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

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

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.

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.

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.

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.

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.

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.

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.

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

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

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.

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.

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.

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

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

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.

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.

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.

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.

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.

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

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

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.

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.

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.

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.

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.

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.

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....

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

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

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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.

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 ...

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)

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....

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

A Label-Free and Sensitive Fluorescent Qualitative Assay for Bisphenol A Based on Rolling Circle Amplification/Exonuclease III-Combined Cascade Amplification

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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.

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.

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.

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

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

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.

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

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.

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

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.

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.

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

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%

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

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.

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.

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.

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%.

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.

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 ...

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.

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)

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....

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.

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.

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.

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.

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.

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.

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...

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.

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.

[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.

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.

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.

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.

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 ...

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.

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.

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.)

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.

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

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

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.

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.

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.

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

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)

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

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.

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)

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%

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....

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.

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

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

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.

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...

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.

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.

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.

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.

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,

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...

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.

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...

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.

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

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

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.

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...

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 ...

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.

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.

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.

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.

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.

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.

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%.

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.

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...

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...

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.

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

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

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

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.

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).

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.

[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.

Restriction Cascade Exponential Amplification (RCEA) assay with an attomolar detection limit: a novel, highly specific, isothermal alternative to qPCR.

Science.gov (United States)

Ghindilis, Andrey L; Smith, Maria W; Simon, Holly M; Seoudi, Ihab A; Yazvenko, Nina S; Murray, Iain A; Fu, Xiaoqing; Smith, Kenneth; Jen-Jacobson, Linda; Xu, Shuang-Yong

2015-01-13

An alternative to qPCR was developed for nucleic acid assays, involving signal rather than target amplification. The new technology, Restriction Cascade Exponential Amplification (RCEA), relies on specific cleavage of probe-target hybrids by restriction endonucleases (REase). Two mutant REases for amplification (Ramp), S17C BamHI and K249C EcoRI, were conjugated to oligonucleotides, and immobilized on a solid surface. The signal generation was based on: (i) hybridization of a target DNA to a Ramp-oligonucleotide probe conjugate, followed by (ii) specific cleavage of the probe-target hybrid using a non-immobilized recognition REase. The amount of Ramp released into solution upon cleavage was proportionate to the DNA target amount. Signal amplification was achieved through catalysis, by the free Ramp, of a restriction cascade containing additional oligonucleotide-conjugated Ramp and horseradish peroxidase (HRP). Colorimetric quantification of free HRP indicated that the RCEA achieved a detection limit of 10 aM (10(-17) M) target concentration, or approximately 200 molecules, comparable to the sensitivity of qPCR-based assays. The RCEA assay had high specificity, it was insensitive to non-specific binding, and detected target sequences in the presence of foreign DNA. RCEA is an inexpensive isothermal assay that allows coupling of the restriction cascade signal amplification with any DNA target of interest.

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

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.

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.

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)

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.

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.

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.

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...

Twin target self-amplification-based DNA machine for highly sensitive detection of cancer-related gene.

Science.gov (United States)

Xu, Huo; Jiang, Yifan; Liu, Dengyou; Liu, Kai; Zhang, Yafeng; Yu, Suhong; Shen, Zhifa; Wu, Zai-Sheng

2018-06-29

The sensitive detection of cancer-related genes is of great significance for early diagnosis and treatment of human cancers, and previous isothermal amplification sensing systems were often based on the reuse of target DNA, the amplification of enzymatic products and the accumulation of reporting probes. However, no reporting probes are able to be transformed into target species and in turn initiate the signal of other probes. Herein we reported a simple, isothermal and highly sensitive homogeneous assay system for tumor suppressor p53 gene detection based on a new autonomous DNA machine, where the signaling probe, molecular beacon (MB), was able to execute the function similar to target DNA besides providing the common signal. In the presence of target p53 gene, the operation of DNA machine can be initiated, and cyclical nucleic acid strand-displacement polymerization (CNDP) and nicking/polymerization cyclical amplification (NPCA) occur, during which the MB was opened by target species and cleaved by restriction endonuclease. In turn, the cleaved fragments could activate the next signaling process as target DNA did. According to the functional similarity, the cleaved fragment was called twin target, and the corresponding fashion to amplify the signal was named twin target self-amplification. Utilizing this newly-proposed DNA machine, the target DNA could be detected down to 0.1 pM with a wide dynamic range (6 orders of magnitude) and single-base mismatched targets were discriminated, indicating a very high assay sensitivity and good specificity. In addition, the DNA machine was not only used to screen the p53 gene in complex biological matrix but also was capable of practically detecting genomic DNA p53 extracted from A549 cell line. This indicates that the proposed DNA machine holds the potential application in biomedical research and early clinical diagnosis. Copyright © 2018 Elsevier B.V. All rights reserved.

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)

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....

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....

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....

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

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.

[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.

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...

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.

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.

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...

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.

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

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.

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

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.

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....

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

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).

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)

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.

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

Sound amplification at a rectangular T-junction with merging mean flows

Science.gov (United States)

Du, Lin; Holmberg, Andreas; Karlsson, Mikael; Åbom, Mats

2016-04-01

This paper reports a numerical study on the aeroacoustic response of a rectangular T-junction with merging mean flows. The primary motivation of the work is to explain the high sound amplification, recently seen experimentally, when introducing a small merging bias flow. The acoustic results are found solving the compressible Linearized Navier-Stokes Equations (LNSEs) in the frequency domain, where the base flow is first obtained using RANS with a k-ε turbulence model. The model predicts the measured scattering data well, including the amplitude and Strouhal number for the peak amplification, if the effect of eddy viscosity damping is included. It is found that the base flow changes significantly with the presence of a small bias flow. Compared to pure grazing flow a strong unstable shear layer is created in the downstream main duct starting from the T-junction trailing edge. This means that the main region of vortex-sound interaction is moved away from the junction to a downstream region much larger than the junction width. To analyze the sound amplification in this region Howe's energy corollary and the growth of acoustic density are used.

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.

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.

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.

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.)

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.)

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)

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.

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.

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.

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.

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

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...

Evaluation of Myc Gene Amplification in Prostate Cancer Using a Dual Color Chromogenic in-Situ Hybridization (Dual CISH Assay

Directory of Open Access Journals (Sweden)

Daniel Lerda

2013-04-01

Full Text Available 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 performed on 40 cases of prostate cancer. Amplification was identified in 12 of 40 (30% tumors. No amplification was seen in 28 of 40 (70% tumors. FISH data were available in total of 40 tumors. All tumors showed concordant results between dual-color CISH and FISH for classifying a tumor as MYC amplified or not amplified. Conclusions: We conclude that dual-color Dako CISH assay is an accurate method for determining MYC gene amplification with added advantages that make it a more practically useful method. [J Interdiscipl Histopathol 2013; 1(2.000: 81-84

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.

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...

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

Design of a readout ASIC for gas detectors with self-amplification

International Nuclear Information System (INIS)

Deng Zhi; Liu Yinong

2009-01-01

A readout ASIC has been designed for gas detectors with self-amplification such as GEM and RPC. It provides amplification and shaping of the detector signals and buffers them to the free running ADCs. The charge gain and the shaping time can be adjusted. The programmability of gain and shaping time is very convenient for studying detector performance under different gas gain and also expands the application range of the chip. The ENC increases as charge gain decreases below 10 mV/fC because the noise from the shaper becomes significant. The chip is designed in Chartered 0.35μm 2P4M CMOS process. Detailed design and simulation results are described in the paper. (authors)

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

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.

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.

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 ...

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.

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.

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.

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.

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

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,

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.

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

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

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.

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

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.

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

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

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

A centrosome-autonomous signal that involves centriole disengagement permits centrosome duplication in G2 phase after DNA damage.

LENUS (Irish Health Repository)

2010-11-15

DNA damage can induce centrosome overduplication in a manner that requires G2-to-M checkpoint function, suggesting that genotoxic stress can decouple the centrosome and chromosome cycles. How this happens is unclear. Using live-cell imaging of cells that express fluorescently tagged NEDD1\\/GCP-WD and proliferating cell nuclear antigen, we found that ionizing radiation (IR)-induced centrosome amplification can occur outside S phase. Analysis of synchronized populations showed that significantly more centrosome amplification occurred after irradiation of G2-enriched populations compared with G1-enriched or asynchronous cells, consistent with G2 phase centrosome amplification. Irradiated and control populations of G2 cells were then fused to test whether centrosome overduplication is allowed through a diffusible stimulatory signal, or the loss of a duplication-inhibiting signal. Irradiated G2\\/irradiated G2 cell fusions showed significantly higher centrosome amplification levels than irradiated G2\\/unirradiated G2 fusions. Chicken-human cell fusions demonstrated that centrosome amplification was limited to the irradiated partner. Our finding that only the irradiated centrosome can duplicate supports a model where a centrosome-autonomous inhibitory signal is lost upon irradiation of G2 cells. We observed centriole disengagement after irradiation. Although overexpression of dominant-negative securin did not affect IR-induced centrosome amplification, Plk1 inhibition reduced radiation-induced amplification. Together, our data support centriole disengagement as a licensing signal for DNA damage-induced centrosome amplification.

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.

Mutation and genomic amplification of the PIK3CA proto-oncogene in pituitary adenomas

International Nuclear Information System (INIS)

Murat, C.B.; Braga, P.B.S.; Fortes, M.A.H.Z.; Bronstein, M.D.; Corrêa-Giannella, M.L.C.; Giorgi, R.R.

2012-01-01

The tumorigenesis of pituitary adenomas is poorly understood. Mutations of the PIK3CA proto-oncogene, which encodes the p110-α catalytic subunit of PI3K, have been reported in various types of human cancers regarding the role of the gene in cell proliferation and survival through activation of the PI3K/Akt signaling pathway. Only one Chinese study described somatic mutations and amplification of the PIK3CA gene in a large series of pituitary adenomas. The aim of the present study was to determine genetic alterations of PIK3CA in a second series that consisted of 33 pituitary adenomas of different subtypes diagnosed by immunohistochemistry: 6 adrenocorticotropic hormone-secreting microadenomas, 5 growth hormone-secreting macroadenomas, 7 prolactin-secreting macroadenomas, and 15 nonfunctioning macroadenomas. Direct sequencing of exons 9 and 20 assessed by qPCR was employed to investigate the presence of mutations and genomic amplification defined as a copy number ≥4. Previously identified PIK3CA mutations (exon 20) were detected in four cases (12.1%). Interestingly, the Chinese study reported mutations only in invasive tumors, while we found a PIK3CA mutation in one noninvasive corticotroph microadenoma. PIK3CA amplification was observed in 21.2% (7/33) of the cases. This study demonstrates the presence of somatic mutations and amplifications of the PIK3CA gene in a second series of pituitary adenomas, corroborating the previously described involvement of the PI3K/Akt signaling pathway in the tumorigenic process of this gland

Mutation and genomic amplification of the PIK3CA proto-oncogene in pituitary adenomas

Energy Technology Data Exchange (ETDEWEB)

Murat, C.B.; Braga, P.B.S.; Fortes, M.A.H.Z. [Laboratório de Endocrinologia Celular e Molecular (LIM-25), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Bronstein, M.D. [Unidade de Neuroendocrinologia, Serviço de Endocrinologia, Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Corrêa-Giannella, M.L.C.; Giorgi, R.R. [Laboratório de Endocrinologia Celular e Molecular (LIM-25), Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

2012-07-13

The tumorigenesis of pituitary adenomas is poorly understood. Mutations of the PIK3CA proto-oncogene, which encodes the p110-α catalytic subunit of PI3K, have been reported in various types of human cancers regarding the role of the gene in cell proliferation and survival through activation of the PI3K/Akt signaling pathway. Only one Chinese study described somatic mutations and amplification of the PIK3CA gene in a large series of pituitary adenomas. The aim of the present study was to determine genetic alterations of PIK3CA in a second series that consisted of 33 pituitary adenomas of different subtypes diagnosed by immunohistochemistry: 6 adrenocorticotropic hormone-secreting microadenomas, 5 growth hormone-secreting macroadenomas, 7 prolactin-secreting macroadenomas, and 15 nonfunctioning macroadenomas. Direct sequencing of exons 9 and 20 assessed by qPCR was employed to investigate the presence of mutations and genomic amplification defined as a copy number ≥4. Previously identified PIK3CA mutations (exon 20) were detected in four cases (12.1%). Interestingly, the Chinese study reported mutations only in invasive tumors, while we found a PIK3CA mutation in one noninvasive corticotroph microadenoma. PIK3CA amplification was observed in 21.2% (7/33) of the cases. This study demonstrates the presence of somatic mutations and amplifications of the PIK3CA gene in a second series of pituitary adenomas, corroborating the previously described involvement of the PI3K/Akt signaling pathway in the tumorigenic process of this gland.

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

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

Coil concepts for rapid and motion-compensated MR-Imaging of small animals

International Nuclear Information System (INIS)

Korn, Matthias

2009-01-01

In this work radiofrequency-coils for the imaging of small animals in clinical whole-body MRI-systems were developed. Therefore in a first step single-channel solenoids were designed and characterized. The solenoids had two and three windings respectively, which were implemented as double wires to increase the homogeneity of the receive profile. These coils allow the acquisition of whole-body images of mice with high signal-to-noise ratio and homogeneity over a distance of at least 6.3 cm. Since many imaging experiments require rapid image acquisition, in the next step a novel coil concept was developed, which, due to its geometry, enables parallel imaging in arbitrary directions. A prototype was assembled and tested on phantom and small-animal experiments. With an accelerating factor of R=2, the difference of the SNR in all directions from the theoretical maximum, was less than 1%. In order to compensate physiological motion by the self-gating technique, in this work a coil is presented for the first time, which selectively amplifies the self-gating signal, while - due to a optical detuning technique - preserving the homogeneous illumination of the image. In vivo experiments on a small animal show an amplification of the self-gating signal by at least 40%. (orig.)

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.

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.

Ultrasensitive Faraday cage-type electrochemiluminescence assay for femtomolar miRNA-141 via graphene oxide and hybridization chain reaction-assisted cascade amplification.

Science.gov (United States)

Lu, Jing; Wu, Lin; Hu, Yufang; Wang, Sui; Guo, Zhiyong

2018-06-30

In this study, a novel electrochemiluminescence (ECL) biosensor for sensitive detection of femtomolar miRNA-141 was constructed on the basis of Faraday cage-type strategy via graphene oxide (GO) and hybridization chain reaction (HCR)-assisted cascade amplification. A capture probe (CP) was immobilized on Fe 3 O 4 @SiO 2 @Au nanoparticles as capture unit, which could catch the miRNA-141, and the immobilization of the signal unit (Ru(phen) 3 2+ -HCR/GO) was allowed via nucleic acid hybridization. The prepared biosensor exhibited two advantages for signal amplification: firstly, GO could lap on the electrode surface directly, extending Outer Helmholtz Plane (OHP) of the sensor due to the large surface area and good electronic transport property; secondly, HCR-assisted cascade amplification was designed by anchoring all HCR products on the GO surface, then embedding Ru(phen) 3 2+ as a signal readout pathway. All these signal molecules could take part in electrochemical reactions, thus further enhancing the ECL signal drastically. Therefore, the proposed sensor constructed by integrating HCR with Faraday cage-type strategy displayed an ultrasensitive detection platform for the miRNA-141 with a low detection limit of 0.03 fM. In addition, this proposed biosensor provides a universal platform for analysis of other microRNAs. Copyright © 2018 Elsevier B.V. All rights reserved.

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.

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

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.

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.

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

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.

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.

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.

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.

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...

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.

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.

Hybridization chain reaction amplification for highly sensitive fluorescence detection of DNA with dextran coated microarrays.

Science.gov (United States)

Chao, Jie; Li, Zhenhua; Li, Jing; Peng, Hongzhen; Su, Shao; Li, Qian; Zhu, Changfeng; Zuo, Xiaolei; Song, Shiping; Wang, Lianhui; Wang, Lihua

2016-07-15

Microarrays of biomolecules hold great promise in the fields of genomics, proteomics, and clinical assays on account of their remarkably parallel and high-throughput assay capability. However, the fluorescence detection used in most conventional DNA microarrays is still limited by sensitivity. In this study, we have demonstrated a novel universal and highly sensitive platform for fluorescent detection of sequence specific DNA at the femtomolar level by combining dextran-coated microarrays with hybridization chain reaction (HCR) signal amplification. Three-dimensional dextran matrix was covalently coated on glass surface as the scaffold to immobilize DNA recognition probes to increase the surface binding capacity and accessibility. DNA nanowire tentacles were formed on the matrix surface for efficient signal amplification by capturing multiple fluorescent molecules in a highly ordered way. By quantifying microscopic fluorescent signals, the synergetic effects of dextran and HCR greatly improved sensitivity of DNA microarrays, with a detection limit of 10fM (1×10(5) molecules). This detection assay could recognize one-base mismatch with fluorescence signals dropped down to ~20%. This cost-effective microarray platform also worked well with samples in serum and thus shows great potential for clinical diagnosis. Copyright © 2016 Elsevier B.V. All rights reserved.

The successes and future prospects of the linear antisense RNA amplification methodology.

Science.gov (United States)

Li, Jifen; Eberwine, James

2018-05-01

It has been over a quarter of a century since the introduction of the linear RNA amplification methodology known as antisense RNA (aRNA) amplification. Whereas most molecular biology techniques are rapidly replaced owing to the fast-moving nature of development in the field, the aRNA procedure has become a base that can be built upon through varied uses of the technology. The technique was originally developed to assess RNA populations from small amounts of starting material, including single cells, but over time its use has evolved to include the detection of various cellular entities such as proteins, RNA-binding-protein-associated cargoes, and genomic DNA. In this Perspective we detail the linear aRNA amplification procedure and its use in assessing various components of a cell's chemical phenotype. This procedure is particularly useful in efforts to multiplex the simultaneous detection of various cellular processes. These efforts are necessary to identify the quantitative chemical phenotype of cells that underlies cellular function.

Method of Menu Selection by Gaze Movement Using AC EOG Signals

Science.gov (United States)

Kanoh, Shin'ichiro; Futami, Ryoko; Yoshinobu, Tatsuo; Hoshimiya, Nozomu

A method to detect the direction and the distance of voluntary eye gaze movement from EOG (electrooculogram) signals was proposed and tested. In this method, AC-amplified vertical and horizontal transient EOG signals were classified into 8-class directions and 2-class distances of voluntary eye gaze movements. A horizontal and a vertical EOGs during eye gaze movement at each sampling time were treated as a two-dimensional vector, and the center of gravity of the sample vectors whose norms were more than 80% of the maximum norm was used as a feature vector to be classified. By the classification using the k-nearest neighbor algorithm, it was shown that the averaged correct detection rates on each subject were 98.9%, 98.7%, 94.4%, respectively. This method can avoid strict EOG-based eye tracking which requires DC amplification of very small signal. It would be useful to develop robust human interfacing systems based on menu selection for severely paralyzed patients.

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.

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

Amplification volume reduction on DNA database samples using FTA™ Classic Cards.

Science.gov (United States)

Wong, Hang Yee; Lim, Eng Seng Simon; Tan-Siew, Wai Fun

2012-03-01

The DNA forensic community always strives towards improvements in aspects such as sensitivity, robustness, and efficacy balanced with cost efficiency. Therefore our laboratory decided to study the feasibility of PCR amplification volume reduction using DNA entrapped in FTA™ Classic Card and to bring cost savings to the laboratory. There were a few concerns the laboratory needed to address. First, the kinetics of the amplification reaction could be significantly altered. Second, an increase in sensitivity might affect interpretation due to increased stochastic effects even though they were pristine samples. Third, statics might cause FTA punches to jump out of its allocated well into another thus causing sample-to-sample contamination. Fourth, the size of the punches might be too small for visual inspection. Last, there would be a limit to the extent of volume reduction due to evaporation and the possible need of re-injection of samples for capillary electrophoresis. The laboratory had successfully optimized a reduced amplification volume of 10 μL for FTA samples. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

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

Aptamer/quantum dot-based simultaneous electrochemical detection of multiple small molecules

Energy Technology Data Exchange (ETDEWEB)

Zhang Haixia [Key Laboratory on Luminescence and Real-Time Analysis, Ministry of Education, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Jiang Bingying [School of Chemistry and Chemical Engineering, Chongqing University of Technology, Chongqing 400040 (China); Xiang Yun, E-mail: yunatswu@swu.edu.cn [Key Laboratory on Luminescence and Real-Time Analysis, Ministry of Education, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Zhang Yuyong; Chai Yaqin [Key Laboratory on Luminescence and Real-Time Analysis, Ministry of Education, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China); Yuan Ruo, E-mail: yuanruo@swu.edu.cn [Key Laboratory on Luminescence and Real-Time Analysis, Ministry of Education, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715 (China)

2011-03-04

A novel strategy for 'signal on' and sensitive one-spot simultaneous detection of multiple small molecular analytes based on electrochemically encoded barcode quantum dot (QD) tags is described. The target analytes, adenosine triphosphate (ATP) and cocaine, respectively, are sandwiched between the corresponding set of surface-immobilized primary binding aptamers and the secondary binding aptamer/QD bioconjugates. The captured QDs yield distinct electrochemical signatures after acid dissolution, whose position and size reflect the identity and level, respectively, of the corresponding target analytes. Due to the inherent amplification feature of the QD labels and the 'signal on' detection scheme, as well as the sensitive monitoring of the metal ions released upon acid dissolution of the QD labels, low detection limits of 30 nM and 50 nM were obtained for ATP and cocaine, respectively, in our assays. Our multi-analyte sensing system also shows high specificity to target analytes and promising applicability to complex sample matrix, which makes the proposed assay protocol an attractive route for screening of small molecules in clinical diagnosis.

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.

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

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.

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.

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.

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.

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)

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.

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.

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.

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

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.

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.

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

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

Directory of Open Access Journals (Sweden)

Yu-hui Kou

2015-01-01

Full Text Available 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 nerve fiber regeneration in the primate peripheral nerve. Rhesus monkey models of distal ulnar nerve defects were established and repaired using muscular branches of the right forearm pronator teres. Proximal muscular branches of the pronator teres were sutured into the distal ulnar nerve using the small gap sleeve bridging method. At 6 months after suture, two-finger flexion and mild wrist flexion were restored in the ulnar-sided injured limbs of rhesus monkey. Neurophysiological examination showed that motor nerve conduction velocity reached 22.63 ± 6.34 m/s on the affected side of rhesus monkey. Osmium tetroxide staining demonstrated that the number of myelinated nerve fibers was 1,657 ± 652 in the branches of pronator teres of donor, and 2,661 ± 843 in the repaired ulnar nerve. The rate of multiple amplification of regenerating myelinated nerve fibers was 1.61. These data showed that when muscular branches of the pronator teres were used to repair ulnar nerve in primates, effective regeneration was observed in regenerating nerve fibers, and functions of the injured ulnar nerve were restored to a certain extent. Moreover, multiple amplification was subsequently detected in ulnar nerve axons.

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

Science.gov (United States)

Kou, Yu-Hui; Zhang, Pei-Xun; Wang, Yan-Hua; Chen, Bo; Han, Na; Xue, Feng; Zhang, Hong-Bo; Yin, Xiao-Feng; Jiang, Bao-Guo

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 nerve fiber regeneration in the primate peripheral nerve. Rhesus monkey models of distal ulnar nerve defects were established and repaired using muscular branches of the right forearm pronator teres. Proximal muscular branches of the pronator teres were sutured into the distal ulnar nerve using the small gap sleeve bridging method. At 6 months after suture, two-finger flexion and mild wrist flexion were restored in the ulnar-sided injured limbs of rhesus monkey. Neurophysiological examination showed that motor nerve conduction velocity reached 22.63 ± 6.34 m/s on the affected side of rhesus monkey. Osmium tetroxide staining demonstrated that the number of myelinated nerve fibers was 1,657 ± 652 in the branches of pronator teres of donor, and 2,661 ± 843 in the repaired ulnar nerve. The rate of multiple amplification of regenerating myelinated nerve fibers was 1.61. These data showed that when muscular branches of the pronator teres were used to repair ulnar nerve in primates, effective regeneration was observed in regenerating nerve fibers, and functions of the injured ulnar nerve were restored to a certain extent. Moreover, multiple amplification was subsequently detected in ulnar nerve axons.

Tip-enhanced fluorescence with radially polarized illumination for monitoring loop-mediated isothermal amplification on Hepatitis C virus cDNA

Science.gov (United States)

Wei, Shih-Chung; Chuang, Tsung-Liang; Wang, Da-Shin; Lu, Hui-Hsin; Gu, Frank X.; Sung, Kung-Bin; Lin, Chii-Wann

2015-02-01

A tip nanobiosensor for monitoring DNA replication was presented. The effects of excitation power and polarization on tip-enhanced fluorescence (TEF) were assessed with the tip immersed in fluorescein isothiocyanate solution first. The photon count rose on average fivefold with radially polarized illumination at 50 mW. We then used polymerase-functionalized tips for monitoring loop-mediated isothermal amplification on Hepatitis C virus cDNA. The amplicon-SYBR Green I complex was detected and compared to real-time loop-mediated isothermal amplification. The signals of the reaction using 4 and 0.004 ng/μl templates were detected 10 and 30 min earlier, respectively. The results showed the potential of TEF in developing a nanobiosensor for real-time DNA amplification.

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

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...

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.

Sensitive electrochemiluminescence biosensor based on Au-ITO hybrid bipolar electrode amplification system for cell surface protein detection.

Science.gov (United States)

Wu, Mei-Sheng; Yuan, Da-Jing; Xu, Jing-Juan; Chen, Hong-Yuan

2013-12-17

Here we developed a novel hybrid bipolar electrode (BPE)-electrochemiluminescence (ECL) biosensor based on hybrid bipolar electrode (BPE) for the measurement of cancer cell surface protein using ferrocence (Fc) labeled aptamer as signal recognition and amplification probe. According to the electric neutrality of BPE, the cathode of U-shaped ITO BPE was electrochemically deposited by Au nanoparticles (NPs) to enhance its conductivity and surface area, decrease the overpotential of O2 reduction, which would correspondingly increase the oxidation current of Ru(bpy)3(2+)/tripropylamine (TPA) on the anode of BPE and resulting a ∼4-fold enhancement of ECL intensity. Then a signal amplification strategy was designed by introducing Fc modified aptamer on the anode surface of BPE through hybridization for detecting the amount of mucin-1 on MCF-7 cells. The presence of Fc could not only inhibit the oxidation of Ru(bpy)3(2+) because of its lower oxidation potential, its oxidation product Fc(+) could also quench the ECL of Ru(bpy)3(2+)/TPA by efficient energy-transfer from the excited-state Ru(bpy)3(2+)* to Fc(+), making the ECL intensity greatly quenched. On the basis of the cathodic Au NPs induced ECL enhancing coupled with anodic Fc induced signal quenching amplification, the approach allowed detection of mucin-1 aptamer at a concentration down to 0.5 fM and was capable of detecting a minimum of 20 MCF-7 cells. Besides, the amount of mucin-1 on MCF-7 cells was calculated to be 9041 ± 388 molecules/cell. This approach therefore shows great promise in bioanalysis.

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...

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.

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.

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...

Synchronous digitization for high dynamic range lock-in amplification in beam-scanning microscopy

Energy Technology Data Exchange (ETDEWEB)

Muir, Ryan D.; Sullivan, Shane Z.; Oglesbee, Robert A.; Simpson, Garth J., E-mail: gsimpson@purdue.edu [Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, Indiana 47907 (United States)

2014-03-15

Digital lock-in amplification (LIA) with synchronous digitization (SD) is shown to provide significant signal to noise (S/N) and linear dynamic range advantages in beam-scanning microscopy measurements using pulsed laser sources. Direct comparisons between SD-LIA and conventional LIA in homodyne second harmonic generation measurements resulted in S/N enhancements consistent with theoretical models. SD-LIA provided notably larger S/N enhancements in the limit of low light intensities, through the smooth transition between photon counting and signal averaging developed in previous work. Rapid beam scanning instrumentation with up to video rate acquisition speeds minimized photo-induced sample damage. The corresponding increased allowance for higher laser power without sample damage is advantageous for increasing the observed signal content.

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.

Morphology-Controlled 9,10-Diphenylanthracene Nanoblocks as Electrochemiluminescence Emitters for MicroRNA Detection with One-Step DNA Walker Amplification.

Science.gov (United States)

Liu, Jia-Li; Tang, Zhi-Ling; Zhang, Jia-Qi; Chai, Ya-Qin; Zhuo, Ying; Yuan, Ruo

2018-04-17

The electrochemiluminescence (ECL) properties of polycyclic aromatic hydrocarbons (PAHs) are excellent on account of the high photoluminescence quantum yield. However, the poor solubility and radical instability of PAHs in the aqueous solution severely restricted further biological application. Here 9,10-diphenylanthracene (DPA) nanoblocks (NBs) with good dispersibility and stability in aqueous solution were prepared according to morphology-controlled technology employing water-soluble polymers as a protectant. Furthermore, an ECL "off-on" switch biosensor was developed based on a novel ECL ternary system with DPA NBs as luminophore, dissolved O 2 as coreactant, and Pt-Ag alloy nanoflowers as the coreaction accelerator, which achieved a high-intense initial ECL signal. Subsequently, the Fc-DNA as ECL signal quencher was assembled on the electrode surface to quench the initial ECL signal for a "signal-off" state. Meanwhile, DNA swing arm was modified on the electrode surface for one-step DNA walker amplification. Interestingly, in the presence of miRNA-141 and T7 Exo, the one-step DNA walker amplification was executed to recover a strong ECL signal as a "signal-on" state by the digestion of Fc-DNA. Thus the developed ECL "off-on" switch biosensor possesses a detection limit down to 29.5 aM for ultrasensitive detection of miRNA-141, which is expected to be applicable to the detection of miRNA in clinic tumor cells.

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)

Factors influencing Recombinase polymerase amplification (RPA) assay outcomes at point of care.

Science.gov (United States)

Lillis, Lorraine; Siverson, Joshua; Lee, Arthur; Cantera, Jason; Parker, Mathew; Piepenburg, Olaf; Lehman, Dara A; Boyle, David S

2016-04-01

Recombinase Polymerase Amplification (RPA) can be used to detect pathogen-specific DNA or RNA in under 20 min without the need for complex instrumentation. These properties enable its potential use in resource limited settings. However, there are concerns that deviations from the manufacturer's protocol and/or storage conditions could influence its performance in low resource settings. RPA amplification relies upon viscous crowding agents for optimal nucleic acid amplification, and thus an interval mixing step after 3-6 min of incubation is recommended to distribute amplicons and improve performance. In this study we used a HIV-1 RPA assay to evaluate the effects of this mixing step on assay performance. A lack of mixing led to a longer time to amplification and inferior detection signal, compromising the sensitivity of the assay. However lowering the assay volume from 50 μL to 5 μL showed similar sensitivity with or without mixing. We present the first peer-reviewed study that assesses long term stability of RPA reagents without a cold chain. Reagents stored at -20 °C, and 25 °C for up to 12 weeks were able to detect 10 HIV-1 DNA copies. Reagents stored at 45 °C for up to 3 weeks were able to detect 10 HIV-1 DNA copies, with reduced sensitivity only after >3 weeks at 45 °C. Together our results show that reducing reaction volumes bypassed the need for the mixing step and that RPA reagents were stable even when stored for 3 weeks at very high temperatures. Copyright © 2016 Elsevier Ltd. All rights reserved.

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...

Cetuximab insufficiently inhibits glioma cell growth due to persistent EGFR downstream signaling

DEFF Research Database (Denmark)

Hasselbalch, Benedikte; Lassen, Ulrik; Poulsen, Hans S

2010-01-01

Overexpression and/or amplification of the epidermal growth factor receptor (EGFR) is present in 35-45% of primary glioblastoma multiforme tumors and has been correlated with a poor prognosis. In this study, we investigated the effect of cetuximab and intracellular signaling pathways downstream...... of EGFR, important for cell survival and proliferation. We show insufficient EGFR downregulation and competition with endogenous EGFR ligands upon cetuximab treatment. Dose-response experiments showed inhibition of EGFR phosphorylation without affecting two of the prominent downstream signaling pathways....... Our results indicate that amplification and/or overexpression of EGFR is an unsatisfactory predictor for response to cetuximab....

A sensitive lateral flow biosensor for Escherichia coli O157:H7 detection based on aptamer mediated strand displacement amplification

Energy Technology Data Exchange (ETDEWEB)

Wu, Wei [College of Food Science and Engineering, Ocean University of China, Qingdao 266003 (China); Zhao, Shiming [Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530 (China); Mao, Yiping [Yueyang Institute for Food and Drug Control, Yueyang 430198 (China); Fang, Zhiyuan [Affiliated Tumor Hospital of Guangzhou Medical University, Guangzhou 510095 (China); Lu, Xuewen [Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530 (China); Zeng, Lingwen, E-mail: zeng6@yahoo.com [Key Laboratory of Regenerative Biology, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530 (China)

2015-02-25

Highlights: • Limit of detection as low as 10 CFU mL{sup −1}Escherichia coli O157:H7. • No need of antibodies and substituted with aptamers. • Isothermal strand displacement amplification for signal amplification. • Results observed by the naked eye. • Great potential application in the area of food control. - Abstract: Foodborne diseases caused by pathogens are one of the major problems in food safety. Convenient and sensitive point-of-care rapid diagnostic tests for food-borne pathogens have been a long-felt need of clinicians. Commonly used methods for pathogen detection rely on conventional culture-based tests, antibody-based assays and polymerase chain reaction (PCR)-based techniques. These methods are costly, laborious and time-consuming. Herein, we present a simple and sensitive aptamer based biosensor for rapid detection of Escherichia coli O157:H7 (E. coli O157:H7). In this assay, two different aptamers specific for the outmembrane of E. coli O157:H7 were used. One of the aptamers was used for magnetic bead enrichment, and the other was used as a signal reporter for this pathogen, which was amplified by isothermal strand displacement amplification (SDA) and further detected by a lateral flow biosensor. Only the captured aptamers on cell membrane were amplified, limitations of conventional DNA amplification based method such as false-positive can be largely reduced. The generated signals (red bands on the test zone of a lateral flow strip) can be unambiguously read out by the naked eye. As low as 10 colony forming units (CFU) of E. coli O157:H7 were detected in this study. Without DNA extraction, the reduced handling and simpler equipment requirement render this assay a simple and rapid alternative to conventional methods.

A sensitive lateral flow biosensor for Escherichia coli O157:H7 detection based on aptamer mediated strand displacement amplification

International Nuclear Information System (INIS)

Wu, Wei; Zhao, Shiming; Mao, Yiping; Fang, Zhiyuan; Lu, Xuewen; Zeng, Lingwen

2015-01-01

Highlights: • Limit of detection as low as 10 CFU mL −1 Escherichia coli O157:H7. • No need of antibodies and substituted with aptamers. • Isothermal strand displacement amplification for signal amplification. • Results observed by the naked eye. • Great potential application in the area of food control. - Abstract: Foodborne diseases caused by pathogens are one of the major problems in food safety. Convenient and sensitive point-of-care rapid diagnostic tests for food-borne pathogens have been a long-felt need of clinicians. Commonly used methods for pathogen detection rely on conventional culture-based tests, antibody-based assays and polymerase chain reaction (PCR)-based techniques. These methods are costly, laborious and time-consuming. Herein, we present a simple and sensitive aptamer based biosensor for rapid detection of Escherichia coli O157:H7 (E. coli O157:H7). In this assay, two different aptamers specific for the outmembrane of E. coli O157:H7 were used. One of the aptamers was used for magnetic bead enrichment, and the other was used as a signal reporter for this pathogen, which was amplified by isothermal strand displacement amplification (SDA) and further detected by a lateral flow biosensor. Only the captured aptamers on cell membrane were amplified, limitations of conventional DNA amplification based method such as false-positive can be largely reduced. The generated signals (red bands on the test zone of a lateral flow strip) can be unambiguously read out by the naked eye. As low as 10 colony forming units (CFU) of E. coli O157:H7 were detected in this study. Without DNA extraction, the reduced handling and simpler equipment requirement render this assay a simple and rapid alternative to conventional methods

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

Survival signalling and apoptosis resistance in glioblastomas: opportunities for targeted therapeutics

Directory of Open Access Journals (Sweden)

Krakstad Camilla

2010-06-01

Full Text Available Abstract Glioblastoma multiforme (GBM is the most common primary brain tumour in adults and one of the most aggressive cancers in man. Despite technological advances in surgical management, combined regimens of radiotherapy with new generation chemotherapy, the median survival for these patients is 14.6 months. This is largely due to a highly deregulated tumour genome with opportunistic deletion of tumour suppressor genes, amplification and/or mutational hyper-activation of receptor tyrosine kinase receptors. The net result of these genetic changes is augmented survival pathways and systematic defects in the apoptosis signalling machinery. The only randomised, controlled phase II trial conducted targeting the epidermal growth factor receptor (EGFR signalling with the small molecule inhibitor, erlotinib, has showed no therapeutic benefit. Survival signalling and apoptosis resistance in GBMs can be viewed as two sides of the same coin. Targeting increased survival is unlikely to be efficacious without at the same time targeting apoptosis resistance. We have critically reviewed the literature regarding survival and apoptosis signalling in GBM, and highlighted experimental, preclinical and recent clinical trials attempting to target these pathways. Combined therapies simultaneously targeting apoptosis and survival signalling defects might shift the balance from tumour growth stasis to cytotoxic therapeutic responses that might be associated with greater therapeutic benefits.

EnVision+, a new dextran polymer-based signal enhancement technique for in situ hybridization (ISH).

Science.gov (United States)

Wiedorn, K H; Goldmann, T; Henne, C; Kühl, H; Vollmer, E

2001-09-01

Seventy paraffin-embedded cervical biopsy specimens and condylomata were tested for the presence of human papillomavirus (HPV) by conventional in situ hybridization (ISH) and ISH with subsequent signal amplification. Signal amplification was performed either by a commercial biotinyl-tyramide-based detection system [GenPoint (GP)] or by the novel two-layer dextran polymer visualization system EnVision+ (EV), in which both EV-horseradish peroxidase (EV-HRP) and EV-alkaline phosphatase (EV-AP) were applied. We could demonstrate for the first time, that EV in combination with preceding ISH results in a considerable increase in signal intensity and sensitivity without loss of specificity compared to conventional ISH. Compared to GP, EV revealed a somewhat lower sensitivity, as measured by determination of the integrated optical density (IOD) of the positively stained cells. However, EV is easier to perform, requires a shorter assay time, and does not raise the background problems that may be encountered with biotinyl-tyramide-based amplification systems. (J Histochem Cytochem 49:1067-1071, 2001)

FGFR2 amplification is predictive of sensitivity to regorafenib in gastric and colorectal cancers in vitro.

Science.gov (United States)

Cha, Yongjun; Kim, Hwang-Phill; Lim, Yoojoo; Han, Sae-Won; Song, Sang-Hyun; Kim, Tae-You

2018-03-24

Although regorafenib has demonstrated survival benefits in patients with metastatic colorectal and gastrointestinal stromal tumors, no proven biomarker has been identified for predicting sensitivity to regorafenib. Here, we investigated preclinical activity of regorafenib in gastric and colorectal cancer cells to identify genetic alterations associated with sensitivity to regorafenib. Mutation profiles and copy number assays of regorafenib target molecules indicated that amplification of FGFR2 was the only genetic alteration associated with in vitro sensitivity to regorafenib. Regorafenib effectively inhibited phosphorylation of FGFR2 and its downstream signaling molecules in a dose-dependent manner and selectively in FGFR2 amplified cells. Regorafenib induced G1 arrest (SNU-16, KATO-III) and apoptosis (NCI-H716), however, no significant changes were seen in cell lines without FGFR2 amplification. In SNU-16 mice xenografts, regorafenib significantly inhibited tumor growth, proliferation, and FGFR signaling compared to treatment with control vehicle. Regorafenib effectively abrogates activated FGFR2 signaling in FGFR2 amplified gastric and colorectal cancer and therefore, might be considered for integration into treatment in patients with FGFR2 amplified gastric and colorectal cancers. This article is protected by copyright. All rights reserved. Molecular Oncology (2018) © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

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.

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

Comparison of monomeric and polymeric horseradish peroxidase as labels in competitive ELISA for small molecule detection

International Nuclear Information System (INIS)

Li, Dongyang; Ying, Yibin; Wu, Jian; Niessner, Reinhard; Knopp, Dietmar

2013-01-01

We have developed a simple and sensitive competitive enzyme-linked immunosorbent assay (ELISA) to determine aflatoxin B1 (as a model small analyte) and using streptavidin-polymeric horseradish peroxidase complex (SApolyHRP) as a label for signal amplification. The performance of the assay was evaluated by comparing it with the classical indirect competitive ELISA using HRP labeled anti-mouse IgG as the tracer antibody. The results indicate that the SApolyHRP-based competitive ELISA exhibits a typically 2.4-fold steeper slope of the linear working range of the calibration curve compared to the monomeric HRP based classical ELISA, i.e., the sensitivity was increased. The SApolyHRP conjugate causes a typically 19-fold stronger signal generation in comparison to the traditional HRP labeled anti-mouse IgG at the same concentration (25 ng mL −1 ). Moreover, the SApolyHRP-based assay has a much wider linear range and a 3.8-fold better signal-to-noise ratio. Considering its simplicity, sensitivity and ease of operation, this competitive ELISA is considered to be a promising tool for small molecule immuno detection. (author)

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...

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

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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.

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

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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.

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.

Mechanisms of amplification of ultrashort electromagnetic pulses in gyrotron traveling wave tube with helically corrugated waveguide

International Nuclear Information System (INIS)

Ginzburg, N. S.; Zaslavsky, V. Yu.; Zotova, I. V.; Sergeev, A. S.; Zheleznov, I. V.; Samsonov, S. V.; Mishakin, S. V.

2015-01-01

A time-domain self consistent theory of a gyrotron traveling wave tube with a helically corrugated operating waveguide has been developed. Based on this model, the process of short pulse amplification was studied in regimes of grazing and intersection of the dispersion curves of the electromagnetic wave and the electron beam. In the first case, the possibility of amplification without pulse form distortion was demonstrated for the pulse spectrum width of the order of the gain bandwidth. In the second case, when the electrons' axial velocity was smaller than the wave's group velocity, it was shown that the slippage of the incident signal with respect to the electron beam provides feeding of the signal by “fresh” electrons without initial modulation. As a result, the amplitude of the output pulse can exceed the amplitude of its saturated value for the case of the grazing regime, and, for optimal parameters, the peak output power can be even larger than the kinetic power of the electron beam

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.

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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.

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...

Markovian Dynamics of Josephson Parametric Amplification

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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.

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.

A novel fluorescent biosensor for Adenosine Triphosphate detection based on the polydopamine nanospheres integrating with enzymatic recycling amplification.

Science.gov (United States)

Ji, Xiaoting; Yi, Bingqing; Xu, Yujuan; Zhao, Yanan; Zhong, Hua; Ding, Caifeng

2017-07-01

Based on the protective performance of polydopamine nanospheres (PDANSs) for DNA against nuclease digestion and the specific recognition characteristic of aptamer, we have developed an enzymatic recycling signal amplification method for highly sensitive and selective detection of adenosine triphosphate (ATP). Fluorescence measurements were carried out to verify the DNA polymerase and exonuclease III (Exo III) assisted target recycling process and fluorescence signal amplification. In the absence of the ATP, initially, the signal DNA-PDANSs complex was in the "off" state due to the efficient fluorescence quenching of 6-carboxyfluorescein (FAM) adjacent to the surface of PDANSs. Due to the binding of the aptamer by ATP, it trigger DNA polymerase and Exo III assisted target recycling process by the product of release, the complex would change into the "on" state as a result of the dissociation of the FAM from the surface of PDANSs, thus providing greatly enhanced fluorescence emission intensity. The method allows quantitative detection of ATP in the range of 20-600nM with a detection limit of 8.32nM. This biosensor requires no complex operations, and is a new high efficiency method for ATP detection. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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.

Clinical application of somatosensory amplification in psychosomatic medicine

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Nakao Mutsuhiro

2007-10-01

Full Text Available Abstract Many patients with somatoform disorders are frequently encountered in psychosomatic clinics as well as in primary care clinics. To assess such patients objectively, the concept of somatosensory amplification may be useful. Somatosensory amplification refers to the tendency to experience a somatic sensation as intense, noxious, and disturbing. It may have a role in a variety of medical conditions characterized by somatic symptoms that are disproportionate to demonstrable organ pathology. It may also explain some of the variability in somatic symptomatology found among different patients with the same serious medical disorder. It has been assessed with a self-report questionnaire, the Somatosensory Amplification Scale. This instrument was developed in a clinical setting in the U.S., and the reliability and validity of the Japanese and Turkish versions have been confirmed as well. Many studies have attempted to clarify the specific role of somatosensory amplification as a pathogenic mechanism in somatization. It has been reported that somatosensory amplification does not correlate with heightened sensitivity to bodily sensations and that emotional reactivity exerts its influence on somatization via a negatively biased reporting style. According to our recent electroencephalographic study, somatosensory amplification appears to reflect some aspects of long-latency cognitive processing rather than short-latency interoceptive sensitivity. The concept of somatosensory amplification can be useful as an indicator of somatization in the therapy of a broad range of disorders, from impaired self-awareness to various psychiatric disorders. It also provides useful information for choosing appropriate pharmacological or psychological therapy. While somatosensory amplification has a role in the presentation of somatic symptoms, it is closely associated with other factors, namely, anxiety, depression, and alexithymia that may also influence the same

Homogeneous and label-free detection of microRNAs using bifunctional strand displacement amplification-mediated hyperbranched rolling circle amplification.

Science.gov (United States)

Zhang, Li-rong; Zhu, Guichi; Zhang, Chun-yang

2014-07-01

MicroRNAs (miRNAs) are an emerging class of biomarkers and therapeutic targets for various diseases including cancers. Here, we develop a homogeneous and label-free method for sensitive detection of let-7a miRNA based on bifunctional strand displacement amplification (SDA)-mediated hyperbranched rolling circle amplification (HRCA). The binding of target miRNA with the linear template initiates the bifunctional SDA reaction, generating two different kinds of triggers which can hybridize with the linear template to initiate new rounds of SDA reaction for the production of more and more triggers. In the meantime, the released two different kinds of triggers can function as the first and the second primers, respectively, to initiate the HRCA reaction whose products can be simply monitored by a standard fluorometer with SYBR Green I as the fluorescent indicator. The proposed method exhibits high sensitivity with a detection limit of as low as 1.8 × 10(-13) M and a large dynamic range of 5 orders of magnitude from 0.1 pM to 10 nM, and it can even discriminate the single-base difference among the miRNA family members. Moreover, this method can be used to analyze the total RNA samples from the human lung tissues and might be further applied for sensitive detection of various proteins, small molecules, and metal ions in combination with specific aptamers.

Classification of human cancers based on DNA copy number amplification modeling

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Knuutila Sakari

2008-05-01

Full Text Available Abstract Background DNA amplifications alter gene dosage in cancer genomes by multiplying the gene copy number. Amplifications are quintessential in a considerable number of advanced cancers of various anatomical locations. The aims of this study were to classify human cancers based on their amplification patterns, explore the biological and clinical fundamentals behind their amplification-pattern based classification, and understand the characteristics in human genomic architecture that associate with amplification mechanisms. Methods We applied a machine learning approach to model DNA copy number amplifications using a data set of binary amplification records at chromosome sub-band resolution from 4400 cases that represent 82 cancer types. Amplification data was fused with background data: clinical, histological and biological classifications, and cytogenetic annotations. Statistical hypothesis testing was used to mine associations between the data sets. Results Probabilistic clustering of each chromosome identified 111 amplification models and divided the cancer cases into clusters. The distribution of classification terms in the amplification-model based clustering of cancer cases revealed cancer classes that were associated with specific DNA copy number amplification models. Amplification patterns – finite or bounded descriptions of the ranges of the amplifications in the chromosome – were extracted from the clustered data and expressed according to the original cytogenetic nomenclature. This was achieved by maximal frequent itemset mining using the cluster-specific data sets. The boundaries of amplification patterns were shown to be enriched with fragile sites, telomeres, centromeres, and light chromosome bands. Conclusions Our results demonstrate that amplifications are non-random chromosomal changes and specifically selected in tumor tissue microenvironment. Furthermore, statistical evidence showed that specific chromosomal features

Utility of chromogenic in situ hybridization (CISH) for detection of EGFR amplification in glioblastoma: comparison with fluorescence in situ hybridization (FISH).

Science.gov (United States)

Fischer, Ingeborg; de la Cruz, Clarissa; Rivera, Andreana L; Aldape, Kenneth

2008-12-01

In this study, we test the reliability of chromogenic in situ hybridization (CISH) for the detection of epidermal growth factor receptor (EGFR) gene amplification in glioblastoma. Earlier reports have described EGFR CISH in glioblastoma multiforme, but a comparison of CISH with a "gold standard" testing method, such as fluorescence in situ hybridization (FISH), has not been described. Therapies targeting the EGFR-signaling pathway might increase the importance of assessment of EGFR-amplification status. CISH is a potential alternative to FISH as a testing method. To test its reliability, EGFR-amplification status by CISH was assessed in 89 cases of glioblastoma and compared with FISH results, and correlated with the protein expression using immunohistochemistry (IHC) for EGFR. FISH was scored as being EGFR-amplified in 47/89 tumors, CISH as being amplified in 43/89 tumors. The CISH and FISH results were in agreement in 83/89 cases (93%). Four glioblastomas were scored as being amplified by FISH, but not by CISH; whereas amplification was detected in 2 tumors by CISH that were not amplified using FISH. Forty-eight of the 89 cases were positive for EGFR expression by IHC. EGFR amplification was highly correlated with protein expression by IHC, as 40/48 (83%) EGFR IHC-positive cases were found to be EGFR-amplified. The high concordance of CISH and FISH for the assessment of EGFR gene-amplification status indicates that CISH is a viable alternative to FISH for the detection of EGFR gene amplification in glioblastoma. Detectable EGFR expression by IHC can occur in the absence of gene amplification, but is uncommon.

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.

Influence of spatial beam inhomogeneities on the parameters of a petawatt laser system based on multi-stage parametric amplification

International Nuclear Information System (INIS)

Frolov, S A; Trunov, V I; Pestryakov, Efim V; Leshchenko, V E

2013-01-01

We have developed a technique for investigating the evolution of spatial inhomogeneities in high-power laser systems based on multi-stage parametric amplification. A linearised model of the inhomogeneity development is first devised for parametric amplification with the small-scale self-focusing taken into account. It is shown that the application of this model gives the results consistent (with high accuracy and in a wide range of inhomogeneity parameters) with the calculation without approximations. Using the linearised model, we have analysed the development of spatial inhomogeneities in a petawatt laser system based on multi-stage parametric amplification, developed at the Institute of Laser Physics, Siberian Branch of the Russian Academy of Sciences (ILP SB RAS). (control of laser radiation parameters)

High-throughput genotyping of single nucleotide polymorphisms with rolling circle amplification

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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.

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)

Ducted whistler-mode signals received at two widely spaced locations

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M. A. Clilverd

Full Text Available Whistler-mode signals from a single VLF transmitter that have propagated in the same duct, have been observed simultaneously at Faraday, Antarctica (65°S, 64°W and Dunedin, New Zealand (46°S, 171°E. The signals received have group-delay times that differ in the order of 10 ms, which can be explained by the differences in southern-hemisphere sub-ionospheric propagation time from duct exit region to receiver for the two sites. This difference has been used to determine the location of the duct exit region, with confirmation provided by arrival-bearing information from both sites. The whistler-mode signals typically occur one or two days after geomagnetic activity, with K_pgeq5. The sub-ionospheric-propagation model, LWPC, is used to estimate the whistler-mode power radiated from the duct exit region. These results are then combined with estimated loss values for ionospheric and ducted transmission to investigate the role of wave-particle amplification or absorption. On at least half of the events studied, plasmaspheric amplification of the signals appears to be needed to explain the observed whistler-mode signal strengths.

Ducted whistler-mode signals received at two widely spaced locations

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M. A. Clilverd

1996-06-01

Full Text Available Whistler-mode signals from a single VLF transmitter that have propagated in the same duct, have been observed simultaneously at Faraday, Antarctica (65°S, 64°W and Dunedin, New Zealand (46°S, 171°E. The signals received have group-delay times that differ in the order of 10 ms, which can be explained by the differences in southern-hemisphere sub-ionospheric propagation time from duct exit region to receiver for the two sites. This difference has been used to determine the location of the duct exit region, with confirmation provided by arrival-bearing information from both sites. The whistler-mode signals typically occur one or two days after geomagnetic activity, with Kp\\geq5. The sub-ionospheric-propagation model, LWPC, is used to estimate the whistler-mode power radiated from the duct exit region. These results are then combined with estimated loss values for ionospheric and ducted transmission to investigate the role of wave-particle amplification or absorption. On at least half of the events studied, plasmaspheric amplification of the signals appears to be needed to explain the observed whistler-mode signal strengths.

Phase-matched light amplification by three-wave mixing process in a birefringent fiber due to externally applied stress

International Nuclear Information System (INIS)

Ohashi, M.; Kitayama, K.; Ishida, Y.; Uchida, N.

1982-01-01

A novel method to achieve phase-matched light amplification in a birefringent fiber via the three-wave mixing is proposed by using frequency shift change due to the stress applied to the fiber. It is confirmed that the signal power from a cw laser diode at lambda = 1.292 μm is amplified by 6.1 x 10 3 times in the birefringent fiber pumped with a Q-switched Nd: yttrium aluminum garnet laser at lambda = 1.064 μm. This will provide a new fiber-optic light signal amplifier having a good tolerance for variation of signal wavelengths

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...

Trigeminal ganglion neurons of mice show intracellular chloride accumulation and chloride-dependent amplification of capsaicin-induced responses.

Directory of Open Access Journals (Sweden)

Nicole Schöbel

Full Text Available Intracellular Cl(- concentrations ([Cl(-](i of sensory neurons regulate signal transmission and signal amplification. In dorsal root ganglion (DRG and olfactory sensory neurons (OSNs, Cl(- is accumulated by the Na(+-K(+-2Cl(- cotransporter 1 (NKCC1, resulting in a [Cl(-](i above electrochemical equilibrium and a depolarizing Cl(- efflux upon Cl(- channel opening. Here, we investigate the [Cl(-](i and function of Cl(- in primary sensory neurons of trigeminal ganglia (TG of wild type (WT and NKCC1(-/- mice using pharmacological and imaging approaches, patch-clamping, as well as behavioral testing. The [Cl(-](i of WT TG neurons indicated active NKCC1-dependent Cl(- accumulation. Gamma-aminobutyric acid (GABA(A receptor activation induced a reduction of [Cl(-](i as well as Ca(2+ transients in a corresponding fraction of TG neurons. Ca(2+ transients were sensitive to inhibition of NKCC1 and voltage-gated Ca(2+ channels (VGCCs. Ca(2+ responses induced by capsaicin, a prototypical stimulus of transient receptor potential vanilloid subfamily member-1 (TRPV1 were diminished in NKCC1(-/- TG neurons, but elevated under conditions of a lowered [Cl(-](o suggesting a Cl(--dependent amplification of capsaicin-induced responses. Using next generation sequencing (NGS, we found expression of different Ca(2+-activated Cl(- channels (CaCCs in TGs of mice. Pharmacological inhibition of CaCCs reduced the amplitude of capsaicin-induced responses of TG neurons in Ca(2+ imaging and electrophysiological recordings. In a behavioral paradigm, NKCC1(-/- mice showed less avoidance of the aversive stimulus capsaicin. In summary, our results strongly argue for a Ca(2+-activated Cl(--dependent signal amplification mechanism in TG neurons that requires intracellular Cl(- accumulation by NKCC1 and the activation of CaCCs.

All-optical 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

Phase-preserving amplitude regeneration based on optical parametric amplification has been experimentally demonstrated for a 640 Gbit/s RZ-DPSK signal. Improvement of 2.2 dB in receiver sensitivity at a BER of 10-9 together with 13.3 dB net gain have been successfully achieved.......Phase-preserving amplitude regeneration based on optical parametric amplification has been experimentally demonstrated for a 640 Gbit/s RZ-DPSK signal. Improvement of 2.2 dB in receiver sensitivity at a BER of 10-9 together with 13.3 dB net gain have been successfully achieved....

Phase noise mitigation of QPSK signal utilizing phase-locked multiplexing of signal harmonics and amplitude saturation.

Science.gov (United States)

Mohajerin-Ariaei, Amirhossein; Ziyadi, Morteza; Chitgarha, Mohammad Reza; Almaiman, Ahmed; Cao, Yinwen; Shamee, Bishara; Yang, Jeng-Yuan; Akasaka, Youichi; Sekiya, Motoyoshi; Takasaka, Shigehiro; Sugizaki, Ryuichi; Touch, Joseph D; Tur, Moshe; Langrock, Carsten; Fejer, Martin M; Willner, Alan E

2015-07-15

We demonstrate an all-optical phase noise mitigation scheme based on the generation, delay, and coherent summation of higher order signal harmonics. The signal, its third-order harmonic, and their corresponding delayed variant conjugates create a staircase phase-transfer function that quantizes the phase of quadrature-phase-shift-keying (QPSK) signal to mitigate phase noise. The signal and the harmonics are automatically phase-locked multiplexed, avoiding the need for phase-based feedback loop and injection locking to maintain coherency. The residual phase noise converts to amplitude noise in the quantizer stage, which is suppressed by parametric amplification in the saturation regime. Phase noise reduction of ∼40% and OSNR-gain of ∼3  dB at BER 10(-3) are experimentally demonstrated for 20- and 30-Gbaud QPSK input signals.

Prototype design of singles processing unit for the small animal PET

Science.gov (United States)

Deng, P.; Zhao, L.; Lu, J.; Li, B.; Dong, R.; Liu, S.; An, Q.

2018-05-01

Position Emission Tomography (PET) is an advanced clinical diagnostic imaging technique for nuclear medicine. Small animal PET is increasingly used for studying the animal model of disease, new drugs and new therapies. A prototype of Singles Processing Unit (SPU) for a small animal PET system was designed to obtain the time, energy, and position information. The energy and position is actually calculated through high precison charge measurement, which is based on amplification, shaping, A/D conversion and area calculation in digital signal processing domian. Analysis and simulations were also conducted to optimize the key parameters in system design. Initial tests indicate that the charge and time precision is better than 3‰ FWHM and 350 ps FWHM respectively, while the position resolution is better than 3.5‰ FWHM. Commination tests of the SPU prototype with the PET detector indicate that the system time precision is better than 2.5 ns, while the flood map and energy spectra concored well with the expected.

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.

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...

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

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.

Parametric amplification and cascaded-nonlinearity processes in common atomic system.

Science.gov (United States)

Zheng, Huaibin; Zhang, Xun; Zhang, Zhaoyang; Tian, Yaling; Chen, Haixia; Li, Changbiao; Zhang, Yanpeng

2013-01-01

For the first time, we study the parametric amplification process of multi-wave mixing (PA-MWM) signal and cascaded-nonlinearity process (CNP) in sodium vapors both theoretically and experimentally, based on a conventional phase-conjugate MWM and a self-diffraction four-wave mixing (SD-FWM) processes, which are pumped by laser or amplified spontaneous emission (ASE), respectively. For laser pumping case, SD-FWM process serves as a quantum linear amplifier (a CNP) out (inside) of the resonant absorption region. While for ASE case, only the CNP occurs and the output linewidth is much narrower than that of the MWM signal due to the second selected effect of its electromagnetically induced transparency window. In addition, the phase-sensitive amplifying process seeded by two MWM processes is discussed for the first time. Theoretical fittings agree well with the experiment. The investigations have important potential applications in quantum communication.

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...

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.

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.

Sensitivity enhancement of remotely coupled NMR detectors using wirelessly powered parametric amplification.

Science.gov (United States)

Qian, Chunqi; Murphy-Boesch, Joseph; Dodd, Stephen; Koretsky, Alan

2012-09-01

A completely wireless detection coil with an integrated parametric amplifier has been constructed to provide local amplification and transmission of MR signals. The sample coil is one element of a parametric amplifier using a zero-bias diode that mixes the weak MR signal with a strong pump signal that is obtained from an inductively coupled external loop. The NMR sample coil develops current gain via reduction in the effective coil resistance. Higher gain can be obtained by adjusting the level of the pumping power closer to the oscillation threshold, but the gain is ultimately constrained by the bandwidth requirement of MRI experiments. A feasibility study here shows that on a NaCl/D(2) O phantom, (23) Na signals with 20 dB of gain can be readily obtained with a concomitant bandwidth of 144 kHz. This gain is high enough that the integrated coil with parametric amplifier, which is coupled inductively to external loops, can provide sensitivity approaching that of direct wire connection. Copyright © 2012 Wiley Periodicals, Inc.

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 ...

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...

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.

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

Non-local effect in Brillouin optical time-domain analyzer based on Raman amplification

International Nuclear Information System (INIS)

Jia Xinhong; Rao Yunjiang; Wang Zinan; Zhang Weili; Ran Zengling; Deng Kun; Yang Zixin

2012-01-01

Compared with conventional Brillouin optical time-domain analyzer (BOTDA), the BOTDA based on Raman amplification allows longer sensing range, higher signal-to-noise ratio and higher measurement accuracy. However, the non-local effect induced by pump depletion significantly restricts the probe optical power injected to sensing fiber, thereby limiting the further extension for sensing distance. In this paper, the coupled equations including the interaction of probe light, Brillouin and Raman pumps are applied to the study on the non-local characteristics of BOTDA based on Raman amplification. The results show that, the system error induced by non-local effect worsens with increased powers of probe wave and Raman pump. The frequency-division-multiplexing (cascading the fibers with various Brillouin frequency shifts) and time-division-multiplexing (modulating both of the Brillouin pump and probe lights) technologies are efficient approaches to suppress the non-local effect, through shortening the effective interaction range between Brillouin pump and probe lights. (authors)

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).

SHAPE EFFECT OF ANNULAR CONCENTRATOR IN ULTRASONIC SYSTEM ON AMPLIFICATION FACTOR OF VIBRATIONS AMPLITUDE

Directory of Open Access Journals (Sweden)

D. A. Stepanenko

2016-01-01

Full Text Available The paper contains a theoretical underpinning on creation of ultrasonic vibration concentrators based on annular elastic elements with non-circular (ellipse-like eccentric shape of internal contour. Shape of internal contour in polar coordinates is described by Fourier series relative to angular coordinate that consists of a constant term and first and second harmonics. An effect of geometric parameters of the concentrator on amplification factor and natural vibration frequencies has been investigated with the help of a finite element method. The paper reveals the possibility to control an amplification factor of annular concentrators while varying eccentricity of internal contour and mean value of cross-section thickness. The amplification factor satisfies a condition K < N, where N is thickness ratio of amplifier input and output sections, and it is decreasing with increase of vibration mode order. The similar condition has been satisfied for conical bar concentrator with the difference that in the case of bar concentrators an amplification is ensured due to variation of diameter and N will represent ratio of diameters. It has been proved that modification of internal contour shape makes it possible to carry out a wide-band tuning of natural frequencies of concentrator vibrations without alteration of its overall dimensions and substantial change of amplification factor, which is important for frequency matching of the concentrator and ultrasonic vibratory system. Advantages of the proposed concentrators include simplicity of design and manufacturing, small overall dimensions, possibility for natural frequency tuning by means of static load variation. The developed concentrators can find their application in ultrasonic devices and instruments for technological and medical purposes.

Reliability of chromogenic in situ hybridization for epidermal growth factor receptor gene copy number detection in non-small-cell lung carcinomas: a comparison with fluorescence in situ hybridization study.

Science.gov (United States)

Yoo, Seol Bong; Lee, Hyun Ju; Park, Jung Ok; Choe, Gheeyoung; Chung, Doo Hyun; Seo, Jeong-Wook; Chung, Jin-Haeng

2010-03-01

Fluorescence in situ hybridization (FISH) has been known to be the most representative and standardized test for assessing gene amplification. However, FISH requires a fluorescence microscope, the signals are labile and rapidly fade over time. Recently, chromogenic in situ hybridization (CISH) has emerged as a potential alternative to FISH. The aim of this study is to test the reliability of CISH technique for the detection of epidermal growth factor receptor (EGFR) gene amplification in non-small-cell lung carcinomas (NSCLC), to compare CISH results with FISH. A total of 277 formalin-fixed and paraffin embedded NSCLC tissue samples were retrieved from the surgical pathology archives at Seoul National University Bundang Hospital. CISH and FISH examinations were performed to test EGFR gene amplification status. There was high concordance in the assessment of EGFR gene copy number between CISH and FISH tests (Kappa coefficient=0.83). Excellent concordance was shown between two observers on the interpretation of the CISH results (Kappa coefficient=0.90). In conclusion, CISH result is highly reproducible, accurate and practical method to determine EGFR gene amplification in NSCLC. In addition, CISH allows a concurrent analysis of histological features of the tumors and gene copy numbers.

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.

Analytically Sensitive Protein Detection in Microtiter Plates by Proximity Ligation with Rolling Circle Amplification.

Science.gov (United States)

Ebai, Tonge; Souza de Oliveira, Felipe Marques; Löf, Liza; Wik, Lotta; Schweiger, Caroline; Larsson, Anders; Keilholtz, Ulrich; Haybaeck, Johannes; Landegren, Ulf; Kamali-Moghaddam, Masood

2017-09-01

Detecting proteins at low concentrations in plasma is crucial for early diagnosis. Current techniques in clinical routine, such as sandwich ELISA, provide sensitive protein detection because of a dependence on target recognition by pairs of antibodies, but detection of still lower protein concentrations is often called for. Proximity ligation assay with rolling circle amplification (PLARCA) is a modified proximity ligation assay (PLA) for analytically specific and sensitive protein detection via binding of target proteins by 3 antibodies, and signal amplification via rolling circle amplification (RCA) in microtiter wells, easily adapted to instrumentation in use in hospitals. Proteins captured by immobilized antibodies were detected using a pair of oligonucleotide-conjugated antibodies. Upon target recognition these PLA probes guided oligonucleotide ligation, followed by amplification via RCA of circular DNA strands that formed in the reaction. The RCA products were detected by horseradish peroxidase-labeled oligonucleotides to generate colorimetric reaction products with readout in an absorbance microplate reader. We compared detection of interleukin (IL)-4, IL-6, IL-8, p53, and growth differentiation factor 15 (GDF-15) by PLARCA and conventional sandwich ELISA or immuno-RCA. PLARCA detected lower concentrations of proteins and exhibited a broader dynamic range compared to ELISA and iRCA using the same antibodies. IL-4 and IL-6 were detected in clinical samples at femtomolar concentrations, considerably lower than for ELISA. PLARCA offers detection of lower protein levels and increased dynamic ranges compared to ELISA. The PLARCA procedure may be adapted to routine instrumentation available in hospitals and research laboratories. © 2017 American Association for Clinical Chemistry.

High-energy infrared femtosecond pulses generated by dual-chirped optical parametric amplification.

Science.gov (United States)

Fu, Yuxi; Takahashi, Eiji J; Midorikawa, Katsumi

2015-11-01

We demonstrate high-energy infrared femtosecond pulse generation by a dual-chirped optical parametric amplification (DC-OPA) scheme [Opt. Express19, 7190 (2011)]. By employing a 100 mJ pump laser, a signal pulse energy exceeding 20 mJ at a wavelength of 1.4 μm was achieved before dispersion compensation. A total output energy of 33 mJ was recorded. Under a further energy scaling condition, the signal pulse was compressed to an almost transform-limited duration of 27 fs using a fused silica prism compressor. Since the DC-OPA scheme is efficient and energy scalable, design parameters for obtaining 100 mJ level infrared pulses are presented, which are suitable as driver lasers for the energy scaling of high-order harmonic generation with sub-keV photon energy.

Antigen retrieval, blocking, detection and visualisation systems in immunohistochemistry: a review and practical evaluation of tyramide and rolling circle amplification systems.

Science.gov (United States)

Warford, Anthony; Akbar, Hameed; Riberio, Deise

2014-11-01

To achieve specificity and sensitivity using immunohistochemistry it is necessary to combine the application of validated primary antibodies with optimised pre-treatment, detection and visualisation steps. The influence of these surrounding procedures is reviewed. A practical evaluation of tyramide signal amplification and rolling circle amplification detection methods is provided in which formalin fixed paraffin embedded sections of adenocarcinomas of breast, colon and lung together with squamous metaplasia of lung were immunostained with CD20 and CK19 primary antibodies. The results indicate that the detection systems are of comparable sensitivity and specificity. Copyright © 2014 Elsevier Inc. All rights reserved.

Coil concepts for rapid and motion-compensated MR-Imaging of small animals; Spulenkonzepte zur schnellen und bewegungskompensierten MR-Bildgebung von Kleintieren

Energy Technology Data Exchange (ETDEWEB)

Korn, Matthias

2009-05-06

In this work radiofrequency-coils for the imaging of small animals in clinical whole-body MRI-systems were developed. Therefore in a first step single-channel solenoids were designed and characterized. The solenoids had two and three windings respectively, which were implemented as double wires to increase the homogeneity of the receive profile. These coils allow the acquisition of whole-body images of mice with high signal-to-noise ratio and homogeneity over a distance of at least 6.3 cm. Since many imaging experiments require rapid image acquisition, in the next step a novel coil concept was developed, which, due to its geometry, enables parallel imaging in arbitrary directions. A prototype was assembled and tested on phantom and small-animal experiments. With an accelerating factor of R=2, the difference of the SNR in all directions from the theoretical maximum, was less than 1%. In order to compensate physiological motion by the self-gating technique, in this work a coil is presented for the first time, which selectively amplifies the self-gating signal, while - due to a optical detuning technique - preserving the homogeneous illumination of the image. In vivo experiments on a small animal show an amplification of the self-gating signal by at least 40%. (orig.)

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.

Detection of c-myc amplification in formalin-fixed paraffin-embedded tumor tissue by chromogenic in situ hybridization (CISH).

Science.gov (United States)

Todorović-Raković, Nataša

2013-01-01

In situ hybridization (ISH) allows evaluation of genetic abnormalities, such as changes in chromosome number, chromosome translocations or gene amplifications, by hybridization of tagged DNA (or RNA) probes with complementary DNA (or RNA) sequences in interphase nuclei of target tissue. However, chromogenic in situ hybridization (CISH) is also applicable to formalin-fixed, paraffin-embedded (FFPE) tissues, besides metaphase chromosome spreads. CISH is similar to fluorescent in situ hybridization (FISH) regarding pretreatments and hybridization protocols but differs in the way of visualization. Indeed, CISH signal detection is similar to that used in immunohistochemistry, making use of a peroxidase-based chromogenic reaction instead of fluorescent dyes. In particular, tagged DNA probes are indirectly detected using an enzyme-conjugated antibody targeting the tags. The enzymatic reaction of the chromogenic substrate leads to the formation of strong permanent brown signals that can be visualized by bright-field microscopy at 40 × magnification. The advantage of CISH is that it allows the simultaneous observation of gene amplification and tissue morphology and the slides can be stored for a long time.

Amplification of PVT1 contributes to the pathophysiology ofovarian and breast cancer

Energy Technology Data Exchange (ETDEWEB)

Guan, Yinghui; Kuo, Wen-Lin; Stilwell, Jackie; Takano, Hirokuni; Lapuk, Anna; Fridlyand, Jane; Mao, Jian-Hua; Yu, Mami; Ginzinger, David; Gray, Joe W.

2007-10-09

Purpose. This study was designed to elucidate the role of amplification at 8q24 in the pathophysiology of ovarian and breast cancer since increased copy number at this locus is one of the most frequent genomic abnormalities in these cancers. Experimental Design. To accomplish this, we assessed the association of amplification at 8q24 with outcome in ovarian cancers using FISH to tissue microarrays and measured responses of ovarian and breast cancer cell lines to specific small interfering RNAs (siRNA) against the oncogene, MYC, and a putative noncoding RNA, PVT1, both of which map to 8q24. Results. Amplification of 8q24 was associated with significantly reduced survival duration. In addition, siRNA-mediated reduction in either PVT1 or MYC expression inhibited proliferation in breast and ovarian cancer cell lines in which they were both amplified and over expressed but not in lines in which they were not amplified/over expressed. Inhibition of PVT1 expression also induced a strong apoptotic response in cell lines in which it was over expressed but not in lines in which it was not amplified/over expressed. Inhibition of MYC, on the other hand, did not induce an apoptotic response in cell lines in which MYC was amplified and over expressed. Conclusions. These results suggest that MYC and PVT1 contribute independently to ovarian and breast pathogenesis when over expressed because of genomic abnormalities. They also suggest that PVT1 mediated inhibition of apoptosis may explain why amplification of 8q24 is associated with reduced survival duration in patients treated with agents that act through apoptotic mechanisms.

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.

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.

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.

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

An exonuclease-assisted amplification electrochemical aptasensor for Hg(2+) detection based on hybridization chain reaction.

Science.gov (United States)

Bao, Ting; Wen, Wei; Zhang, Xiuhua; Xia, Qinghua; Wang, Shengfu

2015-08-15

In this work, a novel electrochemical aptasensor was developed for Hg(2+) detection based on exonuclease-assisted target recycling and hybridization chain reaction (HCR) dual signal amplification strategy. The presence of Hg(2+) induced the T-rich DNA partly folded into duplex-like structure via the Hg(2+) mediated T-Hg(2+)-T base pairs, which triggered the activity of exonuclease III (Exo III). Exo III selectively digested the double-strand DNA containing multiple T-Hg(2+)-T base pairs from its 3'-end, the released Hg(2+) participated analyte recycle. With each digestion cycle, a digestion product named as help DNA was obtained, which acted as a linkage between the capture DNA and auxiliary DNA. The presence of help DNA and two auxiliary DNA collectively facilitated successful HCR process and formed long double-stranded DNA. [Ru(NH3)6](3+) was used as redox indicator, which electrostatically bound to the double strands and produced an electrochemical signal. Exo III-assisted target recycling and HCR dual amplification significantly improved the sensitivity for Hg(2+) with a detection limit of 0.12 pM (S/N=3). Furthermore, the proposed aptasensor had a promising potential for the application of Hg(2+) detection in real aquatic sample analysis. Copyright © 2015 Elsevier B.V. All rights reserved.

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...

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

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

Electrochemical aptasensor for highly sensitive determination of cocaine using a supramolecular aptamer and rolling circle amplification

International Nuclear Information System (INIS)

Shen, Bo; Yan, Yurong; Tang, Renkuan; Li, Yongguo; Li, Jianbo; Cheng, Wei; Ju, Huangxian; Ding, Shijia

2015-01-01

We report on a novel strategy for the electrochemical detection of cocaine. It is based on the use of a supramolecular aptamer, rolling circle amplification (RCA), and multiplex binding of a biotin-strepavidin system. The aptamer fragments were assembled to a supramolecular aptamer which, in the presence of cocaine, conjugates to streptavidin for anchoring of biotinylated circular DNA. This initiates RCA and enables sensitive electrochemical-enzymatic readout. A significant signal amplification was obtained by using streptavidin linked to alkaline phosphatase that binds to the remaining biotinylated detection probes and catalyzes the hydrolysis of the synthetic enzyme substrate α-naphthylphosphate. This dual amplification strategy tremendously increases the detection limit of the aptasensor. Under optimal conditions and using differential pulse voltammetry, cocaine can be detected in the concentration range between 2 and 500 nM with a detection limit as low as 1.3 nM (at S/N = 3). The method is specific and acceptably reproducible. It was successfully applied to the detection of cocaine in (spiked) urine samples. The data were in good agreement with those obtained by the GC-MS reference method. (author)

Parametric amplification and bidirectional invisibility in PT -symmetric time-Floquet systems

Science.gov (United States)

Koutserimpas, Theodoros T.; Alù, Andrea; Fleury, Romain

2018-01-01

Parity-time (PT )-symmetric wave devices, which exploit balanced interactions between material gain and loss, exhibit extraordinary properties, including lasing and flux-conserving scattering processes. In a seemingly different research field, periodically driven systems, also known as time-Floquet systems, have been widely studied as a relevant platform for reconfigurable active wave control and manipulation. In this article, we explore the connection between PT -symmetry and parametric time-Floquet systems. Instead of relying on material gain, we use parametric amplification by considering a time-periodic modulation of the refractive index at a frequency equal to twice the incident signal frequency. We show that the scattering from a simple parametric slab, whose dynamics follows the Mathieu equation, can be described by a PT -symmetric scattering matrix, whose PT -breaking threshold corresponds to the Mathieu instability threshold. By combining different parametric slabs modulated out of phase, we create PT -symmetric time-Floquet systems that feature exceptional scattering properties, such as coherent perfect absorption (CPA)-laser operation and bidirectional invisibility. These bidirectional properties, rare for regular PT -symmetric systems, are related to a compensation of parametric amplification due to multiple scattering between two parametric systems modulated with a phase difference.

Multiple signal amplified electrochemiluminescent immunoassay for brombuterol detection using gold nanoparticles and polyamidoamine dendrimers-silver nanoribbon

Energy Technology Data Exchange (ETDEWEB)

Dong, Tiantian; Hu, Liuyi; Zhao, Kang; Deng, Anping, E-mail: denganping@suda.edu.cn; Li, Jianguo, E-mail: lijgsd@suda.edu.cn

2016-11-16

Electrochemiluminescent (ECL) immunosensor with multiple signal amplification was designed based on gold nanoparticles (AuNPs), polyamidoamine dendrimers (PAMAM) and silver-cysteine hybrid nanoribbon (SNR). Low toxic L-cysteine capped CdSe QDs was chosen as the ECL signal probe. To verify the proposed ultrasensitive ECL immunosensor for β-adrenergic agonists (β-AA), we detected Brombuterol (Brom) as a proof-of-principle analyte. Therein, AuNPs as the substrate can simplify the experiment process, accelerate the electron transfer rate, and carry more coating antigen (Ag-OVA) to enlarge ECL signal. On one hand, SNR on the surface of electrode can avoid the aggregation of AuNPs, and SNR-PAMAM-AuNPs also can be acted as a good accelerator for electron transfer. On the other hand, PAMAM (16 -NH{sub 2}) functionalized SNR (SNR-PAMAM) with numerous amino groups could be employed to bond abundant actived QDs to further amplify ECL signal. The new immunosensor can offer a simple, reliable, rapid, and selective detection for Brom, which have a dynamic range of 0.005–700 ng mL{sup −1} with a low detection limit at 1.5 pg mL{sup −1}. The proposed biosensor will extend the application of nanomaterials in ECL immunoassays and open a new road for the detection of Brom and other β-AA in the future. - Highlights: • A multiple signal amplification ECL immunosensor of eco-friendly CdSe QDs for brombuterol determination was developed. • Besides substrates, AuNPs and PAMAM-SNR were creatively used to accelerate the electron transport between electrode and QDs. • SNR-PAMAM with numerous amino groups also could be employed to bond abundant actived QDs to amplify ECL signal. • Competitive immunoassay was performed with ECL to detect small molecules of brombuterol. • It provided a method for detecting Brom and enlarged the usage of QDs, AuNPs and SNR-PAMAM in ECL biosensing.

Multiple signal amplified electrochemiluminescent immunoassay for brombuterol detection using gold nanoparticles and polyamidoamine dendrimers-silver nanoribbon

International Nuclear Information System (INIS)

Dong, Tiantian; Hu, Liuyi; Zhao, Kang; Deng, Anping; Li, Jianguo

2016-01-01

Electrochemiluminescent (ECL) immunosensor with multiple signal amplification was designed based on gold nanoparticles (AuNPs), polyamidoamine dendrimers (PAMAM) and silver-cysteine hybrid nanoribbon (SNR). Low toxic L-cysteine capped CdSe QDs was chosen as the ECL signal probe. To verify the proposed ultrasensitive ECL immunosensor for β-adrenergic agonists (β-AA), we detected Brombuterol (Brom) as a proof-of-principle analyte. Therein, AuNPs as the substrate can simplify the experiment process, accelerate the electron transfer rate, and carry more coating antigen (Ag-OVA) to enlarge ECL signal. On one hand, SNR on the surface of electrode can avoid the aggregation of AuNPs, and SNR-PAMAM-AuNPs also can be acted as a good accelerator for electron transfer. On the other hand, PAMAM (16 -NH_2) functionalized SNR (SNR-PAMAM) with numerous amino groups could be employed to bond abundant actived QDs to further amplify ECL signal. The new immunosensor can offer a simple, reliable, rapid, and selective detection for Brom, which have a dynamic range of 0.005–700 ng mL"−"1 with a low detection limit at 1.5 pg mL"−"1. The proposed biosensor will extend the application of nanomaterials in ECL immunoassays and open a new road for the detection of Brom and other β-AA in the future. - Highlights: • A multiple signal amplification ECL immunosensor of eco-friendly CdSe QDs for brombuterol determination was developed. • Besides substrates, AuNPs and PAMAM-SNR were creatively used to accelerate the electron transport between electrode and QDs. • SNR-PAMAM with numerous amino groups also could be employed to bond abundant actived QDs to amplify ECL signal. • Competitive immunoassay was performed with ECL to detect small molecules of brombuterol. • It provided a method for detecting Brom and enlarged the usage of QDs, AuNPs and SNR-PAMAM in ECL biosensing.

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....

Quantum phase amplification for temporal pulse shaping and super-resolution in remote sensing

Science.gov (United States)

Yin, Yanchun

The use of nonlinear optical interactions to perform nonclassical transformations of electromagnetic field is an area of considerable interest. Quantum phase amplification (QPA) has been previously proposed as a method to perform nonclassical manipulation of coherent light, which can be experimentally realized by use of nonlinear optical mixing processes, of which phase-sensitive three-wave mixing (PSTWM) is one convenient choice. QPA occurs when PSTWM is operated in the photon number deamplification mode, i.e., when the energy is coherently transferred among the low-frequency signal and idler waves and the high-frequency pump wave. The final state is nonclassical, with the field amplitude squeezed and the phase anti-squeezed. In the temporal domain, the use of QPA has been studied to facilitate nonlinear pulse shaping. This novel method directly shapes the temporal electric field amplitude and phase using the PSTWM in a degenerate and collinear configuration, which has been analyzed using a numerical model. Several representative pulse shaping capabilities of this technique have been identified, which can augment the performance of common passive pulse shaping methods operating in the Fourier domain. The analysis indicates that a simple quadratic variation of temporal phase facilitates pulse compression and self-steepening, with features significantly shorter than the original transform-limited pulse. Thus, PSTWM can act as a direct pulse compressor based on the combined effects of phase amplification and group velocity mismatch, even without the subsequent linear phase compensation. Furthermore, it is shown numerically that pulse doublets and pulse trains can be produced at the pump frequency by utilizing the residual linear phase of the signal. Such pulse shaping capabilities are found to be within reach of this technique in common nonlinear optical crystals pumped by pulses available from compact femtosecond chirped-pulse amplification laser systems. The use of

Improving Mobile Phone Speech Recognition by Personalized Amplification: Application in People with Normal Hearing and Mild-to-Moderate Hearing Loss.

Science.gov (United States)

Kam, Anna Chi Shan; Sung, John Ka Keung; Lee, Tan; Wong, Terence Ka Cheong; van Hasselt, Andrew

In this study, the authors evaluated the effect of personalized amplification on mobile phone speech recognition in people with and without hearing loss. This prospective study used double-blind, within-subjects, repeated measures, controlled trials to evaluate the effectiveness of applying personalized amplification based on the hearing level captured on the mobile device. The personalized amplification settings were created using modified one-third gain targets. The participants in this study included 100 adults of age between 20 and 78 years (60 with age-adjusted normal hearing and 40 with hearing loss). The performance of the participants with personalized amplification and standard settings was compared using both subjective and speech-perception measures. Speech recognition was measured in quiet and in noise using Cantonese disyllabic words. Subjective ratings on the quality, clarity, and comfortableness of the mobile signals were measured with an 11-point visual analog scale. Subjective preferences of the settings were also obtained by a paired-comparison procedure. The personalized amplification application provided better speech recognition via the mobile phone both in quiet and in noise for people with hearing impairment (improved 8 to 10%) and people with normal hearing (improved 1 to 4%). The improvement in speech recognition was significantly better for people with hearing impairment. When the average device output level was matched, more participants preferred to have the individualized gain than not to have it. The personalized amplification application has the potential to improve speech recognition for people with mild-to-moderate hearing loss, as well as people with normal hearing, in particular when listening in noisy environments.

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.

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.

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.

Optical coherence tomography: Monte Carlo simulation and improvement by optical amplification

DEFF Research Database (Denmark)

Tycho, Andreas

2002-01-01

An advanced novel Monte Carlo simulation model of the detection process of an optical coherence tomography (OCT) system is presented. For the first time it is shown analytically that the applicability of the incoherent Monte Carlo approach to model the heterodyne detection process of an OCT system...... is firmly justified. This is obtained by calculating the heterodyne mixing of the reference and sample beams in a plane conjugate to the discontinuity in the sample probed by the system. Using this approach, a novel expression for the OCT signal is derived, which only depends uopon the intensity...... flexibility of Monte Carlo simulations, this new model is demonstrated to be excellent as a numerical phantom, i.e., as a substitute for otherwise difficult experiments. Finally, a new model of the signal-to-noise ratio (SNR) of an OCT system with optical amplification of the light reflected from the sample...

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

Direct amplification of casework bloodstains using the Promega PowerPlex(®) 21 PCR amplification system.

Science.gov (United States)

Gray, Kerryn; Crowle, Damian; Scott, Pam

2014-09-01

A significant number of evidence items submitted to Forensic Science Service Tasmania (FSST) are blood swabs or bloodstained items. Samples from these items routinely undergo phenol:chloroform:isoamyl alcohol organic extraction and quantitative Polymerase Chain Reaction (qPCR) testing prior to PowerPlex(®) 21 amplification. This multi-step process has significant cost and timeframe implications in a fiscal climate of tightening government budgets, pressure towards improved operating efficiencies, and an increasing emphasis on rapid techniques better supporting intelligence-led policing. Direct amplification of blood and buccal cells on cloth and Whatman FTA™ card with PowerPlex(®) 21 has already been successfully implemented for reference samples, eliminating the requirement for sample pre-treatment. Scope for expanding this method to include less pristine casework blood swabs and samples from bloodstained items was explored in an endeavour to eliminate lengthy DNA extraction, purification and qPCR steps for a wider subset of samples. Blood was deposited onto a range of substrates including those historically found to inhibit STR amplification. Samples were collected with micro-punch, micro-swab, or both. The potential for further fiscal savings via reduced volume amplifications was assessed by amplifying all samples at full and reduced volume (25 and 13μL). Overall success rate data showed 80% of samples yielded a complete profile at reduced volume, compared to 78% at full volume. Particularly high success rates were observed for the blood on fabric/textile category with 100% of micro-punch samples yielding complete profiles at reduced volume and 85% at full volume. Following the success of this trial, direct amplification of suitable casework blood samples has been implemented at reduced volume. Significant benefits have been experienced, most noticeably where results from crucial items have been provided to police investigators prior to interview of

Membrane-Dependent Bystander Effect Contributes to Amplification of the Response to Alpha-Particle Irradiation in Targeted and Nontargeted Cells

International Nuclear Information System (INIS)

Hanot, Maite; Hoarau, Jim; Carriere, Marie; Angulo, Jaime F.; Khodja, Hicham

2009-01-01

Purpose: Free radicals are believed to play an active role in the bystander response. This study investigated their origin as well as their temporal and spatial impacts in the bystander effect. Methods and Materials: We employed a precise alpha-particle microbeam to target a small fraction of subconfluent osteoblastic cells (MC3T3-E1). γH2AX-53BP1 foci, oxidative metabolism changes, and micronuclei induction in targeted and bystander cells were assessed. Results: Cellular membranes and mitochondria were identified as two distinct reactive oxygen species producers. The global oxidative stress observed after irradiation was significantly attenuated after cells were treated with filipin, evidence for the primal role of membrane in the bystander effect. To determine the membrane's impact at a cellular level, micronuclei yield was measured when various fractions of the cell population were individually targeted while the dose per cell remained constant. Induction of micronuclei increased in bystander cells as well as in targeted cells and was attenuated by filipin treatment, demonstrating a role for bystander signals between irradiated cells in an autocrine/paracrine manner. Conclusions: A complex interaction of direct irradiation and bystander signals leads to a membrane-dependent amplification of cell responses that could influence therapeutic outcomes in tissues exposed to low doses or to environmental exposure.

Pleiotropic functions of embryonic sonic hedgehog expression link jaw and taste bud amplification with eye loss during cavefish evolution.

Science.gov (United States)

Yamamoto, Yoshiyuki; Byerly, Mardi S; Jackman, William R; Jeffery, William R

2009-06-01

This study addresses the role of sonic hedgehog (shh) in increasing oral-pharyngeal constructive traits (jaws and taste buds) at the expense of eyes in the blind cavefish Astyanax mexicanus. In cavefish embryos, eye primordia degenerate under the influence of hyperactive Shh signaling. In concert, cavefish show amplified jaw size and taste bud numbers as part of a change in feeding behavior. To determine whether pleiotropic effects of hyperactive Shh signaling link these regressive and constructive traits, shh expression was compared during late development of the surface-dwelling (surface fish) and cave-dwelling (cavefish) forms of Astyanax. After an initial expansion along the midline of early embryos, shh was elevated in the oral-pharyngeal region in cavefish and later was confined to taste buds. The results of shh inhibition and overexpression experiments indicate that Shh signaling has an important role in oral and taste bud development. Conditional overexpression of an injected shh transgene at specific times in development showed that taste bud amplification and eye degeneration are sensitive to shh overexpression during the same early developmental period, although taste buds are not formed until much later. Genetic crosses between cavefish and surface fish revealed an inverse relationship between eye size and jaw size/taste bud number, supporting a link between oral-pharyngeal constructive traits and eye degeneration. The results suggest that hyperactive Shh signaling increases oral and taste bud amplification in cavefish at the expense of eyes. Therefore, selection for constructive oral-pharyngeal traits may be responsible for eye loss during cavefish evolution via pleiotropic function of the Shh signaling pathway.

Self-induced parametric amplification arising from nonlinear elastic coupling in a micromechanical resonating disk gyroscope.

Science.gov (United States)

Nitzan, Sarah H; Zega, Valentina; Li, Mo; Ahn, Chae H; Corigliano, Alberto; Kenny, Thomas W; Horsley, David A

2015-03-12

Parametric amplification, resulting from intentionally varying a parameter in a resonator at twice its resonant frequency, has been successfully employed to increase the sensitivity of many micro- and nano-scale sensors. Here, we introduce the concept of self-induced parametric amplification, which arises naturally from nonlinear elastic coupling between the degenerate vibration modes in a micromechanical disk-resonator, and is not externally applied. The device functions as a gyroscope wherein angular rotation is detected from Coriolis coupling of elastic vibration energy from a driven vibration mode into a second degenerate sensing mode. While nonlinear elasticity in silicon resonators is extremely weak, in this high quality-factor device, ppm-level nonlinear elastic effects result in an order-of-magnitude increase in the observed sensitivity to Coriolis force relative to linear theory. Perfect degeneracy of the primary and secondary vibration modes is achieved through electrostatic frequency tuning, which also enables the phase and frequency of the parametric coupling to be varied, and we show that the resulting phase and frequency dependence of the amplification follow the theory of parametric resonance. We expect that this phenomenon will be useful for both fundamental studies of dynamic systems with low dissipation and for increasing signal-to-noise ratio in practical applications such as gyroscopes.

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)

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)

Added Value of HER-2 Amplification Testing by Multiplex Ligation-Dependent Probe Amplification in Invasive Breast Cancer

Science.gov (United States)

Kuijpers, Chantal C. H. J.; Moelans, Cathy B.; van Slooten, Henk-Jan; Horstman, Anja; Hinrichs, John W. J.; Al-Janabi, Shaimaa; van Diest, Paul J.; Jiwa, Mehdi

2013-01-01

Background HER-2 is a prognostic and predictive marker, but as yet no technique is perfectly able to identify patients likely to benefit from HER-2 targeted therapies. We aimed to prospectively assess the added value of first-line co-testing by IHC, and multiplex ligation-dependent probe amplification (MLPA) and chromogenic in situ hybridization (CISH). Methods As local validation, HER-2 MLPA and CISH were compared in 99 breast cancers. Next, we reviewed 937 invasive breast cancers, from 4 Dutch pathology laboratories, that were prospectively assessed for HER-2 by IHC and MLPA (and CISH in selected cases). Results The validation study demonstrated 100% concordance between CISH and MLPA, if both methods were assessable and conclusive (81.8% of cases). Significant variation regarding percentages IHC 0/1+ and 2+ cases was observed between the laboratories (pCISH was 98.1% (575/586) (Kappa = 0.94). Of the IHC 3+ cases, 6.7% failed to reveal gene amplification, whereas 0.8% of the IHC 0/1+ cases demonstrated gene amplification. Results remained discordant after retrospective review in 3/11 discordant cases. In the remaining 8 cases the original IHC score was incorrect or adapted after repeated IHC staining. Conclusions MLPA is a low-cost and quantitative high-throughput technique with near perfect concordance with CISH. The use of MLPA in routinely co-testing all breast cancers may reduce HER-2 testing variation between laboratories, may serve as quality control for IHC, will reveal IHC 0/1+ patients with gene amplification, likely responsive to trastuzumab, and identify IHC 3+ cases without gene amplification that may respond less well. PMID:24324739

Added value of HER-2 amplification testing by multiplex ligation-dependent probe amplification in invasive breast cancer.

Directory of Open Access Journals (Sweden)

Chantal C H J Kuijpers

Full Text Available BACKGROUND: HER-2 is a prognostic and predictive marker, but as yet no technique is perfectly able to identify patients likely to benefit from HER-2 targeted therapies. We aimed to prospectively assess the added value of first-line co-testing by IHC, and multiplex ligation-dependent probe amplification (MLPA and chromogenic in situ hybridization (CISH. METHODS: As local validation, HER-2 MLPA and CISH were compared in 99 breast cancers. Next, we reviewed 937 invasive breast cancers, from 4 Dutch pathology laboratories, that were prospectively assessed for HER-2 by IHC and MLPA (and CISH in selected cases. RESULTS: The validation study demonstrated 100% concordance between CISH and MLPA, if both methods were assessable and conclusive (81.8% of cases. Significant variation regarding percentages IHC 0/1+ and 2+ cases was observed between the laboratories (p<0.0001. Overall concordance between IHC and MLPA/CISH was 98.1% (575/586 (Kappa = 0.94. Of the IHC 3+ cases, 6.7% failed to reveal gene amplification, whereas 0.8% of the IHC 0/1+ cases demonstrated gene amplification. Results remained discordant after retrospective review in 3/11 discordant cases. In the remaining 8 cases the original IHC score was incorrect or adapted after repeated IHC staining. CONCLUSIONS: MLPA is a low-cost and quantitative high-throughput technique with near perfect concordance with CISH. The use of MLPA in routinely co-testing all breast cancers may reduce HER-2 testing variation between laboratories, may serve as quality control for IHC, will reveal IHC 0/1+ patients with gene amplification, likely responsive to trastuzumab, and identify IHC 3+ cases without gene amplification that may respond less well.

Detection of MYCN Gene Amplification in Neuroblastoma by Fluorescence In Situ Hybridization: A Pediatric Oncology Group Study

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Prasad Mathew

2001-01-01

Full Text Available To assess the utility of fluorescence in situ hybridization (FISH for analysis of MYCN gene amplification in neuroblastoma, we compared this assay with Southern blot analysis using tumor specimens collected from 232 patients with presenting characteristics typical of this disease. The FISH technique identified MYCN amplification in 47 cases, compared with 39 by Southern blotting, thus increasing the total number of positive cases by 21%. The major cause of discordancy was a low fraction of tumor cells (≤30% replacement in clinical specimens, which prevented an accurate estimate of MYCN copy number by Southern blotting. With FISH, by contrast, it was possible to analyze multiple interphase nuclei of tumor cells, regardless of the proportion of normal peripheral blood, bone marrow, or stromal cells in clinical samples. Thus, FISH could be performed accurately with very small numbers of tumor cells from touch preparations of needle biopsies. Moreover, this procedure allowed us to discern the heterogeneous pattern of MYCN amplification that is characteristic of neuroblastoma. We conclude that FISH improves the detection of MYCN gene amplification in childhood neuroblastomas in a clinical setting, thus facilitating therapeutic decisions based on the presence or absence of this prognostically important biologic marker.

Strand Invasion Based Amplification (SIBA®): a novel isothermal DNA amplification technology demonstrating high specificity and sensitivity for a single molecule of target analyte.

Science.gov (United States)

Hoser, Mark J; Mansukoski, Hannu K; Morrical, Scott W; Eboigbodin, Kevin E

2014-01-01

Isothermal nucleic acid amplification technologies offer significant advantages over polymerase chain reaction (PCR) in that they do not require thermal cycling or sophisticated laboratory equipment. However, non-target-dependent amplification has limited the sensitivity of isothermal technologies and complex probes are usually required to distinguish between non-specific and target-dependent amplification. Here, we report a novel isothermal nucleic acid amplification technology, Strand Invasion Based Amplification (SIBA). SIBA technology is resistant to non-specific amplification, is able to detect a single molecule of target analyte, and does not require target-specific probes. The technology relies on the recombinase-dependent insertion of an invasion oligonucleotide (IO) into the double-stranded target nucleic acid. The duplex regions peripheral to the IO insertion site dissociate, thereby enabling target-specific primers to bind. A polymerase then extends the primers onto the target nucleic acid leading to exponential amplification of the target. The primers are not substrates for the recombinase and are, therefore unable to extend the target template in the absence of the IO. The inclusion of 2'-O-methyl RNA to the IO ensures that it is not extendible and that it does not take part in the extension of the target template. These characteristics ensure that the technology is resistant to non-specific amplification since primer dimers or mis-priming are unable to exponentially amplify. Consequently, SIBA is highly specific and able to distinguish closely-related species with single molecule sensitivity in the absence of complex probes or sophisticated laboratory equipment. Here, we describe this technology in detail and demonstrate its use for the detection of Salmonella.

Strand Invasion Based Amplification (SIBA®: a novel isothermal DNA amplification technology demonstrating high specificity and sensitivity for a single molecule of target analyte.

Directory of Open Access Journals (Sweden)

Mark J Hoser

Full Text Available Isothermal nucleic acid amplification technologies offer significant advantages over polymerase chain reaction (PCR in that they do not require thermal cycling or sophisticated laboratory equipment. However, non-target-dependent amplification has limited the sensitivity of isothermal technologies and complex probes are usually required to distinguish between non-specific and target-dependent amplification. Here, we report a novel isothermal nucleic acid amplification technology, Strand Invasion Based Amplification (SIBA. SIBA technology is resistant to non-specific amplification, is able to detect a single molecule of target analyte, and does not require target-specific probes. The technology relies on the recombinase-dependent insertion of an invasion oligonucleotide (IO into the double-stranded target nucleic acid. The duplex regions peripheral to the IO insertion site dissociate, thereby enabling target-specific primers to bind. A polymerase then extends the primers onto the target nucleic acid leading to exponential amplification of the target. The primers are not substrates for the recombinase and are, therefore unable to extend the target template in the absence of the IO. The inclusion of 2'-O-methyl RNA to the IO ensures that it is not extendible and that it does not take part in the extension of the target template. These characteristics ensure that the technology is resistant to non-specific amplification since primer dimers or mis-priming are unable to exponentially amplify. Consequently, SIBA is highly specific and able to distinguish closely-related species with single molecule sensitivity in the absence of complex probes or sophisticated laboratory equipment. Here, we describe this technology in detail and demonstrate its use for the detection of Salmonella.

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

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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

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

Modeling the amplification dynamics of human Alu retrotransposons.

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Dale J Hedges

2005-09-01

Full Text Available Retrotransposons have had a considerable impact on the overall architecture of the human genome. Currently, there are three lineages of retrotransposons (Alu, L1, and SVA that are believed to be actively replicating in humans. While estimates of their copy number, sequence diversity, and levels of insertion polymorphism can readily be obtained from existing genomic sequence data and population sampling, a detailed understanding of the temporal pattern of retrotransposon amplification remains elusive. Here we pose the question of whether, using genomic sequence and population frequency data from extant taxa, one can adequately reconstruct historical amplification patterns. To this end, we developed a computer simulation that incorporates several known aspects of primate Alu retrotransposon biology and accommodates sampling effects resulting from the methods by which mobile elements are typically discovered and characterized. By modeling a number of amplification scenarios and comparing simulation-generated expectations to empirical data gathered from existing Alu subfamilies, we were able to statistically reject a number of amplification scenarios for individual subfamilies, including that of a rapid expansion or explosion of Alu amplification at the time of human-chimpanzee divergence.

Modeling the amplification dynamics of human alu retrotransposons.

Directory of Open Access Journals (Sweden)

2005-09-01

Full Text Available Retrotransposons have had a considerable impact on the overall architecture of the human genome. Currently, there are three lineages of retrotransposons (Alu, L1, and SVA that are believed to be actively replicating in humans. While estimates of their copy number, sequence diversity, and levels of insertion polymorphism can readily be obtained from existing genomic sequence data and population sampling, a detailed understanding of the temporal pattern of retrotransposon amplification remains elusive. Here we pose the question of whether, using genomic sequence and population frequency data from extant taxa, one can adequately reconstruct historical amplification patterns. To this end, we developed a computer simulation that incorporates several known aspects of primate Alu retrotransposon biology and accommodates sampling effects resulting from the methods by which mobile elements are typically discovered and characterized. By modeling a number of amplification scenarios and comparing simulation-generated expectations to empirical data gathered from existing Alu subfamilies, we were able to statistically reject a number of amplification scenarios for individual subfamilies, including that of a rapid expansion or explosion of Alu amplification at the time of human-chimpanzee divergence.

Magnetic field amplification in interstellar collisionless shock waves

International Nuclear Information System (INIS)

Chevalier, R.A.

1977-01-01

It is stated that it is commonly assumed that a simple compression of the magnetic field occurs in interstellar shock waves. Recent space observations of the Earth's bow shock have shown that turbulent amplification of the magnetic field can occur in a collisionless shock. It is shown here that radio observations of Tycho's supernova remnant indicate the presence of a shock wave with such magnetic field amplification. There is at present no theory for the microinstabilities that give rise to turbulent amplification of the magnetic field. Despite the lack of theoretical understanding the possibility of field amplification in interstellar shock waves is here considered. In Tycho's supernova remnant there is evidence for the presence of a collisionless shock, and this is discussed. On the basis of observations of the Earth's bow shock, it is expected that turbulent magnetic field amplification occurs in the shock wave of this remnant, and this is supported by radio observations of the remnant. Consideration is given as to what extent the magnetic field is amplified in the shock wave on the basis of the non-thermal radio flux. (U.K.)

PCR amplification on microarrays of gel immobilized oligonucleotides

Science.gov (United States)

Strizhkov, Boris; Tillib, Sergei; Mikhailovich, Vladimir; Mirzabekov, Andrei

2003-11-04

The invention relates two general methods for performing PCR amplification, combined with the detection and analysis of the PCR products on a microchip. In the first method, the amplification occurs both outside and within a plurality of gel pads on a microchip, with at least one oligonucleotide primer immobilized in a gel pad. In the second method, PCR amplification also takes place within gel pads on a microchip, but the pads are surrounded by a hydrophobic liquid such as that which separates the individual gel pads into environments which resemble micro-miniaturized test tubes.

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.

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.

HER2 amplification, overexpression and score criteria in esophageal adenocarcinoma

Science.gov (United States)

Hu, Yingchuan; Bandla, Santhoshi; Godfrey, Tony E.; Tan, Dongfeng; Luketich, James D.; Pennathur, Arjun; Qiu, Xing; Hicks, David G.; Peters, Jeffrey; Zhou, Zhongren

2011-01-01

The HER2 oncogene was recently reported to be amplified and overexpressed in esophageal adenocarcinoma. However, the relationship of HER2 amplification in esophageal adenocarcinoma with prognosis has not been well defined. The scoring systems for clinically evaluating HER2 in esophageal adenocarcinoma are not established. The aims of the study were to establish a HER2 scoring system and comprehensively investigate HER2 amplification and overexpression in esophageal adenocarcinoma and its precursor lesion. Using a tissue microarray, containing 116 cases of esophageal adenocarcinoma, 34 cases of BE, 18 cases of low grade dysplasia and 15 cases of high grade dysplasia, HER2 amplification and overexpression were analyzed by HercepTest and CISH methods. The amplification frequency in an independent series of 116 esophageal adenocarcinoma samples was also analyzed using Affymetrix SNP 6.0 microarrays. In our studies, we have found that HER2 amplification does not associate with poor prognosis in total 232 esophageal adenocarcinoma patients by CISH and high density microarrays. We further confirm the similar frequency of HER2 amplification by CISH (18.10%; 21/116) and SNP 6.0 microarrays (16.4%, 19/116) in esophageal adenocarcinoma. HER2 protein overexpression was observed in 12.1 % (14/116) of esophageal adenocarcinoma and 6.67% (1/15) of HGD. No HER2 amplification or overexpression was identified in BE or LGD. All HER2 protein overexpression cases showed HER2 gene amplification. Gene amplification was found to be more frequent by CISH than protein overexpression in esophageal adenocarcinoma (18.10% vs 12.9%). A modified two-step model for esophageal adenocarcinoma HER-2 testing is recommend for clinical esophageal adenocarcinoma HER-2 trial. PMID:21460800

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.

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)

Amplification of Chirality in Hydrogen-Bonded Tetrarosette Helices

NARCIS (Netherlands)

Mateos timoneda, Miguel; Crego Calama, Mercedes; Reinhoudt, David

2006-01-01

The amplification of chirality in hydrogen-bonded tetrarosette assemblies under thermodynamic equilibrium is described. The extent of the chiral amplification obtained by means of “sergeants-and-soldiers” experiments depends only on the structure of the assembly and it is independent of the

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.

Study on Electrophysiological Signal Monitoring of Plant under Stress Based on Integrated Op-Amps and Patch Electrode

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Weiming Cai

2017-01-01

Full Text Available Electrophysiological signal in plant is a weak electrical signal, which can fluctuate with the change of environment. An amplification detection system was designed for plant electrical signal acquisition by using integrated op-amps (CA3140, AD620, and INA118, patch electrode, data acquisition card (NI USB-6008, computer, and shielded box. Plant electrical signals were also studied under pressure and flooding stress. The amplification detection system can make nondestructive acquisition for Aquatic Scindapsus and Guaibcn with high precision, high sensitivity, low power consumption, high common mode rejection ratio, and working frequency bandwidth. Stress experiments were conducted through the system; results show that electrical signals were produced in the leaf of Aquatic Scindapsus under the stress of pressure. Electrical signals in the up-leaf surface of Aquatic Scindapsus were stronger than the down-leaf surface. Electrical signals produced in the leaf of Guaibcn were getting stronger when suffering flooding stress. The more the flooding stress was severe, the faster the electrical signal changed, the longer the time required for returning to a stable state was, and the greater the electrical signal got at the stable state was.

The rolling circle amplification and next generation sequencing ...

African Journals Online (AJOL)

Rolling circle amplification is a simple approach of enriching populations of single-stranded DNA plant begomovirus genomes (genus, Begomovirus; family, Geminiviridae). This is an innovative approach that utilizes the robustness of the bacteriophage phi29 DNA polymerase used in circle amplification, together with deep ...

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...

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

Optical parametric amplification of arbitrarily polarized light in periodically poled LiNbO3.

Science.gov (United States)

Shao, Guang-hao; Song, Xiao-shi; Xu, Fei; Lu, Yan-qing

2012-08-13

Optical parametric amplification (OPA) of arbitrarily polarized light is proposed in a multi-section periodically poled Lithium Niobate (PPLN). External electric field is applied on selected sections to induce the polarization rotation of involved lights, thus the quasi-phase matched optical parametric processes exhibit polarization insensitivity under suitable voltage. In addition to the amplified signal wave, an idler wave with the same polarization is generated simultaneously. As an example, a ~10 times OPA showing polarization independency is simulated. Applications of this technology are also discussed.

FAST MAGNETIC FIELD AMPLIFICATION IN THE EARLY UNIVERSE: GROWTH OF COLLISIONLESS PLASMA INSTABILITIES IN TURBULENT MEDIA

Energy Technology Data Exchange (ETDEWEB)

Falceta-Gonçalves, D. [SUPA, School of Physics and Astronomy, University of St Andrews, North Haugh, St Andrews, Fife KY16 9SS (United Kingdom); Kowal, G. [Escola de Artes, Ciências e Humanidades, Universidade de São Paulo, Rua Arlindo Bettio, 1000, São Paulo, SP 03828-000 (Brazil)

2015-07-20

In this work we report on a numerical study of the cosmic magnetic field amplification due to collisionless plasma instabilities. The collisionless magnetohydrodynamic equations derived account for the pressure anisotropy that leads, in specific conditions, to the firehose and mirror instabilities. We study the time evolution of seed fields in turbulence under the influence of such instabilities. An approximate analytical time evolution of the magnetic field is provided. The numerical simulations and the analytical predictions are compared. We found that (i) amplification of the magnetic field was efficient in firehose-unstable turbulent regimes, but not in the mirror-unstable models; (ii) the growth rate of the magnetic energy density is much faster than the turbulent dynamo; and (iii) the efficient amplification occurs at small scales. The analytical prediction for the correlation between the growth timescales and pressure anisotropy is confirmed by the numerical simulations. These results reinforce the idea that pressure anisotropies—driven naturally in a turbulent collisionless medium, e.g., the intergalactic medium, could efficiently amplify the magnetic field in the early universe (post-recombination era), previous to the collapse of the first large-scale gravitational structures. This mechanism, though fast for the small-scale fields (∼kpc scales), is unable to provide relatively strong magnetic fields at large scales. Other mechanisms that were not accounted for here (e.g., collisional turbulence once instabilities are quenched, velocity shear, or gravitationally induced inflows of gas into galaxies and clusters) could operate afterward to build up large-scale coherent field structures in the long time evolution.

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.

DNA amplification is rare in normal human cells

International Nuclear Information System (INIS)

Wright, J.A.; Watt, F.M.; Hudson, D.L.; Stark, G.R.; Smith, H.S.; Hancock, M.C.

1990-01-01

Three types of normal human cells were selected in tissue culture with three drugs without observing a single amplification event from a total of 5 x 10 8 cells. No drug-resistant colonies were observed when normal foreskin keratinocytes were selected with N-(phosphonacetyl)-L-aspartate or with hydroxyurea or when normal mammary epithelial cells were selected with methotrexate. Some slightly resistant colonies with limited potential for growth were obtained when normal diploid fibroblast cells derived from fetal lung were selected with methotrexate or hydroxyurea but careful copy-number analysis of the dihydrofolate reductase and ribonucleotide reductase genes revealed no evidence of amplification. The rarity of DNA amplification in normal human cells contrasts strongly with the situation in tumors and in established cell lines, where amplification of onogenes and of genes mediating drug resistance is frequent. The results suggest that tumors and cell lines have acquired the abnormal ability to amplify DNA with high frequency

Enhanced DNA Profiling of the Semen Donor in Late Reported Sexual Assaults: Use of Y-Chromosome-Targeted Pre-amplification and Next Generation Y-STR Amplification Systems.

Science.gov (United States)

Hanson, Erin K; Ballantyne, Jack

2016-01-01

In some cases of sexual assault the victim may not report the assault for several days after the incident due to various factors. The ability to obtain an autosomal STR profile of the semen donor from a living victim rapidly diminishes as the post-coital interval is extended due to the presence of only a small amount of male DNA amidst an overwhelming amount of female DNA. Previously, we have utilized various technological tools to overcome the limitations of male DNA profiling in extended interval post-coital samples including the use of Y-chromosome STR profiling, cervical sample, and post-PCR purification permitting the recovery of Y-STR profiles of the male DNA from samples collected 5-6 days after intercourse. Despite this success, the reproductive biology literature reports the presence of spermatozoa in the human cervix up to 7-10 days post-coitus. Therefore, novel and improved methods for recovery of male profiles in extended interval post-coital samples were required. Here, we describe enhanced strategies, including Y-chromosome-targeted pre-amplification and next generation Y-STR amplification kits, that have resulted in the ability to obtain probative male profiles from samples collected 6-9 days after intercourse.

Enhanced acoustic sensing through wave compression and pressure amplification in anisotropic metamaterials.

Science.gov (United States)

Chen, Yongyao; Liu, Haijun; Reilly, Michael; Bae, Hyungdae; Yu, Miao

2014-10-15

Acoustic sensors play an important role in many areas, such as homeland security, navigation, communication, health care and industry. However, the fundamental pressure detection limit hinders the performance of current acoustic sensing technologies. Here, through analytical, numerical and experimental studies, we show that anisotropic acoustic metamaterials can be designed to have strong wave compression effect that renders direct amplification of pressure fields in metamaterials. This enables a sensing mechanism that can help overcome the detection limit of conventional acoustic sensing systems. We further demonstrate a metamaterial-enhanced acoustic sensing system that achieves more than 20 dB signal-to-noise enhancement (over an order of magnitude enhancement in detection limit). With this system, weak acoustic pulse signals overwhelmed by the noise are successfully recovered. This work opens up new vistas for the development of metamaterial-based acoustic sensors with improved performance and functionalities that are highly desirable for many applications.

Label-free and sensitive detection of T4 polynucleotide kinase activity via coupling DNA strand displacement reaction with enzymatic-aided amplification.

Science.gov (United States)

Cheng, Rui; Tao, Mangjuan; Shi, Zhilu; Zhang, Xiafei; Jin, Yan; Li, Baoxin

2015-11-15

Several fluorescence signal amplification strategies have been developed for sensitive detection of T4 polynucleotide kinase (T4 PNK) activity, but they need fluorescence dye labeled DNA probe. We have addressed the limitation and report here a label-free strategy for sensitive detection of PNK activity by coupling DNA strand displacement reaction with enzymatic-aided amplification. A hairpin oligonucleotide (hpDNA) with blunt ends was used as the substrate for T4 PNK phosphorylation. In the presence of T4 PNK, the stem of hpDNA was phosphorylated and further degraded by lambda exonuclease (λ exo) from 5' to 3' direction to release a single-stranded DNA as a trigger of DNA strand displacement reaction (SDR). The trigger DNA can continuously displace DNA P2 from P1/P2 hybrid with the help of specific cleavage of nicking endonuclease (Nt.BbvCI). Then, DNA P2 can form G-quadruplex in the presence of potassium ions and quadruplex-selective fluorphore, N-methyl mesoporphyrin IX (NMM), resulting in a significant increase in fluorescence intensity of NMM. Thus, the accumulative release of DNA P2 led to fluorescence signal amplification for determining T4 PNK activity with a detection limit of 6.6×10(-4) U/mL, which is superior or comparative with established approaches. By ingeniously utilizing T4 PNK-triggered DNA SDR, T4 PNK activity can be specifically and facilely studied in homogeneous solution containing complex matrix without any external fluorescence labeling. Moreover, the influence of different inhibitors on the T4 PNK activity revealed that it also can be explored to screen T4 PNK inhibitors. Therefore, this label-free amplification strategy presents a facile and cost-effective approach for nucleic acid phosphorylation related research. Copyright © 2015 Elsevier B.V. All rights reserved.

Population diversity of ammonium oxidizers investigated by specific PCR amplification

Science.gov (United States)

Ward, B.B.; Voytek, M.A.; Witzel, K.-P.

1997-01-01

The species composition of ammonia-oxidizing bacteria in aquatic environments was investigated using PCR primers for 16S rRNA genes to amplify specific subsets of the total ammonia-oxidizer population. The specificity of the amplification reactions was determined using total genomic DNA from known nitrifying strains and non-nitrifying strains identified as having similar rDNA sequences. Specificity of amplification was determined both for direct amplification, using the nitrifier specific primers, and with nested amplification, in which the nitrifier primers were used to reamplify a fragment obtained from direct amplification with Eubacterial universal primers. The present level of specificity allows the distinction between Nitrosomonas europaea, Nitrosomonas sp. (marine) and the other known ammonia-oxidizers in the beta subclass of the Proteobacteria. Using total DNA extracted from natural samples, we used direct amplification to determine presence/absence of different species groups. Species composition was found to differ among depths in vertical profiles of lake samples and among samples and enrichments from various other aquatic environments. Nested PCR yielded several more positive reactions, which implies that nitrifier DNA was present in most samples, but often at very low levels.

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.

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...

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.

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.

Simplified Real-Time Multiplex Detection of Loop-Mediated Isothermal Amplification Using Novel Mediator Displacement Probes with Universal Reporters.

Science.gov (United States)

Becherer, Lisa; Bakheit, Mohammed; Frischmann, Sieghard; Stinco, Silvina; Borst, Nadine; Zengerle, Roland; von Stetten, Felix

2018-04-03

A variety of real-time detection techniques for loop-mediated isothermal amplification (LAMP) based on the change in fluorescence intensity during DNA amplification enable simultaneous detection of multiple targets. However, these techniques depend on fluorogenic probes containing target-specific sequences. That complicates the adaption to different targets leading to time-consuming assay optimization. Here, we present the first universal real-time detection technique for multiplex LAMP. The novel approach allows simple assay design and is easy to implement for various targets. The innovation features a mediator displacement probe and a universal reporter. During amplification of target DNA the mediator is displaced from the mediator displacement probe. Then it hybridizes to the reporter generating a fluorescence signal. The novel mediator displacement (MD) detection was validated against state-of-the-art molecular beacon (MB) detection by means of a HIV-1 RT-LAMP: MD surpassed MB detection by accelerated probe design (MD: 10 min, MB: 3-4 h), shorter times to positive (MD 4.1 ± 0.1 min shorter than MB, n = 36), improved signal-to-noise fluorescence ratio (MD: 5.9 ± 0.4, MB: 2.7 ± 0.4; n = 15), and showed equally good or better analytical performance parameters. The usability of one universal mediator-reporter set in different multiplex assays was successfully demonstrated for a biplex RT-LAMP of HIV-1 and HTLV-1 and a biplex LAMP of Haemophilus ducreyi and Treponema pallidum, both showing good correlation between target concentration and time to positive. Due to its simple implementation it is suggested to extend the use of the universal mediator-reporter sets to the detection of various other diagnostic panels.

CDK4 amplification predicts recurrence of well-differentiated liposarcoma of the abdomen.

Directory of Open Access Journals (Sweden)

Sanghoon Lee

Full Text Available The absence of CDK4 amplification in liposarcomas is associated with favorable prognosis. We aimed to identify the factors associated with tumor recurrence in patients with well-differentiated (WD and dedifferentiated (DD liposarcomas.From 2000 to 2010, surgical resections for 101 WD and DD liposarcomas were performed. Cases in which complete surgical resections with curative intent were carried out were selected. MDM2 and CDK4 gene amplification were analyzed by quantitative real-time polymerase chain reaction (Q-PCR.There were 31 WD and 17 DD liposarcomas. Locoregional recurrence was observed in 11 WD and 3 DD liposarcomas. WD liposarcomas showed better patient survival compared to DD liposarcomas (P<0.05. Q-PCR analysis of the liposarcomas revealed the presence of CDK4 amplification in 44 cases (91.7% and MDM2 amplification in 46 cases (95.8%. WD liposarcomas with recurrence after surgical resection had significantly higher levels of CDK4 amplification compared to those without recurrence (P = 0.041. High level of CDK4 amplification (cases with CDK4 amplification higher than the median 7.54 was associated with poor recurrence-free survival compared to low CDK4 amplification in both univariate (P = 0.012 and multivariate analyses (P = 0.020.Level of CDK4 amplification determined by Q-PCR was associated with the recurrence of WD liposarcomas after surgical resection.

Explanatory Model for Sound Amplification in a Stethoscope

Science.gov (United States)

Eshach, H.; Volfson, A.

2015-01-01

In the present paper we suggest an original physical explanatory model that explains the mechanism of the sound amplification process in a stethoscope. We discuss the amplification of a single pulse, a continuous wave of certain frequency, and finally we address the resonant frequencies. It is our belief that this model may provide students with…

Generation of recombinant pestiviruses using a full genome amplification strategy

DEFF Research Database (Denmark)

Rasmussen, Thomas Bruun; Reimann, Ilona; Uttenthal, Åse

Aim Complete genome amplification of viral RNA provides a new tool for generation of modified pestiviruses. We have recently reported a full genome amplification strategy for direct recovery of infectious pestivirus (Rasmussen et al., 2008). This comprised rescue of BDV strain “Gifhorn” from a full......-length RT-PCR amplicon demonstrating that long RT-PCR can be used for direct generation of an infectious pestivirus. The strategy is not limited to amplification of BDV “Gifhorn”, but can be further utilized for amplification of a diverse selection of pestivirus strains and for the generation of modified...... was reverse transcribed to cDNA at 50C for 90 minutes using SuperScript III reverse transcriptase (Invitrogen). Full-length PCR amplification was performed using primers specific for the extreme 5’- and 3’-ends of the viral genomes. A T7 promoter was incorporated in the 5’-primers for direct in vitro...

Exponential isothermal amplification of nucleic acids and amplified assays for proteins, cells, and enzyme activities.

Science.gov (United States)

Reid, Michael S; Le, X Chris; Zhang, Hongquan

2018-04-27

Isothermal exponential amplification techniques, such as strand-displacement amplification (SDA), rolling circle amplification (RCA), loop-mediated isothermal amplification (LAMP), nucleic acid sequence-based amplification (NASBA), helicase-dependent amplification (HDA), and recombinase polymerase amplification (RPA), have great potential for on-site, point-of-care, and in-situ assay applications. These amplification techniques eliminate the need for temperature cycling required for polymerase chain reaction (PCR) while achieving comparable amplification yield. We highlight here recent advances in exponential amplification reaction (EXPAR) for the detection of nucleic acids, proteins, enzyme activities, cells, and metal ions. We discuss design strategies, enzyme reactions, detection techniques, and key features. Incorporation of fluorescence, colorimetric, chemiluminescence, Raman, and electrochemical approaches enables highly sensitive detection of a variety of targets. Remaining issues, such as undesirable background amplification resulting from non-specific template interactions, must be addressed to further improve isothermal and exponential amplification techniques. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

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

Diagnostic monitoring of the condition of the amplification-transformer channel of automatic gas protection apparatus

Energy Technology Data Exchange (ETDEWEB)

Karpov, Ye F; Basovskiy, B I; Popov, V V

1978-01-01

A method is suggested for verifying the performance capacity of an amplifier-transformer channel of apparatus for automatic gas protection under operating conditions. Processes are examined which occur in the bridge measurement plan of the sensor during shunting of one of the thermal-transformer elements by a resistor. An expression is obtained for determining the coefficient of transfer of the amplification-transformer channel on the outlet signals of the apparatus in a working regime and after shunting of one of the thermal-transformer elements.

A novel electrochemical sensor for lead ion based on cascade DNA and quantum dots amplification

International Nuclear Information System (INIS)

Tang, Shurong; Lu, Wei; Gu, Fang; Tong, Ping; Yan, Zhiming; Zhang, Lan

2014-01-01

A new enzyme-free and ultrasensitive electrochemical Pb 2+ biosensor was developed. By coupling the DNA-assisted cascade of hybridization reaction with the quantum dots (QDs) for signal amplification, a detection limit as low as 6.1 pM can be obtained for Pb 2+ . In this study, the “8-17” DNAzyme was used for specific recognition of Pb 2+ . In the presence of Pb 2+ , the DNAzyme was activated and cleaved the substrate strand. And then, the hybridization between the linker probe and signal probe was initiated, which resulted in formation of a long cascade DNA structure as well as assemble of numerous QDs at last. By the use of magnetic beads, the free signal probe can be easily removed by external magnetic field. After acid lysis, a great amount of redox cations can be released from the QDs and eventually result in significantly amplified electrochemical signals. This method is highly sensitive, selective and simple without the participation of any protein based enzyme (nuclease), thereby holds great potential for real sample analysis

Basin amplification of seismic waves in the city of Pahrump, Nevada.

Energy Technology Data Exchange (ETDEWEB)

Abbott, Robert E.

2005-07-01

Sedimentary basins can increase the magnitude and extend the duration of seismic shaking. This potential for seismic amplification is investigated for Pahrump Valley, Nevada-California. The Pahrump Valley is located approximately 50 km northwest of Las Vegas and 75 km south of the Nevada Test Site. Gravity data suggest that the city of Pahrump sits atop a narrow, approximately 5 km deep sub-basin within the valley. The seismic amplification, or ''site effect'', was investigated using a combination of in situ velocity modeling and comparison of the waveforms and spectra of weak ground motion recorded in the city of Pahrump, Nevada, and those recorded in the nearby mountains. Resulting spectral ratios indicate seismic amplification factors of 3-6 over the deepest portion of Pahrump Valley. This amplification predominantly occurs at 2-2.5 Hz. Amplification over the deep sub-basin is lower than amplification at the sub-basin edge, location of the John Blume and Associates PAHA seismic station, which recorded many underground nuclear tests at the Nevada Test Site. A comprehensive analysis of basin amplification for the city of Pahrump should include 3-D basin modeling, due to the extreme basement topography of the Pahrump Valley.

Comparison of in situ hybridization methods for the assessment of HER-2/neu gene amplification status in breast cancer using a tissue microarray.

Science.gov (United States)

Malicka-Durczak, Anna; Korski, Konstanty; Ibbs, Matthew

2012-01-01

This project compared HER-2/neu gene status in breast cancers, as demonstrated by FISH (fluorescent in situ hybridization) and CISH (chromogenic in situ hybridization) and using a tissue microarray (TMA). The study also aimed to show whether the TMA technique could be used in clinical diagnostics, rather than remain a scientific tool. A TMA was constructed using 121 breast cancer specimens, 6 cores from each specimen. Demonstration and assessment of HER-2/neu gene status was by FISH (Vysis Path) and CISH (DAKO Duo CISH). The 121 breast cancer specimens were divided into 3 groups by HER-2 status, as determined by immunohistochemistry. In the HER-2 negative group no amplification was observed in 36 out of 40 cases. 3 cases showed amplification by both methods and one by CISH alone. The equivocal HER-2 group showed no amplification in 30 out of 41 cases and amplification in 9 cases. One case was FISH negative CISH positive and one was discarded. In the HER-2 positive group, amplification was confirmed in 37 of the 40 cases by both methods. 3 cases were unsuitable for assessment. This study indicated that CISH is a sensitive alternative to FISH in detecting HER2 gene amplification and may replace FISH in HER2 testing. Good agreement was observed between methods (98.5% - 119 out of 121 cases). Furthermore, as only 4 out of 121 cases were unsuitable for assessment (no signal or missing TMA cores) - it may be feasible to use TMA in diagnostics.

Compartmentalization of NO signaling cascade in skeletal muscles

International Nuclear Information System (INIS)

Buchwalow, Igor B.; Minin, Evgeny A.; Samoilova, Vera E.; Boecker, Werner; Wellner, Maren; Schmitz, Wilhelm; Neumann, Joachim; Punkt, Karla

2005-01-01

Skeletal muscle functions regulated by NO are now firmly established. However, the literature on the compartmentalization of NO signaling in myocytes is highly controversial. To address this issue, we examined localization of enzymes engaged in L-arginine-NO-cGMP signaling in the rat quadriceps muscle. Employing immunocytochemical labeling complemented with tyramide signal amplification and electron microscopy, we found NO synthase expressed not only in the sarcolemma, but also along contractile fibers, in the sarcoplasmic reticulum and mitochondria. The expression pattern of NO synthase in myocytes showed striking parallels with the enzymes engaged in L-arginine-NO-cGMP signaling (arginase, phosphodiesterase, and soluble guanylyl cyclase). Our findings are indicative of an autocrine fashion of NO signaling in skeletal muscles at both cellular and subcellular levels, and challenge the notion that the NO generation is restricted to the sarcolemma

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.

AgNPs-3D nanostructure enhanced electrochemiluminescence of CdSe quantum dot coupled with strand displacement amplification for sensitive biosensing of DNA

International Nuclear Information System (INIS)

Jiao, Meng; Jie, Guifen; Tan, Lu; Niu, Shuyan

2017-01-01

A novel strategy using Ag nanoparticles-3D (AgNPs-3D) nanostructure enhanced electrochemiluminescence (ECL) of CdSe quantum dots (QDs) coupled with strand displacement amplification (SDA) for sensitive biosensing of DNA was successfully designed. The prepared CdSe QDs with intense ECL were assembled on the poly (diallyldimethylammonium chloride) (PDDA) graphene oxide (GO) nanocomposites modified electrode, then gold nanoparticles (NPs) as the quenching probe was conjugated to the QDs, ECL signal was efficiently quenched. The target DNA induced cycling SDA and generated a large number of DNA s1. The released DNA s1 could open the hairpin DNA with quenching probe. So the presence of low levels of target DNA can potentially result in a significant enhancement of ECL signal. Furthermore, large number of AgNPs were then in situ reduced in the 3D DNA skeleton on the electrode, which dramaticlly enhanced ECL signal of QDs owing to the excellent electrical conductivity, and the much amplified ECL signal change has a quantitative relation with the target DNA. So by combining the AgNPs-3D nanostructure and cycling SDA to achieve greatly amplified detection of DNA, the promising ECL strategy could provide a highly sensitive platform for various biomolecules and has a good prospect for clinical diagnosis in the future. - Graphical abstract: A novel strategy using AgNPs-3D nanostructure enhanced electrochemiluminescence of CdSe quantum dot coupled with DNA strand displacement amplification for sensitive biosensing of DNA was successfully designed, the proposed biosensor can be expected to be an emerging alternative for straightforward nucleic acid detection in complex samples with an easy and rapid way. - Highlights: • AgNPs-3D nanostructure for enhancing ECL signal of CdSe QDs was successfully designed. • A new dual amplification strategy for detection of DNA by using AgNPs-3D nanostructure coupled with SDA was developed. • It is for the first time AgNPs-3D nanostructure

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.

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.

High density and ligand affinity confer ultrasensitive signal detection by a guanylyl cyclase chemoreceptor

Science.gov (United States)

Pichlo, Magdalena; Bungert-Plümke, Stefanie; Weyand, Ingo; Seifert, Reinhard; Bönigk, Wolfgang; Strünker, Timo; Kashikar, Nachiket Dilip; Goodwin, Normann; Müller, Astrid; Körschen, Heinz G.; Collienne, Ursel; Pelzer, Patric; Van, Qui; Enderlein, Jörg; Klemm, Clementine; Krause, Eberhard; Trötschel, Christian; Poetsch, Ansgar; Kremmer, Elisabeth

2014-01-01

Guanylyl cyclases (GCs), which synthesize the messenger cyclic guanosine 3′,5′-monophosphate, control several sensory functions, such as phototransduction, chemosensation, and thermosensation, in many species from worms to mammals. The GC chemoreceptor in sea urchin sperm can decode chemoattractant concentrations with single-molecule sensitivity. The molecular and cellular underpinnings of such ultrasensitivity are not known for any eukaryotic chemoreceptor. In this paper, we show that an exquisitely high density of 3 × 105 GC chemoreceptors and subnanomolar ligand affinity provide a high ligand-capture efficacy and render sperm perfect absorbers. The GC activity is terminated within 150 ms by dephosphorylation steps of the receptor, which provides a means for precise control of the GC lifetime and which reduces “molecule noise.” Compared with other ultrasensitive sensory systems, the 10-fold signal amplification by the GC receptor is surprisingly low. The hallmarks of this signaling mechanism provide a blueprint for chemical sensing in small compartments, such as olfactory cilia, insect antennae, or even synaptic boutons. PMID:25135936

Human Sarcoma growth is sensitive to small-molecule mediated AXIN stabilization.

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Alessandra De Robertis

Full Text Available Sarcomas are mesenchymal tumors showing high molecular heterogeneity, reflected at the histological level by the existence of more than fifty different subtypes. Genetic and epigenetic evidences link aberrant activation of the Wnt signaling to growth and progression of human sarcomas. This phenomenon, mainly accomplished by autocrine loop activity, is sustained by gene amplification, over-expression of Wnt ligands and co-receptors or epigenetic silencing of endogenous Wnt antagonists. We previously showed that pharmacological inhibition of Wnt signaling mediated by Axin stabilization produced in vitro and in vivo antitumor activity in glioblastoma tumors. Here, we report that targeting different sarcoma cell lines with the Wnt inhibitor/Axin stabilizer SEN461 produces a less transformed phenotype, as supported by modulation of anchorage-independent growth in vitro. At the molecular level, SEN461 treatment enhanced the stability of the scaffold protein Axin1, a key negative regulator of the Wnt signaling with tumor suppressor function, resulting in downstream effects coherent with inhibition of canonical Wnt signaling. Genetic phenocopy of small molecule Axin stabilization, through Axin1 over-expression, coherently resulted in strong impairment of soft-agar growth. Importantly, sarcoma growth inhibition through pharmacological Axin stabilization was also observed in a xenograft model in vivo in female CD-1 nude mice. Our findings suggest the usefulness of Wnt inhibitors with Axin stabilization activity as a potentialyl clinical relevant strategy for certain types of sarcomas.

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...

Amplification of surface acoustic waves by transverse electric current in piezoelectric semiconductors

DEFF Research Database (Denmark)

Gulyaev, Yuri V.

1974-01-01

acoustoelectric effect but also lead to amplification of surface acoustic waves by electron drift perpendicular to the surface. For Love waves in a piezoelectric semiconductor film on a highly conducting substrate, the amplification coefficient is found and the conditions necessary for amplification...

pH responsive label-assisted click chemistry triggered sensitivity amplification for ultrasensitive electrochemical detection of carbohydrate antigen 24-2.

Science.gov (United States)

Zheng, Yun; Zhao, Lihua; Ma, Zhanfang

2018-05-15

Sensitivity amplification strategy by implementing click chemistry in the construction of biosensing interface can efficiently improve the performance of immunosensor. Herein, we developed a sandwich-type amperometric immunosensor for ultrasensitive detection of carbohydrate antigen 24-2 (CA 242) based on pH responsive label-assisted click chemistry triggered sensitivity amplification strategy. The sensitivity of amperometric immunosensor relies on the current response differences (ΔI) caused by per unit concentration target analyte. The pH responsive Cu 2+ -loaded polydopamine (CuPDA) particles conjugated with detection antibodies were employed as labels, which can release Cu(II) ions by regulating pH. In the presence of ascorbic acid (reductant), Cu(II) ions were reduced to Cu(I) ions. Azide-functionalized double-stranded DNA (dsDNA) as signal enhancer was immobilized on the substrate through Cu + -catalyzed azide/alkyne cycloaddition reaction. With the help of the click reaction, the ΔI caused by target was elevated prominently, resulting in sensitivity amplification of the immunosensor. Under optimal condition, the proposed immunosensor exhibited excellent performance with linear range from 0.0001 to 100 U mL -1 and ultralow detection limit of 20.74 μU mL -1 . This work successfully combines click chemistry with pH-responsive labels in sandwich-type amperometric immunosensor, providing a promising sensitivity amplification strategy to construct immunosensing platform for analysis of other tumor marker. Copyright © 2018 Elsevier B.V. All rights reserved.

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

Active Hearing Mechanisms Inspire Adaptive Amplification in an Acoustic Sensor System.

Science.gov (United States)

Guerreiro, Jose; Reid, Andrew; Jackson, Joseph C; Windmill, James F C

2018-06-01

Over many millions of years of evolution, nature has developed some of the most adaptable sensors and sensory systems possible, capable of sensing, conditioning and processing signals in a very power- and size-effective manner. By looking into biological sensors and systems as a source of inspiration, this paper presents the study of a bioinspired concept of signal processing at the sensor level. By exploiting a feedback control mechanism between a front-end acoustic receiver and back-end neuronal based computation, a nonlinear amplification with hysteretic behavior is created. Moreover, the transient response of the front-end acoustic receiver can also be controlled and enhanced. A theoretical model is proposed and the concept is prototyped experimentally through an embedded system setup that can provide dynamic adaptations of a sensory system comprising a MEMS microphone placed in a closed-loop feedback system. It faithfully mimics the mosquito's active hearing response as a function of the input sound intensity. This is an adaptive acoustic sensor system concept that can be exploited by sensor and system designers within acoustics and ultrasonic engineering fields.

Radiation-induced gene amplification in rodent and human cells

International Nuclear Information System (INIS)

Luecke-Huhle, C.; Gloss, B.; Herrlich, P.

1990-01-01

Ionizing and UV radiations induce amplification of SV40 DNA sequences integrated in the genome of Chinese hamster cells and increase amplification of the dihydrofolate reductase (DHFR) gene during methotrexate selection in human skin fibroblasts of a patient with ataxia telangiectasia. Various types of external (60-Co-γ-rays, 241-Am-α-particles, UV) or internal radiation (caused by the decay of 125 I incorporated into DNA in form of I-UdR) were applied. By cell fusion experiments it could be shown that SV40 gene amplification is mediated by one or several diffusible trans-acting factors induced or activated in a dose dependent manner by all types of radiation. One of these factors binds to a 10 bp sequence within the minimal origin of replication of SV40. In vivo competition with an excess of a synthetic oligonucleotide comprising this sequence blocks radiation-induced amplification. (author) 25 refs.; 8 figs

Probabilistic Sensitivity Amplification Control for Lower Extremity Exoskeleton

Directory of Open Access Journals (Sweden)

Likun Wang

2018-03-01

Full Text Available To achieve ideal force control of a functional autonomous exoskeleton, sensitivity amplification control is widely used in human strength augmentation applications. The original sensitivity amplification control aims to increase the closed-loop control system sensitivity based on positive feedback without any sensors between the pilot and the exoskeleton. Thus, the measurement system can be greatly simplified. Nevertheless, the controller lacks the ability to reject disturbance and has little robustness to the variation of the parameters. Consequently, a relatively precise dynamic model of the exoskeleton system is desired. Moreover, the human-robot interaction (HRI cannot be interpreted merely as a particular part of the driven torque quantitatively. Therefore, a novel control methodology, so-called probabilistic sensitivity amplification control, is presented in this paper. The innovation of the proposed control algorithm is two-fold: distributed hidden-state identification based on sensor observations and evolving learning of sensitivity factors for the purpose of dealing with the variational HRI. Compared to the other state-of-the-art algorithms, we verify the feasibility of the probabilistic sensitivity amplification control with several experiments, i.e., distributed identification model learning and walking with a human subject. The experimental result shows potential application feasibility.

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.

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)

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.

Isothermal Amplification for MicroRNA Detection: From the Test Tube to the Cell.

Science.gov (United States)

Deng, Ruijie; Zhang, Kaixiang; Li, Jinghong

2017-04-18

MicroRNAs (miRNAs) are a class of small noncoding RNAs that act as pivotal post-transcriptional regulators of gene expression, thus involving in many fundamental cellular processes such as cell proliferation, migration, and canceration. The detection of miRNAs has attracted significant interest, as abnormal miRNA expression is identified to contribute to serious human diseases such as cancers. Particularly, miRNAs in peripheral blood have recently been recognized as important biomarkers potential for liquid biopsy. Furthermore, as miRNAs are expressed heterogeneously in different cells, investigations into single-cell miRNA expression will be of great value for resolving miRNA-mediated regulatory circuits and the complexity and heterogeneity of miRNA-related diseases. Thus, the development of miRNA detection methods, especially for complex clinic samples and single cells is in great demand. In this Account, we will present recent progress in the design and application of isothermal amplification enabling miRNA detection transition from the test tube to the clinical sample and single cell, which will significantly advance our knowledge of miRNA functions and disease associations, as well as its translation in clinical diagnostics. miRNAs present a huge challenge in detection because of their extremely short length (∼22 nucleotides) and sequence homology (even with only single-nucleotide variation). The conventional golden method for nucleic acid detection, quantitative PCR (qPCR), is not amenable to directly detecting short RNAs and hardly enables distinguishing between miRNA family members with very similar sequences. Alternatively, isothermal amplification has emerged as a powerful method for quantification of nucleic acids and attracts broad interest for utilization in developing miRNA assays. Compared to PCR, isothermal amplification can be performed without precise control of temperature cycling and is well fit for detecting short RNA or DNA. We and other

Simple system for isothermal DNA amplification coupled to lateral flow detection.

Directory of Open Access Journals (Sweden)

Kristina Roskos

Full Text Available Infectious disease diagnosis in point-of-care settings can be greatly improved through integrated, automated nucleic acid testing devices. We have developed an early prototype for a low-cost system which executes isothermal DNA amplification coupled to nucleic acid lateral flow (NALF detection in a mesofluidic cartridge attached to a portable instrument. Fluid handling inside the cartridge is facilitated through one-way passive valves, flexible pouches, and electrolysis-driven pumps, which promotes a compact and inexpensive instrument design. The closed-system disposable prevents workspace amplicon contamination. The cartridge design is based on standard scalable manufacturing techniques such as injection molding. Nucleic acid amplification occurs in a two-layer pouch that enables efficient heat transfer. We have demonstrated as proof of principle the amplification and detection of Mycobacterium tuberculosis (M.tb genomic DNA in the cartridge, using either Loop Mediated Amplification (LAMP or the Exponential Amplification Reaction (EXPAR, both coupled to NALF detection. We envision that a refined version of this cartridge, including upstream sample preparation coupled to amplification and detection, will enable fully-automated sample-in to answer-out infectious disease diagnosis in primary care settings of low-resource countries with high disease burden.

Fast implementation of length-adaptive privacy amplification in quantum key distribution

International Nuclear Information System (INIS)

Zhang Chun-Mei; Li Mo; Huang Jing-Zheng; Li Hong-Wei; Li Fang-Yi; Wang Chuan; Yin Zhen-Qiang; Chen Wei; Han Zhen-Fu; Treeviriyanupab Patcharapong; Sripimanwat Keattisak

2014-01-01

Post-processing is indispensable in quantum key distribution (QKD), which is aimed at sharing secret keys between two distant parties. It mainly consists of key reconciliation and privacy amplification, which is used for sharing the same keys and for distilling unconditional secret keys. In this paper, we focus on speeding up the privacy amplification process by choosing a simple multiplicative universal class of hash functions. By constructing an optimal multiplication algorithm based on four basic multiplication algorithms, we give a fast software implementation of length-adaptive privacy amplification. “Length-adaptive” indicates that the implementation of privacy amplification automatically adapts to different lengths of input blocks. When the lengths of the input blocks are 1 Mbit and 10 Mbit, the speed of privacy amplification can be as fast as 14.86 Mbps and 10.88 Mbps, respectively. Thus, it is practical for GHz or even higher repetition frequency QKD systems. (general)

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.

Amplification and chromosomal dispersion of human endogenous retroviral sequences

International Nuclear Information System (INIS)

Steele, P.E.; Martin, M.A.; Rabson, A.B.; Bryan, T.; O'Brien, S.J.

1986-01-01

Endogenous retroviral sequences have undergone amplification events involving both viral and flanking cellular sequences. The authors cloned members of an amplified family of full-length endogenous retroviral sequences. Genomic blotting, employing a flanking cellular DNA probe derived from a member of this family, revealed a similar array of reactive bands in both humans and chimpanzees, indicating that an amplification event involving retroviral and associated cellular DNA sequences occurred before the evolutionary separation of these two primates. Southern analyses of restricted somatic cell hybrid DNA preparations suggested that endogenous retroviral segments are widely dispersed in the human genome and that amplification and dispersion events may be linked

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.

DNA sequence responsible for the amplification of adjacent genes.

Science.gov (United States)

Pasion, S G; Hartigan, J A; Kumar, V; Biswas, D K

1987-10-01

A 10.3-kb DNA fragment in the 5'-flanking region of the rat prolactin (rPRL) gene was isolated from F1BGH(1)2C1, a strain of rat pituitary tumor cells (GH cells) that produces prolactin in response to 5-bromodeoxyuridine (BrdU). Following transfection and integration into genomic DNA of recipient mouse L cells, this DNA induced amplification of the adjacent thymidine kinase gene from Herpes simplex virus type 1 (HSV1TK). We confirmed the ability of this "Amplicon" sequence to induce amplification of other linked or unlinked genes in DNA-mediated gene transfer studies. When transferred into the mouse L cells with the 10.3-5'rPRL gene sequence of BrdU-responsive cells, both the human growth hormone and the HSV1TK genes are amplified in response to 5-bromodeoxyuridine. This observation is substantiated by BrdU-induced amplification of the cotransferred bacterial Neo gene. Cotransfection studies reveal that the BrdU-induced amplification capability is associated with a 4-kb DNA sequence in the 5'-flanking region of the rPRL gene of BrdU-responsive cells. These results demonstrate that genes of heterologous origin, linked or unlinked, and selected or unselected, can be coamplified when located within the amplification boundary of the Amplicon sequence.

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.

Amplification of nonspecific products in quantitative polymerase chain reactions (qPCR

Directory of Open Access Journals (Sweden)

Adrián Ruiz-Villalba

2017-12-01

Full Text Available Quantitative PCR allows the precise measurement of DNA concentrations and is generally considered to be straightforward and trouble free. However, a survey with 93 validated assays for genes in the Wnt-pathway showed that the amplification of nonspecific products occurs frequently and is unrelated to Cq or PCR efficiency values. Titration experiments showed that the occurrence of low and high melting temperature artifacts was shown to be determined by annealing temperature, primer concentration and cDNA input. To explore the range of input variations that occur in the normal use of the Cre assay these conditions were mimicked in a complete two-way design of template −plasmid DNA- and non-template −mouse cDNA- concentrations. These experiments showed that the frequency of the amplification of the correct product and the artifact, as well as the valid quantification of the correct product, depended on the concentration of the non-template cDNA. This finding questions the interpretation of dilution series in which template as well as non-template concentrations are simultaneously decreasing. Repetition of this cDNA concentration experiment with other templates revealed that exact reproduction qPCR experiments was affected by the time it takes to complete the pipetting of a qPCR plate. Long bench times were observed to lead to significantly more artifacts. However, the measurement of artifact-associated fluorescence can be avoided by inclusion of a small heating step after the elongation phase in the amplification protocol. Taken together, this trouble-shooting journey showed that reliability and reproducibility of qPCR experiments not only depends on standardization and reporting of the biochemistry and technical aspects but also on hitherto neglected factors as sample dilution and waiting times in the laboratory work flow. Keywords: RT-qPCR, Melting curve analysis, Reaction parameters, Artifacts

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.

Automated brightfield dual-color in situ hybridization for detection of mouse double minute 2 gene amplification in sarcomas.

Science.gov (United States)

Zhang, Wenjun; McElhinny, Abigail; Nielsen, Alma; Wang, Maria; Miller, Melanie; Singh, Shalini; Rueger, Ruediger; Rubin, Brian P; Wang, Zhen; Tubbs, Raymond R; Nagle, Raymond B; Roche, Pat; Wu, Ping; Pestic-Dragovich, Lidija

2011-01-01

The human homolog of the mouse double minute 2 (MDM2) oncogene is amplified in about 20% of sarcomas. The measurement of the MDM2 amplification can aid in classification and may provide a predictive value for recently formulated therapies targeting MDM2. We have developed and validated an automated bright field dual-color in situ hybridization application to detect MDM2 gene amplification. A repeat-depleted MDM2 probe was constructed to target the MDM2 gene region at 12q15. A chromosome 12-specific probe (CHR12) was generated from a pα12H8 plasmid. The in situ hybridization assay was developed by using a dinitrophenyl-labeled MDM2 probe and a digoxigenin-labeled CHR12 probe on the Ventana Medical Systems' automated slide-staining platforms. The specificity of the MDM2 and CHR12 probes was shown on metaphase spreads and further validated against controls, including normal human tonsil and known MDM2-amplified samples. The assay performance was evaluated on a cohort of 100 formalin-fixed, paraffin-embedded specimens by using a conventional bright field microscope. Simultaneous hybridization and signal detection for MDM2 and CHR12 showed that both DNA targets were present in the same cells. One hundred soft tissue specimens were stained for MDM2 and CHR12. Although 26 of 29 lipomas were nonamplified and eusomic, MDM2 amplification was noted in 78% of atypical lipomatous tumors or well-differentiated liposarcomas. Five of 6 dedifferentiated liposarcoma cases were amplified for MDM2. MDM2 amplification was observed in 1 of 8 osteosarcomas; 3 showed CHR12 aneusomy. MDM2 amplification was present in 1 of 4 chondrosarcomas. Nine of 10 synovial sarcomas displayed no evidence of MDM2 amplification in most tumor cells. In pleomorphic sarcoma, not otherwise specified (pleomorphic malignant fibrous histiocytoma), MDM2 was amplified in 38% of cases, whereas 92% were aneusomic for CHR12. One alveolar rhabdomyosarcoma and 2 embryonal rhabdomyosarcomas displayed low-level aneusomy

Amplification-free liquid biopsy by fluorescence approach

DEFF Research Database (Denmark)

Uhd, Jesper; Okholm, Anders; Kjems, Jargen

2017-01-01

Liquid biopsy is an attractive new paradigm of modern cancer research and clinical oncology. Synergy of fluorescence microscopy with mutation specific molecular probes is a method that we developed for the detection of tumor related circulating DNA, ctDNA. The present detection methods of ctDNA...... samples include amplification-based techniques that have multiple challenges, are often time consuming and rather expensive. In this work, we successfully applied the hybridization assay and advanced microscopy for the reliable amplification-free detection and quantification of cancer associated mutations...... in ctDNA....

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.

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.

New perspectives on microbial community distortion after whole-genome amplification

Science.gov (United States)

Whole-genome amplification (WGA) has become an important tool to explore the genomic information of microorganisms in an environmental sample with limited biomass, however potential selective biases during the amplification processes are poorly understood. Here, we describe the e...

A fluorescent biosensing platform based on the polydopamine nanospheres intergrating with Exonuclease III-assisted target recycling amplification.

Science.gov (United States)

Qiang, Weibing; Wang, Xi; Li, Wei; Chen, Xiang; Li, Hui; Xu, Danke

2015-09-15

Rapid, cost-effective, sensitive and specific analysis of biomolecules is important in the modern healthcare system. Here, a fluorescent biosensing platform based on the polydopamine nanospheres (PDANS) intergrating with Exonuclease III (Exo III) was developed. Due to the interaction between the ssDNA and the PDANS, the fluorescence of 6-carboxyfluorescein (FAM) labelled in the probe would been quenched by PDANS through FRET. While, in the present of the target DNA, the probe DNA would hybridize with the target DNA to form the double-strand DNA complex. Thus, Exo III could catalyze the stepwise removal of mononucleotides from 3'-terminus in the probe DNA, releasing the target DNA. As the FAM was released from the probe DNA, the fluorescence would no longer been quenched, led to the signal on. As one target DNA molecule could undergo a number of cycles to trigger the degradation of abundant probe DNA, Exo III-assisted target recycling would led to the amplification of the signal. The detection limit for DNA was 5 pM, which was 20 times lower than that without Exo III. And the assay time was largely shortened due to the faster signal recovery kinetics. What is more, this target recycling strategy was also applied to conduct an aptamer-based biosensing platform. The fluorescence intensity was also enhanced for the assay of adenosine triphosphate (ATP). For the Exo III-assisted target recycling amplification, DNA and ATP were fast detected with high sensitivity and selectivity. This work provides opportunities to develop simple, rapid, economical, and sensitive biosensing platforms for biomedical diagnostics. Copyright © 2015 Elsevier B.V. All rights reserved.

Microfluidic bead-based multienzyme-nanoparticle amplification for detection of circulating tumor cells in the blood using quantum dots labels

Energy Technology Data Exchange (ETDEWEB)

Zhang, He, E-mail: mzhang_he@126.com; Fu, Xin; Hu, Jiayi; Zhu, Zhenjun

2013-05-24

Graphical abstract: A microfluidic beads-based nucleic acid sensor for sensitive detection of circulating tumor cells (CTCs) in the blood using multienzyme-nanoparticle amplification and quantum dots labels was developed. The chip-based CTCs analysis could detect reverse transcription-polymerase chain reaction (RT-PCR) products of tumor cell as low as 1 tumor cell (e.g. CEA expressing cell) in 1 mL blood sample. This microfluidic beads-based nucleic acid sensor is a promising platform for disease-related nucleic acid molecules at the lowest level at their earliest incidence. -- Highlights: •Combination of microfluidic bead-based platform and enzyme–probe–AuNPs is proposed. •The developed nucleic acid sensor could respond to 5 fM of tumor associated DNA. •Microfluidic platform and multienzyme-labeled AuNPs greatly enhanced sensitivity. •The developed nucleic acid sensor could respond to RT-PCR products of tumor cell as low as 1 tumor cell in 1 mL blood sample. •We report a sensitive nucleic acid sensor for detection of circulating tumor cells. -- Abstract: This study reports the development of a microfluidic bead-based nucleic acid sensor for sensitive detection of circulating tumor cells in blood samples using multienzyme-nanoparticle amplification and quantum dot labels. In this method, the microbeads functionalized with the capture probes and modified electron rich proteins were arrayed within a microfluidic channel as sensing elements, and the gold nanoparticles (AuNPs) functionalized with the horseradish peroxidases (HRP) and DNA probes were used as labels. Hence, two signal amplification approaches are integrated for enhancing the detection sensitivity of circulating tumor cells. First, the large surface area of Au nanoparticle carrier allows several binding events of HRP on each nanosphere. Second, enhanced mass transport capability inherent from microfluidics leads to higher capture efficiency of targets because continuous flow within micro

Multiplex, rapid and sensitive isothermal detection of nucleic-acid sequence by endonuclease restriction-mediated real-time multiple cross displacement amplification

Directory of Open Access Journals (Sweden)

Yi eWang

2016-05-01

Full Text Available We have devised a novel isothermal amplification technology, termed endonuclease restriction-mediated real-time multiple cross displacement amplification (ET-MCDA, which facilitated multiplex, rapid, specific and sensitive detection of nucleic-acid sequences at a constant temperature. The ET-MCDA integrated multiple cross displacement amplification strategy, restriction endonuclease cleavage and real-time fluorescence detection technique. In the ET-MCDA system, the functional cross primer E-CP1 or E-CP2 was constructed by adding a short sequence at the 5’ end of CP1 or CP2, respectively, and the new E-CP1 or E-CP2 primer was labelled at the 5’ end with a fluorophore and in the middle with a dark quencher. The restriction endonuclease Nb.BsrDI specifically recognized the short sequence and digested the newly synthesized double-stranded terminal sequences (5’ end short sequences and their complementary sequences, which released the quenching, resulting on a gain of fluorescence signal. Thus, the ET-MCDA allowed real-time detection of single or multiple targets in only a single reaction, and the positive results were observed in as short as 12 minutes, detecting down to 3.125 fg of genomic DNA per tube. Moreover, the analytical specificity and the practical application of the ET-MCDA were also successfully evaluated in this study. Here we provided the details on the novel ET-MCDA technique and expounded the basic ET-MCDA amplification mechanism.

Multiplex, Rapid, and Sensitive Isothermal Detection of Nucleic-Acid Sequence by Endonuclease Restriction-Mediated Real-Time Multiple Cross Displacement Amplification.

Science.gov (United States)

Wang, Yi; Wang, Yan; Zhang, Lu; Liu, Dongxin; Luo, Lijuan; Li, Hua; Cao, Xiaolong; Liu, Kai; Xu, Jianguo; Ye, Changyun

2016-01-01

We have devised a novel isothermal amplification technology, termed endonuclease restriction-mediated real-time multiple cross displacement amplification (ET-MCDA), which facilitated multiplex, rapid, specific and sensitive detection of nucleic-acid sequences at a constant temperature. The ET-MCDA integrated multiple cross displacement amplification strategy, restriction endonuclease cleavage and real-time fluorescence detection technique. In the ET-MCDA system, the functional cross primer E-CP1 or E-CP2 was constructed by adding a short sequence at the 5' end of CP1 or CP2, respectively, and the new E-CP1 or E-CP2 primer was labeled at the 5' end with a fluorophore and in the middle with a dark quencher. The restriction endonuclease Nb.BsrDI specifically recognized the short sequence and digested the newly synthesized double-stranded terminal sequences (5' end short sequences and their complementary sequences), which released the quenching, resulting on a gain of fluorescence signal. Thus, the ET-MCDA allowed real-time detection of single or multiple targets in only a single reaction, and the positive results were observed in as short as 12 min, detecting down to 3.125 fg of genomic DNA per tube. Moreover, the analytical specificity and the practical application of the ET-MCDA were also successfully evaluated in this study. Here, we provided the details on the novel ET-MCDA technique and expounded the basic ET-MCDA amplification mechanism.

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

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.

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...

Increased centrosome amplification in aged stem cells of the Drosophila midgut

International Nuclear Information System (INIS)

Park, Joung-Sun; Pyo, Jung-Hoon; Na, Hyun-Jin; Jeon, Ho-Jun; Kim, Young-Shin; Arking, Robert; Yoo, Mi-Ae

2014-01-01

Highlights: • Increased centrosome amplification in ISCs of aged Drosophila midguts. • Increased centrosome amplification in ISCs of oxidative stressed Drosophila midguts. • Increased centrosome amplification in ISCs by overexpression of PVR, EGFR, and AKT. • Supernumerary centrosomes can be responsible for abnormal ISC polyploid cells. • Supernumerary centrosomes can be a useful marker for aging stem cells. - Abstract: Age-related changes in long-lived tissue-resident stem cells may be tightly linked to aging and age-related diseases such as cancer. Centrosomes play key roles in cell proliferation, differentiation and migration. Supernumerary centrosomes are known to be an early event in tumorigenesis and senescence. However, the age-related changes of centrosome duplication in tissue-resident stem cells in vivo remain unknown. Here, using anti-γ-tubulin and anti-PH3, we analyzed mitotic intestinal stem cells with supernumerary centrosomes in the adult Drosophila midgut, which may be a versatile model system for stem cell biology. The results showed increased centrosome amplification in intestinal stem cells of aged and oxidatively stressed Drosophila midguts. Increased centrosome amplification was detected by overexpression of PVR, EGFR, and AKT in intestinal stem cells/enteroblasts, known to mimic age-related changes including hyperproliferation of intestinal stem cells and hyperplasia in the midgut. Our data show the first direct evidence for the age-related increase of centrosome amplification in intestinal stem cells and suggest that the Drosophila midgut is an excellent model for studying molecular mechanisms underlying centrosome amplification in aging adult stem cells in vivo

Increased centrosome amplification in aged stem cells of the Drosophila midgut

Energy Technology Data Exchange (ETDEWEB)

Park, Joung-Sun; Pyo, Jung-Hoon; Na, Hyun-Jin; Jeon, Ho-Jun; Kim, Young-Shin [Department of Molecular Biology, Pusan National University, Busan 609-735 (Korea, Republic of); Arking, Robert, E-mail: aa2210@wayne.edu [Department of Biological Sciences, Wayne State University, Detroit, MI 48202 (United States); Yoo, Mi-Ae, E-mail: mayoo@pusan.ac.kr [Department of Molecular Biology, Pusan National University, Busan 609-735 (Korea, Republic of)

2014-07-25

Highlights: • Increased centrosome amplification in ISCs of aged Drosophila midguts. • Increased centrosome amplification in ISCs of oxidative stressed Drosophila midguts. • Increased centrosome amplification in ISCs by overexpression of PVR, EGFR, and AKT. • Supernumerary centrosomes can be responsible for abnormal ISC polyploid cells. • Supernumerary centrosomes can be a useful marker for aging stem cells. - Abstract: Age-related changes in long-lived tissue-resident stem cells may be tightly linked to aging and age-related diseases such as cancer. Centrosomes play key roles in cell proliferation, differentiation and migration. Supernumerary centrosomes are known to be an early event in tumorigenesis and senescence. However, the age-related changes of centrosome duplication in tissue-resident stem cells in vivo remain unknown. Here, using anti-γ-tubulin and anti-PH3, we analyzed mitotic intestinal stem cells with supernumerary centrosomes in the adult Drosophila midgut, which may be a versatile model system for stem cell biology. The results showed increased centrosome amplification in intestinal stem cells of aged and oxidatively stressed Drosophila midguts. Increased centrosome amplification was detected by overexpression of PVR, EGFR, and AKT in intestinal stem cells/enteroblasts, known to mimic age-related changes including hyperproliferation of intestinal stem cells and hyperplasia in the midgut. Our data show the first direct evidence for the age-related increase of centrosome amplification in intestinal stem cells and suggest that the Drosophila midgut is an excellent model for studying molecular mechanisms underlying centrosome amplification in aging adult stem cells in vivo.

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.

Acceleration, current amplification and emittance in MBE-4, an experimental beam induction linear accelerator for heavy ions

International Nuclear Information System (INIS)

Warwick, A.I.; Gough, D.E.; Keefe, D.; Meuth, H.

1988-10-01

We report on the implementation of a second schedule of acceleration and current amplification in MBE-4. Control of the beam current within the bunch is improved over that in the first schedule by the addition of several small amplitude induction pulsers to compensate for acceleration errors and to control the ends of the bunch. Measurements of the longitudinal and transverse emittance are presented. 5 refs., 3 figs., 1 tab

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.

Empirical Site Amplification Factors Incorporating Soil Nonlinearity in Taiwan

Science.gov (United States)

Kuo, C. H.; Chung, C. H.; Che-Min, L.; Huang, J. Y.; Wen, K. L.

2017-12-01

Characteristics of site amplifications caused by both crustal and subduction earthquakes are important in Taiwan. For example, seismic waves were amplified and led to significant building damages in the Taipei Basin by the 1986 Hualien offshore (subduction interface) and the 1999 Chi-Chi earthquakes (crustal), for which the epicentral distances were about 100 km. To understand local site amplifications in Taiwan, empirical site amplification factors for horizontal ground motions are studied using recently constructed strong motion and site databases for the free-field TSMIP stations in Taiwan. Records of large magnitude earthquakes of ML larger than six from 1994 to 2014 were selected for this study. Site amplification factors at site conditions with Vs30 of 120 m/s to 1500 m/s and base accelerations up to 0.7g were inferred from intensity ratios of station pairs within specific distances. The reference site condition is assumed as Vs30 of 760 m/s (B/C boundary). Preliminary results indicate: 1. Soil nonlinearity is more obviously at short periods (PGA, Sa0.3) than long periods (PGV, Sa1.0). 2. Soil nonlinearity is significant for stations belong to site classes of B, C, D, and E in Taiwan. 3. Effect of station-pair distance is seen at short periods (PGA and Sa0.3). 4. No significant different is found in site amplifications of crustal and subduction earthquakes. The result could be a reference for the Fa and Fv in Taiwan's building code.

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....

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....

Radiosensitivity and TP 53, EGFR amplification and LOH10 analysis of primary glioma cell cultures

International Nuclear Information System (INIS)

Gerlach, B.; Harder, A.H.; Slotman, B.J.; Sminia, P.; Hulsebos, T.J.M.; Leenstra, S.; Peter Vandertop, W.; Hartmann, K.A.

2002-01-01

Aim: Determination of in-vitro radiosensitivity and genetic alterations of cell cultures derived from human glioma biopsy tissue and established glioma cell lines. Material and Methods: Fresh brain tumor specimens of six patients were processed to early passage cell cultures. In addition the cell lines D 384 and Gli 6 were used. Cell cultures were irradiated with doses from 2 to 10 Gy. Following irradiation, cell survival was determined by clonogenic assay and survival curves were generated. The surviving fractions after 2 Gy (SF2) and 4 Gy (SF4) were used as radiosensitivity parameters. Genetic analysis included determination of the mutational and loss of heterozygosity (LOH) status of TP 53 (exons 5-8), the LOH 10- and epidermal growth factor receptor gene (EGFR) amplification status. Results: The SF2 and SF4 values ranged from 0.54 to 0.88 (mean: 0.70) and from 0.13 to 0.52 (mean: 0.32), respectively. Genetic alterations were found in the Gli 6 cell line and in two primary cell cultures. The genetic profile of Gli 6 showed LOH but no TP 53 mutation, complete LOH 10 and no EGFR amplification. The VU 15 cell culture showed TP 53 mutation but no LOH 10 or EGFR amplification, while VU 24 showed incomplete LOH 10, EGFR amplification and no TP 53 mutation. In the other four cell cultures and D 384 cell line no genetic alterations were diagnosed. Histopathological classification of glioblastoma multiforme and/or genetic alterations resulted in lower radiosensitivity. Conclusion: In this small series of early passage glioma cell cultures low radiosensitivity and alterations in cell regulatory genes were seen. Further testing of biological behavior in larger series of patient-derived material is ongoing. (orig.)

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)

Laser light triggers increased Raman amplification in the regime of nonlinear Landau damping

International Nuclear Information System (INIS)

Depierreux, S.; Goyon, C.; Masson-Laborde, P.E.; Yahia, V.; Loisel, G.; Labaune, C.

2014-01-01

Stimulated Raman backscattering (SRS) has many unwanted effects in megajoule-scale inertially confined fusion (ICF) plasmas. Moreover, attempts to harness SRS to amplify short laser pulses through backward Raman amplification have achieved limited success. In high temperature fusion plasmas, SRS usually occurs in a kinetic regime where the nonlinear response of the Langmuir wave to the laser drive and its host of complicating factors make it difficult to predict the degree of amplification that can be achieved under given experimental conditions. Here we present experimental evidence of reduced Landau damping with increasing Langmuir wave amplitude and determine its effects on Raman amplification. The threshold for trapping effects to influence the amplification is shown to be very low. Above threshold, the complex SRS dynamics results in increased amplification factors, which partly explains previous ICF experiments. These insights could aid the development of more efficient backward Raman amplification schemes in this regime. (authors)

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

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

Multi-chamber nucleic acid amplification and detection device

Science.gov (United States)

Dugan, Lawrence

2017-10-25

A nucleic acid amplification and detection device includes an amplification cartridge with a plurality of reaction chambers for containing an amplification reagent and a visual detection reagent, and a plurality of optically transparent view ports for viewing inside the reaction chambers. The cartridge also includes a sample receiving port which is adapted to receive a fluid sample and fluidically connected to distribute the fluid sample to the reaction chamber, and in one embodiment, a plunger is carried by the cartridge for occluding fluidic communication to the reaction chambers. The device also includes a heating apparatus having a heating element which is activated by controller to generate heat when a trigger event is detected. The heating apparatus includes a cartridge-mounting section which positioned a cartridge in thermal communication with the heating element so that visual changes to the contents of the reaction chambers are viewable through the view ports.

Plasmon enhanced light amplification in metal–insulator–metal waveguides with gain

International Nuclear Information System (INIS)

Zhong, Xiao-Lan; Li, Zhi-Yuan

2012-01-01

In this paper we study the loss compensation and light amplification properties of metal–insulator–metal (MIM) waveguides that are doped with gain material in the dielectric core. An analytical approach based on Maxwell’s equations is developed to evaluate quantitatively the influence of the gain coefficient on the loss compensation and light amplification efficiencies of the waveguide under different values of the waveguide width and working wavelengths. The analytical results agree excellently with all-numerical calculations that directly solve Maxwell’s equations. The results show that the light amplification efficiency obeys a strict linear relationship with the gain coefficient, and MIM waveguides with narrower widths and under shorter wavelengths have better efficiencies. In addition, the MIM waveguides have higher light amplification efficiencies than usual dielectric waveguides, which suggests a very positive role of the plasmonic structure in enhancing the light amplification when gain is introduced. These loss and gain behaviors can be well explained by looking at the modal profile of each transport mode and the corresponding light energy confinement effect and slow light effect. (paper)

Signal processing method for Johnson noise thermometry

International Nuclear Information System (INIS)

Hwang, I. G.; Moon, B. S.; Kinser, Rpger

2003-01-01

The development of Johnson Noise Thermometry requires a high sensitive preamplifier circuit to pick up the temperature-related noise on the sensing element. However, the random noise generated in this amplification circuit causes a significant erroneous influence to the measurement. This paper describes signal processing mechanism of the Johnson Noise Thermometry system which is underway of development in collaboration between KAERI and ORNL. It adopts two identical amplifier channels and utilizes a digital signal processing technique to remove the independent noise of each channel. The CPSD(Cross Power Spectral Density) function is used to cancel the independent noise and the differentiation of narrow or single frequency peak from the CPSD data separates the common mode electromagnetic interference noise

Amplification of the Luminescence Response in Organic Materials Exposed to Ionizing Radiation

International Nuclear Information System (INIS)

Michel, M.; Rocha, L.; Hamel, M.; Normand, S.

2013-06-01

Polymer-based scintillators present interesting features for the field of ionizing radiation detection, related to the high sensitivity of fluorescence techniques coupled to the manufacturing advantages of such materials. Organic materials can indeed be manufactured into large sensing areas with different geometrical conformations through low-cost fabrication techniques. While results herein presented focus on liquids, the same phenomena would occur in solid samples. Widely used for sensing applications because of its high sensitivity, fluorescence has yet been further improved using technologies yielded by research in photonics. It has already been shown that the use of nano-structuring for sensing applications enables previously unattained sensitivities. Herein we propose a technique based on the manipulation of light using nano-structuring of the detection medium in order to enable the amplification of the sensitive material emission. This amplification of the luminescence signal is aimed at reducing the detection limit of low-energy beta emitters such as tritium, well-known issue of major importance. The first step of our study, presented here, consists in demonstrating the ability of well-known scintillators to emit in laser regime when optically excited in a Distributed Feedback scheme. They are, to our knowledge, the first of their kind. The technique here presented, being usable whatever the sample maximum emission wavelength, should also enable a simplification of the devices based on scintillators. (authors)