

    2011-01-01

    Lung cancer is the leading cause of cancer-related death worldwide. Genetic and epigenetic alterations have been identified frequently in lung cancer, such as promoter methylation, gene mutations and genomic amplification. However, the interaction between genetic and epigenetic events and their significance in lung tumorigenesis remains poorly understood. We determined the promoter methylation of 6 genes and PIK3CA amplification using quantitative methylation-specific PCR (Q-MSP) and real-time quantitative PCR, respectively, and explore the association of promoter methylation with PIK3CA amplification in a large cohort of clinically well-characterized non-small cell lung cancer (NSCLC). Highly frequent promoter methylation was observed in NSCLC. With 100% diagnostic specificity, excellent sensitivity, ranging from 45.8 to 84.1%, was found for each of the 6 genes. The promoter methylation was associated with histologic type. Methylation of CALCA, CDH1, DAPK1, and EVX2 was more common in squamous cell carcinomas (SCC) compared to adenocarcinomas (ADC). Conversely, there was a trend toward a higher frequency of RASSF1A methylation in ADC than SCC. In addition, PIK3CA amplification was frequently found in NSCLC, and was associated with certain clinicopathologic features, such as smoking history, histologic type and pleural indentation. Importantly, aberrant promoter methylation of certain genes was significantly associated with PIK3CA amplification. Our data showed highly frequent promoter methylation and PIK3CA amplification in Chinese NSCLC population, and first demonstrated the associations of gene methylation with PIK3CA amplification, suggesting that these epigenetic events may be a consequence of overactivation of PI3K/Akt pathway

  7. Laser-enhanced ionization of mercury atoms in an inert atmosphere with avalanche amplification of the signal.

    Science.gov (United States)

    Clevenger, W L; Matveev, O I; Cabredo, S; Omenetto, N; Smith, B W; Winefordner, J D

    1997-07-01

    A new method for laser-enhanced ionization detection of mercury atoms in an inert gas atmosphere is described. The method, which is based on the avalanche amplification of the signal resulting from the ionization from a selected Rydberg level reached by a three-step laser excitation of mercury vapor in a simple quartz cell, can be applied to the determination of this element in various matrices by the use of conventional cold atomization techniques. The overall (collisional + photo) ionization efficiency is investigated at different temperatures, and the avalanche amplification effect is reported for Ar and P-10 gases at atmospheric pressure. It is shown that the amplified signal is related to the number of charges produced in the laser-irradiated volume. Under amplifier noise-limited conditions, a detection limit of ∼15 Hg atoms/laser pulse in the interaction region is estimated.

  8. Chemiluminescence immunoassay based on dual signal amplification strategy of Au/mesoporous silica and multienzyme functionalized mesoporous silica

    Energy Technology Data Exchange (ETDEWEB)

    Lin Jiehua, E-mail: linjiehua@qust.edu.cn [Key Laboratory of Eco-chemical Engineering, Ministry of Education, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042 (China); Zhao Yue; Wei Zhijing; Wang Wei [Key Laboratory of Eco-chemical Engineering, Ministry of Education, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042 (China)

    2011-11-15

    Highlights: > The increased amount of monoclonal antibody in Au/SiO{sub 2} led to a wider linear range. > Due to the increased HRP tags in HRP-Ab{sub 2}/SiO{sub 2}, signal amplification achieved. > A simple dual amplification immunoassay achieved with flow injection analysis. - Abstract: A chemiluminescent dual signal amplification strategy for the determination of {alpha}-fetoprotein (AFP) was proposed based on a sandwich immunoassay format. Monoclonal antibody of AFP immobilized on the gold nanoparticles doped mesoporous SiO{sub 2} (Au/SiO{sub 2}) were prepared and used as a primary antibody. Horseradish peroxidase (HRP) and HRP-labeled secondary antibody (Ab{sub 2}) co-immobilized into the mesoporous SiO{sub 2} nanoparticles (HRP-Ab{sub 2}/SiO{sub 2}) were used as the labeled immunological probe. Due to the high ratio surface areas and pore volumes of the mesoporous SiO{sub 2}, not only the amount of AFP monoclonal antibody but also the amount of the modified HRP and Ab{sub 2} in HRP-Ab{sub 2}/SiO{sub 2} were largely increased. Thus the chemiluminescent signal was amplified by using the system of luminol and H{sub 2}O{sub 2} under the catalysis of HRP. Under the optimal conditions, two linear ranges for AFP were obtained from 0.01 to 0.5 ng mL{sup -1} and 0.5 to 100 ng mL{sup -1} with a detection limit of 0.005 ng mL{sup -1} (3{sigma}). The fabricated signal amplification strategy showed an excellent promise for sensitive detection of AFP and other tumor markers.

  9. Amplification of ABA biosynthesis and signaling through a positive feedback mechanism in seeds.

    Science.gov (United States)

    Nonogaki, Mariko; Sall, Khadidiatou; Nambara, Eiji; Nonogaki, Hiroyuki

    2014-05-01

    Abscisic acid is an essential hormone for seed dormancy. Our previous study using the plant gene switch system, a chemically induced gene expression system, demonstrated that induction of 9-cis-epoxycarotenoid dioxygenase (NCED), a rate-limiting ABA biosynthesis gene, was sufficient to suppress germination in imbibed Arabidopsis seeds. Here, we report development of an efficient experimental system that causes amplification of NCED expression during seed maturation. The system was created with a Triticum aestivum promoter containing ABA responsive elements (ABREs) and a Sorghum bicolor NCED to cause ABA-stimulated ABA biosynthesis and signaling, through a positive feedback mechanism. The chimeric gene pABRE:NCED enhanced NCED and ABF (ABRE-binding factor) expression in Arabidopsis Columbia-0 seeds, which caused 9- to 73-fold increases in ABA levels. The pABRE:NCED seeds exhibited unusually deep dormancy which lasted for more than 3 months. Interestingly, the amplified ABA pathways also caused enhanced expression of Arabidopsis NCED5, revealing the presence of positive feedback in the native system. These results demonstrated the robustness of positive feedback mechanisms and the significance of NCED expression, or single metabolic change, during seed maturation. The pABRE:NCED system provides an excellent experimental system producing dormant and non-dormant seeds of the same maternal origin, which differ only in zygotic ABA. The pABRE:NCED seeds contain a GFP marker which enables seed sorting between transgenic and null segregants and are ideal for comparative analysis. In addition to its utility in basic research, the system can also be applied to prevention of pre-harvest sprouting during crop production, and therefore contributes to translational biology. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

  10. Signal amplification in electrochemical detection of buckwheat allergenic protein using field effect transistor biosensor by introduction of anionic surfactant

    Directory of Open Access Journals (Sweden)

    Sho Hideshima

    2016-03-01

    Full Text Available Food allergens, especially buckwheat proteins, sometimes induce anaphylactic shock in patients after ingestion. Development of a simple and rapid screening method based on a field effect transistor (FET biosensor for food allergens in food facilities or products is in demand. In this study, we achieved the FET detection of a buckwheat allergenic protein (BWp16, which is not charged enough to be electrically detected by FET biosensors, by introducing additional negative charges from anionic surfactants to the target proteins. A change in the FET characteristics reflecting surface potential caused by the adsorption of target charged proteins was observed when the target sample was coupled with the anionic surfactant (sodium dodecyl sulfate; SDS, while no significant response was detected without any surfactant treatment. It was suggested that the surfactant conjugated with the protein could be useful for the charge amplification of the target proteins. The surface plasmon resonance analysis revealed that the SDS-coupled proteins were successfully captured by the receptors immobilized on the sensing surface. Additionally, we obtained the FET responses at various concentrations of BWp16 ranging from 1 ng/mL to 10 μg/mL. These results suggest that a signal amplification method for FET biosensing is useful for allergen detection in the food industry. Keywords: Field effect transistor biosensor, Food allergen, Signal amplification, Ionic surfactant, Intrinsic charge

  11. Signal-off Electrochemiluminescence Biosensor Based on Phi29 DNA Polymerase Mediated Strand Displacement Amplification for MicroRNA Detection.

    Science.gov (United States)

    Chen, Anyi; Gui, Guo-Feng; Zhuo, Ying; Chai, Ya-Qin; Xiang, Yun; Yuan, Ruo

    2015-06-16

    A target induced cycling strand displacement amplification (SDA) mediated by phi29 DNA polymerase (phi29) was first investigated and applied in a signal-off electrochemiluminescence (ECL) biosensor for microRNA (miRNA) detection. Herein, the target miRNA triggered the phi29-mediated SDA which could produce amounts of single-stranded DNA (assistant probe) with accurate and comprehensive nucleotide sequence. Then, the assistant probe hybridized with the capture probe and the ferrocene-labeled probe (Fc-probe) to form a ternary "Y" structure for ECL signal quenching by ferrocene. Therefore, the ECL intensity would decrease with increasing concentration of the target miRNA, and the sensitivity of biosensor would be promoted on account of the efficient signal amplification of the target induced cycling reaction. Besides, a self-enhanced Ru(II) ECL system was designed to obtain a stable and strong initial signal to further improve the sensitivity. The ECL assay for miRNA-21 detection is developed with excellent sensitivity of a concentration variation from 10 aM to 1.0 pM and limit of detection down to 3.3 aM.

  12. Aptamer based fluorescent cocaine assay based on the use of graphene oxide and exonuclease III-assisted signal amplification

    International Nuclear Information System (INIS)

    Zhang, Yulin; Zhang, Guo-Jun; Sun, Zhongyue; Tang, Lina; Zhang, Hong

    2016-01-01

    The article reports an aptamer based assay for cocaine by employing graphene oxide and exonuclease III-assisted signal amplification. It is based on the following scheme and experimental steps: (1) Exo III can digest dsDNA with blunt or recessed 3-terminus, but it has limited activity to ssDNA or dsDNA with protruding 3-terminus; (2) GO can absorb the FAM-labeled ssDNA probe and quench the fluorescence of probe, while the affinity between FAM-labeled mononucleotide and GO is negligible; (3) Cocaine aptamer can be split into two flexible ssDNA pieces (Probe 1 and Probe 2) without significant perturbation of cocaine-binding abilities; (4) The triple complex consisting of Probe 1, Probe 2 and cocaine can be digested by Exo III with the similar efficiency as normal dsDNA. Cocaine aptamer is split into two flexible ssDNA pieces (Probe 2 and 3′-FAM-labeled Probe 1). Cocaine can mediate the cocaine aptamer fragments forming a triplex. The triple complex has unique characteristic with 3′-FAM-labeled blunt end at the Probe 1 and 3′-overhang end at Probe 2. If exonuclease III is added, it will catalyze the stepwise removal of fluorescein (FAM) labeled mononucleotides from the 3-hydroxy termini of the special triplex complex, resulting in liberation of cocaine. The cocaine released in this step can produce a new cleavage cycle, thereby leading to target recycling. Through such a cyclic bound-hydrolysis process, small amounts of cocaine can induce the cleavage of a large number of FAM-labeled probe 1. The cleaved FAM-labeled mononucleotides are not adsorbed on the surface of graphene oxide (GO), so a strong fluorescence signal enhancement is observed as the cocaine triggers enzymatic digestion. Under optimized conditions, the assay allows cocaine to be detected in the 1 to 500 nM concentration range with a detection limit of 0.1 nM. The method was applied to the determination of cocaine in spiked human plasma, with recoveries ranging from 92.0 to 111.8 % and RSD of <12

  13. Inertial amplification of continuous structures: Large band gaps from small masses

    DEFF Research Database (Denmark)

    Frandsen, Niels Morten Marslev; Bilal, Osama R.; Jensen, Jakob Søndergaard

    2016-01-01

    We investigate wave motion in a continuous elastic rod with a periodically attached inertial amplification mechanism. The mechanism has properties similar to an “inerter” typically used in vehicle suspensions, however here it is constructed and utilized in a manner that alters the intrinsic...

  14. Signal-to-Noise Enhancement of a Nanospring Redox-Based Sensor by Lock-in Amplification

    Directory of Open Access Journals (Sweden)

    Pavel V. Bakharev

    2015-06-01

    Full Text Available A significant improvement of the response characteristics of a redox chemical gas sensor (chemiresistor constructed with a single ZnO coated silica nanospring has been achieved with the technique of lock-in signal amplification. The comparison of DC and analog lock-in amplifier (LIA AC measurements of the electrical sensor response to toluene vapor, at the ppm level, has been conducted. When operated in the DC detection mode, the sensor exhibits a relatively high sensitivity to the analyte vapor, as well as a low detection limit at the 10 ppm level. However, at 10 ppm the signal-to-noise ratio is 5 dB, which is less than desirable. When operated in the analog LIA mode, the signal-to-noise ratio at 10 ppm increases by 30 dB and extends the detection limit to the ppb range.

  15. Parametric amplification and phase preserving amplitude regeneration of a 640 Gbit/s RZ-DPSK signal

    DEFF Research Database (Denmark)

    Lali-Dastjerdi, Zohreh; Galili, Michael; Mulvad, Hans Christian Hansen

    2013-01-01

    We report the first experimental demonstration of parametric amplification and all-optical phase-preserving amplitude regeneration for a 640 Gbit/s return-to-zero (RZ) differential phase-shift keying (DPSK) optical time division multiplexed (OTDM) signal. In the designed gain-flattened single......-pump fiber optical parametric amplifier (FOPA), 620 fs short optical pulses are successfully amplified with 15 dB gain with error-free performance and less than 1 dB power penalty. Phase-preserving amplitude regeneration based on gain saturation in the FOPA is carried out for optical signals with degraded...... optical signal-to-noise ratio. An improvement of 2.2 dB in receiver sensitivity at a bit-error-ratio of 10−9 has been successfully achieved after regeneration, together with 13.3 dB net gain....

  16. Analysis of small-signal intensity modulation of semiconductor ...

    Indian Academy of Sciences (India)

    This paper demonstrates theoretical characterization of intensity modulation of semiconductor lasers (SL's). The study is based on a small-signal model to solve the laser rate equations taking into account suppression of optical gain. Analytical forms of the small-signal modulation response and modulation bandwidth are ...

  17. Towards the use of protein A-tagged gold nanoparticles for signal amplification of electrochemical immunosensors in virus detection

    International Nuclear Information System (INIS)

    Huy Tran, Quang; Thuy Nguyen, Thanh; Chung Pham, Van; Hong Hanh Nguyen, Thi; Tuan Mai, Anh

    2012-01-01

    In this paper we represent a study on the potential use of protein A-tagged gold nanoparticles applied for signal amplification of electrochemical immunosensors. Gold nanoparticles (GNPs) were synthesized by the chemical reduction of tetrachloroauric (III) acid trihydrate using sodium ascorbate, and then tagged with protein A (PrA) via ultracentrifugation. UV-Vis spectroscopy and transmission electron microscopy were used to verify the characteristics of formed GNPs/PrA complex. The analyzed results indicate that GNPs were found spherically, homogeneously, and with an average diameter of about 10 nm. Immunoelectron microscopy was then used to investigate the bioactivity of the GNPs/PrA complex in solution by the effective binding of GNPs to viral particles. Scanning electron and fluorescence microscopies were also used to investigate the distribution and the bioactivity of the GNPs/PrA complex on the surface of the interdigitated sensor. Consequently, this study provided some assumptions of the potential application of protein A-tagged gold nanoparticles for signal amplification of electrochemical immunosensors in virus detection from clinical samples

  18. [Oligonucleotide derivatives in the nucleic acid hybridization analysis. II. Isothermal signal amplification in process of DNA analysis by minisequencing].

    Science.gov (United States)

    Dmitrienko, E V; Khomiakova, E A; Pyshnaia; Bragin, A G; Vedernikov, V E; Pyshnyĭ, D V

    2010-01-01

    The isothermal amplification of reporter signal via limited probe extension (minisequencing) upon hybridization of nucleic acids has been studied. The intensity of reporter signal has been shown to increase due to enzymatic labeling of multiple probes upon consecutive hybridization with one DNA template both in homophase and heterophase assays using various kinds of detection signal: radioisotope label, fluorescent label, and enzyme-linked assay. The kinetic scheme of the process has been proposed and kinetic parameters for each step have been determined. The signal intensity has been shown to correlate with physicochemical characteristics of both complexes: probe/DNA and product/DNA. The maximum intensity has been observed at minimal difference between the thermodynamic stability of these complexes, provided the reaction temperature has been adjusted near their melting temperature values; rising or lowering the reaction temperature reduces the amount of reporting product. The signal intensity has been shown to decrease significantly upon hybridization with the DNA template containing single-nucleotide mismatches. Limited probe extension assay is useful not only for detection of DNA template but also for its quantitative characterization.

  19. Analysis of small-signal intensity modulation of semiconductor ...

    Indian Academy of Sciences (India)

    Computer simulation of the model is applied to 1.55-µm ... Semiconductor laser; small-signal modulation; modulation response; gain suppression. ... originates from intraband relaxation processes of charge carriers that extend for times as ...

  20. Imaging resolution signal-to-noise ratio in transverse phase amplification from classical information theory

    International Nuclear Information System (INIS)

    French, Doug; Huang Zun; Pao, H.-Y.; Jovanovic, Igor

    2009-01-01

    A quantum phase amplifier operated in the spatial domain can improve the signal-to-noise ratio in imaging beyond the classical limit. The scaling of the signal-to-noise ratio with the gain of the quantum phase amplifier is derived from classical information theory

  1. Small instrument to volcanic seismic signals

    Science.gov (United States)

    Carreras, Normandino; Gomariz, Spartacus; Manuel, Antoni

    2014-05-01

    Currently, the presence of volcanoes represents a threat to their local populations, and for this reason, scientific communities invest resources to monitor seismic activity of an area, and to obtain information to identify risk situations. To perform such monitoring, it can use different general purpose acquisition systems commercially available, but these devices do not meet to the specifications of reduced dimensions, low weight, low power consumption and low cost. These features allow the system works in autonomous mode for a long period of time, and it makes easy to be carried and to be installed. In the line of designing a volcanic acquisition system with the previously mentioned specifications, exists the Volcanology Department of CSIC, developers of a system with some of these specifications. The objective of this work is to improve the energy consumption requirements of the previous system, providing three channels of data acquisition and with the possibility to transmit data acquisition via radio frequency to a base station, allowing operation it in remote mode. The developed acquisition system consists of three very low-power acquisition modules of Texas Instruments (ADS1246), and this is designed to capture information of the three coordinate axes. A microprocessor also of Texas Instruments (MSP430F5438) is used to work in low-power, due to it is ready to run this consumption and also takes advantage the power save mode in certain moments when system is not working. This system is configurable by serial port, and it has a SD memory to storage data. Contrast to the previous system, it has a RF communication module incorporated specially to work in remote mode of Lynx (YLX-TRM8053-025-05), and boasts also with a GPS module which keeps the time reference synchronized with module of SANAV (GM-1315LA). Thanks to this last selection of components, it is designed a small system about 106 x 106 mm. Assuming that the power supply system is working during all the

  2. Visual detection and microplate assay for Staphylococcus aureus based on aptamer recognition coupled to tyramine signal amplification

    International Nuclear Information System (INIS)

    Yuan, Jinglei; Li, Can; Ma, Xiaoyuan; Xia, Yu; Chen, Jie; Wang, Zhouping; Yu, Ye

    2014-01-01

    We have developed a specific method for the visual detection of Staphylococcus aureus based on aptamer recognition coupled to tyramine signal amplification technology. A biotinylated aptamer specific for S. aureus was immobilized on the surface of the wells of a microplate via biotin-avidin binding. Then, the target bacteria (S. aureus), the biotinylated-aptamer-streptavidin-HRP conjugates, biotinylated tyramine, hydrogen peroxide and streptavidin-HRP were successively placed in the wells of the microplate. After adding TMB reagent and stop solution, the intensity of the yellow reaction product can be visually inspected or measured with a plate reader. Under optimized conditions, there is a linear relationship between absorbance at 450 nm and the concentration of S. aureus in the 10 to 107 cfu mL −1 concentration range (with an R 2 of 0.9976). The limit of detection is 8 cfu mL −1 . (author)

  3. Detection of lead(II) ions with a DNAzyme and isothermal strand displacement signal amplification.

    Science.gov (United States)

    Li, Wenying; Yang, Yue; Chen, Jian; Zhang, Qingfeng; Wang, Yan; Wang, Fangyuan; Yu, Cong

    2014-03-15

    A DNAzyme based method for the sensitive and selective quantification of lead(II) ions has been developed. A DNAzyme that requires Pb(2+) for activation was selected. An RNA containing DNA substrate was cleaved by the DNAzyme in the presence of Pb(2+). The 2',3'-cyclic phosphate of the cleaved 5'-part of the substrate was efficiently removed by Exonuclease III. The remaining part of the single stranded DNA (9 or 13 base long) was subsequently used as the primer for the strand displacement amplification reaction (SDAR). The method is highly sensitive, 200 pM lead(II) could be easily detected. A number of interference ions were tested, and the sensor showed good selectivity. Underground water samples were also tested, which demonstrated the feasibility of the current approach for real sample applications. It is feasible that our method could be used for DNAzyme or aptazyme based new sensing method developments for the quantification of other target analytes with high sensitivity and selectivity. © 2013 Elsevier B.V. All rights reserved.

  4. Electrochemical immunosensor with nanocellulose-Au composite assisted multiple signal amplification for detection of avian leukosis virus subgroup J.

    Science.gov (United States)

    Liu, Chao; Dong, Jing; Waterhouse, Geoffrey I N; Cheng, Ziqiang; Ai, Shiyun

    2018-03-15

    A sensitive sandwich-type electrochemical immunosensor was developed for the detection of avian leukosis virus subgroup J (ALV-J), which benefitted from multiple signal amplification involving graphene-perylene-3,4,9,10-tetracarboxylic acid nanocomposites (GR-PTCA), nanocellulose-Au NP composites (NC-Au) and the alkaline phosphatase (ALP) catalytic reaction. GR-PTCA nanocomposites on glassy carbon electrodes served as the immunosensor platform. Due to their excellent electrical conductivity and abundant polycarboxylic sites, the GR-PTCA nanocomposites allowed fast electron transfer and good immobilization of primary antibodies, thereby affording a strong immunosensor signal in the presence of ALV-J. The detected signal could be further amplified by the introduction of NC-Au composites as a carrier of secondary antibodies (Ab 2 ) and by harnessing the catalytic properties of Au and ALP. Under optimized testing conditions, the electrochemical immunosensor displayed excellent analytical performance for the detection of ALV-J, showing a linear current response from 10 2.08 to 10 4.0 TCID 50 /mL (TCID 50 : 50% tissue culture infective dose) with a low detection limit of 10 1.98 TCID 50 /mL (S/N = 3). In addition to high sensitivity, the immunosensor showed very good selectivity, reproducibility and operational stability, demonstrating potential application for the quantitative detection of ALV-J in clinical diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Branched-DNA signal amplification combined with paper chromatography hybridization assay and used in hepatitis B virus DNA detection

    International Nuclear Information System (INIS)

    Fu, F.Z.; Liu, L.X.; Wang, W.Q.; Sun, S. H.; Liu, L.B.

    2002-01-01

    Nucleic acids detection method is vital to the clinical pathogen diagnosis. The established method can be classified into target direct amplification and signal amplification format according to the target DNA or RNA being directly amplified or not. Those methods have advantages and disadvantages respectively in the clinical application. In the United States of American, branched-DNA as a strong signal amplifier is broadly used in the quantification of the nucleic acids. To gain satisfied sensitivity, some expensive label molecular and instruments should be adopted. Personnel should be special trained to perform. Hence, those can't be widely carried out in the Third World. To avoid those disadvantages, we used the branched-DNA amplifier in the paper chromatography hybridization assay. Methods: Branched DNA signal amplifier and series of probes complementary to the nucleic acid sequence of hepatitis B virus (HBV) have been synthesized. HBV-DNA or it's capture probe were immobilized on the high flow nitrocellulose strip. Having loaded at one end of the strip in turn, probes or HBV-DNA in the hybridization solution migrate to the opposite end of the strip by capillary forces and hybridizes to the immobilized DNA. The branched-DNA signal amplifier and probe labeled with biotin or 32P were then loaded. Through streptavidin-alkaline phosphatase (SA-AP) conjugate and NBT/BCIP ( the specific chromogenic substrate of AP) or autoradiography, the result can be visualized by color reaction or image production on the X-ray film. Results: The sensitivity of this HBV-DNA detection method used probe labeled with biotin and 32P are 1ng and 10pg. The method using the probe labeled with biotin is simple and rapid (2h) without depending on special instruments, it also avoids the pollution of EtBr which can lead to tumor. And the method using the probe labeled with 32P is simple and sensitive, with the exception of long time autoradiography and the inconvenient isotopic disposal

  6. Multiplex Ligation-Dependent Probe Amplification Technique for Copy Number Analysis on Small Amounts of DNA Material

    DEFF Research Database (Denmark)

    Sørensen, Karina; Andersen, Paal; Larsen, Lars

    2008-01-01

    The multiplex ligation-dependent probe amplification (MLPA) technique is a sensitive technique for relative quantification of up to 50 different nucleic acid sequences in a single reaction, and the technique is routinely used for copy number analysis in various syndromes and diseases. The aim...... of the study was to exploit the potential of MLPA when the DNA material is limited. The DNA concentration required in standard MLPA analysis is not attainable from dried blood spot samples (DBSS) often used in neonatal screening programs. A novel design of MLPA probes has been developed to permit for MLPA...... analysis on small amounts of DNA. Six patients with congenital adrenal hyperplasia (CAH) were used in this study. DNA was extracted from both whole blood and DBSS and subjected to MLPA analysis using normal and modified probes. Results were analyzed using GeneMarker and manual Excel analysis. A total...

  7. Irreversible Catalyst Activation Enables Hyperpolarization and Water Solubility for NMR Signal Amplification by Reversible Exchange

    Science.gov (United States)

    2016-09-12

    G. R.; Duckett, S. B.; Spiess , H. W.; Schreiber, L. M.; Münnemann, K. Continuous Proton Hyperpolarization Via SABRE and Hollow Fibre Membranes. Proc...M.; Kindervater, P.; Raich, H.-P.; Bargon, J.; Spiess , H. W.; Muennemann, K. Continuous H-1 and C-13 Signal Enhancement in NMR Spectroscopy and MRI

  8. PULSE REFERENCED CONTROL METHOD FOR ENHANCED POWER AMPLIFICATION OF A PULSE MODULATED SIGNAL

    DEFF Research Database (Denmark)

    1998-01-01

    , by introducing continuous delays on the individual pulse edges on the basis of error information provided by an error processing block. One preferred embodiment of the invention comprises: a Correction Unit with means to control the delays of the individual pulse edges as a function of a control input signal $i...

  9. Ultrasensitive electrochemical immunoassay of staphylococcal enterotoxin B in food using enzyme-nanosilica-doped carbon nanotubes for signal amplification.

    Science.gov (United States)

    Tang, Dianping; Tang, Juan; Su, Biling; Chen, Guonan

    2010-10-27

    A new sandwich-type electrochemical immunoassay for ultrasensitive detection of staphylococcal enterotoxin B (SEB) in food was developed using horseradish peroxidase-nanosilica-doped multiwalled carbon nanotubes (HRPSiCNTs) for signal amplification. Rabbit polyclonal anti-SEB antibodies immobilized on the screen-printed carbon electrode (SPCE) and covalently bound to the HRPSiCNTs were used as capture antibodies and detection antibodies, respectively. In the presence of SEB analyte, the sandwich-type immunocomplex could be formed between the immobilized anti-SEB on the SPCE and anti-SEB-labeled HRPSiCNTs, and the carried HRP could catalyze the electrochemical reduction of H2O2 with the help of thionine. The high content of HRP in the HRPSiCNTs could greatly amplify the electrochemical signal. Under optimal conditions, the reduction current increased with the increase of SEB in the sample, and exhibited a dynamic range of 0.05-15 ng/mL with a low detection limit (LOD) of 10 pg/mL SEB (at 3σ). Intra- and interassay coefficients of variation were below 10%. In addition, the assay was evaluated with SEB spiked samples including watermelon juice, soymilk, apple juice, and pork food, receiving excellent correlation with results from commercially available enzyme-linked immunosorbent assay (ELISA).

  10. Persistence and dynamics of DNA damage signal amplification determined by microcolony formation and live-cell imaging

    International Nuclear Information System (INIS)

    Oka, Yasuyoshi; Yamauchi, Motohiro; Suzuki, Masatoshi; Yamashita, Shunichi; Suzuki, Keiji

    2011-01-01

    Cell cycle checkpoints are essential cellular process protecting the integrity of the genome from DNA damaging agents. In the present study, we developed a microcolony assay, in which normal human diploid fibroblast-like cells exposed to ionizing radiation, were plated onto coverslips at very low density (3 cells/cm 2 ). Cells were grown for up to 3 days, and phosphorylated ataxia-telangiectasia mutated (ATM) at Ser1981 and 53BP1 foci were analyzed as the markers for an amplified DNA damage signal. We observed a dose-dependent increase in the fraction of non-dividing cells, whose increase was compromised by knocking down p53 expression. While large persistent foci were predominantly formed in non-dividing cells, we observed some growing colonies that contained cells with large foci. As each microcolony was derived from a single cell, it appeared that some cells could proliferate with large foci. A live-imaging analysis using hTERT-immortalized normal human diploid cells transfected with the EGFP-tagged 53BP1 gene revealed that the formation of persistent large foci was highly dynamic. Delayed appearance and disappearance of large foci were frequently observed in exposed cells visualized 12-72 hours after X-irradiation. Thus, our results indicate that amplified DNA damage signal could be ignored, which may be explained in part by the dynamic nature of the amplification process. (author)

  11. Collective Signal Processing in Cluster Chemotaxis: Roles of Adaptation, Amplification, and Co-attraction in Collective Guidance

    Science.gov (United States)

    Camley, Brian A.; Zimmermann, Juliane; Levine, Herbert; Rappel, Wouter-Jan

    2016-01-01

    Single eukaryotic cells commonly sense and follow chemical gradients, performing chemotaxis. Recent experiments and theories, however, show that even when single cells do not chemotax, clusters of cells may, if their interactions are regulated by the chemoattractant. We study this general mechanism of “collective guidance” computationally with models that integrate stochastic dynamics for individual cells with biochemical reactions within the cells, and diffusion of chemical signals between the cells. We show that if clusters of cells use the well-known local excitation, global inhibition (LEGI) mechanism to sense chemoattractant gradients, the speed of the cell cluster becomes non-monotonic in the cluster’s size—clusters either larger or smaller than an optimal size will have lower speed. We argue that the cell cluster speed is a crucial readout of how the cluster processes chemotactic signals; both amplification and adaptation will alter the behavior of cluster speed as a function of size. We also show that, contrary to the assumptions of earlier theories, collective guidance does not require persistent cell-cell contacts and strong short range adhesion. If cell-cell adhesion is absent, and the cluster cohesion is instead provided by a co-attraction mechanism, e.g. chemotaxis toward a secreted molecule, collective guidance may still function. However, new behaviors, such as cluster rotation, may also appear in this case. Co-attraction and adaptation allow for collective guidance that is robust to varying chemoattractant concentrations while not requiring strong cell-cell adhesion. PMID:27367541

  12. Power system small signal stability analysis and control

    CERN Document Server

    Mondal, Debasish; Sengupta, Aparajita

    2014-01-01

    Power System Small Signal Stability Analysis and Control presents a detailed analysis of the problem of severe outages due to the sustained growth of small signal oscillations in modern interconnected power systems. The ever-expanding nature of power systems and the rapid upgrade to smart grid technologies call for the implementation of robust and optimal controls. Power systems that are forced to operate close to their stability limit have resulted in the use of control devices by utility companies to improve the performance of the transmission system against commonly occurring power system

  13. Amplification of Marzagao small scale hydroelectric power plant; Ampliacao da PCH de Marzagao

    Energy Technology Data Exchange (ETDEWEB)

    Zeller, A.R.; Porto, D.S.; Pinto, F.S. [Leme Engenharia, MG (Brazil); Melo, A.U.; Almeida, A.M.; Pereira, D.R. [Fertiligas Industria e Comercio Ltda., MG (Brazil)

    1991-12-31

    This work presents the modernization and power augmentation of Marzagao small scale hydroelectric power plant. In order that the costs of the project be compatible to the total of investments in the project, it was necessary the adoption of methodologies and time scales different from those used for large and medium scale hydroelectric power plants 5 figs.

  14. A signal amplification assay for HSV type 1 viral DNA detection using nanoparticles and direct acoustic profiling

    Directory of Open Access Journals (Sweden)

    Hammond Richard

    2010-02-01

    Full Text Available Abstract Background Nucleic acid based recognition of viral sequences can be used together with label-free biosensors to provide rapid, accurate confirmation of viral infection. To enhance detection sensitivity, gold nanoparticles can be employed with mass-sensitive acoustic biosensors (such as a quartz crystal microbalance by either hybridising nanoparticle-oligonucleotide conjugates to complimentary surface-immobilised ssDNA probes on the sensor, or by using biotin-tagged target oligonucleotides bound to avidin-modified nanoparticles on the sensor. We have evaluated and refined these signal amplification assays for the detection from specific DNA sequences of Herpes Simplex Virus (HSV type 1 and defined detection limits with a 16.5 MHz fundamental frequency thickness shear mode acoustic biosensor. Results In the study the performance of semi-homogeneous and homogeneous assay formats (suited to rapid, single step tests were evaluated utilising different diameter gold nanoparticles at varying DNA concentrations. Mathematical models were built to understand the effects of mass transport in the flow cell, the binding kinetics of targets to nanoparticles in solution, the packing geometries of targets on the nanoparticle, the packing of nanoparticles on the sensor surface and the effect of surface shear stiffness on the response of the acoustic sensor. This lead to the selection of optimised 15 nm nanoparticles that could be used with a 6 minute total assay time to achieve a limit of detection sensitivity of 5.2 × 10-12 M. Larger diameter nanoparticles gave poorer limits of detection than smaller particles. The limit of detection was three orders of magnitude lower than that observed using a hybridisation assay without nanoparticle signal amplification. Conclusions An analytical model was developed to determine optimal nanoparticle diameter, concentration and probe density, which allowed efficient and rapid optimisation of assay parameters

  15. On-chip signal amplification of magnetic bead-based immunoassay by aviating magnetic bead chains.

    Science.gov (United States)

    Jalal, Uddin M; Jin, Gyeong Jun; Eom, Kyu Shik; Kim, Min Ho; Shim, Joon S

    2017-11-06

    In this work, a Lab-on-a-Chip (LOC) platform is used to electromagnetically actuate magnetic bead chains for an enhanced immunoassay. Custom-made electromagnets generate a magnetic field to form, rotate, lift and lower the magnetic bead chains (MBCs). The cost-effective, disposable LOC platform was made with a polymer substrate and an on-chip electrochemical sensor patterned via the screen-printing process. The movement of the MBCs is controlled to improve the electrochemical signal up to 230% when detecting beta-type human chorionic gonadotropin (β-hCG). Thus, the proposed on-chip MBC-based immunoassay is applicable for rapid, qualitative electrochemical point-of-care (POC) analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Multifunctional reduced graphene oxide trigged chemiluminescence resonance energy transfer: Novel signal amplification strategy for photoelectrochemical immunoassay of squamous cell carcinoma antigen.

    Science.gov (United States)

    Zhang, Yan; Sun, Guoqiang; Yang, Hongmei; Yu, Jinghua; Yan, Mei; Song, Xianrang

    2016-05-15

    Herein, a photoelectrochemical (PEC) immunoassay is constructed for squamous cell carcinoma antigen (SCCA) detection using zinc oxide nanoflower-bismuth sulfide (Bi2S3) composites as photoactive materials and reduced graphene oxide (rGO) as signal labels. Horseradish peroxidase is used to block sites against nonspecific binding, and then participated in luminol-based chemiluminescence (CL) system. The induced CL emission is acted as an inner light source to excite photoactive materials, simplifying the instrument. A novel signal amplification strategy is stem from rGO because of the rGO acts as an energy acceptor, while luminol serves as a donor to rGO, triggering the CL resonance energy transfer phenomenon between luminol and rGO. Thus, the efficient CL emission to photoactive materials decreases. Furthermore, the signal amplification caused by rGO labeled signal antibodies is related to photogenerated electron-hole pairs: perfect matching of energy levels between rGO and Bi2S3 makes rGO a sink to capture photogenerated electrons from Bi2S3; the increased steric hindrance hinders the electron donor to the surface of Bi2S3 for reaction with the photogenerated holes. On the basis of the novel signal amplification strategy, the proposed immunosensor exhibits excellent analytical performance for PEC detection of SCCA, ranging from 0.8 pg mL(-1) to 80 ng mL(-1) with a low detection limit of 0.21 pg mL(-1). Meanwhile, the designed signal amplification strategy provides a general format for future development of PEC assays. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Oligomerization of Paramagnetic Substrates Result in Signal Amplification and Can be Used for MR Imaging of Molecular Targets

    Directory of Open Access Journals (Sweden)

    Alexei Bogdanov

    2002-01-01

    Full Text Available Magnetic resonance imaging (MRI has evolved into a sophisticated, noninvasive imaging modality capable of high-resolution anatomical and functional characterization of transgenic animals. To expand the capabilities MRI, we have developed a novel MR signal amplification (MRamp strategy based on enzyme-mediated polymerization of paramagnetic substrates into oligomers of higher magnetic relaxivity. The substrates consist of chelated gadolinium covalently bound to phenols, which then serve as electron donors during enzymatic hydrogen peroxide reduction by peroxidase. The converted monomers undergo rapid condensation into paramagnetic oligomers leading to a threefold increase in atomic relaxivity (R1/Gd. The observed relaxivity changes are largely due to an increase in the rotational correlation time τr of the lanthanide. Three applications of the developed system are demonstrated: (1 imaging of nanomolar amounts of an oxidoreductase (peroxidase; (2 detection of a model ligand using an enzyme-linked immunoadsorbent assay format; and (3 imaging of E-selectin on the surface of endothelial cells probed for with an anti-E-selectin – peroxidase conjugate. The development of “enzyme sensing” probes is expected to have utility for a number of applications including in vivo detection of specific molecular targets. One particular advantage of the MRamp technique is that the same paramagnetic substrate can be potentially used to identify different molecular targets by attaching enzymes to various antibodies or other target-seeking molecules.

  18. Electrochemical DNA probe for Hg(2+) detection based on a triple-helix DNA and Multistage Signal Amplification Strategy.

    Science.gov (United States)

    Wang, Huan; Zhang, Yihe; Ma, Hongmin; Ren, Xiang; Wang, Yaoguang; Zhang, Yong; Wei, Qin

    2016-12-15

    In this work, an ultrasensitive electrochemical sensor was developed for detection of Hg(2+). Gold nanoparticles decorated bovine serum albumin reduction of graphene oxide (AuNP-BSA-rGO) were used as subsurface material for the immobilization of triple-helix DNA. The triple-helix DNA containing a thiol labelled single-stranded DNA (sDNA) and a thymine-rich DNA (T-rich DNA), which could be unwinded in the present of Hg(2+) to form more stable thymine-Hg(2+)-thymine (T-Hg(2+)-T) complex. T-Hg(2+)-T complex was then removed and the sDNA was left on the electrode. At this time, gold nanoparticle carrying thiol labelled cytosine-rich complementary DNA (cDNA-AuNP) could bind with the free sDNA. Meanwhile, the other free cDNA on AuNP could bind with each other in the present of Ag(+) to form the stable cytosine-Ag(+)-cytosine (C-Ag(+)-C) complex and circle amplification. Plenty of C-Ag(+)-C could form silver nanoclusters by electrochemical reduction and the striping signal of Ag could be measured for purpose of the final electrochemical detection of Hg(2+). This sensor could detect Hg(2+) over a wide concentration range from 0.1 to 130nM with a detection limit of 0.03nM. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Signal amplification strategy for biomarkers: Structural origins of epitaxial-growth twinned nanocrystals and D-π-A type polymers.

    Science.gov (United States)

    Liu, He; Gu, Yue; Dong, Tao; Yan, Liuqing; Yan, Xiaoyi; Zhang, Tingting; Lu, Nannan; Xu, Zhiqian; Xu, Haixin; Zhang, Zhiquan; Bian, Ting

    2018-06-30

    The combination of nanoparticles and biomarkers yields functional nanostructured biointerface, which is playing a notable role in biotechnology development. Due to the 5-fold twined structure in the Au-Pt star-shaped decahedra not only allowed it to act as efficient scaffold for immobilization of antibody, but it also exhibits superior electrocatalytic activity toward H 2 O 2 reduction, the nanocrystal as the efficient signal transduction label is first employed to construct an electrochemical immunosensor. Donor-π-Acceptor (D-π-A) linking fashion generates a dipolar push-pull system and assures superior intramolecular charge transfer. It is considered as a suitable π-conjugated backbone for conducting polymer on biointerface application. Under a D-π-A architecture which imidazole as the π-bridge and amino phenyl/phenyl groups as peripheral electron-donating/withdrawing functional groups, 4-(2,4,5-triphenyl-1H-imidazol-1-yl) aniline (TPIDA) is designed and synthesized for good biocompatibility and high conductivity. In this proposal, we attempt to integrate the above-mentioned two features from nanobiotechnology and organic bioelectronics. Then, a novel nonenzymatic sandwich-type immunosensor is performed by Au-Pt core-shell with surface-engineered twinning as a label and π-conjugated D-π-A polymers as the signal amplification platform. Human IgG (HIgG) as the model target protein can be detected with a wide linear range from 0.1 pg mL -1 to 100 ng mL -1 . The detection limit is down to 0.06 pg mL -1 (S/N = 3). Moreover, as a practical application, the prepared biosensor is used to monitor HIgG level in human serum with desirable results obtained. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. A Bioassay System Using Bioelectric Signals from Small Fish

    Science.gov (United States)

    Terawaki, Mitsuru; Soh, Zu; Hirano, Akira; Tsuji, Toshio

    Although the quality of tap water is generally examined using chemical assay, this method cannot be used for examination in real time. Against such a background, the technique of fish bioassay has attracted attention as an approach that enables constant monitoring of aquatic contamination. The respiratory rhythms of fish are considered an efficient indicator for the ongoing assessment of water quality, since they are sensitive to chemicals and can be indirectly measured from bioelectric signals generated by breathing. In order to judge aquatic contamination accurately, it is necessary to measure bioelectric signals from fish swimming freely as well as to stably discriminate measured signals, which vary between individuals. However, no bioassay system meeting the above requirements has yet been established. This paper proposes a bioassay system using bioelectric signals generated from small fish in free-swimming conditions. The system records signals using multiple electrodes to cover the extensive measurement range required in a free-swimming environment, and automatically discriminates changes in water quality from signal frequency components. This discrimination is achieved through an ensemble classification method using probability neural networks to solve the problem of differences between individual fish. The paper also reports on the results of related validation experiments, which showed that the proposed system was able to stably discriminate between water conditions before and after bleach exposure.

  1. Development of an efficient signal amplification strategy for label-free enzyme immunoassay using two site-specific biotinylated recombinant proteins

    International Nuclear Information System (INIS)

    Tang, Jin-Bao; Tang, Ying; Yang, Hong-Ming

    2015-01-01

    Highlights: • An efficient signal amplification strategy for label-free EIA is proposed. • Divalent biotinylated AP and monovalent biotinylated ZZ were prepared via Avitag–BirA system. • The above site-specific biotinylated fusion proteins form complex via SA–biotin interaction. • The mechanism relies on the ZZ–Avi-B/SA/AP–(Avi-B) 2 complex. • The analytical signals are enhanced (32-fold) by the proposed strategy. - Abstract: Constructing a recombinant protein between a reporter enzyme and a detector protein to produce a homogeneous immunological reagent is advantageous over random chemical conjugation. However, the approach hardly recombines multiple enzymes in a difunctional fusion protein, which results in insufficient amplification of the enzymatic signal, thereby limiting its application in further enhancement of analytical signal. In this study, two site-specific biotinylated recombinant proteins, namely, divalent biotinylated alkaline phosphatase (AP) and monovalent biotinylated ZZ domain, were produced by employing the Avitag–BirA system. Through the high streptavidin (SA)–biotin interaction, the divalent biotinylated APs were clustered in the SA–biotin complex and then incorporated with the biotinylated ZZ. This incorporation results in the formation of a functional macromolecule that involves numerous APs, thereby enhancing the enzymatic signal, and in the production of several ZZ molecules for the interaction with immunoglobulin G (IgG) antibody. The advantage of this signal amplification strategy is demonstrated through ELISA, in which the analytical signal was substantially enhanced, with a 32-fold increase in the detection sensitivity compared with the ZZ–AP fusion protein approach. The proposed immunoassay without chemical modification can be an alternative strategy to enhance the analytical signals in various applications involving immunosensors and diagnostic chips, given that the label-free IgG antibody is suitable for

  2. Development of an efficient signal amplification strategy for label-free enzyme immunoassay using two site-specific biotinylated recombinant proteins

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Jin-Bao [School of Pharmacy, Weifang Medical University, Weifang 261053 (China); Tang, Ying [Affiliated Hospital of Weifang Medical University, Weifang 261041 (China); Yang, Hong-Ming, E-mail: yanghongming2006@sohu.com [School of Pharmacy, Weifang Medical University, Weifang 261053 (China)

    2015-02-15

    Highlights: • An efficient signal amplification strategy for label-free EIA is proposed. • Divalent biotinylated AP and monovalent biotinylated ZZ were prepared via Avitag–BirA system. • The above site-specific biotinylated fusion proteins form complex via SA–biotin interaction. • The mechanism relies on the ZZ–Avi-B/SA/AP–(Avi-B){sub 2} complex. • The analytical signals are enhanced (32-fold) by the proposed strategy. - Abstract: Constructing a recombinant protein between a reporter enzyme and a detector protein to produce a homogeneous immunological reagent is advantageous over random chemical conjugation. However, the approach hardly recombines multiple enzymes in a difunctional fusion protein, which results in insufficient amplification of the enzymatic signal, thereby limiting its application in further enhancement of analytical signal. In this study, two site-specific biotinylated recombinant proteins, namely, divalent biotinylated alkaline phosphatase (AP) and monovalent biotinylated ZZ domain, were produced by employing the Avitag–BirA system. Through the high streptavidin (SA)–biotin interaction, the divalent biotinylated APs were clustered in the SA–biotin complex and then incorporated with the biotinylated ZZ. This incorporation results in the formation of a functional macromolecule that involves numerous APs, thereby enhancing the enzymatic signal, and in the production of several ZZ molecules for the interaction with immunoglobulin G (IgG) antibody. The advantage of this signal amplification strategy is demonstrated through ELISA, in which the analytical signal was substantially enhanced, with a 32-fold increase in the detection sensitivity compared with the ZZ–AP fusion protein approach. The proposed immunoassay without chemical modification can be an alternative strategy to enhance the analytical signals in various applications involving immunosensors and diagnostic chips, given that the label-free IgG antibody is suitable

  3. Comparative study of probabilistic methodologies for small signal stability assessment

    Energy Technology Data Exchange (ETDEWEB)

    Rueda, J.L.; Colome, D.G. [Universidad Nacional de San Juan (IEE-UNSJ), San Juan (Argentina). Inst. de Energia Electrica], Emails: joseluisrt@iee.unsj.edu.ar, colome@iee.unsj.edu.ar

    2009-07-01

    Traditional deterministic approaches for small signal stability assessment (SSSA) are unable to properly reflect the existing uncertainties in real power systems. Hence, the probabilistic analysis of small signal stability (SSS) is attracting more attention by power system engineers. This paper discusses and compares two probabilistic methodologies for SSSA, which are based on the two point estimation method and the so-called Monte Carlo method, respectively. The comparisons are based on the results obtained for several power systems of different sizes and with different SSS performance. It is demonstrated that although with an analytical approach the amount of computation of probabilistic SSSA can be reduced, the different degrees of approximations that are adopted, lead to deceptive results. Conversely, Monte Carlo based probabilistic SSSA can be carried out with reasonable computational effort while holding satisfactory estimation precision. (author)

  4. Improving Small Signal Stability through Operating Point Adjustment

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Zhenyu; Zhou, Ning; Tuffner, Francis K.; Chen, Yousu; Trudnowski, Daniel J.; Mittelstadt, William; Hauer, John F.; Dagle, Jeffery E.

    2010-09-30

    ModeMeter techniques for real-time small signal stability monitoring continue to mature, and more and more phasor measurements are available in power systems. It has come to the stage to bring modal information into real-time power system operation. This paper proposes to establish a procedure for Modal Analysis for Grid Operations (MANGO). Complementary to PSS’s and other traditional modulation-based control, MANGO aims to provide suggestions such as increasing generation or decreasing load for operators to mitigate low-frequency oscillations. Different from modulation-based control, the MANGO procedure proactively maintains adequate damping for all time, instead of reacting to disturbances when they occur. Effect of operating points on small signal stability is presented in this paper. Implementation with existing operating procedures is discussed. Several approaches for modal sensitivity estimation are investigated to associate modal damping and operating parameters. The effectiveness of the MANGO procedure is confirmed through simulation studies of several test systems.

  5. Small-signal model for the series resonant converter

    Science.gov (United States)

    King, R. J.; Stuart, T. A.

    1985-01-01

    The results of a previous discrete-time model of the series resonant dc-dc converter are reviewed and from these a small signal dynamic model is derived. This model is valid for low frequencies and is based on the modulation of the diode conduction angle for control. The basic converter is modeled separately from its output filter to facilitate the use of these results for design purposes. Experimental results are presented.

  6. Amplification of an Autodyne Signal in a Bistable Vertical-Cavity Surface-Emitting Laser with the Use of a Vibrational Resonance

    Science.gov (United States)

    Chizhevsky, V. N.

    2018-01-01

    For the first time, it is demonstrated experimentally that a vibrational resonance in a polarization-bistable vertical-cavity surface-emitting laser can be used to increase the laser response in autodyne detection of microvibrations from reflecting surfaces. In this case, more than 25-fold signal amplification is achieved. The influence of the asymmetry of the bistable potential on the microvibration-detection efficiency is studied.

  7. Kerr nonlinearity mitigation in 5 × 28-GBd PDM16-QAM signal transmission over a dispersion-uncompensated link with backward-pumpeddistributed Raman amplification

    DEFF Research Database (Denmark)

    Sackey, I.; Da Ros, Francesco; Jazayerifar, M.

    2014-01-01

    We present experimental and numerical investigations of Kerr nonlinearity compensation in a 400-km standard single-mode fiber link with distributed Raman amplification with backward pumping. A dual-pump polarization-independent fiber-based optical parametric amplifier is used for mid-link spectra...... to numerical simulations with good agreement. It is also shown with simulations that a maximum transmission reach of 2400 km enabled by the optical phase conjugator is possible for the WDM signal...

  8. Small signal gain measurements in a small scale HF overtone laser

    Energy Technology Data Exchange (ETDEWEB)

    Wisniewski, C.F.; Hewett, K.B.; Manke, G.C. II; Hager, G.D. [Air Force Research Laboratory, Directed Energy Directorate, 3550 Aberdeen Ave SE, Kirtland AFB, NM 87117-5776 (United States); Crowell, P.G. [Northrup Grumman Information Technology, Science and Technology Operating Unit, Advanced Technology Division, P.O. Box 9377, Albuquerque, NM 87119-9377 (United States); Truman, C.R. [Mechanical Engineering Department, University of New Mexico, Albuquerque, NM 87131 (United States)

    2003-07-01

    The overtone gain medium of a small-scale HF overtone laser was probed using a sub-Doppler tunable diode laser. Two-dimensional spatially resolved small signal gain and temperature maps were generated for several ro-vibrational transitions in the HF (v=2{yields}v=0) overtone band. Our results compare well with previous measurements of the overtone gain in a similar HF laser device. (orig.)

  9. The clinical pathological characteristics and prognosis of FGFR1 gene amplification in non-small-cell lung cancer: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Xie FJ

    2016-01-01

    Full Text Available Fa-Jun Xie,1,2 Hong-Yang Lu,1,3 Qiu-Qing Zheng,3 Jing Qin,1,3 Yun Gao,3 Yi-Ping Zhang,1,3 Xun Hu,2 Wei-Min Mao3,4 1Department of Medical Oncology, Zhejiang Cancer Hospital, 2Cancer Institute (Key Laboratory for Cancer Intervention and Prevention, China National Ministry of Education, Zhejiang Provincial Key Laboratory of Molecular Biology in Medical Sciences, Second Affiliated Hospital, Zhejiang University School of Medicine,3Zhejiang Key Laboratory of Diagnosis and Treatment Technology on Thoracic Oncology (Lung and Esophagus, Hangzhou, 4Department of Thoracic Surgery, Zhejiang Cancer Hospital, Hangzhou, People’s Republic of China Abstract: FGFR1 amplification is recognized as a novel therapy target for non-small-cell lung cancer (NSCLC, especially in squamous cell carcinoma (SCC. However, the association between FGFR1 amplification and the clinicopathological characteristics of NSCLC remains controversial. We performed a meta-analysis of 17 eligible studies to examine the correlation between FGFR1 gene amplification and clinicopathological characteristics. FGFR1 amplification was closely related to these clinicopathological features, including sex (odds ratio [OR] 2.05, 95% confidence interval [CI] 1.50–2.80, smoking (OR 3.31, 95% CI 2.02–5.44, and histology (OR 3.60, 95% CI 2.82–4.59. FGFR1 amplification was associated with shorter overall survival, and no significant heterogeneity existed between studies (I2=3.8%. We should note that publication bias may partly account for these results, but our findings remained significant after the trim-and-fill method (hazard ratio 1.22, 95% CI 1.06–1.40. However, no significant correlation was found with poor disease-free survival (hazard ratio 1.43, 95% CI 0.96–2.12. In conclusion, this study showed that FGFR1 amplification was significantly associated with sex, smoking, and histology. FGFR1 amplification could be a marker of poor prognosis in NSCLC patients, especially in SCC patients

  10. Enzyme-free and label-free ultrasensitive electrochemical detection of DNA and adenosine triphosphate by dendritic DNA concatamer-based signal amplification.

    Science.gov (United States)

    Liu, Shufeng; Lin, Ying; Liu, Tao; Cheng, Chuanbin; Wei, Wenji; Wang, Li; Li, Feng

    2014-06-15

    Hybridization chain reaction (HCR) strategy has been well developed for the fabrication of various biosensing platforms for signal amplification. Herein, a novel enzyme-free and label-free ultrasensitive electrochemical DNA biosensing platform for the detection of target DNA and adenosine triphosphate (ATP) was firstly proposed, in which three auxiliary DNA probes were ingeniously designed to construct the dendritic DNA concatamer via HCR strategy and used as hexaammineruthenium(III) chloride (RuHex) carrier for signal amplification. With the developed dendritic DNA concatamer-based signal amplification strategy, the DNA biosensor could achieve an ultrasensitive electrochemical detection of DNA and ATP with a superior detection limit as low as 5 aM and 20 fM, respectively, and also demonstrate a high selectivity for DNA and ATP detection. The currently proposed dendritic DNA concatamer opens a promising direction to construct ultrasensitive DNA biosensing platform for biomolecular detection in bioanalysis and clinical biomedicine, which offers the distinct advantages of simplicity and cost efficiency owing to no need of any kind of enzyme, chemical modification or labeling. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. The origin and effect of small RNA signaling in plants

    Directory of Open Access Journals (Sweden)

    Jean-Sébastien eParent

    2012-08-01

    Full Text Available Given their sessile condition, land plants need to integrate environmental cues rapidly and send signal throughout the organism to modify their metabolism accordingly. Small RNA (sRNA molecules are among the messengers that plant cells use to carry such signals. These molecules originate from fold-back stem-loops transcribed from endogenous loci or from perfect double-stranded RNA produced through the action of RNA-dependent RNA polymerases. Once produced, sRNAs associate with Argonaute and other proteins to form the RNA-induced silencing complex (RISC that executes silencing of complementary RNA molecules. Depending on the nature of the RNA target and the Argonaute protein involved, RISC triggers either DNA methylation and chromatin modification (leading to transcriptional gene silencing, TGS or RNA cleavage or translational inhibition (leading to post-transcriptional gene silencing, PTGS. In some cases, sRNAs move to neighboring cells and/or to the vascular tissues for long-distance trafficking. Many genes are involved in the biogenesis of sRNAs and recent studies have shown that both their origin and their protein partners have great influence on their activity and range. Here we summarize the work done to uncover the mode of action of the different classes of small RNA with special emphasis on their movement and how plants can take advantage of their mobility. We also review the various genetic requirements needed for production, movement and perception of the silencing signal.

  12. TSH Receptor Signaling Abrogation by a Novel Small Molecule.

    Science.gov (United States)

    Latif, Rauf; Realubit, Ronald B; Karan, Charles; Mezei, Mihaly; Davies, Terry F

    2016-01-01

    Pathological activation of the thyroid-stimulating hormone receptor (TSHR) is caused by thyroid-stimulating antibodies in patients with Graves' disease (GD) or by somatic and rare genomic mutations that enhance constitutive activation of the receptor influencing both G protein and non-G protein signaling. Potential selective small molecule antagonists represent novel therapeutic compounds for abrogation of such abnormal TSHR signaling. In this study, we describe the identification and in vitro characterization of a novel small molecule antagonist by high-throughput screening (HTS). The identification of the TSHR antagonist was performed using a transcription-based TSH-inhibition bioassay. TSHR-expressing CHO cells, which also expressed a luciferase-tagged CRE response element, were optimized using bovine TSH as the activator, in a 384 well plate format, which had a Z score of 0.3-0.6. Using this HTS assay, we screened a diverse library of ~80,000 compounds at a final concentration of 16.7 μM. The selection criteria for a positive hit were based on a mean signal threshold of ≥50% inhibition of control TSH stimulation. The screening resulted in 450 positive hits giving a hit ratio of 0.56%. A secondary confirmation screen against TSH and forskolin - a post receptor activator of adenylyl cyclase - confirmed one TSHR-specific candidate antagonist molecule (named VA-K-14). This lead molecule had an IC 50 of 12.3 μM and a unique chemical structure. A parallel analysis for cell viability indicated that the lead inhibitor was non-cytotoxic at its effective concentrations. In silico docking studies performed using a TSHR transmembrane model showed the hydrophobic contact locations and the possible mode of inhibition of TSHR signaling. Furthermore, this molecule was capable of inhibiting TSHR stimulation by GD patient sera and monoclonal-stimulating TSHR antibodies. In conclusion, we report the identification of a novel small molecule TSHR inhibitor, which has the

  13. Target-induced formation of gold amalgamation on DNA-based sensing platform for electrochemical monitoring of mercury ion coupling with cycling signal amplification strategy

    International Nuclear Information System (INIS)

    Chen, Jinfeng; Tang, Juan; Zhou, Jun; Zhang, Lan; Chen, Guonan; Tang, Dianping

    2014-01-01

    Graphical abstract: -- Highlights: •We report a new electrochemical sensing protocol for the detection of mercury ion. •Gold amalgamation on DNA-based sensing platform was used as nanocatalyst. •The signal was amplified by cycling signal amplification strategy. -- Abstract: Heavy metal ion pollution poses severe risks in human health and environmental pollutant, because of the likelihood of bioaccumulation and toxicity. Driven by the requirement to monitor trace-level mercury ion (Hg 2+ ), herein we construct a new DNA-based sensor for sensitive electrochemical monitoring of Hg 2+ by coupling target-induced formation of gold amalgamation on DNA-based sensing platform with gold amalgamation-catalyzed cycling signal amplification strategy. The sensor was simply prepared by covalent conjugation of aminated poly-T (25) oligonucleotide onto the glassy carbon electrode by typical carbodiimide coupling. Upon introduction of target analyte, Hg 2+ ion was intercalated into the DNA polyion complex membrane based on T–Hg 2+ –T coordination chemistry. The chelated Hg 2+ ion could induce the formation of gold amalgamation, which could catalyze the p-nitrophenol with the aid of NaBH 4 and Ru(NH 3 ) 6 3+ for cycling signal amplification. Experimental results indicated that the electronic signal of our system increased with the increasing Hg 2+ level in the sample, and has a detection limit of 0.02 nM with a dynamic range of up to 1000 nM Hg 2+ . The strategy afforded exquisite selectivity for Hg 2+ against other environmentally related metal ions. In addition, the methodology was evaluated for the analysis of Hg 2+ in spiked tap-water samples, and the recovery was 87.9–113.8%

  14. Target-induced formation of gold amalgamation on DNA-based sensing platform for electrochemical monitoring of mercury ion coupling with cycling signal amplification strategy

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Jinfeng; Tang, Juan; Zhou, Jun; Zhang, Lan; Chen, Guonan; Tang, Dianping, E-mail: dianping.tang@fzu.edu.cn

    2014-01-31

    Graphical abstract: -- Highlights: •We report a new electrochemical sensing protocol for the detection of mercury ion. •Gold amalgamation on DNA-based sensing platform was used as nanocatalyst. •The signal was amplified by cycling signal amplification strategy. -- Abstract: Heavy metal ion pollution poses severe risks in human health and environmental pollutant, because of the likelihood of bioaccumulation and toxicity. Driven by the requirement to monitor trace-level mercury ion (Hg{sup 2+}), herein we construct a new DNA-based sensor for sensitive electrochemical monitoring of Hg{sup 2+} by coupling target-induced formation of gold amalgamation on DNA-based sensing platform with gold amalgamation-catalyzed cycling signal amplification strategy. The sensor was simply prepared by covalent conjugation of aminated poly-T{sub (25)} oligonucleotide onto the glassy carbon electrode by typical carbodiimide coupling. Upon introduction of target analyte, Hg{sup 2+} ion was intercalated into the DNA polyion complex membrane based on T–Hg{sup 2+}–T coordination chemistry. The chelated Hg{sup 2+} ion could induce the formation of gold amalgamation, which could catalyze the p-nitrophenol with the aid of NaBH{sub 4} and Ru(NH{sub 3}){sub 6}{sup 3+} for cycling signal amplification. Experimental results indicated that the electronic signal of our system increased with the increasing Hg{sup 2+} level in the sample, and has a detection limit of 0.02 nM with a dynamic range of up to 1000 nM Hg{sup 2+}. The strategy afforded exquisite selectivity for Hg{sup 2+} against other environmentally related metal ions. In addition, the methodology was evaluated for the analysis of Hg{sup 2+} in spiked tap-water samples, and the recovery was 87.9–113.8%.

  15. Signal Formation Processes in Micromegas Detectors and Quality Control for large size Detector Construction for the ATLAS New Small Wheel

    CERN Document Server

    AUTHOR|(INSPIRE)INSPIRE-00387450; Rembser, Christoph

    2017-08-04

    The Micromegas technology is one of the most successful modern gaseous detector concepts and widely utilized in nuclear and particle physics experiments. Twenty years of R & D rendered the technology sufficiently mature to be selected as precision tracking detector for the New Small Wheel (NSW) upgrade of the ATLAS Muon spectrometer. This will be the first large scale application of Micromegas in one of the major LHC experiments. However, many of the fundamental microscopic processes in these gaseous detectors are still not fully understood and studies on several detector aspects, like the micromesh geometry, have never been addressed systematically. The studies on signal formation in Micromegas, presented in the first part of this thesis, focuses on the microscopic signal electron loss mechanisms and the amplification processes in electron gas interaction. Based on a detailed model of detector parameter dependencies, these processes are scrutinized in an iterating comparison between exper- imental result...

  16. Amplification of weak signals via the non-adiabatic regime of stochastic resonance in a bistable dynamical system with time delay

    International Nuclear Information System (INIS)

    Du Luchun; Mei Dongcheng

    2011-01-01

    The non-adiabatic regime of stochastic resonance (SR) in a bistable system with time delay, an additive white noise and a periodic signal was investigated. The signal power amplification η was employed to characterize the SR of the system. The simulation results indicate that (i) in the case of intermediate frequency Ω of the periodic signal, the typical behavior of SR is lowered monotonically by increasing the delay time τ; in the case of large Ω, τ weakens the SR behavior and then enhances it, with a non-monotonic behavior as a function of time delay; (ii) time delay induces SR when A is above the threshold, whereas no such resonance exists in the absence of time delay; (iii) time delay induces a transition from bimodal to unimodal configuration of η; (iv) varying the particular form of time delay results in different phenomena.

  17. Non-enzymolytic adenosine barcode-mediated dual signal amplification strategy for ultrasensitive protein detection using LC-MS/MS.

    Science.gov (United States)

    Yang, Wen; Li, Tengfei; Shu, Chang; Ji, Shunli; Wang, Lei; Wang, Yan; Li, Duo; Mtalimanja, Michael; Sun, Luning; Ding, Li

    2018-05-10

    A method is described for the determination of proteins with LC-MS/MS enabled by a small molecule (adenosine) barcode and based on a double-recognition sandwich structure. The coagulation protein thrombin was chosen as the model analyte. Magnetic nanoparticles were functionalized with aptamer29 (MNP/apt29) and used to capture thrombin from the samples. MNP/apt29 forms a sandwich with functionalized gold nanoparticles modified with (a) aptamer15 acting as thrombin-recognizing element and (b) a large number of adenosine as mass barcodes. The sandwich formed (MNP/apt29-thrombin-apt15/AuNP/adenosine) can ben magnetically separated from the sample. Mass barcodes are subsequently released from the sandwiched structure for further analysis by adding 11-mercaptoundecanoic acid. Adenosine is then detected by LC-MS/MS as it reflects the level of thrombin with impressively amplified signal. Numerous adenosines introduced into the sandwich proportional to the target concentration further amplify the signal. Under optimized conditions, the response is linearly proportional to the thrombin concentration in the range of 0.02 nM to 10 nM, with a detection limit of 9 fM. The application of this method to the determination of thrombin in spiked plasma samples gave recoveries that ranged from 92.3% to 104.7%. Graphical abstract Schematic representation of a method for the determination of thrombin with LC-MS/MS. The method is based on a double-recognition sandwiched structure. With LC-MS/MS, mass barcodes (adenosine) are detected to quantify thrombin, which amplifies the detection signal impressively.

  18. DFIG turbine representation for small signal voltage control studies

    DEFF Research Database (Denmark)

    Garcia, Jorge Martinez; Kjær, Philip Carne; Teodorescu, Remus

    2010-01-01

    This paper addresses the representation of a wind power plant, based on wound rotor asynchronous generators, with a centralized voltage controller, by an equivalent transfer function, valid for small signal voltage control studies. This representation allows to investigate the influence...... introduced recently by several grid codes from around the world, making important to analyze this control when applied to wind power plants. The performance of the equivalent transfer function has been evaluated and compared using an equivalent grid with different short circuit ratios and active power...... of the centralized plant control gain and short circuit ratio on the system stability, for instance, by analyzing the zero-pole placement. Larger percentages of wind power penetration translate to more demanding requirements coming from the grid codes, for example voltage support at the point of connection has been...

  19. Dual-cyclical nucleic acid strand-displacement polymerization based signal amplification system for highly sensitive determination of p53 gene.

    Science.gov (United States)

    Xu, Jianguo; Wu, Zai-Sheng; Li, Hongling; Wang, Zhenmeng; Le, Jingqing; Zheng, Tingting; Jia, Lee

    2016-12-15

    In the present study, we proposed a novel dual-cyclical nucleic acid strand-displacement polymerization (dual-CNDP) based signal amplification system for highly sensitive determination of tumor suppressor genes. The system primarily consisted of a signaling hairpin probe (SHP), a label-free hairpin probe (LHP) and an initiating primer (IP). The presence of target DNA was able to induce one CNDP through continuous process of ligation, polymerization and nicking, leading to extensively accumulation of two nicked triggers (NT1 and NT2). Intriguingly, the NT1 could directly hybridize SHP, while the NT2 could act as the target analog to induce another CNDP. The resulting dual-CNDP contributed the striking signal amplification, and only a very weak blank noise existed since the ligation template of target was not involved. In this case, the target could be detected in a wide linear range (5 orders of magnitude), and a low detection limit (78 fM) was obtained, which is superior to most of the existing fluorescent methods. Moreover, the dual-CNDP sensing system provided a high selectivity towards target DNA against mismatched target and was successfully applied to analysis of target gene extracted from cancer cells or in human serum-contained samples, indicating its great potential for practical applications. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. A Simple Method for the Extraction, PCR-amplification, Cloning, and Sequencing of Pasteuria 16S rDNA from Small Numbers of Endospores.

    Science.gov (United States)

    Atibalentja, N; Noel, G R; Ciancio, A

    2004-03-01

    For many years the taxonomy of the genus Pasteuria has been marred with confusion because the bacterium could not be cultured in vitro and, therefore, descriptions were based solely on morphological, developmental, and pathological characteristics. The current study sought to devise a simple method for PCR-amplification, cloning, and sequencing of Pasteuria 16S rDNA from small numbers of endospores, with no need for prior DNA purification. Results show that DNA extracts from plain glass bead-beating of crude suspensions containing 10,000 endospores at 0.2 x 10 endospores ml(-1) were sufficient for PCR-amplification of Pasteuria 16S rDNA, when used in conjunction with specific primers. These results imply that for P. penetrans and P. nishizawae only one parasitized female of Meloidogyne spp. and Heterodera glycines, respectively, should be sufficient, and as few as eight cadavers of Belonolaimus longicaudatus with an average number of 1,250 endospores of "Candidatus Pasteuria usgae" are needed for PCR-amplification of Pasteuria 16S rDNA. The method described in this paper should facilitate the sequencing of the 16S rDNA of the many Pasteuria isolates that have been reported on nematodes and, consequently, expedite the classification of those isolates through comparative sequence analysis.

  1. Nicking endonuclease-assisted signal amplification of a split molecular aptamer beacon for biomolecule detection using graphene oxide as a sensing platform.

    Science.gov (United States)

    Li, Xiang; Ding, Xuelian; Fan, Jing

    2015-12-07

    Sensitive and selective detection of ultralow concentrations of specific biomolecules is important in early clinical diagnoses and biomedical applications. Many types of aptasensors have been developed for the detection of various biomolecules, but usually suffer from false positive signals and high background signals. In this work, we have developed an amplified fluorescence aptasensor platform for ultrasensitive biomolecule detection based on enzyme-assisted target-recycling signal amplification and graphene oxide. By using a split molecular aptamer beacon and a nicking enzyme, the typical problem of false positive signals can be effectively resolved. Only in the presence of a target biomolecule, the sensor system is able to generate a positive signal, which significantly improves the selectivity of the aptasensor. Moreover, using graphene oxide as a super-quencher can effectively reduce the high background signal of a sensing platform. We select vascular endothelial growth factor (VEGF) and adenosine triphosphate (ATP) as model analytes in the current proof-of-concept experiments. It is shown that under optimized conditions, our strategy exhibits high sensitivity and selectivity for the quantification of VEGF and ATP with a low detection limit (1 pM and 4 nM, respectively). In addition, this biosensor has been successfully utilized in the analysis of real biological samples.

  2. Gold nanoparticles and the corresponding filter membrane as chemosensors and adsorbents for dual signal amplification detection and fast removal of mercury(ii).

    Science.gov (United States)

    Chen, Gaosong; Hai, Jun; Wang, Hao; Liu, Weisheng; Chen, Fengjuan; Wang, Baodui

    2017-03-02

    Nowadays, the development of a multifunction system for the simultaneous multiple signal amplification detection and fast removal of Hg 2+ remains a major challenge. Herein, we for the first time used gold nanoparticles (Au NPs) and the corresponding filter membrane as chemosensors and adsorbents for dual signal amplification detection and fast removal of Hg 2+ . Such a system was based on the formation of gold amalgam and a gold amalgam-based reaction between rhodamine B (RhB) and NaBH 4 with fluorescence and colorimetric sensing functions. When the gold amalgam catalyzes the reduction of RhB, the red color and orange fluorescence of RhB gradually changed to colorless by switching the amount of Hg 2+ deposited on 13 nm Au NPs. The detection limit of the fluorescence assay and colorimetric assay is 1.16 nM and 2.54 nM for Hg 2+ , respectively. Interestingly, the color and fluorescence of RhB could be recovered when the above colorless reaction solution was exposed to air for about 2 hours. Taking advantage of the above optical phenomenon, a recyclable paper-based sensor has been developed by immobilizing the Au NPs and RhB dye on filter paper and has been successfully used for detection of Hg 2+ in real water samples. In addition, the filter membrane immobilized Au NPs could allow fast removal of mercury ions in Yellow river water and tap water with the removal efficiency close to 99%.

  3. Targeting MET Amplification as a New Oncogenic Driver

    Energy Technology Data Exchange (ETDEWEB)

    Kawakami, Hisato [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Okamoto, Isamu, E-mail: okamotoi@kokyu.med.kyushu-u.ac.jp [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Center for Clinical and Translational Research, Kyushu University Hospital, 3-1-1 Maidashi, Higashiku, Fukuoka 812-8582 (Japan); Okamoto, Wataru [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Division of Transrlational Research, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577 (Japan); Tanizaki, Junko [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, HIM223, 450 Brookline Avenue, Boston, MA 02215 (United States); Nakagawa, Kazuhiko [Department of Medical Oncology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Nishio, Kazuto [Department of Genome Biology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511 (Japan)

    2014-07-22

    Certain genetically defined cancers are dependent on a single overactive oncogene for their proliferation and survival, a phenomenon known as “oncogene addiction”. A new generation of drugs that selectively target such “driver oncogenes” manifests a clinical efficacy greater than that of conventional chemotherapy in appropriate genetically defined patients. MET is a proto-oncogene that encodes a receptor tyrosine kinase, and aberrant activation of MET signaling occurs in a subset of advanced cancers as result of various genetic alterations including gene amplification, polysomy, and gene mutation. Our preclinical studies have shown that inhibition of MET signaling either with the small-molecule MET inhibitor crizotinib or by RNA interference targeted to MET mRNA resulted in marked antitumor effects in cancer cell lines with MET amplification both in vitro and in vivo. Furthermore, patients with non-small cell lung cancer or gastric cancer positive for MET amplification have shown a pronounced clinical response to crizotinib. Accumulating preclinical and clinical evidence thus suggests that MET amplification is an “oncogenic driver” and therefore a valid target for treatment. However, the prevalence of MET amplification has not been fully determined, possibly in part because of the difficulty in evaluating gene amplification. In this review, we provide a rationale for targeting this genetic alteration in cancer therapy.

  4. Targeting MET Amplification as a New Oncogenic Driver

    International Nuclear Information System (INIS)

    Kawakami, Hisato; Okamoto, Isamu; Okamoto, Wataru; Tanizaki, Junko; Nakagawa, Kazuhiko; Nishio, Kazuto

    2014-01-01

    Certain genetically defined cancers are dependent on a single overactive oncogene for their proliferation and survival, a phenomenon known as “oncogene addiction”. A new generation of drugs that selectively target such “driver oncogenes” manifests a clinical efficacy greater than that of conventional chemotherapy in appropriate genetically defined patients. MET is a proto-oncogene that encodes a receptor tyrosine kinase, and aberrant activation of MET signaling occurs in a subset of advanced cancers as result of various genetic alterations including gene amplification, polysomy, and gene mutation. Our preclinical studies have shown that inhibition of MET signaling either with the small-molecule MET inhibitor crizotinib or by RNA interference targeted to MET mRNA resulted in marked antitumor effects in cancer cell lines with MET amplification both in vitro and in vivo. Furthermore, patients with non-small cell lung cancer or gastric cancer positive for MET amplification have shown a pronounced clinical response to crizotinib. Accumulating preclinical and clinical evidence thus suggests that MET amplification is an “oncogenic driver” and therefore a valid target for treatment. However, the prevalence of MET amplification has not been fully determined, possibly in part because of the difficulty in evaluating gene amplification. In this review, we provide a rationale for targeting this genetic alteration in cancer therapy

  5. Differential transimpedance amplifier circuit for correlated differential amplification

    Science.gov (United States)

    Gresham, Christopher A [Albuquerque, NM; Denton, M Bonner [Tucson, AZ; Sperline, Roger P [Tucson, AZ

    2008-07-22

    A differential transimpedance amplifier circuit for correlated differential amplification. The amplifier circuit increase electronic signal-to-noise ratios in charge detection circuits designed for the detection of very small quantities of electrical charge and/or very weak electromagnetic waves. A differential, integrating capacitive transimpedance amplifier integrated circuit comprising capacitor feedback loops performs time-correlated subtraction of noise.

  6. A sensitive electrochemical aptasensor based on palladium nanoparticles decorated graphene–molybdenum disulfide flower-like nanocomposites and enzymatic signal amplification

    Energy Technology Data Exchange (ETDEWEB)

    Jing, Pei; Yi, Huayu; Xue, Shuyan; Chai, Yaqin; Yuan, Ruo; Xu, Wenju, E-mail: xwju@swu.edu.cn

    2015-01-01

    Highlights: • PDDA–G–MoS{sub 2} nanoflowers were firstly used for the fabrication of thrombin aptasensor. • MoS{sub 2} was adopted to enhance the surface area of graphene and accelerate the electron transfer. • GOD, PdNPs and hemin/G-quadruplex could amplify the electrochemical signal through synergetic catalysis. • The proposed aptasensor displayed an improved sensitivity. - Abstract: In the present study, with the aggregated advantages of graphene and molybdenum disulfide (MoS{sub 2}), we prepared poly(diallyldimethylammonium chloride)–graphene/molybdenum disulfide (PDDA–G–MoS{sub 2}) nanocomposites with flower-like structure, large surface area and excellent conductivity. Furthermore, an advanced sandwich-type electrochemical assay for sensitive detection of thrombin (TB) was fabricated using palladium nanoparticles decorated PDDA–G–MoS{sub 2} (PdNPs/PDDA–G–MoS{sub 2}) as nanocarriers, which were functionalized by hemin/G-quadruplex, glucose oxidase (GOD), and toluidine blue (Tb) as redox probes. The signal amplification strategy was achieved as follows: Firstly, the immobilized GOD could effectively catalyze the oxidation of glucose to gluconolactone, coupling with the reduction of the dissolved oxygen to H{sub 2}O{sub 2}. Then, both PdNPs and hemin/G-quadruplex acting as hydrogen peroxide (HRP)-mimicking enzyme could further catalyze the reduction of H{sub 2}O{sub 2}, resulting in significant electrochemical signal amplification. So the proposed aptasensor showed high sensitivity with a wide dynamic linear range of 0.0001 to 40 nM and a relatively low detection limit of 0.062 pM for TB determination. The strategy showed huge potential of application in protein detection and disease diagnosis.

  7. Target-induced formation of gold amalgamation on DNA-based sensing platform for electrochemical monitoring of mercury ion coupling with cycling signal amplification strategy.

    Science.gov (United States)

    Chen, Jinfeng; Tang, Juan; Zhou, Jun; Zhang, Lan; Chen, Guonan; Tang, Dianping

    2014-01-31

    Heavy metal ion pollution poses severe risks in human health and environmental pollutant, because of the likelihood of bioaccumulation and toxicity. Driven by the requirement to monitor trace-level mercury ion (Hg(2+)), herein we construct a new DNA-based sensor for sensitive electrochemical monitoring of Hg(2+) by coupling target-induced formation of gold amalgamation on DNA-based sensing platform with gold amalgamation-catalyzed cycling signal amplification strategy. The sensor was simply prepared by covalent conjugation of aminated poly-T(25) oligonucleotide onto the glassy carbon electrode by typical carbodiimide coupling. Upon introduction of target analyte, Hg(2+) ion was intercalated into the DNA polyion complex membrane based on T-Hg(2+)-T coordination chemistry. The chelated Hg(2+) ion could induce the formation of gold amalgamation, which could catalyze the p-nitrophenol with the aid of NaBH4 and Ru(NH3)6(3+) for cycling signal amplification. Experimental results indicated that the electronic signal of our system increased with the increasing Hg(2+) level in the sample, and has a detection limit of 0.02nM with a dynamic range of up to 1000nM Hg(2+). The strategy afforded exquisite selectivity for Hg(2+) against other environmentally related metal ions. In addition, the methodology was evaluated for the analysis of Hg(2+) in spiked tap-water samples, and the recovery was 87.9-113.8%. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Broadband Amplification of Low-Terahertz Signals Using Axis-Encircling Electrons in a Helically Corrugated Interaction Region

    Science.gov (United States)

    He, W.; Donaldson, C. R.; Zhang, L.; Ronald, K.; Phelps, A. D. R.; Cross, A. W.

    2017-11-01

    Experimental results are presented of a broadband, high power, gyrotron traveling wave amplifier (gyro-TWA) operating in the (75-110)-GHz frequency band and based on a helically corrugated interaction region. The second harmonic cyclotron mode of a 55-keV, 1.5-A, axis-encircling electron beam is used to resonantly interact with a traveling TE21 -like eigenwave achieving broadband amplification. The gyro-TWA demonstrates a 3-dB gain bandwidth of at least 5.5 GHz in the experimental measurement with 9 GHz predicted for a wideband drive source with a measured unsaturated output power of 3.4 kW and gain of 36-38 dB. The approach may allow a gyro-TWA to operate at 1 THz.

  9. Porous platinum nanotubes labeled with hemin/G-quadruplex based electrochemical aptasensor for sensitive thrombin analysis via the cascade signal amplification.

    Science.gov (United States)

    Sun, Aili; Qi, Qingan; Wang, Xuannian; Bie, Ping

    2014-07-15

    For the first time, a sensitive electrochemical aptasensor for thrombin (TB) was developed by using porous platinum nanotubes (PtNTs) labeled with hemin/G-quadruplex and glucose dehydrogenase (GDH) as labels. Porous PtNTs with large surface area exhibited the peroxidase-like activity. Coupling with GDH and hemin/G-quadruplex as NADH oxidase and HRP-mimicking DNAzyme, the cascade signal amplification was achieved by the following ways: in the presence of glucose and NAD(+) in the working buffer, GDH electrocatalyzed the oxidation of glucose with the production of NADH. Then, hemin/G-quadruplex as NADH oxidase catalyzed the oxidation of NADH to in situ generate H2O2. Based on the corporate electrocatalysis of PtNTs and hemin/G-quadruplex toward H2O2, the electrochemical signal was significantly amplified, allowing the detection limit of TB down to 0.15 pM level. Moreover, the proposed strategy was simple because the intercalated hemin offered the readout signal, avoiding the adding of additional redox mediator as signal donator. Such an electrochemical aptasensor is highly promising for sensitive detection of other proteins in clinical diagnostics. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Direct RNA detection without nucleic acid purification and PCR: Combining sandwich hybridization with signal amplification based on branched hybridization chain reaction.

    Science.gov (United States)

    Xu, Yao; Zheng, Zhi

    2016-05-15

    We have developed a convenient, robust and low-cost RNA detection system suitable for high-throughput applications. This system uses a highly specific sandwich hybridization to capture target RNA directly onto solid support, followed by on-site signal amplification via 2-dimensional, branched hybridizing chain polymerization through toehold-mediated strand displacement reaction. The assay uses SYBR Green to detect targets at concentrations as low as 1 pM, without involving nucleic acid purification or any enzymatic reaction, using ordinary oligonucleotides without modification or labeling. The system was demonstrated in the detection of malaria RNA in blood and GAPDH gene expression in cell lysate. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. KSHV cell attachment sites revealed by ultra sensitive tyramide signal amplification (TSA) localize to membrane microdomains that are up-regulated on mitotic cells.

    Science.gov (United States)

    Garrigues, H Jacques; Rubinchikova, Yelena E; Rose, Timothy M

    2014-03-01

    Cell surface structures initiating attachment of Kaposi's sarcoma-associated herpesvirus (KSHV) were characterized using purified hapten-labeled virions visualized by confocal microscopy with a sensitive fluorescent enhancement using tyramide signal amplification (TSA). KSHV attachment sites were present in specific cellular domains, including actin-based filopodia, lamellipodia, ruffled membranes, microvilli and intercellular junctions. Isolated microdomains were identified on the dorsal surface, which were heterogeneous in size with a variable distribution that depended on cellular confluence and cell cycle stage. KSHV binding domains ranged from scarce on interphase cells to dense and continuous on mitotic cells, and quantitation of bound virus revealed a significant increase on mitotic compared to interphase cells. KSHV also bound to a supranuclear domain that was distinct from microdomains in confluent and interphase cells. These results suggest that rearrangement of the cellular membrane during mitosis induces changes in cell surface receptors implicated in the initial attachment stage of KSHV entry. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Photoelectrochemical sensitive detection of insulin based on CdS/polydopamine co-sensitized WO3 nanorod and signal amplification of carbon nanotubes@polydopamine.

    Science.gov (United States)

    Wang, Rongyu; Ma, Hongmin; Zhang, Yong; Wang, Qi; Yang, Zhongping; Du, Bin; Wu, Dan; Wei, Qin

    2017-10-15

    An ultrasensitive photoelectrochemical sandwich immunosensor was designed for detection of insulin based on WO 3 /CdS/polydopamine (WO 3 /CdS/PDA) co-sensitized and PDA@carbon nanotubes (PDA@CNT) conjugates for signal amplification. The CdS nanoparticles were first deposited on the WO 3 nanorods via sequential chemical bath deposition to form the WO 3 /CdS structure to enhance photocurrent. Then equipped with PDA to form the WO 3 /CdS/PDA photosensitive structure. The PDA was used not only to reduce the toxicity of CdS but also adsorb insulin primary antibodies (Ab 1 ). Meanwhile, insulin secondary antibodies (Ab 2 ) were decorated by PDA@CNT conjugates for signal amplification and further enhance photocurrent. Different photocurrent intensities were obtained by the photoelectrochemical workstation at applied bias of 0V due to the different amount of the PDA@CNT conjugates introduced by the different concentrations of insulin. A good linear relationship was obtained between the increased photocurrent and insulin concentrations range from 0.01ngmL -1 to 50ngmL -1 . And a detection limit of 2.8pgmL -1 was obtained. The proposed sensor was applied to the determination of the insulin in human serum sample, and satisfactory results were obtained. The sensor presented good specificity, reproducibility and stability, thus it might find application in the clinical diagnosis of insulin or other biomarkers in the near future. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Realization of the conceptual ideal for x-ray amplification

    Energy Technology Data Exchange (ETDEWEB)

    Borisov, Alex B; Racz, Ervin; Zhang Ping; McCorkindale, John C; Khan, Shahab F; Poopalasingam, Sankar; Zhao Ji; Rhodes, Charles K [Laboratory for X-Ray Microimaging and Bioinformatics, Department of Physics, University of Illinois at Chicago, Chicago, IL 60607-7059 (United States)

    2008-05-28

    The Xe(L) system is an amplifier with fundamentally different dynamic characteristics from all previously developed laser amplifiers; it represents the conceptual ideal through full utilization of the Kramers-Kronig relations that fundamentally couple the dispersive and absorptive components. The dispersive response of the system, through optimal governance of the power compression, rules the amplification and establishes a minimum gain for the amplifier. Accordingly, the amplification requires a minimum value of the dispersion to be surpassed; the corresponding gain follows automatically. As a leading consequence, since this minimum gain is sufficiently high, the key experimental observation is the uniform presence of saturated amplification signaled by strong spectral hole burning on all transitions exhibiting amplification, including double-vacancy lines. This cardinal signature demonstrates that the amplification is legislated by the saturated gain g{sub s}, not the corresponding small signal value g{sub 0}. The chief outcome is that explosive dispersion yields perforce explosive amplification and the efficient generation of maximally bright coherent power.

  14. Sensitive and fast detection of fructose in complex media via symmetry breaking and signal amplification using surface-enhanced Raman spectroscopy.

    Science.gov (United States)

    Sun, Fang; Bai, Tao; Zhang, Lei; Ella-Menye, Jean-Rene; Liu, Sijun; Nowinski, Ann K; Jiang, Shaoyi; Yu, Qiuming

    2014-03-04

    A new strategy is proposed to sensitively and rapidly detect analytes with weak Raman signals in complex media using surface-enhanced Raman spectroscopy (SERS) via detecting the SERS signal changes of the immobilized probe molecules on SERS-active substrates upon binding of the analytes. In this work, 4-mercaptophenylboronic acid (4-MPBA) was selected as the probe molecule which was immobilized on the gold surface of a quasi-three-dimensional plasmonic nanostructure array (Q3D-PNA) SERS substrate to detect fructose. The molecule of 4-MPBA possesses three key functions: molecule recognition and reversible binding of the analyte via the boronic acid group, amplification of SERS signals by the phenyl group and thus shielding of the background noise of complex media, and immobilization on the surface of SERS-active substrates via the thiol group. Most importantly, the symmetry breaking of the 4-MPBA molecule upon fructose binding leads to the change of area ratio between totally symmetric 8a ring mode and nontotally symmetric 8b ring mode, which enables the detection. The detection curves were obtained in phosphate-buffered saline (PBS) and in undiluted artificial urine at clinically relevant concentrations, and the limit of detection of 0.05 mM was achieved.

  15. small signal analysis of load angle governing and excitation control

    African Journals Online (AJOL)

    Dr Obe

    system stabilizers (PSS) or using terminal voltage for control of exciter and speed signal for governor. ... Vfd= generator field voltage. Xd, Xq ... each other in the frequency domain, and therefore ..... angle sensing equipment, relays and.

  16. Amplification of the Signal Intensity of Fluorescence-Based Fiber-Optic Biosensors Using a Fabry-Perot Resonator Structure

    Directory of Open Access Journals (Sweden)

    Meng-Chang Hsieh

    2015-02-01

    Full Text Available Fluorescent biosensors have been widely used in biomedical applications. To amplify the intensity of fluorescence signals, this study developed a novel structure for an evanescent wave fiber-optic biosensor by using a Fabry-Perot resonator structure. An excitation light was coupled into the optical fiber through a laser-drilled hole on the proximal end of the resonator. After entering the resonator, the excitation light was reflected back and forth inside the resonator, thereby amplifying the intensity of the light in the fiber. Subsequently, the light was used to excite the fluorescent molecules in the reactive region of the sensor. The experimental results showed that the biosensor signal was amplified eight-fold when the resonator reflector was formed using a 92% reflective coating. Furthermore, in a simulation, the biosensor signal could be amplified 20-fold by using a 99% reflector.

  17. A study on the determination of risk factors associated with babesiosis and prevalence of Babesia sp., by PCR amplification, in small ruminants from Southern Punjab (Pakistan

    Directory of Open Access Journals (Sweden)

    Iqbal F.

    2011-08-01

    Full Text Available Babesiosis is a parasitic infection due to the multiplication of tick borne parasite, Babesia sp., in erythrocytes of host, which includes a wide variety of vertebrates including small ruminants causing decreased livestock output and hence economic losses. The objective of the present study was to establish a PCR based method for the detection of Babesia sp. in small ruminant population in Southern Punjab and to determine the risk factors involve in the spread of babesiosis. A total of 107 blood samples were collected from 40 sheep and 67 goats in seven districts of Southern Punjab from randomly selected herds. Data on the characteristics of the animals and the herd were collected through questionnaires. 36 blood samples (34% of total produced the DNA fragment specific for 18S rRNA gene of Babesia sp., by PCR amplification, of which 20 were sheep and 16 were goats. Samples from all seven district contained Babesia positive samples and prevalence varied between 18 to 68%. It was observed that male animals (P = 0.009 and young animals under one year of age (P = 0.01 were more prone to the parasite. It was observed that herds consist of more than 15 animals (P = 0.007, composed of mixed species of small ruminants (P = 0.022, associated with dogs (P = 0.003 and dogs having ticks on their bodies (P = 0.011 were among the major risk factors for the spread of babesiosis in small ruminants.

  18. A study on the determination of risk factors associated with babesiosis and prevalence of Babesia sp., by PCR amplification, in small ruminants from Southern Punjab (Pakistan).

    Science.gov (United States)

    Iqbal, F; Fatima, M; Shahnawaz, S; Naeem, M; Shaikh, Rs; Ali, M; Shaikh, As; Aktas, M; Ali, M

    2011-08-01

    Babesiosis is a parasitic infection due to the multiplication of tick borne parasite, Babesia sp., in erythrocytes of host, which includes a wide variety of vertebrates including small ruminants causing decreased livestock output and hence economic losses. The objective of the present study was to establish a PCR based method for the detection of Babesia sp. in small ruminant population in Southern Punjab and to determine the risk factors involve in the spread of babesiosis. A total of 107 blood samples were collected from 40 sheep and 67 goats in seven districts of Southern Punjab from randomly selected herds. Data on the characteristics of the animals and the herd were collected through questionnaires. 36 blood samples (34% of total) produced the DNA fragment specific for 18S rRNA gene of Babesia sp., by PCR amplification, of which 20 were sheep and 16 were goats. Samples from all seven district contained Babesia positive samples and prevalence varied between 18 to 68%. It was observed that male animals (P = 0.009) and young animals under one year of age (P = 0.01) were more prone to the parasite. It was observed that herds consist of more than 15 animals (P = 0.007), composed of mixed species of small ruminants (P = 0.022), associated with dogs (P = 0.003) and dogs having ticks on their bodies (P = 0.011) were among the major risk factors for the spread of babesiosis in small ruminants.

  19. Wnt/beta-Catenin Signaling and Small Molecule Inhibitors

    Science.gov (United States)

    Voronkov, Andrey; Krauss, Stefan

    2012-01-01

    Wnt/β-catenin signaling is a branch of a functional network that dates back to the first metazoans and it is involved in a broad range of biological systems including stem cells, embryonic development and adult organs. Deregulation of components involved in Wnt/β-catenin signaling has been implicated in a wide spectrum of diseases including a number of cancers and degenerative diseases. The key mediator of Wnt signaling, β-catenin, serves several cellular functions. It functions in a dynamic mode at multiple cellular locations, including the plasma membrane, where β-catenin contributes to the stabilization of intercellular adhesive complexes, the cytoplasm where β-catenin levels are regulated and the nucleus where β-catenin is involved in transcriptional regulation and chromatin interactions. Central effectors of β-catenin levels are a family of cysteine-rich secreted glycoproteins, known as Wnt morphogens. Through the LRP5/6-Frizzled receptor complex, Wnts regulate the location and activity of the destruction complex and consequently intracellular β- catenin levels. However, β-catenin levels and their effects on transcriptional programs are also influenced by multiple other factors including hypoxia, inflammation, hepatocyte growth factor-mediated signaling, and the cell adhesion molecule E-cadherin. The broad implications of Wnt/β-catenin signaling in development, in the adult body and in disease render the pathway a prime target for pharmacological research and development. The intricate regulation of β-catenin at its various locations provides alternative points for therapeutic interventions. PMID:23016862

  20. A novel non-invasive detection method for the FGFR3 gene mutation in maternal plasma for a fetal achondroplasia diagnosis based on signal amplification by hemin-MOFs/PtNPs.

    Science.gov (United States)

    Chen, Jun; Yu, Chao; Zhao, Yilin; Niu, Yazhen; Zhang, Lei; Yu, Yujie; Wu, Jing; He, Junlin

    2017-05-15

    The small amount of cell-free fetal DNA (cffDNA) can be a useful biomarker for early non-invasive prenatal diagnosis (NIPD) of achondroplasia. In this study, a novel non-invasive electrochemical DNA sensor for ultrasensitive detecting FGFR3 mutation gene, a pathogenic gene of achondroplasia, based on biocatalytic signal materials and the biotin-streptavidin system are presented. Notably encapsulation of hemin in metal-organic frameworks-based materials (hemin-MOFs) and platinum nanoparticles (PtNPs) were used to prepare hemin-MOFs/PtNPs composites via a one-beaker-one-step reduction. We utilized hemin-MOFs/PtNPs for signal amplification because the promising hemin-MOFs/PtNPs nanomaterial has remarkable ability of catalyze H 2 O 2 as well as excellent conductivity. To further amplify the electrochemical signal, reduced graphene oxide-tetraethylene pentamine (rGO-TEPA), gold nanoparticles and streptavidin were selected for modification of the electrode to enhance the conductivity and immobilize more biotin-modified capture probe (Bio-CP) through the high specificity and superior affinity between streptavidin and biotin. The electrochemical signal was primarily derived from the synergistic catalysis of H 2 O 2 by hemin and PtNPs and recorded by Chronoamperometry. Under the optimal conditions, this newly designed biosensor exhibited sensitive detection of FGFR3 from 0.1fM to 1nM with a low detection limit of 0.033fM (S/N=3). We proposed that this ultrasensitive biosensor is useful for the early non-invasive prenatal diagnosis of achondroplasia. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Defying c-Abl signaling circuits through small allosteric compounds

    Directory of Open Access Journals (Sweden)

    Stefania eGonfloni

    2014-11-01

    Full Text Available Many extracellular and intracellular signals promote the c-Abl tyrosine kinase activity. c-Abl in turn triggers a multitude of changes either in protein phosphorylation or in gene expression in the cell. Yet, c-Abl takes part in diverse signaling routes because of several domains linked to its catalytic core. Complex conformational changes turn on and off its kinase activity. These changes affect surface features of the c-Abl kinase and likely its capability to bind actin and/or DNA. Two specific inhibitors (ATP-competitive or allosteric compounds regulate the c-Abl kinase through different mechanisms. NMR studies show that a c-Abl fragment (SH3-SH2-linker-SH1 adopts different conformational states upon binding to each inhibitor. This supports an unconventional use for allosteric compounds to unraveling physiological c-Abl signaling circuits.

  2. Small- and large-signal modeling of InP HBTs in transferred-substrate technology

    DEFF Research Database (Denmark)

    Johansen, Tom Keinicke; Rudolph, Matthias; Jensen, Thomas

    2014-01-01

    In this paper, the small- and large-signal modeling of InP heterojunction bipolar transistors (HBTs) in transferred substrate (TS) technology is investigated. The small-signal equivalent circuit parameters for TS-HBTs in two-terminal and three-terminal configurations are determined by employing...

  3. The study of amplification circuit characteristics of photocurrent signal of high-energy industrial CT detection system

    International Nuclear Information System (INIS)

    Wang Jue; Tan Hui; Wang Xin; Chen Jiaoze

    2011-01-01

    According to characteristics of the Photocurrent signal from detection system of high energy industrial CT, sets up the integral amplifier circuit test platform based ACF2101, through the study of this amplifier circuit, a integral capacitor using air as dielectric is proposed in order to get high-gain. After experimental tests, results are good. (authors)

  4. Amplification of R-spondin1 signaling induces granulosa cell fate defects and cancers in mouse adult ovary

    NARCIS (Netherlands)

    De Cian, M-C; Pauper, E.; Bandiera, R.; Vidal, V. P. I.; Sacco, S.; Gregoire, E. P.; Chassot, A-A; Panzolini, C.; WILHELM, D; Pailhoux, E.; Youssef, Sameh A.; de Bruin, A.; Teerds, K.; Schedl, A.; Gillot, I.; Chaboissier, M-C

    2017-01-01

    R-spondin1 is a secreted regulator of WNT signaling, involved in both embryonic development and homeostasis of adult organs. It can have a dual role, acting either as a mitogen or as a tumor suppressor. During ovarian development, Rspo1 is a key factor required for sex determination and

  5. A label-free electrochemical immunosensor based on the novel signal amplification system of AuPdCu ternary nanoparticles functionalized polymer nanospheres.

    Science.gov (United States)

    Yan, Qin; Yang, Yuying; Tan, Zhaoling; Liu, Qing; Liu, Hui; Wang, Ping; Chen, Lei; Zhang, Daopeng; Li, Yueyun; Dong, Yunhui

    2018-04-30

    A sensitive label-free electrochemical immunosensor was designed using a novel signal amplification system for quantitative detecting hepatitis B surface antigen (HBsAg). Nitrogen-doped graphene quantum dots (N-GQDs) supported surfactant-free AuPdCu ternary nanoparticles (AuPdCu/N-GQDs), which featured with good conductivity and excellent catalytic properties for the reduction of hydrogen peroxide (H 2 O 2 ), was synthesized by a simple and benign hydrothermal procedure. At the same time, the electroactive polymer nanospheres (PS) was synthesized by infinite coordination polymers of ferrocenedicarboxylic acid, which could play as carrier and electronic mediator to load AuPdCu/N-GQDs. The PS not only improved the ability to load antibodies because of the good biocompatibility, but also accelerated electron transport of the electrode interface attribute to plentiful ferrocene unit. Thus, the prepared AuPdCu/N-GQDs@PS has abilities of good biocompatibility, catalytic activity and electrical conductivity to be applied as transducing materials to amplify electrochemical signal in detection of HBsAg. Under optimal conditions, the fabricated immunosensor exhibited high sensitivity and stability in the detection of HBsAg. A linear relationship between current signals and the concentrations of HBsAg was obtained in the range from 10fg/mL to 50ng/mL and the detection limit of HBsAg was 3.3fg/mL (signal-to-noise ratio of 3). Moreover, the designed immunosensor with excellent selectivity, reproducibility and stability shows excellent performance in detection of human serum samples. Furthermore, this label-free electrochemical immunosensor has promising application in clinical diagnosis of HBsAg. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Magnetic Particle-Based Immunoassay of Phosphorylated p53 Using Protein-Cage Templated Lead Phosphate and Carbon Nanospheres for Signal Amplification

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Aiqiong; Bao, Yuanwu; Ge, Xiaoxiao; Shin, Yongsoon; Du, Dan; Lin, Yuehe

    2012-11-20

    Phosphorylated p53 at serin 15 (phospho-p53-15) is a potential biomarker of Gamma-radiation exposure. In this paper, we described a new magnetic particles (MPs)-based electrochemical immunoassay of human phospho-p53-15 using carbon nanospheres (CNS) and protein-cage templated lead phosphate nanoparticles for signal amplification. Greatly enhanced sensitivity was achieved by three aspects: 1) The protein-cage nanoparticle (PCN) and p53-15 signal antibody (p53-15 Ab2) are linked to CNS (PCNof each apoferritin; 3) MPs capture a large amount of primary antibodies. Using apoferritin templated metallic phosphate instead of enzyme as label has the advantage of eliminating the addition of mediator or immunoreagents and thus makes the immunoassay system simpler. The subsequent stripping voltammetric analysis of the released lead ions were detected on a disposable screen printed electrode. The response current was proportional to the phospho-p53-15 concentration in the range of 0.02 to 20 ng mL-1 with detection limit of 0.01 ng mL-1. This method shows a good stability, reproducibility and recovery.

  7. Gold nanoparticle labeling with tyramide signal amplification for highly sensitive detection of alpha fetoprotein in human serum by ICP-MS.

    Science.gov (United States)

    Li, Xiaoting; Chen, Beibei; He, Man; Xiao, Guangyang; Hu, Bin

    2018-01-01

    In this work, we developed an immunoassay based on tyramide signal amplification (TSA) and gold nanoparticles (Au NPs) labeling for highly sensitive detection of alpha fetoprotein (AFP) by inductively coupled plasma mass spectrometry (ICP-MS). AFP was captured by anti-AFP1 coating on the 96-well plate and labeled by anti-AFP2-horseradish peroxidase (HRP), in which the HRP can catalyze the deposition of biotinylated tyramine on the nearby protein. Then the streptavidin (SA)-Au NPs was labeled on the deposited biotinylated tyramine as the intensive signal probe for ICP-MS measurement. Under the optimal experimental conditions, the limit of detection of the developed method for AFP was 1.85pg/mL and the linear range was 0.005-2ng/mL. The relative standard deviation for seven replicate detections of 0.01ng/mL AFP was 5.2%. The proposed method was successfully applied to the detection of AFP in human serum with good recoveries. This strategy is highly sensitive and easy to operate, and can be extended to the sensitive detection of other biomolecules in human serum. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Amplification of a bi-phase shift-key modulated signal by a mm-wave FEL

    International Nuclear Information System (INIS)

    Prosnitz, D.; Scharlemann, E.T.; Sheaffer, M.K.

    1991-10-01

    Bi-phase shift keying (BPSK) is a modulation scheme used in communications and radar in which the phase of a transmitted rf signal is switched in a coded pattern between discrete values differing by π radians. The transmitted information rate (in communications) or resolution (in imaging radar) depends on the rate at which the transmitted signal can be modulated. Modulation rates of greater than 1 GHz are generally desired. Although the instantaneous gain bandwidth of a mm-wave FEL amplifier can be much greater than 10 GHz, slippage may limit the BPSK modulation rate that can be amplified. Qualitative slippage arguments would limit the modulation rate to relatively low values; nevertheless, simulations with a time-dependent FEL code (GINGER) indicate that rates of 2 GHz or more are amplified without much loss in modulation integrity. In this paper we describe the effects of slippage in the simulations and discuss the limits of simple arguments

  9. A Carbon Nanotube-based NEMS Parametric Amplifier for Enhanced Radio Wave Detection and Electronic Signal Amplification

    Energy Technology Data Exchange (ETDEWEB)

    Aleman, B J; Sussman, A; Zettl, A [Physics Department, University of California, Berkeley, CA 94720 (United States); Mickelson, W, E-mail: azettl@berkeley.edu [Center of Integrated Nanomechanical Systems, University of California, Berkeley, CA 94720 (United States)

    2011-07-20

    We propose a scheme for a parametric amplifier based on a single suspended carbon nanotube field-emitter. This novel electromechanical nanotube device acts as a phase-sensitive, variable-gain, band-pass-filtering amplifier for electronic signal processing and, at the same time, can operate as a variable-sensitivity, tuneable detector and transducer of radio frequency electromagnetic waves. The amplifier can exhibit infinite gain at pumping voltages much less than 10 Volts. Additionally, the amplifier's low overhead power consumption (10-1000 nW) make it exceptionally attractive for ultra-low-power applications.

  10. A Carbon Nanotube-based NEMS Parametric Amplifier for Enhanced Radio Wave Detection and Electronic Signal Amplification

    International Nuclear Information System (INIS)

    Aleman, B J; Sussman, A; Zettl, A; Mickelson, W

    2011-01-01

    We propose a scheme for a parametric amplifier based on a single suspended carbon nanotube field-emitter. This novel electromechanical nanotube device acts as a phase-sensitive, variable-gain, band-pass-filtering amplifier for electronic signal processing and, at the same time, can operate as a variable-sensitivity, tuneable detector and transducer of radio frequency electromagnetic waves. The amplifier can exhibit infinite gain at pumping voltages much less than 10 Volts. Additionally, the amplifier's low overhead power consumption (10-1000 nW) make it exceptionally attractive for ultra-low-power applications.

  11. Signal amplification and leakage current suppression in amorphous silicon p-i-n diodes by field profile tailoring

    International Nuclear Information System (INIS)

    Hong, W.S.; Zhong, F.; Mireshghi, A.; Perez-Mendez, V.

    1999-01-01

    The performance of amorphous silicon p-i-n diodes as radiation detectors in terms of signal amplitude can be greatly improved when there is a built-in signal gain mechanism. The authors describe an avalanche gain mechanism which is achieved by introducing stacked intrinsic, p-type, and n-type layers into the diode structure. They replaced the intrinsic layer of the conventional p-i-n diode with i 1 -p-i 2 -n-i 3 multilayers. The i 2 layer (typically 1 ∼ 3 microm) achieves an electric field > 10 6 V/cm, while maintaining the p-i interfaces to the metallic contact at electric fields 4 V/cm, when the diode is fully depleted. For use in photo-diode applications the whole structure is less than 10 microm thick. Avalanche gains of 10 ∼ 50 can be obtained when the diode is biased to ∼ 500 V. Also, dividing the electrodes to strips of 2 microm width and 20 microm pitch reduced the leakage current up to an order of magnitude, and increased light transmission without creating inactive regions

  12. Mixed-Signal Architectures for High-Efficiency and Low-Distortion Digital Audio Processing and Power Amplification

    Directory of Open Access Journals (Sweden)

    Pierangelo Terreni

    2010-01-01

    Full Text Available The paper addresses the algorithmic and architectural design of digital input power audio amplifiers. A modelling platform, based on a meet-in-the-middle approach between top-down and bottom-up design strategies, allows a fast but still accurate exploration of the mixed-signal design space. Different amplifier architectures are configured and compared to find optimal trade-offs among different cost-functions: low distortion, high efficiency, low circuit complexity and low sensitivity to parameter changes. A novel amplifier architecture is derived; its prototype implements digital processing IP macrocells (oversampler, interpolating filter, PWM cross-point deriver, noise shaper, multilevel PWM modulator, dead time compensator on a single low-complexity FPGA while off-chip components are used only for the power output stage (LC filter and power MOS bridge; no heatsink is required. The resulting digital input amplifier features a power efficiency higher than 90% and a total harmonic distortion down to 0.13% at power levels of tens of Watts. Discussions towards the full-silicon integration of the mixed-signal amplifier in embedded devices, using BCD technology and targeting power levels of few Watts, are also reported.

  13. FEL small signal dynamics and electron beam prebunching

    International Nuclear Information System (INIS)

    Dattoli, G.

    1993-01-01

    A seed signal and/or a pre-bunched electron beam may provide the start up of a free electron laser (FEL). Recently, interest has grown around FEL's operating with pre-bunched electron beams; this paper is, therefore, devoted to the analysis of the dynamic features of FEL's operating in such a configuration. It exploits a slightly modified form of the FEL high gain equation to derive quantities of practical interest like the dependence of the system growth rate on the bunching coefficients

  14. Acoustic signalling in a small, socially monogamous canid

    DEFF Research Database (Denmark)

    Darden, Safi-Kirstine; Dabelsteen, Torben

    2008-01-01

    Animals that actively defend all or part of their home range for the exclusive use of members of their social group are considered territorial. Defended areas may contain resources such as dens or nests, key foraging sites, or sexual partners that vary in value by season. We investigated territor....... These results suggest that the barking sequence is used in territorial defence and we conclude that at least male swift foxes are territorial in the mating season and they use a long-ranging acoustic signal in territory defence....

  15. Sensing miRNA: Signal Amplification by Cognate RISC for Intracellular Detection of miRNA in Live Cells.

    Science.gov (United States)

    Kavishwar, Amol; Medarova, Zdravka

    2016-01-01

    The ability to detect miRNA expression in live cells would leave these cells available for further manipulation or culture. Here, we describe the design of a miRNA sensor oligonucleotide whose sequence mimics the target mRNA. The sensor has a fluorescent label on one end of the oligo and a quencher on the other. When inside the cell, the sensor is recognized by its cognate miRNA-RISC and gets cleaved, setting the fluorophore free from its quencher. This results in fluorescence "turn on." Since cleavage by the RISC complex is an enzymatic process, the described approach has a very high level of sensitivity (nM). The rate of nonspecific cleavage of the sensor is very slow permitting the collection of meaningful signal over a long period of time.

  16. PCR amplification and sequences of cDNA clones for the small and large subunits of ADP-glucose pyrophosphorylase from barley tissues.

    Science.gov (United States)

    Villand, P; Aalen, R; Olsen, O A; Lüthi, E; Lönneborg, A; Kleczkowski, L A

    1992-06-01

    Several cDNAs encoding the small and large subunit of ADP-glucose pyrophosphorylase (AGP) were isolated from total RNA of the starchy endosperm, roots and leaves of barley by polymerase chain reaction (PCR). Sets of degenerate oligonucleotide primers, based on previously published conserved amino acid sequences of plant AGP, were used for synthesis and amplification of the cDNAs. For either the endosperm, roots and leaves, the restriction analysis of PCR products (ca. 550 nucleotides each) has revealed heterogeneity, suggesting presence of three transcripts for AGP in the endosperm and roots, and up to two AGP transcripts in the leaf tissue. Based on the derived amino acid sequences, two clones from the endosperm, beps and bepl, were identified as coding for the small and large subunit of AGP, respectively, while a leaf transcript (blpl) encoded the putative large subunit of AGP. There was about 50% identity between the endosperm clones, and both of them were about 60% identical to the leaf cDNA. Northern blot analysis has indicated that beps and bepl are expressed in both the endosperm and roots, while blpl is detectable only in leaves. Application of the PCR technique in studies on gene structure and gene expression of plant AGP is discussed.

  17. Effects of HVDC on power systems small signal angle stability

    Energy Technology Data Exchange (ETDEWEB)

    Custodio, D.T.; Paccini, R.O.; Kopcak, I.; Costa, V.F. da [State University of Campinas (UNICAMP), SP (Brazil). School of Electrical and Computer Engineering. Power Systems Dept.], Emails: totti@dsee.fee.unicamp.br, rodrigo@dsee.fee.unicamp.br, kopcak@dsee.fee.unicamp.br, vivaldo@dsee.fee.unicamp.br

    2009-07-01

    In this paper, a didactic method for parameters tuning of the Power Oscillation Damper (POD) coupled to the HVDC constant current controller is proposed utilizing the MATLAB package with a control system toolbox. First, modal analysis is done from the system state matrix to determine the critical mode and oscillation natural frequency. Input and output linearized matrixes are built to single-input and single-output (SISO) control systems. The phase to be compensated between the active power flow in the parallel AC inter-tie and the current reference signal of the HVDC constant current controller is obtained from the Nyquist theorem. Following, the POD time constants are obtained. Finally, the static gain of the POD is tuned based on the root locus method of the classical control theory. Simulations results prove that the DC power modulation is efficient to damp the AC power oscillations. This method is straightforward because only involves matrix operation. (author)

  18. Molecular beacon based biosensor for the sequence-specific detection of DNA using DNA-capped gold nanoparticles-streptavidin conjugates for signal amplification

    International Nuclear Information System (INIS)

    Fang, Xian; Jiang, Wei; Han, Xiaowei; Zhang, Yuzhong

    2013-01-01

    We describe a highly sensitive and selective molecular beacon-based electrochemical impedance biosensor for the sequence-specific detection of DNA. DNA-capped conjugates between gold nanoparticles (Au-NPs) and streptavidin are used for signal amplification. The molecular beacon was labeled with a thiol at its 5′ end and with biotin at its 3′ end, and then immobilized on the surface of a bare gold electrode through the formation of Au-S bonds. Initially, the molecular beacon is present in the “closed” state, and this shields the biotin from being approached by streptavidin due to steric hindrance. In the presence of the target DNA, the target DNA molecules hybridize with the loop and cause a conformational change that moves the biotin away from the surface of the electrode. The biotin thereby becomes accessible for the reporter (the DNA-streptavidin capped Au-NPs), and this results in a distinct increase in electron transfer resistance. Under optimal conditions, the increase in resistance is linearly related to the logarithm of the concentration of complementary target DNA in the range from 1.0 fM to 0.1 μM, with a detection limit of 0.35 fM (at an S/N of 3). This biosensor exhibits good selectivity, and acceptable stability and reproducibility. (author)

  19. Pitfalls using tyramide signal amplification (TSA) in the mouse gastrointestinal tract: endogenous streptavidin-binding sites lead to false positive staining.

    Science.gov (United States)

    Horling, L; Neuhuber, W L; Raab, M

    2012-02-15

    Highly sensitive immunohistochemical detection systems such as tyramide signal amplification (TSA) are widely used, since they allow using two primary antibodies raised in the same species. Most of them are based on the streptavidin-biotin-peroxidase system and include streptavidin-coupled secondary antibodies. Using TSA in cryostat-sectioned tissues of mouse esophagus, we were puzzled by negative controls with unexpected staining mostly in the ganglionic areas. This prompted us to search for the causing agent and to include also other parts of the mouse gastrointestinal tract for comparison. Streptavidin-coupled antibodies bound to endogenous binding sites yet to be characterized, which are present throughout the mouse intestines. Staining was mainly localized around neuronal cell bodies of enteric ganglia. Thus, caution is warranted when applying streptavidin-coupled antibodies in the mouse gastrointestinal tract. The use of endogenous biotin-blocking kits combined with a prolonged post-fixation time could significantly reduce unintentional staining. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Ultrasensitive electrochemical biosensor for detection of DNA from Bacillus subtilis by coupling target-induced strand displacement and nicking endonuclease signal amplification.

    Science.gov (United States)

    Hu, Yuhua; Xu, Xueqin; Liu, Qionghua; Wang, Ling; Lin, Zhenyu; Chen, Guonan

    2014-09-02

    A simple, ultrasensitive, and specific electrochemical biosensor was designed to determine the given DNA sequence of Bacillus subtilis by coupling target-induced strand displacement and nicking endonuclease signal amplification. The target DNA (TD, the DNA sequence from the hypervarient region of 16S rDNA of Bacillus subtilis) could be detected by the differential pulse voltammetry (DPV) in a range from 0.1 fM to 20 fM with the detection limit down to 0.08 fM at the 3s(blank) level. This electrochemical biosensor exhibits high distinction ability to single-base mismatch, double-bases mismatch, and noncomplementary DNA sequence, which may be expected to detect single-base mismatch and single nucleotide polymorphisms (SNPs). Moreover, the applicability of the designed biosensor for detecting the given DNA sequence from Bacillus subtilis was investigated. The result obtained by electrochemical method is approximately consistent with that by a real-time quantitative polymerase chain reaction detecting system (QPCR) with SYBR Green.

  1. A sensitive biosensor using double-layer capillary based immunomagnetic separation and invertase-nanocluster based signal amplification for rapid detection of foodborne pathogen.

    Science.gov (United States)

    Huang, Fengchun; Zhang, Huilin; Wang, Lei; Lai, Weihua; Lin, Jianhan

    2018-02-15

    Combining double-layer capillary based high gradient immunomagnetic separation, invertase-nanocluster based signal amplification and glucose meter based signal detection, a novel biosensor was developed for sensitive and rapid detection of E. coli O157:H7 in this study. The streptavidin modified magnetic nanobeads (MNBs) were conjugated with the biotinylated polyclonal antibodies against E. coli O157:H7 to form the immune MNBs, which were captured by the high gradient magnetic field in the double-layer capillary to specifically separate and efficiently concentrate the target bacteria. Calcium chloride was used with the monoclonal antibodies against E. coli O157:H7 and the invertase to form the immune invertase-nanoclusters (INCs), which were used to react with the target bacteria to form the MNB-bacteria-INC complexes in the capillary. The sucrose was then injected into the capillary and catalyzed by the invertase on the complexes into the glucose, which was detected using the glucose meter to obtain the concentration of the glucose for final determination of the E. coli O157:H7 cells in the sample. A linear relationship between the readout of the glucose meter and the concentration of the E. coli O157:H7 cells (from 10 2 to 10 7 CFU/mL) was found and the lower detection limit of this biosensor was 79 CFU/mL. This biosensor might be extended for the detection of other foodborne pathogens by changing the antibodies and has shown the potential for the detection of foodborne pathogens in a large volume of sample to further increase the sensitivity. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Enhancement of small signal stability of a DFIG-based wind power ...

    African Journals Online (AJOL)

    International Journal of Engineering, Science and Technology ... logic controllers for enhancing the small signal stability of DFIG-based wind integrated power system. ... state space model, eigenvalue analysis, fuzzy logic based tuning circuits ...

  3. Wideband Small-Signal Input dq Admittance Modeling of Six-Pulse Diode Rectifiers

    DEFF Research Database (Denmark)

    Yue, Xiaolong; Wang, Xiongfei; Blaabjerg, Frede

    2018-01-01

    This paper studies the wideband small-signal input dq admittance of six-pulse diode rectifiers. Considering the frequency coupling introduced by ripple frequency harmonics of d-and q-channel switching function, the proposed model successfully predicts the small-signal input dq admittance of six......-pulse diode rectifiers in high frequency regions that existing models fail to explain. Simulation and experimental results verify the accuracy of the proposed model....

  4. Validation of Nonlinear Bipolar Transistor Model by Small-Signal Measurements

    DEFF Research Database (Denmark)

    Vidkjær, Jens; Porra, V.; Zhu, J.

    1992-01-01

    A new method for the validity analysis of nonlinear transistor models is presented based on DC-and small-signal S-parameter measurements and realistic consideration of the measurement and de-embedding errors and singularities of the small-signal equivalent circuit. As an example, some analysis...... results for an extended Gummel Poon model are presented in the case of a UHF bipolar power transistor....

  5. Miniaturized isothermal nucleic acid amplification, a review.

    Science.gov (United States)

    Asiello, Peter J; Baeumner, Antje J

    2011-04-21

    Micro-Total Analysis Systems (µTAS) for use in on-site rapid detection of DNA or RNA are increasingly being developed. Here, amplification of the target sequence is key to increasing sensitivity, enabling single-cell and few-copy nucleic acid detection. The several advantages to miniaturizing amplification reactions and coupling them with sample preparation and detection on the same chip are well known and include fewer manual steps, preventing contamination, and significantly reducing the volume of expensive reagents. To-date, the majority of miniaturized systems for nucleic acid analysis have used the polymerase chain reaction (PCR) for amplification and those systems are covered in previous reviews. This review provides a thorough overview of miniaturized analysis systems using alternatives to PCR, specifically isothermal amplification reactions. With no need for thermal cycling, isothermal microsystems can be designed to be simple and low-energy consuming and therefore may outperform PCR in portable, battery-operated detection systems in the future. The main isothermal methods as miniaturized systems reviewed here include nucleic acid sequence-based amplification (NASBA), loop-mediated isothermal amplification (LAMP), helicase-dependent amplification (HDA), rolling circle amplification (RCA), and strand displacement amplification (SDA). Also, important design criteria for the miniaturized devices are discussed. Finally, the potential of miniaturization of some new isothermal methods such as the exponential amplification reaction (EXPAR), isothermal and chimeric primer-initiated amplification of nucleic acids (ICANs), signal-mediated amplification of RNA technology (SMART) and others is presented.

  6. Prussian blue mediated amplification combined with signal enhancement of ordered mesoporous carbon for ultrasensitive and specific quantification of metolcarb by a three-dimensional molecularly imprinted electrochemical sensor.

    Science.gov (United States)

    Yang, Yukun; Cao, Yaoyu; Wang, Xiaomin; Fang, Guozhen; Wang, Shuo

    2015-02-15

    In this work, we presented a three-dimensional (3D) molecularly imprinted electrochemical sensor (MIECS) with novel strategy for ultrasensitive and specific quantification of metolcarb based on prussian blue (PB) mediated amplification combined with signal enhancement of ordered mesoporous carbon. The molecularly imprinted polymers were synthesized by electrochemically induced redox polymerization of para aminobenzoic acid (p-ABA) in the presence of template metolcarb. Ordered mesoporous carbon material (CMK-3) was introduced to enhance the electrochemical response by improving the structure of the modified electrodes and facilitating charge transfer processes of PB which was used as an inherent electrochemical active probe. The modification process for the working electrodes of the MIECS was characterized by scanning electron microscope (SEM) and cyclic voltammetry (CV), and several important parameters controlling the performance of the MIECS were investigated and optimized in detail. The MIECS with 3D structure had the advantages of ease of preparation, high porous surface structure, speedy response, ultrasensitivity, selectivity, reliable stability, good reproducibility and repeatability. Under the optimal conditions, the MIECS offered an excellent current response for metolcarb in the linear response range of 5.0 × 10(-10)-1.0 × 10(-4) mol L(-1) and the limit of detection (LOD) was calculated to be 9.3 × 10 (-11)mol L(-1) (S/N = 3). The proposed MIECS has been successfully applied for the determination of metolcarb in real samples with satisfactory recoveries. Furthermore, the construction route of this ultrasensitive 3D MIECS may provide a guideline for the determination of non-electroactive analytes in environmental control and food safety. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Amplified amperometric aptasensor for selective detection of protein using catalase-functional DNA-PtNPs dendrimer as a synergetic signal amplification label.

    Science.gov (United States)

    Zhang, Juan; Yuan, Yali; biXie, Shun; Chai, Yaqin; Yuan, Ruo

    2014-10-15

    In this work, we present a new strategy to construct an electrochemical aptasensor for sensitive detection of platelet-derived growth factor BB (PDGF-BB) based on the synergetic amplification of a three-dimensional (3D) nanoscale catalase (CAT) enzyme-functional DNA-platinum nanoparticles (PtNPs) dendrimer through autonomous layer-by-layer assembly. Firstly, polyamidoaminedendrimer (PAMAM) with a hyper-branched and three-dimensional structure was served as nanocarriers to coimmobilize a large number of PDGF-BB binding aptamer (PBA II) and ssDNA 1 (S1) to form PBA II-PAMAM-S1 bioconjugate. In the presence of PDGF-BB, the bioconjugate was self-assembled on the electrode by sandwich assay. Following that, the carried S1 propagated a chain reaction of hybridization events between CAT-PtNPs-S1 and CAT-PtNPs-ssDNA 2 (S2) to form a 3D nanoscale CAT-functional PtNPs-DNA dendrimer, which successfully immobilized substantial CAT enzyme and PtNPs with superior catalysis activity. In this process, the formed negatively charged double-helix DNA could cause the intercalation of hexaammineruthenium(III) chloride (RuHex) into the groove via electrostatic interactions. Thus, numerous RuHex redox probes and CAT were decorated inside/outside of the dendrimer. In the presence of H2O2 in electrolytic cell, the synergistic reaction of CAT and PtNPs towards electrocatalysis could further amplify electrochemical signal. Under optimal condition, the CAT-PtNPs-DNA dendrimer-based sensing system presented a linear dependence between the reduction peak currents and logarithm of PDGF-BB concentrations in the range of 0.00005-35 nM with a relatively low detection limit of 0.02 pM. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Highly sensitive and label-free electrochemical detection of microRNAs based on triple signal amplification of multifunctional gold nanoparticles, enzymes and redox-cycling reaction.

    Science.gov (United States)

    Liu, Lin; Xia, Ning; Liu, Huiping; Kang, Xiaojing; Liu, Xiaoshuan; Xue, Chan; He, Xiaoling

    2014-03-15

    MicroRNAs (miRNAs) are believed to be important for cancer diagnosis and prognosis, serving as reliable molecular biomarkers. In this work, we presented a label-free and highly sensitive electrochemical genosensor for miRNAs detection with the triple signal amplification of gold nanoparticles (AuNPs), alkaline phosphatase (ALP) and p-aminophenol (p-AP) redox cycling. The label-free strategy is based on the difference in the structures of RNA and DNA. Specifically, miRNAs were first captured by the pre-immobilized DNA probes on a gold electrode. Next, the cis-diol group of ribose sugar at the end of the miRNAs chain allowed 3-aminophenylboronic acid (APBA)/biotin-modified multifunctional AuNPs (denoted as APBA-biotin-AuNPs) to be attached through the formation of a boronate ester covalent bond, which facilitated the capture of streptavidin-conjugated alkaline phosphatase (SA-ALP) via the biotin-streptavidin interaction. After the addition of the 4-aminophenylphosphate (p-APP) substrate, the enzymatic conversion from p-APP to p-AP occurred. The resulting p-AP could be cycled by a chemical reducing reagent after its electro-oxidization on the electrode (known as p-AP redox cycling), thus enabling an increase in the anodic current. As a result, the current increased linearly with the miRNAs concentration over a range of 10 fM-5 pM, and a detection limit of 3 fM was achieved. We believe that this work will be valuable for the design of new types of label-free and sensitive electrochemical biosensors. © 2013 Published by Elsevier B.V.

  9. Highly sensitive photoelectrochemical biosensor for kinase activity detection and inhibition based on the surface defect recognition and multiple signal amplification of metal-organic frameworks.

    Science.gov (United States)

    Wang, Zonghua; Yan, Zhiyong; Wang, Feng; Cai, Jibao; Guo, Lei; Su, Jiakun; Liu, Yang

    2017-11-15

    A turn-on photoelectrochemical (PEC) biosensor based on the surface defect recognition and multiple signal amplification of metal-organic frameworks (MOFs) was proposed for highly sensitive protein kinase activity analysis and inhibitor evaluation. In this strategy, based on the phosphorylation reaction in the presence of protein kinase A (PKA), the Zr-based metal-organic frameworks (UiO-66) accommodated with [Ru(bpy) 3 ] 2+ photoactive dyes in the pores were linked to the phosphorylated kemptide modified TiO 2 /ITO electrode through the chelation between the Zr 4+ defects on the surface of UiO-66 and the phosphate groups in kemptide. Under visible light irradiation, the excited electrons from [Ru(bpy) 3 ] 2+ adsorbed in the pores of UiO-66 injected into the TiO 2 conduction band to generate photocurrent, which could be utilized for protein kinase activities detection. The large surface area and high porosities of UiO-66 facilitated a large number of [Ru(bpy) 3 ] 2+ that increased the photocurrent significantly, and afforded a highly sensitive PEC analysis of kinase activity. The detection limit of the as-proposed PEC biosensor was 0.0049UmL -1 (S/N!=!3). The biosensor was also applied for quantitative kinase inhibitor evaluation and PKA activities detection in MCF-7 cell lysates. The developed visible-light PEC biosensor provides a simple detection procedure and a cost-effective manner for PKA activity assays, and shows great potential in clinical diagnosis and drug discoveries. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Small Signal Stability Improvement of Power Systems Using Optimal Load Responses in Competitive Electricity Markets

    DEFF Research Database (Denmark)

    Hu, Weihao; Su, Chi; Chen, Zhe

    2011-01-01

    Since the hourly spot market price is available one day ahead in Denmark, the price could be transferred to the consumers and they may shift some of their loads from high price periods to the low price periods in order to save their energy costs. The optimal load response to an electricity price...... price is proposed. A 17-bus power system with high wind power penetrations, which resembles the Eastern Danish power system, is chosen as the study case. Simulation results show that the optimal load response to electricity prices is an effective measure to improve the small signal stability of power...... for demand side management generates different load profiles and may provide an opportunity to improve the small signal stability of power systems with high wind power penetrations. In this paper, the idea of power system small signal stability improvement by using optimal load response to the electricity...

  11. Small-Signal Dynamic Analysis of LCC-HVDC with STATCOM at the Inverter Busbar

    Science.gov (United States)

    Liu, Dong; Jiang, Wen; Guo, Chunyi; Rehman, Atiq Ur; Zhao, Chengyong

    2018-01-01

    This paper develops a linearized small-signal dynamic model of a Line-Commutated-Converter based HVDC (LCC-HVDC) system with STATCOM at the inverter busbar, and validates its accuracy by comparing time-domain responses from small-signal model and PSCAD-based simulation results. Considering the potential impact of Phase-Locked-Loop (PLL) parameters on the study system and the close connection of STATCOM and LCC inverter station at AC busbar, this paper investigates the impact of PLL gains and AC voltage control parameters of STATCOM on the system small-signal stability. The studies show that (i) the PLL gain has highly impact on the study system and smaller PLL gains are preferable; (ii) larger values of both the proportional gain and the integral gain of AC voltage controller of STATCOM could result in oscillation/instability of the system.

  12. Small Displacement Detection of Biological Signals Using the Cyclic Frequency Method

    Directory of Open Access Journals (Sweden)

    Dan Zhang

    2015-01-01

    Full Text Available A new signal processing method called the Cyclic Frequency method is proposed for small displacement detection of vital signals such as heart rate and respiration using the CW radar method. We have presented experimental results of small displacement detection to confirm the validity of the method. The displacement amplitude 2.5 mm can be detected with a propagation frequency of 24.15 GHz. We may increase the propagation frequency for smaller displacement amplitude or target velocity.

  13. Benchmarking of small-signal dynamics of single-phase PLLs

    DEFF Research Database (Denmark)

    Zhang, Chong; Wang, Xiongfei; Blaabjerg, Frede

    2015-01-01

    Phase-looked Loop (PLL) is a critical component for the control and grid synchronization of grid-connected power converters. This paper presents a benchmarking study on the small-signal dynamics of three commonly used PLLs for single-phase converters, including enhanced PLL, second......-order generalized integrator based PLL, and the inverse-PLL. First, a unified small-signal model of those PLLs is established for comparing their dynamics. Then, a systematic design guideline for parameters tuning of the PLLs is formulated. To confirm the validity of theoretical analysis, nonlinear time...

  14. A novel method, digital genome scanning detects KRAS gene amplification in gastric cancers: involvement of overexpressed wild-type KRAS in downstream signaling and cancer cell growth

    Directory of Open Access Journals (Sweden)

    Yanagihara Kazuyoshi

    2009-06-01

    Full Text Available Abstract Background Gastric cancer is the third most common malignancy affecting the general population worldwide. Aberrant activation of KRAS is a key factor in the development of many types of tumor, however, oncogenic mutations of KRAS are infrequent in gastric cancer. We have developed a novel quantitative method of analysis of DNA copy number, termed digital genome scanning (DGS, which is based on the enumeration of short restriction fragments, and does not involve PCR or hybridization. In the current study, we used DGS to survey copy-number alterations in gastric cancer cells. Methods DGS of gastric cancer cell lines was performed using the sequences of 5000 to 15000 restriction fragments. We screened 20 gastric cancer cell lines and 86 primary gastric tumors for KRAS amplification by quantitative PCR, and investigated KRAS amplification at the DNA, mRNA and protein levels by mutational analysis, real-time PCR, immunoblot analysis, GTP-RAS pull-down assay and immunohistochemical analysis. The effect of KRAS knock-down on the activation of p44/42 MAP kinase and AKT and on cell growth were examined by immunoblot and colorimetric assay, respectively. Results DGS analysis of the HSC45 gastric cancer cell line revealed the amplification of a 500-kb region on chromosome 12p12.1, which contains the KRAS gene locus. Amplification of the KRAS locus was detected in 15% (3/20 of gastric cancer cell lines (8–18-fold amplification and 4.7% (4/86 of primary gastric tumors (8–50-fold amplification. KRAS mutations were identified in two of the three cell lines in which KRAS was amplified, but were not detected in any of the primary tumors. Overexpression of KRAS protein correlated directly with increased KRAS copy number. The level of GTP-bound KRAS was elevated following serum stimulation in cells with amplified wild-type KRAS, but not in cells with amplified mutant KRAS. Knock-down of KRAS in gastric cancer cells that carried amplified wild

  15. A novel method, digital genome scanning detects KRAS gene amplification in gastric cancers: involvement of overexpressed wild-type KRAS in downstream signaling and cancer cell growth

    International Nuclear Information System (INIS)

    Mita, Hiroaki; Yanagihara, Kazuyoshi; Fujita, Masahiro; Hosokawa, Masao; Kusano, Masanobu; Sabau, Sorin Vasile; Tatsumi, Haruyuki; Imai, Kohzoh; Shinomura, Yasuhisa; Tokino, Takashi; Toyota, Minoru; Aoki, Fumio; Akashi, Hirofumi; Maruyama, Reo; Sasaki, Yasushi; Suzuki, Hiromu; Idogawa, Masashi; Kashima, Lisa

    2009-01-01

    Gastric cancer is the third most common malignancy affecting the general population worldwide. Aberrant activation of KRAS is a key factor in the development of many types of tumor, however, oncogenic mutations of KRAS are infrequent in gastric cancer. We have developed a novel quantitative method of analysis of DNA copy number, termed digital genome scanning (DGS), which is based on the enumeration of short restriction fragments, and does not involve PCR or hybridization. In the current study, we used DGS to survey copy-number alterations in gastric cancer cells. DGS of gastric cancer cell lines was performed using the sequences of 5000 to 15000 restriction fragments. We screened 20 gastric cancer cell lines and 86 primary gastric tumors for KRAS amplification by quantitative PCR, and investigated KRAS amplification at the DNA, mRNA and protein levels by mutational analysis, real-time PCR, immunoblot analysis, GTP-RAS pull-down assay and immunohistochemical analysis. The effect of KRAS knock-down on the activation of p44/42 MAP kinase and AKT and on cell growth were examined by immunoblot and colorimetric assay, respectively. DGS analysis of the HSC45 gastric cancer cell line revealed the amplification of a 500-kb region on chromosome 12p12.1, which contains the KRAS gene locus. Amplification of the KRAS locus was detected in 15% (3/20) of gastric cancer cell lines (8–18-fold amplification) and 4.7% (4/86) of primary gastric tumors (8–50-fold amplification). KRAS mutations were identified in two of the three cell lines in which KRAS was amplified, but were not detected in any of the primary tumors. Overexpression of KRAS protein correlated directly with increased KRAS copy number. The level of GTP-bound KRAS was elevated following serum stimulation in cells with amplified wild-type KRAS, but not in cells with amplified mutant KRAS. Knock-down of KRAS in gastric cancer cells that carried amplified wild-type KRAS resulted in the inhibition of cell growth and

  16. Wide Area Prosumption Control and Sensitivities of Aperiodic Small Signal Stability Indicators

    DEFF Research Database (Denmark)

    Wittrock, Martin Lindholm; Jóhannsson, Hjörtur; Nielsen, Arne Hejde

    2014-01-01

    and patterns, stability indicators for aperiodic small signal angular stability (ASSA) are examined, while the concept of prosumption is described. The methodology presented is shown to be able to assess the margin to instability and to predict how this margin can be affected if a load is changed in the grid...

  17. Wide-Area Assessment of Aperiodic Small Signal Rotor Angle Stability in Real-Time

    DEFF Research Database (Denmark)

    Jóhannsson, Hjörtur; Nielsen, Arne Hejde; Østergaard, Jacob

    2014-01-01

    in rotor angle and a loss of synchronism, referred to as aperiodic small signal instability. The paper provides the theoretical background of the method and an analytical assessment criterion. Furthermore, a mathematical mapping of the generators' operating points that enables informative visualization...

  18. Assessment of intrinsic small signal parameters of submicron SiC MESFETs

    Science.gov (United States)

    Riaz, Mohammad; Ahmed, Muhammad Mansoor; Rafique, Umair; Ahmed, Umer Farooq

    2018-01-01

    In this paper, a technique has been developed to estimate intrinsic small signal parameters of submicron SiC MESFETs, designed for high power microwave applications. In the developed technique, small signal parameters are extracted by involving drain-to-source current, Ids instead of Schottky barrier depletion layer expression. It has been demonstrated that in SiC MESFETs, the depletion layer gets modified due to intense transverse electric field and/or self-heating effects, which are conventionally not taken into account. Thus, assessment of AC small signal parameters by employing depletion layer expression loses its accuracy for devices meant for high power applications. A set of expressions for AC small signal elements has been developed using Ids and its dependence on device biasing has been discussed. The validity of the proposed technique has been demonstrated using experimental data. Dr. Ahmed research interests are in Microelectronics, Microwave and RF Engineering and he has supervised numerous MS and PhD research projects. He authored over 100 research papers in the field of microelectronics. Dr. Ahmed is a fellow of the Institution of Engineering and Technology (IET), UK.; a Chartered Engineer (CEng) from the UK Engineering Council and holds the title of European Engineer (Eur Ing) from the European Federation of National Engineering Association (FEANI), Brussels. He is a life member of PEC (Pak); EDS & MTTS (USA).

  19. Security region-based small signal stability analysis of power systems with FSIG based wind farm

    Science.gov (United States)

    Qin, Chao; Zeng, Yuan; Yang, Yang; Cui, Xiaodan; Xu, Xialing; Li, Yong

    2018-02-01

    Based on the Security Region approach, the impact of fixed-speed induction generator based wind farm on the small signal stability of power systems is analyzed. Firstly, the key factors of wind farm on the small signal stability of power systems are analyzed and the parameter space for small signal stability region is formed. Secondly, the small signal stability region of power systems with wind power is established. Thirdly, the corresponding relation between the boundary of SSSR and the dominant oscillation mode is further studied. Results show that the integration of fixed-speed induction generator based wind farm will cause the low frequency oscillation stability of the power system deteriorate. When the output of wind power is high, the oscillation stability of the power system is mainly concerned with the inter-area oscillation mode caused by the integration of the wind farm. Both the active power output and the capacity of reactive power compensation of the wind farm have a significant influence on the SSSR. To improve the oscillation stability of power systems with wind power, it is suggested to reasonably set the reactive power compensation capacity for the wind farm through SSSR.

  20. Background Noises Versus Intraseasonal Variation Signals: Small vs. Large Convective Cloud Objects From CERES Aqua Observations

    Science.gov (United States)

    Xu, Kuan-Man

    2015-01-01

    During inactive phases of Madden-Julian Oscillation (MJO), there are plenty of deep but small convective systems and far fewer deep and large ones. During active phases of MJO, a manifestation of an increase in the occurrence of large and deep cloud clusters results from an amplification of large-scale motions by stronger convective heating. This study is designed to quantitatively examine the roles of small and large cloud clusters during the MJO life cycle. We analyze the cloud object data from Aqua CERES (Clouds and the Earth's Radiant Energy System) observations between July 2006 and June 2010 for tropical deep convective (DC) and cirrostratus (CS) cloud object types according to the real-time multivariate MJO index, which assigns the tropics to one of the eight MJO phases each day. The cloud object is a contiguous region of the earth with a single dominant cloud-system type. The criteria for defining these cloud types are overcast footprints and cloud top pressures less than 400 hPa, but DC has higher cloud optical depths (=10) than those of CS (background noises resulting from various types of the tropical waves with different wavenumbers and propagation speeds/directions.

  1. Visualization of mcr mRNA in a methanogen by fluorescence in situ hybridization with an oligonucleotide probe and two-pass tyramide signal amplification (two-pass TSA-FISH).

    Science.gov (United States)

    Kubota, Kengo; Ohashi, Akiyoshi; Imachi, Hiroyuki; Harada, Hideki

    2006-09-01

    Two-pass tyramide signal amplification-fluorescence in situ hybridization (two-pass TSA-FISH) with a horseradish peroxidase (HRP)-labeled oligonucleotide probe was applied to detect prokaryotic mRNA. In this study, mRNA of a key enzyme for methanogenesis, methyl coenzyme M reductase (mcr), in Methanococcus vannielii was targeted. Applicability of mRNA-targeted probes to in situ hybridization was verified by Clone-FISH. It was observed that sensitivity of two-pass TSA-FISH was significantly higher than that of TSA-FISH, which was further increased by the addition of dextran sulphate in TSA working solution. Signals from two-pass TSA-FISH were more reliable compared to the weak, spotty signals yielded by TSA-FISH.

  2. Discovery of novel small molecule activators of β-catenin signaling.

    Directory of Open Access Journals (Sweden)

    Folkert Verkaar

    Full Text Available Wnt/β-catenin signaling plays a major role in embryonic development and adult stem cell maintenance. Reduced activation of the Wnt/β-catenin pathway underlies neurodegenerative disorders and aberrations in bone formation. Screening of a small molecule compound library with a β-galactosidase fragment complementation assay measuring β-catenin nuclear entry revealed bona fide activators of β-catenin signaling. The compounds stabilized cytoplasmic β-catenin and activated β-catenin-dependent reporter gene activity. Although the mechanism through which the compounds activate β-catenin signaling has yet to be determined, several key regulators of Wnt/β-catenin signaling, including glycogen synthase kinase 3 and Frizzled receptors, were excluded as the molecular target. The compounds displayed remarkable selectivity, as they only induced β-catenin signaling in a human osteosarcoma U2OS cell line and not in a variety of other cell lines examined. Our data indicate that differences in cellular Wnt/β-catenin signaling machinery can be exploited to identify cell type-specific activators of Wnt/β-catenin signaling.

  3. Small-signal analysis in high-energy physics: A Bayesian approach

    International Nuclear Information System (INIS)

    Prosper, H.B.

    1988-01-01

    The statistics of small signals masked by a background of imprecisely known magnitude is addressed from a Bayesian viewpoint using a simple statistical model which may be derived from the principle of maximum entropy. The issue of the correct assignment of prior probabilities is resolved by invoking an invariance principle proposed by Jaynes. We calculate the posterior probability and use it to calculate point estimates and upper limits for the magnitude of the signal. The results are applicable to high-energy physics experiments searching for new phenomena. We illustrate this by reanalyzing some published data from a few experiments

  4. A transfer function approach to the small-signal response of saturated semiconductor optical amplifiers

    DEFF Research Database (Denmark)

    Nielsen, Mads Lønstrup; Blumenthal, D. J.; Mørk, Jesper

    2000-01-01

    A theoretical analysis of the small-signal frequency response (SSFR) of a wavelength converter based on cross-gain modulation in a semiconductor optical amplifier with a finite waveguide loss is presented. We use a transfer function formalism to explain the resonant behavior of the frequency...... response. The limitations to the magnitude of the spectral overshoot are also accounted for. Operating with the data and CW signals in a co-propagating configuration, we End that the resonance only exists for a finite waveguide loss. In a counter-propagating scheme, a resonance can exist regardless...

  5. Small Molecules Affect Human Dental Pulp Stem Cell Properties Via Multiple Signaling Pathways

    Science.gov (United States)

    Al-Habib, Mey; Yu, Zongdong

    2013-01-01

    One fundamental issue regarding stem cells for regenerative medicine is the maintenance of stem cell stemness. The purpose of the study was to test whether small molecules can enhance stem cell properties of mesenchymal stem cells (MSCs) derived from human dental pulp (hDPSCs), which have potential for multiple clinical applications. We identified the effects of small molecules (Pluripotin (SC1), 6-bromoindirubin-3-oxime and rapamycin) on the maintenance of hDPSC properties in vitro and the mechanisms involved in exerting the effects. Primary cultures of hDPSCs were exposed to optimal concentrations of these small molecules. Treated hDPSCs were analyzed for their proliferation, the expression levels of pluripotent and MSC markers, differentiation capacities, and intracellular signaling activations. We found that small molecule treatments decreased cell proliferation and increased the expression of STRO-1, NANOG, OCT4, and SOX2, while diminishing cell differentiation into odonto/osteogenic, adipogenic, and neurogenic lineages in vitro. These effects involved Ras-GAP-, ERK1/2-, and mTOR-signaling pathways, which may preserve the cell self-renewal capacity, while suppressing differentiation. We conclude that small molecules appear to enhance the immature state of hDPSCs in culture, which may be used as a strategy for adult stem cell maintenance and extend their capacity for regenerative applications. PMID:23573877

  6. Parametric amplifications in the nonlinear transmission line

    Energy Technology Data Exchange (ETDEWEB)

    Kawata, T; Sakai, J; Inoue, H [Toyama Univ., Takaoka (Japan). Faculty of Engineering

    1980-03-01

    The parametric amplification in a transmission line with nonlinear capacitors is analysed theoretically using the equations of three wave interactions. Since this line has two modes, high frequency and low frequency modes, there may occur some mode coupling phenomena through the resonant interactions. We consider three waves with wave number k sub(j) and frequency ..omega..sub(j) in resonance with each other, that is, ..omega../sub 1/ + ..omega../sub 2/ = ..omega../sub 3/ and k/sub 1/ + k/sub 2/ = k/sub 3/, where 0 <= ..omega../sub 1/ <= ..omega../sub 2/ <= ..omega../sub 3/ and k/sub 3/ >= 0. Such conditions are realized in our network and there exist two states: ''forward state'' (each group velocity is positive) and ''backward state'' (one of the group velocities is negative). The coupled equations of three waves has two constant pumps: high frequency (HF) pump and low frequency (LF) pump. Using linear approximations, we examine the possible types of parametric amplification and obtain the power gains depending on the frequency deviation. For only the case of HF pump we get the gain between signals with seme frequency and also get the gain from the low frequency signal to the high frequency signal (''up-conversion'') for the LF pump. The nonlinear analysis gives the exact relation between input and output signals. For the forward state the gain is absolutely suppressed by the ratio of pumping power to input power, while the gain of backward state has no finite maximum and there may appear an ''oscillating state'' if the pumping power is comparatively small.

  7. A method for release and multiple strand amplification of small quantities of DNA from endospores of the fastidious bacterium Pasteuria penetrans.

    Science.gov (United States)

    Mauchline, T H; Mohan, S; Davies, K G; Schaff, J E; Opperman, C H; Kerry, B R; Hirsch, P R

    2010-05-01

    To establish a reliable protocol to extract DNA from Pasteuria penetrans endospores for use as template in multiple strand amplification, thus providing sufficient material for genetic analyses. To develop a highly sensitive PCR-based diagnostic tool for P. penetrans. An optimized method to decontaminate endospores, release and purify DNA enabled multiple strand amplification. DNA purity was assessed by cloning and sequencing gyrB and 16S rRNA gene fragments obtained from PCR using generic primers. Samples indicated to be 100%P. penetrans by the gyrB assay were estimated at 46% using the 16S rRNA gene. No bias was detected on cloning and sequencing 12 housekeeping and sporulation gene fragments from amplified DNA. The detection limit by PCR with Pasteuria-specific 16S rRNA gene primers following multiple strand amplification of DNA extracted using the method was a single endospore. Generation of large quantities DNA will facilitate genomic sequencing of P. penetrans. Apparent differences in sample purity are explained by variations in 16S rRNA gene copy number in Eubacteria leading to exaggerated estimations of sample contamination. Detection of single endospores will facilitate investigations of P. penetrans molecular ecology. These methods will advance studies on P. penetrans and facilitate research on other obligate and fastidious micro-organisms where it is currently impractical to obtain DNA in sufficient quantity and quality.

  8. Extreme Temperature Performance of Automotive-Grade Small Signal Bipolar Junction Transistors

    Science.gov (United States)

    Boomer, Kristen; Damron, Benny; Gray, Josh; Hammoud, Ahmad

    2018-01-01

    Electronics designed for space exploration missions must display efficient and reliable operation under extreme temperature conditions. For example, lunar outposts, Mars rovers and landers, James Webb Space Telescope, Europa orbiter, and deep space probes represent examples of missions where extreme temperatures and thermal cycling are encountered. Switching transistors, small signal as well as power level devices, are widely used in electronic controllers, data instrumentation, and power management and distribution systems. Little is known, however, about their performance in extreme temperature environments beyond their specified operating range; in particular under cryogenic conditions. This report summarizes preliminary results obtained on the evaluation of commercial-off-the-shelf (COTS) automotive-grade NPN small signal transistors over a wide temperature range and thermal cycling. The investigations were carried out to establish a baseline on functionality of these transistors and to determine suitability for use outside their recommended temperature limits.

  9. Small-Signal Modeling and Analysis of Grid-Connected Inverter with Power Differential Droop Control

    Directory of Open Access Journals (Sweden)

    Xin Chen

    2016-01-01

    Full Text Available The conventional voltage and frequency droop control strategy in grid-connected inverter suffers a major setback in the presence of disturbance by producing oscillations. Adding a power differential term in droop controller is an effective way to address such drawback. In this paper, grid-connected inverter’s small-signal models of the conventional droop control and the power differential droop control are established. The eigenvalues of the models are then determined by system matrix. The eigenvalues analysis is presented which helps in identifying the relationship between the system stability and controller parameters. It is concluded that the damping ratio of dominant low-frequency eigenvalues increased and the oscillation caused by the disturbance is suppressed when a power differential term is added to the droop control method. The MATLAB/Simulink models of grid-connected inverter with both control strategies are also established to validate the results of small-signal analysis.

  10. Small-Signal Stability of Wind Power System With Full-Load Converter Interfaced Wind Turbines

    DEFF Research Database (Denmark)

    Knüppel, Thyge; Nielsen, Jørgen Nygaard; Jensen, Kim Høj

    2012-01-01

    Small-signal stability analysis of power system oscillations is a well established field within power system analysis, but not much attention has yet been paid to systems with a high penetration of wind turbines and with large wind power plants (WPP). In this paper a comprehensive analysis...... is presented which assesses the impact of full-load converter interfaced wind turbines on power system small-signal stability. The study is based on a 7 generator network with lightly damped inter-area modes. A detailed wind turbine (WT) model with all grid relevant control functions is used in the study....... The WT is, furthermore, equipped with a park level WPP voltage controller and comparisons are presented. The WT model for this work is a validated dynamic model of the 3.6 MW Siemens Wind Power WT. The study is based on modal analysis which is complemented with time domain simulations on the nonlinear...

  11. Small-Signal Stability Analysis of Full-Load Converter Interfaced Wind Turbines

    DEFF Research Database (Denmark)

    Knüppel, Thyge; Akhmatov, Vladislav; Nielsen, Jørgen Nygård

    2009-01-01

    focus since the share of wind power increases substituting power generation from conventional power plants. Here, a study based on modal analysis is presented which investigate the effect of large scale integration of full-load converter interfaced wind turbines on inter-area oscillations in a three...... generator network. A detailed aggregated wind turbine model is employed which includes all necessary control functions. It is shown that the wind urbines have very low participation in the inter-area power oscillation.......Power system stability investigations of wind farms often cover the tasks of low-voltage-fault-ride-through, voltage and reactive power control, and power balancing, but not much attention has yet been paid to the task of small-signal stability. Small-signal stability analysis needs increasing...

  12. Towards a time-domain modeling framework for small-signal analysis of unbalanced microgrids

    OpenAIRE

    Ojo, Y; Schiffer, JF

    2017-01-01

    Small-signal analysis is one of the most frequently used techniques to assess the operating conditions of power systems. Typically, this analysis is conducted by employing a phasor-based model of the power network derived under the assumption of balanced operating conditions. However, distribution networks and, amongst these, microgrids are often unbalanced. Hence, their analysis requires the development of tools and methods valid under such conditions. Motivated by this, we propose a modelin...

  13. A summary of impacts of wind power integration on power system small-signal stability

    Science.gov (United States)

    Yan, Lei; Wang, Kewen

    2017-05-01

    Wind power has been increasingly integrated into power systems over the last few decades because of the global energy crisis and the pressure on environmental protection, and the stability of the system connected with wind power is becoming more prominent. This paper summaries the research status, achievements as well as deficiencies of the research on the impact of wind power integration on power system small-signal stability. In the end, the further research needed are discussed.

  14. Signal formation processes in Micromegas detectors and quality control for large size detector construction for the ATLAS new small wheel

    Energy Technology Data Exchange (ETDEWEB)

    Kuger, Fabian

    2017-07-31

    The Micromegas technology is one of the most successful modern gaseous detector concepts and widely utilized in nuclear and particle physics experiments. Twenty years of R and D rendered the technology sufficiently mature to be selected as precision tracking detector for the New Small Wheel (NSW) upgrade of the ATLAS Muon spectrometer. This will be the first large scale application of Micromegas in one of the major LHC experiments. However, many of the fundamental microscopic processes in these gaseous detectors are still not fully understood and studies on several detector aspects, like the micromesh geometry, have never been addressed systematically. The studies on signal formation in Micromegas, presented in the first part of this thesis, focuses on the microscopic signal electron loss mechanisms and the amplification processes in electron gas interaction. Based on a detailed model of detector parameter dependencies, these processes are scrutinized in an iterating comparison between experimental results, theory prediction of the macroscopic observables and process simulation on the microscopic level. Utilizing the specialized detectors developed in the scope of this thesis as well as refined simulation algorithms, an unprecedented level of accuracy in the description of the microscopic processes is reached, deepening the understanding of the fundamental process in gaseous detectors. The second part is dedicated to the challenges arising with the large scale Micromegas production for the ATLAS NSW. A selection of technological choices, partially influenced or determined by the herein presented studies, are discussed alongside a final report on two production related tasks addressing the detectors' core components: For the industrial production of resistive anode PCBs a detailed quality control (QC) and quality assurance (QA) scheme as well as the therefore required testing tools have been developed. In parallel the study on micromesh parameter optimization

  15. Signal formation processes in Micromegas detectors and quality control for large size detector construction for the ATLAS new small wheel

    International Nuclear Information System (INIS)

    Kuger, Fabian

    2017-01-01

    The Micromegas technology is one of the most successful modern gaseous detector concepts and widely utilized in nuclear and particle physics experiments. Twenty years of R and D rendered the technology sufficiently mature to be selected as precision tracking detector for the New Small Wheel (NSW) upgrade of the ATLAS Muon spectrometer. This will be the first large scale application of Micromegas in one of the major LHC experiments. However, many of the fundamental microscopic processes in these gaseous detectors are still not fully understood and studies on several detector aspects, like the micromesh geometry, have never been addressed systematically. The studies on signal formation in Micromegas, presented in the first part of this thesis, focuses on the microscopic signal electron loss mechanisms and the amplification processes in electron gas interaction. Based on a detailed model of detector parameter dependencies, these processes are scrutinized in an iterating comparison between experimental results, theory prediction of the macroscopic observables and process simulation on the microscopic level. Utilizing the specialized detectors developed in the scope of this thesis as well as refined simulation algorithms, an unprecedented level of accuracy in the description of the microscopic processes is reached, deepening the understanding of the fundamental process in gaseous detectors. The second part is dedicated to the challenges arising with the large scale Micromegas production for the ATLAS NSW. A selection of technological choices, partially influenced or determined by the herein presented studies, are discussed alongside a final report on two production related tasks addressing the detectors' core components: For the industrial production of resistive anode PCBs a detailed quality control (QC) and quality assurance (QA) scheme as well as the therefore required testing tools have been developed. In parallel the study on micromesh parameter optimization

  16. Small Molecules Inspired by the Natural Product Withanolides as Potent Inhibitors of Wnt Signaling.

    Science.gov (United States)

    Sheremet, Michael; Kapoor, Shobhna; Schröder, Peter; Kumar, Kamal; Ziegler, Slava; Waldmann, Herbert

    2017-09-19

    Wnt signaling is a fundamental pathway that drives embryonic development and is essential for stem cell maintenance and tissue homeostasis. Dysregulation of Wnt signaling is linked to various diseases, and a constitutively active Wnt pathway drives tumorigenesis. Thus, disruption of the Wnt response is deemed a promising strategy for cancer drug discovery. However, only few clinical drug candidates that target Wnt signaling are available so far, and new small-molecule modulators of Wnt-related processes are in high demand. Here we describe the synthesis of small molecules inspired by withanolide natural products by using a pregnenolone-derived β-lactone as the key intermediate that was transformed into a δ-lactone appended to the D-ring of the steroidal scaffold. This natural-product-inspired compound library contained potent inhibitors of Wnt signaling that act upstream of the destruction complex to stabilize Axin in a tankyrase-independent manner. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. The sandwich-type electrochemiluminescence immunosensor for {alpha}-fetoprotein based on enrichment by Fe{sub 3}O{sub 4}-Au magnetic nano probes and signal amplification by CdS-Au composite nanoparticles labeled anti-AFP

    Energy Technology Data Exchange (ETDEWEB)

    Zhou Hankun [State Key Laboratory Base of Novel Functional Materials and Preparation Science, Faculty of Material Science and Chemical Engineering of Ningbo University, Ningbo 315211 (China); Gan Ning, E-mail: ganning@nbu.edu.cn [State Key Laboratory Base of Novel Functional Materials and Preparation Science, Faculty of Material Science and Chemical Engineering of Ningbo University, Ningbo 315211 (China); Li Tianhua; Cao Yuting; Zeng Saolin [State Key Laboratory Base of Novel Functional Materials and Preparation Science, Faculty of Material Science and Chemical Engineering of Ningbo University, Ningbo 315211 (China); Zheng Lei, E-mail: nfyyzl@163.com [Department of Laboratory Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515 (China); Guo Zhiyong [State Key Laboratory Base of Novel Functional Materials and Preparation Science, Faculty of Material Science and Chemical Engineering of Ningbo University, Ningbo 315211 (China)

    2012-10-09

    Highlights: Black-Right-Pointing-Pointer Sandwich immunoreaction, testing a large number of samples simultaneously. Black-Right-Pointing-Pointer The magnetic separation and enrichment by Fe{sub 3}O{sub 4}-Au magnetic nano probes. Black-Right-Pointing-Pointer The amplification of detection signal by CdS-Au composite nanoparticles labeled anti-AFP. Black-Right-Pointing-Pointer Almost no background signal, which greatly improve the sensitivity of detection. - Abstract: A novel and sensitive sandwich-type electrochemiluminescence (ECL) immunosensor was fabricated on a glassy carbon electrode (GCE) for ultra trace levels of {alpha}-fetoprotein (AFP) based on sandwich immunoreaction strategy by enrichment using magnetic capture probes and quantum dots coated with Au shell (CdS-Au) as the signal tag. The capture probe was prepared by immobilizing the primary antibody of AFP (Ab1) on the core/shell Fe{sub 3}O{sub 4}-Au nanoparticles, which was first employed to capture AFP antigens to form Fe{sub 3}O{sub 4}-Au/Ab1/AFP complex from the serum after incubation. The product can be separated from the background solution through the magnetic separation. Then the CdS-Au labeled secondary antibody (Ab2) as signal tag (CdS-Au/Ab2) was conjugated successfully with Fe{sub 3}O{sub 4}-Au/Ab1/AFP complex to form a sandwich-type immunocomplex (Fe{sub 3}O{sub 4}-Au/Ab1/AFP/Ab2/CdS-Au), which can be further separated by an external magnetic field and produce ECL signals at a fixed voltage. The signal was proportional to a certain concentration range of AFP for quantification. Thus, an easy-to-use immunosensor with magnetic probes and a quantum dots signal tag was obtained. The immunosensor performed at a level of high sensitivity and a broad concentration range for AFP between 0.0005 and 5.0 ng mL{sup -1} with a detection limit of 0.2 pg mL{sup -1}. The use of magnetic probes was combined with pre-concentration and separation for trace levels of tumor markers in the serum. Due to the

  18. Krüppel-like factor 4 promotes c-Met amplification-mediated gefitinib resistance in non-small-cell lung cancer.

    Science.gov (United States)

    Feng, Wei; Xie, Qianyi; Liu, Suo; Ji, Ying; Li, Chunyun; Wang, Chunle; Jin, Longyu

    2018-06-01

    Gefitinib has been widely used in the first-line treatment of advanced EGFR-mutated non-small-cell lung cancer (NSCLC). However, many NSCLC patients will acquire resistance to gefitinib after 9-14 months of treatment. This study revealed that Krüppel-like factor 4 (KLF4) contributes to the formation of gefitinib resistance in c-Met-overexpressing NSCLC cells. We observed that KLF4 was overexpressed in c-Met-overexpressing NSCLC cells and tissues. Knockdown of KLF4 increased tumorigenic properties in gefitinib-resistant NSCLC cell lines without c-Met overexpression, but it reduced tumorigenic properties and increased gefitinib sensitivity in gefitinib-resistant NSCLC cells with c-Met overexpression, whereas overexpression of KLF4 reduced gefitinib sensitivity in gefitinib-sensitive NSCLC cells. Furthermore, Western blot analysis revealed that KLF4 contributed to the formation of gefitinib resistance in c-Met-overexpressing NSCLC cells by inhibiting the expression of apoptosis-related proteins under gefitinib treatment and activating the c-Met/Akt signaling pathway by decreasing the inhibition of β-catenin on phosphorylation of c-Met to prevent blockade by gefitinib. In summary, this study's results suggest that KLF4 is a promising candidate molecular target for both prevention and therapy of NSCLC with c-Met overexpression. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  19. Development of Optical Molecular Imaging System for the Acquisition of Bioluminescence Signals from Small Animals

    International Nuclear Information System (INIS)

    Lee, Byeong Il; Kim, Hyeon Sik; Jeong, Hye Jin; Lee, Hyung Jae; Moon, Seung Min; Kwon, Seung Young; Jeong, Shin Young; Bom, Hee Seung; Min, Jung Joon; Choi, Eun Seo

    2009-01-01

    Optical imaging is providing great advance and improvement in genetic and molecular imaging of animals and humans. Optical imaging system consists of optical imaging devices, which carry out major function for monitoring, tracing, and imaging in most of molecular in-vivo researches. In bio-luminescent imaging, small animals containing luciferase gene locally irradiate light, and emitted photons transmitted through skin of the small animals are imaged by using a high sensitive charged coupled device (CCD) camera. In this paper, we introduced optical imaging system for the image acquisition of bio-luminescent signals emitted from small animals. In the system, Nikon lens and four LED light sources were mounted at the inside of a dark box. A cooled CCD camera equipped with a control module was used. We tested the performance of the optical imaging system using effendorf tube and light emitting bacteria which injected intravenously into CT26 tumor bearing nude mouse. The performance of implemented optical imaging system for bio-luminescence imaging was demonstrated and the feasibility of the system in small animal imaging application was proved. We anticipate this system could be a useful tool for the molecular imaging of small animals adaptable for various experimental conditions in future

  20. Extraction of the respiratory signal from small-animal CT projections for a retrospective gating method

    International Nuclear Information System (INIS)

    ChavarrIas, C; Vaquero, J J; Sisniega, A; RodrIguez-Ruano, A; Soto-Montenegro, M L; GarcIa-Barreno, P; Desco, M

    2008-01-01

    We propose a retrospective respiratory gating algorithm to generate dynamic CT studies. To this end, we compared three different methods of extracting the respiratory signal from the projections of small-animal cone-beam computed tomography (CBCT) scanners. Given a set of frames acquired from a certain axial angle, subtraction of their average image from each individual frame produces a set of difference images. Pixels in these images have positive or negative values (according to the respiratory phase) in those areas where there is lung movement. The respiratory signals were extracted by analysing the shape of the histogram of these difference images: we calculated the first four central and non-central moments. However, only odd-order moments produced the desired breathing signal, as the even-order moments lacked information about the phase. Each of these curves was compared to a reference signal recorded by means of a pneumatic pillow. Given the similar correlation coefficients yielded by all of them, we selected the mean to implement our retrospective protocol. Respiratory phase bins were separated, reconstructed independently and included in a dynamic sequence, suitable for cine playback. We validated our method in five adult rat studies by comparing profiles drawn across the diaphragm dome, with and without retrospective respiratory gating. Results showed a sharper transition in the gated reconstruction, with an average slope improvement of 60.7%

  1. Extraction of the respiratory signal from small-animal CT projections for a retrospective gating method

    Energy Technology Data Exchange (ETDEWEB)

    ChavarrIas, C; Vaquero, J J; Sisniega, A; RodrIguez-Ruano, A; Soto-Montenegro, M L; GarcIa-Barreno, P; Desco, M [Unidad de Medicina y CirugIa Experimental, Hospital General Universitario Gregorio Maranon, Anexo PsiquiatrIa, 1 Planta. C/Ibiza, 43. Madrid 28007 (Spain)

    2008-09-07

    We propose a retrospective respiratory gating algorithm to generate dynamic CT studies. To this end, we compared three different methods of extracting the respiratory signal from the projections of small-animal cone-beam computed tomography (CBCT) scanners. Given a set of frames acquired from a certain axial angle, subtraction of their average image from each individual frame produces a set of difference images. Pixels in these images have positive or negative values (according to the respiratory phase) in those areas where there is lung movement. The respiratory signals were extracted by analysing the shape of the histogram of these difference images: we calculated the first four central and non-central moments. However, only odd-order moments produced the desired breathing signal, as the even-order moments lacked information about the phase. Each of these curves was compared to a reference signal recorded by means of a pneumatic pillow. Given the similar correlation coefficients yielded by all of them, we selected the mean to implement our retrospective protocol. Respiratory phase bins were separated, reconstructed independently and included in a dynamic sequence, suitable for cine playback. We validated our method in five adult rat studies by comparing profiles drawn across the diaphragm dome, with and without retrospective respiratory gating. Results showed a sharper transition in the gated reconstruction, with an average slope improvement of 60.7%.

  2. Comparison Study of Power System Small Signal Stability Improvement Using SSSC and STATCOM

    DEFF Research Database (Denmark)

    Hu, Weihao; Su, Chi; Fang, Jiakun

    2013-01-01

    the connected power system, both SSSC and STATCOM are able to participate in the power system inter-area oscillation damping by changing the compensated reactance or the provided reactive power. This paper analyses the influence of SSSC and STATCOM on power system small signal stability. The damping controller...... schemes for SSSC and STATCOM are presented and discussed. The IEEE 39-bus New England system model as the test system is built in DIgSIELNT PowerFactory, in which the damping control strategies for both SSSC and STATCOM are validated by time domain simulations and modal analysis. Furthermore, comparison......A static synchronous series compensator (SSSC) has the ability to emulate a reactance in series with the connected transmission line. A static synchronous compensator (STATCOM) is able to provide the reactive power to an electricity network. When fed with some supplementary signals from...

  3. RFID Technology for Continuous Monitoring of Physiological Signals in Small Animals.

    Science.gov (United States)

    Volk, Tobias; Gorbey, Stefan; Bhattacharyya, Mayukh; Gruenwald, Waldemar; Lemmer, Björn; Reindl, Leonhard M; Stieglitz, Thomas; Jansen, Dirk

    2015-02-01

    Telemetry systems enable researchers to continuously monitor physiological signals in unrestrained, freely moving small rodents. Drawbacks of common systems are limited operation time, the need to house the animals separately, and the necessity of a stable communication link. Furthermore, the costs of the typically proprietary telemetry systems reduce the acceptance. The aim of this paper is to introduce a low-cost telemetry system based on common radio frequency identification technology optimized for battery-independent operational time, good reusability, and flexibility. The presented implant is equipped with sensors to measure electrocardiogram, arterial blood pressure, and body temperature. The biological signals are transmitted as digital data streams. The device is able of monitoring several freely moving animals housed in groups with a single reader station. The modular concept of the system significantly reduces the costs to monitor multiple physiological functions and refining procedures in preclinical research.

  4. Small-Signal Analysis of the Microgrid Secondary Control Considering a Communication Time Delay

    DEFF Research Database (Denmark)

    Coelho, Ernane Antônio Alves; Wu, Dan; Guerrero, Josep M.

    2016-01-01

    This paper presents a small-signal analysis of an islanded microgrid composed of two or more voltage-source inverters connected in parallel. The primary control of each inverter is integrated through an internal current and voltage loops using proportional resonant compensators, a virtual impedance......, and an external power controller based on frequency and voltage droops. The frequency restoration function is implemented at the secondary control level, which executes a consensus algorithm that consists of a load-frequency control and a single time delay communication network. The consensus network consists...... the behavior of the system considering control parameters and time delay variation....

  5. Observation of small sub-pulses out of the delayed-interference signal-wavelength converter

    DEFF Research Database (Denmark)

    Sakaguchi, J.; Nielsen, Mads Lønstrup; Ohira, T.

    2005-01-01

    The generation of small sub-pulses in the delayed-interference signal-wavelength converter (DISC), which has been studied for use in future 160-Gb/s optical time division multiplexing-wavelength division multiplexing (OTDM-WDM) communication systems, was recently predicted as a potential problem....... In this work, we have experimentally verified the generation of such pulses and its mechanism. In the experiments we used 3.8-ps-long 1.56-mu m input pulses with repetition frequencies from 12.5 to 25.0 GHz and a cross-correlation monitoring system with a time resolution of approximately 2 ps....

  6. Using reservoir-engineering to convert a coherent signal in optomechanics with small optomechanical cooperativity

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Tao, E-mail: suiyueqiaoqiao@163.com [Key Lab of Coherent Light, Atomic and Molecular Spectroscopy, Ministry of Education, and College of Physics, Jilin University, Changchun 130012 (China); College of Physics, Tonghua Normal University, Tonghua 134000 (China); Wang, Tie [Department of Physics, College of Science, Yanbian University, Yanji, Jilin 133002 (China); Fu, Changbao [College of Physics, Tonghua Normal University, Tonghua 134000 (China); Su, Xuemei, E-mail: suxm@jlu.edu.cn [Key Lab of Coherent Light, Atomic and Molecular Spectroscopy, Ministry of Education, and College of Physics, Jilin University, Changchun 130012 (China)

    2017-05-10

    Optomechanical dark mode plays a central role in effective mechanically-mediated conversion of two different cavity fields. In this paper, we present a more efficient method to utilize the dark mode to transfer a coherent signal. When an auxiliary cavity mode is exploited, two approaches are proposed to effectively eliminate the optomechanical bright mode, and only the optomechanical dark mode is left to facilitate state transfer. Even with small cooperativity and different losses for the two target modes, the internal cavity mode-conversion efficiency can also reach unity. - Highlights: • Reservoir-engineering is used for state conversion. • The optomechanical bright mode can be absolutely eliminated. • Small cooperativity and different losses are feasible for ideal conversion efficiency.

  7. From human monocytes to genome-wide binding sites--a protocol for small amounts of blood: monocyte isolation/ChIP-protocol/library amplification/genome wide computational data analysis.

    Directory of Open Access Journals (Sweden)

    Sebastian Weiterer

    Full Text Available Chromatin immunoprecipitation in combination with a genome-wide analysis via high-throughput sequencing is the state of the art method to gain genome-wide representation of histone modification or transcription factor binding profiles. However, chromatin immunoprecipitation analysis in the context of human experimental samples is limited, especially in the case of blood cells. The typically extremely low yields of precipitated DNA are usually not compatible with library amplification for next generation sequencing. We developed a highly reproducible protocol to present a guideline from the first step of isolating monocytes from a blood sample to analyse the distribution of histone modifications in a genome-wide manner.The protocol describes the whole work flow from isolating monocytes from human blood samples followed by a high-sensitivity and small-scale chromatin immunoprecipitation assay with guidance for generating libraries compatible with next generation sequencing from small amounts of immunoprecipitated DNA.

  8. Amplification of pico-scale DNA mediated by bacterial carrier DNA for small-cell-number transcription factor ChIP-seq

    DEFF Research Database (Denmark)

    Jakobsen, Janus S; Bagger, Frederik O; Hasemann, Marie S

    2015-01-01

    BACKGROUND: Chromatin-Immunoprecipitation coupled with deep sequencing (ChIP-seq) is used to map transcription factor occupancy and generate epigenetic profiles genome-wide. The requirement of nano-scale ChIP DNA for generation of sequencing libraries has impeded ChIP-seq on in vivo tissues of low...... transcription factor (CEBPA) and histone mark (H3K4me3) ChIP. We further demonstrate that genomic profiles are highly resilient to changes in carrier DNA to ChIP DNA ratios. CONCLUSIONS: This represents a significant advance compared to existing technologies, which involve either complex steps of pre...... cell numbers. RESULTS: We describe a robust, simple and scalable methodology for ChIP-seq of low-abundant cell populations, verified down to 10,000 cells. By employing non-mammalian genome mapping bacterial carrier DNA during amplification, we reliably amplify down to 50 pg of ChIP DNA from...

  9. Gut microbial colonization orchestrates TLR2 expression, signaling and epithelial proliferation in the small intestinal mucosa.

    Directory of Open Access Journals (Sweden)

    Nives Hörmann

    Full Text Available The gut microbiota is an environmental factor that determines renewal of the intestinal epithelium and remodeling of the intestinal mucosa. At present, it is not resolved if components of the gut microbiota can augment innate immune sensing in the intestinal epithelium via the up-regulation of Toll-like receptors (TLRs. Here, we report that colonization of germ-free (GF Swiss Webster mice with a complex gut microbiota augments expression of TLR2. The microbiota-dependent up-regulation of components of the TLR2 signaling complex could be reversed by a 7 day broad-spectrum antibiotic treatment. TLR2 downstream signaling via the mitogen-activated protein kinase (ERK1/2 and protein-kinase B (AKT induced by bacterial TLR2 agonists resulted in increased proliferation of the small intestinal epithelial cell line MODE-K. Mice that were colonized from birth with a normal gut microbiota (conventionally-raised; CONV-R showed signs of increased small intestinal renewal and apoptosis compared with GF controls as indicated by elevated mRNA levels of the proliferation markers Ki67 and Cyclin D1, elevated transcripts of the apoptosis marker Caspase-3 and increased numbers of TUNEL-positive cells per intestinal villus structure. In accordance, TLR2-deficient mice showed reduced proliferation and reduced apoptosis. Our findings suggest that a tuned proliferation response of epithelial cells following microbial colonization could aid to protect the host from its microbial colonizers and increase intestinal surface area.

  10. Gray bootstrap method for estimating frequency-varying random vibration signals with small samples

    Directory of Open Access Journals (Sweden)

    Wang Yanqing

    2014-04-01

    Full Text Available During environment testing, the estimation of random vibration signals (RVS is an important technique for the airborne platform safety and reliability. However, the available methods including extreme value envelope method (EVEM, statistical tolerances method (STM and improved statistical tolerance method (ISTM require large samples and typical probability distribution. Moreover, the frequency-varying characteristic of RVS is usually not taken into account. Gray bootstrap method (GBM is proposed to solve the problem of estimating frequency-varying RVS with small samples. Firstly, the estimated indexes are obtained including the estimated interval, the estimated uncertainty, the estimated value, the estimated error and estimated reliability. In addition, GBM is applied to estimating the single flight testing of certain aircraft. At last, in order to evaluate the estimated performance, GBM is compared with bootstrap method (BM and gray method (GM in testing analysis. The result shows that GBM has superiority for estimating dynamic signals with small samples and estimated reliability is proved to be 100% at the given confidence level.

  11. The sandwich-type electrochemiluminescence immunosensor for α-fetoprotein based on enrichment by Fe3O4-Au magnetic nano probes and signal amplification by CdS-Au composite nanoparticles labeled anti-AFP.

    Science.gov (United States)

    Zhou, Hankun; Gan, Ning; Li, Tianhua; Cao, Yuting; Zeng, Saolin; Zheng, Lei; Guo, Zhiyong

    2012-10-09

    A novel and sensitive sandwich-type electrochemiluminescence (ECL) immunosensor was fabricated on a glassy carbon electrode (GCE) for ultra trace levels of α-fetoprotein (AFP) based on sandwich immunoreaction strategy by enrichment using magnetic capture probes and quantum dots coated with Au shell (CdS-Au) as the signal tag. The capture probe was prepared by immobilizing the primary antibody of AFP (Ab1) on the core/shell Fe(3)O(4)-Au nanoparticles, which was first employed to capture AFP antigens to form Fe(3)O(4)-Au/Ab1/AFP complex from the serum after incubation. The product can be separated from the background solution through the magnetic separation. Then the CdS-Au labeled secondary antibody (Ab2) as signal tag (CdS-Au/Ab2) was conjugated successfully with Fe(3)O(4)-Au/Ab1/AFP complex to form a sandwich-type immunocomplex (Fe(3)O(4)-Au/Ab1/AFP/Ab2/CdS-Au), which can be further separated by an external magnetic field and produce ECL signals at a fixed voltage. The signal was proportional to a certain concentration range of AFP for quantification. Thus, an easy-to-use immunosensor with magnetic probes and a quantum dots signal tag was obtained. The immunosensor performed at a level of high sensitivity and a broad concentration range for AFP between 0.0005 and 5.0 ng mL(-1) with a detection limit of 0.2 pg mL(-1). The use of magnetic probes was combined with pre-concentration and separation for trace levels of tumor markers in the serum. Due to the amplification of the signal tag, the immunosensor is highly sensitive, which can offer great promise for rapid, simple, selective and cost-effective detection of effective biomonitoring for clinical application. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Ultrasonic Detection of Small Crack in Studs[Bolts] by Time Difference of Thread Signals(TDTS)

    International Nuclear Information System (INIS)

    Suh, D. M.; Park, D. Y.; Kim, C. K.

    1990-01-01

    It is difficult to detect such flaws as stress - corrosion cracking or corrosion wastage(loss of bolt diameter) in the threads. In many cases the critical size of a flaw is very small(1-2 mm order). This paper describes how it is possible to discriminate small flaw indications in threads using the time difference or thread signals(TDTS) by a signal-conditioning technique

  13. Small Molecule Modulator of p53 Signaling Pathway: Application for Radiosensitizing or Radioprotection Agents

    International Nuclear Information System (INIS)

    Oh, Sang Taek; Cho, Mun Ju; Gwak, Jung Sug; Ryu, Min Jung; Song, Jie Young; Yun, Yeon Sook

    2009-01-01

    The tumor suppressor p53 is key molecule to protect the cell against genotoxic stress and..the most frequently mutated..protein..in cancer cells. Lack of functional p53..is accompanied by high rate of genomic instability, rapid tumor progression, resistance to anticancer therapy, and increased angiogenesis. In response to DNA damage, p53 protein rapidly accumulated through attenuated proteolysis and is also activated as transcription factor. Activated p53 up-regulates target genes involved in cell cycle arrest and/or apoptosis and then lead to suppression of malignant transformation and the maintenance of genomic integrity. Chemical genetics is a new technology to uncover the signaling networks that regulated biological phenotype using exogenous reagents such as small molecules. Analogous to classical forward genetic screens in model organism, this approach makes use of high throughput, phenotypic assay to identify small molecules that disrupt gene product function in a way that alters a phenotype of interest. Recently, interesting small molecules were identified from cell based high throughput screening and its target protein or mechanism of action were identified by various methods including affinity chromatography, protein array profiling, mRNA or phage display, transcription profiling, and RNA interference

  14. Small Molecule Modulator of p53 Signaling Pathway: Application for Radiosensitizing or Radioprotection Agents

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Sang Taek; Cho, Mun Ju; Gwak, Jung Sug; Ryu, Min Jung [PharmacoGenomics Research Center, Inje University, Busan (Korea, Republic of); Song, Jie Young; Yun, Yeon Sook [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2009-05-15

    The tumor suppressor p53 is key molecule to protect the cell against genotoxic stress and..the most frequently mutated..protein..in cancer cells. Lack of functional p53..is accompanied by high rate of genomic instability, rapid tumor progression, resistance to anticancer therapy, and increased angiogenesis. In response to DNA damage, p53 protein rapidly accumulated through attenuated proteolysis and is also activated as transcription factor. Activated p53 up-regulates target genes involved in cell cycle arrest and/or apoptosis and then lead to suppression of malignant transformation and the maintenance of genomic integrity. Chemical genetics is a new technology to uncover the signaling networks that regulated biological phenotype using exogenous reagents such as small molecules. Analogous to classical forward genetic screens in model organism, this approach makes use of high throughput, phenotypic assay to identify small molecules that disrupt gene product function in a way that alters a phenotype of interest. Recently, interesting small molecules were identified from cell based high throughput screening and its target protein or mechanism of action were identified by various methods including affinity chromatography, protein array profiling, mRNA or phage display, transcription profiling, and RNA interference.

  15. Maturation and integration of adult born hippocampal neurons: signal convergence onto small Rho GTPases

    Directory of Open Access Journals (Sweden)

    Krishna eVadodaria

    2013-08-01

    Full Text Available Adult neurogenesis, restricted to specific regions in the mammalian brain, represents one of the most interesting forms of plasticity in the mature nervous system. Adult-born hippocampal neurons play important roles in certain forms of learning and memory, and altered hippocampal neurogenesis has been associated with a number of neuropsychiatric diseases such as major depression and epilepsy. Newborn neurons go through distinct developmental steps from a dividing neurogenic precursor to a synaptically integrated mature neuron. Previous studies have uncovered several molecular signaling pathways involved in distinct steps of this maturational process. In this context, the small Rho GTPases, Cdc42, Rac1 and RhoA have recently been shown to regulate the morphological and synaptic maturation of adult-born dentate granule cells in vivo. Distinct upstream regulators, including several growth factors that modulate maturation and integration of newborn neurons have been shown to also recruit the small Rho GTPases. Here we review recent findings and highlight the possibility that small Rho GTPases may act as central assimilators, downstream of critical input onto adult-born hippocampal neurons contributing to their maturation and integration into the existing dentate gyrus circuitry.

  16. Research on a Small Signal Stability Region Boundary Model of the Interconnected Power System with Large-Scale Wind Power

    Directory of Open Access Journals (Sweden)

    Wenying Liu

    2015-03-01

    Full Text Available For the interconnected power system with large-scale wind power, the problem of the small signal stability has become the bottleneck of restricting the sending-out of wind power as well as the security and stability of the whole power system. Around this issue, this paper establishes a small signal stability region boundary model of the interconnected power system with large-scale wind power based on catastrophe theory, providing a new method for analyzing the small signal stability. Firstly, we analyzed the typical characteristics and the mathematic model of the interconnected power system with wind power and pointed out that conventional methods can’t directly identify the topological properties of small signal stability region boundaries. For this problem, adopting catastrophe theory, we established a small signal stability region boundary model of the interconnected power system with large-scale wind power in two-dimensional power injection space and extended it to multiple dimensions to obtain the boundary model in multidimensional power injection space. Thirdly, we analyzed qualitatively the topological property’s changes of the small signal stability region boundary caused by large-scale wind power integration. Finally, we built simulation models by DIgSILENT/PowerFactory software and the final simulation results verified the correctness and effectiveness of the proposed model.

  17. Amplification biases: possible differences among deviating gene expressions

    Directory of Open Access Journals (Sweden)

    Piumi Francois

    2008-01-01

    Full Text Available Abstract Background Gene expression profiling has become a tool of choice to study pathological or developmental questions but in most cases the material is scarce and requires sample amplification. Two main procedures have been used: in vitro transcription (IVT and polymerase chain reaction (PCR, the former known as linear and the latter as exponential. Previous reports identified enzymatic pitfalls in PCR and IVT protocols; however the possible differences between the sequences affected by these amplification defaults were only rarely explored. Results Screening a bovine cDNA array dedicated to embryonic stages with embryonic (n = 3 and somatic tissues (n = 2, we proceeded to moderate amplifications starting from 1 μg of total RNA (global PCR or IVT one round. Whatever the tissue, 16% of the probes were involved in deviating gene expressions due to amplification defaults. These distortions were likely due to the molecular features of the affected sequences (position within a gene, GC content, hairpin number but also to the relative abundance of these transcripts within the tissues. These deviating genes mainly encoded housekeeping genes from physiological or cellular processes (70% and constituted 2 subsets which did not overlap (molecular features, signal intensities, gene ID. However, the differential expressions identified between embryonic stages were both reliable (minor intersect with biased expressions and relevant (biologically validated. In addition, the relative expression levels of those genes were biologically similar between amplified and unamplified samples. Conclusion Conversely to the most recent reports which challenged the use of intense amplification procedures on minute amounts of RNA, we chose moderate PCR and IVT amplifications for our gene profiling study. Conclusively, it appeared that systematic biases arose even with moderate amplification procedures, independently of (i the sample used: brain, ovary or embryos, (ii

  18. Demonstration of soft x-ray amplification by optical-field-induced ionization

    International Nuclear Information System (INIS)

    Midorikawa, Katsumi; Nagata, Yutaka; Kubodera, Shoichi; Obara, Minoru; Tashiro, Hideo; Toyoda, Koichi

    1995-01-01

    We have demonstrated the amplification of the 13.5-nm Lyman-α transition in hydrogen-like Li + ions, using a novel optical-field-induced ionization. A small-signal gain coefficient of 20 cm -1 was obtained. The use of preformed Li + plasma as an initial laser medium plays important roles for the production of suitable plasma conditions for an optical-field-induced ionization x-ray laser. (author)

  19. Performance scaling via passive pulse shaping in cavity-enhanced optical parametric chirped-pulse amplification.

    Science.gov (United States)

    Siddiqui, Aleem M; Moses, Jeffrey; Hong, Kyung-Han; Lai, Chien-Jen; Kärtner, Franz X

    2010-06-15

    We show that an enhancement cavity seeded at the full repetition rate of the pump laser can automatically reshape small-signal gain across the interacting pulses in an optical parametric chirped-pulse amplifier for close-to-optimal operation, significantly increasing both the gain bandwidth and the conversion efficiency, in addition to boosting gain for high-repetition-rate amplification. Applied to a degenerate amplifier, the technique can provide an octave-spanning gain bandwidth.

  20. Amplification of the angiogenic signal through the activation of the TSC/mTOR/HIF axis by the KSHV vGPCR in Kaposi's sarcoma.

    Directory of Open Access Journals (Sweden)

    Bruno C Jham

    2011-04-01

    Full Text Available Kaposi's sarcoma (KS is a vascular neoplasm characterized by the dysregulated expression of angiogenic and inflammatory cytokines. The driving force of the KS lesion, the KSHV-infected spindle cell, secretes elevated levels of vascular endothelial growth factor (VEGF, essential for KS development. However, the origin of VEGF in this tumor remains unclear.Here we report that the KSHV G protein-coupled receptor (vGPCR upregulates VEGF in KS through an intricate paracrine mechanism. The cytokines secreted by the few vGPCR-expressing tumor cells activate in neighboring cells multiple pathways (including AKT, ERK, p38 and IKKβ that, in turn, converge on TSC1/2, promoting mTOR activation, HIF upregulation, and VEGF secretion. Conditioned media from vGPCR-expressing cells lead to an mTOR-dependent increase in HIF-1α and HIF-2α protein levels and VEGF upregulation. In a mouse allograft model for KS, specific inhibition of the paracrine activation of mTOR in non-vGPCR-expressing cells was sufficient to inhibit HIF upregulation in these cells, and abolished the ability of the vGPCR-expressing cells to promote tumor formation in vivo. Similarly, pharmacologic inhibition of HIF in this model blocked VEGF secretion and also lead to tumor regression.Our findings provide a compelling explanation for how the few tumor cells expressing vGPCR can contribute to the dramatic amplification of VEGF secretion in KS, and further provide a molecular mechanism for how cytokine dysregulation in KS fuels angiogenesis and tumor development. These data further suggest that activation of HIF by vGPCR may be a vulnerable target for the treatment of patients with KS.

  1. Real-time remedial action against aperiodic small signal rotor angle instability

    DEFF Research Database (Denmark)

    Weckesser, Johannes Tilman Gabriel; Jóhannsson, Hjörtur; Østergaard, Jacob

    2016-01-01

    This paper presents a method that in real-time determines remedial actions, which restore stable operation with respect to aperiodic small signal rotor angle stability (ASSRAS) when insecure or unstable operation has been detected. An ASSRAS assessment method is used to monitor the stability...... impedance plane to determine an active power redispatch among selected generators to restore stable and secure operation. Since the method is purely based on analytically derived expression, the computation of the remedial actions is fast and well suited for real-time operation. The method was tested...... boundary for each generator in real-time. The ASSRAS boundary represents the condition when a generator reaches the maximum steady state active power injection. The proposed control method exploits analytically derived expressions for the ASSRAS boundary and other characteristic curves in the injection...

  2. Wide-Area Assessment of Aperiodic Small Signal Rotor Angle Stability in Real-Time

    DEFF Research Database (Denmark)

    Jóhannsson, Hjörtur; Nielsen, Arne Hejde; Østergaard, Jacob

    2013-01-01

    This paper presents the details of a new real-time stability assessment method. The method assesses a particular mechanism of stability: each generator’s capability to generate sufficient steady state electromechanical torque. The lack of sufficient steady state torque causes aperiodic increase...... of multiple operating points is derived in the paper. Finally, results from time-domain simulation of instability scenarios in the Nordic32 test system are presented and results used for testing the assessment method. The results illustrate the method’s capability to efficiently identify the location...... in rotor angle and a loss of synchronism, referred to as aperiodic small signal instability. The paper provides the theoretical background of the method and an analytical assessment criterion. Furthermore, a mathematical mapping of the generators’ operating points that enables informative visualization...

  3. Influence of Wind Plant Ancillary Voltage Control on System Small Signal Stability

    DEFF Research Database (Denmark)

    Su, Chi; Chen, Zhe

    2012-01-01

    As a common tendency, large-scale wind farms are increasingly connected to the transmission system of modern power grids. This introduces some new challenges to the connected power systems, and the transmission system operators (TSOs) have to put some new requirements as part of the grid codes...... on the integration of wind farms. One common requirement to wind farms is the function of system voltage control which can be implemented in the grid-side convertor controller of a variable speed wind turbine. This ancillary voltage control provided by wind farms could have some influence on the system small signal...... stability. This paper implements an ancillary voltage control strategy on a direct-drive-full-convertor-based wind farm and studies its influence on the damping ratio values of the dominant oscillation mode within the connected power system. All the calculations and simulations are conducted in DIg...

  4. Nitrogen modulation of legume root architecture signaling pathways involves phytohormones and small regulatory molecules.

    Science.gov (United States)

    Mohd-Radzman, Nadiatul A; Djordjevic, Michael A; Imin, Nijat

    2013-10-01

    Nitrogen, particularly nitrate is an important yield determinant for crops. However, current agricultural practice with excessive fertilizer usage has detrimental effects on the environment. Therefore, legumes have been suggested as a sustainable alternative for replenishing soil nitrogen. Legumes can uniquely form nitrogen-fixing nodules through symbiotic interaction with specialized soil bacteria. Legumes possess a highly plastic root system which modulates its architecture according to the nitrogen availability in the soil. Understanding how legumes regulate root development in response to nitrogen availability is an important step to improving root architecture. The nitrogen-mediated root development pathway starts with sensing soil nitrogen level followed by subsequent signal transduction pathways involving phytohormones, microRNAs and regulatory peptides that collectively modulate the growth and shape of the root system. This review focuses on the current understanding of nitrogen-mediated legume root architecture including local and systemic regulations by different N-sources and the modulations by phytohormones and small regulatory molecules.

  5. FEL small signal gain reduction due to phase error of undulator

    International Nuclear Information System (INIS)

    Jia Qika

    2002-01-01

    The effects of undulator phase errors on the Free Electron Laser small signal gain is analyzed and discussed. The gain reduction factor due to the phase error is given analytically for low-gain regimes, it shows that degradation of the gain is similar to that of the spontaneous radiation, has a simple exponential relation with square of the rms phase error, and the linear variation part of phase error induces the position shift of maximum gain. The result also shows that the Madey's theorem still hold in the presence of phase error. The gain reduction factor due to the phase error for high-gain regimes also can be given in a simple way

  6. Analysis of the nuclear localization signal of TRF1 in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    HU JIAN

    2009-01-01

    Full Text Available Several studies revealed a similar down-regulation of telomeric repeat binding factor 1 (TRF1 in tumors. We have previously reported the TRFl expression levels were down-regulation in non-small cell lung cancer (NSCLC. The regulation of TRFl localization is proposed to be important for the function and expression. The nuclear localization signal (NLS and nuclear export signal (NES are often important clues to localization of protein. The objective of the present study was to investigate the NLS and NES of TRFl in NSCLC patients. Thirty (30 patients with NSCLCs had undergone radical operations in The First Affiliated Hospital, College of Medicine, Zhejiang University. DNA sequences of NLSs and NESs were amplified by PCR. The PCR products were analyzed by DNA sequencing. There were four NLSs of the TRFl protein, including two monopartite and two bipartite NLSs. The NLSs sequences were included in 337KKERRVGTPQSTKKKKESRR356. The exon 8 and exon 9 of TRFl DNA were covered the NLS sequences. The sequences of predicted NESs were 11WMLDFLCLSL86 and 174NLLKLQALAV183, respectively. The exon 1, exon 3 and exon 4 of TRFl were covered the NES sequences. In NSCLCs, there was no a mutation, deletion, or substitution in NLS and NES of TRFl. We conclude that the NLS and NES sequences in NSCLCs patients did not have mutations. Down-expression of TRFl does not indicate gene mutation of NLS and NES in NSCLCs.

  7. "Smart" gold nanoparticles for photoacoustic imaging: an imaging contrast agent responsive to the cancer microenvironment and signal amplification via pH-induced aggregation.

    Science.gov (United States)

    Song, Jaejung; Kim, Jeesu; Hwang, Sekyu; Jeon, Mansik; Jeong, Sanghwa; Kim, Chulhong; Kim, Sungjee

    2016-07-07

    'Smart' gold nanoparticles can respond to mild acidic environments, rapidly form aggregates, and shift the absorption to red and near-infrared. They were used as a photoacoustic imaging agent responsive to the cancer microenvironment, and have demonstrated the cancer-specific accumulation at the cellular level and an amplified signal which is twice higher than the control in vivo.

  8. Recycling domains in plant cell morphogenesis: small GTPase effectors, plasma membrane signalling and the exocyst.

    Science.gov (United States)

    Zárský, Viktor; Potocký, Martin

    2010-04-01

    The Rho/Rop small GTPase regulatory module is central for initiating exocytotically ACDs (active cortical domains) in plant cell cortex, and a growing array of Rop regulators and effectors are being discovered in plants. Structural membrane phospholipids are important constituents of cells as well as signals, and phospholipid-modifying enzymes are well known effectors of small GTPases. We have shown that PLDs (phospholipases D) and their product, PA (phosphatidic acid), belong to the regulators of the secretory pathway in plants. We have also shown that specific NOXs (NADPH oxidases) producing ROS (reactive oxygen species) are involved in cell growth as exemplified by pollen tubes and root hairs. Most plant cells exhibit several distinct plasma membrane domains (ACDs), established and maintained by endocytosis/exocytosis-driven membrane protein recycling. We proposed recently the concept of a 'recycling domain' (RD), uniting the ACD and the connected endosomal recycling compartment (endosome), as a dynamic spatiotemporal entity. We have described a putative GTPase-effector complex exocyst involved in exocytic vesicle tethering in plants. Owing to the multiplicity of its Exo70 subunits, this complex, along with many RabA GTPases (putative recycling endosome organizers), may belong to core regulators of RD organization in plants.

  9. Aptamer-based electrochemical assay of 17β-estradiol using a glassy carbon electrode modified with copper sulfide nanosheets and gold nanoparticles, and applying enzyme-based signal amplification

    International Nuclear Information System (INIS)

    Huang, Ke-Jing; Liu, Yu-Jie; Zhang, Ji-Zong

    2015-01-01

    We have developed an electrochemical method for the determination of 17β-estradiol. A glassy carbon electrode was modified with a composite made from copper sulfide nanosheets, gold nanoparticles, and glucose oxidase. The copper sulfide nanosheet was prepared by a single-step hydrothermal process, and its properties were characterized by X-ray powder diffraction, X-ray photoelectron spectroscopy, scanning electron microscopy and transmission electron microscopy. Finally, an estradiol-specific aptamer was assembled on the electrode. The copper sulfide nanosheet on the electrode surface acts as a relatively good electrical conductor. Glucose oxidase acts as an indicator, and the dual modification of glucose oxidase and gold nanoparticles for signal amplification. The determination of 17β-estradiol was performed by differential pulse voltammetry of glucose oxidase because the signal measured at typically −0.43 V depends on the concentration of 17β-estradiol because addition of 17β-estradiol at electrode hinders electron transfer. A linear relationship exists between the peak current and the logarithm of concentration of 17β-estradiol in the 0.5 pM to 5 nM range, with a 60 f. detection limit (at 3σ/S). The method displays good selectivity over bisphenol A, 1-aminoanthraquinone and naphthalene even if present in 100-fold concentrations. (author)

  10. Electrochemical immunoassay for the carcinoembryonic antigen based on the use of a glassy carbon electrode modified with an octahedral Cu2O-gold nanocomposite and staphylococcal protein for signal amplification.

    Science.gov (United States)

    Qin, Zhen; Xu, Wei; Chen, Shuai; Chen, Jun; Qiu, Jing Fu; Li, Chao Rui

    2018-04-24

    The authors describe an electrochemical immunoassay for ultrasensitive direct determination of the carcinoembryonic antigen (CEA). A nanocomposite consisting of octahedral Cu2O nanocrystals covered with gold nanoparticles was utilized to modify a glassy carbon electrode which gives a strongly enhanced chronoamperometric signal for H 2 O 2 which is used as an electrochemical probe. The morphology and elemental composition of the the nanocomposite was studied by field emission scanning electron microscopy and energy dispersive X-ray spectroscopy. In addition, staphylococcal protein A was placed on the electrode for efficient capture of antibody to further enhance the sensitivity of the assay. Under optimal conditions and at a typical working voltage of -0.4 V (vs. Ag/AgCl), the response covers the 2 pg·mL -1 to 20 ng·mL -1 CEA concentration range with a 200 fg·mL -1 lower detection limit. The method was successfully applied to the determination of CEA in (spiked) human serum. Graphical abstract Schematic of the fabrication of an electrochemical immunosensor for ultrasensitive detection the carcinoembryonic antigen. The sensor is based on the use of a glassy carbon electrode modified with an octahedral Cu 2 O-gold nanocomposite and staphylococcal protein A for signal amplification.

  11. Privacy amplification for quantum key distribution

    International Nuclear Information System (INIS)

    Watanabe, Yodai

    2007-01-01

    This paper examines classical privacy amplification using a universal family of hash functions. In quantum key distribution, the adversary's measurement can wait until the choice of hash functions is announced, and so the adversary's information may depend on the choice. Therefore the existing result on classical privacy amplification, which assumes the independence of the choice from the other random variables, is not applicable to this case. This paper provides a security proof of privacy amplification which is valid even when the adversary's information may depend on the choice of hash functions. The compression rate of the proposed privacy amplification can be taken to be the same as that of the existing one with an exponentially small loss in secrecy of a final key. (fast track communication)

  12. Electrochemical gene sensor for Mycoplasma pneumoniae DNA using dual signal amplification via a Pt-Pd nanowire and horse radish peroxidase

    International Nuclear Information System (INIS)

    Liu, Linlin; Xiang, Guiming; Jiang, Dongneng; Du, Chunlan; Liu, Chang; Huang, Weiwei; Pu, Xiaoyun

    2016-01-01

    A dually amplified DNA biosensor was constructed for the determination of the DNA of Mycoplasma pneumoniae (M. pneu). A gold electrode was modified with 3,4,9,10-perylenetetracarboxylic acid dianhydride (PTCDA; a π-stacking perylene semiconductor dye with outstanding electronic and optical properties), a layer of gold nanoparticles (nano-Au), and capture DNA. Pt-Pd nanowires served as carriers for the co immobilization of complementary probe (CP2) and the mediator thionine (Thi). Horseradish peroxidase (HRP) acted as a blocking reagent and signal enhancer. Following base pairing, the modified Pt-Pd nanowires were captured on the surface of the gold electrode. After addition of H 2 O 2 , the Pt-Pd nanowires and HRP both catalyzed the reduction of H 2 O 2 and promoted the electron transfer via the mediator Thi, resulting in an amplified electrochemical signal. The electrical signal, best measured at a working voltage of −200 mV (vs a SCE), is logarithmically related to the concentration of the M. pneu DNA in the 0.1 pM to 20 nM concentration range, and the detection limit (at an S/N ratio of 3) is 0.03 pM. The assay is robust, sensitive and specific. Conceivably, it is a cost-effective alternative to the established PCR method for the detection of M. pneu in clinical samples. (author)

  13. GH signaling in human adipose and muscle tissue during 'feast and famine': amplification of exercise stimulation following fasting compared to glucose administration.

    Science.gov (United States)

    Vendelbo, Mikkel H; Christensen, Britt; Grønbæk, Solbritt B; Høgild, Morten; Madsen, Michael; Pedersen, Steen B; Jørgensen, Jens O L; Jessen, Niels; Møller, Niels

    2015-09-01

    Fasting and exercise stimulates, whereas glucose suppresses GH secretion, but it is uncertain how these conditions impact GH signaling in peripheral tissues. To test the original 'feast and famine hypothesis' by Rabinowitz and Zierler, according to which the metabolic effects of GH are predominant during fasting, we specifically hypothesized that fasting and exercise act in synergy to increase STAT-5b target gene expression. Eight healthy men were studied on two occasions in relation to a 1 h exercise bout: i) with a concomitant i.v. glucose infusion ('feast') and ii) after a 36 h fast ('famine'). Muscle and fat biopsy specimens were obtained before, immediately after, and 30 min after exercise. GH increased during exercise on both examination days and this effect was amplified by fasting, and free fatty acid (FFA) levels increased after fasting. STAT-5b phosphorylation increased similarly following exercise on both occasions. In adipose tissue, suppressors of cytokine signaling 1 (SOCS1) and SOCS2 were increased after exercise on the fasting day and both fasting and exercise increased cytokine inducible SH2-containing protein (CISH). In muscle, SOCS2 and CISH mRNA were persistently increased after fasting. Muscle SOCS1, SOCS3, and CISH mRNA expression increased, whereas SOCS2 decreased after exercise on both examination days. This study demonstrates that fasting and exercise act in tandem to amplify STAT-5b target gene expression (SOCS and CISH) in adipose and muscle tissue in accordance with the 'feast and famine hypothesis'; the adipose tissue signaling responses, which hitherto have not been scrutinized, may play a particular role in promoting FFA mobilization. © 2015 European Society of Endocrinology.

  14. Identification of small molecule compounds that inhibit the HIF-1 signaling pathway

    Directory of Open Access Journals (Sweden)

    Sun Yi

    2009-12-01

    Full Text Available Abstract Background Hypoxia-inducible factor-1 (HIF-1 is the major hypoxia-regulated transcription factor that regulates cellular responses to low oxygen environments. HIF-1 is composed of two subunits: hypoxia-inducible HIF-1α and constitutively-expressed HIF-1β. During hypoxic conditions, HIF-1α heterodimerizes with HIF-1β and translocates to the nucleus where the HIF-1 complex binds to the hypoxia-response element (HRE and activates expression of target genes implicated in cell growth and survival. HIF-1α protein expression is elevated in many solid tumors, including those of the cervix and brain, where cells that are the greatest distance from blood vessels, and therefore the most hypoxic, express the highest levels of HIF-1α. Therapeutic blockade of the HIF-1 signaling pathway in cancer cells therefore provides an attractive strategy for development of anticancer drugs. To identify small molecule inhibitors of the HIF-1 pathway, we have developed a cell-based reporter gene assay and screened a large compound library by using a quantitative high-throughput screening (qHTS approach. Results The assay is based upon a β-lactamase reporter under the control of a HRE. We have screened approximate 73,000 compounds by qHTS, with each compound tested over a range of seven to fifteen concentrations. After qHTS we have rapidly identified three novel structural series of HIF-1 pathway Inhibitors. Selected compounds in these series were also confirmed as inhibitors in a HRE β-lactamase reporter gene assay induced by low oxygen and in a VEGF secretion assay. Three of the four selected compounds tested showed significant inhibition of hypoxia-induced HIF-1α accumulation by western blot analysis. Conclusion The use of β-lactamase reporter gene assays, in combination with qHTS, enabled the rapid identification and prioritization of inhibitors specific to the hypoxia induced signaling pathway.

  15. Discovering Small Molecule Inhibitors Targeted to Ligand-Stimulated RAGE-DIAPH1 Signaling Transduction

    Science.gov (United States)

    Pan, Jinhong

    The receptor of advanced glycation end product (RAGE) is a multiligand receptor of the immunoglobulin superfamily of cell surface molecules, which plays an important role in immune responses. Full-length RAGE includes three extracellular immunoglobulin domains, a transmembrane domain and an intracellular domain. It is a pattern recognition receptor that can bind diverse ligands. NMR spectroscopy and x-ray crystallization studies of the extracellular domains of RAGE indicate that RAGE ligands bind by distinct charge- and hydrophobicity-dependent mechanisms. It is found that calgranulin binding to the C1C2 domain or AGEs binding to the V domain activates extracellular signaling, which triggers interactions of the RAGE cytoplasmic tail (ctRAGE) with intracellular effector, such as diaphanous 1 (DIAPH1), to initiate signal transduction cascades. ctRAGE is essential for RAGE-ligand-mediated signal transduction and consequent modulation of gene expression and cellular properties. RAGE is over-expressed in diseased tissues of most RAGE-associated pathogenic conditions, such as complications of Alzheimer's diseases, diabetes, vascular diseases, inflammation, cancers and neurodegeneration. They are the major diseases affecting a large population worldwide. RAGE can function as a biomarker or drug target for these diseases. The cytoplasmic tail of RAGE can be used as a drug target to inhibit RAGE-induced intracellular signaling by small molecule inhibitors to treat RAGE-associated diseases. We developed a high throughput screening assay with which we probed a small molecule library of 58,000 compounds to find that 777 small molecules displayed 50% inhibition and 97 compounds demonstrated dose-dependent inhibition of the binding of ctRAGE-DIAPH1. Eventually, there were 13 compounds which displayed dose-dependent inhibition of ctRAGE binding to DIAPH1 and direct binding to ctRAGE analyzed by 15N HSQC-NMR and native tryptophan fluorescence titration experiments; thus, they were

  16. Effect of placement of droop based generators in distribution network on small signal stability margin and network loss

    DEFF Research Database (Denmark)

    Dheer, D.K.; Doolla, S.; Bandyopadhyay, S.

    2017-01-01

    , small signal stability margin is on the fore. The present research studied the effect of location of droop-controlled DGs on small signal stability margin and network loss on a modified IEEE 13 bus system, an IEEE 33-bus distribution system and a practical 22-bus radial distribution network. A complete...... loss and stability margin is further investigated by identifying the Pareto fronts for modified IEEE 13 bus, IEEE 33 and practical 22-bus radial distribution network with application of Reference point based Non-dominated Sorting Genetic Algorithm (R-NSGA). Results were validated by time domain......For a utility-connected system, issues related to small signal stability with Distributed Generators (DGs) are insignificant due to the presence of a very strong grid. Optimally placed sources in utility connected microgrid system may not be optimal/stable in islanded condition. Among others issues...

  17. Highly sensitive aptasensor based on synergetic catalysis activity of MoS2-Au-HE composite using cDNA-Au-GOD for signal amplification.

    Science.gov (United States)

    Song, Hai-Yan; Kang, Tian-Fang; Lu, Li-Ping; Cheng, Shui-Yuan

    2017-03-01

    Single or few-layer nanosheets of MoS 2 (MoS 2 nanosheets) and a composite composed of MoS 2 nanosheets, Au nanoparticles (AuNPs) and hemin (HE) (denoted as MoS 2 -Au-HE) were prepared. The composites possessed high synergetic catalysis activity towards the electroreduction of hydrogen peroxide. Furthermore, glucose oxidase (GOD) and AuNPs were used as marker of the complementary DNA (cDNA) strand of kanamycin aptamer to prepare a conjugate (reffered as cDNA-Au-GOD) that was designed as the signal probe. Both cDNA-Au-GOD and MoS 2 -Au-HE were applied to fabricate aptasensor for kanamycin. MoS 2 -Au-HE acted as solid platform for kanamycin aptamer and signal transmitters. AuNPs were employed as the supporter of cDNA and GOD which catalyze dissolved oxygen to produce hydrogen peroxide in the presence of glucose. Then cathodic peak current of H 2 O 2 was recorded by differential pulse voltammetry (DPV). The electrochemical reduction of H 2 O 2 was catalyzed by MoS 2 -Au-HE that was modified onto the surface of a glassy carbon electrode (GCE). The cathodic peak current of H 2 O 2 was highly linearly decreased with an increase of kanamycin concentrations from 1.0ng/L to 1.0×10 5 ng/L, with a detection limit of 0.8ng/L. This aptasensor can be used to detect kanamycin in milk with high specificity, sensitivity and selectivity. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Digital signal processing applied to crystal identification in Positron Emission Tomography dedicated to small animals

    International Nuclear Information System (INIS)

    Fontaine, Rejean; Viscogliosi, Nicolas; Semmaoui, Hicham; Belanger, Francois; Lemieux, Francois; Tetrault, Marc-Andre; Michaud, Jean-Baptiste; Berard, Philippe; Cadorette, Jules; Pepin, Catherine M.; Lecomte, Roger

    2007-01-01

    The recent introduction of all-digital electronic architecture in Positron Emission Tomography (PET) scanners, enables new paradigms to be explored for extracting relevant information from the detector signals, such as energy, time and crystal identification. The LabPET TM small animal scanner, which implements free-running 45-MHz sampling directly at the output of the charge sensitive preamplifiers, provides an excellent platform to test such advanced digital algorithms. A real-time identification method, based on an Auto-Regressive Moving-Average (ARMA) scheme, was tested for discriminating between LYSO (t r ∼40 ns) and LGSO (t r ∼65 ns) scintillators in phoswich detectors, coupled to a single Avalanche Photodiode (APD). Even with a low energy threshold of 250 keV applied individually, error rates 10%, typically with conventional analog pulse shape discrimination techniques. Such digital crystal identification techniques can be readily implemented with phoswich detectors for improving spatial resolution in PET, either by increasing crystal pixellization or by mitigating parallax errors through depth-of-interaction determination. It also allows to reduce the event rate presented to the real-time coincidence engine by applying a low energy limit at the crystal granularity and rejecting more Compton photons

  19. Digital signal processing applied to crystal identification in Positron Emission Tomography dedicated to small animals

    Energy Technology Data Exchange (ETDEWEB)

    Fontaine, Rejean [Department of Electrical and Computer Engineering, Universite de Sherbrooke, 2500 Boul. Universite, Sherbrooke, Que., J1 K 2R1 (Canada)]. E-mail: Rejean.Fontaine@Usherbrooke.ca; Viscogliosi, Nicolas [Department of Electrical and Computer Engineering, Universite de Sherbrooke, 2500 Boul. Universite, Sherbrooke, Que., J1 K 2R1 (Canada); Semmaoui, Hicham [Department of Electrical and Computer Engineering, Universite de Sherbrooke, 2500 Boul. Universite, Sherbrooke, Que., J1 K 2R1 (Canada); Belanger, Francois [Department of Electrical and Computer Engineering, Universite de Sherbrooke, 2500 Boul. Universite, Sherbrooke, Que., J1 K 2R1 (Canada); Lemieux, Francois [Department of Electrical and Computer Engineering, Universite de Sherbrooke, 2500 Boul. Universite, Sherbrooke, Que., J1 K 2R1 (Canada); Tetrault, Marc-Andre [Department of Electrical and Computer Engineering, Universite de Sherbrooke, 2500 Boul. Universite, Sherbrooke, Que., J1 K 2R1 (Canada); Michaud, Jean-Baptiste [Department of Electrical and Computer Engineering, Universite de Sherbrooke, 2500 Boul. Universite, Sherbrooke, Que., J1 K 2R1 (Canada); Berard, Philippe [Department of Nuclear Medicine and Radiobiology, Universite de Sherbrooke, 2500 Boul. Universite, Sherbrooke, Que., J1 K 2R1 (Canada); Cadorette, Jules [Department of Nuclear Medicine and Radiobiology, Universite de Sherbrooke, 2500 Boul. Universite, Sherbrooke, Que., J1 K 2R1 (Canada); Pepin, Catherine M. [Department of Nuclear Medicine and Radiobiology, Universite de Sherbrooke, 2500 Boul. Universite, Sherbrooke, Que., J1 K 2R1 (Canada); Lecomte, Roger [Department of Nuclear Medicine and Radiobiology, Universite de Sherbrooke, 2500 Boul. Universite, Sherbrooke, Que., J1 K 2R1 (Canada)

    2007-02-01

    The recent introduction of all-digital electronic architecture in Positron Emission Tomography (PET) scanners, enables new paradigms to be explored for extracting relevant information from the detector signals, such as energy, time and crystal identification. The LabPET{sup TM} small animal scanner, which implements free-running 45-MHz sampling directly at the output of the charge sensitive preamplifiers, provides an excellent platform to test such advanced digital algorithms. A real-time identification method, based on an Auto-Regressive Moving-Average (ARMA) scheme, was tested for discriminating between LYSO (t{sub r}{approx}40 ns) and LGSO (t{sub r}{approx}65 ns) scintillators in phoswich detectors, coupled to a single Avalanche Photodiode (APD). Even with a low energy threshold of 250 keV applied individually, error rates<4% can be achieved, as compared to >10%, typically with conventional analog pulse shape discrimination techniques. Such digital crystal identification techniques can be readily implemented with phoswich detectors for improving spatial resolution in PET, either by increasing crystal pixellization or by mitigating parallax errors through depth-of-interaction determination. It also allows to reduce the event rate presented to the real-time coincidence engine by applying a low energy limit at the crystal granularity and rejecting more Compton photons.

  20. Performance Comparison of Adaptive Estimation Techniques for Power System Small-Signal Stability Assessment

    Directory of Open Access Journals (Sweden)

    E. A. Feilat

    2010-12-01

    Full Text Available This paper demonstrates the assessment of the small-signal stability of a single-machine infinite- bus power system under widely varying loading conditions using the concept of synchronizing and damping torques coefficients. The coefficients are calculated from the time responses of the rotor angle, speed, and torque of the synchronous generator. Three adaptive computation algorithms including Kalman filtering, Adaline, and recursive least squares have been compared to estimate the synchronizing and damping torque coefficients. The steady-state performance of the three adaptive techniques is compared with the conventional static least squares technique by conducting computer simulations at different loading conditions. The algorithms are compared to each other in terms of speed of convergence and accuracy. The recursive least squares estimation offers several advantages including significant reduction in computing time and computational complexity. The tendency of an unsupplemented static exciter to degrade the system damping for medium and heavy loading is verified. Consequently, a power system stabilizer whose parameters are adjusted to compensate for variations in the system loading is designed using phase compensation method. The effectiveness of the stabilizer in enhancing the dynamic stability over wide range of operating conditions is verified through the calculation of the synchronizing and damping torque coefficients using recursive least square technique.

  1. Nitrogen modulation of legume root architecture signalling pathways involves phytohormones and small regulatory molecules

    Directory of Open Access Journals (Sweden)

    Nadiatul Akmal Mohd-Radzman

    2013-10-01

    Full Text Available Nitrogen, particularly nitrate is an important yield determinant for crops. However, current agricultural practice with excessive fertilizer usage has detrimental effects on the environment. Therefore, legumes have been suggested as a sustainable alternative for replenishing soil nitrogen. Legumes can uniquely form nitrogen-fixing nodules through symbiotic interaction with specialized soil bacteria. Legumes possess a highly plastic root system which modulates its architecture according to the nitrogen availability in the soil. Understanding how legumes regulate root development in response to nitrogen availability is an important step to improving root architecture. The nitrogen-mediated root development pathway starts with sensing soil nitrogen level followed by subsequent signal transduction pathways involving phytohormones, microRNAs and regulatory peptides that collectively modulate the growth and shape of the root system. This review focuses on the current understanding of nitrogen-mediated legume root architecture including local and systemic regulations by different N-sources and the modulations by phytohormones and small regulatory molecules.

  2. Identification of small molecules that disrupt signaling between ABL and its positive regulator RIN1.

    Directory of Open Access Journals (Sweden)

    Pamela Y Ting

    Full Text Available Constitutively active BCR-ABL kinase fusions are causative mutations in the pathogenesis of hematopoietic neoplasias including chronic myelogenous leukemia (CML. Although these fusions have been successfully targeted with kinase inhibitors, drug-resistance and relapse continue to limit long-term survival, highlighting the need for continued innovative drug discovery. We developed a time-resolved Förster resonance energy transfer (TR-FRET -based assay to identify compounds that disrupt stimulation of the ABL kinase by blocking its ability to bind the positive regulator RIN1. This assay was used in a high throughput screen (HTS of two small molecule libraries totaling 444,743 compounds. 708 confirmed hits were counter-screened to eliminate off-target inhibitors and reanalyzed to prioritize compounds with IC50 values below 10 μM. The CML cell line K562 was then used to identify five compounds that decrease MAPK1/3 phosphorylation, which we determined to be an indicator of RIN1-dependent ABL signaling. One of these compounds is a thiadiazole, and the other four are structurally related acyl piperidine amides. Notably, these five compounds lower cellular BCR-ABL1 kinase activity by blocking a positive regulatory interaction rather than directly inhibiting ABL catalytic function.

  3. Generalised small signal analysis of a DAR /Double Avalanche Region/ IMPATT diode

    Science.gov (United States)

    Datta, D. N.; Pal, B. B.

    1982-06-01

    A generalized small signal analysis of a DAR IMPATT diode is carried out using recent values of ionization rates and saturated drift velocities of electrons and holes for Si and GaAs taking both the drift and the diffusion of charge carriers into account. The results show similar discrete negative conductance frequency bands separated by positive conductance frequency bands for an asymmetrical structure as in the ideal case (Som et al., 1974), establishing that the harmonically related frequencies can be avoided in the Si DAR IMPATT diode. In contrast to the ideal case, however, the symmetrical DAR IMPATT here also exhibits finite negative conductance. The GaAs DAR IMPATT shows variations of negative conductance that are similar to those in Si at high frequencies (in the mm wave range); at the low frequency side (less than 1 GHz), however, the IMPATT gives uniform negative conductances unlike Si where the negative conductance comes only at higher frequencies. Consideration is given in the calculations to thin depletion layers (0.8, 1, and 2 microns) to show the usefulness of the device in the mm wave range.

  4. Small leucine rich proteoglycan family regulates multiple signalling pathways in neural development and maintenance.

    Science.gov (United States)

    Dellett, Margaret; Hu, Wanzhou; Papadaki, Vasiliki; Ohnuma, Shin-ichi

    2012-04-01

    The small leucine-rich repeat proteoglycan (SLRPs) family of proteins currently consists of five classes, based on their structural composition and chromosomal location. As biologically active components of the extracellular matrix (ECM), SLRPs were known to bind to various collagens, having a role in regulating fibril assembly, organization and degradation. More recently, as a function of their diverse proteins cores and glycosaminoglycan side chains, SLRPs have been shown to be able to bind various cell surface receptors, growth factors, cytokines and other ECM components resulting in the ability to influence various cellular functions. Their involvement in several signaling pathways such as Wnt, transforming growth factor-β and epidermal growth factor receptor also highlights their role as matricellular proteins. SLRP family members are expressed during neural development and in adult neural tissues, including ocular tissues. This review focuses on describing SLRP family members involvement in neural development with a brief summary of their role in non-neural ocular tissues and in response to neural injury. © 2012 The Authors Development, Growth & Differentiation © 2012 Japanese Society of Developmental Biologists.

  5. Camera-based ratiometric fluorescence transduction of nucleic acid hybridization with reagentless signal amplification on a paper-based platform using immobilized quantum dots as donors.

    Science.gov (United States)

    Noor, M Omair; Krull, Ulrich J

    2014-10-21

    Paper-based diagnostic assays are gaining increasing popularity for their potential application in resource-limited settings and for point-of-care screening. Achievement of high sensitivity with precision and accuracy can be challenging when using paper substrates. Herein, we implement the red-green-blue color palette of a digital camera for quantitative ratiometric transduction of nucleic acid hybridization on a paper-based platform using immobilized quantum dots (QDs) as donors in fluorescence resonance energy transfer (FRET). A nonenzymatic and reagentless means of signal enhancement for QD-FRET assays on paper substrates is based on the use of dry paper substrates for data acquisition. This approach offered at least a 10-fold higher assay sensitivity and at least a 10-fold lower limit of detection (LOD) as compared to hydrated paper substrates. The surface of paper was modified with imidazole groups to assemble a transduction interface that consisted of immobilized QD-probe oligonucleotide conjugates. Green-emitting QDs (gQDs) served as donors with Cy3 as an acceptor. A hybridization event that brought the Cy3 acceptor dye in close proximity to the surface of immobilized gQDs was responsible for a FRET-sensitized emission from the acceptor dye, which served as an analytical signal. A hand-held UV lamp was used as an excitation source and ratiometric analysis using an iPad camera was possible by a relative intensity analysis of the red (Cy3 photoluminescence (PL)) and green (gQD PL) color channels of the digital camera. For digital imaging using an iPad camera, the LOD of the assay in a sandwich format was 450 fmol with a dynamic range spanning 2 orders of magnitude, while an epifluorescence microscope detection platform offered a LOD of 30 fmol and a dynamic range spanning 3 orders of magnitude. The selectivity of the hybridization assay was demonstrated by detection of a single nucleotide polymorphism at a contrast ratio of 60:1. This work provides an

  6. Identification of a c-Jun N-terminal kinase-2-dependent signal amplification cascade that regulates c-Myc levels in ras transformation

    DEFF Research Database (Denmark)

    Mathiasen, D.P.; Egebjerg, C.; Andersen, S.H.

    2012-01-01

    are essential for ras transformation. Previous studies show that ERK-mediated serine 62 phosphorylation protects c-Myc from proteasomal degradation. ERK is, however, not alone sufficient to stabilize c-Myc but requires the cooperation of cancerous inhibitor of protein phosphatase 2A (CIP2A), an oncogene...... that counteracts protein phosphatase 2A-mediated dephosphorylation of c-Myc. Here we show that JNK2 regulates Cip2a transcription via ATF2. ATF2 and c-Myc cooperate to activate the transcription of ATF3. Remarkably, not only ectopic JNK2, but also ectopic ATF2, CIP2A, c-Myc and ATF3 are sufficient to rescue...... the defective ras transformation of JNK2-deficient cells. Thus, these data identify the key signal converging point of JNK2 and ERK pathways and underline the central role of CIP2A in ras transformation.Oncogene advance online publication, 27 June 2011; doi:10.1038/onc.2011.230....

  7. Static and Dynamic Amplification Using Strong Mechanical Coupling

    KAUST Repository

    Ilyas, Saad; Jaber, Nizar; Younis, Mohammad I.

    2016-01-01

    Amplifying the signal-to-noise ratio of resonant sensors is vital toward the effort to miniaturize devices into the sub-micro and nano regimes. In this paper, we demonstrate theoretically and experimentally, amplification through mechanically

  8. A PSP-based small-signal MOSFET model for both quasi-static and nonquasi-static operations

    NARCIS (Netherlands)

    Aarts, A.C.T.; Smit, G.D.J.; Scholten, A.J.; Klaassen, D.B.M.

    2008-01-01

    In this paper, a small-signal MOSFET model is described, which takes the local effects of both velocity saturation and transverse mobility reduction into account. The model is based on the PSP model and is valid for both quasi-static and nonquasi-static (NQS) operations. Recently, it has been found

  9. Self-field effects on small-signal gain in two-stage free-electron lasers

    Indian Academy of Sciences (India)

    Self-field effects, induced by charge and current densities of the electron beam, on gain in two-stage free-electron laser with nonuniform guide magnetic field is presented. The gain equation for small-signal has been derived analytically. The results of numerical calculations show a gain decrement for group I orbits and a ...

  10. Detection of biological molecules using chemical amplification and optical sensors

    Science.gov (United States)

    Van Antwerp, William Peter; Mastrototaro, John Joseph

    2000-01-01

    Methods are provided for the determination of the concentration of biological levels of polyhydroxylated compounds, particularly glucose. The methods utilize an amplification system that is an analyte transducer immobilized in a polymeric matrix, where the system is implantable and biocompatible. Upon interrogation by an optical system, the amplification system produces a signal capable of detection external to the skin of the patient. Quantitation of the analyte of interest is achieved by measurement of the emitted signal.

  11. Signal and data processing of small targets 1991; Proceedings of the Meeting, Orlando, FL, Apr. 1-3, 1991

    Science.gov (United States)

    Drummond, Oliver E.

    Attention is given to signal processing; track-before-detect; systems and simulations; association and filtering in tracking; and data processing. Particular attention is given to a linear modeling algorithm for tracking time-varying signals, an optoelectric Gabor detector for transient signals, small-target acquisition and typing by AASAP, model-based analysis of 3D spatial-temporal IR clutter suppression filtering, algorithms and architectures for implementing large-velocity filter banks, an end-to-end scenario-generating model for IRST performance analysis, detection and tracking of small targets in persistence, an incremental model for target maneuver estimation, implementation of an angle-only tracking filter, a global modeling approach for multisensor problems, passive-sensor data fusion, midcourse multitarget racking using continuous representation, neural data association, and statistical initial orbit determination. (For individual items see A93-26797 to A93-26799)

  12. Gene amplification in carcinogenesis

    Directory of Open Access Journals (Sweden)

    Lucimari Bizari

    2006-01-01

    Full Text Available Gene amplification increases the number of genes in a genome and can give rise to karyotype abnormalities called double minutes (DM and homogeneously staining regions (HSR, both of which have been widely observed in human tumors but are also known to play a major role during embryonic development due to the fact that they are responsible for the programmed increase of gene expression. The etiology of gene amplification during carcinogenesis is not yet completely understood but can be considered a result of genetic instability. Gene amplification leads to an increase in protein expression and provides a selective advantage during cell growth. Oncogenes such as CCND1, c-MET, c-MYC, ERBB2, EGFR and MDM2 are amplified in human tumors and can be associated with increased expression of their respective proteins or not. In general, gene amplification is associated with more aggressive tumors, metastases, resistance to chemotherapy and a decrease in the period during which the patient stays free of the disease. This review discusses the major role of gene amplification in the progression of carcinomas, formation of genetic markers and as possible therapeutic targets for the development of drugs for the treatment of some types of tumors.

  13. Laser driven X-ray parametric amplification in neutral gases-a new brilliant light source in the XUV

    International Nuclear Information System (INIS)

    Aurand, B.; Seres, J.; Bagnoud, V.; Ecker, B.; Hochhaus, D.C.; Neumayer, P.; Seres, E.; Spielmann, C.; Zielbauer, B.; Zimmer, D.; Kuehl, T.

    2011-01-01

    In this paper we present the experimental setup and results showing a new type of strong-field parametric amplification of high-order harmonic radiation. With a simple semi-classical model, we can identify the most important experimental parameters, the spectral range and the small signal gain in gases. Using a single stage amplifier, a small signal gain of 8000 has been obtained in argon for the spectral range of 40-50 eV, using 350 fs, 7 mJ pulses at 1.05 μm. An outlook for an experiment employing a double stage gas system will be given.

  14. Laser driven X-ray parametric amplification in neutral gases-a new brilliant light source in the XUV

    Energy Technology Data Exchange (ETDEWEB)

    Aurand, B., E-mail: b.aurand@gsi.de [GSI Helmholtz Centre for Heavy Ion Research, Planckstr. 1, 64291 Darmstadt (Germany); ExtreMe Matter Institute, Planckstr. 1, 64291 Darmstadt (Germany); Johannes Gutenberg University Mainz, Saarstr. 21, 55099 Mainz (Germany); Seres, J. [Friedrich-Schiller-University Jena, Max-Wien-Platz 1, 07743 Jena (Germany); Bagnoud, V. [GSI Helmholtz Centre for Heavy Ion Research, Planckstr. 1, 64291 Darmstadt (Germany); Ecker, B. [GSI Helmholtz Centre for Heavy Ion Research, Planckstr. 1, 64291 Darmstadt (Germany); Helmholtz Institut Jena, Helmholtzweg 4, 07743 Jena (Germany); Johannes Gutenberg University Mainz, Saarstr. 21, 55099 Mainz (Germany); Hochhaus, D.C.; Neumayer, P. [GSI Helmholtz Centre for Heavy Ion Research, Planckstr. 1, 64291 Darmstadt (Germany); ExtreMe Matter Institute, Planckstr. 1, 64291 Darmstadt (Germany); Johann-Wolfgang von Goethe University, 60325 Frankfurt (Germany); Seres, E.; Spielmann, C. [Friedrich-Schiller-University Jena, Max-Wien-Platz 1, 07743 Jena (Germany); Zielbauer, B. [GSI Helmholtz Centre for Heavy Ion Research, Planckstr. 1, 64291 Darmstadt (Germany); Helmholtz Institut Jena, Helmholtzweg 4, 07743 Jena (Germany); Zimmer, D. [GSI Helmholtz Centre for Heavy Ion Research, Planckstr. 1, 64291 Darmstadt (Germany); Kuehl, T. [GSI Helmholtz Centre for Heavy Ion Research, Planckstr. 1, 64291 Darmstadt (Germany); ExtreMe Matter Institute, Planckstr. 1, 64291 Darmstadt (Germany); Johannes Gutenberg University Mainz, Saarstr. 21, 55099 Mainz (Germany)

    2011-10-11

    In this paper we present the experimental setup and results showing a new type of strong-field parametric amplification of high-order harmonic radiation. With a simple semi-classical model, we can identify the most important experimental parameters, the spectral range and the small signal gain in gases. Using a single stage amplifier, a small signal gain of 8000 has been obtained in argon for the spectral range of 40-50 eV, using 350 fs, 7 mJ pulses at 1.05 {mu}m. An outlook for an experiment employing a double stage gas system will be given.

  15. Impact of Wind Power Plants with Full Converter Wind Turbines on Power System Small-Signal Stability

    DEFF Research Database (Denmark)

    Knüppel, Thyge; Nygaard Nielsen, Jørgen; Dixon, Andrew

    Wind power is being developed in power systems all around the world, and already today wind power covers more than 20 % of the electricity consumption in some countries. As the size of each wind power plant (WPP) increases and as the levels of penetration reaches certain magnitudes, the inclusion...... of the dynamic properties of the WPPs in the power system stability studies become important. The work presented in this report deal with the impact of WPPs based on full converter wind turbines (WTs) on the power system small-signal rotor angle stability. During small disturbances in the power system, the rotor...... speed of the synchronous machines will eventually return to its steady state if the power system is small-signal stable. The dynamic properties of a WPP are fundamentally dierent from those of a synchronous machine, and the interaction of WPPs with the synchronous machines in power system oscillations...

  16. Social amplification of risk

    International Nuclear Information System (INIS)

    Kasperson, R.E.; Renn, O.; Slovic, P.; Kasperson, J.X.; Emani, S.

    1989-01-01

    The risks associated with radioactive and other hazardous waste disposal may be expected to interact with societal processes to enlarge or attenuate the consequences of risks and risk events. This article summarizes a conceptual framework that depicts the social amplification of risk. Using a data base of 128 hazard events that have occurred largely over the past ten years, the authors examine the role of physical consequences, media coverage, and public perceptions of risk in generating social and economic impacts. The analysis concludes that social amplification processes substantially shape the nature and magnitude of those impacts but also that such social amplification appears to be systematically related to characteristics of the risks and risk events

  17. Weak wide-band signal detection method based on small-scale periodic state of Duffing oscillator

    Science.gov (United States)

    Hou, Jian; Yan, Xiao-peng; Li, Ping; Hao, Xin-hong

    2018-03-01

    The conventional Duffing oscillator weak signal detection method, which is based on a strong reference signal, has inherent deficiencies. To address these issues, the characteristics of the Duffing oscillatorʼs phase trajectory in a small-scale periodic state are analyzed by introducing the theory of stopping oscillation system. Based on this approach, a novel Duffing oscillator weak wide-band signal detection method is proposed. In this novel method, the reference signal is discarded, and the to-be-detected signal is directly used as a driving force. By calculating the cosine function of a phase space angle, a single Duffing oscillator can be used for weak wide-band signal detection instead of an array of uncoupled Duffing oscillators. Simulation results indicate that, compared with the conventional Duffing oscillator detection method, this approach performs better in frequency detection intervals, and reduces the signal-to-noise ratio detection threshold, while improving the real-time performance of the system. Project supported by the National Natural Science Foundation of China (Grant No. 61673066).

  18. Unconstrained and Noninvasive Measurement of Swimming Behavior of Small Fish Based on Ventilatory Signals

    Science.gov (United States)

    Kitayama, Shigehisa; Soh, Zu; Hirano, Akira; Tsuji, Toshio; Takiguchi, Noboru; Ohtake, Hisao

    Ventilatory signal is a kind of bioelectric signals reflecting the ventilatory conditions of fish, and has received recent attention as an indicator for assessment of water quality, since breathing is adjusted by the respiratory center according to changes in the underwater environment surrounding the fish. The signals are thus beginning to be used in bioassay systems for water examination. Other than ventilatory conditions, swimming behavior also contains important information for water examination. The conventional bioassay systems, however, only measure either ventilatory signals or swimming behavior. This paper proposes a new unconstrained and noninvasive measurement method that is capable of conducting ventilatory signal measurement and behavioral analysis of fish at the same time. The proposed method estimates the position and the velocity of a fish in free-swimming conditions using power spectrum distribution of measured ventilatory signals from multiple electrodes. This allowed the system to avoid using a camera system which requires light sources. In order to validate estimation accuracy, the position and the velocity estimated by the proposed method were compared to those obtained from video analysis. The results confirmed that the estimated error of the fish positions was within the size of fish, and the correlation coefficient between the velocities was 0.906. The proposed method thus not only can measure the ventilatory signals, but also performs behavioral analysis as accurate as using a video camera.

  19. Biomaterials in light amplification

    Science.gov (United States)

    Mysliwiec, Jaroslaw; Cyprych, Konrad; Sznitko, Lech; Miniewicz, Andrzej

    2017-03-01

    Biologically produced or inspired materials can serve as optical gain media, i.e. they can exhibit the phenomenon of light amplification. Some of these materials, under suitable dye-doping and optical pumping conditions, show lasing phenomena. The emerging branch of research focused on obtaining lasing action in highly disordered and highly light scattering materials, i.e. research on random lasing, is perfectly suited for biological materials. The use of biomaterials in light amplification has been extensively reported in the literature. In this review we attempt to report on progress in the development of biologically derived systems able to show the phenomena of light amplification and random lasing together with the contribution of our group to this field. The rich world of biopolymers modified with molecular aggregates and nanocrystals, and self-organized at the nanoscale, offers a multitude of possibilities for tailoring luminescent and light scattering properties that are not easily replicated in conventional organic or inorganic materials. Of particular importance and interest are light amplification and lasing, or random lasing studies in biological cells and tissues. In this review we will describe nucleic acids and their complexes employed as gain media due to their favorable optical properties and ease of manipulation. We will report on research conducted on various biomaterials showing structural analogy to nucleic acids such as fluorescent proteins, gelatins in which the first distributed feedback laser was realized, and also amyloids or silks, which, due to their dye-doped fiber-like structure, allow for light amplification. Other materials that were investigated in that respect include polysaccharides, like starch exhibiting favorable photostability in comparison to other biomaterials, and chitosan, which forms photonic crystals or cellulose. Light amplification and random lasing was not only observed in processed biomaterials but also in living

  20. Signal amplification of dopamine using lanthanum hexacyanoferrate ...

    Indian Academy of Sciences (India)

    rare earth metal hexacyanoferrates, for e.g., lanthanum ... to facilitate the electrochemical reactions of biological molecules.9,10 In general ... bic acid and potassium hexacyanoferrate (Merck) were ... were prepared using doubly distilled water.

  1. On understanding crosstalk in the face of small, quantized, signals highly smeared by Poisson statistics

    International Nuclear Information System (INIS)

    Lincoln, D.; Hsieh, F.; Li, H.

    1995-01-01

    As detectors become smaller and more densely packed, signals become smaller and crosstalk between adjacent channels generally increases. Since it is often appropriate to use the distribution of signals in adjacent channels to make a useful measurement, it is imperative that inter-channel crosstalk be well understood. In this paper we shall describe the manner in which Poissonian fluctuations can give counter-intuitive results and offer some methods for extracting the desired information from the highly smeared, observed distributions. (orig.)

  2. Signal and data processing of small targets 1992; Proceedings of the Meeting, Orlando, FL, Apr. 20-22, 1992

    Science.gov (United States)

    Drummond, Oliver E.

    This volume on signal and data processing of small targets contains chapters devoted to signal processing, low observable detection, systems and simulations, association and filtering in tracking, multiple sensor processing and fusion, and data processing. Papers included are on multisensor predetection fusion, adaptive whitening filters for small target detection, unified framework for IR target detection and tracking, and target detection from image sequences using pixel-based decision criterion. Attention is also given to automatic acquisition and tracking of rounds and targets for electrooptic fire control, advanced surveillance testbed and background modeling, an interacting-multiple-model algorithm for tracking targets that maneuver through coordinated turns, and angular momentum and ballistic tracking. Other papers are on a data integration (fusion) tree paradigm, single-scan tracking using N IR sensors, and track monitoring with single and multiple 2D passive sensors. (No individual items are abstracted in this volume)

  3. On Small-Signal Stability of Wind Power System with Full-Load Converter Interfaced Wind Turbines

    DEFF Research Database (Denmark)

    Knüppel, Thyge; Akhmatov, Vladislav; Nielsen, Jørgen Nygård

    2010-01-01

    the impact of full-load converter interfaced wind turbines on power system small-signal stability. The study is based on a 7 generator network with lightly damped inter-area modes. A detailed wind turbine model with all grid relevant control functions is used in the study. Furthermore is the wind power plant......Small-signal stability analysis of power system oscillations is a well established field within power system analysis, but not much attention has yet been paid to systems with a high penetration of wind turbines and with large wind power plants. In this paper an analysis is presented which assess...... (WPP) equipped with a WPP voltage controller and comparisons are presented. The models of wind turbine and WPP voltage controller are kindly provided by Siemens Wind Power A/S for this work. The study is based on modal analysis which are complemented with simulations on the nonlinear system....

  4. Identifying Neutrino Mass Hierarchy at Extremely Small θ13 through Earth Matter Effects in a Supernova Signal

    International Nuclear Information System (INIS)

    Dasgupta, Basudeb; Dighe, Amol; Mirizzi, Alessandro

    2008-01-01

    Collective neutrino flavor transformations deep inside a supernova are sensitive to the neutrino mass hierarchy even at extremely small values of θ 13 . Exploiting this effect, we show that comparison of the antineutrino signals from a galactic supernova in two megaton class water Cherenkov detectors, one of which is shadowed by Earth, will enable us to distinguish between the hierarchies if sin 2 θ 13 -5 , where long baseline neutrino experiments would be ineffectual

  5. Inhibition of TLR2 signaling by small molecule inhibitors targeting a pocket within the TLR2 TIR domain

    Science.gov (United States)

    Mistry, Pragnesh; Laird, Michelle H. W.; Schwarz, Ryan S.; Greene, Shannon; Dyson, Tristan; Snyder, Greg A.; Xiao, Tsan Sam; Chauhan, Jay; Fletcher, Steven; Toshchakov, Vladimir Y.; MacKerell, Alexander D.; Vogel, Stefanie N.

    2015-01-01

    Toll-like receptor (TLR) signaling is initiated by dimerization of intracellular Toll/IL-1 receptor resistance (TIR) domains. For all TLRs except TLR3, recruitment of the adapter, myeloid differentiation primary response gene 88 (MyD88), to TLR TIR domains results in downstream signaling culminating in proinflammatory cytokine production. Therefore, blocking TLR TIR dimerization may ameliorate TLR2-mediated hyperinflammatory states. The BB loop within the TLR TIR domain is critical for mediating certain protein–protein interactions. Examination of the human TLR2 TIR domain crystal structure revealed a pocket adjacent to the highly conserved P681 and G682 BB loop residues. Using computer-aided drug design (CADD), we sought to identify a small molecule inhibitor(s) that would fit within this pocket and potentially disrupt TLR2 signaling. In silico screening identified 149 compounds and 20 US Food and Drug Administration-approved drugs based on their predicted ability to bind in the BB loop pocket. These compounds were screened in HEK293T-TLR2 transfectants for the ability to inhibit TLR2-mediated IL-8 mRNA. C16H15NO4 (C29) was identified as a potential TLR2 inhibitor. C29, and its derivative, ortho-vanillin (o-vanillin), inhibited TLR2/1 and TLR2/6 signaling induced by synthetic and bacterial TLR2 agonists in human HEK-TLR2 and THP-1 cells, but only TLR2/1 signaling in murine macrophages. C29 failed to inhibit signaling induced by other TLR agonists and TNF-α. Mutagenesis of BB loop pocket residues revealed an indispensable role for TLR2/1, but not TLR2/6, signaling, suggesting divergent roles. Mice treated with o-vanillin exhibited reduced TLR2-induced inflammation. Our data provide proof of principle that targeting the BB loop pocket is an effective approach for identification of TLR2 signaling inhibitors. PMID:25870276

  6. Breakdown of hot-spot model in determining convective amplification in large homogeneous systems

    International Nuclear Information System (INIS)

    Mounaix, Philippe; Divol, Laurent

    2004-01-01

    Convective amplification in large homogeneous systems is studied, both analytically and numerically, in the case of a linear diffraction-free stochastic amplifier. Overall amplification does not result from successive amplifications in small scale high intensity hot spots, but from a single amplification in a delocalized mode of the driver field spreading over the whole interaction length. For this model, the hot-spot approach is found to systematically underestimate the gain factor by more than 50%

  7. PI3K-AKT signaling pathway is involved in hypoxia/thermal-induced immunosuppression of small abalone Haliotis diversicolor.

    Science.gov (United States)

    Sun, Yulong; Zhang, Xin; Wang, Guodong; Lin, Shi; Zeng, Xinyang; Wang, Yilei; Zhang, Ziping

    2016-12-01

    The PI3K-AKT signal pathway has been found to be involved in many important physiological and pathological processes of the innate immune system of vertebrates and invertebrates. In this study, the AKT (HdAKT) and PI3K (HdPI3K) gene of small abalone Haliotis diversicolor were cloned and characterized for the important status of PI3K and AKT protein in PI3K-AKT signaling pathway. The full length cDNAs of HdAKT and HdPI3K are 2126 bp and 6052 bp respectively, encoding proteins of 479 amino acids and 1097 amino acids, respectively. The mRNA expression level of fourteen genes in the PI3K-AKT signaling pathway were detected by quantitative real-time PCR. The results showed that all these fourteen genes were ubiquitously expressed in seven selected tissues. Meanwhile, HdAKT was expressed in haemocytes with the highest expression level (p abalone. The mRNA expression of these genes in gills, haemocytes and hepatopancreas was significantly down-regulated after the Vibrio parahaemolyticus stimulation with environment stimulation (thermal, hypoxia and thermal & hypoxia). These results indicate that the dual/multiple stresses defeat the immune system and lead to immunosuppression in abalone. PI3K-AKT signaling pathway may be involved in hypoxia/thermal-induced immunosuppression of small abalone Haliotis diversicolor. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Parametric nanomechanical amplification at very high frequency.

    Science.gov (United States)

    Karabalin, R B; Feng, X L; Roukes, M L

    2009-09-01

    Parametric resonance and amplification are important in both fundamental physics and technological applications. Here we report very high frequency (VHF) parametric resonators and mechanical-domain amplifiers based on nanoelectromechanical systems (NEMS). Compound mechanical nanostructures patterned by multilayer, top-down nanofabrication are read out by a novel scheme that parametrically modulates longitudinal stress in doubly clamped beam NEMS resonators. Parametric pumping and signal amplification are demonstrated for VHF resonators up to approximately 130 MHz and provide useful enhancement of both resonance signal amplitude and quality factor. We find that Joule heating and reduced thermal conductance in these nanostructures ultimately impose an upper limit to device performance. We develop a theoretical model to account for both the parametric response and nonequilibrium thermal transport in these composite nanostructures. The results closely conform to our experimental observations, elucidate the frequency and threshold-voltage scaling in parametric VHF NEMS resonators and sensors, and establish the ultimate sensitivity limits of this approach.

  9. Application of small-size antennas for estimation of angles of arrival of HF signals scattered by ionospheric irregularities

    Science.gov (United States)

    Guo, Qiang; Galushko, Volodymyr G.; Zalizovski, Andriy V.; Kashcheyev, Sergiy B.; Zheng, Yu

    2018-05-01

    A modification of the Doppler Interferometry Technique is suggested to enable estimating angles of arrival of comparatively broadband HF signals scattered by random irregularities of the ionospheric plasma with the use of small-size weakly directional antennas. The technique is based on the measurements of cross-spectra phases of the probe radiation recorded at least in three spatially separated points. The developed algorithm has been used to investigate the angular and frequency-time characteristics of HF signals propagating at frequencies above the maximum usable one (MUF) for the direct radio path Moscow-Kharkiv. The received signal spectra show presence of three families of spatial components attributed, respectively, to scattering by plasma irregularities near the middle point of the radio path, ground backscatter signals and scattering of the sounding signals by the intense plasma turbulence associated with auroral activations. It has been shown that the regions responsible for the formation of the third family components are located well inside the auroral oval. The drift velocity and direction of the auroral ionosphere plasma have been determined. The obtained estimates are consistent with the classical conception of the ionospheric plasma convection at high latitudes and do not contradict the results of investigations of the auroral ionosphere dynamics using the SuperDARN network.

  10. High throughput screening for small molecule enhancers of the interferon signaling pathway to drive next-generation antiviral drug discovery.

    Directory of Open Access Journals (Sweden)

    Dhara A Patel

    Full Text Available Most of current strategies for antiviral therapeutics target the virus specifically and directly, but an alternative approach to drug discovery might be to enhance the immune response to a broad range of viruses. Based on clinical observation in humans and successful genetic strategies in experimental models, we reasoned that an improved interferon (IFN signaling system might better protect against viral infection. Here we aimed to identify small molecular weight compounds that might mimic this beneficial effect and improve antiviral defense. Accordingly, we developed a cell-based high-throughput screening (HTS assay to identify small molecules that enhance the IFN signaling pathway components. The assay is based on a phenotypic screen for increased IFN-stimulated response element (ISRE activity in a fully automated and robust format (Z'>0.7. Application of this assay system to a library of 2240 compounds (including 2160 already approved or approvable drugs led to the identification of 64 compounds with significant ISRE activity. From these, we chose the anthracycline antibiotic, idarubicin, for further validation and mechanism based on activity in the sub-µM range. We found that idarubicin action to increase ISRE activity was manifest by other members of this drug class and was independent of cytotoxic or topoisomerase inhibitory effects as well as endogenous IFN signaling or production. We also observed that this compound conferred a consequent increase in IFN-stimulated gene (ISG expression and a significant antiviral effect using a similar dose-range in a cell-culture system inoculated with encephalomyocarditis virus (EMCV. The antiviral effect was also found at compound concentrations below the ones observed for cytotoxicity. Taken together, our results provide proof of concept for using activators of components of the IFN signaling pathway to improve IFN efficacy and antiviral immune defense as well as a validated HTS approach to identify

  11. Inhibition of receptor tyrosine kinase signalling by small molecule agonist of T-cell protein tyrosine phosphatase

    International Nuclear Information System (INIS)

    Mattila, Elina; Marttila, Heidi; Sahlberg, Niko; Kohonen, Pekka; Tähtinen, Siri; Halonen, Pasi; Perälä, Merja; Ivaska, Johanna

    2010-01-01

    T-cell protein tyrosine phosphatase (TCPTP/TC45) is a ubiquitously expressed intra-cellular non-receptor protein tyrosine phosphatase involved in the negative regulation of several cancer relevant cellular signalling pathways. We have previously shown that interaction between the α-cytoplasmic tail of α1β1 integrin and TCPTP activates TCPTP by disrupting an inhibitory intra-molecular bond in TCPTP. Thus, inhibition of the regulatory interaction in TCPTP is a desirable strategy for TCPTP activation and attenuation of oncogenic RTK signalling. However, this is challenging with low molecular weight compounds. We developed a high-throughput compatible assay to analyse activity of recombinant TCPTP in vitro. Using this assay we have screened 64280 small molecules to identify novel agonists for TCPTP. Dose-dependent response to TCPTP agonist was performed using the in vitro assay. Inhibition effects and specificity of TCPTP agonists were evaluated using TCPTP expressing and null mouse embryonic fibroblasts. Western blot analysis was used to evaluate attenuation of PDGFRβ and EGFR phosphorylation. Inhibition of VEGF signalling was analysed with VEGF-induced endothelial cell sprouting assays. From the screen we identified six TCPTP agonists. Two compounds competed with α1-cytoplasmic domain for binding to TCPTP, suggesting that they activate TCPTP similar to α1-cyt by disrupting the intra-molecular bond in TCPTP. Importantly, one of the compounds (spermidine) displayed specificity towards TCPTP in cells, since TCPTP -/- cells were 43-fold more resistant to the compound than TCPTP expressing cells. This compound attenuates PDGFRβ and VEGFR2 signalling in cells in a TCPTP-dependent manner and functions as a negative regulator of EGFR phosphorylation in cancer cells. In this study we showed that small molecules mimicking TCPTP-α1 interaction can be used as TCPTP agonists. These data provide the first proof-of-concept description of the use of high-throughput screening

  12. Study on high gain broadband optical parametric chirped pulse amplification

    International Nuclear Information System (INIS)

    Zhang, S.K.; Fujita, M.; Yamanaka, C.; Yoshida, H.; Kodama, R.; Fujita, H.; Nakatsuka, M.; Izawa, Y.

    2000-01-01

    Optical parametric chirped pulse amplification has apparent advantages over the current schemes for high energy ultrashort pulse amplification. High gain in a single pass amplification, small B-integral, low heat deposition, high contrast ratio and, especially the extremely broad gain bandwidth with large-size crystals available bring people new hope for over multi-PW level at which the existing Nd:glass systems suffered difficulties. In this paper we present simulation and experimental studies for a high gain optical parametric chirped pulse amplification system which may be used as a preamplifier to replace the current complicated regenerative system or multi-pass Ti:sapphire amplifiers. Investigations on the amplification bandwidth and gain with BBO are performed. Analysis and discussions are also given. (author)

  13. Phasor Measurement Unit Test and Applications for Small Signal Stability Assessment and Improvement of Power System

    DEFF Research Database (Denmark)

    Ghiga, Radu

    to be less predictable. Therefore, the methods used for stability and security assessment will most likely use information from the wide-area measurements systems (WAMS). The work presented in this thesis deals on one hand with the development of test methods and validation of phasor measurement units (PMUs......) which are considered to be one of the key technologies in WAMS, and on the other hand with the possibility of using PMU measurements together with large wind power plants (WPPs) to help improve the damping of inter area oscillations. To validate the PMUs, a laboratory test setup is assembled....... The hardware components are capable of generating, with the required accuracy, the test signals injected in the PMUs. The signals are created according to the requirements defined in the current IEEE C37.118.1-2011 standard, to test the steady-state and dynamic compliance of the PMUs. The performance...

  14. Social amplification of risk: a conceptual framework

    International Nuclear Information System (INIS)

    Kasperson, R.E.; Renn, O.; Slovic, P.; Brown, H.S.; Emel, J.; Goble, R.; Kasperson, J.X.; Ratick, S.

    1988-01-01

    One of the most perplexing problems in risk analysis is why some relatively minor risks or risk events, as assessed by technical experts, often elicit strong public concerns and result in substantial impacts upon society and economy. This article sets forth a conceptual framework that seeks to link systematically the technical assessment of risk with psychological, sociological, and cultural perspectives of risk perception and risk-related behavior. The main thesis is that hazards interact with psychological, social, institutional, and cultural processes in ways that may amplify or attenuate public responses to the risk or risk event. A structural description of the social amplification of risk is now possible. Amplification occurs at two stages: in the transfer of information about the risk, and in the response mechanisms of society. Signals about risk are processed by individual and social amplification stations, including the scientist who communicates the risk assessment, the news media, cultural groups, interpersonal networks, and others. Key steps of amplifications can be identified at each stage. The amplified risk leads to behavioral responses, which, in turn, result in secondary impacts. Models are presented that portray the elements and linkages in the proposed conceptual framework

  15. Best Signal Quality in Cellular Networks: Asymptotic Properties and Applications to Mobility Management in Small Cell Networks

    Directory of Open Access Journals (Sweden)

    Baccelli François

    2010-01-01

    Full Text Available The quickly increasing data traffic and the user demand for a full coverage of mobile services anywhere and anytime are leading mobile networking into a future of small cell networks. However, due to the high-density and randomness of small cell networks, there are several technical challenges. In this paper, we investigate two critical issues: best signal quality and mobility management. Under the assumptions that base stations are uniformly distributed in a ring-shaped region and that shadowings are lognormal, independent, and identically distributed, we prove that when the number of sites in the ring tends to infinity, then (i the maximum signal strength received at the center of the ring tends in distribution to a Gumbel distribution when properly renormalized, and (ii it is asymptotically independent of the interference. Using these properties, we derive the distribution of the best signal quality. Furthermore, an optimized random cell scanning scheme is proposed, based on the evaluation of the optimal number of sites to be scanned for maximizing the user data throughput.

  16. Small-Signal Stability Analysis of Inverter-Fed Power Systems Using Component Connection Method

    DEFF Research Database (Denmark)

    Wang, Yanbo; Wang, Xiongfei; Blaabjerg, Frede

    2018-01-01

    The small time constants of power electronics devices lead to dynamic couplings with the electromagnetic transients of power networks, and thus complicate the modeling and stability analysis of power-electronics-based power systems. This paper presents a computationally-efficient approach to asse...

  17. High-throughput screening identifies small molecules that bind to the RAS:SOS:RAS complex and perturb RAS signaling.

    Science.gov (United States)

    Burns, Michael C; Howes, Jennifer E; Sun, Qi; Little, Andrew J; Camper, DeMarco V; Abbott, Jason R; Phan, Jason; Lee, Taekyu; Waterson, Alex G; Rossanese, Olivia W; Fesik, Stephen W

    2018-05-01

    K-RAS is mutated in approximately 30% of human cancers, resulting in increased RAS signaling and tumor growth. Thus, RAS is a highly validated therapeutic target, especially in tumors of the pancreas, lung and colon. Although directly targeting RAS has proven to be challenging, it may be possible to target other proteins involved in RAS signaling, such as the guanine nucleotide exchange factor Son of Sevenless (SOS). We have previously reported on the discovery of small molecules that bind to SOS1, activate SOS-mediated nucleotide exchange on RAS, and paradoxically inhibit ERK phosphorylation (Burns et al., PNAS, 2014). Here, we describe the discovery of additional, structurally diverse small molecules that also bind to SOS1 in the same pocket and elicit similar biological effects. We tested >160,000 compounds in a fluorescence-based assay to assess their effects on SOS-mediated nucleotide exchange. X-Ray structures revealed that these small molecules bind to the CDC25 domain of SOS1. Compounds that elicited high levels of nucleotide exchange activity in vitro increased RAS-GTP levels in cells, and inhibited phospho ERK levels at higher treatment concentrations. The identification of structurally diverse SOS1 binding ligands may assist in the discovery of new molecules designed to target RAS-driven tumors. Copyright © 2018 Elsevier Inc. All rights reserved.

  18. TUSC3 induces autophagy in human non-small cell lung cancer cells through Wnt/β-catenin signaling.

    Science.gov (United States)

    Peng, Yun; Cao, Jun; Yao, Xiao-Yi; Wang, Jian-Xin; Zhong, Mei-Zuo; Gan, Ping-Ping; Li, Jian-Huang

    2017-08-08

    We investigated the effects of tumor suppressor candidate 3 ( TUSC3 ) on autophagy in human non-small cell lung cancer (NSCLC) cells. A total of 118 NSCLC patients (88 males and 30 females) who underwent surgery at our institute were enrolled in the study. Immunohistochemical analysis revealed that TUSC3 protein expression was lower in NSCLC specimens than adjacent normal tissue. Correspondingly, there was greater methylation of TUSC3 in NSCLC than adjacent normal tissue. After transient transfection of A549 NSCLC cells with constructs designed to up-regulate or down-regulate TUSC3 expression, we analyzed the effects of inhibiting the Wnt pathway (XAV939) and autophagy (chloroquine, CQ) on the behavior of NSCLC cells. We also performed TOP/FOP-Flash reporter assays, MTT assays, Annexin V-FITC/propidium iodide staining, and acridine orange staining to evaluate Wnt/β-catenin signaling, cell proliferation, apoptosis, and autophagy, respectively. Expression of Wnt/β-catenin pathway components and autophagy-related proteins was analyzed using qRT-PCR and Western blotting. We found that TUSC3 inhibited cell proliferation and promoted both apoptosis and autophagy in A549 cells. In addition, TUSC3 increased expression of autophagy-related proteins. It also increased expression of Wnt/β-catenin signaling pathway components and promoted nuclear transfer of β-catenin, resulting in activation of Wnt/β-catenin signaling. TUSC3 thus induces autophagy in human NSCLC cells through activation of the Wnt/β-catenin signaling pathway.

  19. Improvements to the extraction of an AlGaN/GaN HEMT small-signal model

    International Nuclear Information System (INIS)

    Pu Yan; Pang Lei; Wang Liang; Chen Xiaojuan; Li Chengzhan; Liu Xinyu

    2009-01-01

    The accurate extraction of AlGaN/GaN HEMT small-signal models, which is an important step in large-signal modeling, can exactly reflect the microwave performance of the physical structure of the device. A new method of extracting the parasitic elements is presented, and an open dummy structure is introduced to obtain the parasitic capacitances. With a Schottky resistor in the gate, a new method is developed to extract R g . In order to characterize the changes of the depletion region under various drain voltages, the drain delay factor is involved in the output conductance of the device. Compared to the traditional method, the fitting of S 11 and S 22 is improved, and f T and f max can be better predicted. The validity of the proposed method is verified with excellent correlation between the measured and simulated S-parameters in the range of 0.1 to 26.1 GHz. (semiconductor devices)

  20. Signal and data processing of small targets 1989; Proceedings of the Meeting, Orlando, FL, Mar. 27-29, 1989

    Science.gov (United States)

    Drummond, Oliver E. (Editor)

    1989-01-01

    The present conference on digital signal processing, association and filtering techniques, and multiple-sensor/multiple-tracking techniques, discusses single-frame velocity estimation, efficient target extraction for laser radar imagery, precision target tracking for small extended objects, IR clutter partitioning for matched filter design, the maximum-likelihood approach to gamma circumvention, position estimation for optical point targets using staring detector arrays, and a multiple-scan signal processing technique for area-moving target indication. Also discussed are a proportional integral estimator, the prediction of track purity in tracking performance evaluations, synchronization and fault-tolerance in a distributed tracker, the benefits of soft sensors and probabilistic fusion, and testing track initiation algorithms fusing two-dimensional tracks.

  1. Can we use PCA to detect small signals in noisy data?

    Science.gov (United States)

    Spiegelberg, Jakob; Rusz, Ján

    2017-01-01

    Principal component analysis (PCA) is among the most commonly applied dimension reduction techniques suitable to denoise data. Focusing on its limitations to detect low variance signals in noisy data, we discuss how statistical and systematical errors occur in PCA reconstructed data as a function of the size of the data set, which extends the work of Lichtert and Verbeeck, (2013) [16]. Particular attention is directed towards the estimation of bias introduced by PCA and its influence on experiment design. Aiming at the denoising of large matrices, nullspace based denoising (NBD) is introduced. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. A small animal PET based on GAPDs and charge signal transmission approach for hybrid PET-MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Jihoon; Choi, Yong; Hong, Key Jo; Hu, Wei; Jung, Jin Ho; Huh, Yoonsuk [Department of Electronic Engineering, Sogang University, 1 Shinsu-Dong, Mapo-Gu, Seoul 121-742 (Korea, Republic of); Kim, Byung-Tae, E-mail: ychoi.image@gmail.com [Department of Nuclear Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-Dong, Gangnam-Gu, Seoul 135-710 (Korea, Republic of)

    2011-08-15

    Positron emission tomography (PET) employing Geiger-mode avalanche photodiodes (GAPDs) and charge signal transmission approach was developed for small animal imaging. Animal PET contained 16 LYSO and GAPD detector modules that were arranged in a 70 mm diameter ring with an axial field of view of 13 mm. The GAPDs charge output signals were transmitted to a preamplifier located remotely using 300 cm flexible flat cables. The position decoder circuits (PDCs) were used to multiplex the PET signals from 256 to 4 channels. The outputs of the PDCs were digitized and further-processed in the data acquisition unit. The cross-compatibilities of the PET detectors and MRI were assessed outside and inside the MRI. Experimental studies of the developed full ring PET were performed to examine the spatial resolution and sensitivity. Phantom and mouse images were acquired to examine the imaging performance. The mean energy and time resolution of the PET detector were 17.6% and 1.5 ns, respectively. No obvious degradation on PET and MRI was observed during simultaneous PET-MRI data acquisition. The measured spatial resolution and sensitivity at the CFOV were 2.8 mm and 0.7%, respectively. In addition, a 3 mm diameter line source was clearly resolved in the hot-sphere phantom images. The reconstructed transaxial PET images of the mouse brain and tumor displaying the glucose metabolism patterns were imaged well. These results demonstrate GAPD and the charge signal transmission approach can allow the development of high performance small animal PET with improved MR compatibility.

  3. ANALYSIS OF MONTE CARLO SIMULATION SAMPLING TECHNIQUES ON SMALL SIGNAL STABILITY OF WIND GENERATOR- CONNECTED POWER SYSTEM

    Directory of Open Access Journals (Sweden)

    TEMITOPE RAPHAEL AYODELE

    2016-04-01

    Full Text Available Monte Carlo simulation using Simple Random Sampling (SRS technique is popularly known for its ability to handle complex uncertainty problems. However, to produce a reasonable result, it requires huge sample size. This makes it to be computationally expensive, time consuming and unfit for online power system applications. In this article, the performance of Latin Hypercube Sampling (LHS technique is explored and compared with SRS in term of accuracy, robustness and speed for small signal stability application in a wind generator-connected power system. The analysis is performed using probabilistic techniques via eigenvalue analysis on two standard networks (Single Machine Infinite Bus and IEEE 16–machine 68 bus test system. The accuracy of the two sampling techniques is determined by comparing their different sample sizes with the IDEAL (conventional. The robustness is determined based on a significant variance reduction when the experiment is repeated 100 times with different sample sizes using the two sampling techniques in turn. Some of the results show that sample sizes generated from LHS for small signal stability application produces the same result as that of the IDEAL values starting from 100 sample size. This shows that about 100 sample size of random variable generated using LHS method is good enough to produce reasonable results for practical purpose in small signal stability application. It is also revealed that LHS has the least variance when the experiment is repeated 100 times compared to SRS techniques. This signifies the robustness of LHS over that of SRS techniques. 100 sample size of LHS produces the same result as that of the conventional method consisting of 50000 sample size. The reduced sample size required by LHS gives it computational speed advantage (about six times over the conventional method.

  4. Small-Signal Modeling, Analysis and Testing of Parallel Three-Phase-Inverters with A Novel Autonomous Current Sharing Controller

    DEFF Research Database (Denmark)

    Guan, Yajuan; Quintero, Juan Carlos Vasquez; Guerrero, Josep M.

    2015-01-01

    A novel simple and effective autonomous currentsharing controller for parallel three-phase inverters is employed in this paper. The novel controller is able to endow to the system high speed response and precision in contrast to the conventional droop control as it does not require calculating any...... active or reactive power, instead it uses a virtual impedance loop and a SFR phase-locked loop. The small-signal model of the system was developed for the autonomous operation of inverter-based microgrid with the proposed controller. The developed model shows large stability margin and fast transient...

  5. Attitude determination for small satellites using GPS signal-to-noise ratio

    Science.gov (United States)

    Peters, Daniel

    An embedded system for GPS-based attitude determination (AD) using signal-to-noise (SNR) measurements was developed for CubeSat applications. The design serves as an evaluation testbed for conducting ground based experiments using various computational methods and antenna types to determine the optimum AD accuracy. Raw GPS data is also stored to non-volatile memory for downloading and post analysis. Two low-power microcontrollers are used for processing and to display information on a graphic screen for real-time performance evaluations. A new parallel inter-processor communication protocol was developed that is faster and uses less power than existing standard protocols. A shorted annular patch (SAP) antenna was fabricated for the initial ground-based AD experiments with the testbed. Static AD estimations with RMS errors in the range of 2.5° to 4.8° were achieved over a range of off-zenith attitudes.

  6. Consequence and impact of electric utility industry restructuring on transient stability and small-signal stability analysis

    International Nuclear Information System (INIS)

    Vittal, V.

    2000-01-01

    The electric utility industry is undergoing unprecedented changes in its structure worldwide. With the advent of an open market environment and competition in the industry, and restructuring of the industry into separate generation, transmission, and distribution entities, new issues in power system operation and planning are inevitable. One of the major consequences of this new electric utility environment is the greater emphasis on reliability and secure operation of the power system. This paper examines the impact of restructuring on power system dynamic analysis. It specifically addresses issues related to transient stability analysis and small-signal stability analysis. Four major topics to examine the effect on the nature of studies conducted are considered. These topics are (1) system adequacy and security, (2) system modeling data requirements, (3) system protection and control, and (4) system restoration. The consequences and impact of each of these topics on the nature of the studies conducted are examined and discussed. The emphasis on greater reliability has led to a clearer enunciation of standards, measurements, and guides in some countries. These requirements will result in: (1) more measurements on existing systems, (2) rigorous analysis of transient stability and small-signal stability to determine operating limits and plan systems, (3) greater emphasis on studies to verify coordination and proper performance of protection and controls, and (4) development of a detailed plan for system restoration in the case of wide-spread outages

  7. CdTe amplification nanoplatforms capped with thioglycolic acid for electrochemical aptasensing of ultra-traces of ATP

    Energy Technology Data Exchange (ETDEWEB)

    Shamsipur, Mojtaba, E-mail: mshamsipur@yahoo.com [Department of Chemistry, Razi University, P.O. Box 67149-67346, Kermanshah (Iran, Islamic Republic of); Farzin, Leila [Department of Analytical Chemistry, School of Chemistry, College of Science, University of Tehran, P.O. Box 14174-66191, Tehran (Iran, Islamic Republic of); Tabrizi, Mahmoud Amouzadeh [Research Center for Science and Technology in Medicine,Tehran University of Medical Sciences, P.O. Box 14197-33131, Tehran (Iran, Islamic Republic of); Shanehsaz, Maryam [Analytical Chemistry Research Laboratory, Mobin Shimi Azma Company, P.O. Box 14768-44949, Tehran (Iran, Islamic Republic of)

    2016-12-01

    A “signal off” voltammetric aptasensor was developed for the sensitive and selective detection of ultra-low levels of adenosine triphosphate (ATP). For this purpose, a new strategy based on the principle of recognition-induced switching of aptamers from DNA/DNA duplex to DNA/target complex was designed using thioglycolic acid (TGA)-capped CdTe quantum dots (QDs) as the signal amplifying nano-platforms. Owing to the small size, high surface-to-volume ratio and good conductivity, quantum dots were immobilized on the electrode surface for signal amplification. In this work, methylene blue (MB) adsorbed to DNA was used as a sensitive redox reporter. The intensity of voltammetric signal of MB was found to decrease linearly upon ATP addition over a concentration range of 0.1 nM to 1.6 μM with a correlation coefficient of 0.9924. Under optimized conditions, the aptasensor was able to selectively detect ATP with a limit of detection of 45 pM at 3σ. The results also demonstrated that the QDs-based amplification strategy could be feasible for ATP assay and presented a potential universal method for other small biomolecular aptasensors. - Highlights: • A “signal off” voltammetric aptasensor has been reported. • The DPV technique was used for the determination of ATP. • The determination of ATP up to 1.6 μM with a detection limit 45 pM, respectively.

  8. Small molecule inhibitors of the Candida albicans budded-to-hyphal transition act through multiple signaling pathways.

    Directory of Open Access Journals (Sweden)

    John Midkiff

    Full Text Available The ability of the pathogenic yeast Candida albicans to interconvert between budded and hyphal growth states, herein termed the budded-to-hyphal transition (BHT, is important for C. albicans development and virulence. The BHT is under the control of multiple cell signaling pathways that respond to external stimuli, including nutrient availability, high temperature, and pH. Previous studies identified 21 small molecules that could inhibit the C. albicans BHT in response to carbon limitation in Spider media. However, the studies herein show that the BHT inhibitors had varying efficacies in other hyphal-inducing media, reflecting their varying abilities to block signaling pathways associated with the different media. Chemical epistasis analyses suggest that most, but not all, of the BHT inhibitors were acting through either the Efg1 or Cph1 signaling pathways. Notably, the BHT inhibitor clozapine, a FDA-approved drug used to treat atypical schizophrenia by inhibiting G-protein-coupled dopamine receptors in the brain, and several of its functional analogs were shown to act at the level of the Gpr1 G-protein-coupled receptor. These studies are the first step in determining the target and mechanism of action of these BHT inhibitors, which may have therapeutic anti-fungal utility in the future.

  9. Unique players in the BMP pathway: Small C-terminal domain phosphatases dephosphorylate Smad1 to attenuate BMP signaling

    Science.gov (United States)

    Knockaert, Marie; Sapkota, Gopal; Alarcón, Claudio; Massagué, Joan; Brivanlou, Ali H.

    2006-01-01

    Smad transcription factors are key signal transducers for the TGF-β/bone morphogenetic protein (BMP) family of cytokines and morphogens. C-terminal serine phosphorylation by TGF-β and BMP membrane receptors drives Smads into the nucleus as transcriptional regulators. Dephosphorylation and recycling of activated Smads is an integral part of this process, which is critical for agonist sensing by the cell. However, the nuclear phosphatases involved have remained unknown. Here we provide functional, biochemical, and embryological evidence identifying the SCP (small C-terminal domain phosphatase) family of nuclear phosphatases as mediators of Smad1 dephosphorylation in the BMP signaling pathway in vertebrates. Xenopus SCP2/Os4 inhibits BMP activity in the presumptive ectoderm and leads to neuralization. In Xenopus embryos, SCP2/Os4 and human SCP1, 2, and 3 cause selective dephosphorylation of Smad1 compared with Smad2, inhibiting BMP- and Smad1-dependent transcription and leading to the induction of the secondary dorsal axis. In human cells, RNAi-mediated depletion of SCP1 and SCP2 increases the extent and duration of Smad1 phosphorylation in response to BMP, the transcriptional action of Smad1, and the strength of endogenous BMP gene responses. The present identification of the SCP family as Smad C-terminal phosphatases sheds light on the events that attenuate Smad signaling and reveals unexpected links to the essential phosphatases that control RNA polymerase II in eukaryotes. PMID:16882717

  10. Evidence of high-elevation amplification versus Arctic amplification.

    Science.gov (United States)

    Wang, Qixiang; Fan, Xiaohui; Wang, Mengben

    2016-01-12

    Elevation-dependent warming in high-elevation regions and Arctic amplification are of tremendous interest to many scientists who are engaged in studies in climate change. Here, using annual mean temperatures from 2781 global stations for the 1961-2010 period, we find that the warming for the world's high-elevation stations (>500 m above sea level) is clearly stronger than their low-elevation counterparts; and the high-elevation amplification consists of not only an altitudinal amplification but also a latitudinal amplification. The warming for the high-elevation stations is linearly proportional to the temperature lapse rates along altitudinal and latitudinal gradients, as a result of the functional shape of Stefan-Boltzmann law in both vertical and latitudinal directions. In contrast, neither altitudinal amplification nor latitudinal amplification is found within the Arctic region despite its greater warming than lower latitudes. Further analysis shows that the Arctic amplification is an integrated part of the latitudinal amplification trend for the low-elevation stations (≤500 m above sea level) across the entire low- to high-latitude Northern Hemisphere, also a result of the mathematical shape of Stefan-Boltzmann law but only in latitudinal direction.

  11. Modeling the response of small myelinated axons in a compound nerve to kilohertz frequency signals.

    Science.gov (United States)

    Pelot, N A; Behrend, C E; Grill, W M

    2017-08-01

    There is growing interest in electrical neuromodulation of peripheral nerves, particularly autonomic nerves, to treat various diseases. Electrical signals in the kilohertz frequency (KHF) range can produce different responses, including conduction block. For example, EnteroMedics' vBloc ® therapy for obesity delivers 5 kHz stimulation to block the abdominal vagus nerves, but the mechanisms of action are unclear. We developed a two-part computational model, coupling a 3D finite element model of a cuff electrode around the human abdominal vagus nerve with biophysically-realistic electrical circuit equivalent (cable) model axons (1, 2, and 5.7 µm in diameter). We developed an automated algorithm to classify conduction responses as subthreshold (transmission), KHF-evoked activity (excitation), or block. We quantified neural responses across kilohertz frequencies (5-20 kHz), amplitudes (1-8 mA), and electrode designs. We found heterogeneous conduction responses across the modeled nerve trunk, both for a given parameter set and across parameter sets, although most suprathreshold responses were excitation, rather than block. The firing patterns were irregular near transmission and block boundaries, but otherwise regular, and mean firing rates varied with electrode-fibre distance. Further, we identified excitation responses at amplitudes above block threshold, termed 're-excitation', arising from action potentials initiated at virtual cathodes. Excitation and block thresholds decreased with smaller electrode-fibre distances, larger fibre diameters, and lower kilohertz frequencies. A point source model predicted a larger fraction of blocked fibres and greater change of threshold with distance as compared to the realistic cuff and nerve model. Our findings of widespread asynchronous KHF-evoked activity suggest that conduction block in the abdominal vagus nerves is unlikely with current clinical parameters. Our results indicate that compound neural or downstream muscle

  12. Modeling the response of small myelinated axons in a compound nerve to kilohertz frequency signals

    Science.gov (United States)

    Pelot, N. A.; Behrend, C. E.; Grill, W. M.

    2017-08-01

    Objective. There is growing interest in electrical neuromodulation of peripheral nerves, particularly autonomic nerves, to treat various diseases. Electrical signals in the kilohertz frequency (KHF) range can produce different responses, including conduction block. For example, EnteroMedics’ vBloc® therapy for obesity delivers 5 kHz stimulation to block the abdominal vagus nerves, but the mechanisms of action are unclear. Approach. We developed a two-part computational model, coupling a 3D finite element model of a cuff electrode around the human abdominal vagus nerve with biophysically-realistic electrical circuit equivalent (cable) model axons (1, 2, and 5.7 µm in diameter). We developed an automated algorithm to classify conduction responses as subthreshold (transmission), KHF-evoked activity (excitation), or block. We quantified neural responses across kilohertz frequencies (5-20 kHz), amplitudes (1-8 mA), and electrode designs. Main results. We found heterogeneous conduction responses across the modeled nerve trunk, both for a given parameter set and across parameter sets, although most suprathreshold responses were excitation, rather than block. The firing patterns were irregular near transmission and block boundaries, but otherwise regular, and mean firing rates varied with electrode-fibre distance. Further, we identified excitation responses at amplitudes above block threshold, termed ‘re-excitation’, arising from action potentials initiated at virtual cathodes. Excitation and block thresholds decreased with smaller electrode-fibre distances, larger fibre diameters, and lower kilohertz frequencies. A point source model predicted a larger fraction of blocked fibres and greater change of threshold with distance as compared to the realistic cuff and nerve model. Significance. Our findings of widespread asynchronous KHF-evoked activity suggest that conduction block in the abdominal vagus nerves is unlikely with current clinical parameters. Our

  13. Efficient Audio Power Amplification - Challenges

    DEFF Research Database (Denmark)

    Andersen, Michael Andreas E.

    2005-01-01

    For more than a decade efficient audio power amplification has evolved and today switch-mode audio power amplification in various forms are the state-of-the-art. The technical steps that lead to this evolution are described and in addition many of the challenges still to be faced and where...

  14. Efficient audio power amplification - challenges

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, Michael A.E.

    2005-07-01

    For more than a decade efficient audio power amplification has evolved and today switch-mode audio power amplification in various forms are the state-of-the-art. The technical steps that lead to this evolution are described and in addition many of the challenges still to be faced and where extensive research and development are needed is covered. (au)

  15. Optical parametric amplification and oscillation assisted by low-frequency stimulated emission

    OpenAIRE

    Longhi, Stefano

    2016-01-01

    Optical parametric amplification/oscillation provide a powerful tool for coherent light generation in spectral regions inaccessible to lasers. Parametric gain is based on a frequency {\\it down-conversion} process, and thus it can not be realized for signal waves at a frequency $\\omega_3$ {\\it higher} than the frequency of the pump wave $\\omega_1$. In this work we suggest a route toward the realization of {\\it up-conversion} optical parametric amplification and oscillation, i.e. amplification ...

  16. Millimeter-wave small-signal modeling with optimizing sensitive-parameters for metamorphic high electron mobility transistors

    International Nuclear Information System (INIS)

    Moon, S-W; Baek, Y-H; Han, M; Rhee, J-K; Kim, S-D; Oh, J-H

    2010-01-01

    In this paper, we present a simple and reliable technique for determining the small-signal equivalent circuit model parameters of the 0.1 µm metamorphic high electron mobility transistors (MHEMTs) in a millimeter-wave frequency range. The initial eight extrinsic parameters of the MHEMT are extracted using two S-parameter (scattering parameter) sets measured under the pinched-off and zero-biased cold field-effect transistor conditions by avoiding the forward gate biasing. Furthermore, highly calibration-sensitive values of the R s , L s and C pd are optimized by using a gradient optimization method to improve the modeling accuracy. The accuracy enhancement of this procedure is successfully verified with an excellent correlation between the measured and calculated S-parameters up to 65 GHz

  17. Small-Signal Analysis of Autonomous Hybrid Distributed Generation Systems in Presence of Ultracapacitor and Tie-Line Operation

    Science.gov (United States)

    Ray, Prakash K.; Mohanty, Soumya R.; Kishor, Nand

    2010-07-01

    This paper presents small-signal analysis of isolated as well as interconnected autonomous hybrid distributed generation system for sudden variation in load demand, wind speed and solar radiation. The hybrid systems comprise of different renewable energy resources such as wind, photovoltaic (PV) fuel cell (FC) and diesel engine generator (DEG) along with the energy storage devices such as flywheel energy storage system (FESS) and battery energy storage system (BESS). Further ultracapacitors (UC) as an alternative energy storage element and interconnection of hybrid systems through tie-line is incorporated into the system for improved performance. A comparative assessment of deviation of frequency profile for different hybrid systems in the presence of different storage system combinations is carried out graphically as well as in terms of the performance index (PI), ie integral square error (ISE). Both qualitative and quantitative analysis reflects the improvements of the deviation in frequency profiles in the presence of the ultracapacitors (UC) as compared to other energy storage elements.

  18. Current collapse modeling in AlGaN/GaN HEMT using small signal equivalent circuit for high power application

    Science.gov (United States)

    Nirmal, D.; Arivazhagan, L.; Fletcher, A. S. Augustine; Ajayan, J.; Prajoon, P.

    2018-01-01

    In this paper, the drain current collapse in AlGaN/GaN High Electron Mobility Transistor (HEMT) with field plate engineering is investigated. A small signal equivalent circuit of AlGaN/GaN HEMT is developed and a new drain current model is derived. This model is useful to correlate the impact of intrinsic capacitance and conductance on drain current collapse. The proposed device suppressed the current collapse phenomena by 10% compared with the conventional AlGaN/GaN HEMT. Moreover, the DC characteristics of the simulated device shows a drain current of 900 mA/mm, breakdown voltage of 291 V and transconductance of 175 mS/mm. Besides, the intrinsic capacitance and conductance parameters are extracted and its impact on drain current is analysed. Finally, the simulation results obtained were in compliance with the derived mathematical model of AlGaN/GaN HEMT.

  19. An aptasensor for staphylococcus aureus based on nicking enzyme amplification reaction and rolling circle amplification.

    Science.gov (United States)

    Xu, Jingguo; Guo, Jia; Maina, Sarah Wanjiku; Yang, Yumeng; Hu, Yimin; Li, Xuanxuan; Qiu, Jiarong; Xin, Zhihong

    2018-05-15

    An ultra-sensitive aptamer-based biosensor for the detection of staphylococcus aureus was established by adopting the nicking enzyme amplification reaction (NEAR) and the rolling circle amplification (RCA) technologies. Aptamer-probe (AP), containing an aptamer and a probe sequence, was developed to act as the recognition unit of the biosensor, which was specifically bound to S. aureus. The probe was released from AP and initiated into the subsequent DNA amplification reactions where S. aureus was present, converting the detection of S. aureus to the investigation of probe oligonucleotide. The RCA amplification products contained a G-quadruplex motif and formed a three dimensional structure in presence of hemin. The G4/hemin complex showed horseradish peroxidase (HRP)-mimic activity and catalyzed the chemiluminescence reaction of luminol mediated by H 2 O 2 . The results showed that the established biosensor could detect S. aureus specifically with a good linear correlation at 5-10 4  CFU/mL. The signal values based on NEAR-RCA two-step cycle were boosted acutely, much higher than that relied on one-cycle magnification. The limit of detection (LoD) was determined to be as low as 5 CFU/mL. The established aptasensor exhibited a good discrimination of living against dead S. aureus, and can be applied to detect S. aureus in the food industry. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Redefining the functional roles of the gastrointestinal migrating motor complex and motilin in small bacterial overgrowth and hunger signaling.

    Science.gov (United States)

    Deloose, Eveline; Tack, Jan

    2016-02-15

    During the fasting state the upper gastrointestinal tract exhibits a specific periodic migrating contraction pattern that is known as the migrating motor complex (MMC). Three different phases can be distinguished during the MMC. Phase III of the MMC is the most active of the three and can start either in the stomach or small intestine. Historically this pattern was designated to be the housekeeper of the gut since disturbances in the pattern were associated with small intestinal bacterial overgrowth; however, its role in the involvement of hunger sensations was already hinted in the beginning of the 20th century by both Cannon (Cannon W, Washburn A. Am J Physiol 29: 441-454, 1912) and Carlson (Carlson A. The Control of Hunger in Health and Disease. Chicago, IL: Univ. of Chicago Press, 1916). The discovery of motilin in 1973 shed more light on the control mechanisms of the MMC. Motilin plasma levels fluctuate together with the phases of the MMC and induce phase III contractions with a gastric onset. Recent research suggests that these motilin-induced phase III contractions signal hunger in healthy subjects and that this system is disturbed in morbidly obese patients. This minireview describes the functions of the MMC in the gut and its regulatory role in controlling hunger sensations. Copyright © 2016 the American Physiological Society.

  1. RNA amplification for successful gene profiling analysis

    Directory of Open Access Journals (Sweden)

    Wang Ena

    2005-07-01

    Full Text Available Abstract The study of clinical samples is often limited by the amount of material available to study. While proteins cannot be multiplied in their natural form, DNA and RNA can be amplified from small specimens and used for high-throughput analyses. Therefore, genetic studies offer the best opportunity to screen for novel insights of human pathology when little material is available. Precise estimates of DNA copy numbers in a given specimen are necessary. However, most studies investigate static variables such as the genetic background of patients or mutations within pathological specimens without a need to assess proportionality of expression among different genes throughout the genome. Comparative genomic hybridization of DNA samples represents a crude exception to this rule since genomic amplification or deletion is compared among different specimens directly. For gene expression analysis, however, it is critical to accurately estimate the proportional expression of distinct RNA transcripts since such proportions directly govern cell function by modulating protein expression. Furthermore, comparative estimates of relative RNA expression at different time points portray the response of cells to environmental stimuli, indirectly informing about broader biological events affecting a particular tissue in physiological or pathological conditions. This cognitive reaction of cells is similar to the detection of electroencephalographic patterns which inform about the status of the brain in response to external stimuli. As our need to understand human pathophysiology at the global level increases, the development and refinement of technologies for high fidelity messenger RNA amplification have become the focus of increasing interest during the past decade. The need to increase the abundance of RNA has been met not only for gene specific amplification, but, most importantly for global transcriptome wide, unbiased amplification. Now gene

  2. Optimization of an Optical Parametric Chirped Pulse Amplification System for the OMEGA EP Laser System

    International Nuclear Information System (INIS)

    Begishev, I.; Bagnoud, V.; Guardalben, M.; Waxer, L.; Puth, J.; Zuegel, J.

    2003-01-01

    OAK B204 We report on the experimental achievements of the optical parametric chirped-pulse amplification (OPCPA) system, including 29% pump-to-signal conversion efficiency and 107 gain using two LBO crystals configured as a single amplification stage. Temporal and spatial shaping of the pump laser pulse is required to achieve both high-gain and high-conversion efficiency

  3. DNAzyme Feedback Amplification: Relaying Molecular Recognition to Exponential DNA Amplification.

    Science.gov (United States)

    Liu, Meng; Yin, Qingxin; McConnell, Erin M; Chang, Yangyang; Brennan, John D; Li, Yingfu

    2018-03-26

    Technologies capable of linking DNA amplification to molecular recognition are very desirable for ultrasensitive biosensing applications. We have developed a simple but powerful isothermal DNA amplification method, termed DNAzyme feedback amplification (DFA), that is capable of relaying molecular recognition to exponential DNA amplification. The method incorporates both an RNA-cleaving DNAzyme (RCD) and rolling circle amplification (RCA) carried out by a special DNA polymerase using a circular DNA template. DFA begins with a stimulus-dependent RCA reaction, producing tandemly linked RCDs in long-chain DNA products. These RCDs cleave an RNA-containing DNA sequence to form additional primers that hybridize to the circular DNA molecule, giving rise to DNA assemblies that act as the new inputs for RCA. The RCA reaction and the cleavage event keep on feeding each other autonomously, resulting in exponential growth of repetitive DNA sequences that can be easily detected. This method can be used for the detection of both nucleic acid based targets and non-nucleic acid analytes. In this article, we discuss the conceptual framework of the feedback amplification approach, the essential features of this method as well as remaining challenges and possible solutions. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Small signal audio design

    CERN Document Server

    Self, Douglas

    2014-01-01

    Learn to use inexpensive and readily available parts to obtain state-of-the-art performance in all the vital parameters of noise, distortion, crosstalk and so on. With ample coverage of preamplifiers and mixers and a new chapter on headphone amplifiers, this practical handbook provides an extensive repertoire of circuits that can be put together to make almost any type of audio system.A resource packed full of valuable information, with virtually every page revealing nuggets of specialized knowledge not found elsewhere. Essential points of theory that bear on practical performance are lucidly

  5. Next generation Chirped Pulse Amplification

    Energy Technology Data Exchange (ETDEWEB)

    Nees, J; Biswal, S; Mourou, G [Univ. Michigan, Center for Ultrafast Optical Science, Ann Arbor, MI (United States); Nishimura, Akihiko; Takuma, Hiroshi

    1998-03-01

    The limiting factors of Chirped Pulse Amplification (CPA) are discussed and experimental results of CPA in Yb:glass regenerative amplifier are given. Scaling of Yb:glass to the petawatt level is briefly discussed. (author)

  6. Amplification Effects and Unconventional Monetary Policies

    Directory of Open Access Journals (Sweden)

    Cécile BASTIDON GILLES

    2012-02-01

    Full Text Available Global financial crises trigger off amplification effects, which allow relatively small shocks to propagate through the whole financial system. For this reason, the range of Central banks policies is now widening beyond conventional monetary policies and lending of last resort. The aim of this paper is to establish a rule for this practice. The model is based on the formalization of funding conditions in various types of markets. We conduct a comprehensive analysis of the “unconventional monetary policies”, and especially quantify government bonds purchases by the Central bank.

  7. Reverse-phase phosphoproteome analysis of signaling pathways induced by Rift valley fever virus in human small airway epithelial cells.

    Directory of Open Access Journals (Sweden)

    Taissia G Popova

    Full Text Available Rift valley fever virus (RVFV infection is an emerging zoonotic disease endemic in many countries of sub-Saharan Africa and in Egypt. In this study we show that human small airway epithelial cells are highly susceptible to RVFV virulent strain ZH-501 and the attenuated strain MP-12. We used the reverse-phase protein arrays technology to identify phosphoprotein signaling pathways modulated during infection of cultured airway epithelium. ZH-501 infection induced activation of MAP kinases (p38, JNK and ERK and downstream transcriptional factors [STAT1 (Y701, ATF2 (T69/71, MSK1 (S360 and CREB (S133]. NF-κB phosphorylation was also increased. Activation of p53 (S15, S46 correlated with the increased levels of cleaved effector caspase-3, -6 and -7, indicating activation of the extrinsic apoptotic pathway. RVFV infection downregulated phosphorylation of a major anti-apoptotic regulator of survival pathways, AKT (S473, along with phosphorylation of FOX 01/03 (T24/31 which controls cell cycle arrest downstream from AKT. Consistent with this, the level of apoptosis inhibitor XIAP was decreased. However, the intrinsic apoptotic pathway marker, caspase-9, demonstrated only a marginal activation accompanied by an increased level of the inhibitor of apoptosome formation, HSP27. Concentration of the autophagy marker, LC3B, which often accompanies the pro-survival signaling, was decreased. Cumulatively, our analysis of RVFV infection in lung epithelium indicated a viral strategy directed toward the control of cell apoptosis through a number of transcriptional factors. Analyses of MP-12 titers in challenged cells in the presence of MAPK inhibitors indicated that activation of p38 represents a protective cell response while ERK activation controls viral replication.

  8. Spin noise amplification and giant noise in optical microcavity

    Energy Technology Data Exchange (ETDEWEB)

    Ryzhov, I. I.; Poltavtsev, S. V.; Kozlov, G. G.; Zapasskii, V. S. [Spin-Optics Laboratory, St. Petersburg State University, 198504 St. Petersburg (Russian Federation); Kavokin, A. V. [Department of Physics and Astronomy, University of Southampton, Southampton SO17 1BJ (United Kingdom); Spin-Optics Laboratory, St. Petersburg State University, 198504 St. Petersburg (Russian Federation); Lagoudakis, P. V. [Department of Physics and Astronomy, University of Southampton, Southampton SO17 1BJ (United Kingdom)

    2015-06-14

    When studying the spin-noise-induced fluctuations of Kerr rotation in a quantum-well microcavity, we have found a dramatic increase of the noise signal (by more than two orders of magnitude) in the vicinity of anti-crossing of the polariton branches. The effect is explained by nonlinear optical instability of the microcavity giving rise to the light-power-controlled amplification of the polarization noise signal. In the framework of the developed model of built-in amplifier, we also interpret the nontrivial spectral and intensity-related properties of the observed noise signal below the region of anti-crossing of polariton branches. The discovered effect of optically controllable amplification of broadband polarization signals in microcavities in the regime of optical instability may be of interest for detecting weak oscillations of optical anisotropy in fundamental research and for other applications in optical information processing.

  9. Clinical development of galunisertib (LY2157299 monohydrate, a small molecule inhibitor of transforming growth factor-beta signaling pathway

    Directory of Open Access Journals (Sweden)

    Herbertz S

    2015-08-01

    Full Text Available Stephan Herbertz,1 J Scott Sawyer,2 Anja J Stauber,2 Ivelina Gueorguieva,3 Kyla E Driscoll,4 Shawn T Estrem,2 Ann L Cleverly,3 Durisala Desaiah,2 Susan C Guba,2 Karim A Benhadji,2 Christopher A Slapak,2 Michael M Lahn21Lilly Deutschland GmbH, Bad Homburg, Germany; 2Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA; 3Lilly Research Laboratories, Eli Lilly and Company, Windlesham, Surrey, UK; 4Lilly Research Laboratories, Eli Lilly and Company, New York, NY, USA Abstract: Transforming growth factor-beta (TGF-β signaling regulates a wide range of biological processes. TGF-β plays an important role in tumorigenesis and contributes to the hallmarks of cancer, including tumor proliferation, invasion and metastasis, inflammation, angiogenesis, and escape of immune surveillance. There are several pharmacological approaches to block TGF-β signaling, such as monoclonal antibodies, vaccines, antisense oligonucleotides, and small molecule inhibitors. Galunisertib (LY2157299 monohydrate is an oral small molecule inhibitor of the TGF-β receptor I kinase that specifically downregulates the phosphorylation of SMAD2, abrogating activation of the canonical pathway. Furthermore, galunisertib has antitumor activity in tumor-bearing animal models such as breast, colon, lung cancers, and hepatocellular carcinoma. Continuous long-term exposure to galunisertib caused cardiac toxicities in animals requiring adoption of a pharmacokinetic/pharmacodynamic-based dosing strategy to allow further development. The use of such a pharmacokinetic/pharmacodynamic model defined a therapeutic window with an appropriate safety profile that enabled the clinical investigation of galunisertib. These efforts resulted in an intermittent dosing regimen (14 days on/14 days off, on a 28-day cycle of galunisertib for all ongoing trials. Galunisertib is being investigated either as monotherapy or in combination with standard antitumor regimens (including nivolumab

  10. A large ungated TPC with GEM amplification

    Science.gov (United States)

    Berger, M.; Ball, M.; Fabbietti, L.; Ketzer, B.; Arora, R.; Beck, R.; Böhmer, F. V.; Chen, J.-C.; Cusanno, F.; Dørheim, S.; García, F.; Hehner, J.; Herrmann, N.; Höppner, C.; Kaiser, D.; Kis̆, M.; Kleipa, V.; Konorov, I.; Kunkel, J.; Kurz, N.; Leifels, Y.; Müllner, P.; Münzer, R.; Neubert, S.; Rauch, J.; Schmidt, C. J.; Schmitz, R.; Soyk, D.; Vandenbroucke, M.; Voss, B.; Walther, D.; Zmeskal, J.

    2017-10-01

    A Time Projection Chamber (TPC) is an ideal device for the detection of charged particle tracks in a large volume covering a solid angle of almost 4 π. The high density of hits on a given particle track facilitates the task of pattern recognition in a high-occupancy environment and in addition provides particle identification by measuring the specific energy loss for each track. For these reasons, TPCs with Multiwire Proportional Chamber (MWPC) amplification have been and are widely used in experiments recording heavy-ion collisions. A significant drawback, however, is the large dead time of the order of 1 ms per event generated by the use of a gating grid, which is mandatory to prevent ions created in the amplification region from drifting back into the drift volume, where they would severely distort the drift path of subsequent tracks. For experiments with higher event rates this concept of a conventional TPC operating with a triggered gating grid can therefore not be applied without a significant loss of data. A continuous readout of the signals is the more appropriate way of operation. This, however, constitutes a change of paradigm with considerable challenges to be met concerning the amplification region, the design and bandwidth of the readout electronics, and the data handling. A mandatory prerequisite for such an operation is a sufficiently good suppression of the ion backflow from the avalanche region, which otherwise limits the tracking and particle identification capabilities of such a detector. Gas Electron Multipliers (GEM) are a promising candidate to combine excellent spatial resolution with an intrinsic suppression of ions. In this paper we describe the design, construction and the commissioning of a large TPC with GEM amplification and without gating grid (GEM-TPC). The design requirements have driven innovations in the construction of a light-weight field-cage, a supporting media flange, the GEM amplification and the readout system, which are

  11. Scintillation light detectors with Neganov Luke amplification

    Science.gov (United States)

    Isaila, C.; Boslau, O.; Coppi, C.; Feilitzsch, F. v.; Goldstraß, P.; Jagemann, T.; Jochum, J.; Kemmer, J.; Lachenmaier, T.; Lanfranchi, J.-C.; Pahlke, A.; Potzel, W.; Rau, W.; Stark, M.; Wernicke, D.; Westphal, W.

    2006-04-01

    For an active suppression of the gamma and electron background in the Cryogenic Rare Event Search with Superconducting Thermometers (CRESST) dark matter experiment both phonons and scintillation light generated in a CaWO 4 crystal are detected simultaneously. The phonon signal is read out by a transition edge sensor (TES) on the CaWO 4 crystal. For light detection a silicon absorber equipped with a TES is employed. An efficient background discrimination requires very sensitive light detectors. The threshold can be improved by applying an electric field to the silicon crystal leading to an amplification of the thermal signal due to the Neganov-Luke effect. Measurements showing the improved sensitivity of the light detectors as well as future steps for reducing the observed extra noise will be presented.

  12. Proton density differences in signal characteristics of multiple sclerosis plaques versus white matter lesions of small vessel disease and vasculitis on high-field strength MR images

    International Nuclear Information System (INIS)

    Peyster, R.G.; Siegal, T.L.

    1990-01-01

    This paper determines if variations in signal intensity characteristics on multi-spin-echo images obtained with a high-field-strength magnet can be useful in differentiating demyelinating plaques of multiple sclerosis from other pathologic white matter processes due to small vessel disease and vasculities. Using the first of two multi-spin-echo images obtained with a General Electric 1.5-T magnet, the investigators compared signal intensity characteristics in 30 patients with a firm clinical diagnosis of multiple sclerosis versus a control group of 30 patients with a known clinical history of small-vessel disease and vasculitis are isodense to gray matter on proton-density images

  13. Small-signal analysis and particle-in-cell simulations of planar dielectric Cherenkov masers for use as high-frequency, moderate-power broadband amplifiers

    International Nuclear Information System (INIS)

    Carlsten, Bruce E.

    2002-01-01

    A small-signal gain analysis of the planar dielectric Cherenkov maser is presented. The analysis results in a Pierce gain solution, with three traveling-wave modes. The analysis shows that the dielectric Cherenkov maser has a remarkable broadband tuning ability near cutoff, while maintaining reasonable gain rates. Numerical simulations verifying the small-signal gain results are presented, using a particle-in-cell code adapted specifically for planar traveling-wave tubes. An instantaneous bandwidth is numerically shown to be very large, and saturated efficiency for a nominal high-power design is shown to be in the range of standard untapered traveling-wave tubes

  14. Signal and data processing of small targets 1990; Proceedings of the Meeting, Orlando, FL, Apr. 16-18, 1990

    Science.gov (United States)

    Drummond, Oliver E.

    Various papers on signal and data processing of small targets are presented. Individual topics addressed include: clutter rejection using multispectral processing, new sensor for automatic guidance, Doppler domain localized generalized-likelihood-ratio detector, linear filter for resolution of point sources, analysis of order-statistic filters for robust detection, distribution functions for additive Gaussian and gamma noise, temperature discrimination of closely space objects, knowledge-based tracking algorithm, detecting and tracking low-observable targets using IR, weak target detection using the entropy concept, measurement-based neural-net multitarget tracker, object-track closed-form solution in angle space, passive-sensor data association for tracking. Also discussed are: application of MHT to dim moving targets, automatic static covariance analysis with mathematica, neural network implementation of plot/track association, application of Bayesian networks to multitarget tracking, tracking clusters and extended objects with multiple sensors, target tracking by human operator, finite impulse response estimator, multitarget tracking using an extended Kalman filter, maneuvering target tracking using a two-state model algorithm, mixture reduction algorithms for target tracking in clutter, scene interpretation approach to high-level target tracking.

  15. Similar mitochondrial signaling responses to a single bout of continuous or small-sided-games-based exercise in sedentary men.

    Science.gov (United States)

    Mendham, Amy E; Duffield, Rob; Coutts, Aaron J; Marino, Frank E; Boyko, Andriy; McAinch, Andrew J; Bishop, David John

    2016-12-01

    This study assessed the mitochondrial related signaling responses to a single bout of noncontact, modified football (touch rugby), played as small-sided games (SSG), or cycling (CYC) exercise in sedentary, obese, middle-aged men. In a randomized, crossover design, nine middle-aged, sedentary, obese men completed two, 40-min exercise conditions (CYC and SSG) separated by a 21-day recovery period. Heart rate (HR) and ratings of perceived exertion (RPE) were collected during each bout. Needle biopsies from the vastus lateralis muscle were collected at rest and 30 and 240 min postexercise for analysis of protein content and phosphorylation (PGC-1α, SIRT1, p53, p53 Ser15 , AMPK, AMPK Thr172 , CAMKII, CAMKII Thr286 , p38MAPK, and p38MAPK Thr180/Tyr182 ) and mRNA expression (PGC-1α, p53, NRF1, NRF2, Tfam, and cytochrome c). A main effect of time effect for both conditions was evident for HR, RPE, and blood lactate (P 0.05). Both conditions increased PGC1-α protein and mRNA expression at 240 min (P 0.05). CYC increased p53 protein content at 240 min to a greater extent than SSG (P benefit for stimulating mitochondrial biogenesis. Differences between conditions regarding fluctuation in exercise intensity and type of muscle contraction may explain the increase of p53 and AMPK within CYC and not SSG (noncontact, modified football). Copyright © 2016 the American Physiological Society.

  16. Weak value amplification via second-order correlated technique

    International Nuclear Information System (INIS)

    Cui Ting; Huang Jing-Zheng; Zeng Gui-Hua; Liu Xiang

    2016-01-01

    We propose a new framework combining weak measurement and second-order correlated technique. The theoretical analysis shows that weak value amplification (WVA) experiment can also be implemented by a second-order correlated system. We then build two-dimensional second-order correlated function patterns for achieving higher amplification factor and discuss the signal-to-noise ratio influence. Several advantages can be obtained by our proposal. For instance, detectors with high resolution are not necessary. Moreover, detectors with low saturation intensity are available in WVA setup. Finally, type-one technical noise can be effectively suppressed. (paper)

  17. Isothermal amplification detection of nucleic acids by a double-nicked beacon.

    Science.gov (United States)

    Shi, Chao; Zhou, Meiling; Pan, Mei; Zhong, Guilin; Ma, Cuiping

    2016-03-01

    Isothermal and rapid amplification detection of nucleic acids is an important technology in environmental monitoring, foodborne pathogen detection, and point-of-care clinical diagnostics. Here we have developed a novel method of isothermal signal amplification for single-stranded DNA (ssDNA) detection. The ssDNA target could be used as an initiator, coupled with a double-nicked molecular beacon, to originate amplification cycles, achieving cascade signal amplification. In addition, the method showed good specificity and strong anti-jamming capability. Overall, it is a one-pot and isothermal strand displacement amplification method without the requirement of a stepwise procedure, which greatly simplifies the experimental procedure and decreases the probability of contamination of samples. With its advantages, the method would be very useful to detect nucleic acids in point-of-care or field use. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Signal detection

    International Nuclear Information System (INIS)

    Tholomier, M.

    1985-01-01

    In a scanning electron microscope, whatever is the measured signal, the same set is found: incident beam, sample, signal detection, signal amplification. The resulting signal is used to control the spot luminosity with the observer cathodoscope. This is synchronized with the beam scanning on the sample; on the cathodoscope, the image in secondary electrons, backscattered electrons,... of the sample surface is reconstituted. The best compromise must be found between a register time low enough to remove eventual variations (under the incident beam) of the nature of the observed phenomenon, and a good spatial resolution of the image and a signal-to-noise ratio high enough. The noise is one of the basic limitations of the scanning electron microscope performance. The whose measurement line must be optimized to reduce it [fr

  19. A ribonuclease coordinates siRNA amplification and mRNA cleavage during RNAi.

    Science.gov (United States)

    Tsai, Hsin-Yue; Chen, Chun-Chieh G; Conte, Darryl; Moresco, James J; Chaves, Daniel A; Mitani, Shohei; Yates, John R; Tsai, Ming-Daw; Mello, Craig C

    2015-01-29

    Effective silencing by RNA-interference (RNAi) depends on mechanisms that amplify and propagate the silencing signal. In some organisms, small-interfering RNAs (siRNAs) are amplified from target mRNAs by RNA-dependent RNA polymerase (RdRP). Both RdRP recruitment and mRNA silencing require Argonaute proteins, which are generally thought to degrade RNAi targets by directly cleaving them. However, in C. elegans, the enzymatic activity of the primary Argonaute, RDE-1, is not required for silencing activity. We show that RDE-1 can instead recruit an endoribonuclease, RDE-8, to target RNA. RDE-8 can cleave RNA in vitro and is needed for the production of 3' uridylated fragments of target mRNA in vivo. We also find that RDE-8 promotes RdRP activity, thereby ensuring amplification of siRNAs. Together, our findings suggest a model in which RDE-8 cleaves target mRNAs to mediate silencing, while generating 3' uridylated mRNA fragments to serve as templates for the RdRP-directed amplification of the silencing signal. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Detection of biological molecules using boronate-based chemical amplification and optical sensors

    Science.gov (United States)

    Van Antwerp, William Peter; Mastrototaro, John Joseph; Lane, Stephen M.; Satcher, Jr., Joe H.; Darrow, Christopher B.; Peyser, Thomas A.; Harder, Jennifer

    1999-01-01

    Methods are provided for the determination of the concentration of biological levels of polyhydroxylated compounds, particularly glucose. The methods utilize an amplification system that is an analyte transducer immobilized in a polymeric matrix, where the system is implantable and biocompatible. Upon interrogation by an optical system, the amplification system produces a signal capable of detection external to the skin of the patient. Quantitation of the analyte of interest is achieved by measurement of the emitted signal.

  1. Fiber Optical Parametric Chirped Pulse Amplification of Sub-Picosecond Pulses

    DEFF Research Database (Denmark)

    Cristofori, Valentina; Lali-Dastjerdi, Zohreh; Da Ros, Francesco

    2013-01-01

    We demonstrate experimentally, for the first time to our knowledge, fiber optical parametric chirped pulse amplification of 400-fs pulses. The 400-fs signal is stretched, amplified by 26 dB and compressed back to 500 fs.......We demonstrate experimentally, for the first time to our knowledge, fiber optical parametric chirped pulse amplification of 400-fs pulses. The 400-fs signal is stretched, amplified by 26 dB and compressed back to 500 fs....

  2. Sleeve bridging of the rhesus monkey ulnar nerve with muscular branches of the pronator teres: multiple amplification of axonal regeneration

    OpenAIRE

    Yu-hui Kou; Pei-xun Zhang; Yan-hua Wang; Bo Chen; Na Han; Feng Xue; Hong-bo Zhang; Xiao-feng Yin; Bao-guo Jiang

    2015-01-01

    Multiple-bud regeneration, i.e., multiple amplification, has been shown to exist in peripheral nerve regeneration. Multiple buds grow towards the distal nerve stump during proximal nerve fiber regeneration. Our previous studies have verified the limit and validity of multiple amplification of peripheral nerve regeneration using small gap sleeve bridging of small donor nerves to repair large receptor nerves in rodents. The present study sought to observe multiple amplification of myelinated ne...

  3. Controlling the amplification of chirality in hydrogen-bonded assemblies

    NARCIS (Netherlands)

    Mateos timoneda, Miguel; Crego Calama, Mercedes; Reinhoudt, David

    2005-01-01

    The amplification of chirality (a high enantiomeric or diastereomeric excess induced by a small initial amount of chiral bias) on hydrogen-bonded assemblies has been studied using “sergeants-and-soldiers” experiments under thermodynamically controlled conditions. Here it is shown that different

  4. Small molecule ErbB inhibitors decrease proliferative signaling and promote apoptosis in philadelphia chromosome-positive acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Mary E Irwin

    Full Text Available The presence of the Philadelphia chromosome in patients with acute lymphoblastic leukemia (Ph(+ALL is a negative prognostic indicator. Tyrosine kinase inhibitors (TKI that target BCR/ABL, such as imatinib, have improved treatment of Ph(+ALL and are generally incorporated into induction regimens. This approach has improved clinical responses, but molecular remissions are seen in less than 50% of patients leaving few treatment options in the event of relapse. Thus, identification of additional targets for therapeutic intervention has potential to improve outcomes for Ph+ALL. The human epidermal growth factor receptor 2 (ErbB2 is expressed in ~30% of B-ALLs, and numerous small molecule inhibitors are available to prevent its activation. We analyzed a cohort of 129 ALL patient samples using reverse phase protein array (RPPA with ErbB2 and phospho-ErbB2 antibodies and found that activity of ErbB2 was elevated in 56% of Ph(+ALL as compared to just 4.8% of Ph(-ALL. In two human Ph+ALL cell lines, inhibition of ErbB kinase activity with canertinib resulted in a dose-dependent decrease in the phosphorylation of an ErbB kinase signaling target p70S6-kinase T389 (by 60% in Z119 and 39% in Z181 cells at 3 µM. Downstream, phosphorylation of S6-kinase was also diminished in both cell lines in a dose-dependent manner (by 91% in both cell lines at 3 µM. Canertinib treatment increased expression of the pro-apoptotic protein Bim by as much as 144% in Z119 cells and 49% in Z181 cells, and further produced caspase-3 activation and consequent apoptotic cell death. Both canertinib and the FDA-approved ErbB1/2-directed TKI lapatinib abrogated proliferation and increased sensitivity to BCR/ABL-directed TKIs at clinically relevant doses. Our results suggest that ErbB signaling is an additional molecular target in Ph(+ALL and encourage the development of clinical strategies combining ErbB and BCR/ABL kinase inhibitors for this subset of ALL patients.

  5. Alternative Chemical Amplification Methods for Peroxy Radical Detection

    Science.gov (United States)

    Wood, E. C. D.

    2014-12-01

    Peroxy radicals (HO2, CH3O2, etc.) are commonly detected by the chemical amplification technique, in which ambient air is mixed with high concentrations of CO and NO, initiating a chain reaction that produces 30 - 200 NO2 molecules per sampled peroxy radical. The NO2 is then measured by one of several techniques. With the exception of CIMS-based techniques, the chemical amplification method has undergone only incremental improvements since it was first introduced in 1982. The disadvantages of the technique include the need to use high concentrations of CO and the greatly reduced sensitivity of the amplification chain length in the presence of water vapor. We present a new chemical amplification scheme in which either ethane or acetaldehyde is used in place of CO, with the NO2 product detected using Cavity Attenuated Phase Shift spectroscopy (CAPS). Under dry conditions, the amplification factor of the alternative amplifiers are approximately six times lower than the CO-based amplifier. The relative humidity "penalty" is not as severe, however, such that at typical ambient relative humidity (RH) values the amplification factor is within a factor of three of the CO-based amplifier. Combined with the NO2 sensitivity of CAPS and a dual-channel design, the detection limit of the ethane amplifier is less than 2 ppt (1 minute average, signal-to-noise ratio 2). The advantages of these alternative chemical amplification schemes are improved safety, a reduced RH correction, and increased sensitivity to organic peroxy radicals relative to HO2.

  6. Small-signal stability analysis for two-area interconnected power system with load frequency controller in coordination with FACTS and energy storage device

    Directory of Open Access Journals (Sweden)

    Ravi Shankar

    2016-06-01

    Full Text Available This paper deals with the modelling and small signal stability analysis for the two areas interconnected power system using a load frequency controller. The eigenvalues and the participation factor analysis are used to examine the small signal stability and contribution of different states in a particular eigenvalue of the system, respectively. A load frequency controller is designed to stabilize the frequency deviations which occur due to the small perturbation in the system. In this paper, the proposed control scheme consists of an integral controller in coordination with the Redox Flow Energy Storage System (RFESS and the Static Synchronous Series Compensator (SSSC. The dynamic responses of the overall system have been improved by the proposed controller, which is also verified with the help of eigenvalue and participation factor analysis. This analysis shows that overall system oscillation has been reduced through a proposed controller.

  7. Radioactive wastes and the social amplification of risk

    International Nuclear Information System (INIS)

    Kasperson, R.E.; Emel, J.; Goble, R.; Hohenemser, C.; Kasperson, J.X.; Renn, O.

    1987-01-01

    A significant problem in radioactive waste facility siting is that apparent small risks or minor risks events produce substantial public concern and social impacts. The reasons for this difference in public health and societal impacts is not well understood. This paper explores the issues involved in the social amplification of risk, using the risk associated with site characterization as the example. Noteworthy as sources of amplification are the information flow associated with risks and risk events including the large volume of information, the extent of dispute, and misinformation and rumor. Such information passes through the mass media and interpersonal networks. The major mechanisms involved in risk amplifications are discussed and their likely impacts on society described

  8. Genome position and gene amplification

    Czech Academy of Sciences Publication Activity Database

    Jirsová, Pavla; Snijders, A.M.; Kwek, S.; Roydasgupta, R.; Fridlyand, J.; Tokuyasu, T.; Pinkel, D.; Albertson, D. G.

    2007-01-01

    Roč. 8, č. 6 (2007), r120 ISSN 1474-760X Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : gene amplification * array comparative genomic hybridization * oncogene Subject RIV: BO - Biophysics Impact factor: 6.589, year: 2007

  9. Gas amplification properties of GEM foils

    International Nuclear Information System (INIS)

    Beck, Jeannine

    2009-01-01

    In the framework of the detector concept International Linear Detector for the future accelerator project International Linear Collider, in which electrons and positrons at c. m. energies of 500 GeV are brought to collision, a time projection chamber shall be applied as central track detector. By the application of such a chamber as track detector a three-dimensional reconstruction of the track points is possible. If a particle passes the gas volume within the chamber it ionizises single gas atoms and the arising electrons move after the amplification in the GEM arrangement to the anode, so that a two-dimensional projection of the particle track is possible. The third dimension is calculated from the drift time of the electrons. The advances of this readout system consist therein that a better position resolution than by a multiwire proportional chamber is reached and the back-drifting ions can be strongly suppressed. Aim of this thesis are studies for a GEM module, which shall be used in a large TPC prototype. Concerning different requirements it is valid to compare different GEMs in order to can meet an optimal choice. In a small prototype present at DESY measurements for the acquisition of GEM-describing parameters were performed. The taking into operation of the test TPC was part of this thesis. Tracks were generated by a radioactive source, by means of which the gas amplification was determined. With the measurement arrangement gas-amplifier foils of different kind were compared in view of their amplification properties and their energy resolution power and systematically studied. Five different GEM performances were studied in the test TPC. These foils differ in their geometrical classification parameters, the fabrication process, or the materials. The GEMs produced at CERN possess in comparison with GEMs of the Japanese firm SciEnergy and a GEM of the US-American firm Tech-Etch the best amplification and resolution properties. Furthermore a new GEM framing

  10. Metformin inhibits age-related centrosome amplification in Drosophila midgut stem cells through AKT/TOR pathway.

    Science.gov (United States)

    Na, Hyun-Jin; Park, Joung-Sun; Pyo, Jung-Hoon; Jeon, Ho-Jun; Kim, Young-Shin; Arking, Robert; Yoo, Mi-Ae

    2015-07-01

    We delineated the mechanism regulating the inhibition of centrosome amplification by metformin in Drosophila intestinal stem cells (ISCs). Age-related changes in tissue-resident stem cells may be closely associated with tissue aging and age-related diseases, such as cancer. Centrosome amplification is a hallmark of cancers. Our recent work showed that Drosophila ISCs are an excellent model for stem cell studies evaluating age-related increase in centrosome amplification. Here, we showed that metformin, a recognized anti-cancer drug, inhibits age- and oxidative stress-induced centrosome amplification in ISCs. Furthermore, we revealed that this effect is mediated via down-regulation of AKT/target of rapamycin (TOR) activity, suggesting that metformin prevents centrosome amplification by inhibiting the TOR signaling pathway. Additionally, AKT/TOR signaling hyperactivation and metformin treatment indicated a strong correlation between DNA damage accumulation and centrosome amplification in ISCs, suggesting that DNA damage might mediate centrosome amplification. Our study reveals the beneficial and protective effects of metformin on centrosome amplification via AKT/TOR signaling modulation. We identified a new target for the inhibition of age- and oxidative stress-induced centrosome amplification. We propose that the Drosophila ISCs may be an excellent model system for in vivo studies evaluating the effects of anti-cancer drugs on tissue-resident stem cell aging. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  11. Small-Signal Modeling, Stability Analysis and Design Optimization of Single-Phase Delay-Based PLLs

    DEFF Research Database (Denmark)

    Golestan, Saeed; Guerrero, Josep M.; Vidal, Ana

    2016-01-01

    Generally speaking, designing single-phase phaselocked loops (PLLs) is more complicated than three-phase ones, as their implementation often involves the generation of a fictitious orthogonal signal for the frame transformation. In recent years, many approaches to generate the orthogonal signal...... these issues and explore new methods to enhance their performance. The stability analysis, control design guidelines and performance comparison with the state-of-the-art PLLs are presented as well....

  12. Progesterone receptor (PR) polyproline domain (PPD) mediates inhibition of epidermal growth factor receptor (EGFR) signaling in non-small cell lung cancer cells.

    Science.gov (United States)

    Kawprasertsri, Sornsawan; Pietras, Richard J; Marquez-Garban, Diana C; Boonyaratanakornkit, Viroj

    2016-05-01

    Recent evidence has suggested a possible role for progesterone receptor (PR) in the progression of non-small cell lung cancer (NSCLC). However, little is known concerning roles of PR in NSCLC. PR contains a polyproline domain (PPD), which directly binds to the SH3 domain of signaling molecules. Because PPD-SH3 interactions are essential for EGFR signaling, we hypothesized that the presence of PR-PPD interfered with EGFR-mediated signaling and cell proliferation. We examined the role of PR-PPD in cell proliferation and signaling by stably expressing PR-B, or PR-B with disrupting mutations in the PPD (PR-BΔSH3), from a tetracycline-regulated promoter in A549 NSCLC cells. PR-B dose-dependently inhibited cell growth in the absence of ligand, and progestin (R5020) treatment further suppressed the growth. Treatment with RU486 abolished PR-B- and R5020-mediated inhibition of cell proliferation. Expression of PR-BΔSH3 and treatment with R5020 or RU486 had no effect on cell proliferation. Furthermore, PR-B expression but not PR-BΔSH3 expression reduced EGF-induced A549 proliferation and activation of ERK1/2, in the absence of ligand. Taken together, our data demonstrated the significance of PR extranuclear signaling through PPD interactions in EGFR-mediated proliferation and signaling in NSCLC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Circulation and Directional Amplification in the Josephson Parametric Converter

    Science.gov (United States)

    Hatridge, Michael

    Nonreciprocal transport and directional amplification of weak microwave signals are fundamental ingredients in performing efficient measurements of quantum states of flying microwave light. This challenge has been partly met, as quantum-limited amplification is now regularly achieved with parametrically-driven, Josephson-junction based superconducting circuits. However, these devices are typically non-directional, requiring external circulators to separate incoming and outgoing signals. Recently this limitation has been overcome by several proposals and experimental realizations of both directional amplifiers and circulators based on interference between several parametric processes in a single device. This new class of multi-parametrically driven devices holds the promise of achieving a variety of desirable characteristics simultaneously- directionality, reduced gain-bandwidth constraints and quantum-limited added noise, and are good candidates for on-chip integration with other superconducting circuits such as qubits.

  14. Small-signal modulation and differential gain of red-emitting (λ = 630 nm) InGaN/GaN quantum dot lasers

    Energy Technology Data Exchange (ETDEWEB)

    Frost, Thomas; Banerjee, Animesh; Bhattacharya, Pallab, E-mail: pkb@eecs.umich.edu [Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, Michigan 48109-2122 (United States)

    2013-11-18

    We report small-signal modulation bandwidth and differential gain measurements of a ridge waveguide In{sub 0.4}Ga{sub 0.6}N/GaN quantum dot laser grown by molecular beam epitaxy. The laser peak emission is at λ = 630 nm. The −3 dB bandwidth of an 800 μm long device was measured to be 2.4 GHz at 250 mA under pulsed biasing, demonstrating the possibility of high-speed operation of these devices. The differential gain was measured to be 5.3 × 10{sup −17} cm{sup 2}, and a gain compression factor of 2.87 × 10{sup −17} cm{sup 3} is also derived from the small-signal modulation response.

  15. Improvement of small-signal stability of power system by controlling doubly fed induction generators of a large-capacity wind farm

    Directory of Open Access Journals (Sweden)

    Tomohiro Adachi

    2016-01-01

    Full Text Available Many wind turbine generations have been installed into power systems around the world, where in recent years doubly fed induction generator (DFIG attracts a lot of attentions because of its efficiency and controllability. However, the DFIG is connected to the power system through inverters and originally does not have an ability to release the kinetic energy of the rotor or resorb the surplus power of the power system as the kinetic energy. Therefore, it has not been made clear how the DFIGs have an influence on small-signal stability in power systems. In this paper, we propose a control scheme of the DFIG and analyse its effect on the small-signal stability of the power system by eigenvalue calculations and time-domain simulations.

  16. Small-Signal Modeling of the PVR-Based AD Scheme and Controller Design for Three-Phase Standalone DG System

    DEFF Research Database (Denmark)

    Shen, Pan; Han, Yang; Lu, Chang

    2016-01-01

    This paper presents the small-signal state-space modeling and a new multifunctional multi-loop control strategy for three-phase inverter-based islanded DG systems under unbalanced and/or nonlinear load conditions. The proposed control methodology utilizes the parallel virtual resistance (PVR...... controllers are based on an enhanced proportional resonant (PR) structure to achieve zero steady-state error, and multi-resonant harmonic compensator (MRHC) plus PR controller to prevent low-order load current harmonics to distort the output voltage. The proposed small-signal model of the islanded DG system...... with multi-loop control strategy in the stationary reference frame is presented. Moreover, an enhanced delay compensation (EDC) scheme based on two integrators of the discrete PR controller is presented to improve stability margins with a higher accuracy compared with the existing methods. Then, a detailed...

  17. Design, Construction, and Use of a Single Board Computer Beowulf Cluster: Application of the Small-Footprint, Low-Cost, InSignal 5420 Octa Board

    OpenAIRE

    Cusick, James J.; Miller, William; Laurita, Nicholas; Pitt, Tasha

    2014-01-01

    In recent years development in the area of Single Board Computing has been advancing rapidly. At Wolters Kluwer's Corporate Legal Services Division a prototyping effort was undertaken to establish the utility of such devices for practical and general computing needs. This paper presents the background of this work, the design and construction of a 64 core 96 GHz cluster, and their possibility of yielding approximately 400 GFLOPs from a set of small footprint InSignal boards created for just o...

  18. Study of reconstruction methods for a time projection chamber with GEM gas amplification system

    Energy Technology Data Exchange (ETDEWEB)

    Diener, R.

    2006-12-15

    A new e{sup +}e{sup -} linear collider with an energy range up to 1TeV is planned in an international collaboration: the International Linear Collider (ILC). This collider will be able to do precision measurements of the Higgs particle and of physics beyond the Standard Model. In the Large Detector Concept (LDC) - which is one proposal for a detector at the ILC - a Time Projection Chamber (TPC) is foreseen as the main tracking device. To meet the requirements on the resolution and to be able to work in the environment at the ILC, the application of new gas amplification technologies in the TPC is necessary. One option is an amplification system based on Gas Electron Multipliers (GEMs). Due to the - in comparison with older technologies - small spatial width of the signals, this technology poses new requirements on the readout structures and the reconstruction methods. In this work, the performance and the systematics of different reconstruction methods have been studied, based on data measured with a TPC prototype in high magnetic fields of up to 4T and data from a Monte Carlo simulation. The latest results of the achievable point resolution are presented and their limitations have been investigated. (orig.)

  19. Study of reconstruction methods for a time projection chamber with GEM gas amplification system

    International Nuclear Information System (INIS)

    Diener, R.

    2006-12-01

    A new e + e - linear collider with an energy range up to 1TeV is planned in an international collaboration: the International Linear Collider (ILC). This collider will be able to do precision measurements of the Higgs particle and of physics beyond the Standard Model. In the Large Detector Concept (LDC) - which is one proposal for a detector at the ILC - a Time Projection Chamber (TPC) is foreseen as the main tracking device. To meet the requirements on the resolution and to be able to work in the environment at the ILC, the application of new gas amplification technologies in the TPC is necessary. One option is an amplification system based on Gas Electron Multipliers (GEMs). Due to the - in comparison with older technologies - small spatial width of the signals, this technology poses new requirements on the readout structures and the reconstruction methods. In this work, the performance and the systematics of different reconstruction methods have been studied, based on data measured with a TPC prototype in high magnetic fields of up to 4T and data from a Monte Carlo simulation. The latest results of the achievable point resolution are presented and their limitations have been investigated. (orig.)

  20. Laser amplification in excited dielectrics

    Science.gov (United States)

    Winkler, Thomas; Haahr-Lillevang, Lasse; Sarpe, Cristian; Zielinski, Bastian; Götte, Nadine; Senftleben, Arne; Balling, Peter; Baumert, Thomas

    2018-01-01

    Wide-bandgap dielectrics such as glasses or water are transparent at visible and infrared wavelengths. This changes when they are exposed to ultrashort and highly intense laser pulses. Different interaction mechanisms lead to the appearance of various transient nonlinear optical phenomena. Using these, the optical properties of dielectrics can be controlled from the transparent to the metal-like state. Here we expand this range by a yet unexplored mechanism in excited dielectrics: amplification. In a two-colour pump-probe experiment, we show that a 400 nm femtosecond laser pulse is coherently amplified inside an excited sapphire sample on a scale of a few micrometres. Simulations strongly support the proposed two-photon stimulated emission process, which is temporally and spatially controllable. Consequently, we expect applications in all fields that demand strongly localized amplification.

  1. Measuring the amplification of attention

    OpenAIRE

    Blaser, Erik; Sperling, George; Lu, Zhong-Lin

    1999-01-01

    An ambiguous motion paradigm, in which the direction of apparent motion is determined by salience (i.e., the extent to which an area is perceived as figure versus ground), is used to assay the amplification of color by attention to color. In the red–green colored gratings used in these experiments, without attention instructions, salience depends on the chromaticity difference between colored stripes embedded in the motion sequence and the yellow background. Selective attention to red (or to ...

  2. An ultrasensitive sandwich-type electrochemical immunosensor based on the signal amplification system of double-deck gold film and thionine unite with platinum nanowire inlaid globular SBA-15 microsphere.

    Science.gov (United States)

    Wang, Ping; Li, Mingdang; Pei, Fubin; Li, Yueyun; Liu, Qing; Dong, Yunhui; Chu, Qingyan; Zhu, Hongjun

    2017-05-15

    A novel thionine unites with platinum nanowire inlaid globular SBA-15 (Pt NWs@g-SBA-15/Thi) not only utilizes as an efficient electrical signal probe but also constitutes an amplifying system with double-deck gold film (D-Au film) have been applied to the fabrication of sandwich-type immunosensor for detecting hepatitis B surface antigen (HBs Ag). The D-Au film can accelerate the electron transfer on the electrode interface due to the tunneling effect between the two Au films and can improve the load capacity of primary antibodies (Ab 1 ) because of the good biocompatibility. The Pt NWs@g-SBA-15/Thi with uniform globular morphology not only can effectively reduce the spatial limitation for loading the secondary antibodies (Ab 2 ) but also can provide outstanding pore accessibility of guest species from outside and offer catalytically active sites in a large scale. Besides, the presence of Thi can well enhance the electrical conductivity of Pt NWs@g-SBA-15/Thi. With the good cooperation between D-Au film and Pt NWs@g-SBA-15/Thi, a linear relationship between current signals and the concentrations of HBs Ag was obtained in the wide range from 10 fg/mL to 100ng/mL and the detection limit of HBs Ag was 3.3 fg/mL (signal-to-noise ratio of 3). Furthermore, the designed immunosensor with excellent selectivity, reproducibility and stability shows excellent performance in detection of human serum samples and provides a promising capacity for detecting a wide range of other tumor markers in clinical application. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. Spheromak Impedance and Current Amplification

    International Nuclear Information System (INIS)

    Fowler, T K; Hua, D D; Stallard, B W

    2002-01-01

    It is shown that high current amplification can be achieved only by injecting helicity on the timescale for reconnection, τ REC , which determines the effective impedance of the spheromak. An approximate equation for current amplification is: dI TOR 2 /dt ∼ I 2 /τ REC - I TOR 2 /τ closed where I is the gun current, I TOR is the spheromak toroidal current and τ CLOSED is the ohmic decay time of the spheromak. Achieving high current amplification, I TOR >> I, requires τ REC CLOSED . For resistive reconnection, this requires reconnection in a cold zone feeding helicity into a hot zone. Here we propose an impedance model based on these ideas in a form that can be implemented in the Corsica-based helicity transport code. The most important feature of the model is the possibility that τ REC actually increases as the spheromak temperature increases, perhaps accounting for the ''voltage sag'' observed in some experiments, and a tendency toward a constant ratio of field to current, B ∝ I, or I TOR ∼ I. Program implications are discussed

  4. Tungsten disulfide nanosheet and exonuclease III co-assisted amplification strategy for highly sensitive fluorescence polarization detection of DNA glycosylase activity

    International Nuclear Information System (INIS)

    Zhao, Jingjin; Ma, Yefei; Kong, Rongmei; Zhang, Liangliang; Yang, Wen; Zhao, Shulin

    2015-01-01

    Herein, we introduced a tungsten disulfide (WS 2 ) nanosheet and exonuclease III (Exo III) co-assisted signal amplification strategy for highly sensitive fluorescent polarization (FP) assay of DNA glycosylase activity. Two DNA glycosylases, uracil-DNA glycosylase (UDG) and human 8-oxoG DNA glycosylase 1 (hOGG1), were tested. A hairpin-structured probe (HP) which contained damaged bases in the stem was used as the substrate. The removal of damaged bases from substrate by DNA glycosylase would lower the melting temperature of HP. The HP was then opened and hybridized with a FAM dye-labeled single strand DNA (DP), generating a duplex with a recessed 3′-terminal of DP. This design facilitated the Exo III-assisted amplification by repeating the hybridization and digestion of DP, liberating numerous FAM fluorophores which could not be adsorbed on WS 2 nanosheet. Thus, the final system exhibited a small FP signal. However, in the absence of DNA glycosylases, no hybridization between DP and HP was occurred, hampering the hydrolysis of DP by Exo III. The intact DP was then adsorbed on the surface of WS 2 nanosheet that greatly amplified the mass of the labeled-FAM fluorophore, resulting in a large FP value. With the co-assisted amplification strategy, the sensitivity was substantially improved. In addition, this method was applied to detect UDG activity in cell extracts. The study of the inhibition of UDG was also performed. Furthermore, this method is simple in design, easy in implementation, and selective, which holds potential applications in the DNA glycosylase related mechanism research and molecular diagnostics. - Highlights: • A fluorescence polarization strategy for DNA glycosylase activity detection was developed. • The present method was based on WS 2 nanosheet and exonuclease III co-assisted signal amplification. • A high sensitivity and desirable selectivity were achieved. • This method provides a promising universal platform for DNA glycosylase

  5. [Prognostic significance of MYCN amplification in children neuroblastic tumors].

    Science.gov (United States)

    Niu, Huilin; Xu, Tao; Wang, Fenghua; Chen, Zhengrong; Gao, Qiu; Yi, Peng; Xia, Jianqing

    2015-02-01

    To summarize the clinicopathologic features of neuroblastic tumors (NT), and to explore the prognostic significance of MYCN amplification in NT. The clinicopathologic data of 267 NT were reviewed. MYCN gene amplification was detected by fluorescence in situ hybridization (FISH) in 119 cases and the relationship with pathological characteristics and prognostic significance were analyzed. The study included 267 cases of children NT from patients aged from 1 day to 13 years (median 27 months). The male to female ratio was 1.43. There were 38 cases (14.2%), 43 cases (16.1%), 71 cases (26.6%), and 115 cases (43.1%) of INSS stages I, II, III and IV respectively.Favorable histology group had 157 cases (59.9%); unfavorable histology group had 110 cases (40.1%).Of the 119 NT cases with MYCN FISH performed, 18 cases (15.1%) showed amplification and the signal ratio of MYCN to CEP2 was 4.08-43.29. One hundred and one cases of non-amplified MYCN included MYCN gain in 79 cases (66.3%) and MYCN negative in 22 cases (18.5%). MYCN expression showed significant difference (P = 0.000) between ages, gender, NT type and MKI, but not INPC and clinical stage (P > 0.05).Of the 18 cases with MYCN amplification, 3 were undifferentiated, and 15 poorly differentiated; 17 had high MKI and one moderate MKI. All 18 cases were in unfavorable histology group; the overall survival rate was 3/18, with an average survival time of (17.9 ± 2.4) months.Of the 101 MYCN non-amplification cases, the overall survival rate was 68.3% (69/101), with an average survival time of (29.8 ± 1.3) months. Survival analysis showed the cases with MYCN amplification had worse prognosis (P < 0.05). NT were commonly diagnosed in early ages and easily to metastasize. Most of cases with favorable histology. The cases of MYCN amplification showed unfavorable histology, and the majority cases with high MKI; The patients with MYCN gene amplification had poor prognosis.

  6. Small Molecule Inhibitors of AI-2 Signaling in Bacteria: State-of-the-Art and Future Perspectives for Anti-Quorum Sensing Agents

    Science.gov (United States)

    Guo, Min; Gamby, Sonja; Zheng, Yue; Sintim, Herman O.

    2013-01-01

    Bacteria respond to different small molecules that are produced by other neighboring bacteria. These molecules, called autoinducers, are classified as intraspecies (i.e., molecules produced and perceived by the same bacterial species) or interspecies (molecules that are produced and sensed between different bacterial species). AI-2 has been proposed as an interspecies autoinducer and has been shown to regulate different bacterial physiology as well as affect virulence factor production and biofilm formation in some bacteria, including bacteria of clinical relevance. Several groups have embarked on the development of small molecules that could be used to perturb AI-2 signaling in bacteria, with the ultimate goal that these molecules could be used to inhibit bacterial virulence and biofilm formation. Additionally, these molecules have the potential to be used in synthetic biology applications whereby these small molecules are used as inputs to switch on and off AI-2 receptors. In this review, we highlight the state-of-the-art in the development of small molecules that perturb AI-2 signaling in bacteria and offer our perspective on the future development and applications of these classes of molecules. PMID:23994835

  7. A small molecule inhibitor of signal peptide peptidase inhibits Plasmodium development in the liver and decreases malaria severity.

    Directory of Open Access Journals (Sweden)

    Iana Parvanova

    Full Text Available The liver stage of Plasmodium's life cycle is the first, obligatory step in malaria infection. Decreasing the hepatic burden of Plasmodium infection decreases the severity of disease and constitutes a promising strategy for malaria prophylaxis. The efficacy of the gamma-secretase and signal peptide peptidase inhibitor LY411,575 in targeting Plasmodium liver stages was evaluated both in human hepatoma cell lines and in mouse primary hepatocytes. LY411,575 was found to prevent Plasmodium's normal development in the liver, with an IC(50 of approximately 80 nM, without affecting hepatocyte invasion by the parasite. In vivo results with a rodent model of malaria showed that LY411,575 decreases the parasite load in the liver and increases by 55% the resistance of mice to cerebral malaria, one of the most severe malaria-associated syndromes. Our data show that LY411,575 does not exert its effect via the Notch signaling pathway suggesting that it may interfere with Plasmodium development through an inhibition of the parasite's signal peptide peptidase. We therefore propose that selective signal peptide peptidase inhibitors could be potentially used for preventive treatment of malaria in humans.

  8. Markovian Dynamics of Josephson Parametric Amplification

    Directory of Open Access Journals (Sweden)

    W. Kaiser

    2017-09-01

    Full Text Available In this work, we derive the dynamics of the lossy DC pumped non-degenerate Josephson parametric amplifier (DCPJPA. The main element in a DCPJPA is the superconducting Josephson junction. The DC bias generates the AC Josephson current varying the nonlinear inductance of the junction. By this way the Josephson junction acts as the pump oscillator as well as the time varying reactance of the parametric amplifier. In quantum-limited amplification, losses and noise have an increased impact on the characteristics of an amplifier. We outline the classical model of the lossy DCPJPA and derive the available noise power spectral densities. A classical treatment is not capable of including properties like spontaneous emission which is mandatory in case of amplification at the quantum limit. Thus, we derive a quantum mechanical model of the lossy DCPJPA. Thermal losses are modeled by the quantum Langevin approach, by coupling the quantized system to a photon heat bath in thermodynamic equilibrium. The mode occupation in the bath follows the Bose-Einstein statistics. Based on the second quantization formalism, we derive the Heisenberg equations of motion of both resonator modes. We assume the dynamics of the system to follow the Markovian approximation, i.e. the system only depends on its actual state and is memory-free. We explicitly compute the time evolution of the contributions to the signal mode energy and give numeric examples based on different damping and coupling constants. Our analytic results show, that this model is capable of including thermal noise into the description of the DC pumped non-degenerate Josephson parametric amplifier.

  9. Markovian Dynamics of Josephson Parametric Amplification

    Science.gov (United States)

    Kaiser, Waldemar; Haider, Michael; Russer, Johannes A.; Russer, Peter; Jirauschek, Christian

    2017-09-01

    In this work, we derive the dynamics of the lossy DC pumped non-degenerate Josephson parametric amplifier (DCPJPA). The main element in a DCPJPA is the superconducting Josephson junction. The DC bias generates the AC Josephson current varying the nonlinear inductance of the junction. By this way the Josephson junction acts as the pump oscillator as well as the time varying reactance of the parametric amplifier. In quantum-limited amplification, losses and noise have an increased impact on the characteristics of an amplifier. We outline the classical model of the lossy DCPJPA and derive the available noise power spectral densities. A classical treatment is not capable of including properties like spontaneous emission which is mandatory in case of amplification at the quantum limit. Thus, we derive a quantum mechanical model of the lossy DCPJPA. Thermal losses are modeled by the quantum Langevin approach, by coupling the quantized system to a photon heat bath in thermodynamic equilibrium. The mode occupation in the bath follows the Bose-Einstein statistics. Based on the second quantization formalism, we derive the Heisenberg equations of motion of both resonator modes. We assume the dynamics of the system to follow the Markovian approximation, i.e. the system only depends on its actual state and is memory-free. We explicitly compute the time evolution of the contributions to the signal mode energy and give numeric examples based on different damping and coupling constants. Our analytic results show, that this model is capable of including thermal noise into the description of the DC pumped non-degenerate Josephson parametric amplifier.

  10. Cascade DNA nanomachine and exponential amplification biosensing.

    Science.gov (United States)

    Xu, Jianguo; Wu, Zai-Sheng; Shen, Weiyu; Xu, Huo; Li, Hongling; Jia, Lee

    2015-11-15

    DNA is a versatile scaffold for the assembly of multifunctional nanostructures, and potential applications of various DNA nanodevices have been recently demonstrated for disease diagnosis and treatment. In the current study, a powerful cascade DNA nanomachine was developed that can execute the exponential amplification of p53 tumor suppressor gene. During the operation of the newly-proposed DNA nanomachine, dual-cyclical nucleic acid strand-displacement polymerization (dual-CNDP) was ingeniously introduced, where the target trigger is repeatedly used as the fuel molecule and the nicked fragments are dramatically accumulated. Moreover, each displaced nicked fragment is able to activate the another type of cyclical strand-displacement amplification, increasing exponentially the value of fluorescence intensity. Essentially, one target binding event can induce considerable number of subsequent reactions, and the nanodevice was called cascade DNA nanomachine. It can implement several functions, including recognition element, signaling probe, polymerization primer and template. Using the developed autonomous operation of DNA nanomachine, the p53 gene can be quantified in the wide concentration range from 0.05 to 150 nM with the detection limit of 50 pM. If taking into account the final volume of mixture, the detection limit is calculated as lower as 6.2 pM, achieving an desirable assay ability. More strikingly, the mutant gene can be easily distinguished from the wild-type one. The proof-of-concept demonstrations reported herein is expected to promote the development and application of DNA nanomachine, showing great potential value in basic biology and medical diagnosis. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Processes of synchronization, chaotization and amplification in a germanium oscillistor

    Energy Technology Data Exchange (ETDEWEB)

    Abakarova, N.S.; Aliev, K.M.; Ibragimov, Kh.O.; Kamilov, I.K. [Institute of Physics, Dagestan Science Centre, RAS, Makhachkala (Russian Federation)

    2001-12-03

    The effect of an external harmonic signal on the screw instability of the current in the electron-hole plasma has been studied experimentally in Ge at 77 K and 300 K. The influence exerted by external signals with various amplitudes and frequencies, applied to a sample both additively and multiplicatively, on the synchronization, amplification and stability of the system in absolute and convective modes of instability excitation has been investigated at points of bifurcation in a wide region of the parametric space. (author)

  12. Single-molecule tracking of small GTPase Rac1 uncovers spatial regulation of membrane translocation and mechanism for polarized signaling

    Science.gov (United States)

    Das, Sulagna; Yin, Taofei; Yang, Qingfen; Zhang, Jingqiao; Wu, Yi I.; Yu, Ji

    2015-01-01

    Polarized Rac1 signaling is a hallmark of many cellular functions, including cell adhesion, motility, and cell division. The two steps of Rac1 activation are its translocation to the plasma membrane and the exchange of nucleotide from GDP to GTP. It is, however, unclear whether these two processes are regulated independent of each other and what their respective roles are in polarization of Rac1 signaling. We designed a single-particle tracking (SPT) method to quantitatively analyze the kinetics of Rac1 membrane translocation in living cells. We found that the rate of Rac1 translocation was significantly elevated in protrusions during cell spreading on collagen. Furthermore, combining FRET sensor imaging with SPT measurements in the same cell, the recruitment of Rac1 was found to be polarized to an extent similar to that of the nucleotide exchange process. Statistical analysis of single-molecule trajectories and optogenetic manipulation of membrane lipids revealed that Rac1 membrane translocation precedes nucleotide exchange, and is governed primarily by interactions with phospholipids, particularly PI(3,4,5)P3, instead of protein factors. Overall, the study highlights the significance of membrane translocation in spatial Rac1 signaling, which is in addition to the traditional view focusing primarily on GEF distribution and exchange reaction. PMID:25561548

  13. Small things matter: Implications of APP intracellular domain AICD nuclear signaling in the progression and pathogenesis of Alzheimer's disease.

    Science.gov (United States)

    Bukhari, Hassan; Glotzbach, Annika; Kolbe, Katharina; Leonhardt, Gregor; Loosse, Christina; Müller, Thorsten

    2017-09-01

    Alzheimer's disease (AD) is the most common neurodegenerative disease with tens of millions of people affected worldwide. The pathogenesis is still poorly understood and various therapeutical approaches targeting the amyloid β (Aβ) peptide, a product of the amyloidogenic cleavage of the amyloid precursor protein (APP), failed. Moreover, a couple of studies critically questioned the relevance of Aβ in the pathogenesis of AD. Thus, new ideas need to be studied and one highly interesting hypothesis is the APP mediated signal transduction to the nucleus. As a consequence nuclear -potentially toxic- structures emerge, which were recently found to a high extent in human AD tissue and thus, may contribute to neurodegeneration. Relevant for the signaling machinery are modifications at the very C-terminal end of the precursor protein, the APP intracellular domain (AICD). In this review we update the knowledge on mechanisms on AICD referring to our 2008 article: The amyloid precursor protein intracellular domain (AICD) as modulator of gene expression, apoptosis, and cytoskeletal dynamics-Relevance for Alzheimer's disease (T. Muller, et al., 2008). We summarize how AICD is generated and degraded, we describe its intramolecular motifs, translational modifications, and how those as well as APP dimerization influence AICD generation and function. Moreover, we resume the AICD interactome and elucidate AICDs involvement in nuclear signaling, transcriptional regulation, cell death, DNA repair and cell cycle re-entry and we give insights in its physiological function. Results are summarized in the comprehensive poster "The world of AICD". Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Magnetoelectric coupling study in multiferroic Pb(Fe0.5Nb0.5)O3 ceramics through small and large electric signal standard measurements

    International Nuclear Information System (INIS)

    Raymond, Oscar; Siqueiros, Jesus M.; Font, Reynaldo; Portelles, Jorge

    2011-01-01

    Multifunctional multiferroic materials such as the single phase compound Pb(Fe 0.5 Nb 0.5 )O 3 (PFN), where ferroelectric and antiferromagnetic order coexist, are very promising and have great interest from the academic and technological points of view. In this work, coupling of the ferroelectric and magnetic moments is reported. For this study, a combination of the small signal response using the impedance spectroscopy technique and the electromechanical resonance method with the large signal response through standard ferroelectric hysteresis measurement, has been used with and without an applied magnetic field. The measurements to determine the electrical properties of the ceramic were performed as functions of the bias and poling electric fields. A simultaneous analysis of the complex dielectric constant ε-tilde, impedance Z-tilde, electric modulus M-tilde, admittance Y-tilde, and the electromechanical parameters and coupling factors is presented. The results are correlated with a previous study of structural, morphological, small signal dielectric frequency-temperature response, and the ferroelectric hysteretic, magnetic and magnetodielectric behaviors. The observed shifts of the resonance and antiresonance frequency values can be associated with change of the ferroelectric domain size favored by the readjustment of the oxygen octahedron when the magnetic field is applied. From P-E hysteresis loops obtained without and with an external applied magnetic field, a dc magnetoelectric coupling effect with maximum value of 4 kV/cm T (400 mV/cm Oe) was obtained.

  15. Laser amplification in excited dielectrics

    DEFF Research Database (Denmark)

    Winkler, Thomas; Haahr-Lillevang, Lasse; Sarpe, Cristian

    2018-01-01

    Wide-bandgap dielectrics such as glasses or water are transparent at visible and infrared wavelengths. This changes when they are exposed to ultrashort and highly intense laser pulses. Different interaction mechanisms lead to the appearance of various transient nonlinear optical phenomena. Using...... these, the optical properties of dielectrics can be controlled from the transparent to the metal-like state. Here we expand this range by a yet unexplored mechanism in excited dielectrics: amplification. In a two-colour pump-probe experiment, we show that a 400nm femtosecond laser pulse is coherently...

  16. Telomerase Repeated Amplification Protocol (TRAP).

    Science.gov (United States)

    Mender, Ilgen; Shay, Jerry W

    2015-11-20

    Telomeres are found at the end of eukaryotic linear chromosomes, and proteins that bind to telomeres protect DNA from being recognized as double-strand breaks thus preventing end-to-end fusions (Griffith et al. , 1999). However, due to the end replication problem and other factors such as oxidative damage, the limited life span of cultured cells (Hayflick limit) results in progressive shortening of these protective structures (Hayflick and Moorhead, 1961; Olovnikov, 1973). The ribonucleoprotein enzyme complex telomerase-consisting of a protein catalytic component hTERT and a functional RNA component hTR or hTERC - counteracts telomere shortening by adding telomeric repeats to the end of chromosomes in ~90% of primary human tumors and in some transiently proliferating stem-like cells (Shay and Wright, 1996; Shay and Wright, 2001). This results in continuous proliferation of cells which is a hallmark of cancer. Therefore, telomere biology has a central role in aging, cancer progression/metastasis as well as targeted cancer therapies. There are commonly used methods in telomere biology such as Telomere Restriction Fragment (TRF) (Mender and Shay, 2015b), Telomere Repeat Amplification Protocol (TRAP) and Telomere dysfunction Induced Foci (TIF) analysis (Mender and Shay, 2015a). In this detailed protocol we describe Telomere Repeat Amplification Protocol (TRAP). The TRAP assay is a popular method to determine telomerase activity in mammalian cells and tissue samples (Kim et al. , 1994). The TRAP assay includes three steps: extension, amplification, and detection of telomerase products. In the extension step, telomeric repeats are added to the telomerase substrate (which is actually a non telomeric oligonucleotide, TS) by telomerase. In the amplification step, the extension products are amplified by the polymerase chain reaction (PCR) using specific primers (TS upstream primer and ACX downstream primer) and in the detection step, the presence or absence of telomerase is

  17. Resonant primordial gravitational waves amplification

    Directory of Open Access Journals (Sweden)

    Chunshan Lin

    2016-01-01

    Full Text Available We propose a mechanism to evade the Lyth bound in models of inflation. We minimally extend the conventional single-field inflation model in general relativity (GR to a theory with non-vanishing graviton mass in the very early universe. The modification primarily affects the tensor perturbation, while the scalar and vector perturbations are the same as the ones in GR with a single scalar field at least at the level of linear perturbation theory. During the reheating stage, the graviton mass oscillates coherently and leads to resonant amplification of the primordial tensor perturbation. After reheating the graviton mass vanishes and we recover GR.

  18. High peak-power kilohertz laser system employing single-stage multi-pass amplification

    Science.gov (United States)

    Shan, Bing; Wang, Chun; Chang, Zenghu

    2006-05-23

    The present invention describes a technique for achieving high peak power output in a laser employing single-stage, multi-pass amplification. High gain is achieved by employing a very small "seed" beam diameter in gain medium, and maintaining the small beam diameter for multiple high-gain pre-amplification passes through a pumped gain medium, then leading the beam out of the amplifier cavity, changing the beam diameter and sending it back to the amplifier cavity for additional, high-power amplification passes through the gain medium. In these power amplification passes, the beam diameter in gain medium is increased and carefully matched to the pump laser's beam diameter for high efficiency extraction of energy from the pumped gain medium. A method of "grooming" the beam by means of a far-field spatial filter in the process of changing the beam size within the single-stage amplifier is also described.

  19. MET amplification, expression, and exon 14 mutations in colorectal adenocarcinoma.

    Science.gov (United States)

    Zhang, Meng; Li, Guichao; Sun, Xiangjie; Ni, Shujuan; Tan, Cong; Xu, Midie; Huang, Dan; Ren, Fei; Li, Dawei; Wei, Ping; Du, Xiang

    2018-04-08

    MET amplification, expression, and splice mutations at exon 14 result in dysregulation of the MET signaling pathway. The aim of this study was to identify the relationship between MET amplification, protein or mRNA expression, and mutations in colorectal cancer (CRC). MET immunohistochemistry (IHC) was used for MET protein expression analysis and fluorescence in situ hybridization (FISH) was used for MET amplification detection. Both analyses were performed in tissue microarrays (TMA) containing 294 of colorectal adenocarcinoma tissue samples and 131 samples of adjacent normal epithelial tissue. MET mRNA expression was examined by real-time quantitative polymerase chain reaction (qRT-PCR) in 72 fresh colorectal adenocarcinoma tissue samples and adjacent normal colon tissue. PCR sequencing was performed to screen for MET exon 14 splice mutations in 59 fresh CRC tissue samples. Our results showed that MET protein expression was higher in colorectal tumor tissue than in adjacent normal intestinal epithelium. Positive MET protein expression was associated with significantly poorer overall survival (OS) and disease-free survival (DFS). Multivariate analysis revealed that positive MET protein expression was an independent risk factor for DFS, but not for OS. MET mRNA expression was upregulated in tumor tissues compared with the adjacent normal tissues. The incidence of MET amplification was 4.4%. None of the patients was positive for MET mutation. Collectively, MET was overexpressed in colorectal adenocarcinoma, and its positive protein expression predicted a poorer outcome in CRC patients. Furthermore, according to our results, MET amplification and 14 exon mutation are extremely rare events in colorectal adenocarcinoma. Copyright © 2018. Published by Elsevier Inc.

  20. 85 km Long Reach PON System Using a Reflective SOA-EA Modulator and Distributed Raman Fiber Amplification

    DEFF Research Database (Denmark)

    Tafur Monroy, Idelfonso; Öhman, Filip; Yvind, Kresten

    2006-01-01

    We report on a bidirectional 85 km long reach PON system supported by distributed fiber Raman amplification with a record 7.5 Gb/s remote carrier modulated upstream signal by employing a reflective SOA-EA monolithically integrated circuit......We report on a bidirectional 85 km long reach PON system supported by distributed fiber Raman amplification with a record 7.5 Gb/s remote carrier modulated upstream signal by employing a reflective SOA-EA monolithically integrated circuit...

  1. Direct Targeting of β-Catenin by a Small Molecule Stimulates Proteasomal Degradation and Suppresses Oncogenic Wnt/β-Catenin Signaling

    Directory of Open Access Journals (Sweden)

    So-Young Hwang

    2016-06-01

    Full Text Available The Wnt/β-catenin signaling pathway plays a major role in tissue homeostasis, and its dysregulation can lead to various human diseases. Aberrant activation of β-catenin is oncogenic and is a critical driver in the development and progression of human cancers. Despite the significant potential of targeting the oncogenic β-catenin pathway for cancer therapy, the development of specific inhibitors remains insufficient. Using a T cell factor (TCF-dependent luciferase-reporter system, we screened for small-molecule compounds that act against Wnt/β-catenin signaling and identified MSAB (methyl 3-{[(4-methylphenylsulfonyl]amino}benzoate as a selective inhibitor of Wnt/β-catenin signaling. MSAB shows potent anti-tumor effects selectively on Wnt-dependent cancer cells in vitro and in mouse cancer models. MSAB binds to β-catenin, promoting its degradation, and specifically downregulates Wnt/β-catenin target genes. Our findings might represent an effective therapeutic strategy for cancers addicted to the Wnt/β-catenin signaling pathway.

  2. Ras-dva1 small GTPase regulates telencephalon development in Xenopus laevis embryos by controlling Fgf8 and Agr signaling at the anterior border of the neural plate

    Directory of Open Access Journals (Sweden)

    Maria B. Tereshina

    2014-07-01

    Full Text Available We previously found that the small GTPase Ras-dva1 is essential for the telencephalic development in Xenopus laevis because Ras-dva1 controls the Fgf8-mediated induction of FoxG1 expression, a key telencephalic regulator. In this report, we show, however, that Ras-dva1 and FoxG1 are expressed in different groups of cells; whereas Ras-dva1 is expressed in the outer layer of the anterior neural fold, FoxG1 and Fgf8 are activated in the inner layer from which the telencephalon is derived. We resolve this paradox by demonstrating that Ras-dva1 is involved in the transduction of Fgf8 signal received by cells in the outer layer, which in turn send a feedback signal that stimulates FoxG1 expression in the inner layer. We show that this feedback signal is transmitted by secreted Agr proteins, the expression of which is activated in the outer layer by mediation of Ras-dva1 and the homeodomain transcription factor Otx2. In turn, Agrs are essential for maintaining Fgf8 and FoxG1 expression in cells at the anterior neural plate border. Our finding reveals a novel feedback loop mechanism based on the exchange of Fgf8 and Agr signaling between neural and non-neural compartments at the anterior margin of the neural plate and demonstrates a key role of Ras-dva1 in this mechanism.

  3. TUSC3 induces autophagy in human non-small cell lung cancer cells through Wnt/?-catenin signaling

    OpenAIRE

    Peng, Yun; Cao, Jun; Yao, Xiao-Yi; Wang, Jian-Xin; Zhong, Mei-Zuo; Gan, Ping-Ping; Li, Jian-Huang

    2017-01-01

    We investigated the effects of tumor suppressor candidate 3 (TUSC3) on autophagy in human non-small cell lung cancer (NSCLC) cells. A total of 118 NSCLC patients (88 males and 30 females) who underwent surgery at our institute were enrolled in the study. Immunohistochemical analysis revealed that TUSC3 protein expression was lower in NSCLC specimens than adjacent normal tissue. Correspondingly, there was greater methylation of TUSC3 in NSCLC than adjacent normal tissue. After transient transf...

  4. Dual small-molecule targeting of SMAD signaling stimulates human induced pluripotent stem cells toward neural lineages.

    Directory of Open Access Journals (Sweden)

    Methichit Wattanapanitch

    Full Text Available Incurable neurological disorders such as Parkinson's disease (PD, Huntington's disease (HD, and Alzheimer's disease (AD are very common and can be life-threatening because of their progressive disease symptoms with limited treatment options. To provide an alternative renewable cell source for cell-based transplantation and as study models for neurological diseases, we generated induced pluripotent stem cells (iPSCs from human dermal fibroblasts (HDFs and then differentiated them into neural progenitor cells (NPCs and mature neurons by dual SMAD signaling inhibitors. Reprogramming efficiency was improved by supplementing the histone deacethylase inhibitor, valproic acid (VPA, and inhibitor of p160-Rho associated coiled-coil kinase (ROCK, Y-27632, after retroviral transduction. We obtained a number of iPS colonies that shared similar characteristics with human embryonic stem cells in terms of their morphology, cell surface antigens, pluripotency-associated gene and protein expressions as well as their in vitro and in vivo differentiation potentials. After treatment with Noggin and SB431542, inhibitors of the SMAD signaling pathway, HDF-iPSCs demonstrated rapid and efficient differentiation into neural lineages. Six days after neural induction, neuroepithelial cells (NEPCs were observed in the adherent monolayer culture, which had the ability to differentiate further into NPCs and neurons, as characterized by their morphology and the expression of neuron-specific transcripts and proteins. We propose that our study may be applied to generate neurological disease patient-specific iPSCs allowing better understanding of disease pathogenesis and drug sensitivity assays.

  5. Targeting PERK signaling with the small molecule GSK2606414 prevents neurodegeneration in a model of Parkinson's disease.

    Science.gov (United States)

    Mercado, Gabriela; Castillo, Valentina; Soto, Paulina; López, Nélida; Axten, Jeffrey M; Sardi, Sergio P; Hoozemans, Jeroen J M; Hetz, Claudio

    2018-04-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder, leading to the progressive decline of motor control due to the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Accumulating evidence suggest that altered proteostasis is a salient feature of PD, highlighting perturbations to the endoplasmic reticulum (ER), the main compartment involved in protein folding and secretion. PERK is a central ER stress sensor that enforces adaptive programs to recover homeostasis through a block of protein translation and the induction of the transcription factor ATF4. In addition, chronic PERK signaling results in apoptosis induction and neuronal dysfunction due to the repression in the translation of synaptic proteins. Here we confirmed the activation of PERK signaling in postmortem brain tissue derived from PD patients and three different rodent models of the disease. Pharmacological targeting of PERK by the oral administration of GSK2606414 demonstrated efficient inhibition of the pathway in the SNpc after experimental ER stress stimulation. GSK2606414 protected nigral-dopaminergic neurons against a PD-inducing neurotoxin, improving motor performance. The neuroprotective effects of PERK inhibition were accompanied by an increase in dopamine levels and the expression of synaptic proteins. However, GSK2606414 treated animals developed secondary effects possibly related to pancreatic toxicity. This study suggests that strategies to attenuate ER stress levels may be effective to reduce neurodegeneration in PD. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Risk Perception and Social Amplification

    International Nuclear Information System (INIS)

    Smith, R.E.

    2001-01-01

    This paper seeks to consider social amplification as it applies to risk perception. Perceptions of the magnitude of a risk are conditioned by issues such as the degree of uncertainty in probability and consequences, the nature of the consequences and the relative weightings placed on probability and consequences. Risk perceptions are also influenced by factors such as confidence in the operator of an industrial process, trust in the regulator and the perceived fairness of regulatory decision-making. Different people may hold different views about these issues and there may also be difficulties in communication. The paper identifies and discusses self-reinforcing mechanisms, which will be labelled 'lock-in' here. They appear to apply in many situations where social amplification is observed. Historically, the term 'lock-in' has been applied mainly in the technological context but, in this paper, four types of lock-in are identified, namely scientific/technological, economic, social and institutional lock-in. One type of lock-in tends to lead to the next and all are buttressed by people's general acceptance of the familiar, fear of the unknown and resistance to change. The regulator seeks to make decisions which achieve the common good rather than supporting or perpetuating any set of vested interests. In this regard the locked-in positions of stakeholders, whether organisations, interest groups, or individual members of the public, are obstacles and challenges. Existing methods of consultation are unsatisfactory in terms of achieving a proper and productive level of dialogue with stakeholders

  7. Small signal modulation characteristics of red-emitting (λ = 610 nm) III-nitride nanowire array lasers on (001) silicon

    KAUST Repository

    Jahangir, Shafat; Frost, Thomas; Hazari, Arnab; Yan, Lifan; Stark, Ethan; LaMountain, Trevor; Millunchick, Joanna M.; Ooi, Boon S.; Bhattacharya, Pallab

    2015-01-01

    The small signal modulation characteristics of an InGaN/GaN nanowire array edge- emitting laser on (001) silicon are reported. The emission wavelength is 610 nm. Lattice matched InAlN cladding layers were incorporated in the laser heterostructure for better mode confinement. The suitability of the nanowire lasers for use in plastic fiber communication systems with direct modulation is demonstrated through their modulation bandwidth of f-3dB,max = 3.1 GHz, very low values of chirp (0.8 Å) and α-parameter, and large differential gain (3.1 × 10-17 cm2).

  8. Small signal modulation characteristics of red-emitting (λ = 610 nm) III-nitride nanowire array lasers on (001) silicon

    KAUST Repository

    Jahangir, Shafat

    2015-02-16

    The small signal modulation characteristics of an InGaN/GaN nanowire array edge- emitting laser on (001) silicon are reported. The emission wavelength is 610 nm. Lattice matched InAlN cladding layers were incorporated in the laser heterostructure for better mode confinement. The suitability of the nanowire lasers for use in plastic fiber communication systems with direct modulation is demonstrated through their modulation bandwidth of f-3dB,max = 3.1 GHz, very low values of chirp (0.8 Å) and α-parameter, and large differential gain (3.1 × 10-17 cm2).

  9. Catechol-chitosan redox capacitor for added amplification in electrochemical immunoanalysis.

    Science.gov (United States)

    Yan, Kun; Liu, Yi; Guan, Yongguang; Bhokisham, Narendranath; Tsao, Chen-Yu; Kim, Eunkyoung; Shi, Xiao-Wen; Wang, Qin; Bentley, William E; Payne, Gregory F

    2018-05-22

    Antibodies are common recognition elements for molecular detection but often the signals generated by their stoichiometric binding must be amplified to enhance sensitivity. Here, we report that an electrode coated with a catechol-chitosan redox capacitor can amplify the electrochemical signal generated from an alkaline phosphatase (AP) linked immunoassay. Specifically, the AP product p-aminophenol (PAP) undergoes redox-cycling in the redox capacitor to generate amplified oxidation currents. We estimate an 8-fold amplification associated with this redox-cycling in the capacitor (compared to detection by a bare electrode). Importantly, this capacitor-based amplification is generic and can be coupled to existing amplification approaches based on enzyme-linked catalysis or magnetic nanoparticle-based collection/concentration. Thus, the capacitor should enhance sensitivities in conventional immunoassays and also provide chemical to electrical signal transduction for emerging applications in molecular communication. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Optical parametric amplification and oscillation assisted by low-frequency stimulated emission.

    Science.gov (United States)

    Longhi, Stefano

    2016-04-15

    Optical parametric amplification and oscillation provide powerful tools for coherent light generation in spectral regions inaccessible to lasers. Parametric gain is based on a frequency down-conversion process and, thus, it cannot be realized for signal waves at a frequency ω3 higher than the frequency of the pump wave ω1. In this Letter, we suggest a route toward the realization of upconversion optical parametric amplification and oscillation, i.e., amplification of the signal wave by a coherent pump wave of lower frequency, assisted by stimulated emission of the auxiliary idler wave. When the signal field is resonated in an optical cavity, parametric oscillation is obtained. Design parameters for the observation of upconversion optical parametric oscillation at λ3=465 nm are given for a periodically poled lithium-niobate (PPLN) crystal doped with Nd(3+) ions.

  11. A Label-Free and Sensitive Fluorescent Qualitative Assay for Bisphenol A Based on Rolling Circle Amplification/Exonuclease III-Combined Cascade Amplification.

    Science.gov (United States)

    Li, Xia; Song, Juan; Xue, Qing-Wang; You, Fu-Heng; Lu, Xia; Kong, Yan-Cong; Ma, Shu-Yi; Jiang, Wei; Li, Chen-Zhong

    2016-10-21

    Bisphenol A (BPA) detection in drinking water and food packaging materials has attracted much attention since the discovery that BPA can interfere with normal physiological processes and cause adverse health effects. Here, we constructed a label-free aptamer fluorescent assay for selective and sensitive detection of BPA based on the rolling circle amplification (RCA)/Exonuclease III (Exo III)-combined cascade amplification strategy. First, the duplex DNA probe (RP) with anti-BPA aptamer and trigger sequence was designed for BPA recognition and signal amplification. Next, under the action of BPA, the trigger probe was liberated from RP to initiate RCA reaction as primary amplification. Subsequently, the RCA products were used to trigger Exo III assisted secondary amplification with the help of hairpin probes, producing plenty of "G-quadruplex" in lantern-like structures. Finally, the continuously enriched "G-quadruplex lanterns" were lightened by zinc(II)-protoporphyrin IX (ZnPPIX) generating enhanced fluorescence signals. By integrating the primary RCA and secondary Exo III mediated cascade amplification strategy, this method displayed an excellent sensitivity with the detection limits of 5.4 × 10 -17 M. In addition, the anti-BPA aptamer exhibits high recognition ability with BPA, guaranteeing the specificity of detection. The reporter signal probe (G-quadruplex with ZnPPIX) provides a label-free fluorescence signals readout without complicated labeling procedures, making the method simple in design and cost-effective in operation. Moreover, environmental samples analysis was also performed, suggesting that our strategy was reliable and had a great potential application in environmental monitoring.

  12. A Label-Free and Sensitive Fluorescent Qualitative Assay for Bisphenol A Based on Rolling Circle Amplification/Exonuclease III-Combined Cascade Amplification

    Directory of Open Access Journals (Sweden)

    Xia Li

    2016-10-01

    Full Text Available Bisphenol A (BPA detection in drinking water and food packaging materials has attracted much attention since the discovery that BPA can interfere with normal physiological processes and cause adverse health effects. Here, we constructed a label-free aptamer fluorescent assay for selective and sensitive detection of BPA based on the rolling circle amplification (RCA/Exonuclease III (Exo III-combined cascade amplification strategy. First, the duplex DNA probe (RP with anti-BPA aptamer and trigger sequence was designed for BPA recognition and signal amplification. Next, under the action of BPA, the trigger probe was liberated from RP to initiate RCA reaction as primary amplification. Subsequently, the RCA products were used to trigger Exo III assisted secondary amplification with the help of hairpin probes, producing plenty of “G-quadruplex” in lantern-like structures. Finally, the continuously enriched “G-quadruplex lanterns” were lightened by zinc(II-protoporphyrin IX (ZnPPIX generating enhanced fluorescence signals. By integrating the primary RCA and secondary Exo III mediated cascade amplification strategy, this method displayed an excellent sensitivity with the detection limits of 5.4 × 10−17 M. In addition, the anti-BPA aptamer exhibits high recognition ability with BPA, guaranteeing the specificity of detection. The reporter signal probe (G-quadruplex with ZnPPIX provides a label-free fluorescence signals readout without complicated labeling procedures, making the method simple in design and cost-effective in operation. Moreover, environmental samples analysis was also performed, suggesting that our strategy was reliable and had a great potential application in environmental monitoring.

  13. Small tyrosine kinase inhibitors interrupt EGFR signaling by interacting with erbB3 and erbB4 in glioblastoma cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Carrasco-Garcia, Estefania; Saceda, Miguel [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Unidad de Investigacion, Hospital General Universitario de Elche, 03203 Elche (Alicante) (Spain); Grasso, Silvina; Rocamora-Reverte, Lourdes; Conde, Mariano; Gomez-Martinez, Angeles [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Garcia-Morales, Pilar [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Unidad de Investigacion, Hospital General Universitario de Elche, 03203 Elche (Alicante) (Spain); Ferragut, Jose A. [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Martinez-Lacaci, Isabel, E-mail: imlacaci@umh.es [Instituto de Biologia Molecular y Celular, Universidad Miguel Hernandez, 03202 Elche (Alicante) (Spain); Unidad AECC de Investigacion Traslacional en Cancer, Hospital Universitario Virgen de la Arrixaca, 30120 Murcia (Spain)

    2011-06-10

    Signaling through the epidermal growth factor receptor (EGFR) is relevant in glioblastoma. We have determined the effects of the EGFR inhibitor AG1478 in glioblastoma cell lines and found that U87 and LN-229 cells were very sensitive to this drug, since their proliferation diminished and underwent a marked G{sub 1} arrest. T98 cells were a little more refractory to growth inhibition and A172 cells did not undergo a G{sub 1} arrest. This G{sub 1} arrest was associated with up-regulation of p27{sup kip1}, whose protein turnover was stabilized. EGFR autophosphorylation was blocked with AG1478 to the same extent in all the cell lines. Other small-molecule EGFR tyrosine kinase inhibitors employed in the clinic, such as gefitinib, erlotinib and lapatinib, were able to abrogate proliferation of glioblastoma cell lines, which underwent a G{sub 1} arrest. However, the EGFR monoclonal antibody, cetuximab had no effect on cell proliferation and consistently, had no effect on cell cycle either. Similarly, cetuximab did not inhibit proliferation of U87 {Delta}EGFR cells or primary glioblastoma cell cultures, whereas small-molecule EGFR inhibitors did. Activity of downstream signaling molecules of EGFR such as Akt and especially ERK1/2 was interrupted with EGFR tyrosine kinase inhibitors, whereas cetuximab treatment could not sustain this blockade over time. Small-molecule EGFR inhibitors were able to prevent phosphorylation of erbB3 and erbB4, whereas cetuximab only hindered EGFR phosphorylation, suggesting that EGFR tyrosine kinase inhibitors may mediate their anti-proliferative effects through other erbB family members. We can conclude that small-molecule EGFR inhibitors may be a therapeutic approach for the treatment of glioblastoma patients.

  14. DUAL INHIBITION OF PI3K/AKT AND mTOR SIGNALING IN HUMAN NON-SMALL CELL LUNG CANCER CELLS BY A DIETARY FLAVONOID FISETIN

    Science.gov (United States)

    Khan, Naghma; Afaq, Farrukh; Khusro, Fatima H.; Adhami, Vaqar Mustafa; Suh, Yewseok; Mukhtar, Hasan

    2011-01-01

    Lung cancer is one of the most commonly occurring malignancies. It has been reported that mTOR is phosphorylated in lung cancer and its activation was more frequent in tumors with over-expression of PI3K/Akt. Therefore, dual inhibitors of PI3K/Akt and mTOR signaling could be valuable agents for treating lung cancer. In the present study, we show that fisetin, a dietary tetrahydroxyflavone inhibits cell-growth with the concomitant suppression of PI3K/Akt and mTOR signaling in human non-small cell lung cancer (NSCLC) cells. Using autodock 4, we found that fisetin physically interacts with the mTOR complex at two sites. Fisetin treatment was also found to reduce the formation of A549 cell colonies in a dose-dependent manner. Treatment of cells with fisetin caused decrease in the protein expression of PI3K (p85 and p110), inhibition of phosphorylation of Akt, mTOR, p70S6K1, eIF-4E and 4E-BP1. Fisetin-treated cells also exhibited dose-dependent inhibition of the constituents of mTOR signaling complex like Rictor, Raptor, GβL and PRAS40. There was increase in the phosphorylation of AMPKα and decrease in the phosphorylation of TSC2 on treatment of cells with fisetin. We also found that treatment of cells with mTOR inhibitor rapamycin and mTOR-siRNA caused decrease in phosphorylation of mTOR and its target proteins which were further downregulated on treatment with fisetin, suggesting that these effects are mediated in part, through mTOR signaling. Our results show that fisetin suppressed PI3K/Akt and mTOR signaling in NSCLC cells and thus, could be developed as a chemotherapeutic agent against human lung cancer. PMID:21618507

  15. Ultrashort pulse shaping by optical parametric chirped amplification

    International Nuclear Information System (INIS)

    Nelet, Ambre

    2007-01-01

    The aim of this work is to propose new laser architectures based on optical parametric chirped pulse amplification (OPCPA). Common goals of OPCPA pre-amplifiers are to reach high energy level while maintaining the spectrum width and to adapt geometry of the amplified beam to the high power laser chain optics. We consider OPCPA as a way to control and to sculpt ultrashort pulses. Our first set-up aims at thwarting possible time recovery default between pump and signal pulses, which lower the energy extraction. A regenerative OPCPA, idler resonant, is a way to produce a high-intensity and high-repetition rate train of amplified signal replicas. Our second laser system pre-compensates the spectral gain narrowing by sculpting pulses directly within the OPCPA section, where a temporal shaping of the pump beam permits a spectro-spectral shaping of the amplified signal. Finally, we propose an OPCPA based on spatial coding and uniform amplification of spectral signal components by using a fan-out periodically poled crystal and a zero dispersion line. (author) [fr

  16. Ectopic expression of miR-34a enhances radiosensitivity of non-small cell lung cancer cells, partly by suppressing the LyGDI signaling pathway

    International Nuclear Information System (INIS)

    Duan Weiming; Xu Yaxiang; Dong Yujin; Cao Lili; Tong Jian; Zhou Xinwen

    2013-01-01

    miR-34a is transcriptionally induced by the tumor suppressor gene p53, which is often downregulated in non-small cell lung cancer (NSCLC). To address whether the downstream signal of miR-34a is sufficient to induce apoptosis and to alter cellular radiosensitivity, a chemical synthetic miR-34a mimic was delivered into A549 and H1299 cells, with or without co-treatment of γ-irradiation. Results showed that ectopic expression of miR-34a induced dose-dependent cell growth inhibition and apoptosis in a p53-independent manner in both NSCLC cell lines. Interestingly, LyGDI was discovered as a new target gene of miR-34a, and downregulation of LyGDI promoted Rac1 activation and membrane translocation, resulting in cell apoptosis. Furthermore, restoration of miR-34a indirectly reduced cyclooxygenase-2 (COX-2) expression. Taken together, these results demonstrate that restoration of miR-34a expression enhances radiation-induced apoptosis, partly by suppressing the LyGDI signaling pathway, and miR-34a could possibly be used as a radiosensitizer for non-small cell lung cancer therapy. (author)

  17. AsHSP17, a creeping bentgrass small heat shock protein modulates plant photosynthesis and ABA-dependent and independent signalling to attenuate plant response to abiotic stress.

    Science.gov (United States)

    Sun, Xinbo; Sun, Chunyu; Li, Zhigang; Hu, Qian; Han, Liebao; Luo, Hong

    2016-06-01

    Heat shock proteins (HSPs) are molecular chaperones that accumulate in response to heat and other abiotic stressors. Small HSPs (sHSPs) belong to the most ubiquitous HSP subgroup with molecular weights ranging from 12 to 42 kDa. We have cloned a new sHSP gene, AsHSP17 from creeping bentgrass (Agrostis stolonifera) and studied its role in plant response to environmental stress. AsHSP17 encodes a protein of 17 kDa. Its expression was strongly induced by heat in both leaf and root tissues, and by salt and abscisic acid (ABA) in roots. Transgenic Arabidopsis plants constitutively expressing AsHSP17 exhibited enhanced sensitivity to heat and salt stress accompanied by reduced leaf chlorophyll content and decreased photosynthesis under both normal and stressed conditions compared to wild type. Overexpression of AsHSP17 also led to hypersensitivity to exogenous ABA and salinity during germination and post-germinative growth. Gene expression analysis indicated that AsHSP17 modulates expression of photosynthesis-related genes and regulates ABA biosynthesis, metabolism and ABA signalling as well as ABA-independent stress signalling. Our results suggest that AsHSP17 may function as a protein chaperone to negatively regulate plant responses to adverse environmental stresses through modulating photosynthesis and ABA-dependent and independent signalling pathways. © 2015 John Wiley & Sons Ltd.

  18. Digital Droplet Multiple Displacement Amplification (ddMDA for Whole Genome Sequencing of Limited DNA Samples.

    Directory of Open Access Journals (Sweden)

    Minsoung Rhee

    Full Text Available Multiple displacement amplification (MDA is a widely used technique for amplification of DNA from samples containing limited amounts of DNA (e.g., uncultivable microbes or clinical samples before whole genome sequencing. Despite its advantages of high yield and fidelity, it suffers from high amplification bias and non-specific amplification when amplifying sub-nanogram of template DNA. Here, we present a microfluidic digital droplet MDA (ddMDA technique where partitioning of the template DNA into thousands of sub-nanoliter droplets, each containing a small number of DNA fragments, greatly reduces the competition among DNA fragments for primers and polymerase thereby greatly reducing amplification bias. Consequently, the ddMDA approach enabled a more uniform coverage of amplification over the entire length of the genome, with significantly lower bias and non-specific amplification than conventional MDA. For a sample containing 0.1 pg/μL of E. coli DNA (equivalent of ~3/1000 of an E. coli genome per droplet, ddMDA achieves a 65-fold increase in coverage in de novo assembly, and more than 20-fold increase in specificity (percentage of reads mapping to E. coli compared to the conventional tube MDA. ddMDA offers a powerful method useful for many applications including medical diagnostics, forensics, and environmental microbiology.

  19. Multiscale image contrast amplification (MUSICA)

    Science.gov (United States)

    Vuylsteke, Pieter; Schoeters, Emile P.

    1994-05-01

    This article presents a novel approach to the problem of detail contrast enhancement, based on multiresolution representation of the original image. The image is decomposed into a weighted sum of smooth, localized, 2D basis functions at multiple scales. Each transform coefficient represents the amount of local detail at some specific scale and at a specific position in the image. Detail contrast is enhanced by non-linear amplification of the transform coefficients. An inverse transform is then applied to the modified coefficients. This yields a uniformly contrast- enhanced image without artefacts. The MUSICA-algorithm is being applied routinely to computed radiography images of chest, skull, spine, shoulder, pelvis, extremities, and abdomen examinations, with excellent acceptance. It is useful for a wide range of applications in the medical, graphical, and industrial area.

  20. Measuring the amplification of attention.

    Science.gov (United States)

    Blaser, E; Sperling, G; Lu, Z L

    1999-09-28

    An ambiguous motion paradigm, in which the direction of apparent motion is determined by salience (i.e., the extent to which an area is perceived as figure versus ground), is used to assay the amplification of color by attention to color. In the red-green colored gratings used in these experiments, without attention instructions, salience depends on the chromaticity difference between colored stripes embedded in the motion sequence and the yellow background. Selective attention to red (or to green) alters the perceived direction of motion and is found to be equivalent to increasing the physical redness (or greenness) by 25-117%, depending on the observer and color. Whereas attention to a color drastically alters the salience of that color, it leaves color appearance unchanged. A computational model, which embodies separate, parallel pathways for object perception and for salience, accounts for 99% of the variance of the experimental data.

  1. New small molecule inhibitors of UPR activation demonstrate that PERK, but not IRE1α signaling is essential for promoting adaptation and survival to hypoxia

    International Nuclear Information System (INIS)

    Cojocari, Dan; Vellanki, Ravi N.; Sit, Brandon; Uehling, David; Koritzinsky, Marianne; Wouters, Bradly G.

    2013-01-01

    Background and purpose: The unfolded protein response (UPR) is activated in response to hypoxia-induced stress in the endoplasmic reticulum (ER) and consists of three distinct signaling arms. Here we explore the potential of targeting two of these arms with new potent small-molecule inhibitors designed against IRE1α and PERK. Methods: We utilized shRNAs and small-molecule inhibitors of IRE1α (4μ8c) and PERK (GSK-compound 39). XBP1 splicing and DNAJB9 mRNA was measured by qPCR and was used to monitor IRE1α activity. PERK activity was monitored by immunoblotting eIF2α phosphorylation and qPCR of DDIT3 mRNA. Hypoxia tolerance was measured using proliferation and clonogenic cell survival assays of cells exposed to mild or severe hypoxia in the presence of the inhibitors. Results: Using knockdown experiments we show that PERK is essential for survival of KP4 cells while knockdown of IRE1α dramatically decreases the proliferation and survival of HCT116 during hypoxia. Further, we show that in response to both hypoxia and other ER stress-inducing agents both 4μ8c and the PERK inhibitor are selective and potent inhibitors of IRE1α and PERK activation, respectively. However, despite potent inhibition of IRE1α activation, 4μ8c had no effect on cell proliferation or clonogenic survival of cells exposed to hypoxia. This was in contrast to the inactivation of PERK signaling with the PERK inhibitor, which reduced tolerance to hypoxia and other ER stress inducing agents. Conclusions: Our results demonstrate that IRE1α but not its splicing activity is important for hypoxic cell survival. The PERK signaling arm is uniquely important for promoting adaptation and survival during hypoxia-induced ER stress and should be the focus of future therapeutic efforts

  2. A novel role for small molecule glycomimetics in the protection against lipid-induced endothelial dysfunction: Involvement of Akt/eNOS and Nrf2/ARE signaling.

    Science.gov (United States)

    Mahmoud, Ayman M; Wilkinson, Fiona L; Jones, Alan M; Wilkinson, James A; Romero, Miguel; Duarte, Juan; Alexander, M Yvonne

    2017-01-01

    Glycomimetics are a diverse array of saccharide-inspired compounds, designed to mimic the bioactive functions of glycosaminoglycans. Therefore, glycomimetics represent a unique source of novel therapies to target aberrant signaling and protein interactions in a wide range of diseases. We investigated the protective effects of four newly synthesized small molecule glycomimetics against lipid-induced endothelial dysfunction, with an emphasis on nitric oxide (NO) and oxidative stress. Four aromatic sugar mimetics were synthesized by the stepwise transformation of 2,5-dihydroxybenzoic acid to derivatives (C1-C4) incorporating sulfate groups to mimic the structure of heparan sulfate. Glycomimetic-treated human umbilical vein endothelial cells (HUVECs) were exposed to palmitic acid to model lipid-induced oxidative stress. Palmitate-induced impairment of NO production was restored by the glycomimetics, through activation of Akt/eNOS signaling. Furthermore, C1-C4 significantly inhibited palmitate-induced reactive oxygen species (ROS) production, lipid peroxidation, and activity and expression of NADPH oxidase. These effects were attributed to activation of the Nrf2/ARE pathway and downstream activation of cellular antioxidant and cytoprotective proteins. In ex vivo vascular reactivity studies, the glycomimetics (C1-C4) also demonstrated a significant improvement in endothelium-dependent relaxation and decreased ROS production and NADPH oxidase activity in isolated mouse thoracic aortic rings exposed to palmitate. The small molecule glycomimetics, C1-C4, protect against lipid-induced endothelial dysfunction through up-regulation of Akt/eNOS and Nrf2/ARE signaling pathways. Thus, carbohydrate-derived therapeutics are a new class of glycomimetic drugs targeting endothelial dysfunction, regarded as the first line of defense against vascular complications in cardiovascular disease. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Risk Perception and Social Amplification

    Energy Technology Data Exchange (ETDEWEB)

    Smith, R.E. [Environment Agency (United Kingdom)

    2001-07-01

    This paper seeks to consider social amplification as it applies to risk perception. Perceptions of the magnitude of a risk are conditioned by issues such as the degree of uncertainty in probability and consequences, the nature of the consequences and the relative weightings placed on probability and consequences. Risk perceptions are also influenced by factors such as confidence in the operator of an industrial process, trust in the regulator and the perceived fairness of regulatory decision-making. Different people may hold different views about these issues and there may also be difficulties in communication. The paper identifies and discusses self-reinforcing mechanisms, which will be labelled 'lock-in' here. They appear to apply in many situations where social amplification is observed. Historically, the term 'lock-in' has been applied mainly in the technological context but, in this paper, four types of lock-in are identified, namely scientific/technological, economic, social and institutional lock-in. One type of lock-in tends to lead to the next and all are buttressed by people's general acceptance of the familiar, fear of the unknown and resistance to change. The regulator seeks to make decisions which achieve the common good rather than supporting or perpetuating any set of vested interests. In this regard the locked-in positions of stakeholders, whether organisations, interest groups, or individual members of the public, are obstacles and challenges. Existing methods of consultation are unsatisfactory in terms of achieving a proper and productive level of dialogue with stakeholders.

  4. Inhibitor of PI3K/Akt Signaling Pathway Small Molecule Promotes Motor Neuron Differentiation of Human Endometrial Stem Cells Cultured on Electrospun Biocomposite Polycaprolactone/Collagen Scaffolds.

    Science.gov (United States)

    Ebrahimi-Barough, Somayeh; Hoveizi, Elham; Yazdankhah, Meysam; Ai, Jafar; Khakbiz, Mehrdad; Faghihi, Faezeh; Tajerian, Roksana; Bayat, Neda

    2017-05-01

    Small molecules as useful chemical tools can affect cell differentiation and even change cell fate. It is demonstrated that LY294002, a small molecule inhibitor of phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway, can inhibit proliferation and promote neuronal differentiation of mesenchymal stem cells (MSCs). The purpose of this study was to investigate the differentiation effect of Ly294002 small molecule on the human endometrial stem cells (hEnSCs) into motor neuron-like cells on polycaprolactone (PCL)/collagen scaffolds. hEnSCs were cultured in a neurogenic inductive medium containing 1 μM LY294002 on the surface of PCL/collagen electrospun fibrous scaffolds. Cell attachment and viability of cells on scaffolds were characterized by scanning electron microscope (SEM) and 3-(4,5-dimethylthiazoyl-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay. The expression of neuron-specific markers was assayed by real-time PCR and immunocytochemistry analysis after 15 days post induction. Results showed that attachment and differentiation of hEnSCs into motor neuron-like cells on the scaffolds with Ly294002 small molecule were higher than that of the cells on tissue culture plates as control group. In conclusion, PCL/collagen electrospun scaffolds with Ly294002 have potential for being used in neural tissue engineering because of its bioactive and three-dimensional structure which enhances viability and differentiation of hEnSCs into neurons through inhibition of the PI3K/Akt pathway. Thus, manipulation of this pathway by small molecules can enhance neural differentiation.

  5. Small-molecule synthetic compound norcantharidin reverses multi-drug resistance by regulating Sonic hedgehog signaling in human breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Yu-Jen Chen

    Full Text Available Multi-drug resistance (MDR, an unfavorable factor compromising treatment efficacy of anticancer drugs, involves upregulated ATP binding cassette (ABC transporters and activated Sonic hedgehog (Shh signaling. By preparing human breast cancer MCF-7 cells resistant to doxorubicin (DOX, we examined the effect and mechanism of norcantharidin (NCTD, a small-molecule synthetic compound, on reversing multidrug resistance. The DOX-prepared MCF-7R cells also possessed resistance to vinorelbine, characteristic of MDR. At suboptimal concentration, NCTD significantly inhibited the viability of DOX-sensitive (MCF-7S and DOX-resistant (MCF-7R cells and reversed the resistance to DOX and vinorelbine. NCTD increased the intracellular accumulation of DOX in MCF-7R cells and suppressed the upregulated the mdr-1 mRNA, P-gp and BCRP protein expression, but not the MRP-1. The role of P-gp was strengthened by partial reversal of the DOX and vinorelbine resistance by cyclosporine A. NCTD treatment suppressed the upregulation of Shh expression and nuclear translocation of Gli-1, a hallmark of Shh signaling activation in the resistant clone. Furthermore, the Shh ligand upregulated the expression of P-gp and attenuated the growth inhibitory effect of NCTD. The knockdown of mdr-1 mRNA had not altered the expression of Shh and Smoothened in both MCF-7S and MCF-7R cells. This indicates that the role of Shh signaling in MDR might be upstream to mdr-1/P-gp, and similar effect was shown in breast cancer MDA-MB-231 and BT-474 cells. This study demonstrated that NCTD may overcome multidrug resistance through inhibiting Shh signaling and expression of its downstream mdr-1/P-gp expression in human breast cancer cells.

  6. Importance of a diffusion-dominant small volume to activate cell-secreted soluble factor signaling in embryonic stem cell culture in microbioreactors: a mathematical model based study.

    Science.gov (United States)

    Chowdhury, Mohammad Mahfuz; Fujii, Teruo; Sakai, Yasuyuki

    2013-07-01

    In our previous studies, we observed that cell-secreted BMP4 had a prominent influence on mouse embryonic stem cell (mESC) behaviors in a membrane-based two-chambered microbioreactor (MB), but not in a macro-scale culture (6-well plate/6WP). In this study, we investigated how the physical aspects of these cultures regulated BMP4 signaling by developing mathematical models of the cultures. The models estimated signaling activity in the cultures by considering size of the undifferentiated mESC colonies and their growth, diffusion of BMP4, and BMP4 trafficking process in the colonies. The models successfully depicted measured profile of BMP4 concentration in the culture medium which was two times higher in the MB than that in the 6WP during 5-day culture. The models estimated that, owing to the small volume and the membrane, cells were exposed to a higher BMP4 concentration in the top chamber of the MB than that in the 6WP culture. The higher concentration of BMP4 induced a higher concentration of BMP4-bound receptor in the colony in the MB than in the 6WP, thereby leading to the higher activation of BMP4 signaling in the MB. The models also predicted that the size of the MB, but not that of the 6WP, was suitable for maximizing BMP4 accumulation and upregulating its signaling. This study will be helpful in analyzing culture systems, designing microfluidic devices for controlling ESC or other cell behavior. Copyright © 2013 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  7. Coordinated regulation by two VPS9 domain-containing guanine nucleotide exchange factors in small GTPase Rab5 signaling pathways in fission yeast

    International Nuclear Information System (INIS)

    Tsukamoto, Yuta; Kagiwada, Satoshi; Shimazu, Sayuri; Takegawa, Kaoru; Noguchi, Tetsuko; Miyamoto, Masaaki

    2015-01-01

    The small GTPase Rab5 is reported to regulate various cellular functions, such as vesicular transport and endocytosis. VPS9 domain-containing proteins are thought to activate Rab5(s) by their guanine-nucleotide exchange activities. Numerous VPS9 proteins have been identified and are structurally conserved from yeast to mammalian cells. However, the functional relationships among VPS9 proteins in cells remain unclear. Only one Rab5 and two VPS9 proteins were identified in the Schizosaccharomyces pombe genome. Here, we examined the cellular function of two VPS9 proteins and the relationship between these proteins in cellular functions. Vps901-GFP and Vps902-GFP exhibited dotted signals in vegetative and differentiated cells. vps901 deletion mutant (Δvps901) cells exhibited a phenotype deficient in the mating process and responses to high concentrations of ions, such as calcium and metals, and Δvps901Δvps902 double mutant cells exhibited round cell shapes similar to ypt5-909 (Rab5 mutant allele) cells. Deletion of both vps901 and vps902 genes completely abolished the mating process and responses to various stresses. A lack of vacuole formation and aberrant inner cell membrane structures were also observed in Δvps901Δvps902 cells by electron microscopy. These data strongly suggest that Vps901 and Vps902 are cooperatively involved in the regulation of cellular functions, such as cell morphology, sexual development, response to ion stresses, and vacuole formation, via Rab5 signaling pathways in fission yeast cells. - Highlights: • Roles of Rab5 activator VPS9 proteins in cellular functions. • Cooperation between VPS9 proteins in Rab5 signaling pathway. • Roles of each VPS9 protein in Rab5 signaling pathway are discussed

  8. Coordinated regulation by two VPS9 domain-containing guanine nucleotide exchange factors in small GTPase Rab5 signaling pathways in fission yeast

    Energy Technology Data Exchange (ETDEWEB)

    Tsukamoto, Yuta [Department of Biology, Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501 (Japan); Kagiwada, Satoshi [Department of Biological Sciences, Faculty of Science, Nara Women' s University, Kitauoyanishi-machi, Nara 630-8506 (Japan); Shimazu, Sayuri [Center for Supports to Research and Education Activities, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501 (Japan); Takegawa, Kaoru [Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan); Noguchi, Tetsuko [Department of Biological Sciences, Faculty of Science, Nara Women' s University, Kitauoyanishi-machi, Nara 630-8506 (Japan); Miyamoto, Masaaki, E-mail: miya@kobe-u.ac.jp [Department of Biology, Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501 (Japan); Center for Supports to Research and Education Activities, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501 (Japan)

    2015-03-20

    The small GTPase Rab5 is reported to regulate various cellular functions, such as vesicular transport and endocytosis. VPS9 domain-containing proteins are thought to activate Rab5(s) by their guanine-nucleotide exchange activities. Numerous VPS9 proteins have been identified and are structurally conserved from yeast to mammalian cells. However, the functional relationships among VPS9 proteins in cells remain unclear. Only one Rab5 and two VPS9 proteins were identified in the Schizosaccharomyces pombe genome. Here, we examined the cellular function of two VPS9 proteins and the relationship between these proteins in cellular functions. Vps901-GFP and Vps902-GFP exhibited dotted signals in vegetative and differentiated cells. vps901 deletion mutant (Δvps901) cells exhibited a phenotype deficient in the mating process and responses to high concentrations of ions, such as calcium and metals, and Δvps901Δvps902 double mutant cells exhibited round cell shapes similar to ypt5-909 (Rab5 mutant allele) cells. Deletion of both vps901 and vps902 genes completely abolished the mating process and responses to various stresses. A lack of vacuole formation and aberrant inner cell membrane structures were also observed in Δvps901Δvps902 cells by electron microscopy. These data strongly suggest that Vps901 and Vps902 are cooperatively involved in the regulation of cellular functions, such as cell morphology, sexual development, response to ion stresses, and vacuole formation, via Rab5 signaling pathways in fission yeast cells. - Highlights: • Roles of Rab5 activator VPS9 proteins in cellular functions. • Cooperation between VPS9 proteins in Rab5 signaling pathway. • Roles of each VPS9 protein in Rab5 signaling pathway are discussed.

  9. Association Mapping of Malting Quality Quantitative Trait Loci in Winter Barley: Positive Signals from Small Germplasm Arrays

    Directory of Open Access Journals (Sweden)

    Lucía Gutiérrez

    2011-11-01

    Full Text Available Malting quality comprises one of the most economically relevant set of traits in barley ( L.. It is a complex phenotype, expensive and difficult to measure, that would benefit from a marker-assisted selection strategy. Malting quality is a target of the U.S. Barley Coordinated Agricultural Project (CAP and development of winter habit malting barley varieties is a key objective of the U.S. barley research community. The objective of this work was to detect quantitative trait loci (QTL for malting quality traits in a winter breeding program that is a component of the U.S. Barley CAP. We studied the association between five malting quality traits and 3072 single nucleotide polymorphisms (SNPs from the barley oligonucleotide pool assay (BOPA 1 and 2, assayed in advanced inbred lines from the Oregon State University (OSU breeding program from three germplasm arrays (CAP I, CAP II, and CAP III. After comparing 16 models we selected a structured association model with posterior probabilities inferred from software STRUCTURE (QK approach to use on all germplasm arrays. Most of the marker-trait associations are germplasm- and environment-specific and close to previously mapped genes and QTL relevant for malt and beer quality. We found alleles fixed by random genetic drift, novel unmasked alleles, and genetic-background interaction. In a relatively small population size study we provide strong evidence for detecting true QTL.

  10. Call for Action: Invasive Fungal Infections Associated With Ibrutinib and Other Small Molecule Kinase Inhibitors Targeting Immune Signaling Pathways.

    Science.gov (United States)

    Chamilos, Georgios; Lionakis, Michail S; Kontoyiannis, Dimitrios P

    2018-01-06

    Opportunistic infections caused by Pneumocystis jirovecii, Cryptococcus neoformans, and ubiquitous airborne filamentous fungi have been recently reported in patients with hematological cancers historically considered at low risk for invasive fungal infections (IFIs), after receipt of the Bruton tyrosine kinase inhibitor ibrutinib. The spectrum and severity of IFIs often observed in these patients implies the presence of a complex immunodeficiency that may not be solely attributed to mere inhibition of Bruton tyrosine kinase. In view of the surge in development of small molecule kinase inhibitors for treatment of malignant and autoimmune diseases, it is possible that there would be an emergence of IFIs associated with the effects of these molecules on the immune system. Preclinical assessment of the immunosuppressive effects of kinase inhibitors and human studies aimed at improving patient risk stratification for development of IFIs could lead to prevention, earlier diagnosis, and better outcomes in affected patients. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  11. FGFR-1 amplification in metastatic lymph-nodal and haematogenous lobular breast carcinoma

    Directory of Open Access Journals (Sweden)

    Brunello Eleonora

    2012-12-01

    Full Text Available Abstract Background Lobular breast carcinoma usually shows poor responsiveness to chemotherapies and often lacks targeted therapies. Since FGFR1 expression has been shown to play pivotal roles in primary breast cancer tumorigenesis, we sought to analyze the status of FGFR1 gene in a metastatic setting of lobular breast carcinoma, since promising FGFR1 inhibitors has been recently developed. Methods Fifteen tissue metastases from lobular breast carcinomas with matched primary infiltrative lobular breast carcinoma were recruited. Eleven cases showed loco-regional lymph-nodal and four haematogenous metastases. FGFR-1 gene (8p12 amplification was evaluated by chromogenic in situ hybridization (CISH analysis. Her-2/neu and topoisomerase-IIα gene status was assessed. E-cadherin and Hercept Test were also performed. We distinguished amplification (>6 or cluster of signals versus gains (3–6 signals of the locus specific FGFR-1 gene. Results Three (20% primary lobular breast carcinomas showed >6 or cluster of FGFR1 signals (amplification, six cases (40% had a mean of three (range 3–6 chromogenic signals (gains whereas in 6 (40% was not observed any abnormality. Three of 15 metastasis (20% were amplified, 2/15 (13,4% did not. The ten remaining cases (66,6% showed three chromogenic signals. The three cases with FGFR-1 amplification matched with those primary breast carcinomas showing FGFR-1 amplification. The six cases showing FGFR-1 gains in the primary tumour again showed FGFR-1 gains in the metastases. Four cases showed gains of FGFR-1 gene signals in the metastases and not in the primary tumours. Her-2/neu gene amplification was not observed in all cases but one (6% case. Topoisomerase-IIα was not amplified in all cases. Conclusions 1 a subset of metastatic lobular breast carcinoma harbors FGFR-1 gene amplification or gains of chromogenic signals; 2 a minor heterogeneity has been observed after matching primary and metastatic carcinomas; 3 in the

  12. Ultrasmall volume molecular isothermal amplification in microfluidic chip with advanced surface processing

    International Nuclear Information System (INIS)

    Huang Guoliang; Yang Xiaoyong; Ma Li; Yang Xu

    2011-01-01

    In this paper, we developed a metal micro-fluidic chip with advanced surface processing for ultra-small volume molecular isothermal amplification. This method takes advantages of the nucleic acid amplification with good stability and consistency, high sensitivity about 31 genomic DNA copies and bacteria specific gene identification. Based on the advanced surface processing, the bioreaction assays of nucleic acid amplification was dropped about 392nl in volume. A high numerical aperture confocal optical detection system was advanced to sensitively monitor the DNA amplification with low noise and high power collecting fluorescence near to the optical diffraction limit. A speedy nucleic acid isothermal amplification was performed in the ultra-small volume microfluidic chip, where the time at the inflexions of second derivative to DNA exponential amplified curves was brought forward and the sensitivity was improved about 65 folds to that of in current 25μl Ep-tube amplified reaction, which indicates a promising clinic molecular diagnostics in the droplet amplification.

  13. A novel steric effect-regulated isothermal exponential amplification technology for the one-step homogeneous sensing of proteins.

    Science.gov (United States)

    Wu, Wanghua; Pan, Wufan; Yu, Dongdong; Yuan, Zhen; Qin, Yazhou; Lu, Yuxiang; Zhang, Tao; Zhou, Jianguang

    2018-02-12

    A simple and homogeneous technology, the steric effect-regulated isothermal exponential amplification reaction (SER-EXPAR), was developed to sense proteins. By using a small molecule linked DNA nanostructure, termed enzyme-binding hairpin (EBH), the protein-small molecule binding events could be readily sensed by utilizing the steric effect generated between the protein and enzyme. It set free the enzyme to be active again, thus regulating the amplification rate of EXPAR.

  14. Phase Sensitive Amplification using Parametric Processes in Optical Fibers

    DEFF Research Database (Denmark)

    Kang, Ning

    . Further, phase sensitive parametric processes in a nano-engineered silicon waveguide have been measured experimentally for the first time. Numerical optimizations show that with reduced waveguide propagation loss and reduced carrier life time, larger signal phase sensitive extinction ratio is achievable......Phase sensitive amplification using the parametric processes in fiber has the potential of delivering high gain and broadband operation with ultralow noise. It is able to regenerate both amplitude and phase modulated signals, simultaneously, with the appropriate design. This thesis concerns...... types. The regeneration capability of PSAs on phase encoded signal in an optical link has been optimized. Flat-top phase sensitive profile has been synthesized. It is able to provide simultaneous amplitude and phase noise squeezing, with enhanced phase noise margin compared to conventional designs...

  15. Synergistic Inhibition of Thalidomide and Icotinib on Human Non-Small Cell Lung Carcinomas Through ERK and AKT Signaling.

    Science.gov (United States)

    Sun, Xiang; Xu, Yang; Wang, Yi; Chen, Qian; Liu, Liu; Bao, Yangyi

    2018-05-15

    BACKGROUND Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have been widely used in the treatment of non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations. However, the survival of patients with EGFR-TKI administration is limited by the inevitable development of acquired drug resistance. Recently, multi-targeted drugs combination has been shown to be a promising strategy to improve the efficacy of EGFR-TKI treatment and enable the reduction of drug resistance in NSCLC. MATERIAL AND METHODS Humanized NSCLC cell lines PC9 and A549 were co-cultured with thalidomide and/or icotinib to test for anti-tumor efficiency. Cell proliferation was measured by MTT assay, cell apoptosis by flow cytometry and cell migration by wound healing assay. Western blot was performed to determine the expression of caspase-3, -8, -9, Bax, EGFR, VEGF-R, AKT, ERK, MMP2, MMP9, and NF-κB. The xenograft mouse model was used to explore the effects of thalidomide and icotinib in vivo. Immunohistochemical testing was used to determine the expression of Ki-67 and TUNEL staining in tumor tissues. RESULTS Treatments of thalidomide and/or icotinib reduced cell viability, induced apoptosis, and suppressed migration. Attenuation of pEGFR and pVEGF-R resulted in deactivation of ERK and AKT pathways, which eventually increased the anti-proliferative response. In PC9 xenograft model, combined administration of thalidomide and icotinib restrained tumor growth with remarkable reduced Ki-67 index and increased TUNEL positive cells. CONCLUSIONS Thalidomide sensitizes icotinib to increase apoptosis and prevent migration, and it may be a potentially promising anti-tumor drug in lung cancer multi-modality therapy.

  16. Suppression of Wnt signaling by the miR-29 family is mediated by demethylation of WIF-1 in non-small-cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Tan, Min [Department of Respiratory Medicine, Shanghai Tenth People’s Hospital, Tongji University, Shanghai 200072 (China); Wu, Junjie, E-mail: wujunjiesh@126.com [Department of Pneumology, Changhai Hospital of Shanghai, Second Military Medical University, Shanghai 200433 (China); State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200433 (China); Cai, Yong, E-mail: dryongcai@126.com [Department of Radiation Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433 (China)

    2013-09-06

    Highlights: •Dnmt3A and Dnmt3B are involved in the down-regulation of WIF-1 expression in non-small-cell lung cancer. •MiR-29 family members could restore WIF-1 expression through demethylation. •MiR-29s suppress Wnt/β-catenin signaling pathway and inhibit tumor growth. •The expression of miR-29a and miR-29b could be regulated partially in a positive feedback loop. -- Abstract: Wnt inhibitory factor-1 (WIF-1) silencing induced by promoter hypermethylation is a common mechanism of aberrant activation of the Wnt signaling pathway in non-small-cell lung cancer (NSCLC). However, the activity of regulators associated with the methylation of the WIF-1 gene remains unclear. Here, we investigated the role of three DNA methyltransferases (DNMT1, DNMT3A and DNMT3B) in the expression of WIF-1. The three DNMTs were up-regulated in NSCLC tumor tissues and suppression of DNMT3A and DNMT3B restored the expression of WIF-1 in NSCLC cells. The miR-29 family (miR-29a, -29b, and -29c), which negatively regulates DNMT3A and DNMT3B, was examined in association with the Wnt/β-catenin signaling pathway. A positive correlation between the expression of WIF-1 and that of MiR-29s was observed in NSCLC tissues. Methylation-specific PCR and Western blotting indicated that miR-29s positively regulate WIF-1 expression by inhibiting the methylation of its promoter. Furthermore, miR-29 overexpression downregulated β-catenin expression, inhibited cell proliferation and induced apoptosis. The expression of miR-29a and miR-29b was partially regulated by DNMT3A and DNMT3B in a positive feedback loop. Taken together, our findings show that miR-29s suppress the Wnt signaling pathway through demethylation of WIF-1 in NSCLC.

  17. CXCL12 suppresses cisplatin-induced apoptosis through activation of JAK2/STAT3 signaling in human non-small-cell lung cancer cells

    Directory of Open Access Journals (Sweden)

    Wang M

    2017-06-01

    Full Text Available Meng Wang,1 Tie Lin,2 Yicun Wang,3 Song Gao,4 Zhaoyang Yang,1 Xuan Hong,1 Gongyan Chen1 1Department of Respiratory Medicine, Harbin Medical University Cancer Hospital, 2Department of Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, 3Jilin Provincial Key Laboratory on Molecular and Chemical Genetics, The Second Hospital of Jilin University, Changchun, 4Department of Clinical Oncology, Shengjing Hospital, China Medical University, Shenyang, People’s Republic of China Aims: Poor efficacy of chemotherapy drugs in non-small-cell lung cancer (NSCLC is the key reason for the failure of treatment, but the mechanism of this remains largely unknown. Stromal cell-derived factor 1-alpha (SDF-1α/CXCL12 is a small chemotactic cytokine protein that plays an important role in tumor progression. In this study, we investigated the anti-apoptotic mechanism of the CXCL12/CXCR4 axis in response to cisplatin, a commonly used chemotherapeutic drug, in human lung adenocarcinoma A549 cells.Methods: CXCL12 blocks cisplatin-induced apoptosis in A549, and the results were shown by propidium iodide/annexin V staining in vitro. The mechanism of CXCL12 stimulating phosphorylation of STAT3 through CXCR4/JAK2 was demonstrated by immunofluorescence and Western blotting. The expression of CXCL12 and p-STAT3 in clinical specimens was examined by immunohistochemistry.Results: CXCL12 significantly decreased the ratio of apoptotic cells and stimulation of phospho-signal transducer and activator of transcription (p-STAT-3 in a time-dependent manner through interaction with CXCR4. Among the signaling molecules downstream of CXCR4, the JAK2/STAT3 pathway plays a predominant role in the anti-apoptotic effect of CXCL12. Analysis of clinical specimens revealed that increased CXCL12 and p-STAT3 expression correlates with enhanced lung cancer progression.Conclusion: These data suggest that CXCR4 contributes to CXCL12-mediated anti-apoptosis by activating JAK2

  18. Precision phase estimation based on weak-value amplification

    Science.gov (United States)

    Qiu, Xiaodong; Xie, Linguo; Liu, Xiong; Luo, Lan; Li, Zhaoxue; Zhang, Zhiyou; Du, Jinglei

    2017-02-01

    In this letter, we propose a precision method for phase estimation based on the weak-value amplification (WVA) technique using a monochromatic light source. The anomalous WVA significantly suppresses the technical noise with respect to the intensity difference signal induced by the phase delay when the post-selection procedure comes into play. The phase measured precision of this method is proportional to the weak-value of a polarization operator in the experimental range. Our results compete well with the wide spectrum light phase weak measurements and outperform the standard homodyne phase detection technique.

  19. The yeast three-hybrid system as an experimental platform to identify proteins interacting with small signaling molecules in plant cells: Potential and limitations

    Directory of Open Access Journals (Sweden)

    Stéphanie eCottier

    2011-12-01

    Full Text Available Chemical genetics is a powerful scientific strategy that utilizes small bioactive molecules as experimental tools to unravel biological processes. Bioactive compounds occurring in nature represent an enormous diversity of structures that can be used to dissect functions of biological systems. Once the bioactivity of a natural or synthetic compound has been critically evaluated the challenge remains to identify its molecular target and mode of action, which usually is a time consuming and labor-intensive process. To facilitate this task, we decided to implement the yeast three-hybrid (Y3H technology as a general experimental platform to scan the whole Arabidopsis proteome for targets of small signaling molecules. The Y3H technology is based on the yeast two-hybrid system and allows direct cloning of proteins that interact in vivo with a synthetic hybrid ligand, which comprises the biologically active molecule of interest covalently linked to methotrexate (Mtx. In yeast nucleus the hybrid ligand connects two fusion proteins: the Mtx part binding to dihydrofolate reductase fused to a DNA binding domain (encoded in the yeast strain, and the bioactive molecule part binding to its potential protein target fused to a DNA activating domain (encoded on a cDNA expression vector. During cDNA library screening, the formation of this ternary, transcriptional activator complex leads to reporter gene activation in yeast cells, and thereby allows selection of the putative targets of small bioactive molecules of interest. Here we present the strategy and experimental details for construction and application of a Y3H platform, including chemical synthesis of different hybrid ligands, construction of suitable cDNA libraries, the choice of yeast strains, and appropriate screening conditions. Based on the results obtained and the current literature we discussed the perspectives and limitations of the Y3H approach for identifying targets of small bioactive molecules.

  20. Four-Wave Optical Parametric Amplification in a Raman-Active Gas

    Directory of Open Access Journals (Sweden)

    Yuichiro Kida

    2015-08-01

    Full Text Available Four-wave optical parametric amplification (FWOPA in a Raman-active medium is experimentally investigated by use of an air-filled hollow fiber. A femtosecond pump pulse shorter than the period of molecular motion excites the coherent molecular motion of the Raman-active molecules during the parametric amplification of a signal pulse. The excited coherent motion modulates the frequency of the signal pulse during the parametric amplification, and shifts it to lower frequencies. The magnitude of the frequency redshift depends on the pump intensity, resulting in intensity-dependent spectral characteristics that are different from those in the FWOPA induced in a noble-gas-filled hollow fiber.

  1. A cascade amplification strategy based on rolling circle amplification and hydroxylamine amplified gold nanoparticles enables chemiluminescence detection of adenosine triphosphate.

    Science.gov (United States)

    Wang, Ping; Zhang, Tonghuan; Yang, Taoyi; Jin, Nan; Zhao, Yanjun; Fan, Aiping

    2014-08-07

    A highly sensitive and selective chemiluminescent (CL) biosensor for adenosine triphosphate (ATP) was developed by taking advantage of the ATP-dependent enzymatic reaction (ATP-DER), the powerful signal amplification capability of rolling circle amplification (RCA), and hydroxylamine-amplified gold nanoparticles (Au NPs). The strategy relies on the ability of ATP, a cofactor of T4 DNA ligase, to trigger the ligation-RCA reaction. In the presence of ATP, the T4 DNA ligase catalyzes the ligation reaction between the two ends of the padlock probe, producing a closed circular DNA template that initiates the RCA reaction with phi29 DNA polymerase and dNTP. Therein, many complementary copies of the circular template can be generated. The ATP-DER is eventually converted into a detectable CL signal after a series of processes, including gold probe hybridization, hydroxylamine amplification, and oxidative gold metal dissolution coupled with a simple and sensitive luminol CL reaction. The CL signal is directly proportional to the ATP level. The results showed that the detection limit of the assay is 100 pM of ATP, which compares favorably with those of other ATP detection techniques. In addition, by taking advantage of ATP-DER, the proposed CL sensing system exhibits extraordinary specificity towards ATP and could distinguish the target molecule ATP from its analogues. The proposed method provides a new and versatile platform for the design of novel DNA ligation reaction-based CL sensing systems for other cofactors. This novel ATP-DER based CL sensing system may find wide applications in clinical diagnosis as well as in environmental and biomedical fields.

  2. Diagnostic Devices for Isothermal Nucleic Acid Amplification

    Directory of Open Access Journals (Sweden)

    Chia-Chen Chang

    2012-06-01

    Full Text Available Since the development of the polymerase chain reaction (PCR technique, genomic information has been retrievable from lesser amounts of DNA than previously possible. PCR-based amplifications require high-precision instruments to perform temperature cycling reactions; further, they are cumbersome for routine clinical use. However, the use of isothermal approaches can eliminate many complications associated with thermocycling. The application of diagnostic devices for isothermal DNA amplification has recently been studied extensively. In this paper, we describe the basic concepts of several isothermal amplification approaches and review recent progress in diagnostic device development.

  3. Diagnostic devices for isothermal nucleic acid amplification.

    Science.gov (United States)

    Chang, Chia-Chen; Chen, Chien-Cheng; Wei, Shih-Chung; Lu, Hui-Hsin; Liang, Yang-Hung; Lin, Chii-Wann

    2012-01-01

    Since the development of the polymerase chain reaction (PCR) technique, genomic information has been retrievable from lesser amounts of DNA than previously possible. PCR-based amplifications require high-precision instruments to perform temperature cycling reactions; further, they are cumbersome for routine clinical use. However, the use of isothermal approaches can eliminate many complications associated with thermocycling. The application of diagnostic devices for isothermal DNA amplification has recently been studied extensively. In this paper, we describe the basic concepts of several isothermal amplification approaches and review recent progress in diagnostic device development.

  4. Fisetin induces apoptosis and endoplasmic reticulum stress in human non-small cell lung cancer through inhibition of the MAPK signaling pathway.

    Science.gov (United States)

    Kang, Kyoung Ah; Piao, Mei Jing; Madduma Hewage, Susara Ruwan Kumara; Ryu, Yea Seong; Oh, Min Chang; Kwon, Taeg Kyu; Chae, Sungwook; Hyun, Jin Won

    2016-07-01

    Fisetin (3,3',4',7-tetrahydroxyflavone), a dietary flavonoid compound, is currently being investigated for its anticancer effect in various cancer models, including lung cancer. Recent studies show that fisetin induces cell growth inhibition and apoptosis in the human non-small cell lung cancer line NCI-H460. In this study, we investigated whether fisetin can induce endoplasmic reticulum (ER) stress-mediated apoptosis in NCI-H460 cells. Fisetin induced mitochondrial reactive oxygen species (ROS) and characteristic signs of ER stress: ER staining; mitochondrial Ca(2+) overload; expression of ER stress-related proteins; glucose-regulated protein (GRP)-78, phosphorylation of protein kinase RNA (PKR)-like endoplasmic reticulum kinase (PERK) and phosphorylation of eukaryotic initiation factor-2 α subunit; cleavage of activating transcription factor-6; phosphorylation of inositol-requiring kinase-1 and splicing of X-box transcription factor-1; induction of C/EBP homologous protein and cleaved caspase-12. siRNA-mediated knockdown of CHOP and ATF-6 attenuated fisetin-induced apoptotic cell death. In addition, fisetin induced phosphorylation of ERK, JNK, and p38 MAPK. Moreover, silencing of the MAPK signaling pathway prevented apoptotic cell death. In summary, our results indicate that, in NCI-H460 cells, fisetin induces apoptosis and ER stress that is mediated by induction of the MAPK signaling pathway.

  5. Small G proteins in insulin action: Rab and Rho families at the crossroads of signal transduction and GLUT4 vesicle traffic.

    Science.gov (United States)

    Ishikura, S; Koshkina, A; Klip, A

    2008-01-01

    Insulin stimulates glucose uptake into muscle and adipose tissues through glucose transporter 4 (GLUT4). GLUT4 cycles between the intracellular compartments and the plasma membrane. GLUT4 traffic-regulating insulin signals are largely within the insulin receptor-insulin receptor substrate-phosphatidylinositol 3-kinase (IR-IRS-PI3K) axis. In muscle cells, insulin signal bifurcates downstream of the PI3K into one arm leading to the activation of the Ser/Thr kinases Akt and atypical protein kinase C, and another leading to the activation of Rho family protein Rac1 leading to actin remodelling. Activated Akt inactivates AS160, a GTPase-activating protein for Rab family small G proteins. Here we review the roles of Rab and Rho proteins, particularly Rab substrates of AS160 and Rac1, in insulin-stimulated GLUT4 traffic. We discuss: (1) how distinct steps in GLUT4 traffic may be regulated by discrete Rab proteins, and (2) the importance of Rac1 activation in insulin-induced actin remodelling in muscle cells, a key element for the net gain in surface GLUT4.

  6. Proteomics and pathway analysis identifies JNK signaling as critical for high linear energy transfer radiation-induced apoptosis in non-small lung cancer cells.

    Science.gov (United States)

    Ståhl, Sara; Fung, Eva; Adams, Christopher; Lengqvist, Johan; Mörk, Birgitta; Stenerlöw, Bo; Lewensohn, Rolf; Lehtiö, Janne; Zubarev, Roman; Viktorsson, Kristina

    2009-05-01

    During the past decade, we have witnessed an explosive increase in generation of large proteomics data sets, not least in cancer research. There is a growing need to extract and correctly interpret information from such data sets to generate biologically relevant hypotheses. A pathway search engine (PSE) has recently been developed as a novel tool intended to meet these requirements. Ionizing radiation (IR) is an anticancer treatment modality that triggers multiple signal transduction networks. In this work, we show that high linear energy transfer (LET) IR induces apoptosis in a non-small cell lung cancer cell line, U-1810, whereas low LET IR does not. PSE was applied to study changes in pathway status between high and low LET IR to find pathway candidates of importance for high LET-induced apoptosis. Such pathways are potential clinical targets, and they were further validated in vitro. We used an unsupervised shotgun proteomics approach where high resolution mass spectrometry coupled to nanoflow liquid chromatography determined the identity and relative abundance of expressed proteins. Based on the proteomics data, PSE suggested the JNK pathway (p = 6.10(-6)) as a key event in response to high LET IR. In addition, the Fas pathway was found to be activated (p = 3.10(-5)) and the p38 pathway was found to be deactivated (p = 0.001) compared with untreated cells. Antibody-based analyses confirmed that high LET IR caused an increase in phosphorylation of JNK. Moreover pharmacological inhibition of JNK blocked high LET-induced apoptotic signaling. In contrast, neither an activation of p38 nor a role for p38 in high LET IR-induced apoptotic signaling was found. We conclude that, in contrast to conventional low LET IR, high LET IR can trigger activation of the JNK pathway, which in turn is critical for induction of apoptosis in these cells. Thus PSE predictions were largely confirmed, and PSE was proven to be a useful hypothesis-generating tool.

  7. Alternative signaling pathways as potential therapeutic targets for overcoming EGFR and c-Met inhibitor resistance in non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Jason T Fong

    Full Text Available The use of tyrosine kinase inhibitors (TKIs against EGFR/c-Met in non-small cell lung cancer (NSCLC has been shown to be effective in increasing patient progression free survival (PFS, but their efficacy is limited due to the development of resistance and tumor recurrence. Therefore, understanding the molecular mechanisms underlying development of drug resistance in NSCLC is necessary for developing novel and effective therapeutic approaches to improve patient outcome. This study aims to understand the mechanism of EGFR/c-Met tyrosine kinase inhibitor (TKI resistance in NSCLC. H2170 and H358 cell lines were made resistant to SU11274, a c-Met inhibitor, and erlotinib, an EGFR inhibitor, through step-wise increases in TKI exposure. The IC50 concentrations of resistant lines exhibited a 4-5 and 11-22-fold increase for SU11274 and erlotinib, respectively, when compared to parental lines. Furthermore, mTOR and Wnt signaling was studied in both cell lines to determine their roles in mediating TKI resistance. We observed a 2-4-fold upregulation of mTOR signaling proteins and a 2- to 8-fold upregulation of Wnt signaling proteins in H2170 erlotinib and SU11274 resistant cells. H2170 and H358 cells were further treated with the mTOR inhibitor everolimus and the Wnt inhibitor XAV939. H358 resistant cells were inhibited by 95% by a triple combination of everolimus, erlotinib and SU11274 in comparison to 34% by a double combination of these drugs. Parental H2170 cells displayed no sensitivity to XAV939, while resistant cells were significantly inhibited (39% by XAV939 as a single agent, as well as in combination with SU11274 and erlotinib. Similar results were obtained with H358 resistant cells. This study suggests a novel molecular mechanism of drug resistance in lung cancer.

  8. Rational design of DKK3 structure-based small peptides as antagonists of Wnt signaling pathway and in silico evaluation of their efficiency.

    Directory of Open Access Journals (Sweden)

    Mansour Poorebrahim

    Full Text Available Dysregulated Wnt signaling pathway is highly associated with the pathogenesis of several human cancers. Dickkopf proteins (DKKs are thought to inhibit Wnt signaling pathway through binding to lipoprotein receptor-related protein (LRP 5/6. In this study, based on the 3-dimensional (3D structure of DKK3 Cys-rich domain 2 (CRD2, we have designed and developed several peptide inhibitors of Wnt signaling pathway. Modeller 9.15 package was used to predict 3D structure of CRD2 based on the Homology modeling (HM protocol. After refinement and minimization with GalaxyRefine and NOMAD-REF servers, the quality of selected models was evaluated utilizing VADAR, SAVES and ProSA servers. Molecular docking studies as well as literature-based information revealed two distinct boxes located at CRD2 which are actively involved in the DKK3-LRP5/6 interaction. A peptide library was constructed conducting the backrub sequence tolerance scanning protocol in Rosetta3.5 according to the DKK3-LRP5/6 binding sites. Seven tolerated peptides were chosen and their binding affinity and stability were improved by some logical amino acid substitutions. Molecular dynamics (MD simulations of peptide-LRP5/6 complexes were carried out using GROMACS package. After evaluation of binding free energies, stability, electrostatic potential and some physicochemical properties utilizing computational approaches, three peptides (PEP-I1, PEP-I3 and PEP-II2 demonstrated desirable features. However, all seven improved peptides could sufficiently block the Wnt-binding site of LRP6 in silico. In conclusion, we have designed and improved several small peptides based on the LRP6-binding site of CRD2 of DKK3. These peptides are highly capable of binding to LRP6 in silico, and may prevent the formation of active Wnt-LRP6-Fz complex.

  9. Signal flow analysis

    CERN Document Server

    Abrahams, J R; Hiller, N

    1965-01-01

    Signal Flow Analysis provides information pertinent to the fundamental aspects of signal flow analysis. This book discusses the basic theory of signal flow graphs and shows their relation to the usual algebraic equations.Organized into seven chapters, this book begins with an overview of properties of a flow graph. This text then demonstrates how flow graphs can be applied to a wide range of electrical circuits that do not involve amplification. Other chapters deal with the parameters as well as circuit applications of transistors. This book discusses as well the variety of circuits using ther

  10. HER2 induces cell proliferation and invasion of non-small-cell lung cancer by upregulating COX-2 expression via MEK/ERK signaling pathway

    Directory of Open Access Journals (Sweden)

    Chi F

    2016-05-01

    Full Text Available Feng Chi, Rong Wu, Xueying Jin, Min Jiang, Xike Zhu Department of Medical Oncology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China Abstract: HER2 positivity has been well studied in various cancers, but its importance in non-small-cell lung cancer (NSCLC is still being explored. In this study, quantitative reverse transcription polymerase chain reaction (qRT-PCR was performed to detect HER2 and COX-2 expression in NSCLC tissues. Then, pcDNA3.1-HER2 was used to overexpress HER2, while HER2 siRNA and COX-2 siRNA were used to silence HER2 and COX-2 expression. MTT assay and invasion assay were used to detect the effects of HER2 on cell proliferation and invasion. Our study revealed that HER2 and COX-2 expression were upregulated in NSCLC tissues and HER2 exhibited a significant positive correlation with the levels of COX-2 expression. Overexpression of HER2 evidently elevated COX-2 expression, while silencing of HER2 evidently decreased COX-2 expression. Furthermore, overexpressed HER2 induced the ERK phosphorylation, and this was abolished by the treatment with U0126, a pharmacological inhibitor of MEK, an upstream kinase of ERK. HER2-induced expression and promoter activity of COX-2 were also suppressed by U0126, suggesting that the MEK/ERK signaling pathway regulates COX-2 expression. In addition, HER2 induced activation of AKT signaling pathway, which was reversed by pretreatment with U0126 and COX-2 siRNA. MTT and invasion assays revealed that HER2 induced cell proliferation and invasion that were reversed by pretreatment with U0126 and COX-2 siRNA. In this study, our results demonstrated for the first time that HER2 elevated COX-2 expression through the activation of MEK/ERK pathway, which subsequently induced cell proliferation and invasion via AKT pathway in NSCLC tissues. Keywords: HER2, MEK/ERK, COX-2, AKT signaling pathway, non-small-cell lung cancer

  11. Dynamic characterization and amplification of sub-picosecond pulses in fiber optical parametric chirped pulse amplifiers

    DEFF Research Database (Denmark)

    Cristofori, Valentina; Lali-Dastjerdi, Zohreh; Rishøj, Lars Søgaard

    2013-01-01

    We show a first-time demonstration of amplification of 400 fs pulses in a fiber optical parametric amplifier. The 400 fs signal is stretched in time, amplified by 26 dB and compressed back to 500 fs. A significant broadening of the pulses is experimentally shown due to dispersion and limited gain...

  12. MOSFET-Only Mixer/IIR Filter with Gain using Parametric Amplification

    DEFF Research Database (Denmark)

    Custódio, José R.; Oliveira, J.; Oliveira, L. B.

    2010-01-01

    This paper describes the design of a discrete-time passive Mixer/IIR filter. The use of an improved MOS Parametric Amplification leads to a moderate gain in the signal path and improved noise performance, instead of the conversion loss inherent to passive mixers. Simulation results demonstrate th...

  13. Rolling circle amplification of metazoan mitochondrialgenomes

    Energy Technology Data Exchange (ETDEWEB)

    Simison, W. Brian; Lindberg, D.R.; Boore, J.L.

    2005-07-31

    Here we report the successful use of rolling circle amplification (RCA) for the amplification of complete metazoan mt genomes to make a product that is amenable to high-throughput genome sequencing techniques. The benefits of RCA over PCR are many and with further development and refinement of RCA, the sequencing of organellar genomics will require far less time and effort than current long PCR approaches.

  14. Amplification of the epidermal growth factor receptor gene in glioblastoma: an analysis of the relationship between genotype and phenotype by CISH method.

    Science.gov (United States)

    Miyanaga, Tomomi; Hirato, Junko; Nakazato, Yoichi

    2008-04-01

    We examined epidermal growth factor receptor (EGFR) overexpression and EGFR gene amplification using immunohistochemistry (IHC) and chromogenic in situ hybridization (CISH) in 109 glioblastomas, including 98 primary glioblastomas and 11 secondary glioblastomas. EGFR overexpression and EGFR gene amplification were found in 33% and 24% of glioblastoma, respectively, and all of those cases were primary glioblastoma. Large ischemic necrosis was significantly more frequent in primary glioblastomas than in secondary glioblastomas (54% vs. 18%), but pseudopalisading necrosis was not (65% vs. 54%). EGFR gene amplification was detected significantly more frequently in cases with both types of necrosis. Although glioblastomas with EGFR gene amplification invariably exhibited EGFR overexpression at the level of the whole tumor, tumor cells with EGFR gene amplification did not always show EGFR overexpression at the level of individual tumor cells. Cases of "strong" EGFR overexpression on IHC could be regarded as having EGFR gene amplification, and cases without EGFR overexpression could not. Cases of "weak" EGFR overexpression should be tested with CISH to confirm the presence of EGFR gene amplification. We found that 54% of glioblastomas with EGFR gene amplification were composed of areas with and without EGFR gene amplification; however, there were no obvious differences in morphology between tumor cells with and without EGFR gene amplification. Although small cell architecture might be associated with EGFR gene amplification at the level of the whole tumor, it did not always suggest amplification of the EGFR gene at the level of individual tumor cells. In one case, it seemed to suggest that a clone with EGFR gene amplification may arise in pre-existing tumor tissue and extend into the surrounding area. In cases of overall EGFR amplification, CISH would be a useful tool to decide the tumor border in areas infiltrated by tumor cells.

  15. Static and Dynamic Amplification Using Strong Mechanical Coupling

    KAUST Repository

    Ilyas, Saad

    2016-07-28

    Amplifying the signal-to-noise ratio of resonant sensors is vital toward the effort to miniaturize devices into the sub-micro and nano regimes. In this paper, we demonstrate theoretically and experimentally, amplification through mechanically coupled microbeams. The device is composed of two identical clamped-clamped beams, made of polyimide, connected at their middle through a third beam, which acts as a mechanical coupler. Each of the clamped-clamped microbeams and the coupler are designed to be actuated separately, hence providing various possibilities of actuation and sensing. The coupled resonator is driven into resonance near its first resonance mode and its dynamic behavior is explored via frequency sweeps. The results show significant amplification in the resonator amplitude when the signal is measured at the midpoint of the coupler compared with the response of the individual uncoupled beams. The static pull-in characteristics of the resonator are also studied. It is shown that the compliant mechanical coupler can serve as a low-power radio frequency switch actuated at low voltage loads. [2016-0100

  16. Hedgehog signaling pathway in neuroblastoma differentiation.

    Science.gov (United States)

    Souzaki, Ryota; Tajiri, Tatsuro; Souzaki, Masae; Kinoshita, Yoshiaki; Tanaka, Sakura; Kohashi, Kenichi; Oda, Yoshinao; Katano, Mitsuo; Taguchi, Tomoaki

    2010-12-01

    The hedgehog (Hh) signaling pathway is activated in some adult cancers. On the other hand, the Hh signaling pathway plays an important role in the development of the neural crest in embryos. The aim of this study is to show the activation of Hh signaling pathway in neuroblastoma (NB), a pediatric malignancy arising from neural crest cells, and to reveal the meaning of the Hh signaling pathway in NB development. This study analyzed the expression of Sonic hedgehog (Shh), GLI1, and Patched 1 (Ptch1), transactivators of Hh signaling pathway, by immunohistochemistry in 82 NB and 10 ganglioneuroblastoma cases. All 92 cases were evaluated for the status of MYCN amplification. Of the 92 cases, 67 (73%) were positive for Shh, 62 cases (67%) were positive for GLI1, and 73 cases (79%) were positive for Ptch1. Only 2 (10%) of the 20 cases with MYCN amplification were positive for Shh and GLI1, and 4 cases (20%) were positive for Ptch1 (MYCN amplification vs no MYCN amplification, P ≦ .01). The percentage of GLI1-positive cells in the cases with INSS stage 1 without MYCN amplification was significantly higher than that with INSS stage 4. Of 72 cases without MYCN amplification, 60 were GLI1-positive. Twelve cases were GLI1-negative, and the prognosis of the GLI1-positive cases was significantly better than that of the GLI1-negative cases (P = .015). Most of NBs without MYCN amplification were positive for Shh, GLI1, and Ptch1. In the cases without MYCN amplification, the high expression of GLI1 was significantly associated with early clinical stage and a good prognosis of the patients. In contrast to adult cancers, the activation of the Hh signaling pathway in NB may be associated with the differentiation of the NB. Copyright © 2010 Elsevier Inc. All rights reserved.

  17. Scintillation light detectors with Neganov-Luke amplification

    Energy Technology Data Exchange (ETDEWEB)

    Isaila, C. [Physik Department E15, Technische Universitaet Muenchen, James Franck Strasse, 85748 Garching (Germany)]. E-mail: cisaila@ph.tum.de; Boslau, O. [Ketek GmbH, Gustav Heinemann Ring 125, 81739 Munich (Germany); Coppi, C. [Physik Department E15, Technische Universitaet Muenchen, James Franck Strasse, 85748 Garching (Germany); Feilitzsch, F. von [Physik Department E15, Technische Universitaet Muenchen, James Franck Strasse, 85748 Garching (Germany); Goldstrass, P. [Ketek GmbH, Gustav Heinemann Ring 125, 81739 Munich (Germany); Jagemann, T. [Eberhard Karls Universitaet Tuebingen, Auf der Morgenstelle 14, 72076 Tuebingen (Germany); Jochum, J. [Eberhard Karls Universitaet Tuebingen, Auf der Morgenstelle 14, 72076 Tuebingen (Germany); Kemmer, J. [Ketek GmbH, Gustav Heinemann Ring 125, 81739 Munich (Germany); Lachenmaier, T. [Physik Department E15, Technische Universitaet Muenchen, James Franck Strasse, 85748 Garching (Germany); Lanfranchi, J.-C. [Physik Department E15, Technische Universitaet Muenchen, James Franck Strasse, 85748 Garching (Germany); Pahlke, A. [Ketek GmbH, Gustav Heinemann Ring 125, 81739 Munich (Germany); Potzel, W. [Physik Department E15, Technische Universitaet Muenchen, James Franck Strasse, 85748 Garching (Germany); Rau, W. [Physik Department E15, Technische Universitaet Muenchen, James Franck Strasse, 85748 Garching (Germany); Stark, M. [Physik Department E15, Technische Universitaet Muenchen, James Franck Strasse, 85748 Garching (Germany); Wernicke, D. [Physik Department E15, Technische Universitaet Muenchen, James Franck Strasse, 85748 Garching (Germany); VeriCold Technologies GmbH, Bahnhofstrasse 21, 85737 Ismaning (Germany); Westphal, W. [Physik Department E15, Technische Universitaet Muenchen, James Franck Strasse, 85748 Garching (Germany)

    2006-04-15

    For an active suppression of the gamma and electron background in the Cryogenic Rare Event Search with Superconducting Thermometers (CRESST) dark matter experiment both phonons and scintillation light generated in a CaWO{sub 4} crystal are detected simultaneously. The phonon signal is read out by a transition edge sensor (TES) on the CaWO{sub 4} crystal. For light detection a silicon absorber equipped with a TES is employed. An efficient background discrimination requires very sensitive light detectors. The threshold can be improved by applying an electric field to the silicon crystal leading to an amplification of the thermal signal due to the Neganov-Luke effect. Measurements showing the improved sensitivity of the light detectors as well as future steps for reducing the observed extra noise will be presented.

  18. Scintillation light detectors with Neganov-Luke amplification

    International Nuclear Information System (INIS)

    Isaila, C.; Boslau, O.; Coppi, C.; Feilitzsch, F. von; Goldstrass, P.; Jagemann, T.; Jochum, J.; Kemmer, J.; Lachenmaier, T.; Lanfranchi, J.-C.; Pahlke, A.; Potzel, W.; Rau, W.; Stark, M.; Wernicke, D.; Westphal, W.

    2006-01-01

    For an active suppression of the gamma and electron background in the Cryogenic Rare Event Search with Superconducting Thermometers (CRESST) dark matter experiment both phonons and scintillation light generated in a CaWO 4 crystal are detected simultaneously. The phonon signal is read out by a transition edge sensor (TES) on the CaWO 4 crystal. For light detection a silicon absorber equipped with a TES is employed. An efficient background discrimination requires very sensitive light detectors. The threshold can be improved by applying an electric field to the silicon crystal leading to an amplification of the thermal signal due to the Neganov-Luke effect. Measurements showing the improved sensitivity of the light detectors as well as future steps for reducing the observed extra noise will be presented

  19. A small diffusible signal molecule is responsible for the global control of virulence and exoenzyme production in the plant pathogen Erwinia carotovora.

    Science.gov (United States)

    Pirhonen, M; Flego, D; Heikinheimo, R; Palva, E T

    1993-06-01

    Virulence of the plant pathogen Erwinia carotovora subsp. carotovora is dependent on the production and secretion of a complex arsenal of plant cell wall-degrading enzymes. Production of these exoenzymes is controlled by a global regulatory mechanism. A virulent mutants in one of the regulatory loci, expI, show a pleiotropic defect in the growth phase-dependent transcriptional activation of exoenzyme gene expression. The expI gene encodes a 26 kDa polypeptide that is structurally and functionally related to the luxI gene product of Vibrio fischeri. Functional similarity of expI and luxI has been demonstrated by reciprocal genetic complementation experiments. LuxI controls bioluminescence in V.fischeri in a growth phase-dependent manner by directing the synthesis of the diffusible autoinducer, N-(3-oxohexanoyl) homoserine lactone. E.c. subsp. carotovora expI+ strains or Escherichia coli harboring the cloned expI gene excrete a small diffusible signal molecule that complements the expI mutation of Erwinia as well as a luxI mutation of V.fischeri. This extracellular complementation can also be achieved by E.coli harboring the luxI gene from V.fischeri or by adding the synthetic V.fischeri autoinducer. Both the production of the plant tissue-macerating exoenzymes and the ability of the bacteria to propagate in planta are restored in expI mutants by autoinducer addition. These data suggest that the same signal molecule is employed in control of such diverse processes as virulence in a plant pathogen and bioluminescence in a marine bacterium, and may represent a general mechanism by which bacteria modulate gene expression in response to changing environmental conditions.

  20. Proteomics and Pathway Analysis Identifies JNK Signaling as Critical for High Linear Energy Transfer Radiation-induced Apoptosis in Non-small Lung Cancer Cells*S⃞

    Science.gov (United States)

    Ståhl, Sara; Fung, Eva; Adams, Christopher; Lengqvist, Johan; Mörk, Birgitta; Stenerlöw, Bo; Lewensohn, Rolf; Lehtiö, Janne; Zubarev, Roman; Viktorsson, Kristina

    2009-01-01

    During the past decade, we have witnessed an explosive increase in generation of large proteomics data sets, not least in cancer research. There is a growing need to extract and correctly interpret information from such data sets to generate biologically relevant hypotheses. A pathway search engine (PSE) has recently been developed as a novel tool intended to meet these requirements. Ionizing radiation (IR) is an anticancer treatment modality that triggers multiple signal transduction networks. In this work, we show that high linear energy transfer (LET) IR induces apoptosis in a non-small cell lung cancer cell line, U-1810, whereas low LET IR does not. PSE was applied to study changes in pathway status between high and low LET IR to find pathway candidates of importance for high LET-induced apoptosis. Such pathways are potential clinical targets, and they were further validated in vitro. We used an unsupervised shotgun proteomics approach where high resolution mass spectrometry coupled to nanoflow liquid chromatography determined the identity and relative abundance of expressed proteins. Based on the proteomics data, PSE suggested the JNK pathway (p = 6·10−6) as a key event in response to high LET IR. In addition, the Fas pathway was found to be activated (p = 3·10−5) and the p38 pathway was found to be deactivated (p = 0.001) compared with untreated cells. Antibody-based analyses confirmed that high LET IR caused an increase in phosphorylation of JNK. Moreover pharmacological inhibition of JNK blocked high LET-induced apoptotic signaling. In contrast, neither an activation of p38 nor a role for p38 in high LET IR-induced apoptotic signaling was found. We conclude that, in contrast to conventional low LET IR, high LET IR can trigger activation of the JNK pathway, which in turn is critical for induction of apoptosis in these cells. Thus PSE predictions were largely confirmed, and PSE was proven to be a useful hypothesis-generating tool. PMID:19168796

  1. EGFR/Src/Akt signaling modulates Sox2 expression and self-renewal of stem-like side-population cells in non-small cell lung cancer.

    Science.gov (United States)

    Singh, Sandeep; Trevino, Jose; Bora-Singhal, Namrata; Coppola, Domenico; Haura, Eric; Altiok, Soner; Chellappan, Srikumar P

    2012-09-25

    Cancer stem cells are thought to be responsible for the initiation and progression of cancers. In non-small cell lung cancers (NSCLCs), Hoechst 33342 dye effluxing side population (SP) cells are shown to have stem cell like properties. The oncogenic capacity of cancer stem-like cells is in part due to their ability to self-renew; however the mechanistic correlation between oncogenic pathways and self-renewal of cancer stem-like cells has remained elusive. Here we characterized the SP cells at the molecular level and evaluated its ability to generate tumors at the orthotopic site in the lung microenvironment. Further, we investigated if the self-renewal of SP cells is dependent on EGFR mediated signaling. SP cells were detected and isolated from multiple NSCLC cell lines (H1650, H1975, A549), as well as primary human tumor explants grown in nude mice. SP cells demonstrated stem-like properties including ability to self-renew and grow as spheres; they were able to generate primary and metastatic tumors upon orthotopic implantation into the lung of SCID mice. In vitro study revealed elevated expression of stem cell associated markers like Oct4, Sox2 and Nanog as well as demonstrated intrinsic epithelial to mesenchymal transition features in SP cells. Further, we show that abrogation of EGFR, Src and Akt signaling through pharmacological or genetic inhibitors suppresses the self-renewal growth and expansion of SP-cells and resulted in specific downregulation of Sox2 protein expression. siRNA mediated depletion of Sox2 significantly blocked the SP phenotype as well as its self-renewal capacity; whereas other transcription factors like Oct4 and Nanog played a relatively lesser role in regulating self-renewal. Interestingly, Sox2 was elevated in metastatic foci of human NSCLC samples. Our findings suggest that Sox2 is a novel target of EGFR-Src-Akt signaling in NSCLCs that modulates self-renewal and expansion of stem-like cells from NSCLC. Therefore, the outcome of the

  2. EGFR/Src/Akt signaling modulates Sox2 expression and self-renewal of stem-like side-population cells in non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Singh Sandeep

    2012-09-01

    Full Text Available Abstract Background Cancer stem cells are thought to be responsible for the initiation and progression of cancers. In non-small cell lung cancers (NSCLCs, Hoechst 33342 dye effluxing side population (SP cells are shown to have stem cell like properties. The oncogenic capacity of cancer stem-like cells is in part due to their ability to self-renew; however the mechanistic correlation between oncogenic pathways and self-renewal of cancer stem-like cells has remained elusive. Here we characterized the SP cells at the molecular level and evaluated its ability to generate tumors at the orthotopic site in the lung microenvironment. Further, we investigated if the self-renewal of SP cells is dependent on EGFR mediated signaling. Results SP cells were detected and isolated from multiple NSCLC cell lines (H1650, H1975, A549, as well as primary human tumor explants grown in nude mice. SP cells demonstrated stem-like properties including ability to self-renew and grow as spheres; they were able to generate primary and metastatic tumors upon orthotopic implantation into the lung of SCID mice. In vitro study revealed elevated expression of stem cell associated markers like Oct4, Sox2 and Nanog as well as demonstrated intrinsic epithelial to mesenchymal transition features in SP cells. Further, we show that abrogation of EGFR, Src and Akt signaling through pharmacological or genetic inhibitors suppresses the self-renewal growth and expansion of SP-cells and resulted in specific downregulation of Sox2 protein expression. siRNA mediated depletion of Sox2 significantly blocked the SP phenotype as well as its self-renewal capacity; whereas other transcription factors like Oct4 and Nanog played a relatively lesser role in regulating self-renewal. Interestingly, Sox2 was elevated in metastatic foci of human NSCLC samples. Conclusions Our findings suggest that Sox2 is a novel target of EGFR-Src-Akt signaling in NSCLCs that modulates self-renewal and expansion of

  3. [Investigation of RNA viral genome amplification by multiple displacement amplification technique].

    Science.gov (United States)

    Pang, Zheng; Li, Jian-Dong; Li, Chuan; Liang, Mi-Fang; Li, De-Xin

    2013-06-01

    In order to facilitate the detection of newly emerging or rare viral infectious diseases, a negative-strand RNA virus-severe fever with thrombocytopenia syndrome bunyavirus, and a positive-strand RNA virus-dengue virus, were used to investigate RNA viral genome unspecific amplification by multiple displacement amplification technique from clinical samples. Series of 10-fold diluted purified viral RNA were utilized as analog samples with different pathogen loads, after a series of reactions were sequentially processed, single-strand cDNA, double-strand cDNA, double-strand cDNA treated with ligation without or with supplemental RNA were generated, then a Phi29 DNA polymerase depended isothermal amplification was employed, and finally the target gene copies were detected by real time PCR assays to evaluate the amplification efficiencies of various methods. The results showed that multiple displacement amplification effects of single-strand or double-strand cDNA templates were limited, while the fold increases of double-strand cDNA templates treated with ligation could be up to 6 X 10(3), even 2 X 10(5) when supplemental RNA existed, and better results were obtained when viral RNA loads were lower. A RNA viral genome amplification system using multiple displacement amplification technique was established in this study and effective amplification of RNA viral genome with low load was achieved, which could provide a tool to synthesize adequate viral genome for multiplex pathogens detection.

  4. Inhibition of Dengue Virus Replication by a Class of Small-Molecule Compounds That Antagonize Dopamine Receptor D4 and Downstream Mitogen-Activated Protein Kinase Signaling

    Science.gov (United States)

    Smith, Jessica L.; Stein, David A.; Shum, David; Fischer, Matthew A.; Radu, Constantin; Bhinder, Bhavneet; Djaballah, Hakim; Nelson, Jay A.; Früh, Klaus

    2014-01-01

    ABSTRACT Dengue viruses (DENV) are endemic pathogens of tropical and subtropical regions that cause significant morbidity and mortality worldwide. To date, no vaccines or antiviral therapeutics have been approved for combating DENV-associated disease. In this paper, we describe a class of tricyclic small-molecule compounds—dihydrodibenzothiepines (DHBTs), identified through high-throughput screening—with potent inhibitory activity against DENV serotype 2. SKI-417616, a highly active representative of this class, displayed activity against all four serotypes of DENV, as well as against a related flavivirus, West Nile virus (WNV), and an alphavirus, Sindbis virus (SINV). This compound was characterized to determine its mechanism of antiviral activity. Investigation of the stage of the viral life cycle affected revealed that an early event in the life cycle is inhibited. Due to the structural similarity of the DHBTs to known antagonists of the dopamine and serotonin receptors, we explored the roles of two of these receptors, serotonin receptor 2A (5HTR2A) and the D4 dopamine receptor (DRD4), in DENV infection. Antagonism of DRD4 and subsequent downstream phosphorylation of epidermal growth factor receptor (EGFR)-related kinase (ERK) were found to impact DENV infection negatively, and blockade of signaling through this network was confirmed as the mechanism of anti-DENV activity for this class of compounds. IMPORTANCE The dengue viruses are mosquito-borne, reemerging human pathogens that are the etiological agents of a spectrum of febrile diseases. Currently, there are no approved therapeutic treatments for dengue-associated disease, nor is there a vaccine. This study identifies a small molecule, SKI-417616, with potent anti-dengue virus activity. Further analysis revealed that SKI-417616 acts through antagonism of the host cell dopamine D4 receptor and subsequent repression of the ERK phosphorylation pathway. These results suggest that SKI-417616, or other

  5. Oral curcumin has anti-arthritic efficacy through somatostatin generation via cAMP/PKA and Ca(2+)/CaMKII signaling pathways in the small intestine.

    Science.gov (United States)

    Yang, Yan; Wu, Xin; Wei, Zhifeng; Dou, Yannong; Zhao, Di; Wang, Ting; Bian, Difei; Tong, Bei; Xia, Ying; Xia, Yufeng; Dai, Yue

    2015-01-01

    Curcumin (CUR) has been proven to be clinically effective in rheumatoid arthritis (RA) therapy, but its low oral bioavailability eclipses existent evidence that attempts to explain the underlying mechanism. Small intestine, the only organ exposed to a relatively high concentration of CUR, is the main site that generates gut hormones which are involved in the pathogenesis of RA. This study aims at addressing the hypothesis that one or more gut hormones serve as an intermediary agent for the anti-arthritic action of CUR. The protein and mRNA levels of gut hormones in CUR-treated rats were analyzed by ELISA and RT-PCR. Somatostatin (SOM) depletor and receptor antagonist were used to verify the key role of SOM in CUR-mediated anti-arthritic effect. The mechanisms underlying CUR-induced upregulation of SOM levels were explored by cellular experiments and immunohistochemical staining. The data showed that oral administration of CUR (100 mg/kg) for consecutive two weeks in adjuvant-induced arthritis rats still exhibited an extremely low plasma exposure despite of a dramatic amelioration of arthritis symptoms. When injected intraperitoneally, CUR lost anti-arthritic effect in rats, suggesting that it functions in an intestine-dependent manner. CUR elevated SOM levels in intestines and sera, and SOM depletor and non-selective SOM receptor antagonist could abolish the inhibitory effect of CUR on arthritis. Immunohistochemical assay demonstrated that CUR markedly increased the number of SOM-positive cells in both duodenum and jejunum. In vitro experiments demonstrated that CUR could augment SOM secretion from intestinal endocrine cells, and this effect could be hampered by either MEK1/2 or Ca(2+)/calmodulin-dependent kinase II (CAMKII) inhibitor. In summary, oral administration of CUR exhibits anti-arthritic effect through augmenting SOM secretion from the endocrine cells in small intestines via cAMP/PKA and Ca(2+)/CaMKII signaling pathways. Copyright © 2015 Elsevier Ltd

  6. Optical Sound Generation and Amplification

    Science.gov (United States)

    1983-01-15

    acoustic cavitation threshold of water with concentration of the polymer additives polyethylene oxide and guar gum . It was found that small amounts of...Technical Library 2800 Powder Mill Road Adelphi, Maryland 20783 1 copy 3 copies 1 copy 1 copy 1 copy 1 copy 1 copy Naval Air Development Center

  7. Helicase-dependent amplification of nucleic acids.

    Science.gov (United States)

    Cao, Yun; Kim, Hyun-Jin; Li, Ying; Kong, Huimin; Lemieux, Bertrand

    2013-10-11

    Helicase-dependent amplification (HDA) is a novel method for the isothermal in vitro amplification of nucleic acids. The HDA reaction selectively amplifies a target sequence by extension of two oligonucleotide primers. Unlike the polymerase chain reaction (PCR), HDA uses a helicase enzyme to separate the deoxyribonucleic acid (DNA) strands, rather than heat denaturation. This allows DNA amplification without the need for thermal cycling. The helicase used in HDA is a helicase super family II protein obtained from a thermophilic organism, Thermoanaerobacter tengcongensis (TteUvrD). This thermostable helicase is capable of unwinding blunt-end nucleic acid substrates at elevated temperatures (60° to 65°C). The HDA reaction can also be coupled with reverse transcription for ribonucleic acid (RNA) amplification. The products of this reaction can be detected during the reaction using fluorescent probes when incubations are conducted in a fluorimeter. Alternatively, products can be detected after amplification using a disposable amplicon containment device that contains an embedded lateral flow strip. Copyright © 2013 John Wiley & Sons, Inc.

  8. Ascorbic Acid-Induced Cardiac Differentiation of Murine Pluripotent Stem Cells: Transcriptional Profiling and Effect of a Small Molecule Synergist of Wnt/β-Catenin Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Dina Ivanyuk

    2015-05-01

    Full Text Available Background: Reproducible and efficient differentiation of pluripotent stem cells (PSCs to cardiomyocytes (CMs is essential for their use in regenerative medicine, drug testing and disease modeling. The aim of this study was to evaluate the effect of some previously reported cardiogenic substances on cardiac differentiation of mouse PSCs. Methods: Differentiation was performed by embryoid body (EB-based method using three different murine PSC lines. The differentiation efficiency was monitored by RT-qPCR, immunocytochemistry and flow cytometry, and the effect mechanistically evaluated by transcriptome analysis of treated EBs. Results: Among the five tested compounds (ascorbic acid, dorsomorphin, cyclic adenosine 3',5'-monophosphate, cardiogenol C, cyclosporin A only ascorbic acid (AA exerted a strong and reproducible cardiogenic effect in CGR8 cells which was less consistent in other two PSC lines. AA induced only minor changes in transcriptome of CGR8 cells after administration during the initial two days of differentiation. Cardiospecific genes and transcripts involved in angiogenesis, erythropoiesis and hematopoiesis were up-regulated on day 5 but not on days 2 or 3 of differentiation. The cardiac differentiation efficiency was improved when QS11, a small-molecule synergist of Wnt/β-catenin signaling pathway, was added to cultures after AA-treatment. Conclusion: This study demonstrates that only minor transcriptional changes are sufficient for enhancement of cardiogenesis of murine PSCs by AA and that AA and QS11 exhibit synergistic effects and enhance the efficiency of CM differentiation of murine PSCs.

  9. A small and efficient dimerization/packaging signal of rat VL30 RNA and its use in murine leukemia virus-VL30-derived vectors for gene transfer.

    Science.gov (United States)

    Torrent, C; Gabus, C; Darlix, J L

    1994-02-01

    Retroviral genomes consist of two identical RNA molecules associated at their 5' ends by the dimer linkage structure located in the packaging element (Psi or E) necessary for RNA dimerization in vitro and packaging in vivo. In murine leukemia virus (MLV)-derived vectors designed for gene transfer, the Psi + sequence of 600 nucleotides directs the packaging of recombinant RNAs into MLV virions produced by helper cells. By using in vitro RNA dimerization as a screening system, a sequence of rat VL30 RNA located next to the 5' end of the Harvey mouse sarcoma virus genome and as small as 67 nucleotides was found to form stable dimeric RNA. In addition, a purine-rich sequence located at the 5' end of this VL30 RNA seems to be critical for RNA dimerization. When this VL30 element was extended by 107 nucleotides at its 3' end and inserted into an MLV-derived vector lacking MLV Psi +, it directed the efficient encapsidation of recombinant RNAs into MLV virions. Because this VL30 packaging signal is smaller and more efficient in packaging recombinant RNAs than the MLV Psi + and does not contain gag or glyco-gag coding sequences, its use in MLV-derived vectors should render even more unlikely recombinations which could generate replication-competent viruses. Therefore, utilization of the rat VL30 packaging sequence should improve the biological safety of MLV vectors for human gene transfer.

  10. P38 pathway as a key downstream signal of connective tissue growth factor to regulate metastatic potential in non-small-cell lung cancer.

    Science.gov (United States)

    Kato, Shinichiro; Yokoyama, Satoru; Hayakawa, Yoshihiro; Li, Luhui; Iwakami, Yusuke; Sakurai, Hiroaki; Saiki, Ikuo

    2016-10-01

    Although the secretory matricellular protein connective tissue growth factor (CTGF) has been reported to be related to lung cancer metastasis, the precise mechanism by which CTGF regulates lung cancer metastasis has not been elucidated. In the present study, we show the molecular link between CTGF secretion and the p38 pathway in the invasive and metastatic potential of non-small-cell lung cancer (NSCLC). Among three different human NSCLC cell lines (PC-14, A549, and PC-9), their in vitro invasiveness was inversely correlated with the level of CTGF secretion. By supplementing or reducing CTGF secretion in NSCLC culture, dysregulation of the invasive and metastatic potential of NSCLC cell lines was largely compensated. By focusing on the protein kinases that are known to be regulated by CTGF, we found that the p38 pathway is a key downstream signal of CTGF to regulate the metastatic potential of NSCLC. Importantly, a negative correlation between CTGF and phosphorylation status of p38 was identified in The Cancer Genome Atlas lung adenocarcinoma dataset. In the context of the clinical importance of our findings, we showed that p38 inhibitor, SB203580, reduced the metastatic potential of NSCLC secreting low levels of CTGF. Collectively, our present findings indicate that the CTGF/p38 axis is a novel therapeutic target of NSCLC metastasis, particularly NSCLC secreting low levels of CTGF. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  11. Two-Stage Battery Energy Storage System (BESS in AC Microgrids with Balanced State-of-Charge and Guaranteed Small-Signal Stability

    Directory of Open Access Journals (Sweden)

    Bing Xie

    2018-02-01

    Full Text Available In this paper, a two-stage battery energy storage system (BESS is implemented to enhance the operation condition of conventional battery storage systems in a microgrid. Particularly, the designed BESS is composed of two stages, i.e., Stage I: integration of dispersed energy storage units (ESUs using parallel DC/DC converters, and Stage II: aggregated ESUs in grid-connected operation. Different from a conventional BESS consisting of a battery management system (BMS and power conditioning system (PCS, the developed two-stage architecture enables additional operation and control flexibility in balancing the state-of-charge (SoC of each ESU and ensures the guaranteed small-signal stability, especially in extremely weak grid conditions. The above benefits are achieved by separating the control functions between the two stages. In Stage I, a localized power sharing scheme based on the SoC of each particular ESU is developed to manage the SoC and avoid over-charge or over-discharge issues; on the other hand, in Stage II, an additional virtual impedance loop is implemented in the grid-interactive DC/AC inverters to enhance the stability margin with multiple parallel-connected inverters integrating at the point of common coupling (PCC simultaneously. A simulation model based on MATLAB/Simulink is established, and simulation results verify the effectiveness of the proposed BESS architecture and the corresponding control diagram.

  12. Amplification of chirality in helical supramolecular polymers: the majority-rules principle.

    NARCIS (Netherlands)

    Gestel, van J.A.M.

    2004-01-01

    Amplification of chirality, being a strongly nonlinear response of the optical activity of helical polymers to a small (net) amount of optically active material, has recently been discovered in supramolecular copolymers. Apart from the sergeants-and-soldiers type we discussed in earlier work,

  13. A universal aptameric biosensor: Multiplexed detection of small analytes via aggregated perylene-based broad-spectrum quencher.

    Science.gov (United States)

    Hu, Rong; Zhang, Xi; Xu, Qiang; Lu, Dan-Qing; Yang, Yun-Hui; Xu, Quan-Qing; Ruan, Qiong; Mo, Liu-Ting; Zhang, Xiao-Bing

    2017-06-15

    A universal aptameric system based on the taking advantage of double-stranded DNA/perylene diimide (dsDNA/PDI) as the signal probe was developed for multiplexed detection of small molecules. Aptamers are single-stranded DNA or RNA oligonucleotides which are selected in vitro by a process known as systematic evolution of ligands by exponential enrichment. In this work, we synthesized a new kind of PDI and reported this aggregated PDI could quench the double-stranded DNA (dsDNA)-labeled fluorophores with a high quenching efficiency. The quenching efficiencies on the fluorescence of FAM, TAMRA and Cy5 could reach to 98.3%±0.9%, 97.2%±0.6% and 98.1%±1.1%, respectively. This broad-spectrum quencher was then adopted to construct a multicolor biosensor via a label-free approach. A structure-switching-triggered enzymatic recycling amplification was employed for signal amplification. High quenching efficiency combined with autocatalytic target recycling amplification afforded the biosensor with high sensitivity towards small analytes. For other targets, changing the corresponding aptamer can achieve the goal. The quencher did not interfere with the catalytic activity of nuclease. The biosensor could be manipulated with similar sensitivity no matter in pre-addition or post-addition manner. Moreover, simultaneous and multiplexed analysis of several small molecules in homogeneous solution was achieved, demonstrating its potential application in the rapid screening of multiple biotargets. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Amplification through chaotic synchronization in spatially extended beam-plasma systems

    Science.gov (United States)

    Moskalenko, Olga I.; Frolov, Nikita S.; Koronovskii, Alexey A.; Hramov, Alexander E.

    2017-12-01

    In this paper, we have studied the relationship between chaotic synchronization and microwave signal amplification in coupled beam-plasma systems. We have considered a 1D particle-in-cell numerical model of unidirectionally coupled beam-plasma oscillatory media being in the regime of electron pattern formation. We have shown the significant gain of microwave oscillation power in coupled beam-plasma media being in the different regimes of generation. The discovered effect has a close connection with the chaotic synchronization phenomenon, so we have observed that amplification appears after the onset of the complete time scale synchronization regime in the analyzed coupled spatially extended systems. We have also provided the numerical study of physical processes in the chain of beam-plasma systems leading to the chaotic synchronization and the amplification of microwave oscillations power, respectively.

  15. Gefitinib inhibits invasive phenotype and epithelial-mesenchymal transition in drug-resistant NSCLC cells with MET amplification.

    Directory of Open Access Journals (Sweden)

    Silvia La Monica

    Full Text Available Despite the initial response, all patients with epidermal growth factor receptor (EGFR-mutant non-small cell lung cancer (NSCLC eventually develop acquired resistance to EGFR tyrosine kinase inhibitors (TKIs. The EGFR-T790M secondary mutation is responsible for half of acquired resistance cases, while MET amplification has been associated with acquired resistance in about 5-15% of NSCLCs. Clinical findings indicate the retained addiction of resistant tumors on EGFR signaling. Therefore, we evaluated the molecular mechanisms supporting the therapeutic potential of gefitinib maintenance in the HCC827 GR5 NSCLC cell line harbouring MET amplification as acquired resistance mechanism. We demonstrated that resistant cells can proliferate and survive regardless of the presence of gefitinib, whereas the absence of the drug significantly enhanced cell migration and invasion. Moreover, the continuous exposure to gefitinib prevented the epithelial-mesenchymal transition (EMT with increased E-cadherin expression and down-regulation of vimentin and N-cadherin. Importantly, the inhibition of cellular migration was correlated with the suppression of EGFR-dependent Src, STAT5 and p38 signaling as assessed by a specific kinase array, western blot analysis and silencing functional studies. On the contrary, the lack of effect of gefitinib on EGFR phosphorylation in the H1975 cells (EGFR-T790M correlated with the absence of effects on cell migration and invasion. In conclusion, our findings suggest that certain EGFR-mutated patients may still benefit from a second-line therapy including gefitinib based on the specific mechanism underlying tumor cell resistance.

  16. Highly sensitive chemiluminescent point mutation detection by circular strand-displacement amplification reaction.

    Science.gov (United States)

    Shi, Chao; Ge, Yujie; Gu, Hongxi; Ma, Cuiping

    2011-08-15

    Single nucleotide polymorphism (SNP) genotyping is attracting extensive attentions owing to its direct connections with human diseases including cancers. Here, we have developed a highly sensitive chemiluminescence biosensor based on circular strand-displacement amplification and the separation by magnetic beads reducing the background signal for point mutation detection at room temperature. This method took advantage of both the T4 DNA ligase recognizing single-base mismatch with high selectivity and the strand-displacement reaction of polymerase to perform signal amplification. The detection limit of this method was 1.3 × 10(-16)M, which showed better sensitivity than that of most of those reported detection methods of SNP. Additionally, the magnetic beads as carrier of immobility was not only to reduce the background signal, but also may have potential apply in high through-put screening of SNP detection in human genome. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. ESTIMATION OF AMPLIFICATION FACTOR IN EARTHQUAKE ENGINEERING

    Directory of Open Access Journals (Sweden)

    Nazarov Yuriy Pavlovich

    2015-03-01

    Full Text Available The authors are the developers of Odyssey Software (Eurosoft Co. for the analysis of seismological data and computing of seismic loads and their parameters. While communicating with the users of the software, the authors have revealed some uncertainty about both understanding of the term "amplification factor (AF" and calculation of the amplification factor using various methods. In this article, a simple example shows that the determination of the amplification factor as the ratio of the acceleration’s spectrum to the maximal acceleration is derived from the classical definition of AF in the form of the ratio of maximal dynamic displacement to the displacement by the action of static load. Deterministic and probabilistic ap-proaches for the calculating of the AF were discussed. There was an example of AFs calculation and their envelopes for translational and rotational components of seismic impact by using Odyssey Software.

  18. Amplification of hofmeister effect by alcohols.

    Science.gov (United States)

    Xu, Yun; Liu, Guangming

    2014-07-03

    We have demonstrated that Hofmeister effect can be amplified by adding alcohols to aqueous solutions. The lower critical solution temperature behavior of poly(N-isopropylacrylamide) has been employed as the model system to study the amplification of Hofmeister effect. The alcohols can more effectively amplify the Hofmeister effect following the series methanol alcohols and following the series d-sorbitol ≈ xylitol ≈ meso-erythritol alcohols. Our study reveals that the relative extent of amplification of Hofmeister effect is determined by the stability of the water/alcohol complex, which is strongly dependent on the chemical structure of alcohols. The more stable solvent complex formed via stronger hydrogen bonds can more effectively differentiate the anions through the anion-solvent complex interactions, resulting in a stronger amplification of Hofmeister effect. This study provides an alternative method to tune the relative strength of Hofmeister effect besides salt concentration.

  19. Lidar using the backscatter amplification effect

    Science.gov (United States)

    Razenkov, Igor A.; Banakh, Victor A.

    2018-04-01

    Experimental data proving the possibility of lidar measurement of the refractive turbulence strength based on the effect of backscatter amplification (BSA) are reported. It is shown that the values of the amplification factor correlate with the variance of random jitter of optical image of an incoherent light source depending on the value of the structure constant of the air refractive index turbulent fluctuations averaged over the probing path. This paper presents the results of measurements of the BSA factor in comparison with the simultaneous measurements of the BSA peak, which is very narrow and only occurs on the laser beam axis. It is constructed the range-time images of the derivative of the amplification factor gives a comprehensive picture of the location of turbulent zones and their temporal dynamics.

  20. Tungsten disulfide nanosheet and exonuclease III co-assisted amplification strategy for highly sensitive fluorescence polarization detection of DNA glycosylase activity

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Jingjin; Ma, Yefei [Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources of Education Ministry, Guangxi Normal University, Guilin, 541004 (China); Kong, Rongmei [The Key Laboratory of Life-Organic Analysis, College of Chemistry and Chemical Engineering, Qufu Normal University, Qufu, Shandong 273165 (China); Zhang, Liangliang, E-mail: liangzhang319@163.com [Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources of Education Ministry, Guangxi Normal University, Guilin, 541004 (China); Yang, Wen; Zhao, Shulin [Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources of Education Ministry, Guangxi Normal University, Guilin, 541004 (China)

    2015-08-05

    Herein, we introduced a tungsten disulfide (WS{sub 2}) nanosheet and exonuclease III (Exo III) co-assisted signal amplification strategy for highly sensitive fluorescent polarization (FP) assay of DNA glycosylase activity. Two DNA glycosylases, uracil-DNA glycosylase (UDG) and human 8-oxoG DNA glycosylase 1 (hOGG1), were tested. A hairpin-structured probe (HP) which contained damaged bases in the stem was used as the substrate. The removal of damaged bases from substrate by DNA glycosylase would lower the melting temperature of HP. The HP was then opened and hybridized with a FAM dye-labeled single strand DNA (DP), generating a duplex with a recessed 3′-terminal of DP. This design facilitated the Exo III-assisted amplification by repeating the hybridization and digestion of DP, liberating numerous FAM fluorophores which could not be adsorbed on WS{sub 2} nanosheet. Thus, the final system exhibited a small FP signal. However, in the absence of DNA glycosylases, no hybridization between DP and HP was occurred, hampering the hydrolysis of DP by Exo III. The intact DP was then adsorbed on the surface of WS{sub 2} nanosheet that greatly amplified the mass of the labeled-FAM fluorophore, resulting in a large FP value. With the co-assisted amplification strategy, the sensitivity was substantially improved. In addition, this method was applied to detect UDG activity in cell extracts. The study of the inhibition of UDG was also performed. Furthermore, this method is simple in design, easy in implementation, and selective, which holds potential applications in the DNA glycosylase related mechanism research and molecular diagnostics. - Highlights: • A fluorescence polarization strategy for DNA glycosylase activity detection was developed. • The present method was based on WS{sub 2} nanosheet and exonuclease III co-assisted signal amplification. • A high sensitivity and desirable selectivity were achieved. • This method provides a promising universal platform for DNA

  1. Optical nano-biosensing interface via nucleic acid amplification strategy: construction and application.

    Science.gov (United States)

    Zhou, Hong; Liu, Jing; Xu, Jing-Juan; Zhang, Shu-Sheng; Chen, Hong-Yuan

    2018-03-21

    Modern optical detection technology plays a critical role in current clinical detection due to its high sensitivity and accuracy. However, higher requirements such as extremely high detection sensitivity have been put forward due to the clinical needs for the early finding and diagnosing of malignant tumors which are significant for tumor therapy. The technology of isothermal amplification with nucleic acids opens up avenues for meeting this requirement. Recent reports have shown that a nucleic acid amplification-assisted modern optical sensing interface has achieved satisfactory sensitivity and accuracy, high speed and specificity. Compared with isothermal amplification technology designed to work completely in a solution system, solid biosensing interfaces demonstrated better performances in stability and sensitivity due to their ease of separation from the reaction mixture and the better signal transduction on these optical nano-biosensing interfaces. Also the flexibility and designability during the construction of these nano-biosensing interfaces provided a promising research topic for the ultrasensitive detection of cancer diseases. In this review, we describe the construction of the burgeoning number of optical nano-biosensing interfaces assisted by a nucleic acid amplification strategy, and provide insightful views on: (1) approaches to the smart fabrication of an optical nano-biosensing interface, (2) biosensing mechanisms via the nucleic acid amplification method, (3) the newest strategies and future perspectives.

  2. NAIMA: target amplification strategy allowing quantitative on-chip detection of GMOs.

    Science.gov (United States)

    Morisset, Dany; Dobnik, David; Hamels, Sandrine; Zel, Jana; Gruden, Kristina

    2008-10-01

    We have developed a novel multiplex quantitative DNA-based target amplification method suitable for sensitive, specific and quantitative detection on microarray. This new method named NASBA Implemented Microarray Analysis (NAIMA) was applied to GMO detection in food and feed, but its application can be extended to all fields of biology requiring simultaneous detection of low copy number DNA targets. In a first step, the use of tailed primers allows the multiplex synthesis of template DNAs in a primer extension reaction. A second step of the procedure consists of transcription-based amplification using universal primers. The cRNA product is further on directly ligated to fluorescent dyes labelled 3DNA dendrimers allowing signal amplification and hybridized without further purification on an oligonucleotide probe-based microarray for multiplex detection. Two triplex systems have been applied to test maize samples containing several transgenic lines, and NAIMA has shown to be sensitive down to two target copies and to provide quantitative data on the transgenic contents in a range of 0.1-25%. Performances of NAIMA are comparable to singleplex quantitative real-time PCR. In addition, NAIMA amplification is faster since 20 min are sufficient to achieve full amplification.

  3. The Caenorhabditis elegans RDE-10/RDE-11 complex regulates RNAi by promoting secondary siRNA amplification.

    Science.gov (United States)

    Zhang, Chi; Montgomery, Taiowa A; Fischer, Sylvia E J; Garcia, Susana M D A; Riedel, Christian G; Fahlgren, Noah; Sullivan, Christopher M; Carrington, James C; Ruvkun, Gary

    2012-05-22

    In nematodes, plants, and fungi, RNAi is remarkably potent and persistent due to the amplification of initial silencing signals by RNA-dependent RNA polymerases (RdRPs). In Caenorhabditis elegans (C. elegans), the interaction between the RNA-induced silencing complex (RISC) loaded with primary small interfering RNAs (siRNAs) and the target messenger RNA (mRNA) leads to the recruitment of RdRPs and synthesis of secondary siRNAs using the target mRNA as the template. The mechanism and genetic requirements for secondary siRNA accumulation are not well understood. From a forward genetic screen for C. elegans genes required for RNAi, we identified rde-10, and through proteomic analysis of RDE-10-interacting proteins, we identified a protein complex containing the new RNAi factor RDE-11, the known RNAi factors RSD-2 and ERGO-1, and other candidate RNAi factors. The RNAi defective genes rde-10 and rde-11 encode a novel protein and a RING-type zinc finger domain protein, respectively. Mutations in rde-10 and rde-11 genes cause dosage-sensitive RNAi deficiencies: these mutants are resistant to low dosage but sensitive to high dosage of double-stranded RNAs. We assessed the roles of rde-10, rde-11, and other dosage-sensitive RNAi-defective genes rsd-2, rsd-6, and haf-6 in both exogenous and endogenous small RNA pathways using high-throughput sequencing and qRT-PCR. These genes are required for the accumulation of secondary siRNAs in both exogenous and endogenous RNAi pathways. The RDE-10/RDE-11 complex is essential for the amplification of RNAi in C. elegans by promoting secondary siRNA accumulation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Numerical study of primordial magnetic field amplification by inflation-produced gravitational waves

    International Nuclear Information System (INIS)

    Kuroyanagi, Sachiko; Tashiro, Hiroyuki; Sugiyama, Naoshi

    2010-01-01

    We numerically study the interaction of inflation-produced magnetic fields with gravitational waves, both of which originate from quantum fluctuations during inflation. The resonance between the magnetic field perturbations and the gravitational waves has been suggested as a possible mechanism for magnetic field amplification. However, some analytical studies suggest that the effect of the inflationary gravitational waves is too small to provide significant amplification. Our numerical study shows more clearly how the interaction affects the magnetic fields and confirms the weakness of the influence of the gravitational waves. We present an investigation based on the magnetohydrodynamic approximation and take into account the differences of the Alfven speed.

  5. High-throughput genotyping of single nucleotide polymorphisms with rolling circle amplification

    Directory of Open Access Journals (Sweden)

    Sun Zhenyu

    2001-08-01

    Full Text Available Abstract Background Single nucleotide polymorphisms (SNPs are the foundation of powerful complex trait and pharmacogenomic analyses. The availability of large SNP databases, however, has emphasized a need for inexpensive SNP genotyping methods of commensurate simplicity, robustness, and scalability. We describe a solution-based, microtiter plate method for SNP genotyping of human genomic DNA. The method is based upon allele discrimination by ligation of open circle probes followed by rolling circle amplification of the signal using fluorescent primers. Only the probe with a 3' base complementary to the SNP is circularized by ligation. Results SNP scoring by ligation was optimized to a 100,000 fold discrimination against probe mismatched to the SNP. The assay was used to genotype 10 SNPs from a set of 192 genomic DNA samples in a high-throughput format. Assay directly from genomic DNA eliminates the need to preamplify the target as done for many other genotyping methods. The sensitivity of the assay was demonstrated by genotyping from 1 ng of genomic DNA. We demonstrate that the assay can detect a single molecule of the circularized probe. Conclusions Compatibility with homogeneous formats and the ability to assay small amounts of genomic DNA meets the exacting requirements of automated, high-throughput SNP scoring.

  6. Enhanced traveling wave amplification of co-planar slow wave structure by extended phase-matching

    International Nuclear Information System (INIS)

    Palm, Andrew; Sirigiri, Jagadishwar; Shin, Young-Min

    2015-01-01

    The electron beam co-propagating with slow waves in a staggered double grating array (SDGA) efficiently amplifies millimeter and sub-millimeter waves over a wide spectrum. Our theoretical and numerical analyses show that the power amplification in the fundamental passband is enhanced by the extended beam-wave phase-matching. Particle-in-cell simulations on the SDGA slow wave structure, designed with 10.4 keV and 50–100 mA sheet beam, indicate that maintaining beam-wave synchronization along the entire length of the circuit improves the gain by 7.3% leading to a total gain of 28 dB, corresponding to 62 W saturated power at the middle of operating band, and a 3-dB bandwidth of 7 GHz with 10.5% at V-band (73.5 GHz center frequency) with saturated peak power reaching 80 W and 28 dB at 71 GHz. These results also show a reasonably good agreement with analytic calculations based on Pierce small signal gain theory

  7. Colorimetric Nucleic Acid Detection on Paper Microchip Using Loop Mediated Isothermal Amplification and Crystal Violet Dye.

    Science.gov (United States)

    Roy, Sharmili; Mohd-Naim, Noor Faizah; Safavieh, Mohammadali; Ahmed, Minhaz Uddin

    2017-11-22

    Nucleic acid detection is of paramount importance in monitoring of microbial pathogens in food safety and infectious disease diagnostic applications. To address these challenges, a rapid, cost-effective label-free technique for nucleic acid detection with minimal instrumentations is highly desired. Here, we present paper microchip to detect and quantify nucleic acid using colorimetric sensing modality. The extracted DNA from food samples of meat as well as microbial pathogens was amplified utilizing loop-mediated isothermal amplification (LAMP). LAMP amplicon was then detected and quantified on a paper microchip fabricated in a cellulose paper and a small wax chamber utilizing crystal violet dye. The affinity of crystal violet dye toward dsDNA and positive signal were identified by changing the color from colorless to purple. Using this method, detection of Sus scrofa (porcine) and Bacillus subtilis (bacteria) DNA was possible at concentrations as low as 1 pg/μL (3.43 × 10 -1 copies/μL) and 10 pg/μL (2.2 × 10 3 copies/μL), respectively. This strategy can be adapted for detection of other DNA samples, with potential for development of a new breed of simple and inexpensive paper microchip at the point-of-need.

  8. Instrument for Real-Time Digital Nucleic Acid Amplification on Custom Microfluidic Devices.

    Directory of Open Access Journals (Sweden)

    David A Selck

    Full Text Available Nucleic acid amplification tests that are coupled with a digital readout enable the absolute quantification of single molecules, even at ultralow concentrations. Digital methods are robust, versatile and compatible with many amplification chemistries including isothermal amplification, making them particularly invaluable to assays that require sensitive detection, such as the quantification of viral load in occult infections or detection of sparse amounts of DNA from forensic samples. A number of microfluidic platforms are being developed for carrying out digital amplification. However, the mechanistic investigation and optimization of digital assays has been limited by the lack of real-time kinetic information about which factors affect the digital efficiency and analytical sensitivity of a reaction. Commercially available instruments that are capable of tracking digital reactions in real-time are restricted to only a small number of device types and sample-preparation strategies. Thus, most researchers who wish to develop, study, or optimize digital assays rely on the rate of the amplification reaction when performed in a bulk experiment, which is now recognized as an unreliable predictor of digital efficiency. To expand our ability to study how digital reactions proceed in real-time and enable us to optimize both the digital efficiency and analytical sensitivity of digital assays, we built a custom large-format digital real-time amplification instrument that can accommodate a wide variety of devices, amplification chemistries and sample-handling conditions. Herein, we validate this instrument, we provide detailed schematics that will enable others to build their own custom instruments, and we include a complete custom software suite to collect and analyze the data retrieved from the instrument. We believe assay optimizations enabled by this instrument will improve the current limits of nucleic acid detection and quantification, improving our

  9. Beyond Words: Amplification of Cancer Risk Communication on Social Media.

    Science.gov (United States)

    Strekalova, Yulia A; Krieger, Janice L

    2017-10-01

    Social media provide a unique channel for disseminating evidence-based information to diverse audiences and organizational and private stakeholders, thus facilitating a dialog about health and health risks. Guided by the social amplification of risk framework, the goal of this study was to assess the level of audience engagement with messages posted on the National Cancer Institute (NCI) Facebook page and evaluate the differences in the audience information behavior toward risk-related and non-risk posts. Data included 1,975 posts published on the NCI Facebook page as well as the corresponding 4,537 comments, 77,298 shares, and 145,462 likes. Links and images were the top two most frequent types of content for both risk-related and non-risk posts, but risk-related messages were more amplified through comments, shares, and likes. Comparing the modality of risk-related messages, videos, contrary to the prediction, were not more effective in attracting audience engagement than images. Finally, comments to risk-related posts did not repeat risk-related language suggesting that future studies should examine risk signal recognition and dissemination as separate behaviors. This study's findings emphasize the importance of focused investigation of message design strategies and message effects on the dissemination and amplification of communication related to health risks.

  10. Mutually incoherent beam combining through optical parametric amplification

    International Nuclear Information System (INIS)

    Tropheme, B.

    2012-01-01

    This work deals with a technique of combination of coherent beams: Optical Parametric Amplification (OPA) with Multiple Pumps. This technique is used to instantly transfer the energy of several pumps on one beam, without energy storage and thus avoiding thermal effects in the amplifying media. It can be useful to combine energy of numerous fiber lasers and to amplify with a high repetition rate very high energy lasers or broadband pulses. With a numerical and experimental study using BBO and LBO as nonlinear crystal, we determine how to dispose the pumps around the signal and the corresponding angular tolerances of such set up. Then we focus our attention on recombining mechanisms between a pump and a non-corresponding idler. We demonstrate experimentally that these cascading effects may decrease the spatial and spectral quality of the amplified signal, and that these phenomena can be avoided with a minimum angle between the different pumps. A novel modelling of multi-pumps OPA links these cascading effects to the gratings generated by the interaction between the pumps. The last part presents a 5 pump OPA experiment. We achieve a pump-to-signal efficiency of 27% and so that a signal more powerful than each pump is obtained. (author) [fr

  11. Knockdown of human serine/threonine kinase 33 suppresses human small cell lung carcinoma by blocking RPS6/BAD signaling transduction.

    Science.gov (United States)

    Sun, E L; Liu, C X; Ma, Z X; Mou, X Y; Mu, X A; Ni, Y H; Li, X L; Zhang, D; Ju, Y R

    2017-01-01

    Small cell lung cancer (SCLC) is characterized by rapid growth rate and a tendency to metastasize to distinct sites of patients' bodies. The human serine/threonine kinase 33 (STK33) gene has shown its potency as a therapeutic target for prevention of lung carcinomas including non-small cell lung cancer (NSCLC), but its function in the oncogenesis and development of SCLC remains unrevealed. In the current study, it was hypothesized that STK33 played a key role in the proliferation, survival, and invasion of SCLC cells. The expression of STK33 in human SCLC cell lines NCI-H466 and DMS153 was inhibited by specific shRNA. The cell proliferation, cell apoptosis, and cell invasion of the cells were assessed with a series of in vitro assays. To explore the mechanism through which STK33 gene exerted its function in the carcinogenesis of SCLC cells, the effect of STK33 knockdown on the activity of S6K1/RPS6/BAD signaling was detected. Then the results were further confirmed with STK33 inhibitor ML281 and in vivo assays. The results demonstrated that inhibition of STK33 in SCLC cells suppressed the cell proliferation and invasion while induced cell apoptosis. Associated with the change in the phenotypic features, knockdown of STK33 also decreased the phosphorylation of RPS6 and BAD while increased the expression of cleaved caspase 9, indicating that apoptosis induced by STK33 suppression was mediated via mitochondrial pathway. Similar to the results of STK33 knockdown, incubating NCI-H466 cells with STK33 inhibitor also reduced the cell viability by suppressing RPS6/BAD pathways. Additionally, STK33 knockdown also inhibited tumor growth and RPS6/BAD activity in mice models. Findings outlined in our study were different from that in NSCLC to some extent: knockdown of STK33 in SCLC cells induced the apoptosis through mitochondrial pathway but independent of S6K1 function, inferring that the function of STK33 might be cancer type specific.

  12. Amplification in Technical Manuals: Theory and Practice.

    Science.gov (United States)

    Killingsworth, M. Jimmie; And Others

    1989-01-01

    Examines how amplification (rhetorical techniques by which discourse is extended to enhance its appeal and information value) tends to increase and improve the coverage, rationale, warnings, behavioral alternatives, examples, previews, and general emphasis of technical manuals. Shows how classical and modern rhetorical theories can be applied to…

  13. Intelligence amplification framework for enhancing scheduling processes

    NARCIS (Netherlands)

    Dobrkovic, Andrej; Liu, Luyao; Iacob, Maria Eugenia; van Hillegersberg, Jos

    2016-01-01

    The scheduling process in a typical business environment consists of predominantly repetitive tasks that have to be completed in limited time and often containing some form of uncertainty. The intelligence amplification is a symbiotic relationship between a human and an intelligent agent. This

  14. Noise amplification of plant gravisensing

    Science.gov (United States)

    Ma, Zhong; Hasenstein, Karl H.

    A common problem in sensory physiology is the detection of weak signals, such as that produced by the repositioning of statoliths (amyloplasts) in gravisensing cells, from a noisy background. As in other studied biological mechanosensory systems, it is conceivable that the gravisensing process may be amplified by stochastic resonance and nonlinear noise-assisted effects. We therefore investigated the possible dependency of gravisensing on vibrational or thermodynamic noise by examining the effect of external oscillation and temperature on the rate of gravitropic curvature in flax (Linum usitatissimum L.) roots. Roots were oscillated for 15 min prior to or during gravistimulation, either parallel or perpendicular to the root axis. The effect of oscillation was dependent on its direction as well as frequency and amplitude. Initial curvature was most effectively enhanced by vertical oscillations of 5 Hz and 0.5 mm amplitude prior to reorientation. Vertically oscillated roots reached half-maximal curvature 32 min after reorientation, about 18 min earlier than non-oscillated roots. The enhancing effect of vibration on curvature subsided with a half-time of about 20 min. The temperature dependency of the graviresponse indicated that thermodynamic noise also impacted gravity perception. For vibrations and temperature studies, the presentation times decreased almost 6-fold. Our data indicate that gravisensing may depend on or be enhanced by thermodynamic or mechanical noise.

  15. Organo-erbium systems for optical amplification at telecommunications wavelengths.

    Science.gov (United States)

    Ye, H Q; Li, Z; Peng, Y; Wang, C C; Li, T Y; Zheng, Y X; Sapelkin, A; Adamopoulos, G; Hernández, I; Wyatt, P B; Gillin, W P

    2014-04-01

    Modern telecommunications rely on the transmission and manipulation of optical signals. Optical amplification plays a vital part in this technology, as all components in a real telecommunications system produce some loss. The two main issues with present amplifiers, which rely on erbium ions in a glass matrix, are the difficulty in integration onto a single substrate and the need of high pump power densities to produce gain. Here we show a potential organic optical amplifier material that demonstrates population inversion when pumped from above using low-power visible light. This system is integrated into an organic light-emitting diode demonstrating that electrical pumping can be achieved. This opens the possibility of direct electrically driven optical amplifiers and optical circuits. Our results provide an alternative approach to producing low-cost integrated optics that is compatible with existing silicon photonics and a different route to an effective integrated optics technology.

  16. Health Risk Information Engagement and Amplification on Social Media.

    Science.gov (United States)

    Strekalova, Yulia A

    2017-04-01

    Emerging pandemics call for unique health communication and education strategies in which public health agencies need to satisfy the public's information needs about possible risks while preventing risk exaggeration and dramatization. As a route to providing a framework for understanding public information behaviors in response to an emerging pandemic, this study examined the characteristics of communicative behaviors of social media audiences in response to Ebola outbreak news. Grounded in the social amplification of risks framework, this study adds to an understanding of information behaviors of online audiences by showing empirical differences in audience engagement with online health information. The data were collected from the Centers for Disease Control and Prevention (CDC) Facebook channel. The final data set included 809 CDC posts and 35,916 audience comments. The analysis identified the differences in audience information behaviors in response to an emerging pandemic, Ebola, and health promotion posts. While the CDC had fewer posts on Ebola than health promotion topics, the former received more attention from active page users. Furthermore, audience members who actively engaged with Ebola news had a small overlap with those who engaged with non-Ebola information during the same period. Overall, this study demonstrated that information behavior and audience engagement is topic dependent. Furthermore, audiences who commented on news about an emerging pandemic were homogenous and varied in their degree of information amplification.

  17. Assessment of whole genome amplification-induced bias through high-throughput, massively parallel whole genome sequencing

    Directory of Open Access Journals (Sweden)

    Plant Ramona N

    2006-08-01

    Full Text Available Abstract Background Whole genome amplification is an increasingly common technique through which minute amounts of DNA can be multiplied to generate quantities suitable for genetic testing and analysis. Questions of amplification-induced error and template bias generated by these methods have previously been addressed through either small scale (SNPs or large scale (CGH array, FISH methodologies. Here we utilized whole genome sequencing to assess amplification-induced bias in both coding and non-coding regions of two bacterial genomes. Halobacterium species NRC-1 DNA and Campylobacter jejuni were amplified by several common, commercially available protocols: multiple displacement amplification, primer extension pre-amplification and degenerate oligonucleotide primed PCR. The amplification-induced bias of each method was assessed by sequencing both genomes in their entirety using the 454 Sequencing System technology and comparing the results with those obtained from unamplified controls. Results All amplification methodologies induced statistically significant bias relative to the unamplified control. For the Halobacterium species NRC-1 genome, assessed at 100 base resolution, the D-statistics from GenomiPhi-amplified material were 119 times greater than those from unamplified material, 164.0 times greater for Repli-G, 165.0 times greater for PEP-PCR and 252.0 times greater than the unamplified controls for DOP-PCR. For Campylobacter jejuni, also analyzed at 100 base resolution, the D-statistics from GenomiPhi-amplified material were 15 times greater than those from unamplified material, 19.8 times greater for Repli-G, 61.8 times greater for PEP-PCR and 220.5 times greater than the unamplified controls for DOP-PCR. Conclusion Of the amplification methodologies examined in this paper, the multiple displacement amplification products generated the least bias, and produced significantly higher yields of amplified DNA.

  18. Biomass changes and trophic amplification of plankton in a warmer ocean

    KAUST Repository

    Chust, Guillem

    2014-05-07

    Ocean warming can modify the ecophysiology and distribution of marine organisms, and relationships between species, with nonlinear interactions between ecosystem components potentially resulting in trophic amplification. Trophic amplification (or attenuation) describe the propagation of a hydroclimatic signal up the food web, causing magnification (or depression) of biomass values along one or more trophic pathways. We have employed 3-D coupled physical-biogeochemical models to explore ecosystem responses to climate change with a focus on trophic amplification. The response of phytoplankton and zooplankton to global climate-change projections, carried out with the IPSL Earth System Model by the end of the century, is analysed at global and regional basis, including European seas (NE Atlantic, Barents Sea, Baltic Sea, Black Sea, Bay of Biscay, Adriatic Sea, Aegean Sea) and the Eastern Boundary Upwelling System (Benguela). Results indicate that globally and in Atlantic Margin and North Sea, increased ocean stratification causes primary production and zooplankton biomass to decrease in response to a warming climate, whilst in the Barents, Baltic and Black Seas, primary production and zooplankton biomass increase. Projected warming characterized by an increase in sea surface temperature of 2.29 ± 0.05 °C leads to a reduction in zooplankton and phytoplankton biomasses of 11% and 6%, respectively. This suggests negative amplification of climate driven modifications of trophic level biomass through bottom-up control, leading to a reduced capacity of oceans to regulate climate through the biological carbon pump. Simulations suggest negative amplification is the dominant response across 47% of the ocean surface and prevails in the tropical oceans; whilst positive trophic amplification prevails in the Arctic and Antarctic oceans. Trophic attenuation is projected in temperate seas. Uncertainties in ocean plankton projections, associated to the use of single global and

  19. Biomass changes and trophic amplification of plankton in a warmer ocean

    KAUST Repository

    Chust, Guillem; Allen, Julian Icarus; Bopp, Laurent; Schrum, Corinna; Holt, Jason T.; Tsiaras, Kostas P.; Zavatarelli, Marco; Chifflet, Marina; Cannaby, Heather; Dadou, Isabelle C.; Daewel, Ute; Wakelin, Sarah L.; Machú , Eric; Pushpadas, Dhanya; Butenschö n, Momme; Artioli, Yuri; Petihakis, George; Smith, Chris J M; Garç on, Vé ronique C.; Goubanova, Katerina; Le Vu, Briac; Fach, Bettina A.; Salihoglu, Baris; Clementi, Emanuela; Irigoien, Xabier

    2014-01-01

    Ocean warming can modify the ecophysiology and distribution of marine organisms, and relationships between species, with nonlinear interactions between ecosystem components potentially resulting in trophic amplification. Trophic amplification (or attenuation) describe the propagation of a hydroclimatic signal up the food web, causing magnification (or depression) of biomass values along one or more trophic pathways. We have employed 3-D coupled physical-biogeochemical models to explore ecosystem responses to climate change with a focus on trophic amplification. The response of phytoplankton and zooplankton to global climate-change projections, carried out with the IPSL Earth System Model by the end of the century, is analysed at global and regional basis, including European seas (NE Atlantic, Barents Sea, Baltic Sea, Black Sea, Bay of Biscay, Adriatic Sea, Aegean Sea) and the Eastern Boundary Upwelling System (Benguela). Results indicate that globally and in Atlantic Margin and North Sea, increased ocean stratification causes primary production and zooplankton biomass to decrease in response to a warming climate, whilst in the Barents, Baltic and Black Seas, primary production and zooplankton biomass increase. Projected warming characterized by an increase in sea surface temperature of 2.29 ± 0.05 °C leads to a reduction in zooplankton and phytoplankton biomasses of 11% and 6%, respectively. This suggests negative amplification of climate driven modifications of trophic level biomass through bottom-up control, leading to a reduced capacity of oceans to regulate climate through the biological carbon pump. Simulations suggest negative amplification is the dominant response across 47% of the ocean surface and prevails in the tropical oceans; whilst positive trophic amplification prevails in the Arctic and Antarctic oceans. Trophic attenuation is projected in temperate seas. Uncertainties in ocean plankton projections, associated to the use of single global and

  20. Biomass changes and trophic amplification of plankton in a warmer ocean.

    Science.gov (United States)

    Chust, Guillem; Allen, J Icarus; Bopp, Laurent; Schrum, Corinna; Holt, Jason; Tsiaras, Kostas; Zavatarelli, Marco; Chifflet, Marina; Cannaby, Heather; Dadou, Isabelle; Daewel, Ute; Wakelin, Sarah L; Machu, Eric; Pushpadas, Dhanya; Butenschon, Momme; Artioli, Yuri; Petihakis, George; Smith, Chris; Garçon, Veronique; Goubanova, Katerina; Le Vu, Briac; Fach, Bettina A; Salihoglu, Baris; Clementi, Emanuela; Irigoien, Xabier

    2014-07-01

    Ocean warming can modify the ecophysiology and distribution of marine organisms, and relationships between species, with nonlinear interactions between ecosystem components potentially resulting in trophic amplification. Trophic amplification (or attenuation) describe the propagation of a hydroclimatic signal up the food web, causing magnification (or depression) of biomass values along one or more trophic pathways. We have employed 3-D coupled physical-biogeochemical models to explore ecosystem responses to climate change with a focus on trophic amplification. The response of phytoplankton and zooplankton to global climate-change projections, carried out with the IPSL Earth System Model by the end of the century, is analysed at global and regional basis, including European seas (NE Atlantic, Barents Sea, Baltic Sea, Black Sea, Bay of Biscay, Adriatic Sea, Aegean Sea) and the Eastern Boundary Upwelling System (Benguela). Results indicate that globally and in Atlantic Margin and North Sea, increased ocean stratification causes primary production and zooplankton biomass to decrease in response to a warming climate, whilst in the Barents, Baltic and Black Seas, primary production and zooplankton biomass increase. Projected warming characterized by an increase in sea surface temperature of 2.29 ± 0.05 °C leads to a reduction in zooplankton and phytoplankton biomasses of 11% and 6%, respectively. This suggests negative amplification of climate driven modifications of trophic level biomass through bottom-up control, leading to a reduced capacity of oceans to regulate climate through the biological carbon pump. Simulations suggest negative amplification is the dominant response across 47% of the ocean surface and prevails in the tropical oceans; whilst positive trophic amplification prevails in the Arctic and Antarctic oceans. Trophic attenuation is projected in temperate seas. Uncertainties in ocean plankton projections, associated to the use of single global and

  1. Comparison of the Soil Dynamic Amplification Factor and Soil Amplification by Using Microtremor and MASW Methods Respectively

    Science.gov (United States)

    Tuncel, Aykut; Cevdet Özdag, Özkan; Pamuk, Eren; Akgün, Mustafa

    2017-12-01

    Single Station Microtremor method, which is widely used nowadays, is an effective and easy applicable method. In this study, dynamic amplification factor distributions of the study area were obtained using scenario earthquake parameters with single station microtremor data gathered at 112 points. In addition, a surface wave active method, which is known as MASW (Multichannel Analysis of Surface Waves), was applied at 43 profiles to calculate the soil amplification values. Dynamic amplification factor (DAF), soil amplification, the predominant soil period (PSP), geology and topography data of the study area were analysed together. Dynamic amplification factor and soil amplification values were obtained 2 or higher at about sea level parts of the study area which are generally composed of alluvial units. Additionally, in high altitude regions that are composed of volcanic rocks, relatively lower dynamic amplification factor and soil amplification values were obtained. The minimum amplification value in the study area was 1.15, while the maximum amplification value was 3.05 according to the dynamic amplification results and the soil amplification values were between 1.16 and 3.85 in harmony. It is seen that the obtained DAF values and the soil amplification values calculated from the seismic velocities are very similar to each other numerically and regionally. Because of this, it is concluded that the values of the soil amplification obtained by the MASW method and the calculated DAF values in this study are in harmony with each other. Although the depths of research in these two calculation methods are different from each other, the similarity of the results allows us to arrive at the result of how effective the ground layer is on the amplification. It has a great importance to calculate the amplification values and other dynamic parameters by in situ measurements for a planned plot because geological units can vary even at very short distances in heterogeneously

  2. Experimental demonstration of spatially coherent beam combining using optical parametric amplification.

    Science.gov (United States)

    Kurita, Takashi; Sueda, Keiichi; Tsubakimoto, Koji; Miyanaga, Noriaki

    2010-07-05

    We experimentally demonstrated coherent beam combining using optical parametric amplification with a nonlinear crystal pumped by random-phased multiple-beam array of the second harmonic of a Nd:YAG laser at 10-Hz repetition rate. In the proof-of-principle experiment, the phase jump between two pump beams was precisely controlled by a motorized actuator. For the demonstration of multiple-beam combining a random phase plate was used to create random-phased beamlets as a pump pulse. Far-field patterns of the pump, the signal, and the idler indicated that the spatially coherent signal beams were obtained on both cases. This approach allows scaling of the intensity of optical parametric chirped pulse amplification up to the exa-watt level while maintaining diffraction-limited beam quality.

  3. Numerical simulation of amplification of space charge waves in n-InP films

    International Nuclear Information System (INIS)

    Garcia-Barrientos, Abel; Palankovski, Vassil

    2011-01-01

    The non-linear interaction of space charge waves including the amplification in microwave and millimeter wave range in n-InP films, possessing the negative differential conductance phenomenon, is investigated theoretically. Both the amplified signal and the generation of harmonics of the input signal are demonstrated, which are due to non-linear effect of the negative differential resistance. It is possible to observe an amplification of the space charge waves in n-InP films of submicron thicknesses at essentially higher frequencies f <70 GHz, when compared with n-GaAs films f < 44 GHz. The increment observed in the gain is due to the larger dynamic range in n-InP than in n-GaAs films.

  4. Ultrafast optical signal processing using semiconductor quantum dot amplifiers

    DEFF Research Database (Denmark)

    Berg, Tommy Winther; Mørk, Jesper

    2002-01-01

    The linear and nonlinear properties of quantum dot amplifiers are discussed on the basis of an extensive theoretical model. These devices show great potential for linear amplification as well as ultrafast signal processing.......The linear and nonlinear properties of quantum dot amplifiers are discussed on the basis of an extensive theoretical model. These devices show great potential for linear amplification as well as ultrafast signal processing....

  5. Real-time monitoring of mycobacterium genomic DNA with target-primed rolling circle amplification by a Au nanoparticle-embedded SPR biosensor.

    Science.gov (United States)

    Xiang, Yang; Zhu, Xiaoyan; Huang, Qing; Zheng, Junsong; Fu, Weiling

    2015-04-15

    In this study, we developed a surface plasmon resonance (SPR) DNA biosensor array based on target-primed rolling circle amplification (RCA) for isothermal and rapid detection of two pathogenic mycobacteria, Mycobacterium tuberculosis complex (MTBC) and Mycobacterium avium complex (MAC).The species-specific padlock probe (PLP) was designed to target the sequence in 16S-23S rRNA gene internal transcribed spacer (ITS). After ligation, the circularized PLP could be primed by the target sequence to initial RCA. The RCA performed simultaneously with the cleavage reaction to produce small fragments of single strand DNA which immediately hybridized with the probe immobilized on the sensor chip without denaturation. This process caused SPR angle changes on the chip surface, which made the detection for analysis from the solution achievable, and dynamic real-time RCA monitoring of mycobacterium possible. Besides, Au nanoparticles (AuNPs) were directly assembled onto the surface of the sensor chip via hexanedithiol (HDT) for the enhancement of sensitivity as a label-free detection system. Experimental results show that the signal enhancement by the target-primed RCA together with AuNPs-embedded surface caused at least10-fold increased sensitivity as compared with conventional RCA on bare SPR chip method. Within 40min amplification duration as low as 20amol of synthetic targets and 10(4)CFUmL(-1) of genomic DNA from clinical samples can be detected. The proposed method not only provides a simple design idea for liquid-phase amplification monitoring, but also apply it in clinical pathogen detection, which holds great promise in ultrasensitive bioassay in the future. Copyright © 2014. Published by Elsevier B.V.

  6. A first-in-human phase I study of SAR125844, a selective MET tyrosine kinase inhibitor, in patients with advanced solid tumours with MET amplification.

    Science.gov (United States)

    Angevin, Eric; Spitaleri, Gianluca; Rodon, Jordi; Dotti, Katia; Isambert, Nicolas; Salvagni, Stefania; Moreno, Victor; Assadourian, Sylvie; Gomez, Corinne; Harnois, Marzia; Hollebecque, Antoine; Azaro, Analia; Hervieu, Alice; Rihawi, Karim; De Marinis, Filippo

    2017-12-01

    Dysregulated MET signalling is implicated in oncogenesis. The safety and preliminary efficacy of a highly selective MET kinase inhibitor (SAR125844) was investigated in patients with advanced solid tumours and MET dysregulation. This was a phase I dose-escalation (3 + 3 design [50-740 mg/m 2 ]) and dose-expansion study. In the dose escalation, patients had high total MET (t-MET) expression by immunohistochemistry (IHC) or MET amplification by fluorescence in situ hybridisation. In the dose expansion, patients had MET amplification (including a subset of patients with non-small cell lung cancer [NSCLC]) or phosphorylated-MET (p-MET) expression (IHC). Objectives were determination of maximum tolerated dose (MTD) of once-weekly intravenous SAR125844 based on dose-limiting toxicities; safety and pharmacokinetic profile; preliminary efficacy of SAR125844 MTD in the expansion cohort. In total, 72 patients were enrolled: dose escalation, N = 33; dose expansion, N = 39; 570 mg/m 2 was established as the MTD. Most frequent treatment-emergent adverse events (AEs) were asthenia/fatigue (58.3%), nausea (31.9%), and abdominal pain, constipation, and dyspnea (27.8% for each); 58.3% of patients reported grade 3 AEs (19.4% were treatment related). Of the 29 evaluable patients with MET amplification treated at 570 mg/m 2 , five achieved a partial response, including four of 22 with NSCLC; 17 patients had stable disease. No response was observed in patients with high p-MET solid tumours. There was no correlation between tumour response and t-MET status or MET gene copy number. The MTD of once-weekly SAR125844 was 570 mg/m 2 ; SAR125844 was well tolerated, with significant antitumour activity in patients with MET-amplified NSCLC. NCT01391533. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  7. Near quantum limited amplification from inelastic Cooper-pair tunneling

    Science.gov (United States)

    Hofheinz, Max; Jebari, Salha; Blanchet, Florian; Grimm, Alexander; Hazra, Dibyendu; Albert, Romain; Portier, Fabien

    Josephson parametric amplifiers approach quantum-limited noise performance but require strong external microwave pump tones which make them more difficult to use than DC powered amplifiers: The pump tone can affect the device under test and requires expensive room-temperature equipment. Inelastic Cooper pair tunneling processes through a small DC voltage-biased Josephson junction, where a tunneling Cooper pair dissipates its energy 2 eV in the form of two photons are reminiscent of parametric down conversion. We show that these processes can be used to provide amplification near the quantum limit without external microwave pump tone. We explain the measured gain and noise based on the P (E) theory of inelastic Cooper pair tunneling and general fluctuation-dissipation relations.

  8. Digital Microfluidics for Nucleic Acid Amplification

    Directory of Open Access Journals (Sweden)

    Beatriz Coelho

    2017-06-01

    Full Text Available Digital Microfluidics (DMF has emerged as a disruptive methodology for the control and manipulation of low volume droplets. In DMF, each droplet acts as a single reactor, which allows for extensive multiparallelization of biological and chemical reactions at a much smaller scale. DMF devices open entirely new and promising pathways for multiplex analysis and reaction occurring in a miniaturized format, thus allowing for healthcare decentralization from major laboratories to point-of-care with accurate, robust and inexpensive molecular diagnostics. Here, we shall focus on DMF platforms specifically designed for nucleic acid amplification, which is key for molecular diagnostics of several diseases and conditions, from pathogen identification to cancer mutations detection. Particular attention will be given to the device architecture, materials and nucleic acid amplification applications in validated settings.

  9. Light amplification by seeded Kerr instability

    Science.gov (United States)

    Vampa, G.; Hammond, T. J.; Nesrallah, M.; Naumov, A. Yu.; Corkum, P. B.; Brabec, T.

    2018-02-01

    Amplification of femtosecond laser pulses typically requires a lasing medium or a nonlinear crystal. In either case, the chemical properties of the lasing medium or the momentum conservation in the nonlinear crystal constrain the frequency and the bandwidth of the amplified pulses. We demonstrate high gain amplification (greater than 1000) of widely tunable (0.5 to 2.2 micrometers) and short (less than 60 femtosecond) laser pulses, up to intensities of 1 terawatt per square centimeter, by seeding the modulation instability in an Y3Al5O12 crystal pumped by femtosecond near-infrared pulses. Our method avoids constraints related to doping and phase matching and therefore can occur in a wider pool of glasses and crystals even at far-infrared frequencies and for single-cycle pulses. Such amplified pulses are ideal to study strong-field processes in solids and highly excited states in gases.

  10. Comparison of Chromogenic In Situ Hybridization and Fluorescence In Situ Hybridization for the Evaluation of MDM2 Amplification in Adipocytic Tumors.

    Science.gov (United States)

    Mardekian, Stacey K; Solomides, Charalambos C; Gong, Jerald Z; Peiper, Stephen C; Wang, Zi-Xuan; Bajaj, Renu

    2015-11-01

    Atypical lipomatous tumor/well-differentiated liposarcoma (ALT-WDLPS) and dedifferentiated liposarcoma (DDLPS) are characterized cytogenetically by a 12q13-15 amplification involving the mouse double minute 2 (MDM2) oncogene. Fluorescence in situ hybridization (FISH) is used frequently to detect this amplification and aid with the diagnosis of these entities, which is difficult by morphology alone. Recently, bright-field in situ hybridization techniques such as chromogenic in situ hybridization (CISH) have been introduced for the determination of MDM2 amplification status. The present study compared the results of FISH and CISH for detecting MDM2 amplification in 41 cases of adipocytic tumors. Amplification was defined in both techniques as a MDM2/CEN12 ratio of 2 or greater. Eleven cases showed amplification with both FISH and CISH, and 26 cases showed no amplification with both methods. Two cases had discordant results between CISH and FISH, and two cases were not interpretable by CISH. CISH is advantageous for allowing pathologists to evaluate the histologic and molecular alterations occurring simultaneously in a specimen. Moreover, CISH is found to be more cost- and time-efficient when used with automation, and the signals do not quench over time. CISH technique is a reliable alternative to FISH in the evaluation of adipocytic tumors for MDM2 amplification. © 2014 Wiley Periodicals, Inc.

  11. Hormonal Involvement in Breast Cancer Gene Amplification

    Science.gov (United States)

    2010-10-01

    been shown to induce DN A amplification in yeast (Gopalakrishnan et al., 2001; Nguy en et al., 2001; Green et al., 2006) an d increased Cdt1 results in...re-replication in human cells (Dorn et al., 2008). The N- terminus of Cdt1 is important for re-replication, perhaps through interactions with PCNA...evolution of a cancer genome. Genome Res. (Epub. Dec. 3, 2008). Harris TD, Buzby PR, Babcock H, Beer E, Bowers J, Bras lavsky I, Causey M

  12. Fast amplification system for gamma spectroscopy

    International Nuclear Information System (INIS)

    Jesus, E.F.O.; Lopes, R.T.

    1992-01-01

    An amplification system for gamma spectroscopy with high counting rates was developed. The system was constructed with operational amplifiers, and tested and compared with ORTEC conventional system, using Iridium-192 as source of 9,25 x 10 1 0 Bq of activity and NaI (Tl) detector. The constructed system showed a better performance in relation to efficiency and resolution parameters, tested before. (C.G.C.)

  13. Optimized thermal amplification in a radiative transistor

    Energy Technology Data Exchange (ETDEWEB)

    Prod' homme, Hugo; Ordonez-Miranda, Jose; Ezzahri, Younes, E-mail: younes.ezzahri@univ-poitiers.fr; Drevillon, Jeremie; Joulain, Karl [Institut Pprime, CNRS, Université de Poitiers, ISAE-ENSMA, F-86962 Futuroscope Chasseneuil (France)

    2016-05-21

    The thermal performance of a far-field radiative transistor made up of a VO{sub 2} base in between a blackbody collector and a blackbody emitter is theoretically studied and optimized. This is done by using the grey approximation on the emissivity of VO{sub 2} and deriving analytical expressions for the involved heat fluxes and transistor amplification factor. It is shown that this amplification factor can be maximized by tuning the base temperature close to its critical one, which is determined by the temperature derivative of the VO{sub 2} emissivity and the equilibrium temperatures of the collector and emitter. This maximization is the result of the presence of two bi-stable temperatures appearing during the heating and cooling processes of the VO{sub 2} base and enables a thermal switching (temperature jump) characterized by a sizeable variation of the collector-to-base and base-to-emitter heat fluxes associated with a slight change of the applied power to the base. This switching effect leads to the optimization of the amplification factor and therefore it could be used for thermal modulation purposes.

  14. HER-2 amplification in tubular carcinoma of the breast.

    Science.gov (United States)

    Oakley, Gerard J; Tubbs, Raymond R; Crowe, Joseph; Sebek, Bruce; Budd, G Thomas; Patrick, Rebecca J; Procop, Gary W

    2006-07-01

    The prognostic and therapeutic implications of HER-2 gene amplification and estrogen and progesterone receptor status in breast cancer are well described. To address the relative paucity of information concerning HER-2 amplification for tubular carcinomas, we assessed the frequency of gene amplification in 55 tubular carcinomas of the breast from 54 patients, 5 of which had axillary node metastases. The HER-2 gene copy number was assessed by fluorescence in situ hybridization for the majority of tumors analyzed, whereas estrogen and progesterone receptor status was achieved by immunohistochemical analysis. HER-2 gene amplification was not observed in any of the tumors examined, and most were estrogen receptor-positive. This HER-2 gene amplification frequency was significantly lower than the frequency of gene amplification previously reported for all invasive ductal carcinoma of no special type (P < .01). HER-2 gene amplification likely occurs infrequently, or not at all, in tubular carcinomas of the breast, whereas most express estrogen receptors.

  15. 85 km long reach PON system using a reflective SOA-EA modulator and distributed Raman fiber amplification

    NARCIS (Netherlands)

    Tafur Monroy, I.; Öhman, F.; Yvind, K.; Kjaer, R.; Peucheret, C.; Koonen, A.M.J.; Jeppesen, P.

    2006-01-01

    We report on a bidirectional 85 km long reach PON system supported by distributed fiber Raman amplification with a record 7.5 Gb/s remote carrier modulated upstream signal by employing a reflective SOA-EA monolithically integrated circuit.

  16. Study of C-MYC amplification and expression in Iranian gastric cancer samples using CISH and IHC methods.

    Science.gov (United States)

    Khaleghian, Malihea; Jahanzad, Issa; Shakoori, Abbas; Ardalan, Farid Azmoudeh; Azimi, Cyrus

    2015-01-01

    Gastric cancer is the fourth most frequent malignancy and the second cause of cancer-related mortality worldwide. It has been suggested that in gastric carcinogenesis, the C-MYC gene has an important function. The objective of this study is to establish the preference of Chromogenic in situ hybridization (CISH) and Immunohistochemistry (IHC) in the diagnosis and prognosis of gastric cancer. Samples comprised of 50 randomly selected patients of whom 40 were male and 10 female. To evaluate the MYC copy number and its protein expression, CISH and IHC analyses were performed for 50 gastric adenocarcinomas, in Iran. The location of the tumor in 64% of the patients was the fundus, and in 72% of patients, the tumors were of a diffuse type; 22 samples showed no amplification, and 28 samples were with amplification. MYC immunoreactivity was observed in 13 samples. Twelve samples showed both MYC amplification and MYC immunoreactivity. In addition, among the 28 CISH+ samples, 12 samples had positive signals for IHC and 16 samples had negative signals for IHC. A majority of the IHC-negative patients had no amplification, but only one patient with IHC positive had no amplification. Our conclusion was that for the management and treatment of gastric cancer, and for special attention of clinicians, for prognosis and tumor progression, the CISH was a better and more feasible test than IHC, in regard to the sensitivity and specificity.

  17. Study of C-MYC amplification and expression in Iranian gastric cancer samples using CISH and IHC methods

    Directory of Open Access Journals (Sweden)

    Malihea Khaleghian

    2015-01-01

    Full Text Available Background: Gastric cancer is the fourth most frequent malignancy and the second cause of cancer-related mortality worldwide. It has been suggested that in gastric carcinogenesis, the C-MYC gene has an important function. The objective of this study is to establish the preference of Chromogenic in situ hybridization (CISH and Immunohistochemistry (IHC in the diagnosis and prognosis of gastric cancer. Materials and Methods: Samples comprised of 50 randomly selected patients of whom 40 were male and 10 female. To evaluate the MYC copy number and its protein expression, CISH and IHC analyses were performed for 50 gastric adenocarcinomas, in Iran. Results: The location of the tumor in 64% of the patients was the fundus, and in 72% of patients, the tumors were of a diffuse type; 22 samples showed no amplification, and 28 samples were with amplification. MYC immunoreactivity was observed in 13 samples. Twelve samples showed both MYC amplification and MYC immunoreactivity. In addition, among the 28 CISH+ samples, 12 samples had positive signals for IHC and 16 samples had negative signals for IHC. A majority of the IHC-negative patients had no amplification, but only one patient with IHC positive had no amplification. Conclusion: Our conclusion was that for the management and treatment of gastric cancer, and for special attention of clinicians, for prognosis and tumor progression, the CISH was a better and more feasible test than IHC, in regard to the sensitivity and specificity.

  18. Loop mediated isothermal amplification: An innovative gene amplification technique for animal diseases

    Directory of Open Access Journals (Sweden)

    Pravas Ranjan Sahoo

    2016-05-01

    Full Text Available India being a developing country mainly depends on livestock sector for its economy. However, nowadays, there is emergence and reemergence of more transboundary animal diseases. The existing diagnostic techniques are not so quick and with less specificity. To reduce the economy loss, there should be a development of rapid, reliable, robust diagnostic technique, which can work with high degree of sensitivity and specificity. Loop mediated isothermal amplification assay is a rapid gene amplification technique that amplifies nucleic acid under an isothermal condition with a set of designed primers spanning eight distinct sequences of the target. This assay can be used as an emerging powerful, innovative gene amplification diagnostic tool against various pathogens of livestock diseases. This review is to highlight the basic concept and methodology of this assay in livestock disease.

  19. Loop mediated isothermal amplification: An innovative gene amplification technique for animal diseases.

    Science.gov (United States)

    Sahoo, Pravas Ranjan; Sethy, Kamadev; Mohapatra, Swagat; Panda, Debasis

    2016-05-01

    India being a developing country mainly depends on livestock sector for its economy. However, nowadays, there is emergence and reemergence of more transboundary animal diseases. The existing diagnostic techniques are not so quick and with less specificity. To reduce the economy loss, there should be a development of rapid, reliable, robust diagnostic technique, which can work with high degree of sensitivity and specificity. Loop mediated isothermal amplification assay is a rapid gene amplification technique that amplifies nucleic acid under an isothermal condition with a set of designed primers spanning eight distinct sequences of the target. This assay can be used as an emerging powerful, innovative gene amplification diagnostic tool against various pathogens of livestock diseases. This review is to highlight the basic concept and methodology of this assay in livestock disease.

  20. Environmental whole-genome amplification to access microbial populations in contaminated sediments

    Energy Technology Data Exchange (ETDEWEB)

    Abulencia, Carl B [Diversa Corporation; Wyborski, Denise L. [Diversa Corporation; Garcia, Joseph A. [Diversa Corporation; Podar, Mircea [ORNL; Chen, Wenqiong [Diversa Corporation; Chang, Sherman H. [Diversa Corporation; Chang, Hwai W. [Diversa Corporation; Watson, David B [ORNL; Brodie, Eoin L. [Lawrence Berkeley National Laboratory (LBNL); Hazen, Terry [Lawrence Berkeley National Laboratory (LBNL); Keller, Martin [ORNL

    2006-05-01

    Low-biomass samples from nitrate and heavy metal contaminated soils yield DNA amounts that have limited use for direct, native analysis and screening. Multiple displacement amplification (MDA) using {phi}29 DNA polymerase was used to amplify whole genomes from environmental, contaminated, subsurface sediments. By first amplifying the genomic DNA (gDNA), biodiversity analysis and gDNA library construction of microbes found in contaminated soils were made possible. The MDA method was validated by analyzing amplified genome coverage from approximately five Escherichia coli cells, resulting in 99.2% genome coverage. The method was further validated by confirming overall representative species coverage and also an amplification bias when amplifying from a mix of eight known bacterial strains. We extracted DNA from samples with extremely low cell densities from a U.S. Department of Energy contaminated site. After amplification, small-subunit rRNA analysis revealed relatively even distribution of species across several major phyla. Clone libraries were constructed from the amplified gDNA, and a small subset of clones was used for shotgun sequencing. BLAST analysis of the library clone sequences showed that 64.9% of the sequences had significant similarities to known proteins, and 'clusters of orthologous groups' (COG) analysis revealed that more than half of the sequences from each library contained sequence similarity to known proteins. The libraries can be readily screened for native genes or any target of interest. Whole-genome amplification of metagenomic DNA from very minute microbial sources, while introducing an amplification bias, will allow access to genomic information that was not previously accessible.

  1. Environmental Whole-Genome Amplification to Access Microbial Diversity in Contaminated Sediments

    Energy Technology Data Exchange (ETDEWEB)

    Abulencia, C.B.; Wyborski, D.L.; Garcia, J.; Podar, M.; Chen, W.; Chang, S.H.; Chang, H.W.; Watson, D.; Brodie,E.I.; Hazen, T.C.; Keller, M.

    2005-12-10

    Low-biomass samples from nitrate and heavy metal contaminated soils yield DNA amounts that have limited use for direct, native analysis and screening. Multiple displacement amplification (MDA) using ?29 DNA polymerase was used to amplify whole genomes from environmental, contaminated, subsurface sediments. By first amplifying the genomic DNA (gDNA), biodiversity analysis and gDNA library construction of microbes found in contaminated soils were made possible. The MDA method was validated by analyzing amplified genome coverage from approximately five Escherichia coli cells, resulting in 99.2 percent genome coverage. The method was further validated by confirming overall representative species coverage and also an amplification bias when amplifying from a mix of eight known bacterial strains. We extracted DNA from samples with extremely low cell densities from a U.S. Department of Energy contaminated site. After amplification, small subunit rRNA analysis revealed relatively even distribution of species across several major phyla. Clone libraries were constructed from the amplified gDNA, and a small subset of clones was used for shotgun sequencing. BLAST analysis of the library clone sequences showed that 64.9 percent of the sequences had significant similarities to known proteins, and ''clusters of orthologous groups'' (COG) analysis revealed that more than half of the sequences from each library contained sequence similarity to known proteins. The libraries can be readily screened for native genes or any target of interest. Whole-genome amplification of metagenomic DNA from very minute microbial sources, while introducing an amplification bias, will allow access to genomic information that was not previously accessible.

  2. Evaluation of Myc Gene Amplification in Prostate Cancer Using a Dual Color Chromogenic in-Situ Hybridization (Dual CISH) Assay

    OpenAIRE

    Daniel Lerda; Marta Cabrera; Jorge Flores; Luis Gutierrez; Armando Chierichetti; Martin Revol; Hernan Garcia Onto

    2013-01-01

    Objetive: The overall purpose of the study was to demonstrate applicability of the Dako dual-color chromogenic in situ hybridization (CISH) assay (DAKO Denmark, Glostrup) with respect to fluorescence in situ hybridization (FISH) probes MYC-C. Methods: MYC gene amplification by FISH and Dako dual-color CISH Results: The study showed that the dual-color CISH assay can convert Texas red and fluorescein isothiocyanate (FITC) signals into chromogenic signals. The dual –color CISH assay was p...

  3. Optimization and characterization of dual-chirped optical parametric amplification

    International Nuclear Information System (INIS)

    Fu, Yuxi; Takahashi, Eiji J; Midorikawa, Katsumi; Zhang, Qingbin; Lu, Peixiang

    2015-01-01

    We report optimization and characterization of a dual-chirped optical parametric amplification (DC-OPA) scheme (2011 Opt. Express 19 7190). By increasing a pump pulse energy to 100 mJ, a total (signal + idler) output energy exceeding 30 mJ was recorded with higher than 30% conversion efficiency. The feasibility of further increasing the output energy to a higher scale using the DC-OPA scheme was confirmed by a proof-of-principle experiment, in which 30%–40% conversion efficiency was observed. The signal pulse with the center wavelength of 1.4 μm was compressed to 27 fs (FWHM), which was very close to a transform-limited pulse duration of 25 fs. Since the DC-OPA scheme is efficient for generating high-energy infrared (IR) pulses with excellent scaling ability, the design parameters for obtaining hundred-mJ-level and even joule-level IR pulses are discussed and presented in detail. (invited article)

  4. Human minisatellite alleles detectable only after PCR amplification.

    Science.gov (United States)

    Armour, J A; Crosier, M; Jeffreys, A J

    1992-01-01

    We present evidence that a proportion of alleles at two human minisatellite loci is undetected by standard Southern blot hybridization. In each case the missing allele(s) can be identified after PCR amplification and correspond to tandem arrays too short to detect by hybridization. At one locus, there is only one undetected allele (population frequency 0.3), which contains just three repeat units. At the second locus, there are at least five undetected alleles (total population frequency 0.9) containing 60-120 repeats; they are not detected because these tandem repeats give very poor signals when used as a probe in standard Southern blot hybridization, and also cross-hybridize with other sequences in the genome. Under these circumstances only signals from the longest tandemly repeated alleles are detectable above the nonspecific background. The structures of these loci have been compared in human and primate DNA, and at one locus the short human allele containing three repeat units is shown to be an intermediate state in the expansion of a monomeric precursor allele in primates to high copy number in the longer human arrays. We discuss the implications of such loci for studies of human populations, minisatellite isolation by cloning, and the evolution of highly variable tandem arrays.

  5. Plasma wave instability and amplification of terahertz radiation in field-effect-transistor arrays

    International Nuclear Information System (INIS)

    Popov, V V; Tsymbalov, G M; Shur, M S

    2008-01-01

    We show that the strong amplification of terahertz radiation takes place in an array of field-effect transistors at small DC drain currents due to hydrodynamic plasmon instability of the collective plasmon mode. Planar designs compatible with standard integrated circuit fabrication processes and strong coupling of terahertz radiation to plasmon modes in FET arrays make such arrays very attractive for potential applications in solid-state terahertz amplifiers and emitters

  6. Chromosomal Localization of DNA Amplifications in Neuroblastoma Tumors Using cDNA Microarray Comparative Genomic Hybridization

    Directory of Open Access Journals (Sweden)

    Ben Beheshti

    2003-01-01

    Full Text Available Conventional comparative genomic hybridization (CGH profiling of neuroblastomas has identified many genomic aberrations, although the limited resolution has precluded a precise localization of sequences of interest within amplicons. To map high copy number genomic gains in clinically matched stage IV neuroblastomas, CGH analysis using a 19,200-feature cDNA microarray was used. A dedicated (freely available algorithm was developed for rapid in silico determination of chromosomal localizations of microarray cDNA targets, and for generation of an ideogram-type profile of copy number changes. Using these methodologies, novel gene amplifications undetectable by chromosome CGH were identified, and larger MYCN amplicon sizes (in one tumor up to 6 Mb than those previously reported in neuroblastoma were identified. The genes HPCAL1, LPIN1/KIAA0188, NAG, and NSE1/LOC151354 were found to be coamplified with MYCN. To determine whether stage IV primary tumors could be further subclassified based on their genomic copy number profiles, hierarchical clustering was performed. Cluster analysis of microarray CGH data identified three groups: 1 no amplifications evident, 2 a small MYCN amplicon as the only detectable imbalance, and 3 a large MYCN amplicon with additional gene amplifications. Application of CGH to cDNA microarray targets will help to determine both the variation of amplicon size and help better define amplification-dependent and independent pathways of progression in neuroblastoma.

  7. Single Cell Analysis of Dystrophin and SRY Gene by Using Whole Genome Amplification

    Institute of Scientific and Technical Information of China (English)

    徐晨明; 金帆; 黄荷凤; 陶冶; 叶英辉

    2001-01-01

    Objective To develop a reliable and sensitive method for detection of sex and multiloci of Duchenne muscular dystrophy (DMD) gene in single cell Materials & methods Whole genome of single cell were amplified by using 15-base random primers (primer extension preamplification, PEP), then a small aliquot of PEP product were analyzed by using locus-specific nest PCR amplification. The procedure was evaluated by detection dystrophin exons 8, 17, 19, 44, 45, 48 and human testis-determining gene (SRY)in single lymphocytes from known sources and single blastomeres from the couples with no family history of DMD.Results The amplification efficiency rate of six dystrophin exons from single lymphocytes and single blastomeres were 97. 2% (175/180) and 100% (60/60) respectively.Results of SRY showed that 100% (15/15) amplification in single male-derived lymphocytes and 0% (0/15) amplification in single female-derived lymphocytes. Conclusion The technique of single cell PEP-nest PCR for dystrophin exons 8, 17,19, 44, 45, 48 and SRY is highly specifc. PEP-nest PCR is suitable for Preimplantation genetic diagnosis (PGD) of DMD at single cell level.

  8. Nanoliter reactors improve multiple displacement amplification of genomes from single cells.

    Directory of Open Access Journals (Sweden)

    Yann Marcy

    2007-09-01

    Full Text Available Since only a small fraction of environmental bacteria are amenable to laboratory culture, there is great interest in genomic sequencing directly from single cells. Sufficient DNA for sequencing can be obtained from one cell by the Multiple Displacement Amplification (MDA method, thereby eliminating the need to develop culture methods. Here we used a microfluidic device to isolate individual Escherichia coli and amplify genomic DNA by MDA in 60-nl reactions. Our results confirm a report that reduced MDA reaction volume lowers nonspecific synthesis that can result from contaminant DNA templates and unfavourable interaction between primers. The quality of the genome amplification was assessed by qPCR and compared favourably to single-cell amplifications performed in standard 50-microl volumes. Amplification bias was greatly reduced in nanoliter volumes, thereby providing a more even representation of all sequences. Single-cell amplicons from both microliter and nanoliter volumes provided high-quality sequence data by high-throughput pyrosequencing, thereby demonstrating a straightforward route to sequencing genomes from single cells.

  9. Development of an Automated Microfluidic System for DNA Collection, Amplification, and Detection of Pathogens

    Energy Technology Data Exchange (ETDEWEB)

    Hagan, Bethany S.; Bruckner-Lea, Cynthia J.

    2002-12-01

    This project was focused on developing and testing automated routines for a microfluidic Pathogen Detection System. The basic pathogen detection routine has three primary components; cell concentration, DNA amplification, and detection. In cell concentration, magnetic beads are held in a flow cell by an electromagnet. Sample liquid is passed through the flow cell and bacterial cells attach to the beads. These beads are then released into a small volume of fluid and delivered to the peltier device for cell lysis and DNA amplification. The cells are lysed during initial heating in the peltier device, and the released DNA is amplified using polymerase chain reaction (PCR) or strand displacement amplification (SDA). Once amplified, the DNA is then delivered to a laser induced fluorescence detection unit in which the sample is detected. These three components create a flexible platform that can be used for pathogen detection in liquid and sediment samples. Future developments of the system will include on-line DNA detection during DNA amplification and improved capture and release methods for the magnetic beads during cell concentration.

  10. Social amplification of risk: An empirical study

    International Nuclear Information System (INIS)

    Burns, W.; Slovic, P.; Kasperson, R.; Kasperson, J.; Renn, O.; Emani, S.

    1990-09-01

    The social amplification of risk is a theoretical framework that addresses an important deficiency of formal risk assessment methods and procedures. Typically assessments of risk from technological mishaps have been based upon the expected number of people who could be killed or injured or the amount of property that might be damaged. The diverse and consequential impacts that followed in the aftermath of the Three Mile Island accident make it clear that risk assessments that exclude the role of public perceptions of risk will greatly underestimate the potential costs of certain types of hazards. The accident at Three Mile Island produced no direct fatalities and few, if any, expected deaths due to cancer, yet few other accidents in history have had such costly societal impacts. The experience of amplified impacts argues for the development of a broadened theoretical and methodological perspective capable of integrating technical assessment of risk with public perceptions. This report presents the results to date in an ongoing research effort to better understand the complex processes by which adverse events produce impacts. In particular this research attempts to construct a framework that can account for those events that have produced, or are capable of producing, greater societal impacts than would be forecast by traditional risk assessment methods. This study demonstrates that the social amplification of risk involves interactions between sophisticated technological hazards, public and private institutions, and subtle individual and public perceptions and behaviors. These factors, and the variables underlying the intricate processes of social amplification that occur in modern society, are not fully defined and clarified in this report. 19 refs., 9 figs., 10 tabs

  11. Amplification of curvature perturbations in cyclic cosmology

    International Nuclear Information System (INIS)

    Zhang Jun; Liu Zhiguo; Piao Yunsong

    2010-01-01

    We analytically and numerically show that through the cycles with nonsingular bounce, the amplitude of curvature perturbation on a large scale will be amplified and the power spectrum will redden. In some sense, this amplification will eventually destroy the homogeneity of the background, which will lead to the ultimate end of cycles of the global universe. We argue that for the model with increasing cycles, it might be possible that a fissiparous multiverse will emerge after one or several cycles, in which the cycles will continue only at corresponding local regions.

  12. Parametric Amplification of Gravitational Fluctuations during Reheating

    International Nuclear Information System (INIS)

    Finelli, F.; Brandenberger, R.; Finelli, F.

    1999-01-01

    Cosmological perturbations can undergo amplification by parametric resonance during preheating even on scales larger than the Hubble radius, without violating causality. A unified description of gravitational and matter fluctuations is crucial to determine the strength of the instability. To extract specific signatures of the oscillating inflaton field during reheating, it is essential to focus on a variable describing metric fluctuations which is constant in the standard analyses of inflation. For a massive inflaton without self-coupling, we find no additional growth of superhorizon modes during reheating beyond the usual predictions. For a massless self-coupled inflaton, there is a sub-Hubble scale resonance. copyright 1999 The American Physical Society

  13. Egfr Amplification Specific Gene Expression in Phyllodes Tumours of the Breast

    Directory of Open Access Journals (Sweden)

    Konstantin Agelopoulos

    2007-01-01

    Full Text Available Background: Recently, we were able to show that amplifications of the epidermal growth factor receptor (egfr gene and the overexpression of EGFR were associated with the initiation and progression of phyllodes tumours. Methods: In order to gain further insights into regulation mechanisms associated with egfr amplifications and EGFR expression in phyllodes tumours, we performed global gene expression analysis (Affymetrix A133.2 on a series of 10 phyllodes tumours, of these three with and seven without amplifications of an important regulatory repeat in intron 1 of egfr (CA-SSR I. The results were verified and extended by means of immunohistochemistry using the tissue microarray method on an extensively characterized series of 58 phyllodes tumours with antibodies against caveolin-1, eps15, EGF, TGF-α, pErk, pAkt and mdm2. Results: We were able to show that the presence of egfr CA-SSR I amplifications in phyllodes tumours was associated with 230 differentially expressed genes. Caveolin-1 and eps15, involved in EGFR turnover and signalling, were regulated differentially on the RNA and protein level proportionally to egfr gene dosage. Further immunohistochemical analysis revealed that the expression of caveolin-1 and eps15 were also significantly correlated with the expression of pAkt (p < 0.05, pERK (p < 0.05, mdm2 (p < 0.01 and EGF (p < 0.001 for caveolin-1. Eps15 and pERK were further associated with tumour grade (p < 0.01 and p < 0.001, respectively. Conclusion: Our results show that amplifications within regulatory sequences of egfr are associated with the expression of eps15 and caveolin-1, indicating an increased turnover of EGFR. The interplay between EGFR and caveolin-1, eps15, pAkt, mdm2 and pERK therefore seems to present a major molecular pathway in carcinogenesis and progression of breast phyllodes tumours.

  14. A Sweet Spot for Molecular Diagnostics: Coupling Isothermal Amplification and Strand Exchange Circuits to Glucometers

    Science.gov (United States)

    Du, Yan; Hughes, Randall A.; Bhadra, Sanchita; Jiang, Yu Sherry; Ellington, Andrew D.; Li, Bingling

    2015-06-01

    Strand exchange nucleic acid circuitry can be used to transduce isothermal nucleic acid amplification products into signals that can be readable on an off-the-shelf glucometer. Loop-mediated isothermal amplification (LAMP) is limited by the accumulation of non-specific products, but nucleic acid circuitry can be used to probe and distinguish specific amplicons. By combining this high temperature isothermal amplification method with a thermostable invertase, we can directly transduce Middle-East respiratory syndrome coronavirus and Zaire Ebolavirus templates into glucose signals, with a sensitivity as low as 20-100 copies/μl, equating to atto-molar (or low zepto-mole). Virus from cell lysates and synthetic templates could be readily amplified and detected even in sputum or saliva. An OR gate that coordinately triggered on viral amplicons further guaranteed fail-safe virus detection. The method describes has potential for accelerating point-of-care applications, in that biological samples could be applied to a transducer that would then directly interface with an off-the-shelf, approved medical device.

  15. The μ-RWELL: A compact, spark protected, single amplification-stage MPGD

    Science.gov (United States)

    Poli Lener, M.; Bencivenni, G.; de Olivera, R.; Felici, G.; Franchino, S.; Gatta, M.; Maggi, M.; Morello, G.; Sharma, A.

    2016-07-01

    In this work we present two innovative architectures of resistive MPGDs based on the WELL-amplification concept: - the micro-Resistive WELL (μ-RWELL) is a compact spark-protected single amplification-stage Micro-Pattern Gas Detector (MPGD). The amplification stage, realized with a structure very similar to a GEM foil (called WELL), is embedded through a resistive layer in the readout board. A cathode electrode, defining the gas conversion/drift gap, completes the detector mechanics. The new architecture, showing an excellent space resolution, 50 μm, is a very compact device, robust against discharges and exhibiting a large gain (>104), simple to construct and easy for engineering and then suitable for large area tracking devices as well as digital calorimeters. - the Fast Timing Micro-pattern (FTM): a new device with an architecture based on a stack of several coupled full-resistive layers where drift and multiplication stages (WELL type) alternate in the structure. The signals from each multiplication stage can be read out from any external readout boards through the capacitive couplings, providing a signal with a gain of 104-105. The main advantage of this new device is the improvement of the timing provided by the competition of the ionization processes in the different drift regions, which can be exploited for fast timing at the high luminosity accelerators (e.g. HL-LHC upgrade) as well as for applications like medical imaging.

  16. Detection and quantification of Plasmodium falciparum in blood samples using quantitative nucleic acid sequence-based amplification

    NARCIS (Netherlands)

    Schoone, G. J.; Oskam, L.; Kroon, N. C.; Schallig, H. D.; Omar, S. A.

    2000-01-01

    A quantitative nucleic acid sequence-based amplification (QT-NASBA) assay for the detection of Plasmodium parasites has been developed. Primers and probes were selected on the basis of the sequence of the small-subunit rRNA gene. Quantification was achieved by coamplification of the RNA in the

  17. Design of a ×4 subharmonic sub-millimeter wave diode mixer, based on an analytic expression for small-signal conversion admittance parameters

    DEFF Research Database (Denmark)

    Michaelsen, Rasmus Schandorph; Johansen, Tom Keinicke; Krozer, Viktor

    2013-01-01

    Instead of using frequency multipliers before a fundamental mixer, subharmonic mixers can be used. In order to develop novel subharmonic mixer architectures it is necessary to know the exact signal phase at the nonlinear element. The purpose of this paper is to generalize the description of the s....... With an RF frequency of 640 GHz, this design achieves a conversion gain of −13.5 dB with a LO-power of only −2.5 dBm....

  18. C-MET overexpression and amplification in gliomas.

    Science.gov (United States)

    Kwak, Yoonjin; Kim, Seong-Ik; Park, Chul-Kee; Paek, Sun Ha; Lee, Soon-Tae; Park, Sung-Hye

    2015-01-01

    We investigated c-Met overexpression and MET gene amplification in gliomas to determine their incidence and prognostic significance. c-Met immunohistochemistry and MET gene fluorescence in situ hybridization were carried out on tissue microarrays from 250 patients with gliomas (137 grade IV GBMs and 113 grade II and III diffuse gliomas). Clinicopathological features of these cases were reviewed. c-Met overexpression and MET gene amplification were detected in 13.1% and 5.1% of the GBMs, respectively. All the MET-amplified cases showed c-Met overexpression, but MET amplification was not always concordant with c-Met overexpression. None of grade II and III gliomas demonstrated c-Met overexpression or MET gene amplification. Mean survival of the GBM patients with MET amplification was not significantly different from patients without MET amplification (P=0.155). However, GBM patients with c-Met overexpression survived longer than patients without c-Met overexpression (P=0.035). Although MET amplification was not related to poor GBM prognosis, it is partially associated with the aggressiveness of gliomas, as MET amplification was found only in grade IV, not in grade II and III gliomas. We suggest that MET inhibitor therapy may be beneficial in about 5% GBMs, which was the incidence of MET gene amplification found in the patients included in this study.

  19. Earthquake acceleration amplification based on single microtremor test

    Science.gov (United States)

    Jaya Syahbana, Arifan; Kurniawan, Rahmat; Soebowo, Eko

    2018-02-01

    Understanding soil dynamics is needed to understand soil behaviour, including the parameters of earthquake acceleration amplification. Many researchers now conduct single microtremor tests to obtain amplification of velocity and natural periods of soil at test sites. However, these amplification parameters are rarely used, so a method is needed to convert the velocity amplification to acceleration amplification. This paper will discuss the proposed process of changing the value of amplification. The proposed method is to integrate the time histories of the synthetic earthquake acceleration of the soil surface under the deaggregation at that location so the time histories of the velocity earthquake will be obtained. Next is to conduct a “fitting curve” between amplification by a single microtremor test with amplification of the synthetic earthquake velocity time histories. After obtaining the fitting curve time histories of velocity, differentiation will be conducted to obtain fitting curve acceleration time histories. The final step after obtaining the fitting curve is to compare the acceleration of the “fitting curve” against the histories time of the acceleration of synthetic earthquake at bedrocks to obtain single microtremor acceleration amplification factor.

  20. Enzymatic amplification of a flow-injected thermometric enzyme-linked immunoassay for human insulin.

    Science.gov (United States)

    Mecklenburg, M; Lindbladh, C; Li, H; Mosbach, K; Danielsson, B

    1993-08-01

    A flow-injected thermometric enzyme linked immunoassay for human insulin which employs the lactate dehydrogenase/lactate oxidase (LDH/LOD) substrate recycling system for signal amplification is described. The system is composed of two columns, an immunosorbent column containing immobilized anti-insulin antibodies for sensing and a recycling column containing immobilized LDH/LOD/Catalase for detection. The effect of flow rates, conjugate concentrations, and chromatographic support material upon the sensitivity of the assay are investigated. The assay has a detection limit of 0.025 microgram/ml and a linear range from 0.05 to 2 micrograms/ml. This corresponds to a 10-fold increase in sensitivity over the unamplified system. A recombinant human insulin-proinsulin conjugate was also tested. The results show that enzymatic amplification can be employed to increase the sensitivity and reproducibility of flow injection assay-based biosensors. The implications of these results upon on-line analysis are discussed.