Sample records for gain amplification due

  1. Gain-phase modulation in chirped-pulse amplification

    NASA Astrophysics Data System (ADS)

    Shen, Yijie; Gao, Gan; Meng, Yuan; Fu, Xing; Gong, Mali

    2017-10-01

    The cross-modulation between the gain and chirped phase in chirped-pulse amplification (CPA) is theoretically and experimentally demonstrated. We propose a gain-phase coupled nonlinear Schrödinger equation (GPC-NLSE) for solving chirped-pulse propagation in a nonlinear gain medium involved in the gain-phase modulation (GPM) process. With the GPC-NLSE, the space-time-frequency-dependent gain, chirped phase, pulse, and spectrum evolutions can be precisely calculated. Moreover, a short-length high-gain Yb-doped fiber CPA experiment is presented in which a self-steepening distortion of the seed pulse is automatically compensated after amplification. This phenomenon can be explained by the GPM theory whereas conventional models cannot. The experimental results for the temporal and spectral intensities show excellent agreement with our theory. Our GPM theory paves the way for further investigations of the finer structures of the pulse and spectrum in CPA systems.

  2. Modeling of Semiconductor Optical Amplifier Gain Characteristics for Amplification and Switching

    NASA Astrophysics Data System (ADS)

    Mahad, Farah Diana; Sahmah, Abu; Supa'at, M.; Idrus, Sevia Mahdaliza; Forsyth, David

    2011-05-01

    The Semiconductor Optical Amplifier (SOA) is presently commonly used as a booster or pre-amplifier in some communication networks. However, SOAs are also a strong candidate for utilization as multi-functional elements in future all-optical switching, regeneration and also wavelength conversion schemes. With this in mind, the purpose of this paper is to simulate the performance of the SOA for improved amplification and switching functions. The SOA is modeled and simulated using OptSim software. In order to verify the simulated results, a MATLAB mathematical model is also used to aid the design of the SOA. Using the model, the gain difference between simulated and mathematical results in the unsaturated region is <1dB. The mathematical analysis is in good agreement with the simulation result, with only a small offset due to inherent software limitations in matching the gain dynamics of the SOA.

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

    PubMed Central

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

    2013-01-01

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

  4. An ultra-high gain and efficient amplifier based on Raman amplification in plasma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vieux, G.; Cipiccia, S.; Grant, D. W.

    Raman amplification arising from the excitation of a density echelon in plasma could lead to amplifiers that significantly exceed current power limits of conventional laser media. Here we show that 1–100 J pump pulses can amplify picojoule seed pulses to nearly joule level. The extremely high gain also leads to significant amplification of backscattered radiation from “noise”, arising from stochastic plasma fluctuations that competes with externally injected seed pulses, which are amplified to similar levels at the highest pump energies. The pump energy is scattered into the seed at an oblique angle with 14 J sr -1, and net gainsmore » of more than eight orders of magnitude. The maximum gain coefficient, of 180 cm -1, exceeds high-power solid-state amplifying media by orders of magnitude. The observation of a minimum of 640 J sr -1 directly backscattered from noise, corresponding to ≈10% of the pump energy in the observation solid angle, implies potential overall efficiencies greater than 10%.« less

  5. An ultra-high gain and efficient amplifier based on Raman amplification in plasma

    DOE PAGES

    Vieux, G.; Cipiccia, S.; Grant, D. W.; ...

    2017-05-25

    Raman amplification arising from the excitation of a density echelon in plasma could lead to amplifiers that significantly exceed current power limits of conventional laser media. Here we show that 1–100 J pump pulses can amplify picojoule seed pulses to nearly joule level. The extremely high gain also leads to significant amplification of backscattered radiation from “noise”, arising from stochastic plasma fluctuations that competes with externally injected seed pulses, which are amplified to similar levels at the highest pump energies. The pump energy is scattered into the seed at an oblique angle with 14 J sr -1, and net gainsmore » of more than eight orders of magnitude. The maximum gain coefficient, of 180 cm -1, exceeds high-power solid-state amplifying media by orders of magnitude. The observation of a minimum of 640 J sr -1 directly backscattered from noise, corresponding to ≈10% of the pump energy in the observation solid angle, implies potential overall efficiencies greater than 10%.« less

  6. Biomaterials in light amplification

    NASA Astrophysics Data System (ADS)

    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

  7. Discovery of natural gain amplification in the 10-micrometer carbon dioxide laser bands on Mars - A natural laser

    NASA Technical Reports Server (NTRS)

    Mumma, M. J.; Buhl, D.; Chin, G.; Deming, D.; Espenak, F.; Kostiuk, T.; Zipoy, D.

    1981-01-01

    Fully resolved intensity profiles of various lines in the carbon dioxide band at 10.4 micrometers have been measured on Mars with an infrared heterodyne spectrometer. Analysis of the line shapes shows that the Mars atmosphere exhibits positive gain in these lines. The detection of natural optical gain amplification enables identification of these lines as a definite natural laser.

  8. Sensory gain control (amplification) as a mechanism of selective attention: electrophysiological and neuroimaging evidence.

    PubMed Central

    Hillyard, S A; Vogel, E K; Luck, S J

    1998-01-01

    Both physiological and behavioral studies have suggested that stimulus-driven neural activity in the sensory pathways can be modulated in amplitude during selective attention. Recordings of event-related brain potentials indicate that such sensory gain control or amplification processes play an important role in visual-spatial attention. Combined event-related brain potential and neuroimaging experiments provide strong evidence that attentional gain control operates at an early stage of visual processing in extrastriate cortical areas. These data support early selection theories of attention and provide a basis for distinguishing between separate mechanisms of attentional suppression (of unattended inputs) and attentional facilitation (of attended inputs). PMID:9770220

  9. Phase-preserving wavefront amplification at 590 nm by stimulated Raman scattering

    NASA Astrophysics Data System (ADS)

    Wick, D. V.; Gruneisen, M. T.; Peterson, P. R.

    1998-03-01

    This paper presents an experimental demonstration of high-gain optical-wavefront amplification by stimulated Raman scattering near the D 1 resonance in atomic sodium vapor. Single-pass weak-field gain of nearly 400 is achieved with only 800 mW of pump power. Through judicious focusing, the weak wavefront is confined to the central region of the focused pump wave where saturation of the dispersion profile minimizes phase distortions due to self-focusing effects. Phase-preserving amplification is demonstrated by interferometric measurements of an amplified TEM 00 wavefront.

  10. Discovery of natural gain amplification in the 10 muon m CO2 laser bands on Mars: The first definite natural laser

    NASA Technical Reports Server (NTRS)

    Mumma, M.; Buhl, D.; Chin, G.; Deming, D.; Espenak, F.; Kostiuk, T.; Zipoy, D.

    1980-01-01

    Fully resolved intensity profiles of various lines in the CO2 bands at 9.4 micrometers and 10.4 micrometers were measured on Mars using an infrared heterodyne spectrometer. Analysis of the line shapes shows that the Mars atmosphere exhibits positive gain on these lines, providing the first definite detection of natural optical gain amplification and enabling identification of these lines as the first definite natural laser ever discovered.

  11. Optical back propagation for fiber optic networks with hybrid EDFA Raman amplification.

    PubMed

    Liang, Xiaojun; Kumar, Shiva

    2017-03-06

    We have investigated an optical back propagation (OBP) method to compensate for propagation impairments in fiber optic networks with lumped Erbium doped fiber amplifier (EDFA) and/or distributed Raman amplification. An OBP module consists of an optical phase conjugator (OPC), optical amplifiers and dispersion varying fibers (DVFs). We derived a semi-analytical expression that calculates the dispersion profile of DVF. The OBP module acts as a nonlinear filter that fully compensates for the nonlinear distortions due to signal propagation in a transmission fiber, and is applicable for fiber optic networks with reconfigurable optical add-drop multiplexers (ROADMs). We studied a wavelength division multiplexing (WDM) network with 3000 km transmission distance and 64-quadrature amplitude modulation (QAM) modulation. OBP brings 5.8 dB, 5.9 dB and 6.1 dB Q-factor gains over linear compensation for systems with full EDFA amplification, hybrid EDFA/Raman amplification, and full Raman amplification, respectively. In contrast, digital back propagation (DBP) or OPC-only systems provide only 0.8 ~ 1.5 dB Q-factor gains.

  12. Single-exciton optical gain in semiconductor nanocrystals.

    PubMed

    Klimov, Victor I; Ivanov, Sergei A; Nanda, Jagjit; Achermann, Marc; Bezel, Ilya; McGuire, John A; Piryatinski, Andrei

    2007-05-24

    Nanocrystal quantum dots have favourable light-emitting properties. They show photoluminescence with high quantum yields, and their emission colours depend on the nanocrystal size--owing to the quantum-confinement effect--and are therefore tunable. However, nanocrystals are difficult to use in optical amplification and lasing. Because of an almost exact balance between absorption and stimulated emission in nanoparticles excited with single electron-hole pairs (excitons), optical gain can only occur in nanocrystals that contain at least two excitons. A complication associated with this multiexcitonic nature of light amplification is fast optical-gain decay induced by non-radiative Auger recombination, a process in which one exciton recombines by transferring its energy to another. Here we demonstrate a practical approach for obtaining optical gain in the single-exciton regime that eliminates the problem of Auger decay. Specifically, we develop core/shell hetero-nanocrystals engineered in such a way as to spatially separate electrons and holes between the core and the shell (type-II heterostructures). The resulting imbalance between negative and positive charges produces a strong local electric field, which induces a giant ( approximately 100 meV or greater) transient Stark shift of the absorption spectrum with respect to the luminescence line of singly excited nanocrystals. This effect breaks the exact balance between absorption and stimulated emission, and allows us to demonstrate optical amplification due to single excitons.

  13. Parametric amplification in MoS2 drum resonator.

    PubMed

    Prasad, Parmeshwar; Arora, Nishta; Naik, A K

    2017-11-30

    Parametric amplification is widely used in diverse areas from optics to electronic circuits to enhance low level signals by varying relevant system parameters. Parametric amplification has also been performed in several micro-nano resonators including nano-electromechanical system (NEMS) resonators based on a two-dimensional (2D) material. Here, we report the enhancement of mechanical response in a MoS 2 drum resonator using degenerate parametric amplification. We use parametric pumping to modulate the spring constant of the MoS 2 resonator and achieve a 10 dB amplitude gain. We also demonstrate quality factor enhancement in the resonator with parametric amplification. We investigate the effect of cubic nonlinearity on parametric amplification and show that it limits the gain of the mechanical resonator. Amplifying ultra-small displacements at room temperature and understanding the limitations of the amplification in these devices is key for using these devices for practical applications.

  14. Genomic gains and losses are similar in genetic and histologic subsets of rhabdomyosarcoma, whereas amplification predominates in embryonal with anaplasia and alveolar subtypes.

    PubMed

    Bridge, Julia A; Liu, Jian; Qualman, Stephen J; Suijkerbuijk, Ron; Wenger, Gail; Zhang, Ji; Wan, Xiaoying; Baker, K Scott; Sorensen, Poul; Barr, Frederic G

    2002-03-01

    In this investigation, we selected PAX3/FKHR and PAX7/FKHR fusion transcript-positive and -negative alveolar rhabdomyosarcomas (ARMSs) and embryonal rhabdomyosarcomas (ERMSs) with and without anaplastic features, to ascertain genomic imbalance differences and/or similarities within these histopathologic and genetic rhabdomyosarcoma (RMS) variants. Comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) studies were performed on 45 rhabdomyosarcoma specimens consisting of 23 ARMSs and 22 ERMSs (12 ERMS cases were included from an earlier study). The anaplastic variant of RMS has not previously been subjected to CGH analysis. Overall, the most prominent imbalances were gain of chromosomes or chromosomal regions 2/2q (40%), 7/7q (31%), 8/8p (53%), 11/11q (31%), 12q13-15 (49%), 13q14 (22%), and 20/20p (31%), and loss of 1p36 (27%), 3p14-21 (22%), 9q21-22 (33%), 10q22-qter (18%), 16q (27%), 17p (22%), and 22 (22%). These gains and losses were distributed equally between ARMS and ERMS histologic subtypes (excluding 7/7q and 11/11q gain that were observed chiefly in ERMS), demonstrating that these entities are similar with respect to recurrent genomic imbalances. Moreover, genomic imbalances were also evenly distributed among the ARMS fusion transcript subtypes, providing evidence for a genetic kinship despite the absence of a fusion transcript in some cases. Genomic amplification was detected in 26% and 23% of the ARMS and ERMS cases, respectively (with nearly all of the latter subset exhibiting anaplastic features). One amplicon, involving 15q25-26, corresponds to the locus of the insulin-like growth factor type I receptor (IGF1R) gene. Amplification of IGF1R was confirmed molecularly in the cases exhibiting a 15q25-26 amplicon. In summary, these results indicate that genomic gains and losses involve alike chromosomes with similar frequencies within the histopathologic and genetic subtypes of rhabdomyosarcoma, that genomic amplification is

  15. High peak-power kilohertz laser system employing single-stage multi-pass amplification

    DOEpatents

    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.

  16. Organic field effect transistor with ultra high amplification

    NASA Astrophysics Data System (ADS)

    Torricelli, Fabrizio

    2016-09-01

    High-gain transistors are essential for the large-scale circuit integration, high-sensitivity sensors and signal amplification in sensing systems. Unfortunately, organic field-effect transistors show limited gain, usually of the order of tens, because of the large contact resistance and channel-length modulation. Here we show organic transistors fabricated on plastic foils enabling unipolar amplifiers with ultra-gain. The proposed approach is general and opens up new opportunities for ultra-large signal amplification in organic circuits and sensors.

  17. Ultra-wideband and high-gain parametric amplification in telecom wavelengths with an optimally mode-matched PPLN waveguide.

    PubMed

    Sua, Yong Meng; Chen, Jia-Yang; Huang, Yu-Ping

    2018-06-15

    We report a wideband optical parametric amplification (OPA) over 14 THz covering telecom S, C, and L bands with observed maximum parametric gain of 38.3 dB. The OPA is realized through cascaded second-harmonic generation and difference-frequency generation (cSHG-DFG) in a 2 cm periodically poled LiNbO 3 (PPLN) waveguide. With tailored cross section geometry, the waveguide is optimally mode matched for efficient cascaded nonlinear wave mixing. We also identify and study the effect of competing nonlinear processes in this cSHG-DFG configuration.

  18. Graphene Distributed Amplifiers: Generating Desirable Gain for Graphene Field-Effect Transistors

    PubMed Central

    Lyu, Hongming; Lu, Qi; Huang, Yilin; Ma, Teng; Zhang, Jinyu; Wu, Xiaoming; Yu, Zhiping; Ren, Wencai; Cheng, Hui-Ming; Wu, Huaqiang; Qian, He

    2015-01-01

    Ever since its discovery, graphene bears great expectations in high frequency electronics due to its irreplaceably high carrier mobility. However, it has long been blamed for the weakness in generating gains, which seriously limits its pace of development. Distributed amplification, on the other hand, has successfully been used in conventional semiconductors to increase the amplifiers’ gain-bandwidth product. In this paper, distributed amplification is first applied to graphene. Transmission lines phase-synchronize paralleled graphene field-effect transistors (GFETs), combining the gain of each stage in an additive manner. Simulations were based on fabricated GFETs whose fT ranged from 8.5 GHz to 10.5 GHz and fmax from 12 GHz to 14 GHz. A simulated four-stage graphene distributed amplifier achieved up to 4 dB gain and 3.5 GHz bandwidth, which could be realized with future IC processes. A PCB level graphene distributed amplifier was fabricated as a proof of circuit concept. PMID:26634442

  19. 2.5 TW, two-cycle IR laser pulses via frequency domain optical parametric amplification.

    PubMed

    Gruson, V; Ernotte, G; Lassonde, P; Laramée, A; Bionta, M R; Chaker, M; Di Mauro, L; Corkum, P B; Ibrahim, H; Schmidt, B E; Legaré, F

    2017-10-30

    Broadband optical parametric amplification in the IR region has reached a new milestone through the use of a non-collinear Frequency domain Optical Parametric Amplification system. We report a laser source delivering 11.6 fs pulses with 30 mJ of energy at a central wavelength of 1.8 μm at 10 Hz repetition rate corresponding to a peak power of 2.5 TW. The peak power scaling is accompanied by a pulse shortening of about 20% upon amplification due to the spectral reshaping with higher gain in the spectral wings. This source paves the way for high flux soft X-ray pulses and IR-driven laser wakefield acceleration.

  20. Envelope matching for enhanced backward Raman amplification by using self-ionizing plasmas

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Z. M.; Zhang, B.; Hong, W.

    2014-12-15

    Backward Raman amplification (BRA) in plasmas has been promoted as a means for generating ultrapowerful laser pulses. For the purpose of achieving the maximum intensities over the shortest distances, an envelope matching between the seed pulse and the amplification gain is required, i.e., the seed pulse propagates at the same velocity with the gain such that the peak of the seed pulse can always enjoy the maximum gain. However, such an envelope matching is absent in traditional BRA because in the latter the amplification gain propagates at superluminous velocity while the seed pulse propagates at the group velocity, which ismore » less than the speed of light. It is shown here that, by using self-ionizing plasmas, the speed of the amplification gain can be well reduced to reach the envelope matching regime. This results in a favorable BRA process, in which higher saturated intensity, shorter interaction length and higher energy-transfer efficiency are achieved.« less

  1. Long-range parametric amplification of THz wave with absorption loss exceeding parametric gain.

    PubMed

    Wang, Tsong-Dong; Huang, Yen-Chieh; Chuang, Ming-Yun; Lin, Yen-Hou; Lee, Ching-Han; Lin, Yen-Yin; Lin, Fan-Yi; Kitaeva, Galiya Kh

    2013-01-28

    Optical parametric mixing is a popular scheme to generate an idler wave at THz frequencies, although the THz wave is often absorbing in the nonlinear optical material. It is widely suggested that the useful material length for co-directional parametric mixing with strong THz-wave absorption is comparable to the THz-wave absorption length in the material. Here we show that, even in the limit of the absorption loss exceeding parametric gain, the THz idler wave can grows monotonically from optical parametric amplification over a much longer distance in a nonlinear optical material until pump depletion. The coherent production of the non-absorbing signal wave can assist the growth of the highly absorbing idler wave. We also show that, for the case of an equal input pump and signal in difference frequency generation, the quick saturation of the THz idler wave predicted from a much simplified and yet popular plane-wave model fails when fast diffraction of the THz wave from the co-propagating optical mixing waves is considered.

  2. Optomechanical transistor with mechanical gain

    NASA Astrophysics Data System (ADS)

    Zhang, X. Z.; Tian, Lin; Li, Yong

    2018-04-01

    We study an optomechanical transistor, where an input field can be transferred and amplified unidirectionally in a cyclic three-mode optomechanical system. In this system, the mechanical resonator is coupled simultaneously to two cavity modes. We show that it only requires a finite mechanical gain to achieve the nonreciprocal amplification. Here the nonreciprocity is caused by the phase difference between the linearized optomechanical couplings that breaks the time-reversal symmetry of this system. The amplification arises from the mechanical gain, which provides an effective phonon bath that pumps the mechanical mode coherently. This effect is analogous to the stimulated emission of atoms, where the probe field can be amplified when its frequency is in resonance with that of the anti-Stokes transition. We show that by choosing optimal parameters, this optomechanical transistor can reach perfect unidirectionality accompanied with strong amplification. In addition, the presence of the mechanical gain can result in ultralong delay in the phase of the probe field, which provides an alternative to controlling light transport in optomechanical systems.

  3. Cycling excitation process: An ultra efficient and quiet signal amplification mechanism in semiconductor

    NASA Astrophysics Data System (ADS)

    Liu, Yu-Hsin; Yan, Lujiang; Zhang, Alex Ce; Hall, David; Niaz, Iftikhar Ahmad; Zhou, Yuchun; Sham, L. J.; Lo, Yu-Hwa

    2015-08-01

    Signal amplification, performed by transistor amplifiers with its merit rated by the efficiency and noise characteristics, is ubiquitous in all electronic systems. Because of transistor thermal noise, an intrinsic signal amplification mechanism, impact ionization was sought after to complement the limits of transistor amplifiers. However, due to the high operation voltage (30-200 V typically), low power efficiency, limited scalability, and, above all, rapidly increasing excess noise with amplification factor, impact ionization has been out of favor for most electronic systems except for a few applications such as avalanche photodetectors and single-photon Geiger detectors. Here, we report an internal signal amplification mechanism based on the principle of the phonon-assisted cycling excitation process (CEP). Si devices using this concept show ultrahigh gain, low operation voltage, CMOS compatibility, and, above all, quantum limit noise performance that is 30 times lower than devices using impact ionization. Established on a unique physical effect of attractive properties, CEP-based devices can potentially revolutionize the fields of semiconductor electronics.

  4. Questioning cochlear amplification

    NASA Astrophysics Data System (ADS)

    van der Heijden, Marcel; Versteegh, Corstiaen P. C.

    2015-12-01

    Thirty years ago it was hypothesized that motile processes inject mechanical energy into cochlear traveling waves. This mechanical amplification, alternatively described as negative damping, is invoked to explain both the sensitivity and the nonlinear compression of cochlear responses. There is a recent trend to present cochlear amplification as an established fact, even though the evidence is at most circumstantial and several thorny problems have remained unresolved. We analyze several of these issues, and present new basilar membrane recordings that allowed us to quantify cochlear energy flow. Specifically, we address the following questions: (1) Does auditory sensitivity require narrowband amplification? (2) Has the "RC problem" (lowpass filtering of outer hair cell receptor potential) been resolved? (3) Can OHC motility improve auditory sensitivity? (4) Is there a net power gain between neighboring locations on the basilar membrane? The analyses indicate that mechanical amplification in the cochlea is neither necessary nor useful, and that realizing it by known forms of motility would reduce sensitivity rather than enhance it. Finally, our experimental data show that the peaking of the traveling wave is realized by focusing the acoustic energy rather than amplifying it. (Abbreviations. BM: basilar membrane; CF: characteristic frequency; IHC: inner hair cell; ME: middle ear; MT; mechanotransducer; OHC: outer hair cell; SPL: sound pressure level.)

  5. Possibility of Recombination Gain Increase in CV Ions at 4.0 nm Via Coherence

    NASA Astrophysics Data System (ADS)

    Luo, Y.; Morozov, A.; Gordon, D.; Sprangle, P.; Svidzinsky, A.; Xia, H.; Scully, M.; Suckewer, S.

    This paper is about the recent experimental results on amplification of the CV line in the "water window" at 4.03 nm from resonance transition to the ground level of He-like ions in recombination scheme. The indication of the amplification of the CV line has been observed when an elongated narrow plasma channel was created, where high intensity 100 fs beams, optimal for creating CV ions in high density plasma, was propagated up to 0.5-0.6 mm. Without channeling the effective plasma length was much shorter and there was no indication of amplification.The large interest in gain generation in He-like ions in the transition to ground state is due to the possibility of applying a recently developed theory of Lasing Without Inversion (LWI) in XUV and X-ray regions to largely increase the gain for such transitions. The presented results of the indication of CV line amplifications are being discussed from the point of view of using LWI as a superradiance gain increase, hence to construct a very compact soft X-ray laser in the "water window".The last part of the paper is related to the application of the ultra-intensive fs plasma laser, which is currently in the process of development by using stimulated Raman backscattering (SRBS) to create a plasma amplifier and compressor, as the pump for compact laser operating in the "water window" and also at shorter wavelengths.

  6. Cycling excitation process: An ultra efficient and quiet signal amplification mechanism in semiconductor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, Yu-Hsin; Yan, Lujiang; Zhang, Alex Ce

    2015-08-03

    Signal amplification, performed by transistor amplifiers with its merit rated by the efficiency and noise characteristics, is ubiquitous in all electronic systems. Because of transistor thermal noise, an intrinsic signal amplification mechanism, impact ionization was sought after to complement the limits of transistor amplifiers. However, due to the high operation voltage (30-200 V typically), low power efficiency, limited scalability, and, above all, rapidly increasing excess noise with amplification factor, impact ionization has been out of favor for most electronic systems except for a few applications such as avalanche photodetectors and single-photon Geiger detectors. Here, we report an internal signal amplification mechanismmore » based on the principle of the phonon-assisted cycling excitation process (CEP). Si devices using this concept show ultrahigh gain, low operation voltage, CMOS compatibility, and, above all, quantum limit noise performance that is 30 times lower than devices using impact ionization. Established on a unique physical effect of attractive properties, CEP-based devices can potentially revolutionize the fields of semiconductor electronics.« less

  7. Assessment of palindromes as platforms for DNA amplification in breast cancer

    PubMed Central

    Guenthoer, Jamie; Diede, Scott J.; Tanaka, Hisashi; Chai, Xiaoyu; Hsu, Li; Tapscott, Stephen J.; Porter, Peggy L.

    2012-01-01

    DNA amplification, particularly of chromosomes 8 and 11, occurs frequently in breast cancer and is a key factor in tumorigenesis, often associated with poor prognosis. The mechanisms involved in the amplification of these regions are not fully understood. Studies from model systems have demonstrated that palindrome formation can be an early step in DNA amplification, most notably seen in the breakage–fusion–bridge (BFB) cycle. Therefore, palindromes might be associated with gene amplicons in breast cancer. To address this possibility, we coupled high-resolution palindrome profiling by the Genome-wide Analysis of Palindrome Formation (GAPF) assay with genome-wide copy-number analyses on a set of breast cancer cell lines and primary tumors to spatially associate palindromes and copy-number gains. We identified GAPF-positive regions distributed nonrandomly throughout cell line and tumor genomes, often in clusters, and associated with copy-number gains. Commonly amplified regions in breast cancer, chromosomes 8q and 11q, had GAPF-positive regions flanking and throughout the copy-number gains. We also identified amplification-associated GAPF-positive regions at similar locations in subsets of breast cancers with similar characteristics (e.g., ERBB2 amplification). These shared positive regions offer the potential to evaluate the utility of palindromes as prognostic markers, particularly in premalignant breast lesions. Our results implicate palindrome formation in the amplification of regions with key roles in breast tumorigenesis, particularly in subsets of breast cancers. PMID:21752925

  8. Dynamical amplification of Arctic and global warming

    NASA Astrophysics Data System (ADS)

    Alekseev, Genrikh; Ivanov, Nikolai; Kharlanenkova, Natalia; Kuzmina, Svetlana; Bobylev, Leonid; Gnatiuk, Natalia; Urazgildeeva, Aleksandra

    2015-04-01

    The Arctic is coupled with global climate system by the atmosphere and ocean circulation that provides a major contribution to the Arctic energy budget. Therefore increase of meridional heat transport under global warming can impact on its Arctic amplification. Contribution of heat transport to the recent warming in the Arctic, Northern Hemisphere and the globe are estimated on base of reanalysis data, global climate model data and proposed special index. It is shown that significant part of linear trend during last four decades in average surface air temperature in these areas can be attributed to dynamical amplification. This attribution keeps until 400 mb height with progressive decreasing. The Arctic warming is amplified also due to an increase of humidity and cloudiness in the Arctic atmosphere that follow meridional transport gain. From October to January the Arctic warming trends are amplified as a result of ice edge retreat from the Siberian and Alaska coast and the heating of expanded volume of sea water. This investigation is supported with RFBR project 15-05-03512.

  9. Directional amplifier in an optomechanical system with optical gain

    NASA Astrophysics Data System (ADS)

    Jiang, Cheng; Song, L. N.; Li, Yong

    2018-05-01

    Directional amplifiers are crucial nonreciprocal devices in both classical and quantum information processing. Here we propose a scheme for realizing a directional amplifier between optical and microwave fields based on an optomechanical system with optical gain, where an active optical cavity and two passive microwave cavities are coupled to a common mechanical resonator via radiation pressure. The two passive cavities are coupled via hopping interaction to facilitate the directional amplification between the active and passive cavities. We obtain the condition of achieving optical directional amplification and find that the direction of amplification can be controlled by the phase differences between the effective optomechanical couplings. The effects of the gain rate of the active cavity and the effective coupling strengths on the maximum gain of the amplifier are discussed. We show that the noise added to this amplifier can be greatly suppressed in the large cooperativity limit.

  10. Seismic loading due to mining: Wave amplification and vibration of structures

    NASA Astrophysics Data System (ADS)

    Lokmane, N.; Semblat, J.-F.; Bonnet, G.; Driad, L.; Duval, A.-M.

    2003-04-01

    A vibration induced by the ground motion, whatever its source is, can in certain cases damage surface structures. The scientific works allowing the analysis of this phenomenon are numerous and well established. However, they generally concern dynamic motion from real earthquakes. The goal of this work is to analyse the impact of shaking induced by mining on the structures located on the surface. The methods allowing to assess the consequences of earthquakes of strong amplitude are well established, when the methodology to estimate the consequences of moderate but frequent dynamic loadings is not well defined. The mining such as the "Houillères de Bassin du Centre et du Midi" (HBCM) involves vibrations which are regularly felt on the surface. An extracting work of coal generates shaking similar to those caused by earthquakes (standard waves and laws of propagation) but of rather low magnitude. On the other hand, their recurrent feature makes the vibrations more harmful. A three-dimensional modeling of standard structure of the site was carried out. The first results show that the fundamental frequencies of this structure are compatible with the amplification measurements carried out on site. The motion amplification in the surface soil layers is then analyzed. The modeling works are performed on the surface soil layers of Gardanne (Provence), where measurements of microtremors were performed. The analysis of H/V spectral ratio (horizontal on vertical component) indeed makes it possible to characterize the fundamental frequencies of the surface soil layers. This experiment also allows to characterize local evolution of amplification induced by the topmost soil layers. The numerical methods we consider to model seismic wave propagation and amplification in the site, is the Boundary Element Methode (BEM) The main advantage of the boundary element method is to get rid of artificial truncations of the mesh (as in Finite Element Method) in the case of infinite medium

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

    NASA Astrophysics Data System (ADS)

    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.

  12. Giant enhancement of reflectance due to the interplay between surface confined wave modes and nonlinear gain in dielectric media.

    PubMed

    Kim, Sangbum; Kim, Kihong

    2017-12-11

    We study theoretically the interplay between the surface confined wave modes and the linear and nonlinear gain of the dielectric layer in the Otto configuration. The surface confined wave modes, such as surface plasmons or waveguide modes, are excited in the dielectric-metal bilayer by obliquely incident p waves. In the purely linear case, we find that the interplay between linear gain and surface confined wave modes can generate a large reflectance peak with its value much greater than 1. As the linear gain parameter increases, the peak appears at smaller incident angles, and the associated modes also change from surface plasmons to waveguide modes. When the nonlinear gain is turned on, the reflectance shows very strong multistability near the incident angles associated with surface confined wave modes. As the nonlinear gain parameter is varied, the reflectance curve undergoes complicated topological changes and sometimes displays separated closed curves. When the nonlinear gain parameter takes an optimally small value, a giant amplification of the reflectance by three orders of magnitude occurs near the incident angle associated with a waveguide mode. We also find that there exists a range of the incident angle where the wave is dissipated rather than amplified even in the presence of gain. We suggest that this can provide the basis for a possible new technology for thermal control in the subwavelength scale.

  13. Brillouin Selective Sideband Amplification of Microwave Photonic Signals

    NASA Technical Reports Server (NTRS)

    Yao, S.

    1997-01-01

    We introduce a powerful Brillouin selective sideband amplification technique and demonstrate its application for achieving gain in photonix signal up- and down- conversions in microwave photonic systems.

  14. Noiseless intensity amplification of repetitive signals by coherent addition using the temporal Talbot effect

    PubMed Central

    Maram, Reza; Van Howe, James; Li, Ming; Azaña, José

    2014-01-01

    Amplification of signal intensity is essential for initiating physical processes, diagnostics, sensing, communications and measurement. During traditional amplification, the signal is amplified by multiplying the signal carriers through an active gain process, requiring the use of an external power source. In addition, the signal is degraded by noise and distortions that typically accompany active gain processes. We show noiseless intensity amplification of repetitive optical pulse waveforms with gain from 2 to ~20 without using active gain. The proposed method uses a dispersion-induced temporal self-imaging (Talbot) effect to redistribute and coherently accumulate energy of the original repetitive waveforms into fewer replica waveforms. In addition, we show how our passive amplifier performs a real-time average of the wave-train to reduce its original noise fluctuation, as well as enhances the extinction ratio of pulses to stand above the noise floor. Our technique is applicable to repetitive waveforms in any spectral region or wave system. PMID:25319207

  15. Study of gain homogeneity and radiation effects of Low Gain Avalanche Pad Detectors

    NASA Astrophysics Data System (ADS)

    Gallrapp, C.; Fernández García, M.; Hidalgo, S.; Mateu, I.; Moll, M.; Otero Ugobono, S.; Pellegrini, G.

    2017-12-01

    Silicon detectors with intrinsic charge amplification implementing a n++-p+-p structure are considered as a sensor technology for future tracking and timing applications in high energy physics experiments. The performance of the intrinsic gain in Low Gain Avalanche Detectors (LGAD) after irradiation is crucial for the characterization of radiation hardness and timing properties in this technology. LGAD devices irradiated with reactor neutrons or 800 MeV protons reaching fluences of 2.3 × 1016 neq/cm2 were characterized using Transient Current Technique (TCT) measurements with red and infra-red laser pulses. Leakage current variations observed in different production lots and within wafers were investigated using Thermally Stimulated Current (TSC). Results showed that the intrinsic charge amplification is reduced with increasing fluence up to 1015 neq/cm2 which is related to an effective acceptor removal. Further relevant issues were charge collection homogeneity across the detector surface and leakage current performance before and after irradiation.

  16. Photon number amplification/duplication through parametric conversion

    NASA Technical Reports Server (NTRS)

    Dariano, G. M.; Macchiavello, C.; Paris, M.

    1993-01-01

    The performance of parametric conversion in achieving number amplification and duplication is analyzed. It is shown that the effective maximum gains G(sub *) remain well below their integer ideal values, even for large signals. Correspondingly, one has output Fano factors F(sub *) which are increasing functions of the input photon number. On the other hand, in the inverse (deamplifier/recombiner) operating mode quasi-ideal gains G(sub *) and small factors F(sub *) approximately equal to 10 percent are obtained. Output noise and non-ideal gains are ascribed to spontaneous parametric emission.

  17. First demonstration of high-order QAM signal amplification in PPLN-based phase sensitive amplifier.

    PubMed

    Umeki, T; Tadanaga, O; Asobe, M; Miyamoto, Y; Takenouchi, H

    2014-02-10

    We demonstrate the phase sensitive amplification of a high-order quadrature amplitude modulation (QAM) signal using non-degenerate parametric amplification in a periodically poled lithium niobate (PPLN) waveguide. The interaction between the pump, signal, and phase-conjugated idler enables us to amplify arbitrary phase components of the signal. The 16QAM signals are amplified without distortion because of the high gain linearity of the PPLN-based phase sensitive amplifier (PSA). Both the phase and amplitude noise reduction capabilities of the PSA are ensured. Phase noise cancellation is achieved by using the interaction with the phase-conjugated idler. A degraded signal-to-noise ratio (SNR) is restored by using the gain difference between a phase-correlated signal-idler pair and uncorrelated excess noise. The applicability of the simultaneous amplification of multi-carrier signals and the amplification of two independent polarization signals are also confirmed with a view to realizing ultra-high spectrally efficient signal amplification.

  18. Mid-infrared Raman amplification and wavelength conversion in dispersion engineered silicon-on-sapphire waveguides

    NASA Astrophysics Data System (ADS)

    Wang, Zhaolu; Liu, Hongjun; Huang, Nan; Sun, Qibing; Li, Xuefeng

    2014-01-01

    Raman amplification based on stimulated Stokes Raman scattering (SSRS) and wavelength conversion based on coherent anti-Stokes Raman scattering (CARS) are theoretically investigated in silicon-on-sapphire (SOS) waveguides in the mid-infrared (IR) region. When the linear phase mismatch Δk is close to zero, the Stokes gain and conversion efficiency drop down quickly due to the effect of parametric gain suppression when the Stokes-pump input ratio is sufficiently large. The Stokes gain increases with the increase of Δk, whereas efficient wavelength conversion needs appropriate Δk under different pump intensities. The conversion efficiency at exact linear phase matching (Δk = 0) is smaller than that at optimal linear phase mismatch by a factor of about 28 dB when the pump intensity is 2 GW cm-2.

  19. Entanglement sensitivity to signal attenuation and amplification

    NASA Astrophysics Data System (ADS)

    Filippov, Sergey N.; Ziman, Mário

    2014-07-01

    We analyze general laws of continuous-variable entanglement dynamics during the deterministic attenuation and amplification of the physical signal carrying the entanglement. These processes are inevitably accompanied by noises, so we find fundamental limitations on noise intensities that destroy entanglement of Gaussian and non-Gaussian input states. The phase-insensitive amplification Φ1⊗Φ2⊗⋯ΦN with the power gain κi≥2 (≈3 dB, i =1,...,N) is shown to destroy entanglement of any N-mode Gaussian state even in the case of quantum-limited performance. In contrast, we demonstrate non-Gaussian states with the energy of a few photons such that their entanglement survives within a wide range of noises beyond quantum-limited performance for any degree of attenuation or gain. We detect entanglement preservation properties of the channel Φ1⊗Φ2, where each mode is deterministically attenuated or amplified. Gaussian states of high energy are shown to be robust to very asymmetric attenuations, whereas non-Gaussian states are at an advantage in the case of symmetric attenuation and general amplification. If Φ1=Φ2, the total noise should not exceed 1/2√κ2+1 to guarantee entanglement preservation.

  20. Reflective Amplification without Population Inversion from a Strongly Driven Superconducting Qubit

    NASA Astrophysics Data System (ADS)

    Wen, P. Y.; Kockum, A. F.; Ian, H.; Chen, J. C.; Nori, F.; Hoi, I.-C.

    2018-02-01

    Amplification of optical or microwave fields is often achieved by strongly driving a medium to induce population inversion such that a weak probe can be amplified through stimulated emission. Here we strongly couple a superconducting qubit, an artificial atom, to the field in a semi-infinite waveguide. When driving the qubit strongly on resonance such that a Mollow triplet appears, we observe a 7% amplitude gain for a weak probe at frequencies in between the triplet. This amplification is not due to population inversion, neither in the bare qubit basis nor in the dressed-state basis, but instead results from a four-photon process that converts energy from the strong drive to the weak probe. We find excellent agreement between the experimental results and numerical simulations without any free fitting parameters. Since our device consists of a single two-level artificial atom, the simplest possible quantum system, it can be viewed as the most fundamental version of a four-wave-mixing parametric amplifier.

  1. Four photon parametric amplification. [in unbiased Josephson junction

    NASA Technical Reports Server (NTRS)

    Parrish, P. T.; Feldman, M. J.; Ohta, H.; Chiao, R. Y.

    1974-01-01

    An analysis is presented describing four-photon parametric amplification in an unbiased Josephson junction. Central to the theory is the model of the Josephson effect as a nonlinear inductance. Linear, small signal analysis is applied to the two-fluid model of the Josephson junction. The gain, gain-bandwidth product, high frequency limit, and effective noise temperature are calculated for a cavity reflection amplifier. The analysis is extended to multiple (series-connected) junctions and subharmonic pumping.

  2. Phase-sensitive, through-amplification with a double-pumped JPC

    NASA Astrophysics Data System (ADS)

    Sliwa, K. M.; Hatridge, M.; Frattini, N. E.; Narla, A.; Shankar, S.; Devoret, M. H.

    The Josephson Parametric Converter (JPC) is now routinely used as a quantum-limited signal processing device for superconducting qubit experiments. The JPC consists of two modes, the signal and the idler, that are coupled by a ring of Josephson junctions that implements a non-degenerate, three-wave mixing process. This device is conventionally operated as either a phase-preserving parametric amplifier, or a coherent frequency converter, by pumping it at the sum or difference of the signal and idler frequencies, respectively. Here we present a novel double-pumping scheme based on theory by Metelmann and Clerk where a coherent conversion process and a gain process are simultaneously imposed between the signal and idler modes. The interference of these two processes results in a phase-sensitive amplifier with only forward gain, and which breaks the traditional gain-bandwidth limit of parametric amplification. We present results on phase-sensitive amplification with increased bandwidth, and on noise performance and dynamic range that are comparable to the traditional mode of operation. Work supported by ARO, AFOSR, NSF and YINQE.

  3. Stimulated Raman amplification, oscillation, and linewidth in barium nitrate

    NASA Technical Reports Server (NTRS)

    McCray, Christopher J.; Chyba, Thomas H.

    1998-01-01

    Measurements of Raman gain in a Ba(NO3)2 crystal are reported at 532 nm using a Raman oscillator/amplifier arrangement for differential absorption lidar measurements of ozone. The experimentally determined gain coefficient will be compared with theoretical results. The effect of single and multi-longitudinal mode pumping upon the amplification process will be discussed. Measurement of the Raman linewidth for 1st 2nd and 3d stokes shifts arc presented.

  4. EFFECTS OF LASER RADIATION ON MATTER: Calculation of the gain of a C VI laser plasma expanding as a cylinder and a cylindrical layer

    NASA Astrophysics Data System (ADS)

    Gulov, A. V.; Derzhiev, V. I.; Zhidkov, A. G.; Pritula, A. G.; Chekmezov, A. N.; Yakovlenko, Sergei I.

    1990-08-01

    Calculations are reported of the gain due to the 3-2 transition in the C VI ion in an expanding plasma cylinder or a cylindrical layer. Under the conditions in the experiments at the Rutherford Appleton Laboratory (Chilton, England) amplification was observed as a result of evaporation of a fairly thin (~ 0.1 μm) cylindrical layer. A peak of the gain was reached in a relatively short time (~ 0.1 ns).

  5. Frequency domain optical parametric amplification

    PubMed Central

    Schmidt, Bruno E.; Thiré, Nicolas; Boivin, Maxime; Laramée, Antoine; Poitras, François; Lebrun, Guy; Ozaki, Tsuneyuki; Ibrahim, Heide; Légaré, François

    2014-01-01

    Today’s ultrafast lasers operate at the physical limits of optical materials to reach extreme performances. Amplification of single-cycle laser pulses with their corresponding octave-spanning spectra still remains a formidable challenge since the universal dilemma of gain narrowing sets limits for both real level pumped amplifiers as well as parametric amplifiers. We demonstrate that employing parametric amplification in the frequency domain rather than in time domain opens up new design opportunities for ultrafast laser science, with the potential to generate single-cycle multi-terawatt pulses. Fundamental restrictions arising from phase mismatch and damage threshold of nonlinear laser crystals are not only circumvented but also exploited to produce a synergy between increased seed spectrum and increased pump energy. This concept was successfully demonstrated by generating carrier envelope phase stable, 1.43 mJ two-cycle pulses at 1.8 μm wavelength. PMID:24805968

  6. Frequency non-degenerate phase-sensitive optical parametric amplification based on four-wave-mixing in width-modulated silicon waveguides.

    PubMed

    Wang, Zhaolu; Liu, Hongjun; Sun, Qibing; Huang, Nan; Li, Xuefeng

    2014-12-15

    A width-modulated silicon waveguide is proposed to realize non-degenerate phase sensitive optical parametric amplification. It is found that the relative phase at the input of the phase sensitive amplifier (PSA) θIn-PSA can be tuned by tailoring the width and length of the second segment of the width-modulated silicon waveguide, which will influence the gain in the parametric amplification process. The maximum gain of PSA is larger by 9 dB compared with the phase insensitive amplifier (PIA) gain, and the gain bandwidth of PSA is larger by 35 nm compared with the gain bandwidth of PIA. Our on-chip PSA can find important potential applications in highly integrated optical circuits for optical chip-to-chip communication and computers.

  7. [Effect of sound amplification on parent's communicative modalities].

    PubMed

    Couto, Maria Inês Vieira; Lichtig, Ida

    2007-01-01

    auditory rehabilitation in deaf children users of sign language. to verify the effects of sound amplification on parent's communicative modalities when interacting with their deaf children. participants were twelve deaf children, aged 50 to 80 months and their hearing parents. Children had severe or profound hearing loss in their better ear and were fitted with hearing aids in both ears. Children communicated preferably through sign language. The cause-effect relation between the children's auditory skills profile (insertion gain, functional gain and The Meaningful Auditory Integration Scale--MAIS) and the communicative modalities (auditive-oral, visuo-spacial, bimodal) used by parents was analyzed. Communicative modalities were compared in two different experimental situations during a structured interaction between parents and children, i.e. when children were not fitted with their hearing aids (Situation 1) and when children were fitted with them (Situation 2). Data was analyzed using descriptive statistics. the profile of the deaf children's auditory skills demonstrated to be lower than 53% (unsatisfactory). Parents used predominately the bimodal modality to gain children's attention, to transmit and to end tasks. A slight positive effect of sound amplification on the communicative modalities was observed, once parents presented more turn-takings during communication when using the auditory-oral modality in Situation 2. hearing parents tend to use more turn-takings during communication in the auditory-oral modality to gain children's attention, to transmit and to end tasks, since they observe an improvement in the auditory skills of their children.

  8. Evidence of high-elevation amplification versus Arctic amplification

    NASA Astrophysics Data System (ADS)

    Wang, Qixiang; Fan, Xiaohui; Wang, Mengben

    2016-01-01

    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.

  9. Evidence of high-elevation amplification versus Arctic amplification

    PubMed Central

    Wang, Qixiang; Fan, Xiaohui; Wang, Mengben

    2016-01-01

    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. PMID:26753547

  10. MYC gene amplification is a rare event in atypical fibroxanthoma and pleomorphic dermal sarcoma

    PubMed Central

    Bach, Marisa; Kind, Peter; Helbig, Doris; Quaas, Alexander; Utikal, Jochen; Marx, Alexander; Gaiser, Maria Rita

    2018-01-01

    Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare malignancies typically occurring in elderly patients and predominantly located in skin regions exposed to UV-light. Thus, a role of UV-radiation-induced damage for AFX and PDS tumorigenesis has been postulated. MYC gene amplification has been demonstrated as a distinctive feature of radiation-induced angiosarcoma. In order to investigate whether chronic exposure to UV-light might also lead to MYC copy number changes, 51 AFX and 24 PDS samples were retrospectively analyzed for MYC amplification by fluorescence in situ hybridization using a MYC and a CEP8 gene probe. Of the 44 analyzable AFX samples, one case showed MYC amplification (defined as a MYC/CEP8 ratio ≥2.0), whereas 13 cases demonstrated low level copy number gains (defined as MYC/CEP8 ratio ≥ 1.2−< 2.0). MYC amplification was seen in an AFX sample of extraordinary tumor thickness of 17.5 mm (vs. median 3.25 mm for all samples). Of the 24 PDS cases, five specimen demonstrated MYC low level copy number gains. Immunohistochemically, neither the AFX nor the PDS cases showed MYC protein expression. In summary, these findings rule out that MYC amplification is a major genetic driver in the process of AFX or PDS tumorigenesis. However, MYC amplification may occur as a late event during AFX development and hence might only be detectable in advanced, thick lesions. PMID:29765529

  11. MYC gene amplification is a rare event in atypical fibroxanthoma and pleomorphic dermal sarcoma.

    PubMed

    Gaiser, Timo; Hirsch, Daniela; Orouji, Azadeh; Bach, Marisa; Kind, Peter; Helbig, Doris; Quaas, Alexander; Utikal, Jochen; Marx, Alexander; Gaiser, Maria Rita

    2018-04-20

    Atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) are rare malignancies typically occurring in elderly patients and predominantly located in skin regions exposed to UV-light. Thus, a role of UV-radiation-induced damage for AFX and PDS tumorigenesis has been postulated. MYC gene amplification has been demonstrated as a distinctive feature of radiation-induced angiosarcoma. In order to investigate whether chronic exposure to UV-light might also lead to MYC copy number changes, 51 AFX and 24 PDS samples were retrospectively analyzed for MYC amplification by fluorescence in situ hybridization using a MYC and a CEP8 gene probe. Of the 44 analyzable AFX samples, one case showed MYC amplification (defined as a MYC /CEP8 ratio ≥2.0), whereas 13 cases demonstrated low level copy number gains (defined as MYC /CEP8 ratio ≥ 1.2-< 2.0). MYC amplification was seen in an AFX sample of extraordinary tumor thickness of 17.5 mm (vs. median 3.25 mm for all samples). Of the 24 PDS cases, five specimen demonstrated MYC low level copy number gains. Immunohistochemically, neither the AFX nor the PDS cases showed MYC protein expression. In summary, these findings rule out that MYC amplification is a major genetic driver in the process of AFX or PDS tumorigenesis. However, MYC amplification may occur as a late event during AFX development and hence might only be detectable in advanced, thick lesions.

  12. Calculation of single-pass gain for laser ceramics with losses

    NASA Astrophysics Data System (ADS)

    Vatnik, S. M.

    2018-04-01

    Rate equations describing the single-pass gain in an active medium with losses are analytically solved. The found relations illustrate the dependences of the amplification efficiency of Nd : YAG ceramics on the pump power density and specific losses. It is concluded that specific losses can be estimated from comparative measurements of unsaturated and saturated gains.

  13. Brillouin Amplification--A Powerful New Scheme for Microwave Photonic Communications

    NASA Technical Reports Server (NTRS)

    Yao, S.; Maleki, L.

    1997-01-01

    We introduce the Brillouin selective sideband amplification technique and demonstrate many important applications of this technique in photonic microwave systems, including efficient phase modulation to amplitude modulation conversion, photonic frequency multiplication, photonic signal mixing with gain, and frequency multiplied signal up conversion.

  14. Solid-Phase Nucleic Acid Sequence-Based Amplification and Length-Scale Effects during RNA Amplification.

    PubMed

    Ma, Youlong; Teng, Feiyue; Libera, Matthew

    2018-06-05

    Solid-phase oligonucleotide amplification is of interest because of possible applications to next-generation sequencing, multiplexed microarray-based detection, and cell-free synthetic biology. Its efficiency is, however, less than that of traditional liquid-phase amplification involving unconstrained primers and enzymes, and understanding how to optimize the solid-phase amplification process remains challenging. Here, we demonstrate the concept of solid-phase nucleic acid sequence-based amplification (SP-NASBA) and use it to study the effect of tethering density on amplification efficiency. SP-NASBA involves two enzymes, avian myeloblastosis virus reverse transcriptase (AMV-RT) and RNase H, to convert tethered forward and reverse primers into tethered double-stranded DNA (ds-DNA) bridges from which RNA - amplicons can be generated by a third enzyme, T7 RNA polymerase. We create microgels on silicon surfaces using electron-beam patterning of thin-film blends of hydroxyl-terminated and biotin-terminated poly(ethylene glycol) (PEG-OH, PEG-B). The tethering density is linearly related to the PEG-B concentration, and biotinylated primers and molecular beacon detection probes are tethered to streptavidin-activated microgels. While SP-NASBA is very efficient at low tethering densities, the efficiency decreases dramatically with increasing tethering density due to three effects: (a) a reduced hybridization efficiency of tethered molecular beacon detection probes; (b) a decrease in T7 RNA polymerase efficiency; (c) inhibition of T7 RNA polymerase activity by AMV-RT.

  15. Amplification through chaotic synchronization in spatially extended beam-plasma systems

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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.

  17. Nonreciprocal Gain in Non-Hermitian Time-Floquet Systems

    NASA Astrophysics Data System (ADS)

    Koutserimpas, Theodoros T.; Fleury, Romain

    2018-02-01

    We explore the unconventional wave scattering properties of non-Hermitian systems in which amplification or damping are induced by time-periodic modulation. These non-Hermitian time-Floquet systems are capable of nonreciprocal operations in the frequency domain, which can be exploited to induce novel physical phenomena such as unidirectional wave amplification and perfect nonreciprocal response with zero or even negative insertion losses. This unique behavior is obtained by imparting a specific low-frequency time-periodic modulation to the complex coupling between lossless resonators, promoting only upward frequency conversion, and leading to nonreciprocal parametric gain. We provide a full-wave demonstration of our findings in a one-way microwave amplifier, and establish the potential of non-Hermitian time-Floquet devices for insertion-loss free microwave isolation and unidirectional parametric amplification.

  18. Ultra-flat wideband single-pump Raman-enhanced parametric amplification.

    PubMed

    Gordienko, V; Stephens, M F C; El-Taher, A E; Doran, N J

    2017-03-06

    We experimentally optimize a single pump fiber optical parametric amplifier in terms of gain spectral bandwidth and gain variation (GV). We find that optimal performance is achieved with the pump tuned to the zero-dispersion wavelength of dispersion stable highly nonlinear fiber (HNLF). We demonstrate further improvement of parametric gain bandwidth and GV by decreasing the HNLF length. We discover that Raman and parametric gain spectra produced by the same pump may be merged together to enhance overall gain bandwidth, while keeping GV low. Consequently, we report an ultra-flat gain of 9.6 ± 0.5 dB over a range of 111 nm (12.8 THz) on one side of the pump. Additionally, we demonstrate amplification of a 60 Gbit/s QPSK signal tuned over a portion of the available bandwidth with OSNR penalty less than 1 dB for Q2 below 14 dB.

  19. Light amplification by seeded Kerr instability

    NASA Astrophysics Data System (ADS)

    Vampa, G.; Hammond, T. J.; Nesrallah, M.; Naumov, A. Yu.; Corkum, P. B.; Brabec, T.

    2018-02-01

    Amplification of femtosecond laser pulses typically requires a lasing medium or a nonlinear crystal. In either case, the chemical properties of the lasing medium or the momentum conservation in the nonlinear crystal constrain the frequency and the bandwidth of the amplified pulses. We demonstrate high gain amplification (greater than 1000) of widely tunable (0.5 to 2.2 micrometers) and short (less than 60 femtosecond) laser pulses, up to intensities of 1 terawatt per square centimeter, by seeding the modulation instability in an Y3Al5O12 crystal pumped by femtosecond near-infrared pulses. Our method avoids constraints related to doping and phase matching and therefore can occur in a wider pool of glasses and crystals even at far-infrared frequencies and for single-cycle pulses. Such amplified pulses are ideal to study strong-field processes in solids and highly excited states in gases.

  20. Enhanced Amplification and Fan-Out Operation in an All-Magnetic Transistor

    PubMed Central

    Barman, Saswati; Saha, Susmita; Mondal, Sucheta; Kumar, Dheeraj; Barman, Anjan

    2016-01-01

    Development of all-magnetic transistor with favorable properties is an important step towards a new paradigm of all-magnetic computation. Recently, we showed such possibility in a Magnetic Vortex Transistor (MVT). Here, we demonstrate enhanced amplification in MVT achieved by introducing geometrical asymmetry in a three vortex sequence. The resulting asymmetry in core to core distance in the three vortex sequence led to enhanced amplification of the MVT output. A cascade of antivortices travelling in different trajectories including a nearly elliptical trajectory through the dynamic stray field is found to be responsible for this amplification. This asymmetric vortex transistor is further used for a successful fan-out operation, which gives large and nearly equal gains in two output branches. This large amplification in magnetic vortex gyration in magnetic vortex transistor is proposed to be maintained for a network of vortex transistor. The above observations promote the magnetic vortex transistors to be used in complex circuits and logic operations. PMID:27624662

  1. Years of life gained due to leisure-time physical activity in the U.S.

    PubMed

    Janssen, Ian; Carson, Valerie; Lee, I-Min; Katzmarzyk, Peter T; Blair, Steven N

    2013-01-01

    Physical inactivity is an important modifiable risk factor for noncommunicable disease. The degree to which physical activity affects the life expectancy of Americans is unknown. This study estimated the potential years of life gained due to leisure-time physical activity in the U.S. Data from the National Health and Nutrition Examination Survey (2007-2010); National Health Interview Study mortality linkage (1990-2006); and U.S. Life Tables (2006) were used to estimate and compare life expectancy at each age of adult life for inactive (no moderate to vigorous physical activity); somewhat-active (some moderate to vigorous activity but <500 MET minutes/week); and active (≥ 500 MET minutes/week of moderate to vigorous activity) adults. Analyses were conducted in 2012. Somewhat-active and active non-Hispanic white men had a life expectancy at age 20 years that was ~2.4 years longer than that for the inactive men; this life expectancy advantage was 1.2 years at age 80 years. Similar observations were made in non-Hispanic white women, with a higher life expectancy within the active category of 3.0 years at age 20 years and 1.6 years at age 80 years. In non-Hispanic black women, as many as 5.5 potential years of life were gained due to physical activity. Significant increases in longevity were also observed within somewhat-active and active non-Hispanic black men; however, among Hispanics the years-of-life-gained estimates were not significantly different from 0 years gained. Leisure-time physical activity is associated with increases in longevity. Copyright © 2013 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  2. Years of Life Gained Due to Leisure-Time Physical Activity in the United States

    PubMed Central

    Janssen, Ian; Carson, Valerie; Lee, I-Min; Katzmarzyk, Peter T.; Blair, Steven N.

    2013-01-01

    Background Physical inactivity is an important modifiable risk factor for non-communicable disease. The degree to which physical activity affects the life expectancy of Americans is unknown. This study estimated the potential years of life gained due to leisure-time physical activity across the adult lifespan in the United States. Methods Data from the National Health and Nutrition Examination Survey (2007–2010), National Health Interview Study mortality linkage (1990–2006), and US Life Tables (2006) were used to estimate and compare life expectancy at each age of adult life for inactive (no moderate-to-vigorous physical activity), somewhat active (some moderate-to-vigorous activity but <500 metabolic equivalent min/week) and active (≥500 metabolic equivalent min/week of moderate-to-vigorous activity) adults. Analyses were conducted in 2012. Results Somewhat active and active non-Hispanic white men had a life expectancy at age 20 that was around 2.4 years longer than the inactive men; this life expectancy advantage was 1.2 years at age 80. Similar observations were made in non-Hispanic white women, with a higher life expectancy within the active category of 3.0 years at age 20 and 1.6 years at age 80. In non-Hispanic black women, as many as 5.5 potential years of life were gained due to physical activity. Significant increases in longevity were also observed within somewhat active and active non-Hispanic black men; however, among Hispanics the years of life gained estimates were more variable and not significantly different from 0 years gained. Conclusions Leisure-time physical activity is associated with increases in longevity in the United States. PMID:23253646

  3. GAB2 amplifications refine molecular classification of melanoma.

    PubMed

    Chernoff, Karen A; Bordone, Lindsey; Horst, Basil; Simon, Katherine; Twadell, William; Lee, Keagan; Cohen, Jason A; Wang, Shuang; Silvers, David N; Brunner, Georg; Celebi, Julide Tok

    2009-07-01

    Gain-of-function mutations in BRAF, NRAS, or KIT are associated with distinct melanoma subtypes with KIT mutations and/or copy number changes frequently observed among melanomas arising from sun-protected sites, such as acral skin (palms, soles, and nail bed) and mucous membranes. GAB2 has recently been implicated in melanoma pathogenesis, and increased copy numbers are found in a subset of melanomas. We sought to determine the association of increased copy numbers of GAB2 among melanoma subtypes in the context of genetic alterations in BRAF, NRAS, and KIT. A total of 85 melanomas arising from sun-protected (n = 23) and sun-exposed sites (n = 62) were analyzed for copy number changes using array-based comparative genomic hybridization and for gain-of-function mutations in BRAF, NRAS, and KIT. GAB2 amplifications were found in 9% of the cases and were associated with melanomas arising from acral and mucosal sites (P = 0.005). Increased copy numbers of the KIT locus were observed in 6% of the cases. The overall mutation frequencies for BRAF and NRAS were 43.5% and 14%, respectively, and were mutually exclusive. Among the acral and mucosal melanomas studied, the genetic alteration frequency was 26% for GAB2, 13% for KIT, 30% for BRAF, and 4% for NRAS. Importantly, the majority of GAB2 amplifications occurred independent from genetic events in BRAF, NRAS, and KIT. GAB2 amplification is critical for melanomas arising from sun-protected sites. Genetic alterations in GAB2 will help refine the molecular classification of melanomas.

  4. Performance of a High-Concentration Erbium-Doped Fiber Amplifier with 100 nm Amplification Bandwidth

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hajireza, P.; Shahabuddin, N. S.; Abbasi-Zargaleh, S.

    2010-07-07

    Increasing demand for higher bandwidth has driven the need for higher Wavelength Division Multiplexing (WDM) channels. One of the requirements to achieve this is a broadband amplifier. This paper reports the performance of a broadband, compact, high-concentration and silica-based erbium-doped fiber amplifier. The amplifier optimized to a 2.15 m long erbium-doped fiber with erbium ion concentration of 2000 ppm. The gain spectrum of the amplifier has a measured amplification bandwidth of 100 nm using a 980 nm laser diode with power of 150 mW. This silica-based EDFA shows lower noise figure, higher gain and wider bandwidth in shorter wavelengths comparedmore » to Bismuth-based EDFA with higher erbium ion concentration of 3250 ppm at equivalent EDF length. The silica-based EDF shows peak gain at 22 dB and amplification bandwidth between 1520 nm and 1620 nm. The lowest noise figure is 5 dB. The gain is further improved with the implementation of enhanced EDFA configurations.« less

  5. Broad-spectrum neodymium-doped laser glasses for high-energy chirped-pulse amplification.

    PubMed

    Hays, Greg R; Gaul, Erhard W; Martinez, Mikael D; Ditmire, Todd

    2007-07-20

    We have investigated two novel laser glasses in an effort to generate high-energy, broad-spectrum pulses from a chirped-pulse amplification Nd:glass laser. Both glasses have significantly broader spectra (>38 nm FWHM) than currently available Nd:phosphate and Nd:silicate glasses. We present calculations for small signal pulse amplification to simulate spectral gain narrowing. The technique of spectral shaping using mixed-glass architecture with an optical parametric chirped-pulse amplification front end is evaluated. Our modeling shows that amplified pulses with energies exceeding 10 kJ with sufficient bandwidth to achieve 120 fs pulsewidths are achievable with the use of the new laser glasses. With further development of current technologies, a laser system could be scaled to generate one exawatt in peak power.

  6. Discovery of a photoresponse amplification mechanism in compensated PN junctions

    NASA Astrophysics Data System (ADS)

    Zhou, Yuchun; Liu, Yu-Hsin; Rahman, Samia N.; Hall, David; Sham, L. J.; Lo, Yu-Hwa

    2015-01-01

    We report the experimental evidence of uncovering a photoresponse amplification mechanism in heavily doped, partially compensated silicon p-n junctions under very low bias voltage. We show that the observed photocurrent gain occurs at a bias that is more than an order of magnitude below the threshold voltage for conventional impact ionization. Moreover, contrary to the case of avalanche detectors and p-i-n diodes, the amplified photoresponse is enhanced rather than suppressed with increasing temperature. These distinctive characteristics lead us to hypothesize that the inelastic scattering between energetic electrons (holes) and the ionized impurities in the depletion and charge neutral regions of the p-n junction in a cyclic manner plays a significant role in the amplification process. Such an internal signal amplification mechanism, which occurs at much lower bias than impact ionization and favors room temperature over cryogenic temperature, makes it promising for practical device applications.

  7. Giant amplification in degenerate band edge slow-wave structures interacting with an electron beam

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Othman, Mohamed A. K.; Veysi, Mehdi; Capolino, Filippo

    2016-03-15

    We propose a new amplification regime based on a synchronous operation of four degenerate electromagnetic (EM) modes in a slow-wave structure and the electron beam, referred to as super synchronization. These four EM modes arise in a Fabry-Pérot cavity when degenerate band edge (DBE) condition is satisfied. The modes interact constructively with the electron beam resulting in superior amplification. In particular, much larger gains are achieved for smaller beam currents compared to conventional structures based on synchronization with only a single EM mode. We demonstrate giant gain scaling with respect to the length of the slow-wave structure compared to conventionalmore » Pierce type single mode traveling wave tube amplifiers. We construct a coupled transmission line model for a loaded waveguide slow-wave structure exhibiting a DBE, and investigate the phenomenon of giant gain via super synchronization using the Pierce model generalized to multimode interaction.« less

  8. Error amplification to promote motor learning and motivation in therapy robotics.

    PubMed

    Shirzad, Navid; Van der Loos, H F Machiel

    2012-01-01

    To study the effects of different feedback error amplification methods on a subject's upper-limb motor learning and affect during a point-to-point reaching exercise, we developed a real-time controller for a robotic manipulandum. The reaching environment was visually distorted by implementing a thirty degrees rotation between the coordinate systems of the robot's end-effector and the visual display. Feedback error amplification was provided to subjects as they trained to learn reaching within the visually rotated environment. Error amplification was provided either visually or through both haptic and visual means, each method with two different amplification gains. Subjects' performance (i.e., trajectory error) and self-reports to a questionnaire were used to study the speed and amount of adaptation promoted by each error amplification method and subjects' emotional changes. We found that providing haptic and visual feedback promotes faster adaptation to the distortion and increases subjects' satisfaction with the task, leading to a higher level of attentiveness during the exercise. This finding can be used to design a novel exercise regimen, where alternating between error amplification methods is used to both increase a subject's motor learning and maintain a minimum level of motivational engagement in the exercise. In future experiments, we will test whether such exercise methods will lead to a faster learning time and greater motivation to pursue a therapy exercise regimen.

  9. Renal Cell Carcinoma With Chromosome 6p Amplification Including the TFEB Gene: A Novel Mechanism of Tumor Pathogenesis?

    PubMed

    Williamson, Sean R; Grignon, David J; Cheng, Liang; Favazza, Laura; Gondim, Dibson D; Carskadon, Shannon; Gupta, Nilesh S; Chitale, Dhananjay A; Kalyana-Sundaram, Shanker; Palanisamy, Nallasivam

    2017-03-01

    Amplification of chromosome 6p has been implicated in aggressive behavior in several cancers, but has not been characterized in renal cell carcinoma (RCC). We identified 9 renal tumors with amplification of chromosome 6p including the TFEB gene, 3 by fluorescence in situ hybridization, and 6 from the Cancer Genome Atlas (TCGA) databases. Patients' ages were 28 to 78 years (median, 61 y). Most tumors were high stage (7/9 pT3a, 2/9 pN1). Using immunohistochemistry, 2/4 were positive for melanocytic markers and cathepsin K. Novel TFEB fusions were reported by TCGA in 2; however, due to a small composition of fusion transcripts compared with full-length transcripts (0.5/174 and 3.3/132 FPKM), we hypothesize that these represent secondary fusions due to amplification. Five specimens (4 TCGA, 1 fluorescence in situ hybridization) had concurrent chromosome 3p copy number loss or VHL deletion. However, these did not resemble clear cell RCC, had negative carbonic anhydrase IX labeling, lacked VHL mutation, and had papillary or unclassified histology (2/4 had gain of chromosome 7 or 17). One tumor each had somatic FH mutation and SMARCB1 mutation. Chromosome 6p amplification including TFEB is a previously unrecognized cytogenetic alteration in RCC, associated with heterogenous tubulopapillary eosinophilic and clear cell histology. The combined constellation of features does not fit cleanly into an existing tumor category (unclassified), most closely resembling papillary or translocation RCC. The tendency for high tumor stage, varied tubulopapillary morphology, and a subset with melanocytic marker positivity suggests the possibility of a unique tumor type, despite some variation in appearance and genetics.

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

    PubMed

    Longhi, Stefano

    2016-04-15

    Optical parametric amplification and oscillation provide powerful tools for coherent light generation in spectral regions inaccessible to lasers. Parametric gain is based on a frequency down-conversion process and, thus, it cannot be realized for signal waves at a frequency ω3 higher than the frequency of the pump wave ω1. In this Letter, we suggest a route toward the realization of upconversion optical parametric amplification and oscillation, i.e., amplification of the signal wave by a coherent pump wave of lower frequency, assisted by stimulated emission of the auxiliary idler wave. When the signal field is resonated in an optical cavity, parametric oscillation is obtained. Design parameters for the observation of upconversion optical parametric oscillation at λ3=465 nm are given for a periodically poled lithium-niobate (PPLN) crystal doped with Nd(3+) ions.

  11. ALK gene copy number gain and immunohistochemical expression status using three antibodies in neuroblastoma.

    PubMed

    Kim, Eun Kyung; Kim, Sewha

    2016-03-17

    Anaplastic lymphoma kinase (ALK) gene aberrations-such as mutations, amplifications, and copy number gains-represent a major genetic predisposition to neuroblastoma (NB). This study aimed to evaluate the correlation between ALK gene copy number status, ALK protein expression, and clinicopathological parameters. We retrospectively retrieved 30 cases of poorly differentiated NB and constructed tissue microarrays (TMAs). ALK copy number changes were assessed by fluorescence in situ hybridization (FISH) assays, and ALK immunohistochemistry (IHC) testing was performed using three different antibodies (ALK1, D5F3, and 5A4 clones). ALK amplification and copy number gain were observed in 10% (3/30) and 53.3% (16/30) of the cohort, respectively. There were positive correlations between ALK copy number and IHC positive rate in ALK1 and 5A4 antibodies (p= < 0.001 and 0.019, respectively). ALK1, D5F3, and 5A4 antibodies equally showed 100% sensitivity in detecting ALK amplification. However, the sensitivity for detecting copy number gain differed among the three antibodies, with 75% sensitivity in D5F3 and 0% sensitivity in ALK1. ALK-amplified NBs were correlated with synchronous MYCN amplification and chromosome 1p deletion. ALK IHC positivity was frequently observed in INSS stage IV and high-risk group patients. In conclusion, this study identified that an increase in the ALK copy number is a frequent genetic alteration in poorly differentiated NB. ALK-amplified NBs showed consistent ALK IHC positivity with all kinds of antibodies. In contrast, the detection performance of ALK copy number gain was antibody dependent, with the D5F3 antibody showing the best sensitivity.

  12. ALK Gene Copy Number Gain and Immunohistochemical Expression Status Using Three Antibodies in Neuroblastoma.

    PubMed

    Kim, Eun Kyung; Kim, Sewha

    2017-01-01

    Anaplastic lymphoma kinase ( ALK) gene aberrations-such as mutations, amplifications, and copy number gains-represent a major genetic predisposition to neuroblastoma (NB). This study aimed to evaluate the correlation between ALK gene copy number status, ALK protein expression, and clinicopathological parameters. We retrospectively retrieved 30 cases of poorly differentiated NB and constructed tissue microarrays (TMAs). ALK copy number changes were assessed by fluorescence in situ hybridization (FISH) assays, and ALK immunohistochemistry (IHC) testing was performed using three different antibodies (ALK1, D5F3, and 5A4 clones). ALK amplification and copy number gain were observed in 10% (3/30) and 53.3% (16/30) of the cohort, respectively. There were positive correlations between ALK copy number and IHC-positive rate in ALK1 and 5A4 antibodies ( P < 0.001 and P = 0.019, respectively). ALK1, D5F3, and 5A4 antibodies equally showed 100% sensitivity in detecting ALK amplification. However, the sensitivity for detecting copy number gain differed among the three antibodies, with 75% sensitivity in D5F3 and 0% sensitivity in ALK1. ALK-amplified NBs were correlated with synchronous MYCN amplification and chromosome 1p deletion. ALK IHC positivity was frequently observed in INSS stage IV and high-risk group patients. In conclusion, this study identified that an increase in the ALK copy number is a frequent genetic alteration in poorly differentiated NB. ALK-amplified NBs showed consistent ALK IHC positivity with all kinds of antibodies. In contrast, the detection performance of ALK copy number gain was antibody dependent, with the D5F3 antibody showing the best sensitivity.

  13. [Prognostic significance of MYCN amplification in children neuroblastic tumors].

    PubMed

    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.

  14. Effect of gain contouring in erbium-doped fiber amplifiers on bit error rate performance of wavelength-division multiplexing-based radio over fiber links

    NASA Astrophysics Data System (ADS)

    Jose, Tony; Narayanan, Vijayakumar

    2018-03-01

    Radio over fiber (RoF) systems use a large number of base stations (BSs) and a number of central stations (CSs), which are interlinked together to form the network. RoF systems use multiple wavelengths for communication between CSs or between CSs and BSs to facilitate the huge amount of data traffic due to the multiple services for a large number of users. When erbium-doped fiber amplifiers (EDFAs) are used as amplifiers in such wavelength-division multiplexed systems, the nonuniform gain spectrum of EDFAs causes instability to some of the channels while providing faithful amplification to other channels. To avoid this inconsistency, the gain spectrum of the amplifier needs to be uniform along the whole usable range of wavelengths. A gain contouring technique is proposed to provide uniform gain to all channels irrespective of wavelength. Optical add/drop multiplexers (OADMs) and different lengths of erbium-doped fibers are used to create such a gain contouring mechanism in the optical domain itself. The effect of a cascade of nonuniform gain amplifiers is studied, and the proposed system mitigates the adverse effects caused due to nonuniform gain-induced channel instability effectively.

  15. Discovery of a photoresponse amplification mechanism in compensated PN junctions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhou, Yuchun; Rahman, Samia N.; Hall, David

    2015-01-19

    We report the experimental evidence of uncovering a photoresponse amplification mechanism in heavily doped, partially compensated silicon p-n junctions under very low bias voltage. We show that the observed photocurrent gain occurs at a bias that is more than an order of magnitude below the threshold voltage for conventional impact ionization. Moreover, contrary to the case of avalanche detectors and p-i-n diodes, the amplified photoresponse is enhanced rather than suppressed with increasing temperature. These distinctive characteristics lead us to hypothesize that the inelastic scattering between energetic electrons (holes) and the ionized impurities in the depletion and charge neutral regions ofmore » the p-n junction in a cyclic manner plays a significant role in the amplification process. Such an internal signal amplification mechanism, which occurs at much lower bias than impact ionization and favors room temperature over cryogenic temperature, makes it promising for practical device applications.« less

  16. Sound pressure level gain in an acoustic metamaterial cavity.

    PubMed

    Song, Kyungjun; Kim, Kiwon; Hur, Shin; Kwak, Jun-Hyuk; Park, Jihyun; Yoon, Jong Rak; Kim, Jedo

    2014-12-11

    The inherent attenuation of a homogeneous viscous medium limits radiation propagation, thereby restricting the use of many high-frequency acoustic devices to only short-range applications. Here, we design and experimentally demonstrate an acoustic metamaterial localization cavity which is used for sound pressure level (SPL) gain using double coiled up space like structures thereby increasing the range of detection. This unique behavior occurs within a subwavelength cavity that is 1/10(th) of the wavelength of the incident acoustic wave, which provides up to a 13 dB SPL gain. We show that the amplification results from the Fabry-Perot resonance of the cavity, which has a simultaneously high effective refractive index and effective impedance. We also experimentally verify the SPL amplification in an underwater environment at higher frequencies using a sample with an identical unit cell size. The versatile scalability of the design shows promising applications in many areas, especially in acoustic imaging and underwater communication.

  17. Sound Pressure Level Gain in an Acoustic Metamaterial Cavity

    PubMed Central

    Song, Kyungjun; Kim, Kiwon; Hur, Shin; Kwak, Jun-Hyuk; Park, Jihyun; Yoon, Jong Rak; Kim, Jedo

    2014-01-01

    The inherent attenuation of a homogeneous viscous medium limits radiation propagation, thereby restricting the use of many high-frequency acoustic devices to only short-range applications. Here, we design and experimentally demonstrate an acoustic metamaterial localization cavity which is used for sound pressure level (SPL) gain using double coiled up space like structures thereby increasing the range of detection. This unique behavior occurs within a subwavelength cavity that is 1/10th of the wavelength of the incident acoustic wave, which provides up to a 13 dB SPL gain. We show that the amplification results from the Fabry-Perot resonance of the cavity, which has a simultaneously high effective refractive index and effective impedance. We also experimentally verify the SPL amplification in an underwater environment at higher frequencies using a sample with an identical unit cell size. The versatile scalability of the design shows promising applications in many areas, especially in acoustic imaging and underwater communication. PMID:25502279

  18. Gain curves and hydrodynamic modeling for shock ignition

    NASA Astrophysics Data System (ADS)

    Lafon, M.; Ribeyre, X.; Schurtz, G.

    2010-05-01

    Ignition of a precompressed thermonuclear fuel by means of a converging shock is now considered as a credible scheme to obtain high gains for inertial fusion energy. This work aims at modeling the successive stages of the fuel time history, from compression to final thermonuclear combustion, in order to provide the gain curves of shock ignition (SI). The leading physical mechanism at work in SI is pressure amplification, at first by spherical convergence, and by collision with the shock reflected at center during the stagnation process. These two effects are analyzed, and ignition conditions are provided as functions of the shock pressure and implosion velocity. Ignition conditions are obtained from a non-isobaric fuel assembly, for which we present a gain model. The corresponding gain curves exhibit a significantly lower ignition threshold and higher target gains than conventional central ignition.

  19. Two-dimensional Maxwell-Bloch simulation of quasi-π-pulse amplification in a seeded XUV laser

    NASA Astrophysics Data System (ADS)

    Larroche, O.; Klisnick, A.

    2013-09-01

    The amplification of high-order-harmonics (HOH) seed pulses in a swept-gain XUV laser is investigated through numerical simulations of the full set of Bloch and two-dimensional paraxial propagation equations with our code colax. The needed atomic data are taken from a hydrodynamics and collisional-radiative simulation in the case of a Ni-like Ag plasma created from the interaction of an infrared laser with a solid target and pumped in the transient regime. We show that the interplay of strong population inversion and diffraction or refraction due to the short transverse dimensions and steep density gradient of the active plasma can lead to the amplification of an intense, ultrashort, quasi-“π” pulse triggered by the incoming seed. By properly tuning the system geometry and HOH pulse parameters, we show that an ≃10 fs, 8×1012 W/cm2 amplified pulse can be achieved in a 3-mm-long Ni-like Ag plasma, with a factor of ≳10 intensity contrast with respect to the longer-lasting wake radiation and amplified spontaneous emission.

  20. The μ-RWELL: A compact, spark protected, single amplification-stage MPGD

    NASA Astrophysics Data System (ADS)

    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.

  1. Topographical and geological amplification: case studies and engineering implications

    USGS Publications Warehouse

    Celebi, M.

    1991-01-01

    Topographical and geological amplification that occurred during past earthquakes are quantified using spectral ratios of recorded motions. Several cases are presented from the 1985 Chilean and Mexican earthquakes as well as the 1983 Coalinga (California) and 1987 Supersition Hills (California) earthquake. The strong motions recorded in Mexico City during the 1985 Michoacan earthquake are supplemented by ambient motions recorded within Mexico City to quantify the now well known resonating frequencies of the Mexico City lakebed. Topographical amplification in Canal Beagle (Chile), Coalinga and Superstition Hills (California) are quantified using the ratios derived from the aftershocks following the earthquakes. A special dense array was deployed to record the aftershocks in each case. The implications of both geological and topographical amplification are discussed in light of current code provisions. The observed geological amplifications has already influenced the code provisions. Suggestions are made to the effect that the codes should include further provisions to take the amplification due to topography into account. ?? 1991.

  2. Terahertz amplification in RTD-gated HEMTs with a grating-gate wave coupling topology

    NASA Astrophysics Data System (ADS)

    Condori Quispe, Hugo O.; Encomendero-Risco, Jimy J.; Xing, Huili Grace; Sensale-Rodriguez, Berardi

    2016-08-01

    We theoretically analyze the operation of a terahertz amplifier consisting of a resonant-tunneling-diode gated high-electron-mobility transistor (RTD-gated HEMT) in a grating-gate topology. In these devices, the key element enabling substantial power gain is the efficient coupling of terahertz waves into and out of plasmons in the RTD-gated HEMT channel, i.e., the gain medium, via the grating-gate itself, part of the active device, rather than by an external antenna structure as discussed in previous works, therefore potentially enabling terahertz amplification with associated power gains >40 dB.

  3. Prognostic significance of ESR1 gene amplification, mRNA/protein expression and functional profiles in high-risk early breast cancer: a translational study of the Hellenic Cooperative Oncology Group (HeCOG).

    PubMed

    Pentheroudakis, George; Kotoula, Vassiliki; Eleftheraki, Anastasia G; Tsolaki, Eleftheria; Wirtz, Ralph M; Kalogeras, Konstantine T; Batistatou, Anna; Bobos, Mattheos; Dimopoulos, Meletios A; Timotheadou, Eleni; Gogas, Helen; Christodoulou, Christos; Papadopoulou, Kyriaki; Efstratiou, Ioannis; Scopa, Chrisoula D; Papaspyrou, Irene; Vlachodimitropoulos, Dimitrios; Linardou, Helena; Samantas, Epaminontas; Pectasides, Dimitrios; Pavlidis, Nicholas; Fountzilas, George

    2013-01-01

    Discrepant data have been published on the incidence and prognostic significance of ESR1 gene amplification in early breast cancer. Formalin-fixed paraffin-embedded tumor blocks were collected from women with early breast cancer participating in two HeCOG adjuvant trials. Messenger RNA was studied by quantitative PCR, ER protein expression was centrally assessed using immunohistochemistry (IHC) and ESR1 gene copy number by dual fluorescent in situ hybridization probes. In a total of 1010 women with resected node-positive early breast adenocarcinoma, the tumoral ESR1/CEP6 gene ratio was suggestive of deletion in 159 (15.7%), gene gain in 551 (54.6%) and amplification in 42 cases (4.2%), with only 30 tumors (3%) harboring five or more ESR1 copies. Gene copy number ratio showed a significant, though weak correlation to mRNA and protein expression (Spearman's Rho <0.23, p = 0.01). ESR1 clusters were observed in 9.5% (57 gain, 38 amplification) of cases. In contrast to mRNA and protein expression, which were favorable prognosticators, gene copy number changes did not obtain prognostic significance. When ESR1/CEP6 gene ratio was combined with function (as defined by ER protein and mRNA expression) in a molecular classifier, the Gene Functional profile, it was functional status that impacted on prognosis. In univariate analysis, patients with functional tumors (positive ER protein expression and gene ratio normal or gain/amplification) fared better than those with non-functional tumors with ESR1 gain (HR for relapse or death 0.49-0.64, p = 0.003). Significant interactions were observed between gene gain/amplification and paclitaxel therapy (trend for DFS benefit from paclitaxel only in patients with ESR1 gain/amplification, p = 0.066) and Gene Functional profile with HER2 amplification (Gene Functional profile prognostic only in HER2-normal cases, p = 0.029). ESR1 gene deletion and amplification do not constitute per se prognostic markers, instead they can

  4. Genome amplification of single sperm using multiple displacement amplification.

    PubMed

    Jiang, Zhengwen; Zhang, Xingqi; Deka, Ranjan; Jin, Li

    2005-06-07

    Sperm typing is an effective way to study recombination rate on a fine scale in regions of interest. There are two strategies for the amplification of single meiotic recombinants: repulsion-phase allele-specific PCR and whole genome amplification (WGA). The former can selectively amplify single recombinant molecules from a batch of sperm but is not scalable for high-throughput operation. Currently, primer extension pre-amplification is the only method used in WGA of single sperm, whereas it has limited capacity to produce high-coverage products enough for the analysis of local recombination rate in multiple large regions. Here, we applied for the first time a recently developed WGA method, multiple displacement amplification (MDA), to amplify single sperm DNA, and demonstrated its great potential for producing high-yield and high-coverage products. In a 50 mul reaction, 76 or 93% of loci can be amplified at least 2500- or 250-fold, respectively, from single sperm DNA, and second-round MDA can further offer >200-fold amplification. The MDA products are usable for a variety of genetic applications, including sequencing and microsatellite marker and single nucleotide polymorphism (SNP) analysis. The use of MDA in single sperm amplification may open a new era for studies on local recombination rates.

  5. Stochastic Gain Degradation in III-V Heterojunction Bipolar Transistors due to Single Particle Displacement Damage

    DOE PAGES

    Vizkelethy, Gyorgy; Bielejec, Edward S.; Aguirre, Brandon A.

    2017-11-13

    As device dimensions decrease single displacement effects are becoming more important. We measured the gain degradation in III-V Heterojunction Bipolar Transistors due to single particles using a heavy ion microbeam. Two devices with different sizes were irradiated with various ion species ranging from oxygen to gold to study the effect of the irradiation ion mass on the gain change. From the single steps in the inverse gain (which is proportional to the number of defects) we calculated Cumulative Distribution Functions to help determine design margins. The displacement process was modeled using the Marlowe Binary Collision Approximation (BCA) code. The entiremore » structure of the device was modeled and the defects in the base-emitter junction were counted to be compared to the experimental results. While we found good agreement for the large device, we had to modify our model to reach reasonable agreement for the small device.« less

  6. Stochastic Gain Degradation in III-V Heterojunction Bipolar Transistors due to Single Particle Displacement Damage

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Vizkelethy, Gyorgy; Bielejec, Edward S.; Aguirre, Brandon A.

    As device dimensions decrease single displacement effects are becoming more important. We measured the gain degradation in III-V Heterojunction Bipolar Transistors due to single particles using a heavy ion microbeam. Two devices with different sizes were irradiated with various ion species ranging from oxygen to gold to study the effect of the irradiation ion mass on the gain change. From the single steps in the inverse gain (which is proportional to the number of defects) we calculated Cumulative Distribution Functions to help determine design margins. The displacement process was modeled using the Marlowe Binary Collision Approximation (BCA) code. The entiremore » structure of the device was modeled and the defects in the base-emitter junction were counted to be compared to the experimental results. While we found good agreement for the large device, we had to modify our model to reach reasonable agreement for the small device.« less

  7. Gain loss and noise temperature degradation due to subreflector rotations in a Cassegrain antenna

    NASA Astrophysics Data System (ADS)

    Lamb, J. W.; Olver, A. D.

    An evaluation of performance degradation due to subreflector rotations is reported for the 15 m UK/NL Millimetrewave Radio Telescope Cassegrain antenna. The analytical treatment of the phase errors shows that the optimum point for the center of rotation of the subreflector is the primary focus, indicating astigmatic error, and it is shown that a compromise must be made betwen mechanical and electrical performance. Gain deterioration due to spillover is only weakly dependent on zc, and this loss decreases as z(c) moves towards the subreflector vertex. The associated spillover gives rise to a noise temperature which is calculated to be a few degrees K.

  8. Circulation and Directional Amplification in the Josephson Parametric Converter

    NASA Astrophysics Data System (ADS)

    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.

  9. [Investigation of RNA viral genome amplification by multiple displacement amplification technique].

    PubMed

    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.

  10. Optical nano-biosensing interface via nucleic acid amplification strategy: construction and application.

    PubMed

    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.

  11. Observational Evidence for Desert Amplification Using Multiple Satellite Datasets.

    PubMed

    Wei, Nan; Zhou, Liming; Dai, Yongjiu; Xia, Geng; Hua, Wenjian

    2017-05-17

    Desert amplification identified in recent studies has large uncertainties due to data paucity over remote deserts. Here we present observational evidence using multiple satellite-derived datasets that desert amplification is a real large-scale pattern of warming mode in near surface and low-tropospheric temperatures. Trend analyses of three long-term temperature products consistently confirm that near-surface warming is generally strongest over the driest climate regions and this spatial pattern of warming maximizes near the surface, gradually decays with height, and disappears in the upper troposphere. Short-term anomaly analyses show a strong spatial and temporal coupling of changes in temperatures, water vapor and downward longwave radiation (DLR), indicating that the large increase in DLR drives primarily near surface warming and is tightly associated with increasing water vapor over deserts. Atmospheric soundings of temperature and water vapor anomalies support the results of the long-term temperature trend analysis and suggest that desert amplification is due to comparable warming and moistening effects of the troposphere. Likely, desert amplification results from the strongest water vapor feedbacks near the surface over the driest deserts, where the air is very sensitive to changes in water vapor and thus efficient in enhancing the longwave greenhouse effect in a warming climate.

  12. Terahertz amplification in RTD-gated HEMTs with a grating-gate wave coupling topology

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Condori Quispe, Hugo O.; Sensale-Rodriguez, Berardi; Encomendero-Risco, Jimy J.

    2016-08-08

    We theoretically analyze the operation of a terahertz amplifier consisting of a resonant-tunneling-diode gated high-electron-mobility transistor (RTD-gated HEMT) in a grating-gate topology. In these devices, the key element enabling substantial power gain is the efficient coupling of terahertz waves into and out of plasmons in the RTD-gated HEMT channel, i.e., the gain medium, via the grating-gate itself, part of the active device, rather than by an external antenna structure as discussed in previous works, therefore potentially enabling terahertz amplification with associated power gains >40 dB.

  13. Ultra-high gain diffusion-driven organic transistor

    PubMed Central

    Torricelli, Fabrizio; Colalongo, Luigi; Raiteri, Daniele; Kovács-Vajna, Zsolt Miklós; Cantatore, Eugenio

    2016-01-01

    Emerging large-area technologies based on organic transistors are enabling the fabrication of low-cost flexible circuits, smart sensors and biomedical devices. High-gain transistors are essential for the development of large-scale circuit integration, high-sensitivity sensors and signal amplification in sensing systems. Unfortunately, organic field-effect transistors show limited gain, usually of the order of tens, because of the large contact resistance and channel-length modulation. Here we show a new organic field-effect transistor architecture with a gain larger than 700. This is the highest gain ever reported for organic field-effect transistors. In the proposed organic field-effect transistor, the charge injection and extraction at the metal–semiconductor contacts are driven by the charge diffusion. The ideal conditions of ohmic contacts with negligible contact resistance and flat current saturation are demonstrated. The approach is general and can be extended to any thin-film technology opening unprecedented opportunities for the development of high-performance flexible electronics. PMID:26829567

  14. Ultra-high gain diffusion-driven organic transistor.

    PubMed

    Torricelli, Fabrizio; Colalongo, Luigi; Raiteri, Daniele; Kovács-Vajna, Zsolt Miklós; Cantatore, Eugenio

    2016-02-01

    Emerging large-area technologies based on organic transistors are enabling the fabrication of low-cost flexible circuits, smart sensors and biomedical devices. High-gain transistors are essential for the development of large-scale circuit integration, high-sensitivity sensors and signal amplification in sensing systems. Unfortunately, organic field-effect transistors show limited gain, usually of the order of tens, because of the large contact resistance and channel-length modulation. Here we show a new organic field-effect transistor architecture with a gain larger than 700. This is the highest gain ever reported for organic field-effect transistors. In the proposed organic field-effect transistor, the charge injection and extraction at the metal-semiconductor contacts are driven by the charge diffusion. The ideal conditions of ohmic contacts with negligible contact resistance and flat current saturation are demonstrated. The approach is general and can be extended to any thin-film technology opening unprecedented opportunities for the development of high-performance flexible electronics.

  15. Ultra-high gain diffusion-driven organic transistor

    NASA Astrophysics Data System (ADS)

    Torricelli, Fabrizio; Colalongo, Luigi; Raiteri, Daniele; Kovács-Vajna, Zsolt Miklós; Cantatore, Eugenio

    2016-02-01

    Emerging large-area technologies based on organic transistors are enabling the fabrication of low-cost flexible circuits, smart sensors and biomedical devices. High-gain transistors are essential for the development of large-scale circuit integration, high-sensitivity sensors and signal amplification in sensing systems. Unfortunately, organic field-effect transistors show limited gain, usually of the order of tens, because of the large contact resistance and channel-length modulation. Here we show a new organic field-effect transistor architecture with a gain larger than 700. This is the highest gain ever reported for organic field-effect transistors. In the proposed organic field-effect transistor, the charge injection and extraction at the metal-semiconductor contacts are driven by the charge diffusion. The ideal conditions of ohmic contacts with negligible contact resistance and flat current saturation are demonstrated. The approach is general and can be extended to any thin-film technology opening unprecedented opportunities for the development of high-performance flexible electronics.

  16. 3-dB signal-ASE beat noise reduction of coherent multi-carrier signal utilizing phase sensitive amplification.

    PubMed

    Umeki, Takeshi; Takara, Hidehiko; Miyamoto, Yutaka; Asobe, Masaki

    2012-10-22

    We demonstrated the simultaneous amplification of a coherent multi-carrier signal using a χ(2)-based non-degenerate phase sensitive amplifier (PSA). The signal-to-noise ratio (SNR), which is degraded by the additional amplified spontaneous emission (ASE) noise, can be recovered due to the gain difference between a phase-correlated signal-idler pair and uncorrelated excess noise. Utilizing the second harmonic pumping of a χ(2)-based PSA enables us to observe the SNR recovery directly by comparing the SNR for the input with that for the PSA output. A 3-dB optical-SNR (OSNR) improvement was obtained as a result of the gain difference. We also achieved a 3-dB SNR improvement in the electric domain by reducing the signal-ASE beat noise. The receiver sensitivity for a 10 Gbit/s phase shift keying signal was clearly improved with the PSA.

  17. Gain and frequency tuning within the mouse cochlear apex

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Oghalai, John S.; Raphael, Patrick D.; Gao, Simon

    Normal mammalian hearing requires cochlear outer hair cell active processes that amplify the traveling wave with high gain and sharp tuning, termed cochlear amplification. We have used optical coherence tomography to study cochlear amplification within the apical turn of the mouse cochlea. We measured not only classical basilar membrane vibratory tuning curves but also vibratory responses from the rest of the tissues that compose the organ of Corti. Basilar membrane tuning was sharp in live mice and broad in dead mice, whereas other regions of the organ of Corti demonstrated phase shifts consistent with additional filtering beyond that provided bymore » basilar membrane mechanics. We use these experimental data to support a conceptual framework of how cochlear amplification is tuned within the mouse cochlear apex. We will also study transgenic mice with targeted mutations that affect different biomechanical aspects of the organ of Corti in an effort to localize the underlying processes that produce this additional filtering.« less

  18. Signal amplification by rolling circle amplification on DNA microarrays

    PubMed Central

    Nallur, Girish; Luo, Chenghua; Fang, Linhua; Cooley, Stephanie; Dave, Varshal; Lambert, Jeremy; Kukanskis, Kari; Kingsmore, Stephen; Lasken, Roger; Schweitzer, Barry

    2001-01-01

    While microarrays hold considerable promise in large-scale biology on account of their massively parallel analytical nature, there is a need for compatible signal amplification procedures to increase sensitivity without loss of multiplexing. Rolling circle amplification (RCA) is a molecular amplification method with the unique property of product localization. This report describes the application of RCA signal amplification for multiplexed, direct detection and quantitation of nucleic acid targets on planar glass and gel-coated microarrays. As few as 150 molecules bound to the surface of microarrays can be detected using RCA. Because of the linear kinetics of RCA, nucleic acid target molecules may be measured with a dynamic range of four orders of magnitude. Consequently, RCA is a promising technology for the direct measurement of nucleic acids on microarrays without the need for a potentially biasing preamplification step. PMID:11726701

  19. Methods and devices based on brillouin selective sideband amplification

    NASA Technical Reports Server (NTRS)

    Yao, X. Steve (Inventor)

    2003-01-01

    Opto-electronic devices and techniques using Brillouin scattering to select a sideband in a modulated optical carrier signal for amplification. Two lasers respectively provide a carrier signal beam and a Brillouin pump beam which are fed into an Brillouin optical medium in opposite directions. The relative frequency separation between the lasers is adjusted to align the frequency of the backscattered Brillouin signal with a desired sideband in the carrier signal to effect a Brillouin gain on the sideband. This effect can be used to implement photonic RF signal mixing and conversion with gain, conversion from phase modulation to amplitude modulation, photonic RF frequency multiplication, optical and RF pulse generation and manipulation, and frequency-locking of lasers.

  20. Detection and signal amplification in zebrafish RNA FISH.

    PubMed

    Hauptmann, Giselbert; Lauter, Gilbert; Söll, Iris

    2016-04-01

    In situ hybridization (ISH) has become an invaluable tool for the detection of RNA in cells, tissues and organisms. Due to improvements in target and signal amplification and in probe design remarkable progress has been made concerning sensitivity, specificity and resolution of chromogenic and fluorescent ISH (FISH). These advancements allow for exquisite cellular and sub-cellular resolution and for detecting multiple RNA species at a time by multiplexing. In zebrafish (F)ISH non-enzymatic and enzymatic amplification systems have been employed to obtain enhanced signal intensities and signal-to-noise ratios. These amplification strategies include branched DNA-based RNAscope and in situ hybridization chain reaction (HCR) techniques, as well as alkaline phosphatase (AP)- and horseradish peroxidase (PO)-based immunoassays. For practical application, we provide proven multiplex FISH protocols for AP- and PO-based visualization of mRNAs at high resolution. The protocols take advantage of optimized tyramide signal amplification (TSA) conditions of the PO assay and long-lasting high signal-to-noise ratio of the AP reaction, thereby enabling detection of less abundant transcripts. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. [Principle of LAMP method--a simple and rapid gene amplification method].

    PubMed

    Ushikubo, Hiroshi

    2004-06-01

    So far nucleic acid test (NAT) has been employed in various fields, including infectious disease diagnoses. However, due to its complicated procedures and relatively high cost, it has not been widely utilized in many actual diagnostic applications. We have therefore developed a simple and rapid gene amplification technology, Loop-mediated Isothermal Amplification (LAMP) method, which has shown prominent results of surpassing the performance of the conventional gene amplification methods. LAMP method acquires three main features: (1) all reaction can be carried out under isothermal conditions; (2) the amplification efficiency is extremely high and tremendous amount of amplification products can be obtained; and (3) the reaction is highly specific. Furthermore, developed from the standard LAMP method, a rapid LAMP method, by adding in the loop primers, can reduce the amplification time from the previous 1 hour to less than 30 minutes. Enormous amount of white precipitate of magnesium pyrophosphate is produced as a by-product of the amplification, therefore, direct visual detection is possible without using any reaction indicators and detection equipments. We believe LAMP technology, with the integration of these features, can rightly apply to clinical genetic testing, food and environmental analysis, as well as NAT in different fields.

  2. Amplification and noise properties of an erbium-doped multicore fiber amplifier.

    PubMed

    Abedin, K S; Taunay, T F; Fishteyn, M; Yan, M F; Zhu, B; Fini, J M; Monberg, E M; Dimarcello, F V; Wisk, P W

    2011-08-15

    A multicore erbium-doped fiber (MC-EDF) amplifier for simultaneous amplification in the 7-cores has been developed, and the gain and noise properties of individual cores have been studied. The pump and signal radiation were coupled to individual cores of MC-EDF using two tapered fiber bundled (TFB) couplers with low insertion loss. For a pump power of 146 mW, the average gain achieved in the MC-EDF fiber was 30 dB, and noise figure was less than 4 dB. The net useful gain from the multicore-amplifier, after taking into consideration of all the passive losses, was about 23-27 dB. Pump induced ASE noise transfer between the neighboring channel was negligible. © 2011 Optical Society of America

  3. Role of Sex and the Environment in Moderating Weight Gain Due to Inadequate Sleep.

    PubMed

    Coborn, Jamie E; Houser, Monica M; Perez-Leighton, Claudio E; Teske, Jennifer A

    2017-12-01

    The growing prevalence of obesity, inadequate sleep and sleep disorders together with the negative impact of lack of sleep on overall health highlights the need for therapies targeted towards weight gain due to sleep loss. Sex disparities in obesity and sleep disorders are present; yet, the role of sex is inadequately addressed and thus it is unclear whether sensitivity to sleep disruption differs between men and women. Like sex, environmental factors contribute to the development of obesity and poor sleep. The obesogenic environment is characterized by easy access to palatable foods and a low demand for energy expenditure in daily activities. These and other environmental factors are discussed, as they drive altered sleep or their interaction with food choice and intake can promote obesity. We discuss data that suggest differences in sleep patterns and responses to sleep disruption influence sex disparities in weight gain, and that enviromental disturbances alter sleep and interact with features of the obesogenic environment that together promote obesity.

  4. Acoustical power amplification and damping by temperature gradients.

    PubMed

    Biwa, Tetsushi; Komatsu, Ryo; Yazaki, Taichi

    2011-01-01

    Ceperley proposed a concept of a traveling wave heat engine ["A pistonless Stirling engine-The traveling wave heat engine," J. Acoust. Soc. Am. 66, 1508-1513 (1979).] that provided a starting point of thermoacoustics today. This paper verifies experimentally his idea through observation of amplification and strong damping of a plane acoustic traveling wave as it passes through axial temperature gradients. The acoustic power gain is shown to obey a universal curve specified by a dimensionless parameter ωτα; ω is the angular frequency and τα is the relaxation time for the gas to thermally equilibrate with channel walls. As an application of his idea, a three-stage acoustic power amplifier is developed, which attains the gain up to 10 with a moderate temperature ratio of 2.3.

  5. Magnetic flux amplification by Lenz lenses

    NASA Astrophysics Data System (ADS)

    Schoenmaker, J.; Pirota, K. R.; Teixeira, J. C.

    2013-08-01

    Tailoring magnetic flux distribution is highly desirable in a wide range of applications such as magnetic sensors and biomedicine. In this paper we study the manipulation of induced currents in passive devices in order to engineer the distribution of magnetic flux intensity in a given region. We propose two different approaches, one based on especially designed wire loops (Lenz law) and the other based on solid conductive pieces (eddy currents). The gain of such devices is mainly determined by geometry giving perspective of high amplification. We consistently modeled, simulated, and executed the proposed devices. Doubled magnetic flux intensity is demonstrated experimentally for a moderate aspect ratio.

  6. Magnetic flux amplification by Lenz lenses.

    PubMed

    Schoenmaker, J; Pirota, K R; Teixeira, J C

    2013-08-01

    Tailoring magnetic flux distribution is highly desirable in a wide range of applications such as magnetic sensors and biomedicine. In this paper we study the manipulation of induced currents in passive devices in order to engineer the distribution of magnetic flux intensity in a given region. We propose two different approaches, one based on especially designed wire loops (Lenz law) and the other based on solid conductive pieces (eddy currents). The gain of such devices is mainly determined by geometry giving perspective of high amplification. We consistently modeled, simulated, and executed the proposed devices. Doubled magnetic flux intensity is demonstrated experimentally for a moderate aspect ratio.

  7. Early-Stage Visual Processing and Cortical Amplification Deficits in Schizophrenia

    PubMed Central

    Butler, Pamela D.; Zemon, Vance; Schechter, Isaac; Saperstein, Alice M.; Hoptman, Matthew J.; Lim, Kelvin O.; Revheim, Nadine; Silipo, Gail; Javitt, Daniel C.

    2005-01-01

    Background Patients with schizophrenia show deficits in early-stage visual processing, potentially reflecting dysfunction of the magnocellular visual pathway. The magnocellular system operates normally in a nonlinear amplification mode mediated by glutamatergic (N-methyl-d-aspartate) receptors. Investigating magnocellular dysfunction in schizophrenia therefore permits evaluation of underlying etiologic hypotheses. Objectives To evaluate magnocellular dysfunction in schizophrenia, relative to known neurochemical and neuroanatomical substrates, and to examine relationships between electrophysiological and behavioral measures of visual pathway dysfunction and relationships with higher cognitive deficits. Design, Setting, and Participants Between-group study at an inpatient state psychiatric hospital and out-patient county psychiatric facilities. Thirty-three patients met DSM-IV criteria for schizophrenia or schizoaffective disorder, and 21 nonpsychiatric volunteers of similar ages composed the control group. Main Outcome Measures (1) Magnocellular and parvocellular evoked potentials, analyzed using nonlinear (Michaelis-Menten) and linear contrast gain approaches; (2) behavioral contrast sensitivity measures; (3) white matter integrity; (4) visual and nonvisual neuropsychological measures, and (5) clinical symptom and community functioning measures. Results Patients generated evoked potentials that were significantly reduced in response to magnocellular-biased, but not parvocellular-biased, stimuli (P=.001). Michaelis-Menten analyses demonstrated reduced contrast gain of the magnocellular system (P=.001). Patients showed decreased contrast sensitivity to magnocellular-biased stimuli (P<.001). Evoked potential deficits were significantly related to decreased white matter integrity in the optic radiations (P<.03). Evoked potential deficits predicted impaired contrast sensitivity (P=.002), which was in turn related to deficits in complex visual processing (P≤.04). Both

  8. Gain degradation and amplitude scintillation due to tropospheric turbulence

    NASA Technical Reports Server (NTRS)

    Theobold, D. M.; Hodge, D. B.

    1978-01-01

    It is shown that a simple physical model is adequate for the prediction of the long term statistics of both the reduced signal levels and increased peak-to-peak fluctuations. The model is based on conventional atmospheric turbulence theory and incorporates both amplitude and angle of arrival fluctuations. This model predicts the average variance of signals observed under clear air conditions at low elevation angles on earth-space paths at 2, 7.3, 20 and 30 GHz. Design curves based on this model for gain degradation, realizable gain, amplitude fluctuation as a function of antenna aperture size, frequency, and either terrestrial path length or earth-space path elevation angle are presented.

  9. Copy number gain of MYCN gene is a recurrent genetic aberration and favorable prognostic factor in Chinese pediatric neuroblastoma patients

    PubMed Central

    2013-01-01

    Background Amplification of MYCN oncogene is an established marker indicating aggressive tumor progression of neuroblastoma (NBL). But copy number analyses of MYCN gene in ganglioneuroblastoma (GNBL) and ganglioneuroma(GN) is poorly described in the literature. In the study, we evaluated the copy number aberrations of MYCN gene in clinical samples of NBLs, GNBLs and GNs and analyzed their association with clinical outcome of the patients. Methods In this study, we analyzed MYCN gene and chromosome 2 aneusomy by using fluorescence in situ hybridization (FISH) method in a total of 220 patients with NBL, GNBL and GN cases. Kaplan-Meier curves were generated by using SPSS 12.0 software. Results Of 220 patients, 178 (81.0%) were NBLs, 32 (14.5%) were GNBLs and 10 (4.5%) were GNs. MYCN gain is a recurrent genetic aberration of neuroblastic tumors (71.8%, 158/220), which was found in 129 NBLs (58.6%, 129/220), 25 GNBLs (11.4%, 25/220) and 4 GN cases (1.8%, 4/220). However, MYCN amplification was only present in 24 NBL tumors (13.5%, 24/178) and 1 GNBL case (3.1%, 1/32). Kaplan-Meier survival analysis indicated that MYCN amplification is significantly correlated with decreased overall survival in NBLs (P=0.017). Furthermore, a better prognosis trend was observed in patients with MYCN gain tumors compared with those with MYCN gene normal copy number tumors and MYCN amplification tumors (P=0.012). Conclusions In summary, the frequency of MYCN amplification in NBLs is high and is rarely observed in GNBLs and GNs, which suggest MYCN plays an important role in neuroblastic tumors differentiation. MYCN gain appeared to define a subgroup of NBLs with much better outcome and classification of MYCN gene copy number alteration as three groups (amplification, gain and normal) can provide a powerful prognostic indicator in NBLs. Virtual Slides The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/6417541528559124 PMID:23320395

  10. Absence of estrogen receptor alpha (ESR1) gene amplification in a series of breast cancers in Taiwan.

    PubMed

    Chen, Jim-Ray; Hsieh, Tsan-Yu; Chen, Huang-Yang; Yeh, Kun-Yan; Chen, Kuo-Su; ChangChien, Yi-Che; Pintye, Mariann; Chang, Liang-Che; Hwang, Cheng-Cheng; Chien, Hui-Ping; Hsu, Yuan-Chun

    2014-06-01

    Immunohistochemical expression of ERα, encoded by the ESR1 (estrogen receptor 1) gene located at 6q25.1, is the most important determinant of responsiveness to endocrine therapy in breast cancer. The prevalence and significance of ESR1 amplification in breast cancer remain controversial. We set out to assess ESR1 status and its relevance in breast cancer in Taiwan. We tested tissue samples from 311 invasive carcinomas in a tissue microarray for ESR1 status by fluorescent in situ hybridization (FISH) and chromogenic in situ hybridization (CISH). In order to examine its association with ERα and ESR1 status, HER2 status was determined by FISH. Of the carcinomas, 58.8 % (183/311) was ERα positive. None of the carcinomas showed amplification of ESR1 by either method, whereas 24.1 % (75/311) of the carcinomas harbored HER2 amplification. Of the carcinomas, 9.6 % (26/301) showed ESR1 gain (1.3 ≤ ratio ESR1/chromosome 6 < 2) by FISH and 10 % (24/299) by CISH. FISH and CISH results showed a good correlation (κ-coefficient = 0.786). ESR1 gain by FISH and CISH was significantly associated with high-grade (P = 0.0294 and 0.0417, respectively) but not with ERα expression, HER2 status, or overall survival. ERα positivity was significantly associated with better overall survival (P = 0.039). HER2 amplification was significantly related with poor overall survival (P = 0.002). Our data confirm that in breast cancer, HER2 amplification is a frequent genetic aberration and a negative prognostic factor, and show that ESR1 amplification is not a key genetic abnormality in the tumorigenesis of breast cancer in Taiwan.

  11. High-Gain AlxGa1-xAs/GaAs Transistors For Neural Networks

    NASA Technical Reports Server (NTRS)

    Kim, Jae-Hoon; Lin, Steven H.

    1991-01-01

    High-gain AlxGa1-xAs/GaAs npn double heterojunction bipolar transistors developed for use as phototransistors in optoelectronic integrated circuits, especially in artificial neural networks. Transistors perform both photodetection and saturating-amplification functions of neurons. Good candidates for such application because structurally compatible with laser diodes and light-emitting diodes, detect light, and provide high current gain needed to compensate for losses in holographic optical elements.

  12. Ultra-broadband amplification properties of Ni2+-doped glass-ceramics amplifiers.

    PubMed

    Jiang, Chun

    2009-04-13

    The energy level, transition configuration and mathematical model of Ni(2+)-doped glass-ceramics amplifiers are presented for the first time, to the best of one's knowledge. A quasi-three-level system is employed to model the gain and noise characteristics of the doped system, and the rate and power propagation equations of the mathematical model are solved to analyze the effect of the active ion concentration, fiber length, pump power as well as thermal-quenching on the gain spectra. It is shown that our model is in agreement with experimental result, and when excited at longer wavelength, the center of gain spectra of the amplifier red shifts, the ultra-broad band room-temperature gain spectra can cover 1.25-1.65 microm range for amplification of signal in the low-loss windows of the all-wave fiber without absorption peak caused by OH group.

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

    PubMed

    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.

  14. Detection of MDM2/CDK4 amplification in lipomatous soft tissue tumors from formalin-fixed, paraffin-embedded tissue: comparison of multiplex ligation-dependent probe amplification (MLPA) and fluorescence in situ hybridization (FISH).

    PubMed

    Creytens, David; van Gorp, Joost; Ferdinande, Liesbeth; Speel, Ernst-Jan; Libbrecht, Louis

    2015-02-01

    In this study, the detection of MDM2 and CDK4 amplification was evaluated in lipomatous soft tissue tumors using multiplex ligation-dependent probe amplification (MLPA), a PCR-based technique, in comparison with fluorescence in situ hybridization (FISH). These 2 techniques were evaluated in a series of 77 formalin-fixed, paraffin-embedded lipomatous tumors (27 benign adipose tumors, 28 atypical lipomatous tumors/well-differentiated liposarcomas, 18 dedifferentiated liposarcomas, and 4 pleomorphic liposarcomas). Using MLPA, with a cut-off ratio of >2, 36/71 samples (22 atypical lipomatous tumors/well-differentiated liposarcomas, and 14 dedifferentiated liposarcomas) showed MDM2 and CDK4 amplification. Using FISH as gold standard, MLPA showed a sensitivity of 90% (36/40) and a specificity of 100% (31/31) in detecting amplification of MDM2 and CDK4 in lipomatous soft tissue tumors. In case of high-level amplification (MDM2-CDK4/CEP12 ratio >5), concordance was 100%. Four cases of atypical lipomatous tumor/well-differentiated liposarcoma (4/26, 15%) with a low MDM2 and CDK4 amplification level (MDM2-CDK4/CEP12 ratio ranging between 2 and 2.5) detected by FISH showed no amplification by MLPA, although gain of MDM2 and CDK4 (ratios ranging between 1.6 and 1.9) was seen with MLPA. No amplification was detected in benign lipomatous tumors and pleomorphic liposarcomas. Furthermore, there was a very high concordance between the ratios obtained by FISH and MLPA. In conclusion, MLPA proves to be an appropriate and straightforward technique for screening MDM2/CDK4 amplification in lipomatous tumors, especially when a correct cut-off value and reference samples are chosen, and could be considered a good alternative to FISH to determine MDM2 and CDK4 amplification in liposarcomas. Moreover, because MLPA, as a multiplex technique, allows simultaneous detection of multiple chromosomal changes of interest, it could be in the future a very reliable and fast molecular analysis on

  15. Active control of noise amplification in the flow over a square leading-edge flat plate utilizing DBD plasma actuator

    NASA Astrophysics Data System (ADS)

    Yadong, HUANG; Benmou, ZHOU

    2018-05-01

    Perturbation is generally considered as the flow noise, and its energy can gain transient growth in the separation bubble. The amplified perturbations may cause unstable Kelvin–Helmohltz vortices which induce the three-dimensional transition. Active control of noise amplification via dielectric barrier discharge plasma actuator in the flow over a square leading-edge flat plate is numerically studied. The actuator is installed near the plate leading-edge where the separation bubble is formed. The maximum energy amplification of perturbations is positively correlated with the separation bubble scale which decreases with the increasing control parameters. As the magnitude of noise amplification is reduced, the laminar-turbulent transition is successfully suppressed.

  16. Experimental verification of gain drop due to general ion recombination for a carbon-ion pencil beam

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Tansho, Ryohei, E-mail: r-tansho@nirs.go.jp; Furukawa, Takuji; Hara, Yousuke

    Purpose: Accurate dose measurement in radiotherapy is critically dependent on correction for gain drop, which is the difference of the measured current from the ideal saturation current due to general ion recombination. Although a correction method based on the Boag theory has been employed, the theory assumes that ionized charge density in an ionization chamber (IC) is spatially uniform throughout the irradiation volume. For particle pencil beam scanning, however, the charge density is not uniform, because the fluence distribution of a pencil beam is not uniform. The aim of this study was to verify the effect of the nonuniformity ofmore » ionized charge density on the gain drop due to general ion recombination. Methods: The authors measured the saturation curve, namely, the applied voltage versus measured current, using a large plane-parallel IC and 24-channel parallel-plate IC with concentric electrodes. To verify the effect of the nonuniform ionized charge density on the measured saturation curve, the authors calculated the saturation curve using a method which takes into account the nonuniform ionized charge density and compared it with the measured saturation curves. Results: Measurement values of the different saturation curves in the different channels of the concentric electrodes differed and were consistent with the calculated values. The saturation curves measured by the large plane-parallel IC were also consistent with the calculation results, including the estimation error of beam size and of setup misalignment. Although the impact of the nonuniform ionized charge density on the gain drop was clinically negligible with the conventional beam intensity, it was expected that the impact would increase with higher ionized charge density. Conclusions: For pencil beam scanning, the assumption of the conventional Boag theory is not valid. Furthermore, the nonuniform ionized charge density affects the prediction accuracy of gain drop when the ionized charge

  17. Coherent-state discrimination via nonheralded probabilistic amplification

    NASA Astrophysics Data System (ADS)

    Rosati, Matteo; Mari, Andrea; Giovannetti, Vittorio

    2016-06-01

    A scheme for the detection of low-intensity optical coherent signals was studied which uses a probabilistic amplifier operated in the nonheralded version as the underlying nonlinear operation to improve the detection efficiency. This approach allows us to improve the statistics by keeping track of all possible outcomes of the amplification stage (including failures). When compared with an optimized Kennedy receiver, the resulting discrimination success probability we obtain presents a gain up to ˜1.85 % and it approaches the Helstrom bound appreciably faster than the Dolinar receiver when employed in an adaptive strategy. We also notice that the advantages obtained can ultimately be associated with the fact that, in the high-gain limit, the nonheralded version of the probabilistic amplifier induces a partial dephasing which preserves quantum coherence among low-energy eigenvectors while removing it elsewhere. A proposal to realize such a transformation based on an optical cavity implementation is presented.

  18. Visual Biopsy by Hydrogen Peroxide-Induced Signal Amplification.

    PubMed

    Zhao, Wenjie; Yang, Sheng; Yang, Jinfeng; Li, Jishan; Zheng, Jing; Qing, Zhihe; Yang, Ronghua

    2016-11-01

    Visual biopsy has attracted special interest by surgeons due to its simplicity and practicality; however, the limited sensitivity of the technology makes it difficult to achieve an early diagnosis. To circumvent this problem, herein, we report a visual signal amplification strategy for establishing a marker-recognizable biopsy that enables early cancer diagnosis. In our proposed approach, hydrogen peroxide (H 2 O 2 ) was selected as a potential underlying marker for its compact relationship in cancer progression. For selective recognition of H 2 O 2 in the process of visual biopsy, a benzylbenzeneboronic acid pinacol ester-decorated copolymer, namely, PMPC-Bpe, was synthesized, affording the final formation of the H 2 O 2 -responsive micelles in which amylose was trapped. The presence of H 2 O 2 activates the boronate ester recognition site and induces it releasing abundant indicator amylose, leading to signal amplification. The indicator came across the solution of KI/I 2 added to the sample, and the formative amylose-KI/I 2 complex has a distinct blue color at 574 nm for visual amplification detection. The feasibility of the proposed method is demonstrated by visualizing the H 2 O 2 content of cancer at different stages and three kinds of actual cancerous samples. As far as we know, this is the first paradigm to rationally design a signaling amplification-based molecular recognizable biopsy for visual and sensitive disease identification, which will extend new possibilities for marker-recognition and signal amplification-based biopsy in disease progressing.

  19. Phase sensitive amplification in integrated waveguides (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Schroeder, Jochen B.; Zhang, Youngbin; Husko, Chad A.; LeFrancois, Simon; Eggleton, Benjamin J.

    2017-02-01

    Phase sensitive amplification (PSA) is an attractive technology for integrated all-optical signal processing, due to it's potential for noiseless amplification, phase regeneration and generation of squeezed light. In this talk I will review our results on implementing four-wave-mixing based PSA inside integrated photonic devices. In particular I will discuss PSA in chalcogenide ridge waveguides and silicon slow-light photonic crystals. We achieve PSA in both pump- and signal-degenerate schemes with maximum extinction ratios of 11 (silicon) and 18 (chalcogenide) dB. I will further discuss the influence of two-photon absorption and free carrier effects on the performance of silicon-based PSAs.

  20. Gene amplification during myogenic differentiation

    PubMed Central

    Fischer, Ulrike; Ludwig, Nicole; Raslan, Abdulrahman; Meier, Carola; Meese, Eckart

    2016-01-01

    Gene amplifications are mostly an attribute of tumor cells and drug resistant cells. Recently, we provided evidence for gene amplifications during differentiation of human and mouse neural progenitor cells. Here, we report gene amplifications in differentiating mouse myoblasts (C2C12 cells) covering a period of 7 days including pre-fusion, fusion and post-fusion stages. After differentiation induction we found an increase in copy numbers of CDK4 gene at day 3, of NUP133 at days 4 and 7, and of MYO18B at day 4. The amplification process was accompanied by gamma-H2AX foci that are indicative of double stand breaks. Amplifications during the differentiating process were also found in primary human myoblasts with the gene CDK4 and NUP133 amplified both in human and mouse myoblasts. Amplifications of NUP133 and CDK4 were also identified in vivo on mouse transversal cryosections at stage E11.5. In the course of myoblast differentiation, we found amplifications in cytoplasm indicative of removal of amplified sequences from the nucleus. The data provide further evidence that amplification is a fundamental mechanism contributing to the differentiation process in mammalians. PMID:26760505

  1. High Efficiency Automatic-Power-Controlled and Gain-Clamped EDFA for Broadband Passive Optical Networking Systems

    NASA Astrophysics Data System (ADS)

    Shen, Jyi-Lai; Wei, Shui-Ken; Lin, Chin-Yuan; Iong Li, Ssu; Huang, Chih-Chuan

    2010-04-01

    The configuration of a simple improved high efficiency automatic-power-controlled and gain-clamped EDFA (APC-GC-EDFA) for broadband passive optical networking systems (BPON) is presented here. In order to compensate the phase and amplitude variation due to the different distance between the optical line terminal (OLT) and optical network units (ONU), the APC-GC-EDFA need to be employed. A single 980 nm laser module is employed as the primary pump. To extend the bandwidth, all C-band ASE is recycled as the secondary pump to enhance the gain efficiency. An electrical feedback circuit is used as a multi-wavelength channel transmitter monitor for the automatic power control to improve the gain-flattened flatness for stable amplification. The experimental results prove that the EDFA system can provide flatter clamped gain in both C-band and L-band configurations. The gain flatness wavelength ranging from 1530 to 1610 nm is within 32.83 ± 0.64 dB, i.e. below 1.95 %. The gains are clamped at 33.85 ± 0.65 dB for the input signal power of -40 dBm to -10 dBm. The range of noise figure is between 6.37 and 6.56, which is slightly lower compared to that of unclamped amplifiers. This will be very useful for measuring the gain flatness of APC-GC-EDFA. Finally, we have also demonstrated the records of the overall simultaneous dynamics measurements for the new system stabilization. The carrier to noise ratio (CNR) is 49.5 to 50.8 dBc which is above the National Television System Committee (NTSC) standard of 43 dBc, and both composite second order (CSO) 69.2 to 71.5 dBc and composite triple beat (CTB) of 69.8 to 72.2 dBc are above 53 dBc. The recorded corresponding rise-time of 1.087 ms indicates that the system does not exhibit any overshoot of gain or ASE variation due to the signal at the beginning of the pulse.

  2. Generation of 70 fs broadband pulses in a hybrid nonlinear amplification system with mode-locked Yb:YAG ceramic oscillator

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Wang, Chao; Luo, Daping; Yang, Chao; Li, Jiang; Ge, Lin; Pan, Yubai; Li, Wenxue

    2017-12-01

    We demonstrate the passively mode-locked laser performances of bulk Yb:YAG ceramic prepared by non-aqueous tape casting, which generates initial pulses in temporal width of 3 ps and spectrum width of 3 nm without intra-cavity dispersion management. The ceramic laser is further used as seeding oscillator in a fiber nonlinear amplification system, where ultrashort pulses in maximum output power of ˜100 W and pulse duration of 70 fs are achieved. Moreover, the laser spectrum is broadened to be ˜41 nm due to self-phase modulation effects in the gain fiber, overcoming the narrow spectrum limitations of ceramic materials. Our approach opens a new avenue for power-scaling and spectrum-expanding of femtosecond ceramic lasers.

  3. Fidelity criterion for quantum-domain transmission and storage of coherent states beyond the unit-gain constraint.

    PubMed

    Namiki, Ryo; Koashi, Masato; Imoto, Nobuyuki

    2008-09-05

    We generalize the experimental success criterion for quantum teleportation (memory) in continuous-variable quantum systems to be suitable for a non-unit-gain condition by considering attenuation (amplification) of the coherent-state amplitude. The new criterion can be used for a nonideal quantum memory and long distance quantum communication as well as quantum devices with amplification process. It is also shown that the framework to measure the average fidelity is capable of detecting all Gaussian channels in the quantum domain.

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

    PubMed

    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.

  5. Characterization of genome-wide copy number aberrations in colonic mixed adenoneuroendocrine carcinoma and neuroendocrine carcinoma reveals recurrent amplification of PTGER4 and MYC genes.

    PubMed

    Sinha, Namita; Gaston, Daniel; Manders, Daniel; Goudie, Marissa; Matsuoka, Makoto; Xie, Tao; Huang, Weei-Yuarn

    2018-03-01

    Colonic mixed adenoneuroendocrine carcinoma (MANEC) is an aggressive neoplasm with worse prognosis compared with adenocarcinoma. To gain a better understanding of the molecular features of colonic MANEC, we characterized the genome-wide copy number aberrations of 14 MANECs and 5 neuroendocrine carcinomas using the OncoScan FFPE (Affymetrix, Santa Clara, CA) assay. Compared with 269 colonic adenocarcinomas, 19 of 42 chromosomal arms of MANEC exhibited a similar frequency of major aberrant events as adenocarcinomas, and 13 chromosomal arms exhibited a higher frequency of copy number gains. Among them, the most significant chromosomal arms were 5p (77% versus 13%, P = .000012) and 8q (85% versus 33%, P = .0018). The Genomic Identification of Significant Targets in Cancers algorithm identified 7 peaks that drive the tumorgenesis of MANEC. For all except 5p13.1, the peaks largely overlapped with those of adenocarcinoma. Two tumors exhibited MYC amplification localized in 8q24.21, and 2 tumors exhibited PTGER4 amplification localized in 5p13.1. A total of 8 tumors exhibited high copy number gain of PTGER4 and/or MYC. Whereas the frequency of MYC amplification was similar to adenocarcinoma (10.5% versus 4%, P = .2), the frequency of PTGER4 amplification was higher than adenocarcinoma (10.5% versus 0.3%, P = .01). Our study demonstrates similar, but also distinct, copy number aberrations in MANEC compared with adenocarcinoma and suggests an important role for the MYC pathway of colonic carcinoma with neuroendocrine differentiation. The discovery of recurrent PTGER4 amplification implies a potential of exploring targeting therapy to the prostaglandin synthesis pathways in a subset of these tumors. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Cladding pumped Yb-doped HOM power amplifier with high gain

    NASA Astrophysics Data System (ADS)

    Abedin, Kazi S.; Ahmad, Raja; DeSantolo, Anthony M.; Nicholson, Jeffrey W.; Westbrook, Paul S.; Headley, Clifford; DiGiovanni, David J.

    2018-02-01

    Higher-order mode (HOM) fibers have been engineered to allow propagation of linearly polarized symmetric modes LP0,N in a robust way. Compared with the fundamental mode LP(0,1), HOMs exhibits an effective area that can be larger by over two order magnitude, and thus propagating light in these modes could greatly suppress the effect of nonlinear effects. HOM fibers could also be doped with rare earth ions in order to amplify light propagating in these modes, which offers the enormous potential for generating high-intensity pulses. Excitation of HOM gain fiber using cladding pumping with multimode pump source is attractive for ytterbium based amplifiers, because of the availability of low-cost multimode pump diodes in the 975nm wavelength range. One problem associated with cladding pumping which leads to excitation of the large doped core (over 100 μm diameter) is that it could result in a large amount of amplifiedspontaneous- emission (ASE) noise, particularly when the input signal is weak. Optimization of amplifier design is critical in order to suppress ASE and achieve high gain and pump-to-signal conversion efficiency. We conducted numerical modeling of a cladding pumped HOM-amplifier, which revealed that this problem could be mitigated by using a relatively long gain-fiber that allowed reabsorption of the forward propagating ASE resulting in a further amplification of the signal. We demonstrate efficient amplification of a LP0,10 mode with an effective area 3140μm2 in an Yb-doped HOM amplifier cladding pumped at 975nm. We have successfully obtained a 20.2dB gain for 0.95 W 1064 nm input seed signal to more than 105W.

  7. Soliton-induced relativistic-scattering and amplification.

    PubMed

    Rubino, E; Lotti, A; Belgiorno, F; Cacciatori, S L; Couairon, A; Leonhardt, U; Faccio, D

    2012-01-01

    Solitons are of fundamental importance in photonics due to applications in optical data transmission and also as a tool for investigating novel phenomena ranging from light generation at new frequencies and wave-trapping to rogue waves. Solitons are also moving scatterers: they generate refractive index perturbations moving at the speed of light. Here we found that such perturbations scatter light in an unusual way: they amplify light by the mixing of positive and negative frequencies, as we describe using a first Born approximation and numerical simulations. The simplest scenario in which these effects may be observed is within the initial stages of optical soliton propagation: a steep shock front develops that may efficiently scatter a second, weaker probe pulse into relatively intense positive and negative frequency modes with amplification at the expense of the soliton. Our results show a novel all-optical amplification scheme that relies on soliton induced scattering.

  8. An amorphous silicon photodiode with 2 THz gain-bandwidth product based on cycling excitation process

    NASA Astrophysics Data System (ADS)

    Yan, Lujiang; Yu, Yugang; Zhang, Alex Ce; Hall, David; Niaz, Iftikhar Ahmad; Raihan Miah, Mohammad Abu; Liu, Yu-Hsin; Lo, Yu-Hwa

    2017-09-01

    Since impact ionization was observed in semiconductors over half a century ago, avalanche photodiodes (APDs) using impact ionization in a fashion of chain reaction have been the most sensitive semiconductor photodetectors. However, APDs have relatively high excess noise, a limited gain-bandwidth product, and high operation voltage, presenting a need for alternative signal amplification mechanisms of superior properties. As an amplification mechanism, the cycling excitation process (CEP) was recently reported in a silicon p-n junction with subtle control and balance of the impurity levels and profiles. Realizing that CEP effect depends on Auger excitation involving localized states, we made the counter intuitive hypothesis that disordered materials, such as amorphous silicon, with their abundant localized states, can produce strong CEP effects with high gain and speed at low noise, despite their extremely low mobility and large number of defects. Here, we demonstrate an amorphous silicon low noise photodiode with gain-bandwidth product of over 2 THz, based on a very simple structure. This work will impact a wide range of applications involving optical detection because amorphous silicon, as the primary gain medium, is a low-cost, easy-to-process material that can be formed on many kinds of rigid or flexible substrates.

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

    PubMed

    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.

  10. Non-biased and efficient global amplification of a single-cell cDNA library

    PubMed Central

    Huang, Huan; Goto, Mari; Tsunoda, Hiroyuki; Sun, Lizhou; Taniguchi, Kiyomi; Matsunaga, Hiroko; Kambara, Hideki

    2014-01-01

    Analysis of single-cell gene expression promises a more precise understanding of molecular mechanisms of a living system. Most techniques only allow studies of the expressions for limited numbers of gene species. When amplification of cDNA was carried out for analysing more genes, amplification biases were frequently reported. A non-biased and efficient global-amplification method, which uses a single-cell cDNA library immobilized on beads, was developed for analysing entire gene expressions for single cells. Every step in this analysis from reverse transcription to cDNA amplification was optimized. By removing degrading excess primers, the bias due to the digestion of cDNA was prevented. Since the residual reagents, which affect the efficiency of each subsequent reaction, could be removed by washing beads, the conditions for uniform and maximized amplification of cDNAs were achieved. The differences in the amplification rates for randomly selected eight genes were within 1.5-folds, which could be negligible for most of the applications of single-cell analysis. The global amplification gives a large amount of amplified cDNA (>100 μg) from a single cell (2-pg mRNA), and that amount is enough for downstream analysis. The proposed global-amplification method was used to analyse transcript ratios of multiple cDNA targets (from several copies to several thousand copies) quantitatively. PMID:24141095

  11. Highly Efficient Protein Misfolding Cyclic Amplification

    PubMed Central

    Ostapchenko, Valeriy G.; Savtchenk, Regina; Alexeeva, Irina; Rohwer, Robert G.; Baskakov, Ilia V.

    2011-01-01

    Protein misfolding cyclic amplification (PMCA) provides faithful replication of mammalian prions in vitro and has numerous applications in prion research. However, the low efficiency of conversion of PrPC into PrPSc in PMCA limits the applicability of PMCA for many uses including structural studies of infectious prions. It also implies that only a small sub-fraction of PrPC may be available for conversion. Here we show that the yield, rate, and robustness of prion conversion and the sensitivity of prion detection are significantly improved by a simple modification of the PMCA format. Conducting PMCA reactions in the presence of Teflon beads (PMCAb) increased the conversion of PrPC into PrPSc from ∼10% to up to 100%. In PMCAb, a single 24-hour round consistently amplified PrPSc by 600-700-fold. Furthermore, the sensitivity of prion detection in one round (24 hours) increased by 2-3 orders of magnitude. Using serial PMCAb, a 1012-fold dilution of scrapie brain material could be amplified to the level detectible by Western blotting in 3 rounds (72 hours). The improvements in amplification efficiency were observed for the commonly used hamster 263K strain and for the synthetic strain SSLOW that otherwise amplifies poorly in PMCA. The increase in the amplification efficiency did not come at the expense of prion replication specificity. The current study demonstrates that poor conversion efficiencies observed previously have not been due to the scarcity of a sub-fraction of PrPC susceptible to conversion nor due to limited concentrations of essential cellular cofactors required for conversion. The new PMCAb format offers immediate practical benefits and opens new avenues for developing fast ultrasensitive assays and for producing abundant quantities of PrPSc in vitro. PMID:21347353

  12. Two approximations for the geometric model of signal amplification in an electron-multiplying charge-coupled device detector

    PubMed Central

    Chao, Jerry; Ram, Sripad; Ward, E. Sally; Ober, Raimund J.

    2014-01-01

    The extraction of information from images acquired under low light conditions represents a common task in diverse disciplines. In single molecule microscopy, for example, techniques for superresolution image reconstruction depend on the accurate estimation of the locations of individual particles from generally low light images. In order to estimate a quantity of interest with high accuracy, however, an appropriate model for the image data is needed. To this end, we previously introduced a data model for an image that is acquired using the electron-multiplying charge-coupled device (EMCCD) detector, a technology of choice for low light imaging due to its ability to amplify weak signals significantly above its readout noise floor. Specifically, we proposed the use of a geometrically multiplied branching process to model the EMCCD detector’s stochastic signal amplification. Geometric multiplication, however, can be computationally expensive and challenging to work with analytically. We therefore describe here two approximations for geometric multiplication that can be used instead. The high gain approximation is appropriate when a high level of signal amplification is used, a scenario which corresponds to the typical usage of an EMCCD detector. It is an accurate approximation that is computationally more efficient, and can be used to perform maximum likelihood estimation on EMCCD image data. In contrast, the Gaussian approximation is applicable at all levels of signal amplification, but is only accurate when the initial signal to be amplified is relatively large. As we demonstrate, it can importantly facilitate the analysis of an information-theoretic quantity called the noise coefficient. PMID:25075263

  13. Development of Low Noise-Broadband Raman Amplification Systems Based on Photonic Crystal Fibers for High Capacity DWDM Networks

    NASA Astrophysics Data System (ADS)

    Elgamri, Abdelghafor

    The increased demand from IP traffic, video application and cell backhaul has placed fiber routes under severe stains. The high demands for large bandwidth from enormous numbers from cell sites on a network made the capacity of yesterday's networks not adequate for today's bandwidth demand. Carries considered Dense Wavelength Division Multiplexing (DWDM) network to overcome this issue. Recently, there has been growing interest in fiber Raman amplifiers due to their capability to upgrade the wavelength-division-multiplexing bandwidth, arbitrary gain bandwidth. In addition, photonic crystal fibers have been widely modeled, studied, and fabricated due to their peculiar properties that cannot be achieved with conventional fibers. The focus of this thesis is to develop a low-noise broadband Raman amplification system based on photonic crystal Fiber that can be implemented in high capacity DWDM network successfully. The design a module of photonic crystal fiber Raman amplifier is based on the knowledge of the fiber cross-sectional characteristics i.e. the geometric parameters and the Germania concentration in the dope area. The module allows to study different air-hole dimension and disposition, with or without a central doped area. In addition the design integrates distributed Raman amplifier and nonlinear optical loop mirror to improve the signal to noise ratio and overall gain in large capacity DWDM networks.

  14. Accurate modeling of high-repetition rate ultrashort pulse amplification in optical fibers

    PubMed Central

    Lindberg, Robert; Zeil, Peter; Malmström, Mikael; Laurell, Fredrik; Pasiskevicius, Valdas

    2016-01-01

    A numerical model for amplification of ultrashort pulses with high repetition rates in fiber amplifiers is presented. The pulse propagation is modeled by jointly solving the steady-state rate equations and the generalized nonlinear Schrödinger equation, which allows accurate treatment of nonlinear and dispersive effects whilst considering arbitrary spatial and spectral gain dependencies. Comparison of data acquired by using the developed model and experimental results prove to be in good agreement. PMID:27713496

  15. An evaluation of direct PCR amplification

    PubMed Central

    Hall, Daniel E.; Roy, Reena

    2014-01-01

    Aim To generate complete DNA profiles from blood and saliva samples deposited on FTA® and non-FTA® paper substrates following a direct amplification protocol. Methods Saliva samples from living donors and blood samples from deceased individuals were deposited on ten different FTA® and non-FTA® substrates. These ten paper substrates containing body fluids were kept at room temperature for varying lengths of time ranging from one day to approximately one year. For all assays in this research, 1.2 mm punches were collected from each substrate containing one type of body fluid and amplified with reagents provided in the nine commercial polymerase chain reaction (PCR) amplification kits. The substrates were not subjected to purification reagent or extraction buffer prior to amplification. Results Success rates were calculated for all nine amplification kits and all ten substrates based on their ability to yield complete DNA profiles following a direct amplification protocol. Six out of the nine amplification kits, and four out of the ten paper substrates had the highest success rates overall. Conclusion The data show that it is possible to generate complete DNA profiles following a direct amplification protocol using both standard (non-direct) and direct PCR amplification kits. The generation of complete DNA profiles appears to depend more on the success of the amplification kit rather than the than the FTA®- or non-FTA®-based substrates. PMID:25559837

  16. Prognostic relevance of 20q13 gains in sporadic colorectal cancers: a FISH analysis.

    PubMed

    Aust, D E; Muders, M; Köhler, A; Schmidt, M; Diebold, J; Müller, C; Löhrs, U; Waldman, F M; Baretton, G B

    2004-08-01

    Amplification of 20q13 is a frequent chromosomal alteration in solid tumors and harbors a number of putative oncogenes (CAS/CSE1-L, NABC1, or Aurora2). Amplifications on 20q13 have been identified as an independent prognostic marker indicating worse survival in breast and ovarian cancer. However, little is known about the prognostic significance of 20q13 gains in sporadic colorectal cancers. The aim of this study was to correlate 20q13 gains in sporadic colorectal cancers with other known prognostic factors, tumor progression, and overall survival. Nuclei were extracted from 146 paraffin-embedded colorectal cancers of different UICC stages and used for fluorescence in situ hybridization (FISH) with a directly labeled probe for 20q13.2 (VYSIS). Signals were counted in 120 nuclei per sample. 20q13 was considered gained when > or =40% of the nuclei showed 3 or more FISH signals. Statistical correlations were tested with log-rank tests and Kaplan-Meier survival curves. Signal numbers for 20q13.2 were gained in 78 cases (53%). Cases with gains on 20q13.2 showed worse outcome than cases without: the gain of 20q13.2 was an independent prognostic marker for overall survival (P=0.006) as well as tumor progression (P=0.012) in univariate and multivariate analyses. Gains on 20q13.2 did not correlate with tumor stage. However, there was a significant association between 20q13.2 gains and tumor location in the left-sided colon and an inverse correlation between histologic grade and 20q13.2 gains. These data indicate that gains on 20q13.2 correlate with faster tumor progression and worse patient survival independent from tumor size and lymph node involvement. Therefore, alterations on 20q13 are an important biological event in colorectal tumor progression with independent prognostic relevance.

  17. Telomerase Repeated Amplification Protocol (TRAP).

    PubMed

    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

  18. Two-octave spanning single pump parametric amplification at 1550 nm in a host lead-silicate binary multi-clad microstructure fiber: Influence of multi-order dispersion engineering

    NASA Astrophysics Data System (ADS)

    Chatterjee, Sudip K.; Khan, Saba N.; Chaudhuri, Partha Roy

    2014-12-01

    An ultra-wide 1646 nm (1084-2730 nm), continuous-wave single pump parametric amplification spanning from near-infrared to short-wave infrared band (NIR-SWIR) in a host lead-silicate based binary multi-clad microstructure fiber (BMMF) is analyzed and reported. This ultra-broad band (widest reported to date) parametric amplification with gain more than 10 dB is theoretically achieved by a combination of low input pump power source ~7 W and a short-length of ~70 cm of nonlinear-BMMF through accurately engineered multi-order dispersion coefficients. A highly efficient theoretical formulation based on four-wave-mixing (FWM) is worked out to determine fiber's chromatic dispersion (D) profile which is used to optimise the gain-bandwidth and ripple of the parametric gain profile. It is seen that by appropriately controlling the higher-order dispersion coefficient (up-to sixth order), a great enhancement in the gain-bandwidth (2-3 times) can be achieved when operated very close to zero-dispersion wavelength (ZDW) in the anomalous dispersion regime. Moreover, the proposed theoretical model can predict the maximum realizable spectral width and the required pump-detuning (w.r.t ZDW) of any advanced complex microstructured fiber. Our thorough investigation of the wide variety of broadband gain spectra obtained as an integral part of this research work opens up the way for realizing amplification in the region (SWIR) located far from the pump (NIR) where good amplifiers currently do not exist.

  19. IQ Gains and the Binet Decrements.

    ERIC Educational Resources Information Center

    Flynn, James R.

    1984-01-01

    Thorndike's Stanford-Binet data suggest that from 1932 to 1971-72 preschool children enjoyed greater IQ gains than older children, possibly due to the rise of television. Additional analysis indicated that gains were either due to sampling error or totally antedated 1947. Gains of 12 IQ points were found for Americans. (Author/EGS)

  20. PDGFRA amplification is common in pediatric and adult high-grade astrocytomas and identifies a poor prognostic group in IDH1 mutant glioblastoma

    PubMed Central

    Phillips, Joanna J.; Aranda, Derick; Ellison, David W.; Judkins, Alexander R.; Croul, Sidney E.; Brat, Daniel J.; Ligon, Keith L.; Horbinski, Craig; Venneti, Sriram; Zadeh, Gelareh; Santi, Mariarita; Zhou, Shengmei; Appin, Christina L.; Sioletic, Stefano; Sullivan, Lisa M.; Martinez-Lage, Maria; Robinson, Aaron E.; Yong, William H.; Cloughesy, Timothy; Lai, Albert; Phillips, Heidi S.; Marshall, Roxanne; Mueller, Sabine; Haas-Kogan, Daphne A.; Molinaro, Annette M.; Perry, Arie

    2013-01-01

    High-grade astrocytomas (HGAs), corresponding to WHO grades III (AA) and IV (GBM), are biologically aggressive and their molecular classification is increasingly relevant to clinical management. PDGFRA amplification is common in HGAs, although its prognostic significance remains unclear. Using fluorescence in situ hybridization (FISH), the most sensitive technique for detecting PDGFRA copy number gains, we determined PDGFRA amplification status in 123 pediatric and 263 adult HGAs. A range of PDGFRA FISH patterns were identified and cases were scored as non-amplified (normal and polysomy) or amplified (low-level and high-level). PDGFRA amplification was frequent in pediatric (29.3%) and adult (20.9%) tumors. Amplification was not prognostic in pediatric HGAs. In adult tumors diagnosed initially as GBM, the presence of combined PDGFRA amplification and IDH1R132H mutation was a significant independent prognostic factor (p=0.01). In HGAs, PDGFRA amplification is common and can manifest as high-level and focal or low-level amplifications. Our data indicate that the latter is more prevalent than previously reported with copy number averaging techniques. To our knowledge, this is the largest survey of PDGFRA status in adult and pediatric HGAs and suggests PDGFRA amplification increases with grade and is associated with a less favorable prognosis in IDH1 mutant de novo GBMs. PMID:23438035

  1. Miniaturized isothermal nucleic acid amplification, a review.

    PubMed

    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.

  2. Optical Parametric Amplification of Single Photon: Statistical Properties and Quantum Interference

    NASA Astrophysics Data System (ADS)

    Xu, Xue-Xiang; Yuan, Hong-Chun

    2014-05-01

    By using phase space method, we theoretically investigate the quantum statistical properties and quantum interference of optical parametric amplification of single photon. The statistical properties, such as the Wigner function (WF), average photon number, photon number distribution and parity, are derived analytically for the fields of the two output ports. The results indicate that the fields in the output ports are multiphoton states rather than single photon state due to the amplification of the optical parametric amplifiers (OPA). In addition, the phase sensitivity is also examined by using the detection scheme of parity measurement.

  3. Influence of chirp on laser-pulse amplification in Brillouin backscattering schemes

    NASA Astrophysics Data System (ADS)

    Lehmann, Goetz; Schluck, Friedrich; Spatschek, Karl-Heinz

    2015-11-01

    Plasma-based amplification of laser pulses is currently discussed as a key component for the next generation of high-intensity laser systems, possibly enabling the generation of ultra-short pulses in the exawatt-zetawatt regime. In these scenarios the energy of a long pump pulse (several ps to ns of duration) is transferred to a short seed pulse via a plasma oscillation. Weakly- and strongly-coupled (sc) Brillouin backscattering have been identified as potential candidates for robust amplification scenarios. With the help of three-wave interaction models, we investigate the influence of a chirp of the pump beam on the seed amplification. We show that chirp can mitigate deleterious spontaneous Raman backscattering of the pump off noise and that at the same time the amplification dynamics due to Brillouin scattering is still intact. For the experimentally very interesting case of sc-Brillouin we find a dependence of the efficiency on the sign of the chirp. Funding provided by project B10 of SFB TR18 of the Deutsche Forschungsgemeinschaft (DFG).

  4. Progress towards large gain-length products on the Li-like recombination scheme

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zeitoun, P.; Jamelot, G.; Carillon, A.

    1995-05-01

    Investigating possibilities of attaining large gain-length products on the recombination scheme using lithium-like ions, we have examined two approaches aimed at overcoming the problem of plasma non-uniformity susceptible to destroy gain by a number of processes. In the first approach we studied amplification on the transitions 5f-3d and 4f-3d in Li-like Al{sup 10+} plasma column produced by smoothing optics using lens arrays. Employing this device resulted in the gain holding up significantly longer than when no smoothing optics was used. Second, we have investigated numerically and experimentally the 5g-4f transition in Li-like S{sup 13+}, as the gain should be barelymore » affected by the plasma nonuniformities. Encouraging results were obtained and their various aspects are discussed.« less

  5. Nonlinear Brillouin amplification of finite-duration seeds in the strong coupling regime

    NASA Astrophysics Data System (ADS)

    Lehmann, G.; Spatschek, K. H.

    2013-07-01

    Parametric plasma processes received renewed interest in the context of generating ultra-intense and ultra-short laser pulses up to the exawatt-zetawatt regime. Both Raman as well as Brillouin amplifications of seed pulses were proposed. Here, we investigate Brillouin processes in the one-dimensional (1D) backscattering geometry with the help of numerical simulations. For optimal seed amplification, Brillouin scattering is considered in the so called strong coupling (sc) regime. Special emphasis lies on the dependence of the amplification process on the finite duration of the initial seed pulses. First, the standard plane-wave instability predictions are generalized to pulse models, and the changes of initial seed pulse forms due to parametric instabilities are investigated. Three-wave-interaction results are compared to predictions by a new (kinetic) Vlasov code. The calculations are then extended to the nonlinear region with pump depletion. Generation of different seed layers is interpreted by self-similar solutions of the three-wave interaction model. Similar to Raman amplification, shadowing of the rear layers by the leading layers of the seed occurs. The shadowing is more pronounced for initially broad seed pulses. The effect is quantified for Brillouin amplification. Kinetic Vlasov simulations agree with the three-wave interaction predictions and thereby affirm the universal validity of self-similar layer formation during Brillouin seed amplification in the strong coupling regime.

  6. Weight gain - unintentional

    MedlinePlus

    ... Cushing syndrome Underactive thyroid, or low thyroid (hypothyroidism) Polycystic ovary syndrome Menopause Pregnancy Bloating, or swelling due to a buildup of fluid in the tissues can cause weight gain. This may be due to menstruation, heart ...

  7. Diverse Roles of Axonemal Dyneins in Drosophila Auditory Neuron Function and Mechanical Amplification in Hearing.

    PubMed

    Karak, Somdatta; Jacobs, Julie S; Kittelmann, Maike; Spalthoff, Christian; Katana, Radoslaw; Sivan-Loukianova, Elena; Schon, Michael A; Kernan, Maurice J; Eberl, Daniel F; Göpfert, Martin C

    2015-11-26

    Much like vertebrate hair cells, the chordotonal sensory neurons that mediate hearing in Drosophila are motile and amplify the mechanical input of the ear. Because the neurons bear mechanosensory primary cilia whose microtubule axonemes display dynein arms, we hypothesized that their motility is powered by dyneins. Here, we describe two axonemal dynein proteins that are required for Drosophila auditory neuron function, localize to their primary cilia, and differently contribute to mechanical amplification in hearing. Promoter fusions revealed that the two axonemal dynein genes Dmdnah3 (=CG17150) and Dmdnai2 (=CG6053) are expressed in chordotonal neurons, including the auditory ones in the fly's ear. Null alleles of both dyneins equally abolished electrical auditory neuron responses, yet whereas mutations in Dmdnah3 facilitated mechanical amplification, amplification was abolished by mutations in Dmdnai2. Epistasis analysis revealed that Dmdnah3 acts downstream of Nan-Iav channels in controlling the amplificatory gain. Dmdnai2, in addition to being required for amplification, was essential for outer dynein arms in auditory neuron cilia. This establishes diverse roles of axonemal dyneins in Drosophila auditory neuron function and links auditory neuron motility to primary cilia and axonemal dyneins. Mutant defects in sperm competition suggest that both dyneins also function in sperm motility.

  8. Dynamics and control of DNA sequence amplification

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Marimuthu, Karthikeyan; Chakrabarti, Raj, E-mail: raj@pmc-group.com, E-mail: rajc@andrew.cmu.edu; Division of Fundamental Research, PMC Advanced Technology, Mount Laurel, New Jersey 08054

    2014-10-28

    DNA amplification is the process of replication of a specified DNA sequence in vitro through time-dependent manipulation of its external environment. A theoretical framework for determination of the optimal dynamic operating conditions of DNA amplification reactions, for any specified amplification objective, is presented based on first-principles biophysical modeling and control theory. Amplification of DNA is formulated as a problem in control theory with optimal solutions that can differ considerably from strategies typically used in practice. Using the Polymerase Chain Reaction as an example, sequence-dependent biophysical models for DNA amplification are cast as control systems, wherein the dynamics of the reactionmore » are controlled by a manipulated input variable. Using these control systems, we demonstrate that there exists an optimal temperature cycling strategy for geometric amplification of any DNA sequence and formulate optimal control problems that can be used to derive the optimal temperature profile. Strategies for the optimal synthesis of the DNA amplification control trajectory are proposed. Analogous methods can be used to formulate control problems for more advanced amplification objectives corresponding to the design of new types of DNA amplification reactions.« less

  9. Absorption, Transmission and Amplification in a Double-Cavity Optomechanical System with Coulomb-Interaction

    NASA Astrophysics Data System (ADS)

    Geng, H.; Liu, H. D.

    2018-04-01

    We explore three interesting phenomena in a double-cavity optomechanical system: coherent perfect absorption, coherent perfect transmission and output signal amplification, and find that these phenomena can be realized and controlled by the coulomb-interaction between the dissipative oscillator locates in the cavity and the gain oscillator locates outside. They originate from the efficient hybrid coupling of optical and mechanical modes, and can be used for realizing novel photonic devices in quantum information networks.

  10. Real-time correction of tsunami site effect by frequency-dependent tsunami-amplification factor

    NASA Astrophysics Data System (ADS)

    Tsushima, H.

    2017-12-01

    For tsunami early warning, I developed frequency-dependent tsunami-amplification factor and used it to design a recursive digital filter that can be applicable for real-time correction of tsunami site response. In this study, I assumed that a tsunami waveform at an observing point could be modeled by convolution of source, path and site effects in time domain. Under this assumption, spectral ratio between offshore and the nearby coast can be regarded as site response (i.e. frequency-dependent amplification factor). If the amplification factor can be prepared before tsunamigenic earthquakes, its temporal convolution to offshore tsunami waveform provides tsunami prediction at coast in real time. In this study, tsunami waveforms calculated by tsunami numerical simulations were used to develop frequency-dependent tsunami-amplification factor. Firstly, I performed numerical tsunami simulations based on nonlinear shallow-water theory from many tsuanmigenic earthquake scenarios by varying the seismic magnitudes and locations. The resultant tsunami waveforms at offshore and the nearby coastal observing points were then used in spectral-ratio analysis. An average of the resulted spectral ratios from the tsunamigenic-earthquake scenarios is regarded as frequency-dependent amplification factor. Finally, the estimated amplification factor is used in design of a recursive digital filter that can be applicable in time domain. The above procedure is applied to Miyako bay at the Pacific coast of northeastern Japan. The averaged tsunami-height spectral ratio (i.e. amplification factor) between the location at the center of the bay and the outside show a peak at wave-period of 20 min. A recursive digital filter based on the estimated amplification factor shows good performance in real-time correction of tsunami-height amplification due to the site effect. This study is supported by Japan Society for the Promotion of Science (JSPS) KAKENHI grant 15K16309.

  11. Coherent state amplification using frequency conversion and a single photon source

    NASA Astrophysics Data System (ADS)

    Kasture, Sachin

    2017-11-01

    Quantum state discrimination lies at the heart of quantum communication and quantum cryptography protocols. Quantum Key Distribution (QKD) using coherent states and homodyne detection has been shown to be a feasible method for quantum communication over long distances. However, this method is still limited because of optical losses. Noiseless coherent state amplification has been proposed as a way to overcome this. Photon addition using stimulated Spontaneous Parametric Down-conversion followed by photon subtraction has been used as a way to implement amplification. However, this process occurs with very low probability which makes it very difficult to implement cascaded stages of amplification due to dark count probability in the single photon detectors used to herald the addition and subtraction of single photons. We discuss a scheme using the χ (2) and χ (3) optical non-linearity and frequency conversion (sum and difference frequency generation) along with a single photon source to implement photon addition. Unlike the photon addition scheme using SPDC, this scheme allows us to tune the success probability at the cost of reduced amplification. The photon statistics of the converted field can be controlled using the power of the pump field and the interaction time.

  12. Multipass laser amplification with near-field far-field optical separation

    DOEpatents

    Hagen, Wilhelm F.

    1979-01-01

    This invention discloses two classes of optical configurations for high power laser amplification, one allowing near-field and the other allowing far-field optical separation, for the multiple passage of laser pulses through one or more amplifiers over an open optical path. These configurations may reimage the amplifier or any other part of the cavity on itself so as to suppress laser beam intensity ripples that arise from diffraction and/or non-linear effects. The optical cavities combine the features of multiple passes, spatial filtering and optical reimaging and allow sufficient time for laser gain recovery.

  13. Spectral amplification models for response spectrum addressing the directivity effect

    NASA Astrophysics Data System (ADS)

    Moghimi, Saed; Akkar, Sinan

    2017-04-01

    Ground motions with forward directivity effects are known with their significantly large spectral ordinates in medium-to-long periods. The large spectral ordinates stem from the impulsive characteristics of the forward directivity ground motions. The quantification of these spectral amplifications requires the identification of major seismological parameters that play a role in their generation. After running a suite of probabilistic seismic hazard analysis, Moghimi and Akkar (2016) have shown that fault slip rate, fault characteristic magnitude, fault-site geometry as well as mean annual exceedance rate are important parameters that determine the level of spectral amplification due to directivity. These parameters are considered to develop two separate spectral amplification equations in this study. The proposed equations rely on Shahi and Baker (SHB11; 2011) and Chiou and Spudich (CHS13; Spudic et al., 2013) narrow-band forward directivity models. The presented equations only focus on the estimation of maximum spectral amplifications that occur at the ends of the fault segments. This way we eliminate the fault-site parameter in our equations for simplification. The proposed equations show different trends due to differences in the narrow-band directivity models of SHB11 and CHS13. The equations given in this study can form bases for describing forward directivity effects in seismic design codes. REFERENCES Shahi. S., Baker, J.W. (2011), "An Empirically Calibrated Framework for Including the Effects of Near-Fault Directivity in Probabilistic Seismic Hazard Analysis", Bulletin of the Seismological Society of America, 101(2): 742-755. Spudich, P., Watson-Lamprey, J., Somerville, P., Bayless, J., Shahi, S. K., Baker, J. W., Rowshandel, B., and Chiou, B. (2013), "Final Report of the NGA-West2 Directivity Working Group", PEER Report 2013/09. Moghimi. S., Akkar, S. (2016), "Implications of Forward Directivity Effects on Design Ground Motions", Seismological Society of

  14. Loop mediated isothermal amplification: An innovative gene amplification technique for animal diseases.

    PubMed

    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.

  15. Tailored pump compensation for Brillouin optical time-domain analysis with distributed Brillouin amplification.

    PubMed

    Kim, Young Hoon; Song, Kwang Yong

    2017-06-26

    A Brillouin optical time domain analysis (BOTDA) system utilizing tailored compensation for the propagation loss of the pump pulse is demonstrated for long-range and high-resolution distributed sensing. A continuous pump wave for distributed Brillouin amplification (DBA pump) of the pump pulse co-propagates with the probe wave, where gradual variation of the spectral width is additionally introduced to the DBA pump to obtain a uniform Brillouin gain along the position. In the experimental confirmation, a distributed strain measurement along a 51.2 km fiber under test is presented with a spatial resolution of 20 cm, in which the measurement error (σ) of less than 1.45 MHz and the near-constant Brillouin gain of the probe wave are maintained throughout the fiber.

  16. Impulse-induced optimum signal amplification in scale-free networks.

    PubMed

    Martínez, Pedro J; Chacón, Ricardo

    2016-04-01

    Optimizing information transmission across a network is an essential task for controlling and manipulating generic information-processing systems. Here, we show how topological amplification effects in scale-free networks of signaling devices are optimally enhanced when the impulse transmitted by periodic external signals (time integral over two consecutive zeros) is maximum. This is demonstrated theoretically by means of a star-like network of overdamped bistable systems subjected to generic zero-mean periodic signals and confirmed numerically by simulations of scale-free networks of such systems. Our results show that the enhancer effect of increasing values of the signal's impulse is due to a correlative increase of the energy transmitted by the periodic signals, while it is found to be resonant-like with respect to the topology-induced amplification mechanism.

  17. Control of the amplifications of large-band amplitude-modulated pulses in an Nd-glass amplifier chain

    NASA Astrophysics Data System (ADS)

    Videau, Laurent; Bar, Emmanuel; Rouyer, Claude; Gouedard, Claude; Garnier, Josselin C.; Migus, Arnold

    1999-07-01

    We study nonlinear effects in amplification of partially coherent pulses in a high power laser chain. We compare statistical models with experimental results for temporal and spatial effects. First we show the interplay between self-phase modulation which broadens spectrum bandwidth and gain narrowing which reduces output spectrum. Theoretical results are presented for spectral broadening and energy limitation in case of time-incoherent pulses. In a second part, we introduce spatial incoherence with a multimode optical fiber which provides a smoothed beam. We show with experimental result that spatial filter pinholes are responsible for additive energy losses in the amplification. We develop a statistical model which takes into account the deformation of the focused beam as a function of B integral. We estimate the energy transmission of the spatial filter pinholes and compare this model with experimental data. We find a good agreement between theory and experiments. As a conclusion, we present an analogy between temporal and spatial effects with spectral broadening and spectral filter. Finally, we propose some solutions to control energy limitations in smoothed pulses amplification.

  18. Trophic amplification of climate warming

    PubMed Central

    Kirby, Richard R.; Beaugrand, Gregory

    2009-01-01

    Ecosystems can alternate suddenly between contrasting persistent states due to internal processes or external drivers. It is important to understand the mechanisms by which these shifts occur, especially in exploited ecosystems. There have been several abrupt marine ecosystem shifts attributed either to fishing, recent climate change or a combination of these two drivers. We show that temperature has been an important driver of the trophodynamics of the North Sea, a heavily fished marine ecosystem, for nearly 50 years and that a recent pronounced change in temperature established a new ecosystem dynamic regime through a series of internal mechanisms. Using an end-to-end ecosystem approach that included primary producers, primary, secondary and tertiary consumers, and detritivores, we found that temperature modified the relationships among species through nonlinearities in the ecosystem involving ecological thresholds and trophic amplifications. Trophic amplification provides an alternative mechanism to positive feedback to drive an ecosystem towards a new dynamic regime, which in this case favours jellyfish in the plankton and decapods and detritivores in the benthos. Although overfishing is often held responsible for marine ecosystem degeneration, temperature can clearly bring about similar effects. Our results are relevant to ecosystem-based fisheries management (EBFM), seen as the way forward to manage exploited marine ecosystems. PMID:19740882

  19. Amplification of the EGFR gene can be maintained and modulated by variation of EGF concentrations in in vitro models of glioblastoma multiforme

    PubMed Central

    Mokri, Poroshista; Lamp, Nora; Linnebacher, Michael; Classen, Carl Friedrich; Erbersdobler, Andreas; Schneider, Björn

    2017-01-01

    Glioblastoma multiforme (GBM) is the most common and lethal brain tumor in adults. It is known that amplification of the epidermal growth factor receptor gene (EGFR) occurs in approximately 40% of GBM, leading to enhanced activation of the EGFR signaling pathway and promoting tumor growth. Although GBM mutations are stably maintained in GBM in vitro models, rapid loss of EGFR gene amplification is a common observation during cell culture. To maintain EGFR amplification in vitro, heterotopic GBM xenografts with elevated EGFR copy number were cultured under varying serum conditions and EGF concentrations. EGFR copy numbers were assessed over several passages by quantitative PCR and chromogenic in situ hybridization. As expected, in control assays with 10% FCS, cells lost EGFR amplification with increasing passage numbers. However, cells cultured under serum free conditions stably maintained elevated copy numbers. Furthermore, EGFR protein expression positively correlated with genomic amplification levels. Although elevated EGFR copy numbers could be maintained over several passages in vitro, levels of EGFR amplification were variable and dependent on the EGF concentration in the medium. In vitro cultures of GBM cells with elevated EGFR copy number and corresponding EGFR protein expression should prove valuable preclinical tools to gain a better understanding of EGFR driven glioblastoma and assist in the development of new improved therapies. PMID:28934307

  20. Differential Item Functioning Amplification and Cancellation in a Reading Test

    ERIC Educational Resources Information Center

    Bao, Han; Dayton, C. Mitchell; Hendrickson, Amy B.

    2009-01-01

    When testlet effects and item idiosyncratic features are both considered to be the reasons of DIF in educational tests using testlets (Wainer & Kiely, 1987) or item bundles (Rosenbaum, 1988), it is interesting to investigate the phenomena of DIF amplification and cancellation due to the interactive effects of these two factors. This research…

  1. Experience gained from treating facial injuries due to civil unrest

    PubMed Central

    Whitlock, R I H

    1981-01-01

    During the past 10 years of civil unrest in Northern Ireland a wide variety of facial injuries have been treated at the Royal Victoria Hospital, Belfast. The causes and nature of these injuries are described and the experience gained in their management is reviewed. Imagesp[35]-ap[42]-aFig. 1Fig. 3Fig. 4Fig. 5Fig. 6Fig. 7 PMID:7247260

  2. Ligation with Nucleic Acid Sequence–Based Amplification

    PubMed Central

    Ong, Carmichael; Tai, Warren; Sarma, Aartik; Opal, Steven M.; Artenstein, Andrew W.; Tripathi, Anubhav

    2012-01-01

    This work presents a novel method for detecting nucleic acid targets using a ligation step along with an isothermal, exponential amplification step. We use an engineered ssDNA with two variable regions on the ends, allowing us to design the probe for optimal reaction kinetics and primer binding. This two-part probe is ligated by T4 DNA Ligase only when both parts bind adjacently to the target. The assay demonstrates that the expected 72-nt RNA product appears only when the synthetic target, T4 ligase, and both probe fragments are present during the ligation step. An extraneous 38-nt RNA product also appears due to linear amplification of unligated probe (P3), but its presence does not cause a false-positive result. In addition, 40 mmol/L KCl in the final amplification mix was found to be optimal. It was also found that increasing P5 in excess of P3 helped with ligation and reduced the extraneous 38-nt RNA product. The assay was also tested with a single nucleotide polymorphism target, changing one base at the ligation site. The assay was able to yield a negative signal despite only a single-base change. Finally, using P3 and P5 with longer binding sites results in increased overall sensitivity of the reaction, showing that increasing ligation efficiency can improve the assay overall. We believe that this method can be used effectively for a number of diagnostic assays. PMID:22449695

  3. Raman Amplification and Tunable Pulse Delays in Silicon Waveguides

    NASA Astrophysics Data System (ADS)

    Rukhlenko, Ivan D.; Garanovich, Ivan L.; Premaratne, Malin; Sukhorukov, Andrey A.; Agrawal, Govind P.

    2010-10-01

    The nonlinear process of stimulated Raman scattering is important for silicon photonics as it enables optical amplification and lasing. However, generally employed numerical approaches provide very little insight into the contribution of different silicon Raman amplifier (SRA) parameters. In this paper, we solve the coupled pump-signal equations analytically and derive an exact formula for the envelope of a signal pulse when picosecond optical pulses are amplified inside a SRA pumped by a continuous-wave laser beam. Our solution is valid for an arbitrary pulse shape and fully accounts for the Raman gain-dispersion effects, including temporal broadening and group-velocity reduction. Our results are useful for optimizing the performance of SRAs and for engineering controllable signal delays.

  4. Entangled-Pair Transmission Improvement Using Distributed Phase-Sensitive Amplification

    NASA Astrophysics Data System (ADS)

    Agarwal, Anjali; Dailey, James M.; Toliver, Paul; Peters, Nicholas A.

    2014-10-01

    We demonstrate the transmission of time-bin entangled photon pairs through a distributed optical phase-sensitive amplifier (OPSA). We utilize four-wave mixing at telecom wavelengths in a 5-km dispersion-shifted fiber OPSA operating in the low-gain limit. Measurements of two-photon interference curves show no statistically significant degradation in the fringe visibility at the output of the OPSA. In addition, coincidence counting rates are higher than direct passive transmission because of constructive interference between amplitudes of input photon pairs and those generated in the OPSA. Our results suggest that application of distributed phase-sensitive amplification to transmission of entangled photon pairs could be highly beneficial towards advancing the rate and scalability of future quantum communications systems.

  5. FIBER AND INTEGRATED OPTICS: Amplification of femtosecond pulses in single-mode fiber waveguides activated with Er3+ ions

    NASA Astrophysics Data System (ADS)

    Grudinin, A. B.; Dianov, Evgenii M.; Korobkin, D. V.; Prokhorov, A. M.; Semenov, V. A.; Khrushchev, I. Yu

    1990-08-01

    An experimental investigation was made of the process of amplification of femtosecond pulses in single-mode fiber waveguides activated with erbium ions. The amplified pulses were compressed from 80 to 55 fs in the course of their propagation. The energy of the pulses was estimated to be 5 nJ. The maximum gain was 26 dB.

  6. Amplification of microwaves by superconducting microbridges in a four-wave parametric mode

    NASA Technical Reports Server (NTRS)

    Parrish, P. T.; Chiao, R. Y.

    1974-01-01

    Parametric amplification of microwaves was observed using thin-film junctions of the Anderson-Dayem type. A series of 80 such junctions were incorporated into the upper conductor of a broadband 50-ohm microstrip transmission line with no DC bias. The amplifier was operated in the 'doubly degenerate' mode with signal, pump, and idler frequencies closely and equally spaced. An electronic gain of 12 dB at 10 GHz was observed. The bandwidth was measured to be 1 GHz and the noise temperature to be less than 20 K.

  7. Spectral gain investigation of large size OPCPA based on partially deuterated KDP

    NASA Astrophysics Data System (ADS)

    Galimberti, Marco; Boyle, Alexis; Musgrave, Ian O.; Oliveira, Pedro; Pepler, Dave; Shaikh, Waseem; Winstone, Trevor B.; Wyatt, Adam; Hernandez-Gomez, Cristina

    2018-01-01

    The Optical Parametric Chirped Pulse Amplification is one of the most promising techniques to deliver 20PW laser system. The already available KD*P in large size is a good candidate as nonlinear crystal. In this article we report the experimental analysis of the spectral small signal gain for KD*P at 70% deuteration level for different phase matching and non-collinear angle. The data is also compared with a theoretical model.

  8. RESONANT AMPLIFICATION OF TURBULENCE BY THE BLAST WAVES

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zankovich, A. M.; Kovalenko, I. G., E-mail: ilya.g.kovalenko@gmail.com

    2015-02-10

    We discuss the idea of whether spherical blast waves can amplify by a nonlocal resonant hydrodynamic mechanism inhomogeneities formed by turbulence or phase segregation in the interstellar medium. We consider the problem of a blast-wave-turbulence interaction in the Linear Interaction Approximation. Mathematically, this is an eigenvalue problem for finding the structure and amplitude of eigenfunctions describing the response of the shock-wave flow to forced oscillations by external perturbations in the ambient interstellar medium. Linear analysis shows that the blast wave can amplify density and vorticity perturbations for a wide range of length scales with amplification coefficients of up to 20,more » with increasing amplification the larger the length. There also exist resonant harmonics for which the gain becomes formally infinite in the linear approximation. Their orbital wavenumbers are within the range of macro- (l ∼ 1), meso- (l ∼ 20), and microscopic (l > 200) scales. Since the resonance width is narrow (typically, Δl < 1), resonance should select and amplify discrete isolated harmonics. We speculate on a possible explanation of an observed regular filamentary structure of regularly shaped round supernova remnants such as SNR 1572, 1006, or 0509-67.5. Resonant mesoscales found (l ≈ 18) are surprisingly close to the observed scales (l ≈ 15) of ripples in the shell's surface of SNR 0509-67.5.« less

  9. Loop-mediated isothermal amplification (LAMP) shield for Arduino DNA detection.

    PubMed

    Velders, Aldrik H; Schoen, Cor; Saggiomo, Vittorio

    2018-02-01

    Loop-mediated isothermal amplification (LAMP) of DNA is gaining relevance as a method to detect nucleic acids, as it is easier, faster, and more powerful than conventional Polymerase Chain Reaction. However, LAMP is still mostly used in laboratory settings, because of the lack of a cheap and easy, one-button device that can perform LAMP experiments. Here we show how to build and program an Arduino shield for a LAMP and detection of DNA. The here described Arduino Shield is cheap, easy to assemble, to program and use, it is battery operated and the detection of DNA is done by naked-eye so that it can be used in field.

  10. Enhancement of quantum-enhanced LADAR receiver in nonideal phase-sensitive amplification

    NASA Astrophysics Data System (ADS)

    Zhang, Shuan; Liu, Hongjun; Huang, Nan; Wang, Zhaolu; Han, Jing

    2017-07-01

    The phase-sensitive amplification (PSA) with an injected squeezed vacuum field is theoretically investigated in quantum-enhanced laser detection and ranging (LADAR) receiver. The theoretical model of the amplified process is derived to investigate the quantum fluctuations in detail. A new method of mitigating the unflat gain of nonideal PSA is proposed by adjusting the squeezed angle of the squeezed vacuum field. The simulation results indicate that signal-noise ratio (SNR) of system can be efficiently improved and close to the ideal case by this method. This research will provide an important potential in the applications of quantum-enhanced LADAR receiver.

  11. Quantum tomography enhanced through parametric amplification

    NASA Astrophysics Data System (ADS)

    Knyazev, E.; Spasibko, K. Yu; Chekhova, M. V.; Khalili, F. Ya

    2018-01-01

    Quantum tomography is the standard method of reconstructing the Wigner function of quantum states of light by means of balanced homodyne detection. The reconstruction quality strongly depends on the photodetectors quantum efficiency and other losses in the measurement setup. In this article we analyze in detail a protocol of enhanced quantum tomography, proposed by Leonhardt and Paul [1] which allows one to reduce the degrading effect of detection losses. It is based on phase-sensitive parametric amplification, with the phase of the amplified quadrature being scanned synchronously with the local oscillator phase. Although with sufficiently strong amplification the protocol enables overcoming any detection inefficiency, it was so far not implemented in the experiment, probably due to the losses in the amplifier. Here we discuss a possible proof-of-principle experiment with a traveling-wave parametric amplifier. We show that with the state-of-the-art optical elements, the protocol enables high fidelity tomographic reconstruction of bright non-classical states of light. We consider two examples: bright squeezed vacuum and squeezed single-photon state, with the latter being a non-Gaussian state and both strongly affected by the losses.

  12. Next-Generation in Situ Hybridization Chain Reaction: Higher Gain, Lower Cost, Greater Durability

    PubMed Central

    2014-01-01

    Hybridization chain reaction (HCR) provides multiplexed, isothermal, enzyme-free, molecular signal amplification in diverse settings. Within intact vertebrate embryos, where signal-to-background is at a premium, HCR in situ amplification enables simultaneous mapping of multiple target mRNAs, addressing a longstanding challenge in the biological sciences. With this approach, RNA probes complementary to mRNA targets trigger chain reactions in which metastable fluorophore-labeled RNA hairpins self-assemble into tethered fluorescent amplification polymers. The properties of HCR lead to straightforward multiplexing, deep sample penetration, high signal-to-background, and sharp subcellular signal localization within fixed whole-mount zebrafish embryos, a standard model system for the study of vertebrate development. However, RNA reagents are expensive and vulnerable to enzymatic degradation. Moreover, the stringent hybridization conditions used to destabilize nonspecific hairpin binding also reduce the energetic driving force for HCR polymerization, creating a trade-off between minimization of background and maximization of signal. Here, we eliminate this trade-off by demonstrating that low background levels can be achieved using permissive in situ amplification conditions (0% formamide, room temperature) and engineer next-generation DNA HCR amplifiers that maximize the free energy benefit per polymerization step while preserving the kinetic trapping property that underlies conditional polymerization, dramatically increasing signal gain, reducing reagent cost, and improving reagent durability. PMID:24712299

  13. Direct detection of microRNAs using isothermal amplification and molecular beacon with excellent sensitivity and specificity

    NASA Astrophysics Data System (ADS)

    Zhang, Wancun; Zhang, Qi; Qian, Zhiyu; Gu, Yueqing

    2017-02-01

    MicroRNAs (miRNAs) play important roles in a wide range of biological processes, including proliferation, development, metabolism, immunological response, tumorigenesis, and viral infection. The detection of miRNAs is imperative for gaining a better understanding of the functions of these biomolecules and has great potential for the early diagnosis of human disease as well as the discovery of new drugs through the use of miRNAs as targets. In this article, we develop a highly sensitive, and specific miRNA assay based on the two-stage isothermal amplification reactions and molecular beacon. The two-stage isothermal amplification reactions involves two templates and two-stage amplification reactions under isothermal conditions. The first template enables the amplification of miRNA, and the second template enables the conversion of miRNA to the reporter oligonucleotide(Y). Importantly, different miRNAs can be converted to the same Y seperately, which can hybridize with the same set of molecular beacon to generate fluorescent signals. This assay is highly sensitive and specific with a detection limit of 1 fM and can even discriminate single-nucleotide differences. Moreover, in combination with the specific templates, this method can be applied for multiplex miRNA assay by simply using the same molecular beacon. This method has potential to become a promising miRNA quantification method in biomedical research and clinical diagnosis.

  14. Influence of wave-packet dynamics on the medium gain of an atomic system

    NASA Astrophysics Data System (ADS)

    Delagnes, J. C.; Bouchene, M. A.

    2007-10-01

    A sequence of two femtosecond pulses—a strong driving π -polarized pulse and a weak propagating σ -polarized pulse—excites resonantly the S1/2→P1/2 transition of an atomic system. Strong interference effects take place in the system between absorption and emission paths leading to a substantial amplification of the σ pulse. We study the influence of the fine structure on the medium gain when the contribution of the off-resonant P3/2 level is taken into account. A drastic reduction of the medium gain is obtained. This effect is explained within the bright-state dark-state formalism where the strong driving pulse creates a wave packet that can be trapped in a state—the bright state—leading to a significant reduction of the gain for the σ pulse. Finally, we also show that periodical gain dependence with the driving pulse energy exhibits a significant change in its period value (compared with expected Rabi oscillations).

  15. Helicase-dependent amplification of nucleic acids.

    PubMed

    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.

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

    NASA Astrophysics Data System (ADS)

    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

  17. S-band optical amplification by an internally generated pump in thulium ytterbium codoped fiber.

    PubMed

    Chang, Jun; Wang, Qing-Pu; Zhang, Xingyu; Liu, Zhejin; Liu, Zhaojun; Peng, Gang-Ding

    2005-05-30

    We propose a novel scheme in which Yb3+ codoping and a laser cavity are introduced in Tm3+ doped fiber to achieve efficient S-band optical amplification with a 980 nm pump source. This scheme makes it possible for conventional 980 nm pump sources for Er3+ doped fiber amplifiers to be used for S-band Tm3+ doped fiber amplifiers (TDFAs). By introducing a laser cavity into an amplifier, an internally generated pump from Yb3+ at a desirable wavelength for pumping Tm3+ could be produced. We establish and analyze, for the first time to our knowledge, a new theoretical model that takes into consideration both the internal lasing operation inside the optical amplification process and the energy transfer between the Tm3+ and the Yb3+ ions in TDFAs. Various situations such as Tm3+ doping concentration and cavity reflectivity have been investigated. The results show that high optical gain and high pump efficiency can be achieved by use of 980 nm sources. With a laser cavity of 1050 nm in Tm3+ and Yb3+ codoped fiber, for example, it is possible to achieve high optical gain of greater than 20 dB, a noise figure of approximately 5 dB in the wavelength range from 1450 to 1480 nm with a 0.3 W power at 980 nm pump source.

  18. Physical principles of the amplification of electromagnetic radiation due to negative electron masses in a semiconductor superlattice

    NASA Astrophysics Data System (ADS)

    Shorokhov, A. V.; Pyataev, M. A.; Khvastunov, N. N.; Hyart, T.; Kusmartsev, F. V.; Alekseev, K. N.

    2015-02-01

    In a superlattice placed in crossed static electric and magnetic fields, under certain conditions, the inversion of electron population can appear at which the average energy of electrons is above the middle of the mini-band and the effective mass of the electron is negative. This is the implementation of the negative effective mass amplifier and generator (NEMAG) in the superlattice. It can result in the amplification and generation of terahertz radiation even in the absence of negative differential conductivity.

  19. The effects of control-display gain on performance of race car drivers in an isometric braking task.

    PubMed

    de Winter, J C F; de Groot, S

    2012-12-01

    To minimise lap times during car racing, it is important to build up brake forces rapidly and maintain precise control. We examined the effect of the amplification factor (gain) between brake pedal force and a visually represented output value on a driver's ability to track a target value. The test setup was a formula racing car cockpit fitted with an isometric brake pedal. Thirteen racing drivers performed tracking tasks with four control-display gains and two target functions: a step function (35 trials per gain) and a multisine function (15 trials per gain). The control-display gain had only minor effects on root mean-squared error between output value and target value, but it had large effects on build-up speed, overshoot, within-participants variability, and self-reported physical load. The results confirm the hypothesis that choosing an optimum gain involves balancing stability against physical effort.

  20. Investigation of Extended Bandwidth Hearing Aid Amplification on Speech Intelligibility and Sound Quality in Adults with Mild-to-Moderate Hearing Loss.

    PubMed

    Seeto, Angeline; Searchfield, Grant D

    2018-03-01

    Advances in digital signal processing have made it possible to provide a wide-band frequency response with smooth, precise spectral shaping. Several manufacturers have introduced hearing aids that are claimed to provide gain for frequencies up to 10-12 kHz. However, there is currently limited evidence and very few independent studies evaluating the performance of the extended bandwidth hearing aids that have recently become available. This study investigated an extended bandwidth hearing aid using measures of speech intelligibility and sound quality to find out whether there was a significant benefit of extended bandwidth amplification over standard amplification. Repeated measures study designed to examine the efficacy of extended bandwidth amplification compared to standard bandwidth amplification. Sixteen adult participants with mild-to-moderate sensorineural hearing loss. Participants were bilaterally fit with a pair of Widex Mind 440 behind-the-ear hearing aids programmed with a standard bandwidth fitting and an extended bandwidth fitting; the latter provided gain up to 10 kHz. For each fitting, and an unaided condition, participants completed two speech measures of aided benefit, the Quick Speech-in-Noise test (QuickSIN™) and the Phonak Phoneme Perception Test (PPT; high-frequency perception in quiet), and a measure of sound quality rating. There were no significant differences found between unaided and aided conditions for QuickSIN™ scores. For the PPT, there were statistically significantly lower (improved) detection thresholds at high frequencies (6 and 9 kHz) with the extended bandwidth fitting. Although not statistically significant, participants were able to distinguish between 6 and 9 kHz 50% better with extended bandwidth. No significant difference was found in ability to recognize phonemes in quiet between the unaided and aided conditions when phonemes only contained frequency content <6 kHz. However significant benefit was found with the

  1. Optical chirped beam amplification and propagation

    DOEpatents

    Barty, Christopher P.

    2004-10-12

    A short pulse laser system uses dispersive optics in a chirped-beam amplification architecture to produce high peak power pulses and high peak intensities without the potential for intensity dependent damage to downstream optical components after amplification.

  2. Optimization and evaluation of T7 based RNA linear amplification protocols for cDNA microarray analysis

    PubMed Central

    Zhao, Hongjuan; Hastie, Trevor; Whitfield, Michael L; Børresen-Dale, Anne-Lise; Jeffrey, Stefanie S

    2002-01-01

    Background T7 based linear amplification of RNA is used to obtain sufficient antisense RNA for microarray expression profiling. We optimized and systematically evaluated the fidelity and reproducibility of different amplification protocols using total RNA obtained from primary human breast carcinomas and high-density cDNA microarrays. Results Using an optimized protocol, the average correlation coefficient of gene expression of 11,123 cDNA clones between amplified and unamplified samples is 0.82 (0.85 when a virtual array was created using repeatedly amplified samples to minimize experimental variation). Less than 4% of genes show changes in expression level by 2-fold or greater after amplification compared to unamplified samples. Most changes due to amplification are not systematic both within one tumor sample and between different tumors. Amplification appears to dampen the variation of gene expression for some genes when compared to unamplified poly(A)+ RNA. The reproducibility between repeatedly amplified samples is 0.97 when performed on the same day, but drops to 0.90 when performed weeks apart. The fidelity and reproducibility of amplification is not affected by decreasing the amount of input total RNA in the 0.3–3 micrograms range. Adding template-switching primer, DNA ligase, or column purification of double-stranded cDNA does not improve the fidelity of amplification. The correlation coefficient between amplified and unamplified samples is higher when total RNA is used as template for both experimental and reference RNA amplification. Conclusion T7 based linear amplification reproducibly generates amplified RNA that closely approximates original sample for gene expression profiling using cDNA microarrays. PMID:12445333

  3. Enhanced Arctic Amplification Began at the Mid-Brunhes Event ~400,000 years ago.

    PubMed

    Cronin, T M; Dwyer, G S; Caverly, E K; Farmer, J; DeNinno, L H; Rodriguez-Lazaro, J; Gemery, L

    2017-11-03

    Arctic Ocean temperatures influence ecosystems, sea ice, species diversity, biogeochemical cycling, seafloor methane stability, deep-sea circulation, and CO 2 cycling. Today's Arctic Ocean and surrounding regions are undergoing climatic changes often attributed to "Arctic amplification" - that is, amplified warming in Arctic regions due to sea-ice loss and other processes, relative to global mean temperature. However, the long-term evolution of Arctic amplification is poorly constrained due to lack of continuous sediment proxy records of Arctic Ocean temperature, sea ice cover and circulation. Here we present reconstructions of Arctic Ocean intermediate depth water (AIW) temperatures and sea-ice cover spanning the last ~ 1.5 million years (Ma) of orbitally-paced glacial/interglacial cycles (GIC). Using Mg/Ca paleothermometry of the ostracode Krithe and sea-ice planktic and benthic indicator species, we suggest that the Mid-Brunhes Event (MBE), a major climate transition ~ 400-350 ka, involved fundamental changes in AIW temperature and sea-ice variability. Enhanced Arctic amplification at the MBE suggests a major climate threshold was reached at ~ 400 ka involving Atlantic Meridional Overturning Circulation (AMOC), inflowing warm Atlantic Layer water, ice sheet, sea-ice and ice-shelf feedbacks, and sensitivity to higher post-MBE interglacial CO 2 concentrations.

  4. Enhanced Arctic amplification began at the Mid-Brunhes Event 430,000 years ago

    USGS Publications Warehouse

    Cronin, Thomas M.; Dwyer, Gary S.; Caverly, Emma; Farmer, Jesse; DeNinno, Lauren H.; Rodriguez-Lazaro, Julio; Gemery, Laura

    2017-01-01

    Arctic Ocean temperatures influence ecosystems, sea ice, species diversity, biogeochemical cycling, seafloor methane stability, deep-sea circulation, and CO2 cycling. Today's Arctic Ocean and surrounding regions are undergoing climatic changes often attributed to "Arctic amplification" - that is, amplified warming in Arctic regions due to sea-ice loss and other processes, relative to global mean temperature. However, the long-term evolution of Arctic amplification is poorly constrained due to lack of continuous sediment proxy records of Arctic Ocean temperature, sea ice cover and circulation. Here we present reconstructions of Arctic Ocean intermediate depth water (AIW) temperatures and sea-ice cover spanning the last ~ 1.5 million years (Ma) of orbitally-paced glacial/interglacial cycles (GIC). Using Mg/Ca paleothermometry of the ostracode Krithe and sea-ice planktic and benthic indicator species, we suggest that the Mid-Brunhes Event (MBE), a major climate transition ~ 400-350 ka, involved fundamental changes in AIW temperature and sea-ice variability. Enhanced Arctic amplification at the MBE suggests a major climate threshold was reached at ~ 400 ka involving Atlantic Meridional Overturning Circulation (AMOC), inflowing warm Atlantic Layer water, ice sheet, sea-ice and ice-shelf feedbacks, and sensitivity to higher post-MBE interglacial CO2 concentrations.

  5. Signal amplification strategies for DNA and protein detection based on polymeric nanocomposites and polymerization: A review.

    PubMed

    Zhou, Shaohong; Yuan, Liang; Hua, Xin; Xu, Lingling; Liu, Songqin

    2015-06-02

    Demand is increasing for ultrasensitive bioassays for disease diagnosis, environmental monitoring and other research areas. This requires novel signal amplification strategies to maximize the signal output. In this review, we focus on a series of significant signal amplification strategies based on polymeric nanocomposites and polymerization. Some common polymers are used as carriers to increase the local concentration of signal probes and/or biomolecules on their surfaces or in their interiors. Some polymers with special fluorescence and optical properties can efficiently transfer the excitation energy from a single site to the whole polymer backbone. This results in superior fluorescence signal amplification due to the resulting collective effort (integration of signal). Recent polymerization-based signal amplification strategies that employ atom transfer radical polymerization (ATRP) and photo-initiated polymerization are also summarized. Several distinctive applications of polymers in ultrasensitive bioanalysis are highlighted. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Amplification and overexpression of aurora kinase A (AURKA) in immortalized human ovarian epithelial (HOSE) cells.

    PubMed

    Chung, C M; Man, C; Jin, Y; Jin, C; Guan, X Y; Wang, Q; Wan, T S K; Cheung, A L M; Tsao, S W

    2005-07-01

    Immortalization is an early and essential step of human carcinogenesis. Amplification of chromosome 20q has been shown to be a common event in immortalized cells and cancers. We have previously reported that gain and amplification of chromosome 20q is a non-random and common event in immortalized human ovarian surface epithelial (HOSE) cells. The chromosome 20q harbors genes including TGIF2 (20q11.2-q12), AIB1 (20q12), PTPN1 (20q13.1), ZNF217 (20q13.2), and AURKA (20q13.2-q13.3), which were previously reported to be amplified and overexpressed in ovarian cancers. Some of these genes may be involved in immortalization of HOSE cells and represent crucial premalignant changes in ovarian surface epithelium. Investigation of the involvement of these genes was examined in four pairs of pre-crisis (preimmortalized) and post-crisis (immortalized) HOSE cells. Overexpression of AURKA (Aurora kinase A), also known as BTAK and STK15, by both real time-quantitative polymerase chain reaction (RT-QPCR) and Western blotting was detected in all the four immortalized HOSE cells examined while overexpression of AIB1 and ZNF217 was observed in two of four immortalized HOSE cells examined. Overexpression of TGIF2 and PTPN1 was not significant in our immortalized HOSE cell systems. The degree of overexpression of AURKA was shown to be closely associated with the amplification of chromosome 20q in immortalized HOSE cells. Fluorescence in situ hybridization (FISH) with labeled P1 artificial clone (PAC) confirmed the amplification of the chromosomal region (20q13.2-13.3) where AURKA resides. DNA amplification of AURKA was also confirmed using semi-quantitative PCR. Our study showed that amplification and overexpression of AURKA is a common and significant event during immortalization of HOSE cells and may represent an important premalignant change in ovarian carcinogenesis. Copyright (c) 2005 Wiley-Liss, Inc.

  7. Amplification and generation of surface plasmon polaritons in a semiconductor film - dielectric structure

    NASA Astrophysics Data System (ADS)

    Abramov, A. S.; Zolotovskii, I. O.; Moiseev, S. G.; Sementsov, D. I.

    2018-01-01

    The peculiarities of propagation and amplification of surface waves of plasmon polariton type in a planar semiconductor film - dielectric structure are considered for the THz frequency region, with allowance for dissipation in a semiconductor. Two spectral regions are found, where the group velocity of surface plasmon polaritons is negative. It is shown that in these regions the structure can be considered as an amplifying waveguide with distributed feedback and a high gain with respect to the reflected and transmitted signals. The possibility of generation of electromagnetic radiation in such structures is established.

  8. Empirical evidence for acceleration-dependent amplification factors

    USGS Publications Warehouse

    Borcherdt, R.D.

    2002-01-01

    Site-specific amplification factors, Fa and Fv, used in current U.S. building codes decrease with increasing base acceleration level as implied by the Loma Prieta earthquake at 0.1g and extrapolated using numerical models and laboratory results. The Northridge earthquake recordings of 17 January 1994 and subsequent geotechnical data permit empirical estimates of amplification at base acceleration levels up to 0.5g. Distance measures and normalization procedures used to infer amplification ratios from soil-rock pairs in predetermined azimuth-distance bins significantly influence the dependence of amplification estimates on base acceleration. Factors inferred using a hypocentral distance norm do not show a statistically significant dependence on base acceleration. Factors inferred using norms implied by the attenuation functions of Abrahamson and Silva show a statistically significant decrease with increasing base acceleration. The decrease is statistically more significant for stiff clay and sandy soil (site class D) sites than for stiffer sites underlain by gravely soils and soft rock (site class C). The decrease in amplification with increasing base acceleration is more pronounced for the short-period amplification factor, Fa, than for the midperiod factor, Fv.

  9. A three-parameter two-state model of receptor function that incorporates affinity, efficacy, and signal amplification.

    PubMed

    Buchwald, Peter

    2017-06-01

    A generalized model of receptor function is proposed that relies on the essential assumptions of the minimal two-state receptor theory (i.e., ligand binding followed by receptor activation), but uses a different parametrization and allows nonlinear response (transduction) for possible signal amplification. For the most general case, three parameters are used: K d , the classic equilibrium dissociation constant to characterize binding affinity; ε , an intrinsic efficacy to characterize the ability of the bound ligand to activate the receptor (ranging from 0 for an antagonist to 1 for a full agonist); and γ , a gain (amplification) parameter to characterize the nonlinearity of postactivation signal transduction (ranging from 1 for no amplification to infinity). The obtained equation, E/Emax=εγLεγ+1-εL+Kd, resembles that of the operational (Black and Leff) or minimal two-state (del Castillo-Katz) models, E/Emax=τLτ+1L+Kd, with εγ playing a role somewhat similar to that of the τ efficacy parameter of those models, but has several advantages. Its parameters are more intuitive as they are conceptually clearly related to the different steps of binding, activation, and signal transduction (amplification), and they are also better suited for optimization by nonlinear regression. It allows fitting of complex data where receptor binding and response are measured separately and the fractional occupancy and response are mismatched. Unlike the previous models, it is a true generalized model as simplified forms can be reproduced with special cases of its parameters. Such simplified forms can be used on their own to characterize partial agonism, competing partial and full agonists, or signal amplification.

  10. Harnessing polarisation transfer to indazole and imidazole through signal amplification by reversible exchange to improve their NMR detectability

    PubMed Central

    Fekete, Marianna; Rayner, Peter J.; Green, Gary G. R.

    2017-01-01

    The signal amplification by reversible exchange (SABRE) approach has been used to hyperpolarise the substrates indazole and imidazole in the presence of the co‐ligand acetonitrile through the action of the precataysts [IrCl(COD)(IMes)] and [IrCl(COD)(SIMes)]. 2H‐labelled forms of these catalysts were also examined. Our comparison of the two precatalysts [IrCl(COD)(IMes)] and [IrCl(COD)(SIMes)], coupled with 2H labelling of the N‐heterocyclic carbene and associated relaxation and polarisation field variation studies, demonstrates the critical and collective role these parameters play in controlling the efficiency of signal amplification by reversible exchange. Ultimately, with imidazole, a 700‐fold1H signal gain per proton is produced at 400 MHz, whilst for indazole, a 90‐fold increase per proton is achieved. The co‐ligand acetonitrile proved to optimally exhibit a 190‐fold signal gain per proton in these measurements, with the associated studies revealing the importance the substrate plays in controlling this value. Copyright © 2017 The Authors. Magnetic Resonance in Chemistry published by John Wiley & Sons Ltd. PMID:28497481

  11. Sensitive Detection Using Microfluidics and Nonlinear Amplification

    DTIC Science & Technology

    2011-07-22

    Quantification of Nucleic Acids via Simultaneous Chemical Initiation of Recombinase Polymerase Amplification Reactions on SlipChip" 2011, 83, 3533... Amplification 5a. CONTRACT NUMBER 5b. GRANT NUMBER N00014-08-1-0936 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Rustem F. Ismagilov 5d. PROJECT NUMBER 5e...concentrations by combining controlled chemical autocatalytic amplification and stochastic confinement of small particles with the microfluidic

  12. SOX2 amplification is a common event in squamous cell carcinomas of different organ sites.

    PubMed

    Maier, Sebastian; Wilbertz, Theresia; Braun, Martin; Scheble, Veit; Reischl, Markus; Mikut, Ralf; Menon, Roopika; Nikolov, Pavel; Petersen, Karen; Beschorner, Christine; Moch, Holger; Kakies, Christoph; Protzel, Chris; Bauer, Jürgen; Soltermann, Alex; Fend, Falko; Staebler, Annette; Lengerke, Claudia; Perner, Sven

    2011-08-01

    Acquired chromosomal aberrations, including gene copy number alterations, are involved in the development and progression of human malignancies. SOX2, a transcription factor-coding gene located at 3q26.33, is known to be recurrently and specifically amplified in squamous cell carcinomas of the lung, the esophagus, and the oral cavity. In these organs, the SOX2 protein plays an important role in tumorigenesis and tumor survival. The aim of this study was to determine whether SOX2 amplification is also found in squamous cell carcinomas in other organs commonly affected by this tumor entity. In addition, we examined a large spectrum of lung cancer entities with neuroendocrine differentiation (ie, small cell cancers, large cell cancers, typical and atypical carcinoids) for SOX2 and TTF1 copy number gains to reveal potential molecular ties to squamous cell carcinomas or adenocarcinomas of the lung. Applying fluorescence in situ hybridization, we assessed squamous cell carcinomas of the cervix uteri (n = 47), the skin (n = 57), and the penis (n = 53) for SOX2 copy number alterations and detected amplifications in 28%, 28%, and 32% of tumors, respectively. Furthermore, we performed immunohistochemical SOX2 staining and found that SOX2 amplification is significantly associated with overexpression of the corresponding protein in squamous cell carcinomas (P < .001). Of the lung cancer entities with neuroendocrine differentiation, only small cell cancers and large cell cancers exhibited SOX2 or TTF1 amplifications at significant frequencies, indicating that at least a subset of these might be dedifferentiated forms of squamous cell carcinomas or adenocarcinomas of the lung. We conclude that SOX2 amplification and consequent SOX2 protein overexpression may represent important mechanisms of tumor initiation and progression in a considerable subset of squamous cell carcinomas. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Weight gain and the risk of knee replacement due to primary osteoarthritis: a population based, prospective cohort study of 225,908 individuals.

    PubMed

    Apold, H; Meyer, H E; Nordsletten, L; Furnes, O; Baste, V; Flugsrud, G B

    2014-05-01

    To study the association between weight gain and the risk of knee replacement (KR) due to primary osteoarthritis (OA), and to evaluate whether the association differs by age. 225,908 individuals from national health screenings with repeated measurements of height and weight were followed prospectively with respect to KR identified by linkage to the Norwegian Arthroplasty Register. Cox proportional hazard regression was used to calculate sex-specific relative risks (RR) of KR according to change in Body Mass Index (BMI) and weight, corresponding analyses were done for age categories at first screening. During 12 years of follow up, 1591 participants received a KR due to primary OA. Men in the highest quarter of yearly change in BMI had a RR of 1.5 (95% confidence interval (CI) 1.1-1.9) of having a KR compared to those in the lowest quarter. For women the corresponding RR was 2.4 (95% CI 2.1-2.7). Men under the age of 20 at the first screening had a 26% increased risk for KR per 5 kg weight gain, for women the corresponding increase was 43%. At older age the association became weaker, and in the oldest it was lost. Weight gain increases the risk for later KR both in men and women. The impact of weight gain is strongest in the young, at older age the association is weak or absent. Our study suggests that future OA may be prevented by weight control and that preventive measures should start at an early age. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  14. Chronic centrosome amplification without tumorigenesis

    PubMed Central

    Vitre, Benjamin; Holland, Andrew J.; Kulukian, Anita; Shoshani, Ofer; Hirai, Maretoshi; Wang, Yin; Maldonado, Marcus; Cho, Thomas; Boubaker, Jihane; Swing, Deborah A.; Tessarollo, Lino; Evans, Sylvia M.; Fuchs, Elaine; Cleveland, Don W.

    2015-01-01

    Centrosomes are microtubule-organizing centers that facilitate bipolar mitotic spindle assembly and chromosome segregation. Recognizing that centrosome amplification is a common feature of aneuploid cancer cells, we tested whether supernumerary centrosomes are sufficient to drive tumor development. To do this, we constructed and analyzed mice in which centrosome amplification can be induced by a Cre-recombinase–mediated increase in expression of Polo-like kinase 4 (Plk4). Elevated Plk4 in mouse fibroblasts produced supernumerary centrosomes and enhanced the expected mitotic errors, but proliferation continued only after inactivation of the p53 tumor suppressor. Increasing Plk4 levels in mice with functional p53 produced centrosome amplification in liver and skin, but this did not promote spontaneous tumor development in these tissues or enhance the growth of chemically induced skin tumors. In the absence of p53, Plk4 overexpression generated widespread centrosome amplification, but did not drive additional tumors or affect development of the fatal thymic lymphomas that arise in animals lacking p53. We conclude that, independent of p53 status, supernumerary centrosomes are not sufficient to drive tumor formation. PMID:26578792

  15. Signal Amplification Technologies for the Detection of Nucleic Acids: from Cell-Free Analysis to Live-Cell Imaging.

    PubMed

    Fozooni, Tahereh; Ravan, Hadi; Sasan, Hosseinali

    2017-12-01

    Due to their unique properties, such as programmability, ligand-binding capability, and flexibility, nucleic acids can serve as analytes and/or recognition elements for biosensing. To improve the sensitivity of nucleic acid-based biosensing and hence the detection of a few copies of target molecule, different modern amplification methodologies, namely target-and-signal-based amplification strategies, have already been developed. These recent signal amplification technologies, which are capable of amplifying the signal intensity without changing the targets' copy number, have resulted in fast, reliable, and sensitive methods for nucleic acid detection. Working in cell-free settings, researchers have been able to optimize a variety of complex and quantitative methods suitable for deploying in live-cell conditions. In this study, a comprehensive review of the signal amplification technologies for the detection of nucleic acids is provided. We classify the signal amplification methodologies into enzymatic and non-enzymatic strategies with a primary focus on the methods that enable us to shift away from in vitro detecting to in vivo imaging. Finally, the future challenges and limitations of detection for cellular conditions are discussed.

  16. Space Optical Communications Using Laser Beam Amplification

    NASA Technical Reports Server (NTRS)

    Agrawal, Govind

    2015-01-01

    The Space Optical Communications Using Laser Beam Amplification (SOCLBA) project will provide a capability to amplify a laser beam that is received in a modulating retro-reflector (MRR) located in a satellite in low Earth orbit. It will also improve the pointing procedure between Earth and spacecraft terminals. The technology uses laser arrays to strengthen the reflected laser beam from the spacecraft. The results of first year's work (2014) show amplification factors of 60 times the power of the signal beam. MMRs are mirrors that reflect light beams back to the source. In space optical communications, a high-powered laser interrogator beam is directed from the ground to a satellite. Within the satellite, the beam is redirected back to ground using the MMR. In the MMR, the beam passes through modulators, which encode a data signal onto the returning beam. MMRs can be used in small spacecraft for optical communications. The SOCLBA project is significant to NASA and small spacecraft due to its application to CubeSats for optical data transmission to ground stations, as well as possible application to spacecraft for optical data transmission.

  17. The influence of diet on faecal DNA amplification and sex identification in brown bears (Ursus arctos)

    USGS Publications Warehouse

    Murphy, M.A.; Waits, L.P.; Kendall, K.C.

    2003-01-01

    To evaluate the influence of diet on faecal DNA amplification, 11 captive brown bears (Ursus arctos) were placed on six restricted diets: grass (Trifolium spp., Haplopappus hirtus and Poa pratensis), alfalfa (Lupinus spp.), carrots (Daucus spp.), white-tailed deer (Odocoileus virginianus), blueberries (Vaccinium spp.) and salmon (Salmo spp.). DNA was extracted from 50 faecal samples of each restricted diet, and amplification of brown bear DNA was attempted for a mitochondrial DNA (mtDNA) locus and nuclear DNA (nDNA) locus. For mtDNA, no significant differences were observed in amplification success rates across diets. For nDNA, amplification success rates for salmon diet extracts were significantly lower than all other diet extracts (P < 0.001). To evaluate the accuracy of faecal DNA sex identification when female carnivores consume male mammalian prey, female bears were fed male white-tailed deer. Four of 10 extracts amplified, and all extracts were incorrectly scored as male due to amplification of X and Y-chromosome fragments. The potential biases highlighted in this study have broad implications for researchers using faecal DNA for individual and sex identification, and should be evaluated in other species.

  18. Respiratory system loop gain in normal men and women measured with proportional-assist ventilation.

    PubMed

    Wellman, Andrew; Malhotra, Atul; Fogel, Robert B; Edwards, Jill K; Schory, Karen; White, David P

    2003-01-01

    We hypothesized that increased chemical control instability (CCI) in men could partially explain the male predominance in obstructive sleep apnea (OSA). CCI was assessed by sequentially increasing respiratory control system loop gain (LG) with proportional-assist ventilation (PAV) in 10 men (age 24-48 yr) and 9 women (age 22-36 yr) until periodic breathing or awakening occurred. Women were studied in both the follicular and luteal phases of the menstrual cycle. The amount by which PAV amplified LG was quantified from the tidal volume amplification factor [(VtAF) assisted tidal volume/unassisted tidal volume]. LG was calculated as the inverse of the VtAF occurring at the assist level immediately preceding the emergence of periodic breathing (when LG x VtAF = 1). Only 1 of 10 men and 2 of 9 women developed periodic breathing with PAV. The rest were resistant to periodic breathing despite moderately high levels of PAV amplification. We conclude that LG is low in the majority of normal men and women and that higher volume amplification factors are needed to determine whether gender differences exist in this low range.

  19. Classroom Amplification Technology: Theory and Practice.

    ERIC Educational Resources Information Center

    Crandell, Carl C.; Smaldino, Joseph J.

    2000-01-01

    This article reviews some relevant events in the development of acoustical standards for classrooms, describes classroom challenges to providing clear acoustical signals to children in classrooms, and outlines amplification solutions to some of those classroom challenges. Solutions include personal amplification devices and use of signal-to-noise…

  20. HER-2 amplification in tubular carcinoma of the breast.

    PubMed

    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.

  1. Unusual isothermal multimerization and amplification by the strand-displacing DNA polymerases with reverse transcription activities.

    PubMed

    Wang, Guoping; Ding, Xiong; Hu, Jiumei; Wu, Wenshuai; Sun, Jingjing; Mu, Ying

    2017-10-24

    Existing isothermal nucleic acid amplification (INAA) relying on the strand displacement activity of DNA polymerase usually requires at least two primers. However, in this paper, we report an unusual isothermal multimerization and amplification (UIMA) which only needs one primer and is efficiently initiated by the strand-displacing DNA polymerases with reverse transcription activities. On electrophoresis, the products of UIMA present a cascade-shape band and they are confirmed to be multimeric DNAs with repeated target sequences. In contrast to current methods, UIMA is simple to product multimeric DNA, due to the independent of multiple primers and rolling circle structures. Through assaying the synthesized single-stranded DNA targets, UIMA performs high sensitivity and specificity, as well as the universality. In addition, a plausible mechanism of UIMA is proposed, involving short DNA bending, mismatch extension, and template slippage. UIMA is a good explanation for why nonspecific amplification easily happens in existing INAAs. As the simplest INAA till now, UIMA provides a new insight for deeply understanding INAA and opens a new avenue for thoroughly addressing nonspecific amplification.

  2. Ultra-strong surface plasmon amplification characteristic of a spaser based on gold-silver core-shell nanorods

    NASA Astrophysics Data System (ADS)

    Zhang, Li; Zhou, Jun; Zhang, Haopeng; Jiang, Tao; Lou, Cibo

    2015-03-01

    We proposed an efficient spaser based on gold-silver core-shell nanorods (NRs) encapsulated by an outer silica shell doped with a gain medium. The optical characteristics of the spaser were numerically simulated based on the finite element method (FEM). The results showed that the localized surface plasmon resonance (LSPR) amplification characteristics of the spaser strongly depend on the thickness of silver shell, the aspect ratio of the inner gold NRs, and the polarization direction of the incident light. And, the maximum absolute value of optical cross-section of the spaser can reach 21,824 μm2, which is about 1115, 523, and 18 times higher than that of spasers based on the gold NRs, the silver NRs, and the silver-gold core-shell NRs, respectively. The ultra-strong surface plasmon amplification characteristics of the spaser have potential applications in optical information storage, high sensitivity biochemical sensing, and medical engineering.

  3. Energy Flux in the Cochlea: Evidence Against Power Amplification of the Traveling Wave.

    PubMed

    van der Heijden, Marcel; Versteegh, Corstiaen P C

    2015-10-01

    Traveling waves in the inner ear exhibit an amplitude peak that shifts with frequency. The peaking is commonly believed to rely on motile processes that amplify the wave by inserting energy. We recorded the vibrations at adjacent positions on the basilar membrane in sensitive gerbil cochleae and tested the putative power amplification in two ways. First, we determined the energy flux of the traveling wave at its peak and compared it to the acoustic power entering the ear, thereby obtaining the net cochlear power gain. For soft sounds, the energy flux at the peak was 1 ± 0.6 dB less than the middle ear input power. For more intense sounds, increasingly smaller fractions of the acoustic power actually reached the peak region. Thus, we found no net power amplification of soft sounds and a strong net attenuation of intense sounds. Second, we analyzed local wave propagation on the basilar membrane. We found that the waves slowed down abruptly when approaching their peak, causing an energy densification that quantitatively matched the amplitude peaking, similar to the growth of sea waves approaching the beach. Thus, we found no local power amplification of soft sounds and strong local attenuation of intense sounds. The most parsimonious interpretation of these findings is that cochlear sensitivity is not realized by amplifying acoustic energy, but by spatially focusing it, and that dynamic compression is realized by adjusting the amount of dissipation to sound intensity.

  4. Microwave amplification with nanomechanical resonators.

    PubMed

    Massel, F; Heikkilä, T T; Pirkkalainen, J-M; Cho, S U; Saloniemi, H; Hakonen, P J; Sillanpää, M A

    2011-12-14

    The sensitive measurement of electrical signals is at the heart of modern technology. According to the principles of quantum mechanics, any detector or amplifier necessarily adds a certain amount of noise to the signal, equal to at least the noise added by quantum fluctuations. This quantum limit of added noise has nearly been reached in superconducting devices that take advantage of nonlinearities in Josephson junctions. Here we introduce the concept of the amplification of microwave signals using mechanical oscillation, which seems likely to enable quantum-limited operation. We drive a nanomechanical resonator with a radiation pressure force, and provide an experimental demonstration and an analytical description of how a signal input to a microwave cavity induces coherent stimulated emission and, consequently, signal amplification. This generic scheme, which is based on two linear oscillators, has the advantage of being conceptually and practically simpler than the Josephson junction devices. In our device, we achieve signal amplification of 25 decibels with the addition of 20 quanta of noise, which is consistent with the expected amount of added noise. The generality of the model allows for realization in other physical systems as well, and we anticipate that near-quantum-limited mechanical microwave amplification will soon be feasible in various applications involving integrated electrical circuits.

  5. Resonant absorption and amplification of circularly-polarized waves in inhomogeneous chiral media.

    PubMed

    Kim, Seulong; Kim, Kihong

    2016-01-25

    It has been found that in the media where the dielectric permittivity ε or the magnetic permeability μ is near zero and in transition metamaterials where ε or μ changes from positive to negative values, there occur a strong absorption or amplification of the electromagnetic wave energy in the presence of an infinitesimally small damping or gain and a strong enhancement of the electromagnetic fields. We attribute these phenomena to the mode conversion of transverse electromagnetic waves into longitudinal plasma oscillations and its inverse process. In this paper, we study analogous phenomena occurring in chiral media theoretically using the invariant imbedding method. In uniform isotropic chiral media, right-circularly-polarized and left-circularly-polarized waves are the eigen-modes of propagation with different effective refractive indices n(+) and n(-), whereas in the chiral media with a nonuniform impedance variation, they are no longer the eigenmodes and are coupled to each other. We find that both in uniform chiral slabs where either n(+) or n(-) is near zero and in chiral transition metamaterials where n(+) or n(-) changes from positive to negative values, a strong absorption or amplification of circularly-polarized waves occurs in the presence of an infinitesimally small damping or gain. We present detailed calculations of the mode conversion coefficient, which measures the fraction of the electromagnetic wave energy absorbed into the medium, for various configurations of ε and μ with an emphasis on the influence of a nonuniform impedance. We propose possible applications of these phenomena to linear and nonlinear optical devices that react selectively to the helicity of the circular polarization.

  6. Hotspot Selective Preference of the Chimeric Sequences Formed in Multiple Displacement Amplification.

    PubMed

    Tu, Jing; Lu, Na; Duan, Mengqin; Huang, Mengting; Chen, Liang; Li, Junji; Guo, Jing; Lu, Zuhong

    2017-02-24

    Multiple displacement amplification (MDA) is considered to be a conventional approach to comprehensive amplification from low input DNA. The chimeric reads generated in MDA lead to severe disruption in some studies, including those focusing on heterogeneity, structural variation, and genetic recombination. Meanwhile, the generation of by-products gives a new approach to gain insights into the reaction process of φ29 polymerase. Here, we analyzed 36.7 million chimeras and screened 196 billion chimeric hotspots in the human genome, as well as evaluating the hotspot selective preference of chimeras. No significant preference was captured in the distributions of chimeras and hotspots among chromosomes. Hotspots with overlaps for 12-13 nucleotides (nt) were most likely to be selected as templates in chimera generation. Meanwhile, a regularly selective preference was noticed in overlap GC content. The preferences in overlap length and GC content was shown to be pertinent to the sequence denaturation temperature, which pointed out the optimization direction for reducing chimeras. Distance preference between two segments of chimeras was 80-280 nt. The analysis is beneficial for reducing the chimeras in MDA, and the characterization of MDA chimeras is helpful in distinguishing MDA chimeras from chimeric sequences caused by disease.

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

    NASA Astrophysics Data System (ADS)

    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.

  8. 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.

    PubMed

    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.

  9. Interference effects in a cavity for optical amplification

    NASA Astrophysics Data System (ADS)

    Cardimona, D. A.; Alsing, P. M.

    2009-08-01

    In space situational awareness scenarios, the objects needed to be characterized and identified are usually quite far away and quite dim. Thus, optical detectors need to be able to sense these very dim optical signals. Quantum interference in a three-level system can lead to amplification of optical signals. If we put a three-level system into a cavity tuned to the frequency of an incoming optical signal, we anticipate the amplification possibilities should be increased proportional to the quality factor of the cavity. Our vision is to utilize quantum dots in photonic crystal cavities, but as a stepping stone we first investigate a simple three-level system in a free-space optical cavity. We investigate quantum interference and classical interference effects when a three-level system interacts with both a cavity field mode and an external driving field mode. We find that under certain circumstances the cavity field evolves to be equal in magnitude to, but 180° out-of-phase with the external pump field when the pump field frequency equals the cavity frequency. At this point the resonance fluorescence from the atom in the cavity goes to zero due to a purely classical interference effect between the two out-of-phase fields. This is quite different from the quantum interference that occurs under the right circumstances, when the state populations are coherently driven into a linear combination that is decoupled from any applied field - and population is trapped in the excited states, thus allowing for a population inversion and an amplification of incoming optical signals.

  10. Enhanced traveling wave amplification of co-planar slow wave structure by extended phase-matching

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Palm, Andrew; Sirigiri, Jagadishwar; Shin, Young-Min, E-mail: yshin@niu.edu

    2015-09-15

    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 bandwidthmore » 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.« less

  11. Hyperpolarization of “Neat” Liquids by NMR Signal Amplification by Reversible Exchange

    PubMed Central

    2016-01-01

    We report NMR Signal Amplification by Reversible Exchange (SABRE) hyperpolarization of the rare isotopes in “neat” liquids, each composed only of an otherwise pure target compound with isotopic natural abundance (n.a.) and millimolar concentrations of dissolved catalyst. Pyridine (Py) or Py derivatives are studied at 0.4% isotopic natural abundance 15N, deuterated, 15N enriched, and in various combinations using the SABRE-SHEATH variant (microTesla magnetic fields to permit direct 15N polarization from parahydrogen via reversible binding and exchange with an Ir catalyst). We find that the dilute n.a. 15N spin bath in Py still channels spin order from parahydrogen to dilute 15N spins, without polarization losses due to the presence of 14N or 2H. We demonstrate P15N ≈ 1% (a gain of 2900 fold relative to thermal polarization at 9.4 T) at high substrate concentrations. This fundamental finding has a significant practical benefit for screening potentially hyperpolarizable contrast agents without labeling. The capability of screening at n.a. level of 15N is demonstrated on examples of mono- and dimethyl-substituted Py (picolines and lutidines previously identified as promising pH sensors), showing that the presence of a methyl group in the ortho position significantly decreases SABRE hyperpolarization. PMID:26029349

  12. New methods to characterize site amplification

    USGS Publications Warehouse

    Safak, Erdal

    1993-01-01

    Methods alternative to spectral ratios are introduced to characterize site amplification. The methods are developed by using a range of models, from the simple constant amplification model to the time-varying filter model. Examples are given for each model by using a pair of rock- and soil-site recordings from the Loma Prieta earthquake.

  13. High Intensity Mirror-Free Nanosecond Ytterbium Fiber Laser System in Master Oscillator Power Amplification

    NASA Astrophysics Data System (ADS)

    Chun-Lin, Louis Chang

    Rare-earth-doped fiber lasers and amplifiers are relatively easy to efficiently produce a stable and high quality laser beam in a compact, robust, and alignment-free configuration. Recently, high power fiber laser systems have facilitated wide spread applications in academics, industries, and militaries in replacement of bulk solid-state laser systems. The master oscillator power amplifier (MOPA) composed of a highly-controlled seed, high-gain preamplifiers, and high-efficiency power amplifiers are typically utilized to scale up the pulse energy, peak power, or average power. Furthermore, a direct-current-modulated nanosecond diode laser in single transverse mode can simply provide a compact and highly-controlled seed to result in the flexible output parameters, such as repetition rate, pulse duration, and even temporal pulse shape. However, when scaling up the peak power for high intensity applications, such a versatile diode-seeded nanosecond MOPA laser system using rare-earth-doped fibers is unable to completely save its own advantages compared to bulk laser systems. Without a strong seeding among the amplifiers, the guided amplified spontaneous amplification is easy to become dominant during the amplification, leading to the harmful self-lasing or pulsing effects, and the difficulty of the quantitative numerical comparison. In this dissertation, we study a high-efficiency and intense nanosecond ytterbium fiber MOPA system with good beam quality and stability for high intensity applications. The all-PM-fiber structure is achieved with the output extinction ratio of >12 dB by optimizing the interconnection of high power optical fibers. The diode-seeded MOPA configuration without parasitic stimulated amplification (PAS) is implemented using the double-pass scheme to extract energy efficiently for scaling peak power. The broadband PAS was studied experimentally, which matches well with our numerical simulation. The 1064-nm nanosecond seed was a direct

  14. Flux amplification in helicity injected spherical tori

    NASA Astrophysics Data System (ADS)

    Tang, X. Z.; Boozer, A. H.

    2005-04-01

    An important measure of the effective current drive by helicity injection into spheromaks and spherical tori is provided by the flux amplification factor, defined as the ratio between the closed poloidal flux in the relaxed mean field and the initial injector vacuum poloidal flux. Flux amplification in magnetic helicity injection is governed by a resonant behavior for Taylor-relaxed plasmas satisfying j =kB. Under the finite net toroidal flux constraint in a spherical torus (ST), the constrained linear resonance k1c is upshifted substantially from the primary Jensen-Chu resonance k1 that was known to be responsible for flux amplification in spheromak formation. Standard coaxial helicity injection into a ST operates at large M, with M the characteristic dimensionless parameter defined as the ratio between the toroidal flux in the discharge chamber and the injector poloidal flux. Meaningful flux amplification for ST plasmas is limited by a critical kr at which edge toroidal field reverses its direction. The kr is downshifted from k1 by a small amount inversely proportional to M. The maximum flux amplification factor Ar≡A(k=kr) scales linearly with M. At the other end of k, substantial flux amplification A(k =ko)˜1 becomes available for ko that scales inversely proportional to M, a significant departure from that in spheromak formation. These important parameters follow the inequality koamplification factor in a ST to be smaller than M. The scaling laws are given analytically in the asymptotic limit of M ≫1, but numerical solutions indicate that they are useful even for M ˜1.

  15. Magnetic Field Amplification in Supernova Remnants

    NASA Astrophysics Data System (ADS)

    Xu, Siyao; Lazarian, Alex

    2017-12-01

    Based on the new findings on the turbulent dynamo in Xu & Lazarian, we examine the magnetic field amplification in the context of supernova remnants. Due to the strong ion-neutral collisional damping in the weakly ionized interstellar medium, the dynamo in the preshock turbulence remains in the damping kinematic regime, which leads to a linear-in-time growth of the magnetic field strength. The resultant magnetic field structure enables effective diffusion upstream and shock acceleration of cosmic rays to energies above the “knee.” Differently, the nonlinear dynamo in the postshock turbulence leads to a linear-in-time growth of the magnetic energy due to the turbulent magnetic diffusion. Given a weak initial field strength in the postshock region, the magnetic field saturates at a significant distance from the shock front as a result of the inefficiency of the nonlinear dynamo. This result is in a good agreement with existing numerical simulations and well explains the X-ray spots detected far behind the shock front.

  16. Amplification of Angular Rotations Using Weak Measurements

    NASA Astrophysics Data System (ADS)

    Magaña-Loaiza, Omar S.; Mirhosseini, Mohammad; Rodenburg, Brandon; Boyd, Robert W.

    2014-05-01

    We present a weak measurement protocol that permits a sensitive estimation of angular rotations based on the concept of weak-value amplification. The shift in the state of a pointer, in both angular position and the conjugate orbital angular momentum bases, is used to estimate angular rotations. This is done by an amplification of both the real and imaginary parts of the weak-value of a polarization operator that has been coupled to the pointer, which is a spatial mode, via a spin-orbit coupling. Our experiment demonstrates the first realization of weak-value amplification in the azimuthal degree of freedom. We have achieved effective amplification factors as large as 100, providing a sensitivity that is on par with more complicated methods that employ quantum states of light or extremely large values of orbital angular momentum.

  17. Diagnostic devices for isothermal nucleic acid amplification.

    PubMed

    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.

  18. Diagnostic Devices for Isothermal Nucleic Acid Amplification

    PubMed Central

    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. PMID:22969402

  19. Changes in southern hemispheric polar amplification over the past 5 million years revealed by climate modelling

    NASA Astrophysics Data System (ADS)

    Hoencamp, Jori; Stap, Lennert; Tuenter, Erik; Lourens, Luc; van de Wal, Roderik

    2016-04-01

    Knowledge on polar amplification is important to relate high latitude climate records to global mean temperature changes. Several studies have pointed out that the strength of polar amplification in the Northern Hemisphere varies considerably due to the presence of large ice sheets and more sea ice during colder climate conditions. As a result, the polar amplification in the Northern Hemisphere decreases for warmer climates. In this study, we address the fact that these changes in the Northern Hemisphere also affect the polar amplification in the Southern Hemisphere. We study the Southern and Northern Hemisphere amplification together over the past 5 million years with the CLIMBER-2 intermediate complexity model. Radiation, land ice extent and height, and greenhouse gases are prescribed as forcing. We find that in contrast to the reduction in polar amplification in the Northern Hemisphere, polar amplification in the Southern Hemisphere increases for warmer climates. The amplification decreases in the Northern Hemisphere from 2.7 during glacial conditions to 1.6 for a pre-industrial climate, which is line with other climate simulations. Over the same CO2 range the southern hemispheric polar amplification increases from 1 to 1.6. This is caused by the fact that the atmospheric transport needed to balance the radiation surplus in the equatorial region needs to be compensated by relatively stronger transport of energy in Southern direction while the transport in Northern direction reduces. This reduction in Northern direction is driven by less (land and sea) ice resulting in a smaller meridional gradient in Northern direction and hence a smaller atmospheric transport. As a consequence, the traditional scaled (with LGM temperature) Dome C record needs to be corrected with a maximum of 0.6 degrees half-way glacial and interglacial conditions, if it is to be interpreted as global mean temperature change indicator. While this changes the amplitude, the phasing of

  20. Oncogene-like induction of cellular invasion from centrosome amplification

    PubMed Central

    Godinho, Susana A.; Picone, Remigio; Burute, Mithila; Dagher, Regina; Su, Ying; Leung, Cheuk T.; Polyak, Kornelia; Brugge, Joan S.; Thery, Manuel; Pellman, David

    2014-01-01

    Centrosome amplification has long been recognized as a feature of human tumors, however its role in tumorigenesis remains unclear1. Centrosome amplification is poorly tolerated by non-transformed cells, and, in the absence of selection, extra centrosomes are spontaneously lost2. Thus, the high frequency of centrosome amplification, particularly in more aggressive tumors3, raises the possibility that extra centrosomes could, in some contexts, confer advantageous characteristics that promote tumor progression. Using a three-dimensional model system and other approaches to culture human mammary epithelial cells, we find that centrosome amplification triggers cell invasion. This invasive behavior is similar to that induced by overexpression of the breast cancer oncogene ErbB24 and indeed enhances invasiveness triggered by ErbB2. We show that, through increased centrosomal microtubule nucleation, centrosome amplification increases Rac1 activity, which disrupts normal cell-cell adhesion and promotes invasion. These findings demonstrate that centrosome amplification, a structural alteration of the cytoskeleton, can promote features of malignant transformation. PMID:24739973

  1. A bootstrapped, low-noise, and high-gain photodetector for shot noise measurement

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhou, Haijun; Yang, Wenhai; Li, Zhixiu

    2014-01-15

    We presented a low-noise, high-gain photodetector based on the bootstrap structure and the L-C (inductance and capacitance) combination. Electronic characteristics of the photodetector, including electronic noise, gain and frequency response, and dynamic range, were verified through a single-frequency Nd:YVO{sub 4} laser at 1064 nm with coherent output. The measured shot noise of 50 μW laser was 13 dB above the electronic noise at the analysis frequency of 2 MHz, and 10 dB at 3 MHz. And a maximum clearance of 28 dB at 2 MHz was achieved when 1.52 mW laser was illuminated. In addition, the photodetector showed excellent linearitiesmore » for both DC and AC amplifications in the laser power range between 12.5 μW and 1.52 mW.« less

  2. Tunable Fano resonance using weak-value amplification with asymmetric spectral response as a natural pointer

    NASA Astrophysics Data System (ADS)

    Singh, Ankit K.; Ray, Subir K.; Chandel, Shubham; Pal, Semanti; Gupta, Angad; Mitra, P.; Ghosh, N.

    2018-05-01

    Weak measurement enables faithful amplification and high-precision measurement of small physical parameters and is under intensive investigation as an effective tool in metrology and for addressing foundational questions in quantum mechanics. Here we demonstrate weak-value amplification using the asymmetric spectral response of Fano resonance as the pointer arising naturally in precisely designed metamaterials, namely, waveguided plasmonic crystals. The weak coupling between the polarization degree of freedom and the spectral response of Fano resonance arises due to a tiny shift in the asymmetric spectral response between two orthogonal linear polarizations. By choosing the preselected and postselected polarization states to be nearly mutually orthogonal, we observe both real and imaginary weak-value amplifications manifested as a spectacular shift of the Fano-resonance peak and narrowing (or broadening) of the resonance linewidth, respectively. The remarkable control and tunability of Fano resonance in a single device enabled by weak-value amplification may enhance active Fano-resonance-based applications in the nano-optical domain. In general, weak measurements using Fano-type spectral response broadens the domain of applicability of weak measurements using natural spectral line shapes as a pointer in a wide range of physical systems.

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

    PubMed

    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.

  4. Localized damage caused by topographic amplification during the 2010 M7.0 Haiti earthquake

    USGS Publications Warehouse

    Hough, S.E.; Altidor, J.R.; Anglade, D.; Given, D.; Janvier, M.G.; Maharrey, J.Z.; Meremonte, M.; Mildor, B.S.-L.; Prepetit, C.; Yong, A.

    2010-01-01

    Local geological conditions, including both near-surface sedimentary layers and topographic features, are known to significantly influence ground motions caused by earthquakes. Microzonation maps use local geological conditions to characterize seismic hazard, but commonly incorporate the effect of only sedimentary layers. Microzonation does not take into account local topography, because significant topographic amplification is assumed to be rare. Here we show that, although the extent of structural damage in the 2010 Haiti earthquake was primarily due to poor construction, topographic amplification contributed significantly to damage in the district of Petionville, south of central Port-au-Prince. A large number of substantial, relatively well-built structures situated along a foothill ridge in this district sustained serious damage or collapse. Using recordings of aftershocks, we calculate the ground motion response at two seismic stations along the topographic ridge and at two stations in the adjacent valley. Ground motions on the ridge are amplified relative to both sites in the valley and a hard-rock reference site, and thus cannot be explained by sediment-induced amplification. Instead, the amplitude and predominant frequencies of ground motion indicate the amplification of seismic waves by a narrow, steep ridge. We suggest that microzonation maps can potentially be significantly improved by incorporation of topographic effects. ?? 2010 Macmillan Publishers Limited. All rights reserved.

  5. Helicase dependent OnChip-amplification and its use in multiplex pathogen detection.

    PubMed

    Andresen, Dennie; von Nickisch-Rosenegk, Markus; Bier, Frank F

    2009-05-01

    The need for fast, specific and sensitive multiparametric detection methods is an ever growing demand in molecular diagnostics. Here we report on a newly developed method, the helicase dependent OnChip amplification (OnChip-HDA). This approach integrates the analysis and detection in one single reaction thus leading to time and cost savings in multiparametric analysis. HDA is an isothermal amplification method that is not depending on thermocycling as known from PCR due to the helicases' ability to unwind DNA double-strands. We have combined the HDA with microarray based detection, making it suitable for multiplex detection. As an example we used the OnChip HDA in single and multiplex amplifications for the detection of the two pathogens N. gonorrhoeae and S. aureus directly on surface bound primers. We have successfully shown the OnChip-HDA and applied it for single- and duplex-detection of the pathogens N. gonorrhoeae and S. aureus. We have developed a new method, the OnChip-HDA for the multiplex detection of pathogens. Its simplicity in reaction setup and potential for miniaturization and multiparametric analysis is advantageous for the integration in miniaturized Lab on Chip systems, e.g. needed in point of care diagnostics.

  6. Protein Detection via Direct Enzymatic Amplification of Short DNA Aptamers

    PubMed Central

    Fischer, Nicholas O.; Tarasow, Theodore M.; Tok, Jeffrey B.-H.

    2008-01-01

    Aptamers are single-stranded nucleic acids that fold into defined tertiary structures to bind target molecules with high specificities and affinities. DNA aptamers have garnered much interest as recognition elements for biodetection and diagnostic applications due to their small size, ease of discovery and synthesis, and chemical and thermal stability. Herein, we describe the design and application of a short DNA molecule capable of both protein target binding and amplifiable bioreadout processes. As both recognition and readout capabilities are incorporated into a single DNA molecule, tedious conjugation procedures required for protein-DNA hybrids can be omitted. The DNA aptamer is designed to be amplified directly by either the polymerase chain reaction (PCR) or rolling circle amplification (RCA) processes, taking advantage of real-time amplification monitoring techniques for target detection. A combination of both RCA and PCR provides a wide protein target dynamic range (1 μM to 10 pM). PMID:17980857

  7. Desert Amplification in a Warming Climate

    PubMed Central

    Zhou, Liming

    2016-01-01

    Here I analyze the observed and projected surface temperature anomalies over land between 50°S-50°N for the period 1950–2099 by large-scale ecoregion and find strongest warming consistently and persistently seen over driest ecoregions such as the Sahara desert and the Arabian Peninsula during various 30-year periods, pointing to desert amplification in a warming climate. This amplification enhances linearly with the global mean greenhouse gases(GHGs) radiative forcing and is attributable primarily to a stronger GHGs-enhanced downward longwave radiation forcing reaching the surface over drier ecoregions as a consequence of a warmer and thus moister atmosphere in response to increasing GHGs. These results indicate that desert amplification may represent a fundamental pattern of global warming associated with water vapor feedbacks over land in low- and mid- latitudes where surface warming rates depend inversely on ecosystem dryness. It is likely that desert amplification might involve two types of water vapor feedbacks that maximize respectively in the tropical upper troposphere and near the surface over deserts, with both being very dry and thus extremely sensitive to changes of water vapor. PMID:27538725

  8. Conceptual design of sub-exa-watt system by using optical parametric chirped pulse amplification

    NASA Astrophysics Data System (ADS)

    Kawanaka, J.; Tsubakimoto, K.; Yoshida, H.; Fujioka, K.; Fujimoto, Y.; Tokita, S.; Jitsuno, T.; Miyanaga, N.; Gekko-EXA Design Team

    2016-03-01

    A 50 PW ultrahigh-peak-power laser has been conceptually designed, which is based on optical parametric chirped pulse amplification (OPCPA). A 250 J DPSSL and a flash- lamp-pumped kJ laser are adopted as new repeatable pump source. The existed LFEX-laser with more than ten kilo joules are used in the final amplifier stage and the OPCPA with the 2x2 tiled pump beams in random phase has been proposed with several ten centimeter aperture. A pulse duration of amplified pulses is set at less than 10 fs. A broadband OPCPA with ∼500 nm of the gain spectral width near 1 μm is required. A partially deuterated KDP (p-DKDP) crystal is one of the most promising nonlinear crystals and our numerical calculation ensured such ultra-broad gain width. p-DKDP crystals with several deuteration ratio have been successfully grown.

  9. Gain competition in dual wavelength quantum cascade lasers.

    PubMed

    Geiser, Markus; Pflügl, Christian; Belyanin, Alexey; Wang, Qi Jie; Yu, Nanfang; Edamura, Tadanaka; Yamanishi, Masamichi; Kan, Hirofumi; Fischer, Milan; Wittmann, Andreas; Faist, Jérôme; Capasso, Federico

    2010-05-10

    We investigated dual wavelength mid-infrared quantum cascade lasers based on heterogeneous cascades. We found that due to gain competition laser action tends to start in higher order lateral modes. The mid-infrared mode with the lower threshold current reduces population inversion for the second laser with the higher threshold current due to stimulated emission. We developed a rate equation model to quantitatively describe mode interactions due to mutual gain depletion. (c) 2010 Optical Society of America.

  10. Abnormal Auditory Gain in Hyperacusis: Investigation with a Computational Model

    PubMed Central

    Diehl, Peter U.; Schaette, Roland

    2015-01-01

    Hyperacusis is a frequent auditory disorder that is characterized by abnormal loudness perception where sounds of relatively normal volume are perceived as too loud or even painfully loud. As hyperacusis patients show decreased loudness discomfort levels (LDLs) and steeper loudness growth functions, it has been hypothesized that hyperacusis might be caused by an increase in neuronal response gain in the auditory system. Moreover, since about 85% of hyperacusis patients also experience tinnitus, the conditions might be caused by a common mechanism. However, the mechanisms that give rise to hyperacusis have remained unclear. Here, we have used a computational model of the auditory system to investigate candidate mechanisms for hyperacusis. Assuming that perceived loudness is proportional to the summed activity of all auditory nerve (AN) fibers, the model was tuned to reproduce normal loudness perception. We then evaluated a variety of potential hyperacusis gain mechanisms by determining their effects on model equal-loudness contours and comparing the results to the LDLs of hyperacusis patients with normal hearing thresholds. Hyperacusis was best accounted for by an increase in non-linear gain in the central auditory system. Good fits to the average patient LDLs were obtained for a general increase in gain that affected all frequency channels to the same degree, and also for a frequency-specific gain increase in the high-frequency range. Moreover, the gain needed to be applied after subtraction of spontaneous activity of the AN, which is in contrast to current theories of tinnitus generation based on amplification of spontaneous activity. Hyperacusis and tinnitus might therefore be caused by different changes in neuronal processing in the central auditory system. PMID:26236277

  11. Amplification of chromosomal DNA in situ

    DOEpatents

    Christian, Allen T.; Coleman, Matthew A.; Tucker, James D.

    2002-01-01

    Amplification of chromosomal DNA in situ to increase the amount of DNA associated with a chromosome or chromosome region is described. The amplification of chromosomal DNA in situ provides for the synthesis of Fluorescence in situ Hybridization (FISH) painting probes from single dissected chromosome fragments, the production of cDNA libraries from low copy mRNAs and improved in Comparative Genomic Hybridization (CGH) procedures.

  12. Rolling circle amplification of metazoan mitochondrialgenomes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    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.

  13. Gain-switched laser diode seeded Yb-doped fiber amplifier delivering 11-ps pulses at repetition rates up to 40-MHz

    NASA Astrophysics Data System (ADS)

    Ryser, Manuel; Neff, Martin; Pilz, Soenke; Burn, Andreas; Romano, Valerio

    2012-02-01

    Here, we demonstrate all-fiber direct amplification of 11 picosecond pulses from a gain-switched laser diode at 1063 nm. The diode was driven at a repetition rate of 40 MHz and delivered 13 μW of fiber-coupled average output power. For the low output pulse energy of 0.33 pJ we have designed a multi-stage core pumped preamplifier based on single clad Yb-doped fibers in order to keep the contribution of undesired amplified spontaneous emission as low as possible and to minimize temporal and spectral broadening. After the preamplifier we reduced the 40 MHz repetition rate to 1 MHz using a fiber coupled pulse-picker. The final amplification was done with a cladding pumped Yb-doped large mode area fiber and a subsequent Yb-doped rod-type fiber. With our setup we achieved amplification of 72 dBs to an output pulse energy of 5.7 μJ, pulse duration of 11 ps and peak power of >0.6 MW.

  14. Can Anomalous Amplification be Attained without Postselection?

    PubMed

    Martínez-Rincón, Julián; Liu, Wei-Tao; Viza, Gerardo I; Howell, John C

    2016-03-11

    We present a parameter estimation technique based on performing joint measurements of a weak interaction away from the weak-value-amplification approximation. Two detectors are used to collect full statistics of the correlations between two weakly entangled degrees of freedom. Without discarding of data, the protocol resembles the anomalous amplification of an imaginary-weak-value-like response. The amplification is induced in the difference signal of both detectors allowing robustness to different sources of technical noise, and offering in addition the advantages of balanced signals for precision metrology. All of the Fisher information about the parameter of interest is collected. A tunable phase controls the strength of the amplification response. We experimentally demonstrate the proposed technique by measuring polarization rotations in a linearly polarized laser pulse. We show that in the presence of technical noise the effective sensitivity and precision of a split detector is increased when compared to a conventional continuous-wave balanced detection technique.

  15. Can Anomalous Amplification be Attained without Postselection?

    NASA Astrophysics Data System (ADS)

    Martínez-Rincón, Julián; Liu, Wei-Tao; Viza, Gerardo I.; Howell, John C.

    2016-03-01

    We present a parameter estimation technique based on performing joint measurements of a weak interaction away from the weak-value-amplification approximation. Two detectors are used to collect full statistics of the correlations between two weakly entangled degrees of freedom. Without discarding of data, the protocol resembles the anomalous amplification of an imaginary-weak-value-like response. The amplification is induced in the difference signal of both detectors allowing robustness to different sources of technical noise, and offering in addition the advantages of balanced signals for precision metrology. All of the Fisher information about the parameter of interest is collected. A tunable phase controls the strength of the amplification response. We experimentally demonstrate the proposed technique by measuring polarization rotations in a linearly polarized laser pulse. We show that in the presence of technical noise the effective sensitivity and precision of a split detector is increased when compared to a conventional continuous-wave balanced detection technique.

  16. Lidar using the backscatter amplification effect

    NASA Astrophysics Data System (ADS)

    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.

  17. Amplification, Technology, and Cochlear Implants for Infants.

    ERIC Educational Resources Information Center

    Adam, Arlie J.

    1993-01-01

    Early amplification is crucial to efficient habilitation and development of oral communication skills in hearing-impaired infants. Initial evaluation and fitting of amplification is a joint effort by the audiologist, therapist, and parents, whether the child uses traditional hearing aids or cochlear implants, and should be supplemented by a…

  18. Recurrent amplification of RTEL1 and ABCA13 and its synergistic effect associated with clinicopathological data of gastric adenocarcinoma.

    PubMed

    Araújo, T M; Seabra, A D; Lima, E M; Assumpção, P P; Montenegro, R C; Demachki, S; Burbano, R M; Khayat, A S

    2016-01-01

    Despite progression in treatment of gastric cancer, prognosis of patients remains poor, in part due to the low rate of diagnosis during its early stages. This paradigm implies the necessity to identify molecular biomarkers for early gastric cancer diagnosis, as well as for disease monitoring, thus contributing to the development of new therapeutic approaches. In a previous study, performed by array-Comparative Genomic Hybridization, we described for the first time in literature recurrent amplification of RTEL1 and ABCA13 genes in gastric cancer. Thus, the aim of the present study was to validate recurrent amplification of RTEL1 and ABCA13 genes and associate CNV status with clinicopathological data. Results showed RTEL1 and ABCA13 amplification in 38 % of samples. Statistical analysis demonstrated that RTEL amplification is more common in older patients and more associated with intestinal type and ABCA13 amplification increases the risk of lymph node metastasis and is more common in men. Co-amplification of these genes showed a significant association with advanced staging. aCGH is a very useful tool for investigating novel genes associated with carcinogenesis and RTEL1 amplification may be important for the development of gastric cancer in older patients, besides being a probable event contributing for chromosomal instability in intestinal gastric carcinogenesis. ABCA13 amplification may have age-specific function and could be considered a useful marker for predicting lymph node metastasis in resected gastric cancer patients in early stage. Lastly, RTEL1 and ABCA13 synergistic effect may be considered as a putative marker for advanced staging in gastric cancer patients.

  19. Beam cleaning of an incoherent laser via plasma Raman amplification

    DOE PAGES

    Edwards, Matthew R.; Qu, Kenan; Mikhailova, Julia M.; ...

    2017-09-25

    We show that backward Raman amplification in plasma can efficiently compress a temporally incoherent pump laser into an intense coherent amplified seed pulse, provided that the correlation time of the pump is longer than the inverse plasma frequency. One analytical theory for Raman amplification using pump beams with different correlation functions is developed and compared to numerical calculations and particle-in-cell simulations. Since incoherence on scales shorter than the instability growth time suppresses spontaneous noise amplification, we point out a broad regime where quasi-coherent sources may be used as efficient low-noise Raman amplification pumps. As the amplified seed is coherent, Ramanmore » amplification provides an additional a beam-cleaning mechanism for removing incoherence. At near-infrared wavelengths, finite coherence times as short as 50 fs allow amplification with only minor losses in efficiency.« less

  20. Beam cleaning of an incoherent laser via plasma Raman amplification

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Edwards, Matthew R.; Qu, Kenan; Mikhailova, Julia M.

    We show that backward Raman amplification in plasma can efficiently compress a temporally incoherent pump laser into an intense coherent amplified seed pulse, provided that the correlation time of the pump is longer than the inverse plasma frequency. One analytical theory for Raman amplification using pump beams with different correlation functions is developed and compared to numerical calculations and particle-in-cell simulations. Since incoherence on scales shorter than the instability growth time suppresses spontaneous noise amplification, we point out a broad regime where quasi-coherent sources may be used as efficient low-noise Raman amplification pumps. As the amplified seed is coherent, Ramanmore » amplification provides an additional a beam-cleaning mechanism for removing incoherence. At near-infrared wavelengths, finite coherence times as short as 50 fs allow amplification with only minor losses in efficiency.« less

  1. Rapid detection of Mycobacterium tuberculosis by recombinase polymerase amplification.

    PubMed

    Boyle, David S; McNerney, Ruth; Teng Low, Hwee; Leader, Brandon Troy; Pérez-Osorio, Ailyn C; Meyer, Jessica C; O'Sullivan, Denise M; Brooks, David G; Piepenburg, Olaf; Forrest, Matthew S

    2014-01-01

    Improved access to effective tests for diagnosing tuberculosis (TB) has been designated a public health priority by the World Health Organisation. In high burden TB countries nucleic acid based TB tests have been restricted to centralised laboratories and specialised research settings. Requirements such as a constant electrical supply, air conditioning and skilled, computer literate operators prevent implementation of such tests in many settings. Isothermal DNA amplification technologies permit the use of simpler, less energy intensive detection platforms more suited to low resource settings that allow the accurate diagnosis of a disease within a short timeframe. Recombinase Polymerase Amplification (RPA) is a rapid, low temperature isothermal DNA amplification reaction. We report here RPA-based detection of Mycobacterium tuberculosis complex (MTC) DNA in <20 minutes at 39 °C. Assays for two MTC specific targets were investigated, IS6110 and IS1081. When testing purified MTC genomic DNA, limits of detection of 6.25 fg (IS6110) and 20 fg (IS1081)were consistently achieved. When testing a convenience sample of pulmonary specimens from suspected TB patients, RPA demonstrated superior accuracy to indirect fluorescence microscopy. Compared to culture, sensitivities for the IS1081 RPA and microscopy were 91.4% (95%CI: 85, 97.9) and 86.1% (95%CI: 78.1, 94.1) respectively (n = 71). Specificities were 100% and 88.6% (95% CI: 80.8, 96.1) respectively. For the IS6110 RPA and microscopy sensitivities of 87.5% (95%CI: 81.7, 93.2) and 70.8% (95%CI: 62.9, 78.7) were obtained (n = 90). Specificities were 95.4 (95% CI: 92.3,98.1) and 88% (95% CI: 83.6, 92.4) respectively. The superior specificity of RPA for detecting tuberculosis was due to the reduced ability of fluorescence microscopy to distinguish Mtb complex from other acid fast bacteria. The rapid nature of the RPA assay and its low energy requirement compared to other amplification technologies suggest RPA-based TB assays

  2. Chemical amplification based on fluid partitioning

    DOEpatents

    Anderson, Brian L [Lodi, CA; Colston, Jr., Billy W.; Elkin, Chris [San Ramon, CA

    2006-05-09

    A system for nucleic acid amplification of a sample comprises partitioning the sample into partitioned sections and performing PCR on the partitioned sections of the sample. Another embodiment of the invention provides a system for nucleic acid amplification and detection of a sample comprising partitioning the sample into partitioned sections, performing PCR on the partitioned sections of the sample, and detecting and analyzing the partitioned sections of the sample.

  3. A 16.9 dBm InP DHBT W-band power amplifier with more than 20 dB gain

    NASA Astrophysics Data System (ADS)

    Hongfei, Yao; Yuxiong, Cao; Danyu, Wu; Xiaoxi, Ning; Yongbo, Su; Zhi, Jin

    2013-07-01

    A two-stage MMIC power amplifier has been realized by use of a 1-μm InP double heterojunction bipolar transistor (DHBT). The cascode structure, low-loss matching networks, and low-parasite cell units enhance the power gain. The optimum load impedance is determined from load-pull simulation. A coplanar waveguide transmission line is adopted for its ease of fabrication. The chip size is 1.5 × 1.7 mm2 with the emitter area of 16 × 1 μm × 15 μm in the output stage. Measurements show that small signal gain is more than 20 dB over 75.5-84.5 GHz and the saturated power is 16.9 dBm @ 79 GHz with gain of 15.2 dB. The high power gain makes it very suitable for medium power amplification.

  4. Hotspot Selective Preference of the Chimeric Sequences Formed in Multiple Displacement Amplification

    PubMed Central

    Tu, Jing; Lu, Na; Duan, Mengqin; Huang, Mengting; Chen, Liang; Li, Junji; Guo, Jing; Lu, Zuhong

    2017-01-01

    Multiple displacement amplification (MDA) is considered to be a conventional approach to comprehensive amplification from low input DNA. The chimeric reads generated in MDA lead to severe disruption in some studies, including those focusing on heterogeneity, structural variation, and genetic recombination. Meanwhile, the generation of by-products gives a new approach to gain insights into the reaction process of φ29 polymerase. Here, we analyzed 36.7 million chimeras and screened 196 billion chimeric hotspots in the human genome, as well as evaluating the hotspot selective preference of chimeras. No significant preference was captured in the distributions of chimeras and hotspots among chromosomes. Hotspots with overlaps for 12–13 nucleotides (nt) were most likely to be selected as templates in chimera generation. Meanwhile, a regularly selective preference was noticed in overlap GC content. The preferences in overlap length and GC content was shown to be pertinent to the sequence denaturation temperature, which pointed out the optimization direction for reducing chimeras. Distance preference between two segments of chimeras was 80–280 nt. The analysis is beneficial for reducing the chimeras in MDA, and the characterization of MDA chimeras is helpful in distinguishing MDA chimeras from chimeric sequences caused by disease. PMID:28245591

  5. Explanatory model for sound amplification in a stethoscope

    NASA Astrophysics Data System (ADS)

    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 opportunities to not only better understand the amplification mechanism of a stethoscope, but also to strengthen their understanding of sound, pressure, waves, resonance modes, etc.

  6. Is excessive weight gain after ablative treatment of hyperthyroidism due to inadequate thyroid hormone therapy?

    PubMed

    Tigas, S; Idiculla, J; Beckett, G; Toft, A

    2000-12-01

    There is controversy about the correct dose and form of thyroid hormone therapy for patients with hypothyroidism. Despite restoration of serum thyrotropin (TSH) concentrations to normal, many patients complain of excessive weight gain. We have compared weight at diagnosis of hyperthyroidism with that when euthyroid, evidenced by a stable, normal serum TSH concentration, with or without thyroxine (T4) replacement therapy, in patients treated with an 18-month course of antithyroid drugs (43 patients), surgery (56 patients), or 13I (34 patients) for Graves' disease. In addition, weights were recorded before and after treatment of 25 patients with differentiated thyroid carcinoma by total thyroidectomy, 131I, and long-term T4 suppressive therapy, resulting in undetectable serum TSH concentrations. Mean weight gain in patients with Graves' disease who required T4 replacement therapy following surgery was significantly greater than in those of the same age, sex, and severity of hyperthyroidism rendered euthyroid by surgery (3.9 kg) (p < 0.001) or at the end of a course of antithyroid drugs (4.1 kg) (p < 0.001). Weight gain was similar in those requiring T4 replacement following surgery or 131T therapy (10.4 versus 10.1 kg). In contrast, ablative therapy combined with suppression of TSH secretion by T4 in patients with differentiated thyroid carcinoma did not result in weight gain. The excessive weight gain in patients becoming hypothyroid after destructive therapy for Graves' disease suggests that restoration of serum TSH to the reference range by T4 alone may constitute inadequate hormone replacement.

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

    PubMed

    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

  8. Optical antenna gain. I - Transmitting antennas

    NASA Technical Reports Server (NTRS)

    Klein, B. J.; Degnan, J. J.

    1974-01-01

    The gain of centrally obscured optical transmitting antennas is analyzed in detail. The calculations, resulting in near- and far-field antenna gain patterns, assume a circular antenna illuminated by a laser operating in the TEM-00 mode. A simple polynomial equation is derived for matching the incident source distribution to a general antenna configuration for maximum on-axis gain. An interpretation of the resultant gain curves allows a number of auxiliary design curves to be drawn that display the losses in antenna gain due to pointing errors and the cone angle of the beam in the far field as a function of antenna aperture size and its central obscuration. The results are presented in a series of graphs that allow the rapid and accurate evaluation of the antenna gain which may then be substituted into the conventional range equation.

  9. Study of gain-coupled distributed feedback laser based on high order surface gain-coupled gratings

    NASA Astrophysics Data System (ADS)

    Gao, Feng; Qin, Li; Chen, Yongyi; Jia, Peng; Chen, Chao; Cheng, LiWen; Chen, Hong; Liang, Lei; Zeng, Yugang; Zhang, Xing; Wu, Hao; Ning, Yongqiang; Wang, Lijun

    2018-03-01

    Single-longitudinal-mode, gain-coupled distributed feedback (DFB) lasers based on high order surface gain-coupled gratings are achieved. Periodic surface metal p-contacts with insulated grooves realize gain-coupled mechanism. To enhance gain contrast in the quantum wells without the introduction of effective index-coupled effect, groove length and depth were well designed. Our devices provided a single longitudinal mode with the maximum CW output power up to 48.8 mW/facet at 971.31 nm at 250 mA without facet coating, 3dB linewidth (<3.2 pm) and SMSR (>39 dB). Optical bistable characteristic was observed with a threshold current difference. Experimentally, devices with different cavity lengths were contrasted on power-current and spectrum characteristics. Due to easy fabrication technique and stable performance, it provides a method of fabricating practical gain-coupled distributed feedback lasers for commercial applications.

  10. MET amplification as a potential therapeutic target in gastric cancer

    PubMed Central

    Kawakami, Hisato; Okamoto, Isamu; Arao, Tokuzo; Okamoto, Wataru; Matsumoto, Kazuko; Taniguchi, Hirokazu; Kuwata, Kiyoko; Yamaguchi, Haruka; Nishio, Kazuto; Nakagawa, Kazuhiko; Yamada, Yasuhide

    2013-01-01

    Our aim was to investigate both the prevalence of MET amplification in gastric cancer as well as the potential of this genetic alteration to serve as a therapeutic target in gastric cancer. MET amplification was assessed by initial screening with a PCR-based copy number assay followed by confirmatory FISH analysis in formalin-fixed, paraffin-embedded specimens of gastric cancer obtained at surgery. The effects of MET tyrosine kinase inhibitors (MET-TKIs) in gastric cancer cells with or without MET amplification were also examined. The median MET copy number in 266 cases of gastric cancer was 1.7, with a range of 0.41 to 21.3. We performed FISH analysis for the 15 cases with the highest MET copy numbers. MET amplification was confirmed in the four assessable cases with a MET copy number of at least 4, whereas MET amplification was not detected in those with a gene copy number of <4. The prevalence of MET amplification was thus 1.5% (4 out of 266 cases). Inhibition of MET by MET-TKIs resulted in the induction of apoptosis accompanied by attenuation of downstream MET signaling in gastric cancer cell lines with MET amplification but not in those without this genetic change. MET amplification identifies a small but clinically important subgroup of gastric cancer patients who are likely to respond to MET-TKIs. Furthermore, screening with a PCR-based copy number assay is an efficient way to reduce the number of patients requiring confirmation of MET amplification by FISH analysis. PMID:23327903

  11. Problems encountered when defining Arctic amplification as a ratio.

    PubMed

    Hind, Alistair; Zhang, Qiong; Brattström, Gudrun

    2016-07-27

    In climate change science the term 'Arctic amplification' has become synonymous with an estimation of the ratio of a change in Arctic temperatures compared with a broader reference change under the same period, usually in global temperatures. Here, it is shown that this definition of Arctic amplification comes with a suite of difficulties related to the statistical properties of the ratio estimator itself. Most problematic is the complexity of categorizing uncertainty in Arctic amplification when the global, or reference, change in temperature is close to 0 over a period of interest, in which case it may be impossible to set bounds on this uncertainty. An important conceptual distinction is made between the 'Ratio of Means' and 'Mean Ratio' approaches to defining a ratio estimate of Arctic amplification, as they do not only possess different uncertainty properties regarding the amplification factor, but are also demonstrated to ask different scientific questions. Uncertainty in the estimated range of the Arctic amplification factor using the latest global climate models and climate forcing scenarios is expanded upon and shown to be greater than previously demonstrated for future climate projections, particularly using forcing scenarios with lower concentrations of greenhouse gases.

  12. Organo-erbium systems for optical amplification at telecommunications wavelengths.

    PubMed

    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.

  13. Amplification of seismic waves by the Seattle basin, Washington State

    USGS Publications Warehouse

    Pratt, T.L.; Brocher, T.M.; Weaver, C.S.; Creager, K.C.; Snelson, C.M.; Crosson, R.S.; Miller, K.C.; Trehu, A.M.

    2003-01-01

    Recordings of the 1999 Mw 7.6 Chi-Chi (Taiwan) earthquake, two local earthquakes, and five blasts show seismic-wave amplification over a large sedimentary basin in the U.S. Pacific Northwest. For weak ground motions from the Chi-Chi earthquake, the Seattle basin amplified 0.2- to 0.8-Hz waves by factors of 8 to 16 relative to bedrock sites west of the basin. The amplification and peak frequency change during the Chi-Chi coda: the initial S-wave arrivals (0-30 sec) had maximum amplifications of 12 at 0.5-0.8 Hz, whereas later arrivals (35-65 sec) reached amplifications of 16 at 0.3-0.5 Hz. Analysis of local events in the 1.0- to 10.0-Hz frequency range show fourfold amplifications for 1.0-Hz weak ground motion over the Seattle basin. Amplifications decrease as frequencies increase above 1.0 Hz, with frequencies above 7 Hz showing lower amplitudes over the basin than at bedrock sites. Modeling shows that resonance in low-impedance deposits forming the upper 550 m of the basin beneath our profile could cause most of the observed amplification, and the larger amplification at later arrival times suggests surface waves also play a substantial role. These results emphasize the importance of shallow deposits in determining ground motions over large basins.

  14. Low-noise and high-speed photodetection system using optical feedback with a current amplification function

    NASA Astrophysics Data System (ADS)

    Akiba, M.

    2015-09-01

    A photodetection system with an optical-feedback circuit accompanied by current amplification was fabricated to minimize the drawbacks associated with a transimpedance amplifier (TIA) with a very high resistance feedback resistor. Current amplification was implemented by extracting an output light from the same light source that emitted the feedback light. The current gain corresponds to the ratio of the photocurrent created by the output light to that created by the feedback light because the feedback current value is identical to the input photocurrent value generated by an input light to be measured. The current gain has no theoretical limit. The output light was detected by a photodiode with a TIA having a small feedback resistance. The expression for the input-referred noise current of the optical-feedback photodetection system was derived, and the trade-off between sensitivity and response, which is a characteristic of TIA, was found to considerably improve. An optical-feedback photodetection system with an InGaAs pin photodiode was fabricated. The measured noise equivalent power of the system was 1.7 fW/Hz1/2 at 10 Hz and 1.3 μm, which is consistent with the derived expression. The time response of the system was found to deteriorate with decreasing photocurrent. The 50% rise time for a light pulse input increased from 3.1 μs at a photocurrent of 10 nA to 15 μs at photocurrents below 10 pA. The bandwidth of the input-referred noise current was 7 kHz, which is consistent with rise times below 10 pA.

  15. Low-noise and high-speed photodetection system using optical feedback with a current amplification function.

    PubMed

    Akiba, M

    2015-09-01

    A photodetection system with an optical-feedback circuit accompanied by current amplification was fabricated to minimize the drawbacks associated with a transimpedance amplifier (TIA) with a very high resistance feedback resistor. Current amplification was implemented by extracting an output light from the same light source that emitted the feedback light. The current gain corresponds to the ratio of the photocurrent created by the output light to that created by the feedback light because the feedback current value is identical to the input photocurrent value generated by an input light to be measured. The current gain has no theoretical limit. The output light was detected by a photodiode with a TIA having a small feedback resistance. The expression for the input-referred noise current of the optical-feedback photodetection system was derived, and the trade-off between sensitivity and response, which is a characteristic of TIA, was found to considerably improve. An optical-feedback photodetection system with an InGaAs pin photodiode was fabricated. The measured noise equivalent power of the system was 1.7 fW/Hz(1/2) at 10 Hz and 1.3 μm, which is consistent with the derived expression. The time response of the system was found to deteriorate with decreasing photocurrent. The 50% rise time for a light pulse input increased from 3.1 μs at a photocurrent of 10 nA to 15 μs at photocurrents below 10 pA. The bandwidth of the input-referred noise current was 7 kHz, which is consistent with rise times below 10 pA.

  16. New Fpg probe chemistry for direct detection of recombinase polymerase amplification on lateral flow strips.

    PubMed

    Powell, Michael L; Bowler, Frank R; Martinez, Aurore J; Greenwood, Catherine J; Armes, Niall; Piepenburg, Olaf

    2018-02-15

    Rapid, cost-effective and sensitive detection of nucleic acids has the ability to improve upon current practices employed for pathogen detection in diagnosis of infectious disease and food testing. Furthermore, if assay complexity can be reduced, nucleic acid amplification tests could be deployed in resource-limited and home use scenarios. In this study, we developed a novel Fpg (Formamidopyrimidine DNA glycosylase) probe chemistry, which allows lateral flow detection of amplification in undiluted recombinase polymerase amplification (RPA) reactions. The prototype nucleic acid lateral flow chemistry was applied to a human genomic target (rs1207445), Campylobacter jejuni 16S rDNA and two genetic markers of the important food pathogen E. coli O157:H7. All four assays have an analytical sensitivity between 10 and 100 copies DNA per amplification. Furthermore, the assay is performed with fewer hands-on steps than using the current RPA Nfo lateral flow method as dilution of amplicon is not required for lateral flow analysis. Due to the simplicity of the workflow, we believe that the lateral flow chemistry for direct detection could be readily adapted to a cost-effective single-use consumable, ideal for use in non-laboratory settings. Copyright © 2017. Published by Elsevier Inc.

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

    PubMed

    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.

  18. High contrast research in the Nd:glass laser system based on optical parametric amplification temporal cleaning device

    NASA Astrophysics Data System (ADS)

    Lu, Xiaoming; Leng, Yuxin; Sui, Zhan; Li, Yanyan; Zhang, Zongxin; Xu, Yi; Guo, Xiaoyang; Liu, Yanqi; Li, Ruxin; Xu, Zhizhan

    2014-02-01

    We demonstrate high amplified spontaneous emission (ASE) contrast pulses in a Nd:glass laser system based on the hybrid double chirped pulse amplification (double CPA) scheme. By an OPA temporal cleaning device, ~100 uJ/46 fs/ 1011 clean pulses are generated and amplified in the next Nd:glass laser. After compressor, >150 mJ/~0.5 ps/1 Hz pulses can be obtained. The ASE temporal contrast of amplified pulses is ~1011 with energy gain ~2.5×104 in the Nd:glass amplifiers.

  19. Sequence independent amplification of DNA

    DOEpatents

    Bohlander, S.K.

    1998-03-24

    The present invention is a rapid sequence-independent amplification procedure (SIA). Even minute amounts of DNA from various sources can be amplified independent of any sequence requirements of the DNA or any a priori knowledge of any sequence characteristics of the DNA to be amplified. This method allows, for example, the sequence independent amplification of microdissected chromosomal material and the reliable construction of high quality fluorescent in situ hybridization (FISH) probes from YACs or from other sources. These probes can be used to localize YACs on metaphase chromosomes but also--with high efficiency--in interphase nuclei. 25 figs.

  20. Sequence independent amplification of DNA

    DOEpatents

    Bohlander, Stefan K.

    1998-01-01

    The present invention is a rapid sequence-independent amplification procedure (SIA). Even minute amounts of DNA from various sources can be amplified independent of any sequence requirements of the DNA or any a priori knowledge of any sequence characteristics of the DNA to be amplified. This method allows, for example the sequence independent amplification of microdissected chromosomal material and the reliable construction of high quality fluorescent in situ hybridization (FISH) probes from YACs or from other sources. These probes can be used to localize YACs on metaphase chromosomes but also--with high efficiency--in interphase nuclei.

  1. Biologically relevant effects of mRNA amplification on gene expression profiles.

    PubMed

    van Haaften, Rachel I M; Schroen, Blanche; Janssen, Ben J A; van Erk, Arie; Debets, Jacques J M; Smeets, Hubert J M; Smits, Jos F M; van den Wijngaard, Arthur; Pinto, Yigal M; Evelo, Chris T A

    2006-04-11

    biopsies is representative for the whole left ventricle of the rat heart. However, specific gene transcripts present in parental tissues were undetectable in the minute left ventricular biopsies. Transcripts that were lost due to the amplification process were not randomly distributed, but had higher GC-content and hairpins in the sequence and were mainly found in the lower intensity range which includes many transcription factors from specific signalling pathways.

  2. Biologically relevant effects of mRNA amplification on gene expression profiles

    PubMed Central

    van Haaften, Rachel IM; Schroen, Blanche; Janssen, Ben JA; van Erk, Arie; Debets, Jacques JM; Smeets, Hubert JM; Smits, Jos FM; van den Wijngaard, Arthur; Pinto, Yigal M; Evelo, Chris TA

    2006-01-01

    amplification of mRNA of left ventricular biopsies is representative for the whole left ventricle of the rat heart. However, specific gene transcripts present in parental tissues were undetectable in the minute left ventricular biopsies. Transcripts that were lost due to the amplification process were not randomly distributed, but had higher GC-content and hairpins in the sequence and were mainly found in the lower intensity range which includes many transcription factors from specific signalling pathways. PMID:16608515

  3. Rapid and Sensitive Detection of Norovirus Genomes in Oysters by a Two-Step Isothermal Amplification Assay System Combining Nucleic Acid Sequence-Based Amplification and Reverse Transcription-Loop-Mediated Isothermal Amplification Assays▿

    PubMed Central

    Fukuda, Shinji; Sasaki, Yukie; Seno, Masato

    2008-01-01

    We developed a two-step isothermal amplification assay system, which achieved the detection of norovirus (NoV) genomes in oysters with a sensitivity similar to that of reverse transcription-seminested PCR. The time taken for the amplification of NoV genomes from RNA extracts was shortened to about 3 h. PMID:18456857

  4. Protection from feed-forward amplification in an amplified RNAi mechanism

    PubMed Central

    Pak, Julia; Maniar, Jay Mahesh; Mello, Cecilia Cabral; Fire, Andrew

    2012-01-01

    SUMMARY The effectiveness of RNA interference (RNAi) in many organisms is potentiated through the signal-amplifying activity of a targeted RNA directed RNA polymerase (RdRP) system that can convert a small population of exogenously-encountered dsRNA fragments into an abundant internal pool of small interfering RNA (siRNA). As for any biological amplification system, we expect an underlying architecture that will limit the ability of a randomly encountered trigger to produce an uncontrolled and self-escalating response. Investigating such limits in C. elegans, we find that feed-forward amplification is limited by a critical biosynthetic and structural distinction at the RNA level between (i) triggers that can produce amplification and (ii) siRNA products of the amplification reaction. By assuring that initial (primary) siRNAs can act as triggers but not templates for activation, and that the resulting (secondary) siRNAs can enforce gene silencing on additional targets without unbridled trigger amplification, the system achieves substantial but fundamentally limited signal amplification. PMID:23141544

  5. PCR amplification on microarrays of gel immobilized oligonucleotides

    DOEpatents

    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.

  6. Gain-guided soliton fiber laser with high-quality rectangle spectrum for ultrafast time-stretch microscopy.

    PubMed

    Hu, Song; Yao, Jian; Liu, Meng; Luo, Ai-Ping; Luo, Zhi-Chao; Xu, Wen-Cheng

    2016-05-16

    The ultrafast time-stretch microscopy has been proposed to enhance the temporal resolution of a microscopy system. The optical source is a key component for ultrafast time-stretch microscopy system. Herein, we reported on the gain-guided soliton fiber laser with high-quality rectangle spectrum for ultrafast time-stretch microscopy. By virtue of the excellent characteristics of the gain-guided soliton, the output power and the 3-dB bandwidth of the stable mode-locked soliton could be up to 3 mW and 33.7 nm with a high-quality rectangle shape, respectively. With the proposed robust optical source, the ultrafast time-stretch microscopy with the 49.6 μm resolution and a scan rate of 11 MHz was achieved without the external optical amplification. The obtained results demonstrated that the gain-guided soliton fiber laser could be used as an alternative high-quality optical source for ultrafast time-stretch microscopy and will introduce some applications in fields such as biology, chemical, and optical sensing.

  7. Microsecond gain-switched master oscillator power amplifier (1958 nm) with high pulse energy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ke Yin; Weiqiang Yang; Bin Zhang

    2014-02-28

    An all-fibre master oscillator power amplifier (MOPA) emitting high-energy pulses at 1958 nm is presented. The seed laser is a microsecond gain-switched thulium-doped fibre laser (TDFL) pumped with a commercial 1550-nm pulsed fibre laser. The TDFL operates at a repetition rate f in the range of 10 to 100 kHz. The two-stage thulium-doped fibre amplifier is built to scale the energy of the pulses generated by the seed laser. The maximum output pulse energy higher than 0.5 mJ at 10 kHz is achieved which is comparable with the theoretical maximum extractable pulse energy. The slope efficiency of the second stagemore » amplifier with respect to the pump power is 30.4% at f = 10 kHz. The wavelength of the output pulse laser is centred near 1958 nm at a spectral width of 0.25 nm after amplification. Neither nonlinear effects nor significant amplified spontaneous emission (ASE) is observed in the amplification experiments. (lasers)« less

  8. Describing Site Amplification for Surface Waves in Realistic Basins

    NASA Astrophysics Data System (ADS)

    Bowden, D. C.; Tsai, V. C.

    2017-12-01

    Standard characterizations of site-specific site response assume a vertically-incident shear wave; given a 1D velocity profile, amplification and resonances can be calculated based on conservation of energy. A similar approach can be applied to surface waves, resulting in an estimate of amplification relative to a hard rock site that is different in terms of both amount of amplification and frequency. This prediction of surface-wave site amplification has been well validated through simple simulations, and in this presentation we explore the extent to which a 1D profile can explain observed amplifications in more realistic scenarios. Comparisons of various simple 2D and 3D simulations, for example, allow us to explore the effect of different basin shapes and the relative importance of effects such as focusing, conversion of wave-types and lateral surface wave resonances. Additionally, the 1D estimates for vertically-incident shear waves and for surface waves are compared to spectral ratios of historic events in deep sedimentary basins to demonstrate the appropriateness of the two different predictions. This difference in amplification responses between the wave types implies that a single measurement of site response, whether analytically calculated from 1D models or empirically observed, is insufficient for regions where surface waves play a strong role.

  9. Computation of ground motion amplification in Kolkata megacity (India) using finite-difference method for seismic microzonation

    NASA Astrophysics Data System (ADS)

    Shiuly, Amit; Kumar, Vinay; Narayan, Jay

    2014-06-01

    This paper presents the ground motion amplification scenario along with fundamental frequency (F 0) of sedimentary deposit for the seismic microzonation of Kolkata City, situated on the world's largest delta island with very soft soil deposit. A 4th order accurate SH-wave viscoelastic finite-difference algorithm is used for computation of response of 1D model for each borehole location. Different maps, such as for F 0, amplification at F 0, average spectral amplification (ASA) in the different frequency bandwidth of earthquake engineering interest are developed for a variety of end-users communities. The obtained ASA of the order of 3-6 at most of the borehole locations in a frequency range of 0.25-10.0 Hz reveals that Kolkata City may suffer severe damage even during a moderate earthquake. Further, unexpected severe damage to collapse of multi-storey buildings may occur in localities near Hoogly River and Salt Lake area due to double resonance effects during distant large earthquakes.

  10. Null expectations for disease dynamics in shrinking habitat: dilution or amplification?

    PubMed Central

    McCallum, Hamish I.; Gillespie, Thomas R.

    2017-01-01

    As biodiversity declines with anthropogenic land-use change, it is increasingly important to understand how changing biodiversity affects infectious disease risk. The dilution effect hypothesis, which points to decreases in biodiversity as critical to an increase in infection risk, has received considerable attention due to the allure of a win–win scenario for conservation and human well-being. Yet some empirical data suggest that the dilution effect is not a generalizable phenomenon. We explore the response of pathogen transmission dynamics to changes in biodiversity that are driven by habitat loss using an allometrically scaled multi-host model. With this model, we show that declining habitat, and thus declining biodiversity, can lead to either increasing or decreasing infectious-disease risk, measured as endemic prevalence. Whether larger habitats, and thus greater biodiversity, lead to a decrease (dilution effect) or increase (amplification effect) in infection prevalence depends upon the pathogen transmission mode and how host competence scales with body size. Dilution effects were detected for most frequency-transmitted pathogens and amplification effects were detected for density-dependent pathogens. Amplification effects were also observed over a particular range of habitat loss in frequency-dependent pathogens when we assumed that host competence was greatest in large-bodied species. By contrast, only amplification effects were observed for density-dependent pathogens; host competency only affected the magnitude of the effect. These models can be used to guide future empirical studies of biodiversity–disease relationships across gradients of habitat loss. The type of transmission, the relationship between host competence and community assembly, the identity of hosts contributing to transmission, and how transmission scales with area are essential factors to consider when elucidating the mechanisms driving disease risk in shrinking habitat. This article

  11. Null expectations for disease dynamics in shrinking habitat: dilution or amplification?

    PubMed

    Faust, Christina L; Dobson, Andrew P; Gottdenker, Nicole; Bloomfield, Laura S P; McCallum, Hamish I; Gillespie, Thomas R; Diuk-Wasser, Maria; Plowright, Raina K

    2017-06-05

    As biodiversity declines with anthropogenic land-use change, it is increasingly important to understand how changing biodiversity affects infectious disease risk. The dilution effect hypothesis, which points to decreases in biodiversity as critical to an increase in infection risk, has received considerable attention due to the allure of a win-win scenario for conservation and human well-being. Yet some empirical data suggest that the dilution effect is not a generalizable phenomenon. We explore the response of pathogen transmission dynamics to changes in biodiversity that are driven by habitat loss using an allometrically scaled multi-host model. With this model, we show that declining habitat, and thus declining biodiversity, can lead to either increasing or decreasing infectious-disease risk, measured as endemic prevalence. Whether larger habitats, and thus greater biodiversity, lead to a decrease (dilution effect) or increase (amplification effect) in infection prevalence depends upon the pathogen transmission mode and how host competence scales with body size. Dilution effects were detected for most frequency-transmitted pathogens and amplification effects were detected for density-dependent pathogens. Amplification effects were also observed over a particular range of habitat loss in frequency-dependent pathogens when we assumed that host competence was greatest in large-bodied species. By contrast, only amplification effects were observed for density-dependent pathogens; host competency only affected the magnitude of the effect. These models can be used to guide future empirical studies of biodiversity-disease relationships across gradients of habitat loss. The type of transmission, the relationship between host competence and community assembly, the identity of hosts contributing to transmission, and how transmission scales with area are essential factors to consider when elucidating the mechanisms driving disease risk in shrinking habitat.This article is

  12. Whole-genome multiple displacement amplification from single cells.

    PubMed

    Spits, Claudia; Le Caignec, Cédric; De Rycke, Martine; Van Haute, Lindsey; Van Steirteghem, André; Liebaers, Inge; Sermon, Karen

    2006-01-01

    Multiple displacement amplification (MDA) is a recently described method of whole-genome amplification (WGA) that has proven efficient in the amplification of small amounts of DNA, including DNA from single cells. Compared with PCR-based WGA methods, MDA generates DNA with a higher molecular weight and shows better genome coverage. This protocol was developed for preimplantation genetic diagnosis, and details a method for performing single-cell MDA using the phi29 DNA polymerase. It can also be useful for the amplification of other minute quantities of DNA, such as from forensic material or microdissected tissue. The protocol includes the collection and lysis of single cells, and all materials and steps involved in the MDA reaction. The whole procedure takes 3 h and generates 1-2 microg of DNA from a single cell, which is suitable for multiple downstream applications, such as sequencing, short tandem repeat analysis or array comparative genomic hybridization.

  13. ESR1 gene amplification in endometrial carcinomas: a clinicopathological analysis.

    PubMed

    Rahman, Mohammed Tanjimur; Nakayama, Kentaro; Rahman, Munmun; Ishikawa, Masako; Katagiri, Hiroshi; Katagiri, Atsuko; Ishibashi, Tomoka; Sato, Emi; Iida, Kouji; Ishikawa, Noriyuki; Nakayama, Naomi; Miyazaki, Kohji

    2013-09-01

    This study investigated the clinicopathological significance of estrogen receptor 1 (ESR1) gene amplification and its relationship to phosphatase and tensin homolog (PTEN), human epidermal growth factor receptor 2 (HER2), MutL homolog 1 (MLH1), p53, and AT rich interactive domain 1A (ARID1A) expression in endometrial carcinomas. ESR1 amplification and expression were assessed by fluorescence in situ hybridization and immunohistochemistry. Clinical data were collected by retrospective chart review. ESR1 amplification was identified in 13 out of 111 (11.7%) endometrial carcinomas. No significant association was observed between ESR1 amplification and International Federation of Gynecology and Obstetrics (FIGO) stage (p=0.17), histological grade (p=0.35), lymph node metastasis (p=0.51), or deep myometrial invasion (p=0.46). ESR1 amplification was independent of PTEN, p53, HER2, MLH1, and ARID1A protein expression. Patients without estrogen receptor (ER) or progesterone receptor (PR) expression had shorter progression-free and overall survival than those with ER or PR expression (p<0.01). ESR1 amplification is independent of known clinicopathological factors related to poor prognosis and PTEN, p53, HER2, MLH1, and ARID1A protein expression, suggesting ESR1 amplification may be an early event in endometrial carcinoma development.

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

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ginzburg, N. S., E-mail: ginzburg@appl.sci-nnov.ru; Zaslavsky, V. Yu.; Nizhny Novgorod State University, 23 Gagarin Ave., 603950 Nizhny Novgorod

    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 themore » 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.« less

  15. An assessment of yield gains under climate change due to genetic modification of pearl millet.

    PubMed

    Singh, Piara; Boote, K J; Kadiyala, M D M; Nedumaran, S; Gupta, S K; Srinivas, K; Bantilan, M C S

    2017-12-01

    Developing cultivars with traits that can enhance and sustain productivity under climate change will be an important climate smart adaptation option. The modified CSM-CERES-Pearl millet model was used to assess yield gains by modifying plant traits determining crop maturity duration, potential yield and tolerance to drought and heat in pearl millet cultivars grown at six locations in arid (Hisar, Jodhpur, Bikaner) and semi-arid (Jaipur, Aurangabad and Bijapur) tropical India and two locations in semi-arid tropical West Africa (Sadore in Niamey and Cinzana in Mali). In all the study locations the yields decreased when crop maturity duration was decreased by 10% both in current and future climate conditions; however, 10% increase in crop maturity significantly (p<0.05) increased yields at Aurangabad and Bijapur, but not at other locations. Increasing yield potential traits by 10% increased yields under both the climate situations in India and West Africa. Drought tolerance imparted the lowest yield gain at Aurangabad (6%), the highest at Sadore (30%) and intermediate at the other locations under current climate. Under climate change the contribution of drought tolerance to the yield of cultivars either increased or decreased depending upon changes in rainfall of the locations. Yield benefits of heat tolerance substantially increased under climate change at most locations, having the greatest effects at Bikaner (17%) in India and Sadore (13%) in West Africa. Aurangabad and Bijapur locations had no yield advantage from heat tolerance due to their low temperature regimes. Thus drought and heat tolerance in pearl millet increased yields under climate change in both the arid and semi-arid tropical climates with greater benefit in relatively hotter environments. This study will assists the plant breeders in evaluating new promising plant traits of pearl millet for adapting to climate change at the selected locations and other similar environments. Copyright © 2017 The

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

    PubMed

    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.

  17. A cascade signal amplification strategy for sensitive and label-free DNA detection based on Exo III-catalyzed recycling coupled with rolling circle amplification.

    PubMed

    Liu, Xingti; Xue, Qingwang; Ding, Yongshun; Zhu, Jing; Wang, Lei; Jiang, Wei

    2014-06-07

    A sensitive and label-free fluorescence assay for DNA detection has been developed based on cascade signal amplification combining exonuclease III (Exo III)-catalyzed recycling with rolling circle amplification. In this assay, probe DNA hybridized with template DNA was coupled onto magnetic nanoparticles to prepare a magnetic bead-probe (MNB-probe)-template complex. The complex could hybridize with the target DNA, which transformed the protruding 3' terminus of template DNA into a blunt end. Exo III could then digest template DNA, liberating the MNB-probe and target DNA. The intact target DNA then hybridized with other templates and released more MNB-probes. The liberated MNB-probe captured the primer, circular DNA and then initiated the rolling circle amplification (RCA) reaction, realizing a cascade signal amplification. Using this cascade amplification strategy, a sensitive DNA detection method was developed which was superior to many existing Exo III-based signal amplification methods. Moreover, N-methyl mesoporphyrin IX, which had a pronounced structural selectivity for the G-quadruplex, was used to combine with the G-quadruplex RCA products and generate a fluorescence signal, avoiding the need for any fluorophore-label probes. The spike and recovery experiments in a human serum sample indicated that our assay also had great potential for DNA detection in real biological samples.

  18. Backward Raman amplification in the long-wavelength infrared

    NASA Astrophysics Data System (ADS)

    Johnson, L. A.; Gordon, D. F.; Palastro, J. P.; Hafizi, B.

    2017-03-01

    The wealth of work in backward Raman amplification in plasma has focused on the extreme intensity limit; however, backward Raman amplification may also provide an effective and practical mechanism for generating intense, broad bandwidth, long-wavelength infrared radiation (LWIR). An electromagnetic simulation coupled with a relativistic cold fluid plasma model is used to demonstrate the generation of picosecond pulses at a wavelength of 10 μm with terawatt powers through backward Raman amplification. The effects of collisional damping, Landau damping, pump depletion, and wave breaking are examined, as well as the resulting design considerations for an LWIR Raman amplifier.

  19. Transitioning hearing aid users with severe and profound loss to a new gain/frequency response: benefit, perception, and acceptance.

    PubMed

    Convery, Elizabeth; Keidser, Gitte

    2011-03-01

    Adults with severe and profound hearing loss tend to be long-term, full-time users of amplification who are highly reliant on their hearing aids. As a result of these characteristics, they are often reluctant to update their hearing aids when new features or signal-processing algorithms become available. Due to the electroacoustic constraints of older devices, many severely and profoundly hearing-impaired adults continue to wear hearing aids that provide more low- and mid-frequency gain and less high-frequency gain than would be prescribed by the National Acoustic Laboratories' revised formula with profound correction factor (NAL-RP). To investigate the effect of a gradual change in gain/frequency response on experienced hearing-aid wearers with moderately severe to profound hearing loss. Double-blind, randomized controlled trial. Twenty-three experienced adult hearing-aid users with severe and profound hearing loss participated in the study. Participants were selected for inclusion in the study if the gain/frequency response of their own hearing aids differed significantly from their NAL-RP prescription. Participants were assigned either to a control or to an experimental group balanced for aided ear three-frequency pure-tone average (PTA) and age. Participants were fitted with Siemens Artis 2 SP behind-the-ear (BTE) hearing aids that were matched to the gain/frequency response of their own hearing aids for a 65 dB SPL input level. The experimental group progressed incrementally to their NAL-RP targets over the course of 15 wk, while the control group maintained their initial settings throughout the study. Aided speech discrimination testing, loudness scaling, and structured questionnaires were completed at 3, 6, 9, 12, and 15 wk postfitting. A paired comparison between the old and new gain/frequency responses was completed at 1 and 15 wk postfitting. Statistical analysis was conducted to examine differences between the experimental and control groups and changes

  20. Broadband tunable integrated CMOS pulser with 80-ps minimum pulse width for gain-switched semiconductor lasers.

    PubMed

    Chen, Shaoqiang; Diao, Shengxi; Li, Pengtao; Nakamura, Takahiro; Yoshita, Masahiro; Weng, Guoen; Hu, Xiaobo; Shi, Yanling; Liu, Yiqing; Akiyama, Hidefumi

    2017-07-31

    High power pulsed lasers with tunable pulse widths are highly favored in many applications. When combined with power amplification, gain-switched semiconductor lasers driven by broadband tunable electric pulsers can meet such requirements. For this reason, we designed and produced a low-cost integrated CMOS pulse generator with a minimum pulse width of 80 ps and a wide tuning range of up to 270 ns using a 40-nm microelectronic process technique. We used this pulser to drive a 1.3-µm semiconductor laser diode directly, and thereafter investigated the gain-switching properties of the laser system. The optical pulses consist of a spike followed by a steady state region. Tuning the width of the electrical pulse down to approximately 1.5 ns produces optical pulses consisting only of the spike, which has a minimum pulse-width of 100 ps. Moreover, the duration of the steady state can be tuned continuously by tuning the electrical pulse width, with a peak power of approximately 5 mW. The output voltage of the electric pulser has a tuning range of 0.8-1.5 V that can be used to directly drive semiconductor laser diodes with wavelengths in the near-infrared spectrum, which are suitable for power amplification with rare-earth doped fiber amplifiers.

  1. Amplification, Redundancy, and Quantum Chernoff Information

    NASA Astrophysics Data System (ADS)

    Zwolak, Michael; Riedel, C. Jess; Zurek, Wojciech H.

    2014-04-01

    Amplification was regarded, since the early days of quantum theory, as a mysterious ingredient that endows quantum microstates with macroscopic consequences, key to the "collapse of the wave packet," and a way to avoid embarrassing problems exemplified by Schrödinger's cat. Such a bridge between the quantum microworld and the classical world of our experience was postulated ad hoc in the Copenhagen interpretation. Quantum Darwinism views amplification as replication, in many copies, of the information about quantum states. We show that such amplification is a natural consequence of a broad class of models of decoherence, including the photon environment we use to obtain most of our information. This leads to objective reality via the presence of robust and widely accessible records of selected quantum states. The resulting redundancy (the number of copies deposited in the environment) follows from the quantum Chernoff information that quantifies the information transmitted by a typical elementary subsystem of the environment.

  2. Amplification of hofmeister effect by alcohols.

    PubMed

    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 < ethanol < 1-propanol < 2-propanol for the monohydric alcohols and following the series d-sorbitol ≈ xylitol ≈ meso-erythritol < glycerol < ethylene glycol < methanol for the polyhydric 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.

  3. Frequency-degenerate phase-sensitive optical parametric amplification based on four-wave mixing in graphene–silicon slot waveguide

    NASA Astrophysics Data System (ADS)

    Li, Zhen; Liu, Hongjun; Huang, Nan; Wang, Zhaolu; Han, Jing

    2018-06-01

    The phase-sensitive amplification process of a hybrid graphene–silicon (HyGS) slot waveguide with trilayers of graphene is investigated in this paper. Numerical simulation shows that a relatively high extinction ratio (42 dB) is achieved, because of the ultrahigh nonlinear coefficients, with a waveguide length of only 680 µm. In addition, the graphene layer provides the possibility of modulating the phase status and gain of the output signal. This study is expected to be highly beneficial to applications such as integrated optics and graphene-related active optical devices.

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

    PubMed

    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.

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

    PubMed Central

    Li, Xia; Song, Juan; Xue, Qing-Wang; You, Fu-Heng; Lu, Xia; Kong, Yan-Cong; Ma, Shu-Yi; Jiang, Wei; Li, Chen-Zhong

    2016-01-01

    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. PMID:28335318

  6. Amplification of the basic reproduction number in cattle farm networks

    PubMed Central

    2018-01-01

    The popularly known 20–80 rule or Pareto rule states that 20% of efforts leads to 80% of results. This rule has been applied to the study of infection transmission in contact networks, and specifically, contact networks between cattle farms. Woolhouse and collaborators showed that targeting interventions for disease control and prevention to the 20% of the farms that contribute the most to the basic reproduction number (Ro), could reduce it by 80%. The rule results from the number of incoming and outgoing contacts per farm being highly heterogeneous. Besides, Woolhouse and collaborators showed that this high contact heterogeneity, together with a high positive correlation between the number of incoming and outgoing animal movements per farm leads to an amplification in the Ro. Two previous studies carried out with Scottish cattle transport data found either no correlation or only a weak correlation (rho up to 0.33) when using weighted data. Using data from the contacts between Swiss cattle farms in 2015, we found that the 20–80 rule applies with respect to Ro, although the proportion of highly active farms is smaller (11%). Besides, a positive strong correlation (rho = 0.64, weighted data) between the incoming and outgoing contacts of farms exists. This means that the amplification of Ro (due to the contact heterogeneities and the existing correlation) in cattle contact networks can be much higher than known until now. Our results highlight the importance of an effective active surveillance, more so than in other countries were these amplification mechanisms are absent. PMID:29672512

  7. Whole genome amplification of DNA extracted from FFPE tissues.

    PubMed

    Bosso, Mira; Al-Mulla, Fahd

    2011-01-01

    Whole genome amplification systems were developed to meet the increasing research demands on DNA resources and to avoid DNA shortage. The technology enables amplification of nanogram amounts of DNA into microgram quantities and is increasingly used in the amplification of DNA from multiple origins such as blood, fresh frozen tissue, formalin-fixed paraffin-embedded tissues, saliva, buccal swabs, bacteria, and plant and animal sources. This chapter focuses on the use of GenomePlex(®) tissue Whole Genome Amplification Kit, to amplify DNA directly from archived tissue. In addition, this chapter documents our unique experience with the utilization of GenomePlex(®) amplified DNA using several molecular techniques including metaphase Comparative Genomic Hybridization, array Comparative Genomic Hybridization, and real-time quantitative polymerase chain reaction assays. GenomePlex(®) is a registered trademark of Rubicon Genomics Incorporation.

  8. The focusing effect in backward Raman amplification in plasma

    NASA Astrophysics Data System (ADS)

    Li, Zhaoli; Peng, Hao; Zuo, Yanlei; Su, Jingxin; Yang, Suhui

    2018-04-01

    In this paper, the focusing effect on backward Raman amplification in plasma is investigated. A fluid model, used to simulate the backward Raman amplification and including the relativistic, ponderomotive, and thermal self-focusing and the mutual-focusing effect simultaneously, is proposed and investigated. The focusing effect is shown to severely distort the profile of the seed when the seed intensity was as high as 10 17 W/cm2. Reducing the plasma density can relax the focusing effect, but at the cost of decreasing the amplification efficiency. Changing the profile of the seed has a limited effect on mitigating the focusing effect. A Gaussian profile of the pump and a defocusing shape of the plasma density seem to be an effective way to mitigate the focusing effect without decreasing the amplification efficiency.

  9. Preparation of DNA-containing extract for PCR amplification

    DOEpatents

    Dunbar, John M.; Kuske, Cheryl R.

    2006-07-11

    Environmental samples typically include impurities that interfere with PCR amplification and DNA quantitation. Samples of soil, river water, and aerosol were taken from the environment and added to an aqueous buffer (with or without detergent). Cells from the sample are lysed, releasing their DNA into the buffer. After removing insoluble cell components, the remaining soluble DNA-containing extract is treated with N-phenacylthiazolium bromide, which causes rapid precipitation of impurities. Centrifugation provides a supernatant that can be used or diluted for PCR amplification of DNA, or further purified. The method may provide a DNA-containing extract sufficiently pure for PCR amplification within 5–10 minutes.

  10. Raman amplification in the coherent wave-breaking regime.

    PubMed

    Farmer, J P; Pukhov, A

    2015-12-01

    In regimes far beyond the wave-breaking threshold of Raman amplification, we show that significant amplification can occur after the onset of wave breaking, before phase mixing destroys the coherent coupling between pump, probe, and plasma wave. Amplification in this regime is therefore a transient effect, with the higher-efficiency "coherent wave-breaking" (CWB) regime accessed by using a short, intense probe. Parameter scans illustrate the marked difference in behavior between below wave breaking, in which the energy-transfer efficiency is high but total energy transfer is low, wave breaking, in which efficiency is low, and CWB, in which moderate efficiencies allow the highest total energy transfer.

  11. Topoisomerase expression and amplification in solid tumours: Analysis of 24,262 patients

    PubMed Central

    Heestand, Gregory M.; Schwaederle, Maria; Gatalica, Zoran; Arguello, David; Kurzrock, Razelle

    2017-01-01

    Background Topoisomerase I (TOPO1) and topoisomerase IIα (TOP2A) are specific targets of multiple chemotherapy drugs. Increased expression of TOPO1 protein and amplification of the TOP2A gene have been associated with treatment response in colorectal and breast cancers, respectively. TOPO1 and TOP2A may be potential therapeutic targets in other malignancies as well. Summary of methods We analysed TOPO1 protein expression and TOP2A gene amplification in patients (n = 24,262 specimens) with diverse cancers. Since HER2 and TOP2A co-amplification have been investigated for predictive value regarding anthracycline benefit, we analysed specimens for HER2 amplification as well. Results Overexpressed TOPO1 protein was present in 51% of the tumours. Four percent of the tumours had TOP2A amplification, with gallbladder tumours and gastroesophageal/oesophageal tumours having rates over 10%. Overall, 4903 specimens were assessed for both TOP2A and HER2 amplification; 129 (2.6%) had co-amplification. High rates (>40%) of HER2 amplification were seen in patients with TOP2A amplification in breast, ovarian, gastroesophageal/oesophageal and pancreatic cancer. Conclusion Our data indicate that increased TOPO1 expression and TOP2A amplification, as well as HER2 co-alterations, are present in multiple malignancies. The implications of these observations regarding sensitivity to chemotherapy not traditionally administered to these tumour types merits investigation. PMID:28728050

  12. Population diversity of ammonium oxidizers investigated by specific PCR amplification

    USGS Publications Warehouse

    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.

  13. ALK amplification and protein expression predict inferior prognosis in neuroblastomas.

    PubMed

    Wang, Miao; Zhou, Chunju; Sun, Qinnuan; Cai, Rongqin; Li, Yong; Wang, Daye; Gong, Liping

    2013-10-01

    ALK gene has been identified as a major neuroblastoma (NBL) predisposition gene. But ALK gene copy number and protein expression in ganglioneuroblastoma (GNBL) and ganglioneuroma (GN) are poorly described in the literature. Furthermore, there are controversies on the correlation between ALK protein expression and clinical outcome in NBL. We evaluated MYCN/ALK gene copy number by fluorescence in situ hybridization (FISH) and detected ALK protein expression by immunohistochemistry (IHC) in 188 NBL, 52 GNBL and 6 GN samples and analyzed their association with clinical outcome of the patients. Although ALK gene copy number increase is a recurrent genetic aberration of neuroblastic tumors (NTs) (39.1%, 96/246), ALK amplification was only present in three NBLs (1.2%, 3/246). The frequency of ALK positivity in NBL (50.5%, 51/101) was significantly higher than in GNBL (22.6%, 7/31) and in GN (0.0%, 0/4) (P<0.05). In addition, ALK positivity also significantly correlates with MYCN/ALK gene copy number increases (P<0.05). Kaplan-Meier survival analysis indicated that MYCN/ALK amplification is correlated with decreased overall survival in NBL. A better prognosis trend was observed in patients with MYCN/ALK gain tumors compared with those with MYCN/ALK normal tumors. Furthermore, ALK positivity significantly correlated with inferior survival in NBL (P=0.044). ALK positivity in NTs correlated with advanced tumor types and MYCN/ALK gene copy number increases. ALK positivity predicts inferior prognosis in NBL and IHC is a simplified strategy to screen ALK positivity in clinical practice. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Hybrid chirped pulse amplification system

    DOEpatents

    Barty, Christopher P.; Jovanovic, Igor

    2005-03-29

    A hybrid chirped pulse amplification system wherein a short-pulse oscillator generates an oscillator pulse. The oscillator pulse is stretched to produce a stretched oscillator seed pulse. A pump laser generates a pump laser pulse. The stretched oscillator seed pulse and the pump laser pulse are directed into an optical parametric amplifier producing an optical parametric amplifier output amplified signal pulse and an optical parametric amplifier output unconverted pump pulse. The optical parametric amplifier output amplified signal pulse and the optical parametric amplifier output laser pulse are directed into a laser amplifier producing a laser amplifier output pulse. The laser amplifier output pulse is compressed to produce a recompressed hybrid chirped pulse amplification pulse.

  15. MYC copy number gains are associated with poor outcome in penile squamous cell carcinoma.

    PubMed

    Masferrer, Emili; Ferrándiz-Pulido, Carla; Lloveras, Belén; Masferrer-Niubò, Magalí; Espinet, Blanca; Salido, Marta; Rodríguez-Rivera, María; Alemany, Laia; Placer, Jose; Gelabert, Antoni; Servitje, Octavi; García-Patos, Vicenç; Pujol, Ramon M; Toll, Agustí

    2012-11-01

    We determined MYC gene numerical aberrations and protein expression at different stages of penile squamous cell carcinoma carcinogenesis. We correlated these findings with clinicopathological parameters and HPV infection. We evaluated 79 cases of penile squamous cell carcinoma, including 11 in situ and 68 invasive carcinomas. The MYC cytogenetic profile was evaluated by fluorescence in situ hybridization. HPV was detected by polymerase chain reaction amplification. MYC gains were identified in 4 of 11 in situ carcinomas (36%) and 50 of 68 invasive penile squamous cell carcinomas (73%). A significant association between MYC gains, and tumor progression and poor outcome was demonstrated (p <0.05). HPV DNA was detected in 32 of 79 penile squamous cell carcinomas (39%). High risk type 16 was the most prevalent type. MYC numerical aberrations did not correlate with HPV status. A significant association between HPV and MYC protein over expression was noted. In HPV negative cases MYC gains correlated with MYC over expression. MYC gains progressively increased during penile squamous cell carcinoma progression from in situ samples to metastases. MYC gains were an independent factor for poor prognosis. These findings were independent of HPV infection. MYC expression was increased in samples with HPV infection, probably reflecting direct activation of MYC. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  16. Copy-Number Gains of HUWE1 Due to Replication- and Recombination-Based Rearrangements

    PubMed Central

    Froyen, Guy; Belet, Stefanie; Martinez, Francisco; Santos-Rebouças, Cíntia Barros; Declercq, Matthias; Verbeeck, Jelle; Donckers, Lene; Berland, Siren; Mayo, Sonia; Rosello, Monica; Pimentel, Márcia Mattos Gonçalves; Fintelman-Rodrigues, Natalia; Hovland, Randi; Rodrigues dos Santos, Suely; Raymond, F. Lucy; Bose, Tulika; Corbett, Mark A.; Sheffield, Leslie; van Ravenswaaij-Arts, Conny M.A.; Dijkhuizen, Trijnie; Coutton, Charles; Satre, Veronique; Siu, Victoria; Marynen, Peter

    2012-01-01

    We previously reported on nonrecurrent overlapping duplications at Xp11.22 in individuals with nonsyndromic intellectual disability (ID) harboring HSD17B10, HUWE1, and the microRNAs miR-98 and let-7f-2 in the smallest region of overlap. Here, we describe six additional individuals with nonsyndromic ID and overlapping microduplications that segregate in the families. High-resolution mapping of the 12 copy-number gains reduced the minimal duplicated region to the HUWE1 locus only. Consequently, increased mRNA levels were detected for HUWE1, but not HSD17B10. Marker and SNP analysis, together with identification of two de novo events, suggested a paternally derived intrachromosomal duplication event. In four independent families, we report on a polymorphic 70 kb recurrent copy-number gain, which harbors part of HUWE1 (exon 28 to 3′ untranslated region), including miR-98 and let-7f-2. Our findings thus demonstrate that HUWE1 is the only remaining dosage-sensitive gene associated with the ID phenotype. Junction and in silico analysis of breakpoint regions demonstrated simple microhomology-mediated rearrangements suggestive of replication-based duplication events. Intriguingly, in a single family, the duplication was generated through nonallelic homologous recombination (NAHR) with the use of HUWE1-flanking imperfect low-copy repeats, which drive this infrequent NAHR event. The recurrent partial HUWE1 copy-number gain was also generated through NAHR, but here, the homologous sequences used were identified as TcMAR-Tigger DNA elements, a template that has not yet been reported for NAHR. In summary, we showed that an increased dosage of HUWE1 causes nonsyndromic ID and demonstrated that the Xp11.22 region is prone to recombination- and replication-based rearrangements. PMID:22840365

  17. DHFR and MSH3 co-amplification in childhood acute lymphoblastic leukaemia, in vitro and in vivo.

    PubMed

    Matheson, Elizabeth C; Hogarth, Linda A; Case, Marian C; Irving, Julie A E; Hall, Andrew G

    2007-06-01

    The MSH3 and dihydrofolate reductase (DHFR) genes, located on chromosome 5, share a common promoter but are divergently transcribed. Dysregulation of the mismatch repair (MMR) pathway has been found to occur in cell line models due to co-amplification of MSH3 as a coincident effect of DHFR amplification, acquired as a mechanism generating resistance to methotrexate (MTX). The increased levels of MSH3 perturbed MutSalpha function resulting in hypermutability and increased resistance to thiopurines, drugs whose cytotoxic effects are triggered by MutSalpha. The relevance of this phenomenon in clinical samples is unknown but is extremely pertinent in childhood acute lymphoblastic leukaemia (ALL) in which children are exposed for prolonged periods to both MTX and thiopurines such that a single amplification event involving both the DHFR and the MSH3 genes may cause chemotherapeutic resistance to both agents. Thus, we have generated a leukaemic cell line (PreB697) and a normal human lymphoblastoid cell line (TK6) that are resistant to a pharmacologically relevant dose of MTX and show that while increased DHFR levels result in MTX resistance, the associated increased levels of MSH3 are insufficient to perturb MutSalpha functionality, in terms of MMR capacity or 6-thioguanine sensitivity. In addition, we show that although low-level DHFR amplification occurs alone in a significant number of samples, both at disease onset and relapse, co-amplification of both MSH3 and DHFR is rarely found in primary ALL samples, even after prolonged MTX therapy and is not at a sufficiently high level to perturb MMR function.

  18. Regenerative Amplification of Femtosecond Pulses: Design andConstruction of a sub-100fs, muon J Laser System

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schumacher, Andreas B.

    1996-10-01

    Femtosecond lasers are a powerful tool for a wealth of applications in physics, chemistry and biology. In most cases, however, their use is fundamentally restricted to a rather narrow spectral range. This thesis deals with the construction and characterization of a femtosecond light source for spectroscopic applications which overcomes that restriction. It is demonstrated how the output of a continuously pumped Ti:sapphire femtosecond oscillator is amplified to the μJ level,while the pulse duration remains below 100 fs. A combination of continuous pumping, acousto-optic switching and Ti:Al 2O 3 as a gain medium allows amplification at high repetition rates. By focusingmore » the high energy pulses into a sapphire crystal, a broad-band continuum can be generated, extended in wavelengths over several hundred nanometers. To accomplish amplification of three orders of magnitude while maintaining the pulse length, a regenerative multipass amplifier system was built. The thesis describes theoretical design, realization and characterization of the system. Theoretical calculations and preliminary measurements were carried out and allow a critical evaluation of the final performance.« less

  19. Quality control for quantitative PCR based on amplification compatibility test.

    PubMed

    Tichopad, Ales; Bar, Tzachi; Pecen, Ladislav; Kitchen, Robert R; Kubista, Mikael; Pfaffl, Michael W

    2010-04-01

    Quantitative qPCR is a routinely used method for the accurate quantification of nucleic acids. Yet it may generate erroneous results if the amplification process is obscured by inhibition or generation of aberrant side-products such as primer dimers. Several methods have been established to control for pre-processing performance that rely on the introduction of a co-amplified reference sequence, however there is currently no method to allow for reliable control of the amplification process without directly modifying the sample mix. Herein we present a statistical approach based on multivariate analysis of the amplification response data generated in real-time. The amplification trajectory in its most resolved and dynamic phase is fitted with a suitable model. Two parameters of this model, related to amplification efficiency, are then used for calculation of the Z-score statistics. Each studied sample is compared to a predefined reference set of reactions, typically calibration reactions. A probabilistic decision for each individual Z-score is then used to identify the majority of inhibited reactions in our experiments. We compare this approach to univariate methods using only the sample specific amplification efficiency as reporter of the compatibility. We demonstrate improved identification performance using the multivariate approach compared to the univariate approach. Finally we stress that the performance of the amplification compatibility test as a quality control procedure depends on the quality of the reference set. Copyright 2010 Elsevier Inc. All rights reserved.

  20. Inverse four-wave-mixing and self-parametric amplification effect in optical fibre

    PubMed Central

    Turitsyn, Sergei K.; Bednyakova, Anastasia E.; Fedoruk, Mikhail P.; Papernyi, Serguei B.; Clements, Wallace R.L.

    2015-01-01

    An important group of nonlinear processes in optical fibre involves the mixing of four waves due to the intensity dependence of the refractive index. It is customary to distinguish between nonlinear effects that require external/pumping waves (cross-phase modulation and parametric processes such as four-wave mixing) and self-action of the propagating optical field (self-phase modulation and modulation instability). Here, we present a new nonlinear self-action effect, self-parametric amplification (SPA), which manifests itself as optical spectrum narrowing in normal dispersion fibre, leading to very stable propagation with a distinctive spectral distribution. The narrowing results from an inverse four-wave mixing, resembling an effective parametric amplification of the central part of the spectrum by energy transfer from the spectral tails. SPA and the observed stable nonlinear spectral propagation with random temporal waveform can find applications in optical communications and high power fibre lasers with nonlinear intra-cavity dynamics. PMID:26345290

  1. Approaches to Selection and Fitting of Amplification for Infants and Toddlers.

    ERIC Educational Resources Information Center

    Beauchaine, Kathryn L.

    This paper addresses three areas related to amplification for infants and toddlers with hearing impairments: (1) identification issues as they relate to early amplification; (2) selection of amplification; and (3) assessment of aided function. Identification issues discussed include the goal of early identification of hearing loss and the impact…

  2. Amplification of effects of photons on wound healing

    NASA Astrophysics Data System (ADS)

    Dyson, Mary

    2009-02-01

    Following the absorption of photons by cells either resident in or in transit through the skin at and around a wound site, healing can be modulated. This is due to the primary, secondary and tertiary cellular effects of the photons. The main primary effect of phototherapy is photon absorption. This initiates secondary effects within the cells that have absorbed the photons. Secondary effects are restricted to cells that have absorbed a suprathreshold quantity of photonic energy. Photon absorption can lead to an increase in ATP synthesis and the release of reactive oxygen species that can activate specific transcription factors resulting in changes in synthesis of the enzymes needed for cellular proliferation, migration, phagocytosis and protein synthesis, all essential for wound healing. The amount of ATP production is limited in each cell by the availability of ADP and phosphate. Spatial and temporal amplification of the effects of photon absorption increases the range and duration of phototherapy. It may be caused in part by tertiary effects initiated in cells that have not absorbed photons by regulatory proteins such as cytokines secreted by cells that have absorbed photons. Amplification may also be due to changes induced by photons in immune cells, stem cells and soluble protein mediators while in transit through the dermal capillaries. The peripheral location of these capillaries makes their contents readily accessible to photons. The longer the duration of treatment, the greater will be the number of cells in transit that can be affected by photons. Depth of effect may be increased by transduction of electromagnetic energy into mechanical energy. For a treatment to be clinically effective on wound healing, its duration and power may each be important. Components of the immune system, endocrine system and nervous system may also amplify the effects of photons on wound healing.

  3. Problems encountered when defining Arctic amplification as a ratio

    PubMed Central

    Hind, Alistair; Zhang, Qiong; Brattström, Gudrun

    2016-01-01

    In climate change science the term ‘Arctic amplification’ has become synonymous with an estimation of the ratio of a change in Arctic temperatures compared with a broader reference change under the same period, usually in global temperatures. Here, it is shown that this definition of Arctic amplification comes with a suite of difficulties related to the statistical properties of the ratio estimator itself. Most problematic is the complexity of categorizing uncertainty in Arctic amplification when the global, or reference, change in temperature is close to 0 over a period of interest, in which case it may be impossible to set bounds on this uncertainty. An important conceptual distinction is made between the ‘Ratio of Means’ and ‘Mean Ratio’ approaches to defining a ratio estimate of Arctic amplification, as they do not only possess different uncertainty properties regarding the amplification factor, but are also demonstrated to ask different scientific questions. Uncertainty in the estimated range of the Arctic amplification factor using the latest global climate models and climate forcing scenarios is expanded upon and shown to be greater than previously demonstrated for future climate projections, particularly using forcing scenarios with lower concentrations of greenhouse gases. PMID:27461918

  4. Limits on amplification by Aharonov-Albert-Vaidman weak measurement

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Koike, Tatsuhiko; Tanaka, Saki

    2011-12-15

    We analyze the amplification by the Aharonov-Albert-Vaidman weak quantum measurement on a Sagnac interferometer [Dixon et al., Phys. Rev. Lett. 102, 173601 (2009)] up to all orders of the coupling strength between the measured system and the measuring device. The amplifier transforms a small tilt of a mirror into a large transverse displacement of the laser beam. The conventional analysis has shown that the measured value is proportional to the weak value, so that the amplification can be made arbitrarily large in the cost of decreasing output laser intensity. It is shown that the measured displacement and the amplification factormore » are in fact not proportional to the weak value and rather vanish in the limit of infinitesimal output intensity. We derive the optimal overlap of the pre- and postselected states with which the amplification become maximum. We also show that the nonlinear effects begin to arise in the performed experiments so that any improvements in the experiment, typically with an amplification greater than 100, should require the nonlinear theory in translating the observed value to the original displacement.« less

  5. Femtosecond optical parametric amplification in BBO and KTA driven by a Ti:sapphire laser for LIDT testing and diagnostic development

    NASA Astrophysics Data System (ADS)

    Meadows, Alexander R.; Cupal, Josef; Hříbek, Petr; Durák, Michal; Kramer, Daniel; Rus, Bedřich

    2017-05-01

    We present the design of a collinear femtosecond optical parametric amplification (OPA) system producing a tunable output at wavelengths between 1030 nm and 1080 nm from a Ti:Sapphire pump laser at a wavelength of 795 nm. Generation of a supercontinuum seed pulse is followed by one stage of amplification in Beta Barium Borate (BBO) and two stages of amplification in Potassium Titanyle Arsenate (KTA), resulting in a 225 μJ output pulse with a duration of 90 fs. The output of the system has been measured by self-referenced spectral interferometry to yield the complete spectrum and spectral phase of the pulse. When compared to KTP, the greater transparency of KTA in the spectral range from 3 - 4 μm allows for reduced idler absorption and enhanced gain from the OPA process when it is pumped by the fundamental frequency of a Ti:sapphire laser. In turn, the use of the Ti:sapphire fundamental at 795 nm as a pump improves the efficiency with which light can be converted to wavelengths between 1030 nm and 1080 nm and subsequently used to test components for Nd-based laser systems. This OPA system is operated at 1 kHz for diagnostic development and laser-induced damage threshold testing of optical components for the ELI-Beamlines project.

  6. Accelerated isothermal nucleic acid amplification in betaine-free reaction.

    PubMed

    Ma, Cuiping; Wang, Yifan; Zhang, Pansong; Shi, Chao

    2017-08-01

    Betaine was used as a common additive to isothermal nucleic acid amplification reactions because of lowering the melting temperature (Tm) of DNA. Herein, we reported a novel finding that betaine was inhibiting the reaction efficiency of isothermal amplification reactions. In this work, we have verified this finding by classical loop-mediated isothermal amplification that the addition of 0.8 M betaine inhibited the efficiency of reaction dropping to approximately 1%. Additionally, we clarified the mechanism of betaine hindering isothermal amplification reactions with a molecular barrier to lower associate rate constant K1 for intermolecular hybridization. This finding would be very significant for studies on the interaction between small molecule substance and DNA, and the development of point-of-care testing because of simplifying reaction system and increasing reaction efficiency. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Explanatory Model for Sound Amplification in a Stethoscope

    ERIC Educational Resources Information Center

    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…

  8. Generation of 103 fs mode-locked pulses by a gain linewidth-variable Nd,Y:CaF2 disordered crystal.

    PubMed

    Qin, Z P; Xie, G Q; Ma, J; Ge, W Y; Yuan, P; Qian, L J; Su, L B; Jiang, D P; Ma, F K; Zhang, Q; Cao, Y X; Xu, J

    2014-04-01

    We have demonstrated a diode-pumped passively mode-locked femtosecond Nd,Y:CaF2 disordered crystal laser for the first time to our knowledge. By choosing appropriate Y-doping concentration, a broad fluorescence linewidth of 31 nm has been obtained from the gain linewidth-variable Nd,Y:CaF2 crystal. With the Nd,Y:CaF2 disordered crystal as gain medium, the mode-locked laser generated pulses with pulse duration as short as 103 fs, average output power of 89 mW, and repetition rate of 100 MHz. To our best knowledge, this is the shortest pulse generated from Nd-doped crystal lasers so far. The research results show that the Nd,Y:CaF2 disordered crystal will be a potential alternative as gain medium of repetitive chirped pulse amplification for high-peak-power lasers.

  9. Graphene Ambipolar Nanoelectronics for High Noise Rejection Amplification.

    PubMed

    Liu, Che-Hung; Chen, Qi; Liu, Chang-Hua; Zhong, Zhaohui

    2016-02-10

    In a modern wireless communication system, signal amplification is critical for overcoming losses during multiple data transformations/processes and long-distance transmission. Common mode and differential mode are two fundamental amplification mechanisms, and they utilize totally different circuit configurations. In this paper, we report a new type of dual-gate graphene ambipolar device with capability of operating under both common and differential modes to realize signal amplification. The signal goes through two stages of modulation where the phase of signal can be individually modulated to be either in-phase or out-of-phase at two stages by exploiting the ambipolarity of graphene. As a result, both common and differential mode amplifications can be achieved within one single device, which is not possible in the conventional circuit configuration. In addition, a common-mode rejection ratio as high as 80 dB can be achieved, making it possible for low noise circuit application. These results open up new directions of graphene-based ambipolar electronics that greatly simplify the RF circuit complexity and the design of multifunction device operation.

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

    PubMed

    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.

  11. Detection of MET amplification in gastroesophageal tumor specimens using IQFISH

    PubMed Central

    Nielsen, Karsten Bork; Mollerup, Jens; Jepsen, Anna; Go, Ning

    2017-01-01

    Background The gene mesenchymal epithelial transition factor (MET) is a proto-oncogene that encodes a transmembrane receptor with intrinsic tyrosine kinase activity known as Met or cMet. MET is found to be amplified in several human cancers including gastroesophageal cancer. Methods Here we report the MET amplification prevalence data from 159 consecutive tumor specimens from patients with gastric (G), gastroesophageal junction (GEJ) and esophageal (E) adenocarcinoma, using a novel fluorescence in situ hybridization (FISH) assay, MET/CEN-7 IQFISH Probe Mix [an investigational use only (IUO) assay]. MET amplification was defined as a MET/CEN-7 ratio ≥2.0. Furthermore, the link between the MET signal distribution and amplification status was investigated. Results The prevalence of MET amplification was found to be 6.9%. The FISH assay demonstrated a high inter-observer reproducibility. The inter-observer results showed a 100% overall agreement with respect to the MET status (amplified/non-amplified). The inter-observer CV was estimated to 11.8% (95% CI: 10.2–13.4). For the signal distribution, the inter-observer agreement was reported to be 98.7%. We also report an association of MET amplification and a unique signal distribution pattern in the G/GEJ/E tumor specimens. We found that the prevalence of MET amplification was markedly higher in tumors specimens with a heterogeneous (66.7%) versus homogeneous (2.0%) signal distribution. Furthermore, specimens with a heterogeneous signal distribution had a statically significantly higher median MET/CEN-7 ratio (2.35 versus 1.04; P<0.0001). Conclusions The novel FISH assay showed a high inter-observer reproducibility both with respect to amplification status and signal distribution. Based on the finding in the study it is suggested that MET amplification mainly is associated with tumor cells that is represented by a heterogonous growth pattern. PMID:29285491

  12. Detection of MET amplification in gastroesophageal tumor specimens using IQFISH.

    PubMed

    Jørgensen, Jan Trøst; Nielsen, Karsten Bork; Mollerup, Jens; Jepsen, Anna; Go, Ning

    2017-12-01

    The gene mesenchymal epithelial transition factor ( MET ) is a proto-oncogene that encodes a transmembrane receptor with intrinsic tyrosine kinase activity known as Met or cMet. MET is found to be amplified in several human cancers including gastroesophageal cancer. Here we report the MET amplification prevalence data from 159 consecutive tumor specimens from patients with gastric (G), gastroesophageal junction (GEJ) and esophageal (E) adenocarcinoma, using a novel fluorescence in situ hybridization (FISH) assay, MET /CEN-7 IQFISH Probe Mix [an investigational use only (IUO) assay]. MET amplification was defined as a MET /CEN-7 ratio ≥2.0. Furthermore, the link between the MET signal distribution and amplification status was investigated. The prevalence of MET amplification was found to be 6.9%. The FISH assay demonstrated a high inter-observer reproducibility. The inter-observer results showed a 100% overall agreement with respect to the MET status (amplified/non-amplified). The inter-observer CV was estimated to 11.8% (95% CI: 10.2-13.4). For the signal distribution, the inter-observer agreement was reported to be 98.7%. We also report an association of MET amplification and a unique signal distribution pattern in the G/GEJ/E tumor specimens. We found that the prevalence of MET amplification was markedly higher in tumors specimens with a heterogeneous (66.7%) versus homogeneous (2.0%) signal distribution. Furthermore, specimens with a heterogeneous signal distribution had a statically significantly higher median MET /CEN-7 ratio (2.35 versus 1.04; P<0.0001). The novel FISH assay showed a high inter-observer reproducibility both with respect to amplification status and signal distribution. Based on the finding in the study it is suggested that MET amplification mainly is associated with tumor cells that is represented by a heterogonous growth pattern.

  13. Er3+-doped BaY2F8 crystal waveguides for broadband optical amplification at 1.5 μm

    NASA Astrophysics Data System (ADS)

    Toccafondo, V.; Cerqueira S., A.; Faralli, S.; Sani, E.; Toncelli, A.; Tonelli, M.; Di Pasquale, F.

    2007-01-01

    Integrated waveguide amplifiers based on high concentration Er3+ doped BaY2F8 crystals are numerically studied by combining a full-vectorial finite element based modal analysis and propagation-rate equations. Using realistic input data, such as the absorption/emission cross sections and Er level lifetimes measured on grown crystal samples, we investigate the amplifier performance by optimizing the total Er concentration. We predict optimum gain coefficient up to 5dB/cm and broad amplification bandwidth exceeding 80nm with 1480nm pumping.

  14. Quantum amplification and quantum optical tapping with squeezed states and correlated quantum states

    NASA Technical Reports Server (NTRS)

    Ou, Z. Y.; Pereira, S. F.; Kimble, H. J.

    1994-01-01

    Quantum fluctuations in a nondegenerate optical parametric amplifier (NOPA) are investigated experimentally with a squeezed state coupled into the internal idler mode of the NOPA. Reductions of the inherent quantum noise of the amplifier are observed with a minimum noise level 0.7 dB below the usual noise level of the amplifier with its idler mode in a vacuum state. With two correlated quantum fields as the amplifier's inputs and proper adjustment of the gain of the amplifier, it is shown that the amplifier's intrinsic quantum noise can be completely suppressed so that noise-free amplification is achieved. It is also shown that the NOPA, when coupled to either a squeezed state or a nonclassically correlated state, can realize quantum tapping of optical information.

  15. Multi-level multi-thermal-electron FDTD simulation of plasmonic interaction with semiconducting gain media: applications to plasmonic amplifiers and nano-lasers.

    PubMed

    Chen, X; Bhola, B; Huang, Y; Ho, S T

    2010-08-02

    Interactions between a semiconducting gain medium and confined plasmon-polaritons are studied using a multilevel multi-thermal-electron finite-difference time-domain (MLMTE-FDTD) simulator. We investigated the amplification of wave propagating in a plasmonic metal-semiconductor-metal (MSM) waveguide filled with semiconductor gain medium and obtained the conditions required to achieve net optical gain. The MSM gain waveguide is used to form a plasmonic semiconductor nano-ring laser(PSNRL) with an effective mode volume of 0.0071 microm3, which is about an order of magnitude smaller than the smallest demonstrated integrated photonic crystal based laser cavities. The simulation shows a lasing threshold current density of 1kA/cm2 for a 300 nm outer diameter ring cavity with 80 nm-wide ring. This current density can be realistically achieved in typical III-V semiconductor, which shows the experimental feasibility of the proposed PSNRL structure.

  16. Amplification of the Gp41 gene for detection of mutations conferring resistance to HIV-1 fusion inhibitors on genotypic assay

    NASA Astrophysics Data System (ADS)

    Tanumihardja, J.; Bela, B.

    2017-08-01

    Fusion inhibitors have potential for future use in HIV control programs in Indonesia, so the capacity to test resistance to such drugs needs to be developed. Resistance-detection with a genotypic assay began with amplification of the target gene, gp41. Based on the sequence of the two most common HIV subtypes in Indonesia, AE and B, a primer pair was designed. Plasma samples containing both subtypes were extracted to obtain HIV RNA. Using PCR, the primer pair was used to produce the amplification product, the identity of which was checked based on length under electrophoresis. Eleven plasma samples were included in this study. One-step PCR using the primer pair was able to amplify gp41 from 54.5% of the samples, and an unspecific amplification product was seen in 1.1% of the samples. Amplification failed in 36.4% of the samples, which may be due to an inappropriate primer sequence. It was also found that the optimal annealing temperature for producing the single expected band was 57.2 °C. With one-step PCR, the designed primer pair amplified the HIV-1 gp41 gene from subtypes AE and B. However, further research should be done to determine the conditions that will increase the sensitivity and specificity of the amplification process.

  17. Directional Site Amplification Effect on Tarzana Hill, California

    NASA Astrophysics Data System (ADS)

    Graizer, V.; Shakal, A.

    2003-12-01

    Significantly amplified ground accelerations at the Tarzana Hill station were recorded during the 1987 Mw 5.9 Whittier Narrows and the 1994 Mw 6.7 Northridge earthquakes. Peak horizontal ground acceleration at the Tarzana station during the 1999 Mw 7.1 Hector Mine earthquake was almost twice as large as the accelerations recorded at nearby stations. The Tarzana site was drilled to a depth of 100 m. A low shear-wave velocity near the surface of 100 m/sec increasing to near 750 m/sec at 100 m depth was measured. The 20 m high hill was found to be well drained with a water table near 17 m. Modelo formation (extremely weathered at the surface to fresh at depth) underlies the hill. The subsurface geology and velocities obtained allow classification of this location as a soft-rock site. After the Northridge earthquake the California Strong Motion Instrumentation Program significantly increased instrumentation at Tarzana to study the unusual site amplification effect. Current instrumentation at Tarzana consists of an accelerograph at the top of Tarzana hill (Tarzana - Cedar Hill B), a downhole instrument at 60 m depth, and an accelerograph at the foot of the hill (Tarzana - Clubhouse), 180 m from the Cedar Hill B station. The original station, Tarzana - Cedar Hill Nursery A, was lost in 1999 due to construction. More than twenty events, including the Hector Mine earthquake, were recorded by all these instruments at Tarzana. Comparison of recordings and response spectra demonstrates strong directional resonance on the top of the hill in a direction perpendicular to the strike of the hill in the period range from 0.04 to 0.8 sec (1.2 to 25 Hz). There is practically no amplification from the bottom to the top of the hill for the component parallel to the strike of the hill. In contrast to accelerations recorded during the Hector Mine earthquake (high frequency part of seismic signal), displacements (relatively low frequency part of seismic signal) demonstrate almost no site

  18. CDK4 Amplification Predicts Recurrence of Well-Differentiated Liposarcoma of the Abdomen

    PubMed Central

    Ha, Sang Yun; Paik, Kwang Yeol; Lee, Seung Eun; Kim, Jong Man; Park, Jae Berm; Kwon, Choon Hyuck David; Joh, Jae-Won; Choi, Yoon-La; Kim, Sung Joo

    2014-01-01

    Background 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. Methods 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). Results 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). Conclusions Level of CDK4 amplification determined by Q-PCR was associated with the recurrence of WD liposarcomas after surgical resection. PMID:25121597

  19. Isothermal Amplification Methods for the Detection of Nucleic Acids in Microfluidic Devices

    PubMed Central

    Zanoli, Laura Maria; Spoto, Giuseppe

    2012-01-01

    Diagnostic tools for biomolecular detection need to fulfill specific requirements in terms of sensitivity, selectivity and high-throughput in order to widen their applicability and to minimize the cost of the assay. The nucleic acid amplification is a key step in DNA detection assays. It contributes to improving the assay sensitivity by enabling the detection of a limited number of target molecules. The use of microfluidic devices to miniaturize amplification protocols reduces the required sample volume and the analysis times and offers new possibilities for the process automation and integration in one single device. The vast majority of miniaturized systems for nucleic acid analysis exploit the polymerase chain reaction (PCR) amplification method, which requires repeated cycles of three or two temperature-dependent steps during the amplification of the nucleic acid target sequence. In contrast, low temperature isothermal amplification methods have no need for thermal cycling thus requiring simplified microfluidic device features. Here, the use of miniaturized analysis systems using isothermal amplification reactions for the nucleic acid amplification will be discussed. PMID:25587397

  20. Ultrasensitive and rapid detection of β-conglutin combining aptamers and isothermal recombinase polymerase amplification.

    PubMed

    Jauset-Rubio, Miriam; Sabaté Del Río, Jonathan; Mairal, Teresa; Svobodová, Markéta; El-Shahawi, Mohammad S; Bashammakh, Abdulaziz S; Alyoubi, Abdulrahman O; O'Sullivan, Ciara K

    2017-01-01

    Lupin is increasingly being used in a variety of food products due to its nutritional, functional and nutraceutical properties. However, several examples of severe and even fatal food-associated anaphylaxis due to lupin inhalation or ingestion have been reported, resulting in the lupin subunit β-conglutin, being defined as the Lup an 1 allergen by the International Union of Immunological Societies (IUIS) in 2008. Here, we report an innovative method termed aptamer-recombinase polymerase amplification (Apta-RPA) exploiting the affinity and specificity of a DNA aptamer selected against the anaphylactic β-conglutin allergen termed β-conglutin binding aptamer II (β-CBA II), facilitating ultrasensitive detection via isothermal amplification. Combining magnetic beads as the solid phase with Apta-RPA detection, the total assay time was reduced from 210 min to just 25 min, with a limit of detection of 3.5 × 10 -11  M, demonstrating a rapid and ultrasensitive generic methodology that can be used with any aptamer. Future work will focus on further simplification of the assay to a lateral flow format. Graphical Abstract Schematic representation of the rapid and novel bead-based Apta-RPA assay.

  1. Identification of Genetic Elements Associated with EPSPS Gene Amplification

    PubMed Central

    Gaines, Todd A.; Wright, Alice A.; Molin, William T.; Lorentz, Lothar; Riggins, Chance W.; Tranel, Patrick J.; Beffa, Roland; Westra, Philip; Powles, Stephen B.

    2013-01-01

    Weed populations can have high genetic plasticity and rapid responses to environmental selection pressures. For example, 100-fold amplification of the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene evolved in the weed species Amaranthus palmeri to confer resistance to glyphosate, the world’s most important herbicide. However, the gene amplification mechanism is unknown. We sequenced the EPSPS gene and genomic regions flanking EPSPS loci in A. palmeri, and searched for mobile genetic elements or repetitive sequences. The EPSPS gene was 10,229 bp, containing 8 exons and 7 introns. The gene amplification likely proceeded through a DNA-mediated mechanism, as introns exist in the amplified gene copies and the entire amplified sequence is at least 30 kb in length. Our data support the presence of two EPSPS loci in susceptible (S) A. palmeri, and that only one of these was amplified in glyphosate-resistant (R) A. palmeri. The EPSPS gene amplification event likely occurred recently, as no sequence polymorphisms were found within introns of amplified EPSPS copies from R individuals. Sequences with homology to miniature inverted-repeat transposable elements (MITEs) were identified next to EPSPS gene copies only in R individuals. Additionally, a putative Activator (Ac) transposase and a repetitive sequence region were associated with amplified EPSPS genes. The mechanism controlling this DNA-mediated amplification remains unknown. Further investigation is necessary to determine if the gene amplification may have proceeded via DNA transposon-mediated replication, and/or unequal recombination between different genomic regions resulting in replication of the EPSPS gene. PMID:23762434

  2. Uniform amplification of phage display libraries in monodisperse emulsions.

    PubMed

    Matochko, Wadim L; Ng, Simon; Jafari, Mohammad R; Romaniuk, Joseph; Tang, Sindy K Y; Derda, Ratmir

    2012-09-01

    In this paper, we describe a complete experimental setup for the uniform amplification of libraries of phage. Uniform amplification, which multiplies every phage clone by the same amount irrespective of the growth rate of the clone is essential for phage-display screening. Amplification of phage libraries in a common solution is often non-uniform: it favors fast-growing clones and eliminates those that grow slower. This competition leads to elimination of many useful binding clones, and it is a major barrier to identification of ligands for targets with multiple binding sites such as cells, tissues, or mixtures of proteins. Uniform amplification is achieved by encapsulating individual phage clones into isolated compartments (droplets) of identical volume. Each droplet contains culture medium and an excess of host (Escherichia coli). Here, we describe microfluidics devices that generate mono-disperse droplet-based compartments, and optimal conditions for amplification of libraries of different size. We also describe the detailed synthesis of a perfluoro surfactant, which gives droplets exceptional stability. Droplets stabilized by this compound do not coalesce after many hours in shaking culture. We identified a commercially available compound (Krytox), which destabilizes these droplets to recover the amplified libraries. Overall, uniform amplification is a sequence of three simple steps: (1) encapsulation of mixture of phage and bacteria in droplets using microfluidics; (2) incubation of droplets in a shaking culture; (3) destabilization of droplets to harvest the amplified phage. We anticipate that this procedure can be easily adapted in any academic or industrial laboratory that uses phage display. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Scintillation light detectors with Neganov Luke amplification

    NASA Astrophysics Data System (ADS)

    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.

  4. Heralded amplification of path entangled quantum states

    NASA Astrophysics Data System (ADS)

    Monteiro, F.; Verbanis, E.; Caprara Vivoli, V.; Martin, A.; Gisin, N.; Zbinden, H.; Thew, R. T.

    2017-06-01

    Device-independent quantum key distribution (DI-QKD) represents one of the most fascinating challenges in quantum communication, exploiting concepts of fundamental physics, namely Bell tests of nonlocality, to ensure the security of a communication link. This requires the loophole-free violation of a Bell inequality, which is intrinsically difficult due to losses in fibre optic transmission channels. Heralded photon amplification (HPA) is a teleportation-based protocol that has been proposed as a means to overcome transmission loss for DI-QKD. Here we demonstrate HPA for path entangled states and characterise the entanglement before and after loss by exploiting a recently developed displacement-based detection scheme. We demonstrate that by exploiting HPA we are able to reliably maintain high fidelity entangled states over loss-equivalent distances of more than 50 km.

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

    PubMed

    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.

  6. Amplification of Information by Photons and the Quantum Chernoff Bound

    NASA Astrophysics Data System (ADS)

    Zwolak, Michael; Riedel, C. Jess; Zurek, Wojciech H.

    2014-03-01

    Amplification was regarded, since the early days of quantum theory, as a mysterious ingredient that endows quantum microstates with macroscopic consequences, key to the ``collapse of the wavepacket,'' and a way to avoid embarrassing problems exemplified by Schrödinger's cat. This bridge between the quantum microworld and the classical world of our experience was postulated ad hoc in the Copenhagen Interpretation. Quantum Darwinism views amplification as replication, in many copies, of information about quantum states. We show that such amplification is a natural consequence of a broad class of models of decoherence, including the photon environment we use to obtain most of our information. The resultant amplification is huge, proportional to # ξQCB . Here, #  is the environment size and ξQCB is the ``typical'' Quantum Chernoff Information, which quantifies the efficiency of the amplification. The information communicated though the environment is imprinted in the states of individual environment subsystems, e.g., in single photons, which document the transfer of information into the environment and result in the emergence of the classical world. See, http://mike.zwolak.org

  7. Chirped pulse Raman amplification in warm plasma: towards controlling saturation

    PubMed Central

    Yang, X.; Vieux, G.; Brunetti, E.; Ersfeld, B.; Farmer, J. P.; Hur, M. S.; Issac, R. C.; Raj, G.; Wiggins, S. M.; Welsh, G. H.; Yoffe, S. R.; Jaroszynski, D. A.

    2015-01-01

    Stimulated Raman backscattering in plasma is potentially an efficient method of amplifying laser pulses to reach exawatt powers because plasma is fully broken down and withstands extremely high electric fields. Plasma also has unique nonlinear optical properties that allow simultaneous compression of optical pulses to ultra-short durations. However, current measured efficiencies are limited to several percent. Here we investigate Raman amplification of short duration seed pulses with different chirp rates using a chirped pump pulse in a preformed plasma waveguide. We identify electron trapping and wavebreaking as the main saturation mechanisms, which lead to spectral broadening and gain saturation when the seed reaches several millijoules for durations of 10’s – 100’s fs for 250 ps, 800 nm chirped pump pulses. We show that this prevents access to the nonlinear regime and limits the efficiency, and interpret the experimental results using slowly-varying-amplitude, current-averaged particle-in-cell simulations. We also propose methods for achieving higher efficiencies. PMID:26290153

  8. Parametric Amplification For Detecting Weak Optical Signals

    NASA Technical Reports Server (NTRS)

    Hemmati, Hamid; Chen, Chien; Chakravarthi, Prakash

    1996-01-01

    Optical-communication receivers of proposed type implement high-sensitivity scheme of optical parametric amplification followed by direct detection for reception of extremely weak signals. Incorporates both optical parametric amplification and direct detection into optimized design enhancing effective signal-to-noise ratios during reception in photon-starved (photon-counting) regime. Eliminates need for complexity of heterodyne detection scheme and partly overcomes limitations imposed on older direct-detection schemes by noise generated in receivers and by limits on quantum efficiencies of photodetectors.

  9. Nucleic Acid Amplification Testing in Suspected Child Sexual Abuse

    ERIC Educational Resources Information Center

    Esernio-Jenssen, Debra; Barnes, Marilyn

    2011-01-01

    The American Academy of Pediatrics recommends that site-specific cultures be obtained, when indicated, for sexually victimized children. Nucleic acid amplification testing is a highly sensitive and specific methodology for identifying sexually transmitted infections. Nucleic acid amplification tests are also less invasive than culture, and this…

  10. MET expression and amplification in patients with localized gastric cancer

    PubMed Central

    Janjigian, Yelena Y.; Tang, Laura H.; Coit, Daniel G.; Kelsen, David P.; Francone, Todd D.; Weiser, Martin R.; Jhanwar, Suresh C.; Shah, Manish A.

    2013-01-01

    Background MET, the receptor for hepatocyte growth factor has been proposed as a therapeutic target in gastric cancer. This study assessed the incidence of MET expression and gene amplification in tumors of Western patients with gastric cancer. Methods Tumor specimens from patients enrolled on a preoperative chemotherapy study (NCI 5700) were examined for presence of MET gene amplification by fluorescence in situ hybridization (FISH), MET mRNA expression by quantitative polymerase chain reaction, MET overexpression by immunohistochemistry (IHC), and for evidence of MET pathway activation by p-MET IHC. Results Although high-level of MET protein and mRNA were commonly encountered (in 63% and 50% of resected tumor specimens, respectively), none of these tumors had MET gene amplification by FISH, and only 6.6% had evidence of MET tyrosine kinase activity by p-MET IHC. Conclusions In this cohort of patients with localized gastric cancer, the presence of high MET protein and RNA expression does not correlate with MET gene amplification or pathway activation as evidenced by the absence of amplification by FISH and negative p-MET IHC analysis. Impact This paper demonstrates a lack of MET amplification and pathway activation in a cohort of 38 patients with localized gastric cancer, suggesting that MET-driven gastric cancers are relatively rare in Western patients. PMID:21393565

  11. Genomic amplification of Fanconi anemia complementation group A (FancA) in head and neck squamous cell carcinoma (HNSCC): Cellular mechanisms of radioresistance and clinical relevance.

    PubMed

    Hess, Julia; Unger, Kristian; Orth, Michael; Schötz, Ulrike; Schüttrumpf, Lars; Zangen, Verena; Gimenez-Aznar, Igor; Michna, Agata; Schneider, Ludmila; Stamp, Ramona; Selmansberger, Martin; Braselmann, Herbert; Hieber, Ludwig; Drexler, Guido A; Kuger, Sebastian; Klein, Diana; Jendrossek, Verena; Friedl, Anna A; Belka, Claus; Zitzelsberger, Horst; Lauber, Kirsten

    2017-02-01

    Radio (chemo) therapy is a crucial treatment modality for head and neck squamous cell carcinoma (HNSCC), but relapse is frequent, and the underlying mechanisms remain largely elusive. Therefore, novel biomarkers are urgently needed. Previously, we identified gains on 16q23-24 to be associated with amplification of the Fanconi anemia A (FancA) gene and to correlate with reduced progression-free survival after radiotherapy. Here, we analyzed the effects of FancA on radiation sensitivity in vitro, characterized the underlying mechanisms, and evaluated their clinical relevance. Silencing of FancA expression in HNSCC cell lines with genomic gains on 16q23-24 resulted in significantly impaired clonogenic survival upon irradiation. Conversely, overexpression of FancA in immortalized keratinocytes conferred increased survival accompanied by improved DNA repair, reduced accumulation of chromosomal translocations, but no hyperactivation of the FA/BRCA-pathway. Downregulation of interferon signaling as identified by microarray analyses, enforced irradiation-induced senescence, and elevated production of the senescence-associated secretory phenotype (SASP) appeared to be candidate mechanisms contributing to FancA-mediated radioresistance. Data of the TCGA HNSCC cohort confirmed the association of gains on 16q24.3 with FancA overexpression and impaired overall survival. Importantly, transcriptomic alterations similar to those observed upon FancA overexpression in vitro strengthened the clinical relevance. Overall, FancA amplification and overexpression appear to be crucial for radiotherapeutic failure in HNSCC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. Attributing Contributions of Climate Feedbacks to the Seasonal Cycle of Surface Warming due to CO2 Increase

    NASA Astrophysics Data System (ADS)

    Sejas, S.; Cai, M.

    2012-12-01

    Surfing warming due to CO2 doubling is a robust feature of coupled general circulation models (GCM), as noted in the IPCC AR4 assessment report. In this study, the contributions of different climate feedbacks to the magnitude, spatial distribution, and seasonality of the surface warming is examined using data from NCAR's CCSM4. In particular, a focus is placed on polar regions to see which feedbacks play a role in polar amplification and its seasonal pattern. A new climate feedback analysis method is used to isolate the surface warming or cooling contributions of both radiative and non-radiative (dynamical) climate feedbacks to the total (actual) surface temperature change given by the CCSM4. These contributions (or partial surface temperature changes) are additive and their total is approximately equal to the actual surface temperature change. What is found is that the effects of CO2 doubling alone warms the surface throughout with a maximum in polar regions, which indicates the CO2 forcing alone has a degree of polar warming amplification. Water vapor feedback is a positive feedback throughout but is most responsible for the surface warming found in the tropics. Polar warming amplification is found to be strongest away from summer (especially in NH), which is primarily caused by a positive feedback due to cloud feedbacks but with the surface temperature change due to the CO2 forcing alone and the ocean dynamics and storage feedback also playing an important role. Contrary to popular belief, surface albedo feedback (SAF) does not account for much of the polar amplification. SAF tries to amplify polar warming, but in summer. No major polar amplification is seen in summer for the actual surface temperature, so SAF is not the feedback responsible for polar amplification. This is actually a consequence of the ocean dynamics and storage feedback, which negates the effects of SAF to a large degree.

  13. Spectroscopic analysis of a novel Nd3+-activated barium borate glass for broadband laser amplification

    NASA Astrophysics Data System (ADS)

    Vázquez, G. V.; Muñoz H., G.; Camarillo, I.; Falcony, C.; Caldiño, U.; Lira, A.

    2015-08-01

    Spectroscopic parameters of a novel Nd3+-activated barium borate (BBONd) glass have been analyzed for broadband laser amplification. The Judd-Ofelt (JO) intensity parameters were determined through a systematic analysis of the absorption spectrum of Nd3+ ions in the BBONd glass. High values of the JO intensity parameters reveal a great centro-symmetrical loss of the Nd3+ sites and high covalency degree of the ligand field. The very high Ω6 intensity parameter value makes evident both a great structural distortion of the Nd3+ sites and a strong electron-phonon coupling between Nd3+ and free OH- ions, which is consistent with the phonon energy maximum (3442.1 cm-1) recorded by Raman spectroscopy. This strong electron-phonon coupling favors high effective bandwidth and gain bandwidth values of the laser emission (4F3/2 → 4I11/2) of Nd3+ ions. The electric-dipole oscillator strengths of all the Nd3+ absorption transitions, and in particular that of the hypersensitive transition (4I9/2 → 4G5/2), are enhanced by this great structural distortion of the host. Broadband laser amplification of the 4F3/2 → 4I11/2 emission (1062 nm) of Nd3+ ions in the BBONd glass pumped at 805 nm (4I9/2 → 4F5/2 + 2H9/2) is evaluated through the main fluorescent parameters in competition with non-radiative processes. In general, the BBONd glass exhibits spectroscopic parameters comparable with those reported in the literature for broadband laser amplification into the IR region.

  14. Recent slowdown of atmospheric CO2 amplification due to vegetation-climate feedback over northern lands

    NASA Astrophysics Data System (ADS)

    Li, Z.; Xia, J.; Ahlström, A.; Rinke, A.; Koven, C.; Hayes, D. J.; Ji, D.; Zhang, G.; Krinner, G.; Chen, G.; Dong, J.; Liang, J.; Moore, J.; Jiang, L.; Yan, L.; Ciais, P.; Peng, S.; Wang, Y.; Xiao, X.; Shi, Z.; McGuire, A. D.; Luo, Y.

    2017-12-01

    The enhanced vegetation growth by climate warming plays a pivotal role in amplifying the seasonal cycle of atmospheric CO2 at northern high latitudes since 1960s1-3. It remains unclear that whether this mechanism is still robust since 1990s, because a paused vegetation growth increase4,5 and weakened temperature control on CO2 uptake6,7 have been detected during this period. Here, based on in-situ atmospheric CO2 concentration records above northern 50o N, we found a slowdown of the atmospheric CO2 amplification from the mid-1990s to mid-2000s. This phenomenon is associated with the pause of vegetation greening trend and slowdown of spring warming. We further showed that both the vegetation greenness and its growing season length are positively correlated to spring but not autumn temperature from 1982 to 2010 over the northern lands. However, the state-of-art terrestrial biosphere models produce positive responses of gross primary productivity to both spring and autumn warming. These findings emphasize the importance of vegetation-climate feedback in shaping the atmospheric CO2 seasonality, and call for an improved carbon-cycle response to non-uniform seasonal warming at high latitudes in current models.

  15. Evaluating Sound Field Amplification Technology in New Brunswick Schools

    ERIC Educational Resources Information Center

    Rubin, Rhonda; Aquino-Russell, Catherine; Flagg-Williams, Joan

    2007-01-01

    (Purpose) The purpose of this study was to investigate the effects of classroom sound field amplification on communication in kindergarten through grade 3 classrooms. (Methodology) Sixty classrooms were involved in the study; half of the classrooms were provided with sound field amplification. The flow of communication was measured through…

  16. New primer for specific amplification of the CAG repeat in Huntington disease alleles

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bond, C.E.; Hodes, M.E.

    1994-09-01

    Huntington disease is an autosomal dominant neurodegenerative disorder caused by an expansion of a CAG trinucleotide repeat near the 5{prime} end of the gene for Huntington disease (IT15). The CAG repeat is flanked by a variable-length CCG repeat that is included in the amplification product obtained with most currently used primer sets and PCR protocols. Inclusion of this adjacent CCG repeat complicates the accurate assessment of CAG repeat length and interferes with the genotype determination of those individuals carrying alleles in the intermediate range between normal and expanded sized. Due to the GC-rich nature of this region, attempts at designingmore » a protocol for amplification of only the CAG repeat have proved unreliable and difficult to execute. We report here the development of a compatible primer set and PCR protocol that yields consistent amplification of the CAG-repeat region. PCR products can be visualized in ethidium bromide-stained agarose gels for rapid screening or in 6% polyacrylamide gels for determination of exact repeat length. This assay produces bands that can be sized accurately, while eliminating most nonspecific products. Fifty-five specimens examined showed consistency with another well-known method, but one that amplifies the CCG repeats as well. The results we obtained also matched the known carrier status of the donors.« less

  17. Surface-mode-assisted amplification of radiative heat transfer between nanoparticles

    NASA Astrophysics Data System (ADS)

    Messina, Riccardo; Biehs, Svend-Age; Ben-Abdallah, Philippe

    2018-04-01

    We show that the radiative heat flux between two nanoparticles can be significantly amplified when they are placed in proximity of a planar substrate supporting a surface resonance. The amplification factor goes beyond two orders of magnitude in the case of dielectric nanoparticles, whereas it is lower in the case of metallic nanoparticles. We analyze how this effect depends on the frequency and on the particle-surface distance by clearly identifying the signature of the surface mode producing the amplification. Finally, we show how the presence of a graphene sheet on top of the substrate can modify the effect by making an amplification of two orders of magnitude possible also in the case of metallic nanoparticles. This long-range amplification effect should play an important role in the thermal relaxation dynamics of nanoparticle networks.

  18. Simple System for Isothermal DNA Amplification Coupled to Lateral Flow Detection

    PubMed Central

    Roskos, Kristina; Hickerson, Anna I.; Lu, Hsiang-Wei; Ferguson, Tanya M.; Shinde, Deepali N.; Klaue, Yvonne; Niemz, Angelika

    2013-01-01

    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. PMID:23922706

  19. Frequent amplification of receptor tyrosine kinase genes in welldifferentiated/ dedifferentiated liposarcoma.

    PubMed

    Asano, Naofumi; Yoshida, Akihiko; Mitani, Sachiyo; Kobayashi, Eisuke; Shiotani, Bunsyo; Komiyama, Motokiyo; Fujimoto, Hiroyuki; Chuman, Hirokazu; Morioka, Hideo; Matsumoto, Morio; Nakamura, Masaya; Kubo, Takashi; Kato, Mamoru; Kohno, Takashi; Kawai, Akira; Kondo, Tadashi; Ichikawa, Hitoshi

    2017-02-21

    Well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) are closely related tumors commonly characterized by MDM2/CDK4 gene amplification, and lack clinically effective treatment options when inoperable. To identify novel therapeutic targets, we performed targeted genomic sequencing analysis of 19 WDLPS and 37 DDLPS tumor samples using a panel of 104 cancer-related genes (NCC oncopanel v3) developed specifically for genomic testing to select suitable molecular targeted therapies. The results of this analysis indicated that these sarcomas had very few gene mutations and a high frequency of amplifications of not only MDM2 and CDK4 but also other genes. Potential driver mutations were found in only six (11%) samples; however, gene amplification events (other than MDM2 and CDK4 amplification) were identified in 30 (54%) samples. Receptor tyrosine kinase (RTK) genes in particular were amplified in 18 (32%) samples. In addition, growth of a WDLPS cell line with IGF1R amplification was suppressed by simultaneous inhibition of CDK4 and IGF1R, using palbociclib and NVP-AEW541, respectively. Combination therapy with CDK4 and RTK inhibitors may be an effective therapeutic option for WDLPS/DDLPS patients with RTK gene amplification.

  20. Anomalous amplification of a homodyne signal via almost-balanced weak values.

    PubMed

    Liu, Wei-Tao; Martínez-Rincón, Julián; Viza, Gerardo I; Howell, John C

    2017-03-01

    We propose precision measurements of ultra-small angular velocities of a mirror within a modified Sagnac interferometer, where the counter-propagating beams are spatially separated, using the recently proposed technique of almost-balanced weak values amplification (ABWV) [Phys. Rev. Lett.116, 100803 (2016)PRLTAO0031-900710.1103/PhysRevLett.116.100803]. The separation between the two beams provides additional amplification with respect to using collinear beams in a Sagnac interferometer. Within the same setup, the weak-value amplification technique is also performed for comparison. Much higher amplification factors can be obtained using the almost-balanced weak values technique, with the best one achieved in our experiments being as high as 1.2×107. In addition, the amplification factor monotonically increases with decreasing of the post-selection phase for the ABWV case in our experiments, which is not the case for weak-value amplification (WVA) at small post-selection phases. Both techniques consist of measuring the angular velocity. The sensitivity of the ABWV technique is ∼38  nrad/s per averaged pulse for a repetition rate of 1 Hz and ∼33  nrad/s per averaged pulse for the WVA technique.

  1. Integrated microfluidic systems for cell lysis, mixing/pumping and DNA amplification

    NASA Astrophysics Data System (ADS)

    Lee, Chia-Yen; Lee, Gwo-Bin; Lin, Jr-Lung; Huang, Fu-Chun; Liao, Chia-Sheng

    2005-06-01

    The present paper reports a fully automated microfluidic system for the DNA amplification process by integrating an electroosmotic pump, an active micromixer and an on-chip temperature control system. In this DNA amplification process, the cell lysis is initially performed in a micro cell lysis reactor. Extracted DNA samples, primers and reagents are then driven electroosmotically into a mixing region where they are mixed by the active micromixer. The homogeneous mixture is then thermally cycled in a micro-PCR (polymerase chain reaction) chamber to perform DNA amplification. Experimental results show that the proposed device can successfully automate the sample pretreatment operation for DNA amplification, thereby delivering significant time and effort savings. The new microfluidic system, which facilitates cell lysis, sample driving/mixing and DNA amplification, could provide a significant contribution to ongoing efforts to miniaturize bio-analysis systems by utilizing a simple fabrication process and cheap materials.

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

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

    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.

  3. Estimation of empirical site amplification factors in Taiwan

    NASA Astrophysics Data System (ADS)

    Chung, Chi-Hsuan; Wen, Kuo-Liang; Kuo, Chun-Hsiang

    2017-04-01

    Lots of infrastructures are under construction in metropolises in Taiwan in recent years and thus leads to increasement of population density and urbanization in those area. Taiwan island is located in plate boundaries in which the high seismicity is caused by active tectonic plates. The Chi-Chi earthquake (Mw 7.6) in 1999 caused a fatality of more than 2000, and the Meinong earthquake (Mw 6.5) in 2016 caused a fatality of 117 in Tainan city as well as damages on hundreds of buildings. The cases imply seismic vulnerability of urban area. During the improvements for seismic hazard analysis and seismic design, consideration of seismic site amplifications in different site conditions is one of important issues. This study used selected and processed strong motion records observed by the TSMIP network. The site conditions considered as Vs30 used in this study were investigated at most stations (Kuo et al. 2012; Kuo et al. 2016). Since strong motion records and site conditions are both available, we are able to use the data to analyze site amplifications of seismic waves at different periods. The result may be a reference for future modification of seismic design codes to decrease potential seismic hazards and losses. We adopted the strong motion and site database of the SSHAC (Senior Seismic Hazard Analysis Committee) Level 3 project in Taiwan. The selected significant crustal and subduction events of magnitude larger than six for analysis. The amplification factors of PGA, PGV, PGD, and spectra acceleration at 0.3, 1.0, and 3.0 seconds were evaluated using the processed strong motions. According to the recommendation of SSHAC Level 3 project, the site condition of Vs30 = 760 m/s is considered as the reference rock site in this study. The stations with Vs30 between 600 m/s and 900 m/s and used as the reference rock sites in reality. For each event, we find a reference rock site and other site within a certain distance (region dependent) to calculate site amplifications

  4. Microwave amplification based on quasiparticle SIS up and down frequency converters

    NASA Astrophysics Data System (ADS)

    Kojima, T.; Uzawa, Y.; Shan, W.

    2018-02-01

    Heterodyne instruments have recently attained quantum-limited low-noise performance, particularly in radio astronomy, but it is difficult to develop large heterodyne arrays such as a modern radio camera using cryogenic sensitive detectors based on microwave kinetic inductance detectors, transition edge sensors, etc. In the realization of the heterodyne array, the reduction of power dissipation for semiconductor-based amplifiers remains a major challenge. Alternatively, superconducting parametric amplifiers still seem to have several barriers to application, especially in terms of operating temperature. Here, we show a novel concept of microwave amplification based on up and down frequency-conversion processes using quasiparticle superconductor-insulator-superconductor (SIS) tunnel junctions. We demonstrate positive gain using a proof-of-concept test module, which operates with a power dissipation of several μW at a bath temperature of 4 K. The performance of the module suggests great potential for application in large arrays.

  5. Control of Brillouin short-pulse seed amplification by chirping the pump pulse

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Lehmann, G.; Spatschek, K. H.

    Seed amplification via Brillouin backscattering of a long pump pulse is considered. Similar to Raman amplification, several obstructive effects may occur during short-pulse Brillouin amplification. One is the spontaneous Raman backscattering of the pump before interacting with the seed. Preforming the plasma and/or chirping the pump will reduce unwanted pump backscattering. Optimized regions for low-loss pump propagation were proposed already in conjunction with Raman seed amplification. Hence, the influence of the chirp of the pump during Brillouin interaction with the seed becomes important and will be considered here. Both, the linear as well as the nonlinear evolution phases of themore » seed caused by Brillouin amplification under the action of a chirped pump are investigated. The amplification rate as well as the seed profiles are presented as function of the chirping rate. Also the dependence of superradiant scaling rates on the chirp parameter is discussed.« less

  6. Noiseless amplification of weak coherent fields exploiting energy fluctuations of the field

    NASA Astrophysics Data System (ADS)

    Partanen, Mikko; Häyrynen, Teppo; Oksanen, Jani; Tulkki, Jukka

    2012-12-01

    Quantum optics dictates that amplification of a pure state by any linear deterministic amplifier always introduces noise in the signal and results in a mixed output state. However, it has recently been shown that noiseless amplification becomes possible if the requirement of a deterministic operation is relaxed. Here we propose and analyze a noiseless amplification scheme where the energy required to amplify the signal originates from the stochastic fluctuations in the field itself. In contrast to previous amplification setups, our setup shows that a signal can be amplified even if no energy is added to the signal from external sources. We investigate the relation between the amplification and its success rate as well as the statistics of the output states after successful and failed amplification processes. Furthermore, we also optimize the setup to find the maximum success rates in terms of the reflectivities of the beam splitters used in the setup and discuss the relation of our setup with the previous setups.

  7. Development of a recombinase polymerase amplification assay for the detection of pathogenic Leptospira.

    PubMed

    Ahmed, Ahmed; van der Linden, Hans; Hartskeerl, Rudy A

    2014-05-08

    Detection of leptospires based on DNA amplification techniques is essential for the early diagnosis of leptospirosis when anti-Leptospira antibodies are below the detection limit of most serological tests. In middle and low income countries where leptospirosis is endemic, routine implementation of real-time PCR is financially and technically challenging due to the requirement of expensive thermocycler equipment. In this study we report the development and evaluation of a novel isothermal recombinase polymerase amplification assay (RPA) for detection of pathogenic Leptospira based on TwistAmp chemistry. RPA enabled the detection of less than two genome copies per reaction. Retrospective evaluation revealed a high diagnostic accuracy (sensitivity and specificity of 94.7% and 97.7%, respectively) compared to culturing as the reference standard. RPA presents a powerful tool for the early diagnosis of leptospirosis in humans and in animals. Furthermore, it enables the detection of the causative agent in reservoirs and environment, and as such is a valuable adjunct to current tools for surveillance and early outbreak warning.

  8. Weak-value amplification as an optimal metrological protocol

    NASA Astrophysics Data System (ADS)

    Alves, G. Bié; Escher, B. M.; de Matos Filho, R. L.; Zagury, N.; Davidovich, L.

    2015-06-01

    The implementation of weak-value amplification requires the pre- and postselection of states of a quantum system, followed by the observation of the response of the meter, which interacts weakly with the system. Data acquisition from the meter is conditioned to successful postselection events. Here we derive an optimal postselection procedure for estimating the coupling constant between system and meter and show that it leads both to weak-value amplification and to the saturation of the quantum Fisher information, under conditions fulfilled by all previously reported experiments on the amplification of weak signals. For most of the preselected states, full information on the coupling constant can be extracted from the meter data set alone, while for a small fraction of the space of preselected states, it must be obtained from the postselection statistics.

  9. Amplification and chromosomal dispersion of human endogenous retroviral sequences

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Steele, P.E.; Martin, M.A.; Rabson, A.B.

    1986-09-01

    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 andmore » dispersion events may be linked.« less

  10. Short-pulse amplification by strongly coupled stimulated Brillouin scattering

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Edwards, Matthew R., E-mail: mredward@princeton.edu; Mikhailova, Julia M.; Jia, Qing

    2016-08-15

    We examine the feasibility of strongly coupled stimulated Brillouin scattering as a mechanism for the plasma-based amplification of sub-picosecond pulses. In particular, we use fluid theory and particle-in-cell simulations to compare the relative advantages of Raman and Brillouin amplification over a broad range of achievable parameters.

  11. Target-induced proximity ligation triggers recombinase polymerase amplification and transcription-mediated amplification to detect tumor-derived exosomes in nasopharyngeal carcinoma with high sensitivity.

    PubMed

    Liu, Wanli; Li, Jianpei; Wu, Yixian; Xing, Shan; Lai, Yanzhen; Zhang, Ge

    2018-04-15

    Tumor-derived exosomes (TEXs) are extracellular vesicles that are continuously released into the blood by tumor cells and carry specific surface markers of the original tumor cells. Substantial evidence has implicated TEXs as attractive diagnostic markers for cancer. However, the detection of TEXs in blood at an early tumor stage is challenging due to their very low concentration. Here, we established a method called PLA-RPA-TMA assay that allows TEXs to be detected with high sensitivity and specificity. Based on two proximity ligation assay (PLA) probes that recognize a biomarker on a TEX, we generated a unique surrogate DNA signal for the specific biomarker, which was synchronously amplified twice by recombinase polymerase amplification (RPA) coupled with transcription-mediated amplification (TMA), and then the products of the RPA-TMA reaction were quantitatively detected using a gold nanoparticle-based colorimetric assay. We established proof-of-concept evidence for this approach using TEXs from nasopharyngeal carcinoma (NPC) cells, with a detection limit of 10 2 particles/mL, and reported the measurement of plasma Epstein-Barr virus latent membrane protein 1 (LPM1)-positive (LMP1 + , accuracy: 0.956) and epidermal growth factor receptor (EGFR)-positive (EGFR + , accuracy: 0.906) TEXs as potent early diagnostic biomarkers for NPC. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. DNA sequence responsible for the amplification of adjacent genes.

    PubMed

    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.

  13. Experimental study of microwave photon statistics under parametric amplification from a single-mode thermal state in a cavity

    NASA Astrophysics Data System (ADS)

    Galeazzi, G.; Lombardi, A.; Ruoso, G.; Braggio, C.; Carugno, G.; Della Valle, F.; Zanello, D.; Dodonov, V. V.

    2013-11-01

    In this paper we present theoretical and experimental studies of the modifications of the thermal spectrum inside a microwave resonator due to a parametric amplification process. Both the degenerate and nondegenerate amplifiers are discussed. Theoretical calculations are compared with measurements performed with a microwave cavity parametric amplifier.

  14. NASBA: A detection and amplification system uniquely suited for RNA

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sooknanan, R.; Malek, L.T.

    1995-06-01

    The invention of PCR (polymerase chain reaction) has revolutionized our ability to amplify and manipulate a nucleic acid sequence in vitro. The commercial rewards of this revolution have driven the development of other nuclei acid amplification and detection methodologies. This has created an alphabet soup of technologies that use different amplification methods, including NASBA (nucleic acid sequence-based amplification), LCR (ligase chain reaction), SDA (strand displacement amplification), QBR (Q-beta replicase), CPR (cycling probe reaction), and bDNA (branched DNA). Despite the differences in their processes, these amplification systems can be separated into two broad categories based on how they achieve their goal:more » sequence-based amplification systems, such as PCR, NASBA, and SDA, amplify a target nucleic acid sequence. Signal-based amplification systems, such as LCR, QBR, CPR and bDNA, amplify or alter a signal from a detection reaction that is target-dependent. While the various methods have relative strengths and weaknesses, only NASBA offers the unique ability to homogeneously amplify an RNA analyte in the presence of homologous genomic DNA under isothermal conditions. Since the detection of RNA sequences almost invariably measures biological activity, it is an excellent prognostic indicator of activities as diverse as virus production, gene expression, and cell viability. The isothermal nature of the reaction makes NASBA especially suitable for large-scale manual screening. These features extend NASBA`s application range from research to commercial diagnostic applications. Field test kits are presently under development for human diagnostics as well as the burgeoning fields of food and environmental diagnostic testing. These developments suggest future integration of NASBA into robotic workstations for high-throughput screening as well. 17 refs., 1 tab.« less

  15. Role of Atmospheric Transport on the Arctic Amplification: Adjusting Role

    NASA Astrophysics Data System (ADS)

    KUG, J.; Yim, B.; Jin, F.

    2013-12-01

    It is controversial whether the atmospheric transport plays a role in arctic amplification. Recently, Hwang et al. (2011) showed that the magnitude of the arctic amplification is negatively correlated with anomalous poleward atmospheric transport. That is, when the arctic amplification is strong (weak), the atmospheric transport plays a negative (positive) role in the arctic amplification. In this study, it is discussed what is a physical mechanism to determine the role of atmospheric transport and relation with the arctic amplification. Here, we suggest adjusting roles of atmospheric transport. The strength of local feedback over the Arctic determines zonal wind changes. The zonal wind changes are determined by two factors. The first one is polar cap cooling, and second is surface warming. They play opposite roles. So, there will be two different zonal wind responses in high-latitude to the greenhouse warming. Depending on the zonal wind response, the atmospheric transport can play a different role because the zonal wind changes can organize synoptic eddy feedbacks including heat flux, which largely contributes to poleward energy transport. We show here that when polar cap cooling is strong, and surface warming over Arctic is relatively weak, the Jet stream tends to be shifted poleward, so it leads to poleward atmospheric transport. On the other hand, when the surface warming is too strong, it lead to southward shift of Jet stream and equatorward atmospheric transport, which paly a negative role in the Arctic amplification.

  16. Design of nuclease-based target recycling signal amplification in aptasensors.

    PubMed

    Yan, Mengmeng; Bai, Wenhui; Zhu, Chao; Huang, Yafei; Yan, Jiao; Chen, Ailiang

    2016-03-15

    Compared with conventional antibody-based immunoassay methods, aptasensors based on nucleic acid aptamer have made at least two significant breakthroughs. One is that aptamers are more easily used for developing various simple and rapid homogeneous detection methods by "sample in signal out" without multi-step washing. The other is that aptamers are more easily employed for developing highly sensitive detection methods by using various nucleic acid-based signal amplification approaches. As many substances playing regulatory roles in physiology or pathology exist at an extremely low concentration and many chemical contaminants occur in trace amounts in food or environment, aptasensors for signal amplification contribute greatly to detection of such targets. Among the signal amplification approaches in highly sensitive aptasensors, the nuclease-based target recycling signal amplification has recently become a research focus because it shows easy design, simple operation, and rapid reaction and can be easily developed for homogenous assay. In this review, we summarized recent advances in the development of various nuclease-based target recycling signal amplification with the aim to provide a general guide for the design of aptamer-based ultrasensitive biosensing assays. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Amplification in Double Heterostructure GaAs Lasers.

    DTIC Science & Technology

    1981-03-15

    done, for example, in the book by Siegman . When the laser signal which is to be amplified is a single mode, it is important to include the possibility...k A’AD-A097 862 AEROSPACE CORP EL SEGUNDO CA ELECTRONICS RESEARCH LAP) P 5 20/5 I AMPLIFICATION IN DOUBLE HETEROSTRUCTURE GAAS LASERS .(U IMAR al E...GARMIRE, M CHANG F04701-80-C-0081I UNCLASSIFIED TR GO81(6930 03)-2 SD-TA8-30 NL Amplification in Double Heterostructure GaAs Lasers E. GARMIRE nd M

  18. New perspectives on microbial community distortion after whole-genome amplification

    EPA Science Inventory

    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...

  19. CCNE1 amplification is associated with aggressive potential in endometrioid endometrial carcinomas.

    PubMed

    Nakayama, Kentaro; Rahman, Mohammed Tanjimur; Rahman, Munmun; Nakamura, Kohei; Ishikawa, Masako; Katagiri, Hiroshi; Sato, Emi; Ishibashi, Tomoka; Iida, Kouji; Ishikawa, Noriyuki; Kyo, Satoru

    2016-02-01

    The clinicopathological significance of amplification was investigated of the gene encoding cyclin E (CCNE1) and we assessed whether CCNE1 was a potential target in endometrioid endometrial carcinomas. CCNE1 amplification and CCNE1 or F-box and WD repeat domain-containing 7 (FBXW7) expression in endometrial endometrioid carcinoma was assessed by immunohistochemistry and fluorescence in situ hybridization. CCNE1 knockdown by small interfering RNA (siRNA) was used to assess the CCNE1 function. The results showed that CCNE1 amplification was present in 9 (8.3%) of 108 endometrial carcinomas. CCNE1 amplification was correlated with high histological grade (Grade 3; p=0.0087) and lymphovascular space invasion (p=0.0258). No significant association was observed between CCNE1 amplification and FIGO stage (p=0.851), lymph node metastasis (p=0.078), body mass index (p=0.265), deep myometrial invasion (p=0.256), menopausal status (p=0.289) or patient age (p=0.0817). CCNE1 amplification was significantly correlated with shorter progression-free and overall survival (p=0.0081 and 0.0073, respectively). CCNE1 protein expression or loss of FBXW7 expression in endometrial endometrioid carcinoma tended to be correlated with shorter progression-free and overall survival; however, this difference was not statistically significant. Multivariate analysis showed that CCNE1 amplification was an independent prognostic factor for overall survival but not for progression-free survival (P=0.0454 and 0.2175, respectively). Profound growth inhibition was observed in siRNA-transfected cancer cells with endogenous CCNE1 overexpression compared with that in cancer cells having low CCNE1 expression. CCNE1 amplification was independent of p53, HER2, MLH1 and ARID1A expression but dependent on PTEN expression in endometrial carcinomas. These findings indicated that CCNE1 amplification was critical for the survival of endometrial endometrioid carcinomas. Furthermore, the effects of CCNE1 knockdown

  20. CCNE1 amplification is associated with aggressive potential in endometrioid endometrial carcinomas

    PubMed Central

    NAKAYAMA, KENTARO; RAHMAN, MOHAMMED TANJIMUR; RAHMAN, MUNMUN; NAKAMURA, KOHEI; ISHIKAWA, MASAKO; KATAGIRI, HIROSHI; SATO, EMI; ISHIBASHI, TOMOKA; IIDA, KOUJI; ISHIKAWA, NORIYUKI; KYO, SATORU

    2016-01-01

    The clinicopathological significance of amplification was investigated of the gene encoding cyclin E (CCNE1) and we assessed whether CCNE1 was a potential target in endometrioid endometrial carcinomas. CCNE1 amplification and CCNE1 or F-box and WD repeat domain-containing 7 (FBXW7) expression in endometrial endometrioid carcinoma was assessed by immunohistochemistry and fluorescence in situ hybridization. CCNE1 knockdown by small interfering RNA (siRNA) was used to assess the CCNE1 function. The results showed that CCNE1 amplification was present in 9 (8.3%) of 108 endometrial carcinomas. CCNE1 amplification was correlated with high histological grade (Grade 3; P=0.0087) and lymphovascular space invasion (P=0.0258). No significant association was observed between CCNE1 amplification and FIGO stage (P=0.851), lymph node metastasis (P=0.078), body mass index (P=0.265), deep myometrial invasion (P=0.256), menopausal status (P=0.289) or patient age (P=0.0817). CCNE1 amplification was significantly correlated with shorter progression-free and overall survival (P=0.0081 and 0.0073, respectively). CCNE1 protein expression or loss of FBXW7 expression in endometrial endometrioid carcinoma tended to be correlated with shorter progression-free and overall survival; however, this difference was not statistically significant. Multivariate analysis showed that CCNE1 amplification was an independent prognostic factor for overall survival but not for progression-free survival (P=0.0454 and 0.2175, respectively). Profound growth inhibition was observed in siRNA-transfected cancer cells with endogenous CCNE1 overexpression compared with that in cancer cells having low CCNE1 expression. CCNE1 amplification was independent of p53, HER2, MLH1 and ARID1A expression but dependent on PTEN expression in endometrial carcinomas. These findings indicated that CCNE1 amplification was critical for the survival of endometrial endometrioid carcinomas. Furthermore, the effects of CCNE1 knockdown

  1. Natural genomic amplification of cholinesterase genes in animals.

    PubMed

    Chatonnet, Arnaud; Lenfant, Nicolas; Marchot, Pascale; Selkirk, Murray E

    2017-08-01

    Tight control of the concentration of acetylcholine at cholinergic synapses requires precise regulation of the number and state of the acetylcholine receptors, and of the synthesis and degradation of the neurotransmitter. In particular, the cholinesterase activity has to be controlled exquisitely. In the genome of the first experimental models used (man, mouse, zebrafish and drosophila), there are only one or two genes coding for cholinesterases, whereas there are more genes for their closest relatives the carboxylesterases. Natural amplification of cholinesterase genes was first found to occur in some cancer cells and in insect species subjected to evolutionary pressure by insecticides. Analysis of the complete genome sequences of numerous representatives of the various metazoan phyla show that moderate amplification of cholinesterase genes is not uncommon in molluscs, echinoderms, hemichordates, prochordates or lepidosauria. Amplification of acetylcholinesterase genes is also a feature of parasitic nematodes or ticks. In these parasites, over-production of cholinesterase-like proteins in secreted products and the saliva are presumed to have effector roles related to host infection. These amplification events raise questions about the role of the amplified gene products, and the adaptation processes necessary to preserve efficient cholinergic transmission. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms. © 2017 International Society for Neurochemistry.

  2. Modeling magnetic field amplification in nonlinear diffusive shock acceleration

    NASA Astrophysics Data System (ADS)

    Vladimirov, Andrey

    2009-02-01

    This research was motivated by the recent observations indicating very strong magnetic fields at some supernova remnant shocks, which suggests in-situ generation of magnetic turbulence. The dissertation presents a numerical model of collisionless shocks with strong amplification of stochastic magnetic fields, self-consistently coupled to efficient shock acceleration of charged particles. Based on a Monte Carlo simulation of particle transport and acceleration in nonlinear shocks, the model describes magnetic field amplification using the state-of-the-art analytic models of instabilities in magnetized plasmas in the presence of non-thermal particle streaming. The results help one understand the complex nonlinear connections between the thermal plasma, the accelerated particles and the stochastic magnetic fields in strong collisionless shocks. Also, predictions regarding the efficiency of particle acceleration and magnetic field amplification, the impact of magnetic field amplification on the maximum energy of accelerated particles, and the compression and heating of the thermal plasma by the shocks are presented. Particle distribution functions and turbulence spectra derived with this model can be used to calculate the emission of observable nonthermal radiation.

  3. An Intrinsically Digital Amplification Scheme for Hearing Aids

    NASA Astrophysics Data System (ADS)

    Blamey, Peter J.; Macfarlane, David S.; Steele, Brenton R.

    2005-12-01

    Results for linear and wide-dynamic range compression were compared with a new 64-channel digital amplification strategy in three separate studies. The new strategy addresses the requirements of the hearing aid user with efficient computations on an open-platform digital signal processor (DSP). The new amplification strategy is not modeled on prior analog strategies like compression and linear amplification, but uses statistical analysis of the signal to optimize the output dynamic range in each frequency band independently. Using the open-platform DSP processor also provided the opportunity for blind trial comparisons of the different processing schemes in BTE and ITE devices of a high commercial standard. The speech perception scores and questionnaire results show that it is possible to provide improved audibility for sound in many narrow frequency bands while simultaneously improving comfort, speech intelligibility in noise, and sound quality.

  4. The usability of the optical parametric amplification of light for high-angular-resolution imaging and fast astrometry

    NASA Astrophysics Data System (ADS)

    Kurek, A. R.; Stachowski, A.; Banaszek, K.; Pollo, A.

    2018-05-01

    High-angular-resolution imaging is crucial for many applications in modern astronomy and astrophysics. The fundamental diffraction limit constrains the resolving power of both ground-based and spaceborne telescopes. The recent idea of a quantum telescope based on the optical parametric amplification (OPA) of light aims to bypass this limit for the imaging of extended sources by an order of magnitude or more. We present an updated scheme of an OPA-based device and a more accurate model of the signal amplification by such a device. The semiclassical model that we present predicts that the noise in such a system will form so-called light speckles as a result of light interference in the optical path. Based on this model, we analysed the efficiency of OPA in increasing the angular resolution of the imaging of extended targets and the precise localization of a distant point source. According to our new model, OPA offers a gain in resolved imaging in comparison to classical optics. For a given time-span, we found that OPA can be more efficient in localizing a single distant point source than classical telescopes.

  5. Cascade Signal Amplification Based on Copper Nanoparticle-Reported Rolling Circle Amplification for Ultrasensitive Electrochemical Detection of the Prostate Cancer Biomarker.

    PubMed

    Zhu, Ye; Wang, Huijuan; Wang, Lin; Zhu, Jing; Jiang, Wei

    2016-02-03

    An ultrasensitive and highly selective electrochemical assay was first attempted by combining the rolling circle amplification (RCA) reaction with poly(thymine)-templated copper nanoparticles (CuNPs) for cascade signal amplification. As proof of concept, prostate specific antigen (PSA) was selected as a model target. Using a gold nanoparticle (AuNP) as a carrier, we synthesized the primer-AuNP-aptamer bioconjugate for signal amplification by increasing the primer/aptamer ratio. The specific construction of primer-AuNP-aptamer/PSA/anti-PSA sandwich structure triggered the effective RCA reaction, in which thousands of tandem poly(thymine) repeats were generated and directly served as the specific templates for the subsequent CuNP formation. The signal readout was easily achieved by dissolving the RCA product-templated CuNPs and detecting the released copper ions with differential pulse stripping voltammetry. Because of the designed cascade signal amplification strategy, the newly developed method achieved a linear range of 0.05-500 fg/mL, with a remarkable detection limit of 0.020 ± 0.001 fg/mL PSA. Finally, the feasibility of the developed method for practical application was investigated by analyzing PSA in the real clinical human serum samples. The ultrasensitivity, specificity, convenience, and capability for analyzing the clinical samples demonstrate that this method has great potential for practical disease diagnosis applications.

  6. Word Recognition and Learning: Effects of Hearing Loss and Amplification Feature

    PubMed Central

    Stewart, Elizabeth C.; Willman, Amanda P.; Odgear, Ian S.

    2017-01-01

    Two amplification features were examined using auditory tasks that varied in stimulus familiarity. It was expected that the benefits of certain amplification features would increase as the familiarity with the stimuli decreased. A total of 20 children and 15 adults with normal hearing as well as 21 children and 17 adults with mild to severe hearing loss participated. Three models of ear-level devices were selected based on the quality of the high-frequency amplification or the digital noise reduction (DNR) they provided. The devices were fitted to each participant and used during testing only. Participants completed three tasks: (a) word recognition, (b) repetition and lexical decision of real and nonsense words, and (c) novel word learning. Performance improved significantly with amplification for both the children and the adults with hearing loss. Performance improved further with wideband amplification for the children more than for the adults. In steady-state noise and multitalker babble, performance decreased for both groups with little to no benefit from amplification or from the use of DNR. When compared with the listeners with normal hearing, significantly poorer performance was observed for both the children and adults with hearing loss on all tasks with few exceptions. Finally, analysis of across-task performance confirmed the hypothesis that benefit increased as the familiarity of the stimuli decreased for wideband amplification but not for DNR. However, users who prefer DNR for listening comfort are not likely to jeopardize their ability to detect and learn new information when using this feature. PMID:29169314

  7. Increased centrosome amplification in aged stem cells of the Drosophila midgut

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Park, Joung-Sun; Pyo, Jung-Hoon; Na, Hyun-Jin

    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 tumorigenesismore » 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.« less

  8. Optically Controlled Signal Amplification for DNA Computation.

    PubMed

    Prokup, Alexander; Hemphill, James; Liu, Qingyang; Deiters, Alexander

    2015-10-16

    The hybridization chain reaction (HCR) and fuel-catalyst cycles have been applied to address the problem of signal amplification in DNA-based computation circuits. While they function efficiently, these signal amplifiers cannot be switched ON or OFF quickly and noninvasively. To overcome these limitations, a light-activated initiator strand for the HCR, which enabled fast optical OFF → ON switching, was developed. Similarly, when a light-activated version of the catalyst strand or the inhibitor strand of a fuel-catalyst cycle was applied, the cycle could be optically switched from OFF → ON or ON → OFF, respectively. To move the capabilities of these devices beyond solution-based operations, the components were embedded in agarose gels. Irradiation with customizable light patterns and at different time points demonstrated both spatial and temporal control. The addition of a translator gate enabled a spatially activated signal to travel along a predefined path, akin to a chemical wire. Overall, the addition of small light-cleavable photocaging groups to DNA signal amplification circuits enabled conditional control as well as fast photocontrol of signal amplification.

  9. Empirical Site Amplification Factors Incorporating Soil Nonlinearity in Taiwan

    NASA Astrophysics Data System (ADS)

    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.

  10. The Efficiency of Magnetic Field Amplification at Shocks by Turbulence

    NASA Technical Reports Server (NTRS)

    Ji, Suoqing; Oh, S. Peng; Ruszkowsi, M.; Markevitch, M.

    2016-01-01

    Turbulent dynamo field amplification has often been invoked to explain the strong field strengths in thin rims in supernova shocks (approx.100 micrograms) and in radio relics in galaxy clusters (approx. micrograms). We present high-resolution magnetohydrodynamic simulations of the interaction between pre-shock turbulence, clumping and shocks, to quantify the conditions under which turbulent dynamo amplification can be significant. We demonstrate numerically converged field amplification which scales with Alfven Mach number, B/B0 varies as MA, up to MA approx.150.This implies that the post-shock field strength is relatively independent of the seed field. Amplification is dominated by compression at low MA, and stretching (turbulent amplification) at high MA. For high MA, the B-field grows exponentially and saturates at equipartition with turbulence, while the vorticity jumps sharply at the shock and subsequently decays; the resulting field is orientated predominately along the shock normal (an effect only apparent in 3D and not 2D). This agrees with the radial field bias seen in supernova remnants. By contrast, for low MA, field amplification is mostly compressional, relatively modest, and results in a predominantly perpendicular field. The latter is consistent with the polarization seen in radio relics. Our results are relatively robust to the assumed level of gas clumping. Our results imply that the turbulent dynamo may be important for supernovae, but is only consistent with the field strength, and not geometry, for cluster radio relics. For the latter, this implies strong pre-existing B-fields in the ambient cluster outskirts.

  11. Pre-amplification in the context of high-throughput qPCR gene expression experiment.

    PubMed

    Korenková, Vlasta; Scott, Justin; Novosadová, Vendula; Jindřichová, Marie; Langerová, Lucie; Švec, David; Šídová, Monika; Sjöback, Robert

    2015-03-11

    With the introduction of the first high-throughput qPCR instrument on the market it became possible to perform thousands of reactions in a single run compared to the previous hundreds. In the high-throughput reaction, only limited volumes of highly concentrated cDNA or DNA samples can be added. This necessity can be solved by pre-amplification, which became a part of the high-throughput experimental workflow. Here, we focused our attention on the limits of the specific target pre-amplification reaction and propose the optimal, general setup for gene expression experiment using BioMark instrument (Fluidigm). For evaluating different pre-amplification factors following conditions were combined: four human blood samples from healthy donors and five transcripts having high to low expression levels; each cDNA sample was pre-amplified at four cycles (15, 18, 21, and 24) and five concentrations (equivalent to 0.078 ng, 0.32 ng, 1.25 ng, 5 ng, and 20 ng of total RNA). Factors identified as critical for a success of cDNA pre-amplification were cycle of pre-amplification, total RNA concentration, and type of gene. The selected pre-amplification reactions were further tested for optimal Cq distribution in a BioMark Array. The following concentrations combined with pre-amplification cycles were optimal for good quality samples: 20 ng of total RNA with 15 cycles of pre-amplification, 20x and 40x diluted; and 5 ng and 20 ng of total RNA with 18 cycles of pre-amplification, both 20x and 40x diluted. We set up upper limits for the bulk gene expression experiment using gene expression Dynamic Array and provided an easy-to-obtain tool for measuring of pre-amplification success. We also showed that variability of the pre-amplification, introduced into the experimental workflow of reverse transcription-qPCR, is lower than variability caused by the reverse transcription step.

  12. Drastic disorder-induced reduction of signal amplification in scale-free networks.

    PubMed

    Chacón, Ricardo; Martínez, Pedro J

    2015-07-01

    Understanding information transmission across a network is a fundamental task for controlling and manipulating both biological and manmade information-processing systems. Here we show how topological resonant-like amplification effects in scale-free networks of signaling devices are drastically reduced when phase disorder in the external signals is considered. This is demonstrated theoretically by means of a starlike network of overdamped bistable systems, and confirmed numerically by simulations of scale-free networks of such systems. The taming effect of the phase disorder is found to be sensitive to the amplification's strength, while the topology-induced amplification mechanism is robust against this kind of quenched disorder in the sense that it does not significantly change the values of the coupling strength where amplification is maximum in its absence.

  13. Tension Amplification in Molecular Brushes in Solutions and on Substrates

    PubMed Central

    Panyukov, Sergey; Zhulina, Ekaterina B.; Sheiko, Sergei S.; Randall, Greg C.; Brock, James; Rubinstein, Michael

    2009-01-01

    Molecular bottle-brushes are highly branched macromolecules with side chains densely grafted to a long polymer backbone. The brush-like architecture allows focusing of the side-chain tension to the backbone and its amplification from the picoNewton to nanoNewton range. The backbone tension depends on the overall molecular conformation and the surrounding environment. Here we study the relation between the tension and conformation of the molecular brushes in solutions, melts, and on substrates. In solutions, we find that the backbone tension in dense brushes with side chains attached to every backbone monomer is on the order of f0N3/8 in athermal solvents, f0N1/3 in θ-solvents, and f0 in poor solvents and melts, where N is the degree of polymerization of side chains, f0≃ kBT/b is the maximum tension in side chains, b is the Kuhn length, kB is Boltzmann constant, and T is absolute temperature. Depending on the side chain length and solvent quality, molecular brushes in solutions develop tension on the order of 10–100 picoNewtons, which is sufficient to break hydrogen bonds. Significant amplification of tension occurs upon adsorption of brushes onto a substrate. On a strongly attractive substrate, maximum tension in the brush backbone is ~ f0N, reaching values on the order of several nanoNewtons which exceed the strength of a typical covalent bond. At low grafting density and high spreading parameter the cross-sectional profile of adsorbed molecular brush is approximately rectangular with thicknes ~bA/S, where A is the Hamaker constant and S is the spreading parameter. At a very high spreading parameter (S > A), the brush thickness saturates at monolayer ~ b. At a low spreading parameter, the cross-sectional profile of adsorbed molecular brush has triangular tent-like shape. In the cross-over between these two opposite cases, covering a wide range of parameter space, the adsorbed molecular brush consists of two layers. Side chains in the lower layer gain surface

  14. Impact of primer dimers and self-amplifying hairpins on reverse transcription loop-mediated isothermal amplification detection of viral RNA

    DOE PAGES

    Meagher, Robert J.; Priye, Aashish; Light, Yooli K.; ...

    2018-03-27

    Loop-mediated isothermal amplification (LAMP), coupled with reverse transcription (RT), has become a popular technique for detection of viral RNA due to several desirable characteristics for use in point-of-care or low-resource settings. The large number of primers in LAMP (six per target) leads to an increased likelihood of primer-dimer interactions, and the inner primers in particular are prone to formation of stable hairpin structures due to their length (typically 40-45 bases). Although primer-dimers and hairpin structures are known features to avoid in nucleic acid amplification techniques, there is little quantitative information in literature regarding the impact of these structures on LAMPmore » or RT-LAMP assays. In this study, we examine the impact of primer-dimers and hairpins on previously-published primer sets for dengue virus and yellow fever virus. We demonstrate that minor changes to the primers to eliminate amplifiable primer dimers and hairpins improves the performance of the assays when monitored in real time with intercalating dyes, and when monitoring a fluorescent endpoint using the QUASR technique. We also discuss the thermodynamic implications of these minor changes on the overall stability of amplifiable secondary structures, and we present a single thermodynamic parameter to predict the probability of non-specific amplification associated with LAMP primers.« less

  15. Impact of primer dimers and self-amplifying hairpins on reverse transcription loop-mediated isothermal amplification detection of viral RNA

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Meagher, Robert J.; Priye, Aashish; Light, Yooli K.

    Loop-mediated isothermal amplification (LAMP), coupled with reverse transcription (RT), has become a popular technique for detection of viral RNA due to several desirable characteristics for use in point-of-care or low-resource settings. The large number of primers in LAMP (six per target) leads to an increased likelihood of primer-dimer interactions, and the inner primers in particular are prone to formation of stable hairpin structures due to their length (typically 40-45 bases). Although primer-dimers and hairpin structures are known features to avoid in nucleic acid amplification techniques, there is little quantitative information in literature regarding the impact of these structures on LAMPmore » or RT-LAMP assays. In this study, we examine the impact of primer-dimers and hairpins on previously-published primer sets for dengue virus and yellow fever virus. We demonstrate that minor changes to the primers to eliminate amplifiable primer dimers and hairpins improves the performance of the assays when monitored in real time with intercalating dyes, and when monitoring a fluorescent endpoint using the QUASR technique. We also discuss the thermodynamic implications of these minor changes on the overall stability of amplifiable secondary structures, and we present a single thermodynamic parameter to predict the probability of non-specific amplification associated with LAMP primers.« less

  16. Arctic Amplification and Potential Mid-Latitude Weather Linkages

    NASA Astrophysics Data System (ADS)

    Overland, J. E.

    2014-12-01

    Increasing temperatures and other changes continued in the Arctic over the last decade, even though the rate of global warming has decreased in part due to a cool Pacific Ocean. Thus Arctic temperatures have increased at least 3 times the rate of mid-latitude temperatures. Credibility for persistent Arctic change comes from multiple indicators which are now available for multiple decades. Further, the spatial pattern of Arctic Amplification differs from patterns of natural variability. The role of the Arctic in the global climate system is based on multiple interacting feedbacks represented by these indicators as a causal basis for Arctic Amplification driven by modest global change. Many of these processes act on a regional basis and their non-linear interactions are not well captured by climate models. For example, future loss of sea ice due to increases in CO2 are demonstrated by these models but the rates of loss appear slow. It is reasonable to suspect that Arctic change which can produce the largest temperature anomalies on the planet and demonstrate recent extremes in the polar vortex could be linked to mid-latitude weather, especially as Arctic change will continue over the next decades. The meteorological community remains skeptical, however, in the sense of "not proven." Natural variability in chaotic atmospheric flow remains the main dynamic process, and it is difficult to determine whether Arctic forcing of a north-south linkage is emerging from the most recent period of Arctic change since 2007. Nonetheless, such a hypothesis is worthy of investigation, given the need to further understand Arctic dynamic atmospheric processes, and the potential for improving mid-latitude seasonal forecasts base on high-latitude forcing. Several AGU sessions and other forums over the next year (WWRP, IASC,CliC) address this issue, but the topic is not ready for a firm answer. The very level of controversy indicates the state of the science.

  17. [Application of recombinase polymerase amplification in the detection of Pseudomonas aeruginosa].

    PubMed

    Jin, X J; Gong, Y L; Yang, L; Mo, B H; Peng, Y Z; He, P; Zhao, J N; Li, X L

    2018-04-20

    Objective: To establish an optimized method of recombinase polymerase amplification (RPA) to rapidly detect Pseudomonas aeruginosa in clinic. Methods: (1) The DNA templates of one standard Pseudomonas aeruginosa strain was extracted and detected by polymerase chain reaction (PCR), real-time fluorescence quantitative PCR and RPA. Time of sample loading, time of amplification, and time of detection of the three methods were recorded. (2) One standard Pseudomonas aeruginosa strain was diluted in 7 concentrations of 1×10(7,) 1×10(6,) 1×10(5,) 1×10(4,) 1×10(3,) 1×10(2,) and 1×10(1) colony forming unit (CFU)/mL after recovery and cultivation. The DNA templates of Pseudomonas aeruginosa and negative control strain Pseudomonas putida were extracted and detected by PCR, real-time fluorescence quantitative PCR, and RPA separately. The sensitivity of the three methods in detecting Pseudomonas aeruginosa was analyzed. (3) The DNA templates of one standard Pseudomonas aeruginosa strain and four negative control strains ( Staphylococcus aureus, Acinetobacter baumanii, Candida albicans, and Pseudomonas putida ) were extracted separately, and then they were detected by PCR, real-time fluorescence quantitative PCR, and RPA. The specificity of the three methods in detecting Pseudomonas aeruginosa was analyzed. (4) The DNA templates of 28 clinical strains of Pseudomonas aeruginosa preserved in glycerin, 1 clinical strain of which was taken by cotton swab, and negative control strain Pseudomonas putida were extracted separately, and then they were detected by RPA. Positive amplification signals of the clinical strains were observed, and the detection rate was calculated. All experiments were repeated for 3 times. Sensitivity results were analyzed by GraphPad Prism 5.01 statistical software. Results: (1) The loading time of RPA, PCR, and real-time fluorescence quantitative PCR for detecting Pseudomonas aeruginosa were all 20 minutes. In PCR, time of amplification was 98 minutes

  18. Fluorene- and benzofluorene-cored oligomers as low threshold and high gain amplifying media

    NASA Astrophysics Data System (ADS)

    Kazlauskas, Karolis; Kreiza, Gediminas; Bobrovas, Olegas; AdomÄ--nienÄ--, Ona; AdomÄ--nas, Povilas; Jankauskas, Vygintas; JuršÄ--nas, Saulius

    2015-07-01

    Deliberate control of intermolecular interactions in fluorene- and benzofluorene-cored oligomers was attempted via introduction of different-length alkyl moieties to attain high emission amplification and low amplified spontaneous emission (ASE) threshold at high oligomer concentrations. Containing fluorenyl peripheral groups decorated with different-length alkyl moieties, the oligomers were found to express weak concentration quenching of emission, yet excellent carrier drift mobilities (close to 10-2 cm2/V/s) in the amorphous films. Owing to the larger radiative decay rates (>1.0 × 109 s-1) and smaller concentration quenching, fluorene-cored oligomers exhibited down to one order of magnitude lower ASE thresholds at higher concentrations as compared to those of benzofluorene counterparts. The lowest threshold (300 W/cm2) obtained for the fluorene-cored oligomers at the concentration of 50 wt % in polymer matrix is among the lowest reported for solution-processed amorphous films in ambient conditions, what makes the oligomers promising for lasing application. Great potential in emission amplification was confirmed by high maximum net gain (77 cm-1) revealed for these compounds. Although the photostability of the oligomers was affected by photo-oxidation, it was found to be comparable to that of various organic lasing materials including some commercial laser dyes evaluated under similar excitation conditions.

  19. Noiseless optical amplification in quasi-phase-matched bulk lithium niobate

    NASA Astrophysics Data System (ADS)

    Lovering, D. J.; Levenson, J. A.; Vidakovic, P.; Webjörn, J.; Russell, P. St. J.

    1996-09-01

    An optical parametric amplifier (OPA) has been demonstrated in bulk, periodically poled lithium niobate and is shown to operate with a noise figure well below the classical limit. In contrast to conventional OPA's, this device uses quasi-phase matching to provide the coupling between the pump and the signal. Comparison of the measured performance with that of a theoretical model reveals that the main intrinsic contribution to the output noise is due to spatial and temporal mode mixing, which arises as a consequence of tight focusing of the incident beams. Factors that affect the performance of this amplifier are identified theoretically and their relative importance investigated for both amplification and squeezing.

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

    PubMed

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

    2016-10-24

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

  1. The Interplay Between Estrogen and Replication Origins in Breast Cancer DNA Amplification

    DTIC Science & Technology

    2013-09-01

    Replication Origins in Breast Cancer DNA Amplification PRINCIPAL INVESTIGATOR: Cinzia Casella CONTRACTING ORGANIZATION: Brown...Interplay Between Estrogen and Replication Origins in Breast Cancer DNA Amplification 5b. GRANT NUMBER W81XWH-11-1-0599 5c. PROGRAM ELEMENT NUMBER 6... amplification and oncogenes activation in breast cancer cells? This project aims to understand the role of estrogen in inducing re-replication, thus

  2. Coherent Spin Amplification Using a Beam Splitter

    NASA Astrophysics Data System (ADS)

    Yan, Chengyu; Kumar, Sanjeev; Thomas, Kalarikad; See, Patrick; Farrer, Ian; Ritchie, David; Griffiths, Jonathan; Jones, Geraint; Pepper, Michael

    2018-03-01

    We report spin amplification using a capacitive beam splitter in n -type GaAs where the spin polarization is monitored via a transverse electron focusing measurement. It is shown that partially spin-polarized current injected by the emitter can be precisely controlled, and the spin polarization associated with it can be amplified by the beam splitter, such that a considerably high spin polarization of around 50% can be obtained. Additionally, the spin remains coherent as shown by the observation of quantum interference. Our results illustrate that spin-polarization amplification can be achieved in materials without strong spin-orbit interaction.

  3. Detection of DNA Sequences Refractory to PCR Amplification Using a Biophysical SERRS Assay (Surface Enhanced Resonant Raman Spectroscopy)

    PubMed Central

    Feuillie, Cécile; Merheb, Maxime M.; Gillet, Benjamin; Montagnac, Gilles; Daniel, Isabelle; Hänni, Catherine

    2014-01-01

    The analysis of ancient or processed DNA samples is often a great challenge, because traditional Polymerase Chain Reaction – based amplification is impeded by DNA damage. Blocking lesions such as abasic sites are known to block the bypass of DNA polymerases, thus stopping primer elongation. In the present work, we applied the SERRS-hybridization assay, a fully non-enzymatic method, to the detection of DNA refractory to PCR amplification. This method combines specific hybridization with detection by Surface Enhanced Resonant Raman Scattering (SERRS). It allows the detection of a series of double-stranded DNA molecules containing a varying number of abasic sites on both strands, when PCR failed to detect the most degraded sequences. Our SERRS approach can quickly detect DNA molecules without any need for DNA repair. This assay could be applied as a pre-requisite analysis prior to enzymatic reparation or amplification. A whole new set of samples, both forensic and archaeological, could then deliver information that was not yet available due to a high degree of DNA damage. PMID:25502338

  4. Detection of DNA sequences refractory to PCR amplification using a biophysical SERRS assay (Surface Enhanced Resonant Raman Spectroscopy).

    PubMed

    Feuillie, Cécile; Merheb, Maxime M; Gillet, Benjamin; Montagnac, Gilles; Daniel, Isabelle; Hänni, Catherine

    2014-01-01

    The analysis of ancient or processed DNA samples is often a great challenge, because traditional Polymerase Chain Reaction - based amplification is impeded by DNA damage. Blocking lesions such as abasic sites are known to block the bypass of DNA polymerases, thus stopping primer elongation. In the present work, we applied the SERRS-hybridization assay, a fully non-enzymatic method, to the detection of DNA refractory to PCR amplification. This method combines specific hybridization with detection by Surface Enhanced Resonant Raman Scattering (SERRS). It allows the detection of a series of double-stranded DNA molecules containing a varying number of abasic sites on both strands, when PCR failed to detect the most degraded sequences. Our SERRS approach can quickly detect DNA molecules without any need for DNA repair. This assay could be applied as a pre-requisite analysis prior to enzymatic reparation or amplification. A whole new set of samples, both forensic and archaeological, could then deliver information that was not yet available due to a high degree of DNA damage.

  5. MYCN amplification confers enhanced folate dependence and methotrexate sensitivity in neuroblastoma

    PubMed Central

    Lau, Diana T.; Flemming, Claudia L.; Gherardi, Samuele; Perini, Giovanni; Oberthuer, André; Fischer, Matthias; Juraeva, Dilafruz; Brors, Benedikt; Xue, Chengyuan; Norris, Murray D.; Marshall, Glenn M.; Haber, Michelle

    2015-01-01

    MYCN amplification occurs in 20% of neuroblastomas and is strongly related to poor clinical outcome. We have identified folate-mediated one-carbon metabolism as highly upregulated in neuroblastoma tumors with MYCN amplification and have validated this finding experimentally by showing that MYCN amplified neuroblastoma cell lines have a higher requirement for folate and are significantly more sensitive to the antifolate methotrexate than cell lines without MYCN amplification. We have demonstrated that methotrexate uptake in neuroblastoma cells is mediated principally by the reduced folate carrier (RFC; SLC19A1), that SLC19A1 and MYCN expression are highly correlated in both patient tumors and cell lines, and that SLC19A1 is a direct transcriptional target of N-Myc. Finally, we assessed the relationship between SLC19A1 expression and patient survival in two independent primary tumor cohorts and found that SLC19A1 expression was associated with increased risk of relapse or death, and that SLC19A1 expression retained prognostic significance independent of age, disease stage and MYCN amplification. This study adds upregulation of folate-mediated one-carbon metabolism to the known consequences of MYCN amplification, and suggests that this pathway might be targeted in poor outcome tumors with MYCN amplification and high SLC19A1 expression. PMID:25860940

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

    PubMed Central

    Depierreux, S.; Yahia, V.; Goyon, C.; Loisel, G.; Masson-Laborde, P. -E.; Borisenko, N.; Orekhov, A.; Rosmej, O.; Rienecker, T.; 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. PMID:24938756

  7. Observation of strong amplification at 8.8 nm in the TCE scheme by a table-top pumping system

    NASA Astrophysics Data System (ADS)

    Kawachi, Tetsuya; Tanaka, Momoko; Sasaki, Akira; Kishimoto, Maki; Nishiuchi, Mamiko; Yasuike, Kazuhito; Hasegawa, Noboru; Kilpio, Alexander V.; Lu, Peixiang; Tai, Renzhong

    2002-11-01

    We observed strong amplification of the transition of 4d 4p, J = 0 1 (the transition from (3d3/2, 4d3/2)0 to (3d3/2, 4p1/2)1) of the Ni-like lanthanum (La) ions at a wavelength of 8.8 nm pumped by a compact CPA Nd:Glass laser light at a wavelength of 1.053 mum with a pumping energy of 18 J. The experimental gain coefficient and the achieved gain-length product was 14.5 cm-1 and 7.7, respectively. In this experiment, the pumping laser pulse consisted of a pre-pulse with a duration of 200 ps and a 7ps-duration main pulse, separated by 250 ps. A hydrodynamics simulation coupled with a collisional-radiative model showed that the present experimental condition generated a pre-formed plasma with small volume and made it possible by the main pulse to heat the high density region effectively.

  8. Models and methods to characterize site amplification from a pair of records

    USGS Publications Warehouse

    Safak, E.

    1997-01-01

    The paper presents a tutorial review of the models and methods that are used to characterize site amplification from the pairs of rock- and soil-site records, and introduces some new techniques with better theoretical foundations. The models and methods discussed include spectral and cross-spectral ratios, spectral ratios for downhole records, response spectral ratios, constant amplification factors, parametric models, physical models, and time-varying filters. An extensive analytical and numerical error analysis of spectral and cross-spectral ratios shows that probabilistically cross-spectral ratios give more reliable estimates of site amplification. Spectral ratios should not be used to determine site amplification from downhole-surface recording pairs because of the feedback in the downhole sensor. Response spectral ratios are appropriate for low frequencies, but overestimate the amplification at high frequencies. The best method to be used depends on how much precision is required in the estimates.

  9. Evidence that selected amplification of a bacterial lac frameshift allele stimulates Lac(+) reversion (adaptive mutation) with or without general hypermutability.

    PubMed Central

    Slechta, E Susan; Liu, Jing; Andersson, Dan I; Roth, John R

    2002-01-01

    In the genetic system of Cairns and Foster, a nongrowing population of an E. coli lac frameshift mutant appears to specifically accumulate Lac(+) revertants when starved on medium including lactose (adaptive mutation). This behavior has been attributed to stress-induced general mutagenesis in a subpopulation of starved cells (the hypermutable state model). We have suggested that, on the contrary, stress has no direct effect on mutability but favors only growth of cells that amplify their leaky mutant lac region (the amplification mutagenesis model). Selection enhances reversion primarily by increasing the mutant lac copy number within each developing clone on the selection plate. The observed general mutagenesis is attributed to a side effect of growth with an amplification-induction of SOS by DNA fragments released from a tandem array of lac copies. Here we show that the S. enterica version of the Cairns system shows SOS-dependent general mutagenesis and behaves in every way like the original E. coli system. In both systems, lac revertants are mutagenized during selection. Eliminating the 35-fold increase in mutation rate reduces revertant number only 2- to 4-fold. This discrepancy is due to continued growth of amplification cells until some clones manage to revert without mutagenesis solely by increasing their lac copy number. Reversion in the absence of mutagenesis is still dependent on RecA function, as expected if it depends on lac amplification (a recombination-dependent process). These observations support the amplification mutagenesis model. PMID:12136002

  10. Multi-chamber nucleic acid amplification and detection device

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dugan, Lawrence

    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 whichmore » 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.« less

  11. Multi-turn transmit coil to increase b1 efficiency in current source amplification.

    PubMed

    Gudino, N; Griswold, M A

    2013-04-01

    A multi-turn transmit surface coil design was presented to improve B1 efficiency when used with current source amplification. Three different coil designs driven by an on-coil current-mode class-D amplifier with current envelope feedback were tested on the benchtop and through imaging in a 1.5 T scanner. Case temperature of the power field-effect transistor at the amplifier output stage was measured to evaluate heat dissipation for the different current levels and coil configurations. In addition, a lower power rated device was tested to exploit the potential gain in B1 obtained with the multi-turn coil. As shown both on the benchtop and in a 1.5 T scanner, B1 was increased by almost 3-fold without increasing heat dissipation on the power device at the amplifier's output using a multi-turn surface coil. Similar gain was obtained when connecting a lower power rated field-effect transistor to the multi-turn coil. In addition to reduce heat dissipation per B1 in the device, higher B1 per current efficiency allows the use of field-effect transistors with lower current ratings and lower port capacitances, which could improve the overall performance of the on-coil current source transmit system. Copyright © 2013 Wiley Periodicals, Inc.

  12. Multi-turn transmit coil to increase B1 efficiency in current source amplification

    PubMed Central

    Gudino, N.; Griswold, M.A.

    2013-01-01

    Purpose A multi-turn transmit surface coil design was presented to improve B1 efficiency when used with current source amplification. Methods Three different coil designs driven by an on-coil current-mode class-D (CMCD) amplifier with current envelope feedback were tested on the benchtop and through imaging in a 1.5 T scanner. Case temperature of the power field-effect transistor (FET) at the amplifier output stage was measured to evaluate heat dissipation for the different current levels and coil configurations. In addition, a lower power rated device was tested to exploit the potential gain in B1 obtained with the multi-turn coil. Results As shown both on the benchtop and in a 1.5 T scanner, B1 was increased by almost three-fold without increasing heat dissipation on the power device at the amplifier's output using a multi-turn surface coil. Similar gain was obtained when connecting a lower power rated FET to the multi-turn coil. Conclusion In addition to reduce heat dissipation per B1 in the device, higher B1 per current efficiency allows the use of FETs with lower current ratings and lower port capacitances which could improve the overall performance of the on-coil current source transmit system. PMID:23401060

  13. Advances in the detection of telomerase activity using isothermal amplification

    PubMed Central

    Zhang, Xiaojin; Lou, Xiaoding; Xia, Fan

    2017-01-01

    Telomerase plays a significantly important role in keeping the telomere length of a chromosome. Telomerase overexpresses in nearly all tumor cells, suggesting that telomerase could be not only a promising biomarker but also a potential therapeutic target for cancers. Therefore, numerous efforts focusing on the detection of telomerase activity have been reported from polymerase chain reaction (PCR)-based telomeric repeat amplification protocol (TRAP) assays to PCR-free assays such as isothermal amplification in recent decade. In this review, we highlight the strategies for the detection of telomerase activity using isothermal amplification and discuss some of the challenges in designing future telomerase assays as well. PMID:28638472

  14. Soil amplification with a strong impedance contrast: Boston, Massachusetts

    USGS Publications Warehouse

    Baise, Laurie G.; Kaklamanos, James; Berry, Bradford M; Thompson, Eric M.

    2016-01-01

    In this study, we evaluate the effect of strong sediment/bedrock impedance contrasts on soil amplification in Boston, Massachusetts, for typical sites along the Charles and Mystic Rivers. These sites can be characterized by artificial fill overlying marine sediments overlying glacial till and bedrock, where the depth to bedrock ranges from 20 to 80 m. The marine sediments generally consist of organic silts, sand, and Boston Blue Clay. We chose these sites because they represent typical foundation conditions in the city of Boston, and the soil conditions are similar to other high impedance contrast environments. The sediment/bedrock interface in this region results in an impedance ratio on the order of ten, which in turn results in a significant amplification of the ground motion. Using stratigraphic information derived from numerous boreholes across the region paired with geologic and geomorphologic constraints, we develop a depth-to-bedrock model for the greater Boston region. Using shear-wave velocity profiles from 30 locations, we develop average velocity profiles for sites mapped as artificial fill, glaciofluvial deposits, and bedrock. By pairing the depth-to-bedrock model with the surficial geology and the average shear-wave velocity profiles, we can predict soil amplification in Boston. We compare linear and equivalent-linear site response predictions for a soil layer of varying thickness over bedrock, and assess the effects of varying the bedrock shear-wave velocity (VSb) and quality factor (Q). In a moderate seismicity region like Boston, many earthquakes will result in ground motions that can be modeled with linear site response methods. We also assess the effect of bedrock depth on soil amplification for a generic soil profile in artificial fill, using both linear and equivalent-linear site response models. Finally, we assess the accuracy of the model results by comparing the predicted (linear site response) and observed site response at the Northeastern

  15. A large ungated TPC with GEM amplification

    NASA Astrophysics Data System (ADS)

    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

  16. Laser and gain parameters at 2.7 μm of Er 3+-doped oxyfluoride transparent glass-ceramics

    NASA Astrophysics Data System (ADS)

    Tikhomirov, V. K.; Méndez-Ramos, J.; Rodríguez, V. D.; Furniss, D.; Seddon, A. B.

    2006-07-01

    The room temperature emission spectrum at about 2.7 μm corresponding to the laser transition 4I 11/2 → 4I 13/2 in Er 3+-doped nano-scaled transparent oxyfluoride glass-ceramic has been measured and stimulated emission cross-section for the transition has been calculated. The intensity of the transition has been found to be 40 times stronger and lifetime 50 times longer in the glass-ceramics compared to the precursor glass, which we show to be due to a change of frequency of the phonon involved in non-radiative de-excitation of the 4I 11/2 level from 900 cm -1 in the precursor glass to 240 cm -1 in the ensuing glass-ceramics. The absorption cross-section for the excited state absorption 4I 13/2 → 4I 11/2 has been calculated based on the experimental reciprocal emission spectrum and wavelength dependence of the gain cross-section for the lasing transition 4I 11/2 → 4I 13/2 vs population inversion has been derived. The lasing/optical amplification gain parameters, such as population inversion, pump saturation intensity and product of emission cross-section and fluorescence lifetime have been obtained at the 2.7 μm wavelength. A noteworthy result is that laser action at 2.7 μm is possible in these Er 3+-doped glass-ceramics, already not taking into account energy transfer or up-conversion processes, related to the 4I 13/2 level, which favour the population inversion.

  17. Horizontal localization and speech intelligibility with bilateral and unilateral hearing aid amplification.

    PubMed

    Köbler, S; Rosenhall, U

    2002-10-01

    Speech intelligibility and horizontal localization of 19 subjects with mild-to-moderate hearing loss were studied in order to evaluate the advantages and disadvantages of bilateral and unilateral hearing aid (HA) fittings. Eight loudspeakers were arranged in a circular array covering the horizontal plane around the subjects. Speech signals of a sentence test were delivered by one, randomly chosen, loudspeaker. At the same time, the other seven loudspeakers emitted noise with the same long-term average spectrum as the speech signals. The subjects were asked to repeat the speech signal and to point out the corresponding loudspeaker. Speech intelligibility was significantly improved by HAs, bilateral amplification being superior to unilateral. Horizontal localization could not be improved by HA amplification. However, bilateral HAs preserved the subjects' horizontal localization, whereas unilateral amplification decreased their horizontal localization abilities. Front-back confusions were common in the horizontal localization test. The results indicate that bilateral HA amplification has advantages compared with unilateral amplification.

  18. Development of a Recombinase Polymerase Amplification Assay for the Detection of Pathogenic Leptospira

    PubMed Central

    Ahmed, Ahmed; van der Linden, Hans; Hartskeerl, Rudy A.

    2014-01-01

    Detection of leptospires based on DNA amplification techniques is essential for the early diagnosis of leptospirosis when anti-Leptospira antibodies are below the detection limit of most serological tests. In middle and low income countries where leptospirosis is endemic, routine implementation of real-time PCR is financially and technically challenging due to the requirement of expensive thermocycler equipment. In this study we report the development and evaluation of a novel isothermal recombinase polymerase amplification assay (RPA) for detection of pathogenic Leptospira based on TwistAmp chemistry. RPA enabled the detection of less than two genome copies per reaction. Retrospective evaluation revealed a high diagnostic accuracy (sensitivity and specificity of 94.7% and 97.7%, respectively) compared to culturing as the reference standard. RPA presents a powerful tool for the early diagnosis of leptospirosis in humans and in animals. Furthermore, it enables the detection of the causative agent in reservoirs and environment, and as such is a valuable adjunct to current tools for surveillance and early outbreak warning. PMID:24814943

  19. Optimized thermal amplification in a radiative transistor

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Prod'homme, Hugo; Ordonez-Miranda, Jose; Ezzahri, Younes, E-mail: younes.ezzahri@univ-poitiers.fr

    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 ismore » 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.« less

  20. Signal Amplification by Reversible Exchange (SABRE): From Discovery to Diagnosis.

    PubMed

    Rayner, Peter J; Duckett, Simon B

    2018-06-04

    Signal amplification by reversible exchange (SABRE) turns typically weak magnetic resonance responses into strong signals making previously impractical measurements possible. This technique has gained significant popularity because of its speed and simplicity. This Minireview tracks the development of SABRE from the initial hyperpolarization of pyridine in 2009 to the point in which 50 % 1 H polarization levels have been achieved in a di-deuterio-nicotinate, a key step in the pathway to potential clinical use. Simple routes to highly efficient 15 N hyperpolarization and the creation of hyperpolarized long-lived magnetic states are illustrated. To conclude, we describe how the recently reported SABRE-RELAY approach offers a route for parahydrogen to hyperpolarize a much wider array of molecular scaffolds, such as amides, alcohols, carboxylic acids, and phosphates, than was previously thought possible. We predict that collectively these developments ensure that SABRE will significantly impact on both chemical analysis and the diagnosis of disease in the future. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. MYC and MYCN amplification can be reliably assessed by aCGH in medulloblastoma.

    PubMed

    Bourdeaut, Franck; Grison, Camille; Maurage, Claude-Alain; Laquerriere, Annie; Vasiljevic, Alexandre; Delisle, Marie-Bernadette; Michalak, Sophie; Figarella-Branger, Dominique; Doz, François; Richer, Wilfrid; Pierron, Gaelle; Miquel, Catherine; Delattre, Olivier; Couturier, Jérôme

    2013-04-01

    As prognostic factors, MYC and MYCN amplifications are routinely assessed in medulloblastomas. Fluorescence in situ hybridization (FISH) is currently considered as the technique of reference. Recently, array comparative genomic hybridization (aCGH) has been developed as an alternative technique to evaluate genomic abnormalities in other tumor types; however, this technique has not been widely adopted as a replacement for FISH in medulloblastoma. In this study, 34 tumors were screened by both FISH and aCGH. In all cases showing amplification by FISH, aCGH also unambiguously revealed the abnormality. The aCGH technique was also performed on tumors showing no amplification by FISH, and the absence of amplification was confirmed in all cases. Interestingly, one tumor showed a subclonal MYC amplification by FISH. This subclonal amplification was observed in approximately 20% of tumor cells and was clearly evident on aCGH. In conclusion, our analysis confirms that aCGH is as safe as FISH for the detection of MYC/MYCN gene amplification. Given its cost efficiency in comparison to two FISH tests and the global genomic information additionally provided by an aCGH experiment, this reproducible technique can be safely retained as an alternative to FISH for routine investigation of medulloblastoma. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Novel Bioluminescent Quantitative Detection of Nucleic Acid Amplification in Real-Time

    PubMed Central

    Gandelman, Olga A.; Church, Vicki L.; Moore, Cathy A.; Kiddle, Guy; Carne, Christopher A.; Parmar, Surendra; Jalal, Hamid; Tisi, Laurence C.; Murray, James A. H.

    2010-01-01

    Background The real-time monitoring of polynucleotide amplification is at the core of most molecular assays. This conventionally relies on fluorescent detection of the amplicon produced, requiring complex and costly hardware, often restricting it to specialised laboratories. Principal Findings Here we report the first real-time, closed-tube luminescent reporter system for nucleic acid amplification technologies (NAATs) enabling the progress of amplification to be continuously monitored using simple light measuring equipment. The Bioluminescent Assay in Real-Time (BART) continuously reports through bioluminescent output the exponential increase of inorganic pyrophosphate (PPi) produced during the isothermal amplification of a specific nucleic acid target. BART relies on the coupled conversion of inorganic pyrophosphate (PPi) produced stoichiometrically during nucleic acid synthesis to ATP by the enzyme ATP sulfurylase, and can therefore be coupled to a wide range of isothermal NAATs. During nucleic acid amplification, enzymatic conversion of PPi released during DNA synthesis into ATP is continuously monitored through the bioluminescence generated by thermostable firefly luciferase. The assay shows a unique kinetic signature for nucleic acid amplifications with a readily identifiable light output peak, whose timing is proportional to the concentration of original target nucleic acid. This allows qualitative and quantitative analysis of specific targets, and readily differentiates between negative and positive samples. Since quantitation in BART is based on determination of time-to-peak rather than absolute intensity of light emission, complex or highly sensitive light detectors are not required. Conclusions The combined chemistries of the BART reporter and amplification require only a constant temperature maintained by a heating block and are shown to be robust in the analysis of clinical samples. Since monitoring the BART reaction requires only a simple light

  3. Impact of Topography on Seismic Amplification During the 2005 Kashmir Earthquake

    NASA Astrophysics Data System (ADS)

    Khan, S.; van der Meijde, M.; van der Werff, H.; Shafique, M.

    2016-12-01

    This study assesses topographic amplification of seismic response during the 2005 Kashmir Earthquake in northern Pakistan. Topography scatters seismic waves, which causes variation in seismic response on the surface of the earth. During the Kashmir earthquake, topography induced amplification was suspected to have had major influence on the damage of infrastructure. We did a 3-dimensional simulation of the event using SPECFEM3D software. We first analyzed the impact of data resolution (mesh and Digital Elevation Model) on the derived seismic response. ASTER GDEM elevation data was used to build a 3D finite element mesh, and the parameters (latitude, longitude, depth, moment tensor) of the Kashmir earthquake were used in simulating the event. Our results show amplification of seismic response on ridges and de-amplification in valleys. It was also found that slopes facing away from the source receive an amplified seismic response when compared to slopes facing towards the source. The PGD would regularly fall within the range 0.23-5.8 meters. The topographic amplification causes local changes in the range of -2.50 to +3.50 meters; causing the PGD to fall in the range of 0.36-7.85 meters.

  4. VS30, site amplifications and some comparisons: The Adapazari (Turkey) case

    NASA Astrophysics Data System (ADS)

    Ozcep, Tazegul; Ozcep, Ferhat; Ozel, Oguz

    The aim of this study was to investigate the role of VS30 in site amplifications in the Adapazari region, Turkey. To fulfil this aim, amplifications from VS30 measurements were compared with earthquake data for different soil types in the seismic design codes. The Adapazari area was selected as the study area, and shear-wave velocity distribution was obtained by the multichannel analysis of surface waves (MASWs) method at 100 sites for the top 50 m of soil. Aftershock data following the Mw 7.4 Izmit earthquake of 17 August 1999 gave magnitudes between 4.0 and 5.6 at six stations installed in and around the Adapazari Basin, at Babalı, Şeker, Genç, Hastane, Toyota and Imar. This data was used to estimate site amplifications by the reference-station method. In addition, the fundamental periods of the station sites were estimated by the single station method. Site classifications based on VS30 in the seismic design codes were compared with the fundamental periods and amplification values. It was found that site amplifications (from earthquake data) and relevant spectra (from VS30) are not in good agreement for soils in Adapazari (Turkey).

  5. NAIMA: target amplification strategy allowing quantitative on-chip detection of GMOs.

    PubMed

    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.

  6. NAIMA: target amplification strategy allowing quantitative on-chip detection of GMOs

    PubMed Central

    Morisset, Dany; Dobnik, David; Hamels, Sandrine; Žel, Jana; Gruden, Kristina

    2008-01-01

    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. PMID:18710880

  7. Signal transduction and amplification through enzyme-triggered ligand release and accelerated catalysis.

    PubMed

    Goggins, Sean; Marsh, Barrie J; Lubben, Anneke T; Frost, Christopher G

    2015-08-01

    Signal transduction and signal amplification are both important mechanisms used within biological signalling pathways. Inspired by this process, we have developed a signal amplification methodology that utilises the selectivity and high activity of enzymes in combination with the robustness and generality of an organometallic catalyst, achieving a hybrid biological and synthetic catalyst cascade. A proligand enzyme substrate was designed to selectively self-immolate in the presence of the enzyme to release a ligand that can bind to a metal pre-catalyst and accelerate the rate of a transfer hydrogenation reaction. Enzyme-triggered catalytic signal amplification was then applied to a range of catalyst substrates demonstrating that signal amplification and signal transduction can both be achieved through this methodology.

  8. Detection and quantitation of HER-2/neu gene amplification in human breast cancer archival material using fluorescence in situ hybridization.

    PubMed

    Pauletti, G; Godolphin, W; Press, M F; Slamon, D J

    1996-07-04

    Amplification and overexpression of the HER-2/neu gene occurs in 25-30% of human breast cancers. This genetic alteration is associated with a poor clinical prognosis in women with either node negative or node positive breast cancers. The initial studies testing this association were somewhat controversial and this controversy was due in large part to significant heterogeneity in both the methods and/or reagents used in testing archival material for the presence of the alteration. These methods included a number of solid matrix blotting techniques for DNA, RNA and protein as well as immunohistochemistry. Fluorescence in situ hybridization (FISH) represents the newest methodologic approach for testing for this genetic alteration. In this study, FISH is compared to Southern, Northern and Western blot analyses as well as immunohistochemistry in a large cohort of archival human breast cancer specimens. FISH was found to be superior to all other methodologies tested in assessing formalin fixed, paraffin embedded material for HER-2/neu amplification. The results from this study also confirm that overexpression of HER-2/neu rarely occurs in the absence of gene amplification in breast cancer (approximately 3% of cases). This method of analysis is rapid, reproducible and extremely reliable in detecting presence of HER-2/neu gene amplification and should have clinical utility.

  9. Microwave gain medium with negative refractive index.

    PubMed

    Ye, Dexin; Chang, Kihun; Ran, Lixin; Xin, Hao

    2014-12-19

    Artificial effective media are attractive because of the fantastic applications they may enable, such as super lensing and electromagnetic invisibility. However, the inevitable loss due to their strongly dispersive nature is one of the fundamental challenges preventing such applications from becoming a reality. In this study, we demonstrate an effective gain medium based on negative resistance, to overcompensate the loss of a conventional passive metamaterial, meanwhile keeping its original negative-index property. Energy conservation-based theory, full-wave simulation and experimental measurement show that a fabricated sample consisting of conventional sub-wavelength building blocks with embedded microwave tunnel diodes exhibits a band-limited Lorentzian dispersion simultaneously with a negative refractive index and a net gain. Our work provides experimental evidence to the assertion that a stable net gain in negative-index gain medium is achievable, proposing a potential solution for the critical challenge current metamateiral technology faces in practical applications.

  10. X chromosome gain is related to increased androgen receptor expression in male breast cancer.

    PubMed

    Di Oto, Enrico; Biserni, Giovanni B; Varga, Zsuzsanna; Morandi, Luca; Cucchi, Maria C; Masetti, Riccardo; Foschini, Maria P

    2018-05-25

    X chromosome gain has been previously described in male breast cancer (MBC). Androgen receptor (AR) gene is located on X chromosome. The aim of this study was to investigate the role of the X chromosome gain in the development of MBC and its relation with AR gene copy number and expression.The X chromosome status was assessed in 66 cases of male invasive and in situ duct breast carcinoma, in 34 cases of gynecomastia associated with cancer, and in 11 cases of tumor-free gynecomastia. Cases were tested by fluorescence in situ hybridization (FISH) to assess the X chromosome status and AR amplification. AR expression was studied by immunohistochemistry (IHC). In addition, AR methylation status was assessed.X chromosome gain was observed in 74.7% of invasive duct carcinoma, in 20.6% of in situ duct carcinoma, and in 14.6% of gynecomastia when associated with cancer, while all cases of tumor-free gynecomastia showed wild X chromosome asset. AR gene copy number when increased paralleled the number of X chromosomes. AR IHC expression was observed in 100% of MBC tested. AR gene methylation status revealed low level or absence of methylation.These data suggest that X chromosome can play a role in the neoplastic transformation of male breast epithelium. X chromosome gain is paralleled by AR gene polysomy. Polysomic AR genes show low methylation levels and high AR protein expression on IHC. These data should be taken into consideration for MBC treatment planning.

  11. Digital Microfluidics for Nucleic Acid Amplification

    PubMed Central

    Veigas, Bruno; Fortunato, Elvira; Martins, Rodrigo; Águas, Hugo; Igreja, Rui; Baptista, Pedro V.

    2017-01-01

    Digital Microfluidics (DMF) has emerged as a disruptive methodology for the control and manipulation of low volume droplets. In DMF, each droplet acts as a single reactor, which allows for extensive multiparallelization of biological and chemical reactions at a much smaller scale. DMF devices open entirely new and promising pathways for multiplex analysis and reaction occurring in a miniaturized format, thus allowing for healthcare decentralization from major laboratories to point-of-care with accurate, robust and inexpensive molecular diagnostics. Here, we shall focus on DMF platforms specifically designed for nucleic acid amplification, which is key for molecular diagnostics of several diseases and conditions, from pathogen identification to cancer mutations detection. Particular attention will be given to the device architecture, materials and nucleic acid amplification applications in validated settings. PMID:28672827

  12. MDM2 and CDK4 amplifications are rare events in salivary duct carcinomas

    PubMed Central

    Grünewald, Inga; Trautmann, Marcel; Busch, Alina; Bauer, Larissa; Huss, Sebastian; Schweinshaupt, Petra; Vollbrecht, Claudia; Odenthal, Margarete; Quaas, Alexander; Büttner, Reinhard; Meyer, Moritz F.; Beutner, Dirk; Hüttenbrink, Karl-Bernd; Wardelmann, Eva; Stenner, Markus; Hartmann, Wolfgang

    2016-01-01

    Salivary duct carcinoma (SDC) is an aggressive adenocarcinoma of the salivary glands associated with poor clinical outcome. SDCs are known to carry TP53 mutations in about 50%, however, only little is known about alternative pathogenic mechanisms within the p53 regulatory network. Particularly, data on alterations of the oncogenes MDM2 and CDK4 located in the chromosomal region 12q13-15 are limited in SDC, while genomic rearrangements of the adjacent HMGA2 gene locus are well documented in subsets of SDCs. We here analyzed the mutational status of the TP53 gene, genomic amplification of MDM2, CDK4 and HMGA2 rearrangement/amplification as well as protein expression of TP53 (p53), MDM2 and CDK4 in 51 de novo and ex pleomorphic adenoma SDCs. 25 of 51 cases were found to carry TP53 mutations, associated with extreme positive immunohistochemical p53 staining levels in 13 cases. Three out of 51 tumors had an MDM2 amplification, one of them coinciding with a CDK4 amplification and two with a HMGA2 rearrangement/amplification. Two of the MDM2 amplifications occurred in the setting of a TP53 mutation. Two out of 51 cases showed a CDK4 amplification, one synchronously being MDM2 amplified and the other one displaying concurrent low copy number increases of both, MDM2 and HMGA2. In summary, we here show that subgroups of SDCs display genomic amplifications of MDM2 and/or CDK4, partly in association with TP53 mutations and rearrangement/amplification of HMGA2. Further research is necessary to clarify the role of chromosomal region 12q13-15 alterations in SDC tumorigenesis and their potential prognostic and therapeutic relevance. PMID:27662657

  13. MDM2 and CDK4 amplifications are rare events in salivary duct carcinomas.

    PubMed

    Grünewald, Inga; Trautmann, Marcel; Busch, Alina; Bauer, Larissa; Huss, Sebastian; Schweinshaupt, Petra; Vollbrecht, Claudia; Odenthal, Margarete; Quaas, Alexander; Büttner, Reinhard; Meyer, Moritz F; Beutner, Dirk; Hüttenbrink, Karl-Bernd; Wardelmann, Eva; Stenner, Markus; Hartmann, Wolfgang

    2016-11-15

    Salivary duct carcinoma (SDC) is an aggressive adenocarcinoma of the salivary glands associated with poor clinical outcome. SDCs are known to carry TP53 mutations in about 50%, however, only little is known about alternative pathogenic mechanisms within the p53 regulatory network. Particularly, data on alterations of the oncogenes MDM2 and CDK4 located in the chromosomal region 12q13-15 are limited in SDC, while genomic rearrangements of the adjacent HMGA2 gene locus are well documented in subsets of SDCs. We here analyzed the mutational status of the TP53 gene, genomic amplification of MDM2, CDK4 and HMGA2 rearrangement/amplification as well as protein expression of TP53 (p53), MDM2 and CDK4 in 51 de novo and ex pleomorphic adenoma SDCs.25 of 51 cases were found to carry TP53 mutations, associated with extreme positive immunohistochemical p53 staining levels in 13 cases. Three out of 51 tumors had an MDM2 amplification, one of them coinciding with a CDK4 amplification and two with a HMGA2 rearrangement/amplification. Two of the MDM2 amplifications occurred in the setting of a TP53 mutation. Two out of 51 cases showed a CDK4 amplification, one synchronously being MDM2 amplified and the other one displaying concurrent low copy number increases of both, MDM2 and HMGA2.In summary, we here show that subgroups of SDCs display genomic amplifications of MDM2 and/or CDK4, partly in association with TP53 mutations and rearrangement/amplification of HMGA2. Further research is necessary to clarify the role of chromosomal region 12q13-15 alterations in SDC tumorigenesis and their potential prognostic and therapeutic relevance.

  14. Real-time electrochemical monitoring of isothermal helicase-dependent amplification of nucleic acids.

    PubMed

    Kivlehan, Francine; Mavré, François; Talini, Luc; Limoges, Benoît; Marchal, Damien

    2011-09-21

    We described an electrochemical method to monitor in real-time the isothermal helicase-dependent amplification of nucleic acids. The principle of detection is simple and well-adapted to the development of portable, easy-to-use and inexpensive nucleic acids detection technologies. It consists of monitoring a decrease in the electrochemical current response of a reporter DNA intercalating redox probe during the isothermal DNA amplification. The method offers the possibility to quantitatively analyze target nucleic acids in less than one hour at a single constant temperature, and to perform at the end of the isothermal amplification a DNA melt curve analysis for differentiating between specific and non-specific amplifications. To illustrate the potentialities of this approach for the development of a simple, robust and low-cost instrument with high throughput capability, the method was validated with an electrochemical system capable of monitoring up to 48 real-time isothermal HDA reactions simultaneously in a disposable microplate consisting of 48-electrochemical microwells. Results obtained with this approach are comparable to that obtained with a well-established but more sophisticated and expensive fluorescence-based method. This makes for a promising alternative detection method not only for real-time isothermal helicase-dependent amplification of nucleic acid, but also for other isothermal DNA amplification strategies.

  15. Genome-wide single-nucleotide polymorphism arrays demonstrate high fidelity of multiple displacement-based whole-genome amplification.

    PubMed

    Tzvetkov, Mladen V; Becker, Christian; Kulle, Bettina; Nürnberg, Peter; Brockmöller, Jürgen; Wojnowski, Leszek

    2005-02-01

    Whole-genome DNA amplification by multiple displacement (MD-WGA) is a promising tool to obtain sufficient DNA amounts from samples of limited quantity. Using Affymetrix' GeneChip Human Mapping 10K Arrays, we investigated the accuracy and allele amplification bias in DNA samples subjected to MD-WGA. We observed an excellent concordance (99.95%) between single-nucleotide polymorphisms (SNPs) called both in the nonamplified and the corresponding amplified DNA. This concordance was only 0.01% lower than the intra-assay reproducibility of the genotyping technique used. However, MD-WGA failed to amplify an estimated 7% of polymorphic loci. Due to the algorithm used to call genotypes, this was detected only for heterozygous loci. We achieved a 4.3-fold reduction of noncalled SNPs by combining the results from two independent MD-WGA reactions. This indicated that inter-reaction variations rather than specific chromosomal loci reduced the efficiency of MD-WGA. Consistently, we detected no regions of reduced amplification, with the exception of several SNPs located near chromosomal ends. Altogether, despite a substantial loss of polymorphic sites, MD-WGA appears to be the current method of choice to amplify genomic DNA for array-based SNP analyses. The number of nonamplified loci can be substantially reduced by amplifying each DNA sample in duplicate.

  16. E2F Activators Signal and Maintain Centrosome Amplification in Breast Cancer Cells

    PubMed Central

    Lee, Mi-Young; Moreno, Carlos S.

    2014-01-01

    Centrosomes ensure accurate chromosome segregation by directing spindle bipolarity. Loss of centrosome regulation results in centrosome amplification, multipolar mitosis and aneuploidy. Since centrosome amplification is common in premalignant lesions and breast tumors, it is proposed to play a central role in breast tumorigenesis, a hypothesis that remains to be tested. The coordination between the cell and centrosome cycles is of paramount importance to maintain normal centrosome numbers, and the E2Fs may be responsible for regulating these cycles. However, the role of E2F activators in centrosome amplification is unclear. Because E2Fs are deregulated in Her2+ cells displaying centrosome amplification, we addressed whether they signal this abnormal process. Knockdown of E2F1 or E2F3 in Her2+ cells decreased centrosome amplification without significantly affecting cell cycle progression, whereas the overexpression of E2F1, E2F2, or E2F3 increased centrosome amplification in MCF10A mammary epithelial cells. Our results revealed that E2Fs affect the expression of proteins, including Nek2 and Plk4, known to influence the cell/centrosome cycles and mitosis. Downregulation of E2F3 resulted in cell death and delays/blocks in cytokinesis, which was reversed by Nek2 overexpression. Nek2 overexpression enhanced centrosome amplification in Her2+ breast cancer cells silenced for E2F3, revealing a role for the E2F activators in maintaining centrosome amplification in part through Nek2. PMID:24797070

  17. E2F activators signal and maintain centrosome amplification in breast cancer cells.

    PubMed

    Lee, Mi-Young; Moreno, Carlos S; Saavedra, Harold I

    2014-07-01

    Centrosomes ensure accurate chromosome segregation by directing spindle bipolarity. Loss of centrosome regulation results in centrosome amplification, multipolar mitosis and aneuploidy. Since centrosome amplification is common in premalignant lesions and breast tumors, it is proposed to play a central role in breast tumorigenesis, a hypothesis that remains to be tested. The coordination between the cell and centrosome cycles is of paramount importance to maintain normal centrosome numbers, and the E2Fs may be responsible for regulating these cycles. However, the role of E2F activators in centrosome amplification is unclear. Because E2Fs are deregulated in Her2(+) cells displaying centrosome amplification, we addressed whether they signal this abnormal process. Knockdown of E2F1 or E2F3 in Her2(+) cells decreased centrosome amplification without significantly affecting cell cycle progression, whereas the overexpression of E2F1, E2F2, or E2F3 increased centrosome amplification in MCF10A mammary epithelial cells. Our results revealed that E2Fs affect the expression of proteins, including Nek2 and Plk4, known to influence the cell/centrosome cycles and mitosis. Downregulation of E2F3 resulted in cell death and delays/blocks in cytokinesis, which was reversed by Nek2 overexpression. Nek2 overexpression enhanced centrosome amplification in Her2(+) breast cancer cells silenced for E2F3, revealing a role for the E2F activators in maintaining centrosome amplification in part through Nek2.

  18. On the saturation of stimulated Raman scattering in laser amplification

    NASA Astrophysics Data System (ADS)

    Dodd, E. S.; Ren, J.; Kwan, T. J. T.; Schmitt, M. J.

    2012-10-01

    The use of stimulated Raman scattering (SRS) in plasmas has been proposed as an alternative to the CPA technique for laser pulse amplification and compression [1]. Initial experiments demonstrated the amplification and compression of laser pulses in plasma to an unfocused intensity of ˜10^16 W/cm^2 [2], however the amplification was saturated at this level and was accompanied by deleterious spatial and temporal incoherence. The reasons for this incoherence have not been well understood. A physical picture has been developed with results from PIC simulations using the LSP code where spontaneous SRS in the pump modifies the plasma conditions, and which in turn significantly weakens the coupling strength for seed amplification. This led to the development of a novel experimental method to significantly increase the amplified power in the short-pulses via SRS.[4pt] [1] G. Shvets, N. J. Fisch, A. Pukhov, and J. Meyer-ter-Vehn, Phys. Rev. Lett. 81 4879 (1998).[0pt] [2] J. Ren, W.-F. Cheng, S.-L Li, and S. Suckewer, Nat. Phys. 3 732 (2007). LA-UR-12-22734

  19. Bacteriophage Amplification-Coupled Detection and Identification of Bacterial Pathogens

    NASA Astrophysics Data System (ADS)

    Cox, Christopher R.; Voorhees, Kent J.

    Current methods of species-specific bacterial detection and identification are complex, time-consuming, and often require expensive specialized equipment and highly trained personnel. Numerous biochemical and genotypic identification methods have been applied to bacterial characterization, but all rely on tedious microbiological culturing practices and/or costly sequencing protocols which render them impractical for deployment as rapid, cost-effective point-of-care or field detection and identification methods. With a view towards addressing these shortcomings, we have exploited the evolutionarily conserved interactions between a bacteriophage (phage) and its bacterial host to develop species-specific detection methods. Phage amplification-coupled matrix assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF-MS) was utilized to rapidly detect phage propagation resulting from species-specific in vitro bacterial infection. This novel signal amplification method allowed for bacterial detection and identification in as little as 2 h, and when combined with disulfide bond reduction methods developed in our laboratory to enhance MALDI-TOF-MS resolution, was observed to lower the limit of detection by several orders of magnitude over conventional spectroscopy and phage typing methods. Phage amplification has been combined with lateral flow immunochromatography (LFI) to develop rapid, easy-to-operate, portable, species-specific point-of-care (POC) detection devices. Prototype LFI detectors have been developed and characterized for Yersinia pestis and Bacillus anthracis, the etiologic agents of plague and anthrax, respectively. Comparable sensitivity and rapidity was observed when phage amplification was adapted to a species-specific handheld LFI detector, thus allowing for rapid, simple, POC bacterial detection and identification while eliminating the need for bacterial culturing or DNA isolation and amplification techniques.

  20. Association between somatic amplification, anxiety, depression, stress and migraine

    PubMed Central

    2013-01-01

    Background The aim of this study is to investigate the associations between migraine related disability and somatosensory amplification, depression, anxiety, and stress. Method Fifty-five migraine patients who applied to the outpatient unit of the Neurology Department of Acibadem University School of Medicine, Maslak Hospital in Istanbul, Turkey, and twenty-eight subjects without migraine were recruited for the study. The participants were asked to complete a sociodemographic form, Migraine Disability Assessment Scale (MIDAS), Depression Anxiety Stress Scale, Somatosensory Amplification Scale (SSAS). Results Somatosensory amplification scores were significantly higher in the migraineurs than in the control group (29.85+/−6.63 vs 26.07+/−7.1; p=0.027). Somatosensory amplification scores and depression scores were significantly higher in migraineurs with moderate and severe disability than in patients with minimal and mild disability (31.7+/−6.4 vs 27.71+/−5.49; p=0.01, 11.27+/−8.7 vs 7.38+/−8.11; p=0.04, respectively). A significant positive correlation was found between the frequency of migraine attacks for at least three consecutive months (MIDAS A scores) and the SSAS scores (r=0.363, p=0.007) in migraineurs. The MIDAS total scores were also significantly correlated with the DASS depression subcale scores (r=0.267, p=0.04), and the DASS stress subscale scores (r=0.268, p=0.05). Conclusion Psychological factors, and vulnerability to bodily sensations may incease the burden of migraine. We point out that the timely assessing of somatic amplification and the evaluation of mental status would help improve the quality of life of in migraineurs. PMID:23799958

  1. Single-molecule dilution and multiple displacement amplification for molecular haplotyping.

    PubMed

    Paul, Philip; Apgar, Josh

    2005-04-01

    Separate haploid analysis is frequently required for heterozygous genotyping to resolve phase ambiguity or confirm allelic sequence. We demonstrate a technique of single-molecule dilution followed by multiple strand displacement amplification to haplotype polymorphic alleles. Dilution of DNA to haploid equivalency, or a single molecule, is a simple method for separating di-allelic DNA. Strand displacement amplification is a robust method for non-specific DNA expansion that employs random hexamers and phage polymerase Phi29 for double-stranded DNA displacement and primer extension, resulting in high processivity and exceptional product length. Single-molecule dilution was followed by strand displacement amplification to expand separated alleles to microgram quantities of DNA for more efficient haplotype analysis of heterozygous genes.

  2. The G1 phase Cdks regulate the centrosome cycle and mediate oncogene-dependent centrosome amplification

    PubMed Central

    2011-01-01

    Because centrosome amplification generates aneuploidy and since centrosome amplification is ubiquitous in human tumors, a strong case is made for centrosome amplification being a major force in tumor biogenesis. Various evidence showing that oncogenes and altered tumor suppressors lead to centrosome amplification and aneuploidy suggests that oncogenes and altered tumor suppressors are a major source of genomic instability in tumors, and that they generate those abnormal processes to initiate and sustain tumorigenesis. We discuss how altered tumor suppressors and oncogenes utilize the cell cycle regulatory machinery to signal centrosome amplification and aneuploidy. PMID:21272329

  3. Reversible Gating of Plasmonic Coupling for Optical Signal Amplification.

    PubMed

    Khoury, Christopher G; Fales, Andrew M; Vo-Dinh, Tuan

    2016-07-20

    Amplification of optical signals is useful for a wide variety of applications, ranging from data signal transmission to chemical sensing and biomedical diagnostics. One such application in chemical sensing is surface-enhanced Raman scattering (SERS), an important technique for increasing the Raman signal using the plasmonic effect of enhanced electromagnetic fields associated with metallic nanostructures. One of the most important limitations of SERS-based amplification is the difficulty to reproducibly control the SERS signal. Here, we describe the design and implementation of a unique hybrid system capable of producing reversible gating of plasmonic coupling for Raman signal amplification. The hybrid system is composed of two subsystems: (1) colloidal magneto-plasmonic nanoparticles for SERS enhancement and (2) a micromagnet substrate with an externally applied magnetic field to modulate the colloidal nanoparticles. For this proof of concept demonstration, the nanoparticles were labeled with a Raman-active dye, and it was shown that the detected SERS signal could be reproducibly modulated by controlling the externally applied magnetic field. The developed system provides a simple, robust, inexpensive, and reusable device for SERS signal modulation. These properties will open up new possibilities for optical signal amplification and gating as well for high-throughput, reproducible SERS detection.

  4. Optical gain at 650 nm from a polymer waveguide with dye-doped cladding

    NASA Astrophysics Data System (ADS)

    Reilly, M. A.; Coleman, B.; Pun, E. Y. B.; Penty, R. V.; White, I. H.; Ramon, M.; Xia, R.; Bradley, D. D. C.

    2005-12-01

    Signal amplification at the polymer optical fiber low-loss window of 650 nm is reported in an SU8 rib waveguide coated with Rhodamine-640 doped poly(methyl methacrylate). A signal beam is end-fired into the facet of a 7×100μm waveguide and amplified by top pumping of the 2-μm-thick cladding region with a pulsed pump source focused into a 9-mm-long stripe. A gain of 14dB and a minimum signal-to-noise ratio of around 2 dB are achieved in a 15-mm-long device with a low threshold pump intensity of 0.25μJ/mm2, which is an order of magnitude lower than previously reported.

  5. Efficient design of gain-flattened multi-pump Raman fiber amplifiers using least squares support vector regression

    NASA Astrophysics Data System (ADS)

    Chen, Jing; Qiu, Xiaojie; Yin, Cunyi; Jiang, Hao

    2018-02-01

    An efficient method to design the broadband gain-flattened Raman fiber amplifier with multiple pumps is proposed based on least squares support vector regression (LS-SVR). A multi-input multi-output LS-SVR model is introduced to replace the complicated solving process of the nonlinear coupled Raman amplification equation. The proposed approach contains two stages: offline training stage and online optimization stage. During the offline stage, the LS-SVR model is trained. Owing to the good generalization capability of LS-SVR, the net gain spectrum can be directly and accurately obtained when inputting any combination of the pump wavelength and power to the well-trained model. During the online stage, we incorporate the LS-SVR model into the particle swarm optimization algorithm to find the optimal pump configuration. The design results demonstrate that the proposed method greatly shortens the computation time and enhances the efficiency of the pump parameter optimization for Raman fiber amplifier design.

  6. Construction Strategy for an Internal Amplification Control for Real-Time Diagnostic Assays Using Nucleic Acid Sequence-Based Amplification: Development and Clinical Application

    PubMed Central

    Rodríguez-Lázaro, David; D'Agostino, Martin; Pla, Maria; Cook, Nigel

    2004-01-01

    An important analytical control in molecular amplification-based methods is an internal amplification control (IAC), which should be included in each reaction mixture. An IAC is a nontarget nucleic acid sequence which is coamplified simultaneously with the target sequence. With negative results for the target nucleic acid, the absence of an IAC signal indicates that amplification has failed. A general strategy for the construction of an IAC for inclusion in molecular beacon-based real-time nucleic acid sequence-based amplification (NASBA) assays is presented. Construction proceeds in two phases. In the first phase, a double-stranded DNA molecule that contains nontarget sequences flanked by target sequences complementary to the NASBA primers is produced. At the 5′ end of this DNA molecule is a T7 RNA polymerase binding sequence. In the second phase of construction, RNA transcripts are produced from the DNA by T7 RNA polymerase. This RNA is the IAC; it is amplified by the target NASBA primers and is detected by a molecular beacon probe complementary to the internal nontarget sequences. As a practical example, an IAC for use in an assay for the detection of Mycobacterium avium subsp. paratuberculosis is described, its incorporation and optimization within the assay are detailed, and its application to spiked and natural clinical samples is shown to illustrate the correct interpretation of the diagnostic results. PMID:15583319

  7. Optimizing direct amplification of forensic commercial kits for STR determination.

    PubMed

    Caputo, M; Bobillo, M C; Sala, A; Corach, D

    2017-04-01

    Direct DNA amplification in forensic genotyping reduces analytical time when large sample sets are being analyzed. The amplification success depends mainly upon two factors: on one hand, the PCR chemistry and, on the other, the type of solid substrate where the samples are deposited. We developed a workflow strategy aiming to optimize times and cost when starting from blood samples spotted onto diverse absorbent substrates. A set of 770 blood samples spotted onto Blood cards, Whatman ® 3 MM paper, FTA™ Classic cards, and Whatman ® Grade 1 was analyzed by a unified working strategy including a low-cost pre-treatment, a PCR amplification volume scale-down, and the use of the 3500 Genetic Analyzer as the analytical platform. Samples were analyzed using three different commercial multiplex STR direct amplification kits. The efficiency of the strategy was evidenced by a higher percentage of high-quality profiles obtained (over 94%), a reduced number of re-injections (average 3.2%), and a reduced amplification failure rate (lower than 5%). Average peak height ratio among different commercial kits was 0.91, and the intra-locus balance showed values ranging from 0.92 to 0.94. A comparison with previously reported results was performed demonstrating the efficiency of the proposed modifications. The protocol described herein showed high performance, producing optimal quality profiles, and being both time and cost effective. Copyright © 2017 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

  8. Design of Silicon Photonic Crystal Waveguides for High Gain Raman Amplification Using Two Symmetric Transvers-Electric-Like Slow-Light Modes

    NASA Astrophysics Data System (ADS)

    Hsiao, Yi-Hua; Iwamoto, Satoshi; Arakawa, Yasuhiko

    2013-04-01

    We designed silicon photonic crystal (PhC) waveguides (WGs) for efficient silicon Raman amplifiers and lasers. We adopted narrow-width WGs to utilize two symmetric transvers-electric-like (TE-like) guided modes, which permit efficient external coupling for both the pump and Stokes waves. Modifying the size and shape of air holes surrounding the line-defect WG structures could tune the frequency difference between these two modes, at the Brillouin-zone edge, to match the Raman shift of silicon. Thus, small group velocities are also available both for pump and Stokes waves simultaneously, which results in a large enhancement of Raman gain. The enhancement factor of the Raman gain in the designed structure is more than 100 times that reported previously.

  9. Anisotropic amplification of proton transport in proton exchange membrane fuel cells

    NASA Astrophysics Data System (ADS)

    Thimmappa, Ravikumar; Fawaz, Mohammed; Devendrachari, Mruthyunjayachari Chattanahalli; Gautam, Manu; Kottaichamy, Alagar Raja; Shafi, Shahid Pottachola; Thotiyl, Musthafa Ottakam

    2017-07-01

    Though graphene oxide (GO) membrane shuttles protons under humid conditions, it suffer severe disintegration and anhydrous conditions lead to abysmal ionic conductivity. The trade-off between mechanical integrity and ionic conductivity challenge the amplification of GO's ionic transport under anhydrous conditions. We show anisotropic amplification of GO's ionic transport with a selective amplification of in plane contribution under anhydrous conditions by doping it with a plant extract, phytic acid (PA). The hygroscopic nature of PA stabilized interlayer water molecules and peculiar geometry of sbnd OH functionalities around saturated hydrocarbon ring anisotropically enhanced ionic transport amplifying the fuel cell performance metrics.

  10. Divided-pulse nonlinear amplification and simultaneous compression

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hao, Qiang; Zhang, Qingshan; Sun, Tingting

    2015-03-09

    We report on a fiber laser system delivering 122 fs pulse duration and 600 mW average power at 1560 nm by the interplay between divided pulse amplification and nonlinear pulse compression. A small-core double-clad erbium-doped fiber with anomalous dispersion carries out the pulse amplification and simultaneously compresses the laser pulses such that a separate compressor is no longer necessary. A numeric simulation reveals the existence of an optimum fiber length for producing transform-limited pulses. Furthermore, frequency doubling to 780 nm with 240 mW average power and 98 fs pulse duration is achieved by using a periodically poled lithium niobate crystal at roommore » temperature.« less

  11. Rolling-circle amplification under topological constraints

    PubMed Central

    Kuhn, Heiko; Demidov, Vadim V.; Frank-Kamenetskii, Maxim D.

    2002-01-01

    We have performed rolling-circle amplification (RCA) reactions on three DNA templates that differ distinctly in their topology: an unlinked DNA circle, a linked DNA circle within a pseudorotaxane-type structure and a linked DNA circle within a catenane. In the linked templates, the single-stranded circle (dubbed earring probe) is threaded, with the aid of two peptide nucleic acid openers, between the two strands of double-stranded DNA (dsDNA). We have found that the RCA efficiency of amplification was essentially unaffected when the linked templates were employed. By showing that the DNA catenane remains intact after RCA reactions, we prove that certain DNA polymerases can carry out the replicative synthesis under topological constraints allowing detection of several hundred copies of a dsDNA marker without DNA denaturation. Our finding may have practical implications in the area of DNA diagnostics. PMID:11788721

  12. Reducing gain shifts in photomultiplier tubes

    DOEpatents

    Cohn, Charles E.

    1976-01-01

    A means is provided for reducing gain shifts in multiplier tubes due to varying event count rates. It includes means for limiting the number of cascaded, active dynodes of the multiplier tube to a predetermined number with the last of predetermined number of dynodes being the output terminal of the tube. This output is applied to an amplifier to make up for the gain sacrificed by not totally utilizing all available active stages of the tube. Further reduction is obtained by illuminating the predetermined number of dynodes with a light source of such intensity that noise appearing at the output dynode associated with the illumination is negligible.

  13. Estrogen receptor alpha gene amplification in breast cancer: 25 years of debate

    PubMed Central

    Holst, Frederik

    2016-01-01

    Twenty-five years ago, Nembrot and colleagues reported amplification of the estrogen receptor alpha gene (ESR1) in breast cancer, initiating a broad and still ongoing scientific debate on the prevalence and clinical significance of this genetic aberration, which affects one of the most important genes in breast cancer. Since then, a multitude of studies on this topic has been published, covering a wide range of divergent results and arguments. The reported prevalence of this alteration in breast cancer ranges from 0% to 75%, suggesting that ESR1 copy number analysis is hampered by technical and interpreter issues. To date, two major issues related to ESR1 amplification remain to be conclusively addressed: (1) The extent to which abundant amounts of messenger RNA can mimic amplification in standard fluorescence in situ hybridization assays in the analysis of strongly expressed genes like ESR1, and (2) the clinical relevance of ESR1 amplification: Such relevance is strongly disputed, with data showing predictive value for response as well as for resistance of the cancer to anti-estrogen therapies, or for subsequent development of cancers in the case of precursor lesions that display amplification of ESR1. This review provides a comprehensive summary of the various views on ESR1 amplification, and highlights explanations for the contradictions and conflicting data that could inform future ESR1 research. PMID:27081639

  14. Targeting helicase-dependent amplification products with an electrochemical genosensor for reliable and sensitive screening of genetically modified organisms.

    PubMed

    Moura-Melo, Suely; Miranda-Castro, Rebeca; de-Los-Santos-Álvarez, Noemí; Miranda-Ordieres, Arturo J; Dos Santos Junior, J Ribeiro; da Silva Fonseca, Rosana A; Lobo-Castañón, Maria Jesús

    2015-08-18

    Cultivation of genetically modified organisms (GMOs) and their use in food and feed is constantly expanding; thus, the question of informing consumers about their presence in food has proven of significant interest. The development of sensitive, rapid, robust, and reliable methods for the detection of GMOs is crucial for proper food labeling. In response, we have experimentally characterized the helicase-dependent isothermal amplification (HDA) and sequence-specific detection of a transgene from the Cauliflower Mosaic Virus 35S Promoter (CaMV35S), inserted into most transgenic plants. HDA is one of the simplest approaches for DNA amplification, emulating the bacterial replication machinery, and resembling PCR but under isothermal conditions. However, it usually suffers from a lack of selectivity, which is due to the accumulation of spurious amplification products. To improve the selectivity of HDA, which makes the detection of amplification products more reliable, we have developed an electrochemical platform targeting the central sequence of HDA copies of the transgene. A binary monolayer architecture is built onto a thin gold film where, upon the formation of perfect nucleic acid duplexes with the amplification products, these are enzyme-labeled and electrochemically transduced. The resulting combined system increases genosensor detectability up to 10(6)-fold, allowing Yes/No detection of GMOs with a limit of detection of ∼30 copies of the CaMV35S genomic DNA. A set of general utility rules in the design of genosensors for detection of HDA amplicons, which may assist in the development of point-of-care tests, is also included. The method provides a versatile tool for detecting nucleic acids with extremely low abundance not only for food safety control but also in the diagnostics and environmental control areas.

  15. Improved multiple displacement amplification (iMDA) and ultraclean reagents.

    PubMed

    Motley, S Timothy; Picuri, John M; Crowder, Chris D; Minich, Jeremiah J; Hofstadler, Steven A; Eshoo, Mark W

    2014-06-06

    Next-generation sequencing sample preparation requires nanogram to microgram quantities of DNA; however, many relevant samples are comprised of only a few cells. Genomic analysis of these samples requires a whole genome amplification method that is unbiased and free of exogenous DNA contamination. To address these challenges we have developed protocols for the production of DNA-free consumables including reagents and have improved upon multiple displacement amplification (iMDA). A specialized ethylene oxide treatment was developed that renders free DNA and DNA present within Gram positive bacterial cells undetectable by qPCR. To reduce DNA contamination in amplification reagents, a combination of ion exchange chromatography, filtration, and lot testing protocols were developed. Our multiple displacement amplification protocol employs a second strand-displacing DNA polymerase, improved buffers, improved reaction conditions and DNA free reagents. The iMDA protocol, when used in combination with DNA-free laboratory consumables and reagents, significantly improved efficiency and accuracy of amplification and sequencing of specimens with moderate to low levels of DNA. The sensitivity and specificity of sequencing of amplified DNA prepared using iMDA was compared to that of DNA obtained with two commercial whole genome amplification kits using 10 fg (~1-2 bacterial cells worth) of bacterial genomic DNA as a template. Analysis showed >99% of the iMDA reads mapped to the template organism whereas only 0.02% of the reads from the commercial kits mapped to the template. To assess the ability of iMDA to achieve balanced genomic coverage, a non-stochastic amount of bacterial genomic DNA (1 pg) was amplified and sequenced, and data obtained were compared to sequencing data obtained directly from genomic DNA. The iMDA DNA and genomic DNA sequencing had comparable coverage 99.98% of the reference genome at ≥1X coverage and 99.9% at ≥5X coverage while maintaining both balance

  16. Is Polar Amplification Deeper and Stronger than Dynamicists Assume?

    NASA Astrophysics Data System (ADS)

    Scheff, J.; Maroon, E.

    2017-12-01

    In the CMIP multi-model mean under strong future warming, Arctic amplification is confined to the lower troposphere, so that the meridional gradient of warming reverses around 500 mb and the upper troposphere is characterized by strong "tropical amplification" in which warming weakens with increasing latitude. This model-derived pattern of warming maxima in the upper-level tropics and lower-level Arctic has become a canonical assumption driving theories of the large-scale circulation response to climate change. Yet, several lines of evidence and reasoning suggest that Arctic amplification may in fact extend through the entire depth of the troposphere, and/or may be stronger than commonly modeled. These include satellite Microwave Sounding Unit (MSU) temperature trends as a function of latitude and vertical level, the recent discovery that the extratropical negative cloud phase feedback in models is largely spurious, and the very strong polar amplification observed in past warm and lukewarm climates. Such a warming pattern, with deep, dominant Arctic amplification, would have very different implications for the circulation than a canonical CMIP-like warming: instead of slightly shifting poleward and strengthening, eddies, jets and cells might shift equatorward and considerably weaken. Indeed, surface winds have been mysteriously weakening ("stilling") at almost all stations over the last half-century or so, there has been no poleward shift in northern hemisphere circulation metrics, and past warm climates' subtropics were apparently quite wet (and their global ocean circulations were weak.) To explore these possibilities more deeply, we examine the y-z structure of warming and circulation changes across a much broader range of models, scenarios and time periods than the CMIP future mean, and use an MSU simulator to compare them to the satellite warming record. Specifically, we examine whether the use of historical (rather than future) forcing, AMIP (rather than CMIP

  17. Sources of Uncertainty in Modelling mid-Pliocene Arctic Amplification

    NASA Astrophysics Data System (ADS)

    Dolan, A. M.; Haywood, A.; Howell, F.; Prescott, C.; Pope, J. O.; Hill, D. J.; Voss, J.

    2016-12-01

    The mid-Pliocene Warm Period (mPWP) is an interval between 3.264 and 3.205 million years ago, which has globally warmer temperatures (Haywood et al., 2013) accompanied by levels of CO2 above pre-Industrial ( 400 ppmv; e.g. Bartoli et al. 2011; Badger et al., 2013). Arctic amplification of temperatures is a major characteristic of all proxy-based reconstructions of the mPWP in terms of both oceanic (Dowsett et al., 2010) and land warming (Salzmann et al., 2013). For example, evidence of fossilised forests in the Canadian high-Arctic show summer temperatures of up to 16°C warmer than present (Csank et al., 2010). Also, summer temperatures estimates based on pollen reconstructions at Lake El'gygytgyn in North East Russia are up to 6°C warmer than present day (Brigham-Grette et al., 2013). Nevertheless, results from the first phase of the Pliocene Model Intercomparison Project (PlioMIP) suggest that climate models may underestimate the degree of Arctic amplification suggested by proxy records (Haywood et al., 2013). Here we use a large ensemble of experiments performed with the HadCM3 climate model to explore relative sources of uncertainty in the simulations of Arctic amplification. Within this suite of over 150 simulations, we consider; (i) a range of mPWP-specific orbital configurations to quantify the influence of temporal variability, (ii) a range of CO2 scenarios to take into account uncertainties in this particular greenhouse gas forcing, (iii) a perturbed physics ensemble to investigate parametric uncertainty within the HadCM3 climate model, and also (iv) a number of experiments with altered palaeogeographies (including changes to topography and ice sheets) to assess the impact of different boundary condition realisations on our simulation of Arctic amplification. We also incorporate results from the PlioMIP project to allude to the effect of structural uncertainty on Arctic warming. Following methods used in Yoshimori et al. (2013) and Laine et al. (2016

  18. [Individual Identification of Cartilage by Direct Amplification in Mass Disasters].

    PubMed

    Wang, C H; Xu, C; Li, X Q; Wu, Y; Du, Z

    2017-06-01

    To explore the effectiveness of direct amplification for the STR analysis of cartilage, and to accelerate the effectiveness of disaster victim identification. Eighty-eight cartilage samples were directly amplified by PowerPle® 21 kit, and the results of genotyping were compared with that obtained by the magnetic beads method. In 88 cartilage samples, the STR genotypes were successfully detected from 84 samples by direct amplification and magnetic beads method, and both the results of genotyping by two method were consistent. Direct amplification with PowerPlex® 21 kit can be used for STR genotyping of cartilages. This method is operated easily and promptly, which has a potential application in the individual identification of mass disasters. Copyright© by the Editorial Department of Journal of Forensic Medicine

  19. Evaluation of Direct PCR Amplification Using Various Swabs and Washing Reagents.

    PubMed

    Altshuler, Hallie; Roy, Reena

    2015-11-01

    DNA profiles were generated via direct amplification from blood and saliva samples deposited on various types of swab substrates. Each of the six non-FTA substrates used in this research was punched with a Harris 1.2 mm puncher. After 0.1 μL of blood or 0.5 μL saliva, samples were deposited on each of these punches, samples were pretreated with one of four buffers and washing reagents. Amplification was performed using direct and nondirect autosomal and Y-STR kits. Autosomal and Y-STR profiles were successfully generated from most of these substrates when pretreated with buffer or washing reagents. Concordant profiles were obtained within and between the six substrates, the six amplification kits, and all four reagents. The direct amplification of substrates which do not contain lysing agent would be beneficial to the forensic community as the procedure can be used on evidence samples commonly found at crime scenes. © 2015 American Academy of Forensic Sciences.

  20. Amplification without instability: applying fluid dynamical insights in chemistry and biology

    NASA Astrophysics Data System (ADS)

    McCoy, Jonathan H.

    2013-11-01

    While amplification of small perturbations often arises from instability, transient amplification is possible locally even in asymptotically stable systems. That is, knowledge of a system's stability properties can mislead one's intuition for its transient behaviors. This insight, which has an interesting history in fluid dynamics, has more recently been rediscovered in ecology. Surprisingly, many nonlinear fluid dynamical and ecological systems share linear features associated with transient amplification of noise. This paper aims to establish that these features are widespread in many other disciplines concerned with noisy systems, especially chemistry, cell biology and molecular biology. Here, using classic nonlinear systems and the graphical language of network science, we explore how the noise amplification problem can be reframed in terms of activatory and inhibitory interactions between dynamical variables. The interaction patterns considered here are found in a great variety of systems, ranging from autocatalytic reactions and activator-inhibitor systems to influential models of nerve conduction, glycolysis, cell signaling and circadian rhythms.

  1. Nanoliter reactors improve multiple displacement amplification of genomes from single cells.

    PubMed

    Marcy, Yann; Ishoey, Thomas; Lasken, Roger S; Stockwell, Timothy B; Walenz, Brian P; Halpern, Aaron L; Beeson, Karen Y; Goldberg, Susanne M D; Quake, Stephen R

    2007-09-01

    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.

  2. Adsorption-induced auto-amplification of enantiomeric excess on an achiral surface

    NASA Astrophysics Data System (ADS)

    Yun, Yongju; Gellman, Andrew J.

    2015-06-01

    The homochirality of biomolecules is a signature of life on Earth and has significant implications in, for example, the production of pharmaceutical compounds. It has been suggested that biomolecular homochirality may have arisen from the amplification of a spontaneously formed small enantiomeric excess (e.e.). Many minerals exhibit naturally chiral surfaces and so adsorption has been proposed as one possible mechanism for such an amplification of e.e. Here we show that when gas-phase mixtures of D- and L-aspartic acid are exposed to an achiral Cu(111) surface, a small e.e. in the gas phase, e.e.g, leads to an amplification of the e.e. on the surface, e.e.s, under equilibrium conditions. Adsorption-induced amplification of e.e. does not require a chiral surface. The dependence of e.e.s on e.e.g has been modelled successfully using a Langmuir-like adsorption isotherm that incorporates the formation of homochiral adsorbate clusters on the surface.

  3. Determining generic velocity and density models for crustal amplification calculations, with an update of the Boore and Joyner (1997) Generic Site Amplification for Graphic Site Amplification

    USGS Publications Warehouse

    Boore, David

    2016-01-01

    This short note contains two contributions related to deriving depth‐dependent velocity and density models for use in computing generic crustal amplifications. The first contribution is a method for interpolating two velocity profiles to obtain a third profile with a time‐averaged velocity  to depth Z that is equal to a specified value (e.g., for shear‐wave velocity VS,  for Z=30  m, in which the subscript S has been added to indicate that the average is for shear‐wave velocities). The second contribution is a procedure for obtaining densities from VS. The first contribution is used to extend and revise the Boore and Joyner (1997) generic rock VS model, for which , to a model with the more common . This new model is then used with the densities from the second contribution to compute crustal amplifications for a generic site with .

  4. Laser amplification of incoherent radiation

    NASA Technical Reports Server (NTRS)

    Menegozzi, L. N.; Lamb, W. E., Jr.

    1978-01-01

    The amplification of noise in a laser amplifier is treated theoretically. The model for the active medium and its description using density-matrix techniques, are taken from the theory of laser operation. The spectral behavior of the radiation in the nonlinear regime is studied and the formalism is written from the onset in the frequency domain. The statistics of the light are gradually modified by the nonlinear amplification process, and expressions are derived for the rate of change of fluctuations in intensity as a measure of statistical changes. In addition, the range of validity of Litvak's Gaussian-statistics approximation is discussed. In the homogeneous-broadening case, the evolution of initially broadband Gaussian radiation toward quasimonochromatic oscillations with laserlike statistics is explored in several numerical examples. The connections of this study with the time-domain work on self-pulsing in a ring-laser configuration, are established. Finally, spectral-narrowing and -rebroadening effects in Doppler-broadened media are discussed both analytically and with numerical examples. These examples show the distinct contribution of pulsations in the population ('Raman-type terms'), and saturation phenomena.

  5. Amplification of the induced ferromagnetism in diluted magnetic semiconductor

    NASA Astrophysics Data System (ADS)

    Meilikhov, E. Z.; Farzetdinova, R. M.

    2009-07-01

    Magnetic properties of the planar structure consisting of a ferromagnetic metal and the diluted magnetic semiconductor are considered (by the example of the structure Fe/Ga(Mn)As, experimentally studied in [F. Maccherozzi, M. Sperl, G. Panaccione, J. Mina'r, S. Polesya, H. Ebert, U. Wurstbauer, M. Hochstrasser, G. Rossi, G. Woltersdorf, W. Wegscheider, C.H. Back, Phys. Rev. Lett. 101 (2008) 267201]). In the framework of the mean field theory, we demonstrate the presence of the significant amplification of the ferromagnetism, induced by the ferromagnetic metal in the near-interface semiconductor area, due to the indirect interaction of magnetic impurities. This results in the substantial expansion of the temperature range where the magnetization in the boundary semiconductor region exists, that might be important for possible practical applications.

  6. Enhanced solid-phase recombinase polymerase amplification and electrochemical detection.

    PubMed

    Del Río, Jonathan Sabaté; Lobato, Ivan Magriñà; Mayboroda, Olena; Katakis, Ioanis; O'Sullivan, Ciara K

    2017-05-01

    Recombinase polymerase amplification (RPA) is an elegant method for the rapid, isothermal amplification of nucleic acids. Here, we elucidate the optimal surface chemistry for rapid and efficient solid-phase RPA, which was fine-tuned in order to obtain a maximum signal-to-noise ratio, defining the optimal DNA probe density, probe-to-lateral spacer ratio (1:0, 1:1, 1:10 and 1:100) and length of a vertical spacer of the probe as well as investigating the effect of different types of lateral spacers. The use of different labelling strategies was also examined in order to reduce the number of steps required for the analysis, using biotin or horseradish peroxidase-labelled reverse primers. Optimisation of the amplification temperature used and the use of surface blocking agents were also pursued. The combination of these changes facilitated a significantly more rapid amplification and detection protocol, with a lowered limit of detection (LOD) of 1 · 10 -15 M. The optimised protocol was applied to the detection of Francisella tularensis in real samples from hares and a clear correlation with PCR and qPCR results observed and the solid-phase RPA demonstrated to be capable of detecting 500 fM target DNA in real samples. Graphical abstract Relative size of thiolated lateral spacers tested versus the primer and the uvsx recombinase protein.

  7. MET amplification, expression, and exon 14 mutations in colorectal adenocarcinoma.

    PubMed

    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.

  8. How should gestational weight gain be assessed? A comparison of existing methods and a novel method, area under the weight gain curve

    PubMed Central

    Kleinman, Ken P; Oken, Emily; Radesky, Jenny S; Rich-Edwards, Janet W; Peterson, Karen E; Gillman, Matthew W

    2007-01-01

    Background Gestational weight gain is important to assess for epidemiological and public health purposes: it is correlated with infant growth and may be related to maternal outcomes such as reproductive health and chronic disease risk. Methods commonly used to assess weight gain incorporate assumptions that are usually not borne out, such as a linear weight gain, or do not account for differential length of gestation. Methods We introduce a novel method to assess gestational weight gain, the area under the weight gain curve. This is easily interpretable as the additional pound-days carried due to pregnancy and avoids many flaws in alternative assessments. We compare the performance of the simple difference, weekly gain, Institute of Medicine categories and the area under the weight gain curve in predicting birthweight and maternal weight retention at 6, 12, 24 and 36 months post-partum. The analytic sample comprises 2016 participants in Project Viva, an observational prospective cohort study of pregnant women in Massachusetts. Results For birthweight outcomes, none of the weight gain measures is a meaningfully superior predictor. For 6-month postpartum weight retention the simple difference is superior, while for 12-, 24- and 36-month weight retention the area under the weight gain curve is superior. Conclusions These findings are plausible biologically: the same amount of weight gained early vs later in the pregnancy may reflect increased maternal fat stores. The timing of weight gain is reflected best in the area under the weight gain curve. Different methods of measuring gestational weight gain may be appropriate depending on the context. PMID:17715174

  9. Instrument for Real-Time Digital Nucleic Acid Amplification on Custom Microfluidic Devices

    PubMed Central

    Selck, David A.

    2016-01-01

    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 fundamental

  10. Internal validation of the GlobalFiler™ Express PCR Amplification Kit for the direct amplification of reference DNA samples on a high-throughput automated workflow.

    PubMed

    Flores, Shahida; Sun, Jie; King, Jonathan; Budowle, Bruce

    2014-05-01

    The GlobalFiler™ Express PCR Amplification Kit uses 6-dye fluorescent chemistry to enable multiplexing of 21 autosomal STRs, 1 Y-STR, 1 Y-indel and the sex-determining marker amelogenin. The kit is specifically designed for processing reference DNA samples in a high throughput manner. Validation studies were conducted to assess the performance and define the limitations of this direct amplification kit for typing blood and buccal reference DNA samples on various punchable collection media. Studies included thermal cycling sensitivity, reproducibility, precision, sensitivity of detection, minimum detection threshold, system contamination, stochastic threshold and concordance. Results showed that optimal amplification and injection parameters for a 1.2mm punch from blood and buccal samples were 27 and 28 cycles, respectively, combined with a 12s injection on an ABI 3500xL Genetic Analyzer. Minimum detection thresholds were set at 100 and 120RFUs for 27 and 28 cycles, respectively, and it was suggested that data from positive amplification controls provided a better threshold representation. Stochastic thresholds were set at 250 and 400RFUs for 27 and 28 cycles, respectively, as stochastic effects increased with cycle number. The minimum amount of input DNA resulting in a full profile was 0.5ng, however, the optimum range determined was 2.5-10ng. Profile quality from the GlobalFiler™ Express Kit and the previously validated AmpFlSTR(®) Identifiler(®) Direct Kit was comparable. The validation data support that reliable DNA typing results from reference DNA samples can be obtained using the GlobalFiler™ Express PCR Amplification Kit. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. By-product formation in repetitive PCR amplification of DNA libraries during SELEX.

    PubMed

    Tolle, Fabian; Wilke, Julian; Wengel, Jesper; Mayer, Günter

    2014-01-01

    The selection of nucleic acid aptamers is an increasingly important approach to generate specific ligands binding to virtually any molecule of choice. However, selection-inherent amplification procedures are prone to artificial by-product formation that prohibits the enrichment of target-recognizing aptamers. Little is known about the formation of such by-products when employing nucleic acid libraries as templates. We report on the formation of two different forms of by-products, named ladder- and non-ladder-type observed during repetitive amplification in the course of in vitro selection experiments. Based on sequence information and the amplification behaviour of defined enriched nucleic acid molecules we suppose a molecular mechanism through which these amplification by-products are built. Better understanding of these mechanisms might help to find solutions minimizing by-product formation and improving the success rate of aptamer selection.

  12. By-Product Formation in Repetitive PCR Amplification of DNA Libraries during SELEX

    PubMed Central

    Tolle, Fabian; Wilke, Julian; Wengel, Jesper; Mayer, Günter

    2014-01-01

    The selection of nucleic acid aptamers is an increasingly important approach to generate specific ligands binding to virtually any molecule of choice. However, selection-inherent amplification procedures are prone to artificial by-product formation that prohibits the enrichment of target-recognizing aptamers. Little is known about the formation of such by-products when employing nucleic acid libraries as templates. We report on the formation of two different forms of by-products, named ladder- and non-ladder-type observed during repetitive amplification in the course of in vitro selection experiments. Based on sequence information and the amplification behaviour of defined enriched nucleic acid molecules we suppose a molecular mechanism through which these amplification by-products are built. Better understanding of these mechanisms might help to find solutions minimizing by-product formation and improving the success rate of aptamer selection. PMID:25490402

  13. Clinical Characteristics and Outcome of Patients with Neuroblastoma Presenting Genomic Amplification of Loci Other than MYCN

    PubMed Central

    Guimier, Anne; Ferrand, Sandrine; Pierron, Gaëlle; Couturier, Jérôme; Janoueix-Lerosey, Isabelle; Combaret, Valérie; Mosseri, Véronique; Thebaud, Estelle; Gambart, Marion; Plantaz, Dominique; Marabelle, Aurélien; Coze, Carole; Rialland, Xavier; Fasola, Sylvie; Lapouble, Eve; Fréneaux, Paul; Peuchmaur, Michel; Michon, Jean; Delattre, Olivier; Schleiermacher, Gudrun

    2014-01-01

    Background Somatically acquired genomic alterations with MYCN amplification (MNA) are key features of neuroblastoma (NB), the most common extra-cranial malignant tumour of childhood. Little is known about the frequency, clinical characteristics and outcome of NBs harbouring genomic amplification(s) distinct from MYCN. Methods Genomic profiles of 1100 NBs from French centres studied by array-CGH were re-examined specifically to identify regional amplifications. Patients were included if amplifications distinct from the MYCN locus were seen. A subset of NBs treated at Institut Curie and harbouring MNA as determined by array-CGH without other amplification was also studied. Clinical and histology data were retrospectively collected. Results In total, 56 patients were included and categorised into 3 groups. Group 1 (n = 8) presented regional amplification(s) without MNA. Locus 12q13-14 was a recurrent amplified region (4/8 cases). This group was heterogeneous in terms of INSS stages, primary localisations and histology, with atypical clinical features. Group 2 (n = 26) had MNA as well as other regional amplifications. These patients shared clinical features of those of a group of NBs MYCN amplified (Group 3, n = 22). Overall survival for group 1 was better than that of groups 2 and 3 (5 year OS: 87.5%±11% vs 34.9%±7%, log-rank p<0.05). Conclusion NBs harbouring regional amplification(s) without MNA are rare and seem to show atypical features in clinical presentation and genomic profile. Further high resolution genetic explorations are justified in this heterogeneous group, especially when considering these alterations as predictive markers for targeted therapy. PMID:25013904

  14. Clinical analysis by next-generation sequencing for NSCLC patients with MET amplification resistant to osimertinib.

    PubMed

    Wang, Yubo; Li, Li; Han, Rui; Jiao, Lin; Zheng, Jie; He, Yong

    2018-04-01

    The efficacy of osimertinib was compromised by the development of resistance mechanisms, such as MET amplification. However, cohort studies of osimertinib resistance mechanism, and the correlation of MET and progression-free survival (PFS) after osimertinib resistance have been poorly investigated. This study was carried out to study the acquired MET amplification after osimertinib resistance in advanced lung adenocarcinoma patients, and interrogate the correlation of clinical prognosis and MET amplification. We performed capture-based sequencing on longitudinal plasma and tissue samples obtained before osimertinib treatment and after resistance development from lung adenocarcinoma patients to investigate the underlying resistance mechanism. We also investigated the correlation of MET amplification and patient prognosis after osimertinib resistance using Kaplan-Meier analysis. Paired biopsies before osimertinib treatment and after the resistance development revealed underlying resistance mechanisms. In addition, a cohort of 13 patients who developed disease progression after osimertinib resistance was investigated. Patients with MET amplification after osimertinib resistance commonly had inferior median progression-free survival (mPFS) than patients without MET amplification appearance or increase (3.5 months vs. 9.9 months, p = .117). Patients in MET amplification group also displayed poor median overall survival (mOS) compared to MET amplification negative group (15.6 months vs. 30.7 months, p = .885). Furthermore, combinatorial treatment of first/third-generation EGFR-TKI and crizotinib was efficaciously administrated into two patients with newly acquired MET amplification after osimertinib resistance. Partial responses were achieved by them, both clinically and radiographically. We investigated the osimertinib resistance mechanism in a small cohort of lung adenocarcinoma patients, and demonstrated MET amplification was correlated with inferior PFS

  15. chipPCR: an R package to pre-process raw data of amplification curves.

    PubMed

    Rödiger, Stefan; Burdukiewicz, Michał; Schierack, Peter

    2015-09-01

    Both the quantitative real-time polymerase chain reaction (qPCR) and quantitative isothermal amplification (qIA) are standard methods for nucleic acid quantification. Numerous real-time read-out technologies have been developed. Despite the continuous interest in amplification-based techniques, there are only few tools for pre-processing of amplification data. However, a transparent tool for precise control of raw data is indispensable in several scenarios, for example, during the development of new instruments. chipPCR is an R: package for the pre-processing and quality analysis of raw data of amplification curves. The package takes advantage of R: 's S4 object model and offers an extensible environment. chipPCR contains tools for raw data exploration: normalization, baselining, imputation of missing values, a powerful wrapper for amplification curve smoothing and a function to detect the start and end of an amplification curve. The capabilities of the software are enhanced by the implementation of algorithms unavailable in R: , such as a 5-point stencil for derivative interpolation. Simulation tools, statistical tests, plots for data quality management, amplification efficiency/quantification cycle calculation, and datasets from qPCR and qIA experiments are part of the package. Core functionalities are integrated in GUIs (web-based and standalone shiny applications), thus streamlining analysis and report generation. http://cran.r-project.org/web/packages/chipPCR. Source code: https://github.com/michbur/chipPCR. stefan.roediger@b-tu.de Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. Hetero-enzyme-based two-round signal amplification strategy for trace detection of aflatoxin B1 using an electrochemical aptasensor.

    PubMed

    Zheng, Wanli; Teng, Jun; Cheng, Lin; Ye, Yingwang; Pan, Daodong; Wu, Jingjing; Xue, Feng; Liu, Guodong; Chen, Wei

    2016-06-15

    An electrochemical aptasensor for trace detection of aflatoxin B1 (AFB1) was developed by using an aptamer as the recognition unit while adopting the telomerase and EXO III based two-round signal amplification strategy as the signal enhancement units. The telomerase amplification was used to elongate the ssDNA probes on the surface of gold nanoparticles, by which the signal response range of the signal-off model electrochemical aptasensor could be correspondingly enlarged. Then, the EXO III amplification was used to hydrolyze the 3'-end of the dsDNA after the recognition of target AFB1, which caused the release of bounded AFB1 into the sensing system, where it participated in the next recognition-sensing cycle. With this two-round signal amplified electrochemical aptasensor, target AFB1 was successfully measured at trace concentrations with excellent detection limit of 0.6*10(-4)ppt and satisfied specificity due to the excellent affinity of the aptamer against AFB1. Based on this designed two-round signal amplification strategy, both the sensing range and detection limit were greatly improved. This proposed ultrasensitive electrochemical aptasensor method was also validated by comparison with the classic instrumental methods. Importantly, this hetero-enzyme based two-round signal amplified electrochemical aptasensor offers a great promising protocol for ultrasensitive detection of AFB1 and other mycotoxins by replacing the core recognition sequence of the aptamer. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. AMPLIFICATION OF RIBOSOMAL RNA SEQUENCES - Book Chapter

    EPA Science Inventory

    This book chapter contains the following headings and subheadings: Introduction; Experimental Approach - Precautions, Template, Primers, Reaction Conditions, Enhancers, Post Amplification; Procedures - Template DNA, Basic PCR, Thermal Cycle Parameters, Enzyme Addition, Agarose Ge...

  18. Chemical amplification based on fluid partitioning in an immiscible liquid

    DOEpatents

    Anderson, Brian L.; Colston, Bill W.; Elkin, Christopher J.

    2010-09-28

    A system for nucleic acid amplification of a sample comprises partitioning the sample into partitioned sections and performing PCR on the partitioned sections of the sample. Another embodiment of the invention provides a system for nucleic acid amplification and detection of a sample comprising partitioning the sample into partitioned sections, performing PCR on the partitioned sections of the sample, and detecting and analyzing the partitioned sections of the sample.

  19. Bioengineering bacteriophages to enhance the sensitivity of phage amplification-based paper fluidic detection of bacteria.

    PubMed

    Alcaine, S D; Law, K; Ho, S; Kinchla, A J; Sela, D A; Nugen, S R

    2016-08-15

    Bacteriophage (phage) amplification is an attractive method for the detection of bacteria due to a narrow phage-host specificity, short amplification times, and the phages' ability to differentiate between viable and non-viable bacterial cells. The next step in phage-based bacteria detection is leveraging bioengineered phages to create low-cost, rapid, and easy-to-use detection platforms such as lateral flow assays. Our work establishes the proof-of-concept for the use of bioengineered T7 phage strains to increase the sensitivity of phage amplification-based lateral flow assays. We have demonstrated a greater than 10-fold increase in sensitivity using a phage-based protein reporter, maltose-binding protein, over the detection of replicated T7 phage viron itself, and a greater then 100-fold increase in sensitivity using a phage-based enzymatic reporter, alkaline phosphatase. This increase in sensitivity enabled us to detect 10(3)CFU/mL of Escherichia coli in broth after 7h, and by adding a filter concentration step, the ability to detect a regulatory relevant E. coli concentration of 100CFU/100mL in inoculated river water after 9h, where the current standard requires days for results. The combination of the paper fluidic format with phage-based detection provides a platform for the development of novel diagnostics that are sensitive, rapid, and easy to use. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Biomass changes and trophic amplification of plankton in a warmer ocean.

    PubMed

    Chust, Guillem; Allen, J Icarus; Bopp, Laurent; Schrum, Corinna; Holt, Jason; Tsiaras, Kostas; Zavatarelli, Marco; Chifflet, Marina; Cannaby, Heather; Dadou, Isabelle; Daewel, Ute; Wakelin, Sarah L; Machu, Eric; Pushpadas, Dhanya; Butenschon, Momme; Artioli, Yuri; Petihakis, George; Smith, Chris; Garçon, Veronique; Goubanova, Katerina; Le Vu, Briac; Fach, Bettina A; Salihoglu, Baris; Clementi, Emanuela; Irigoien, Xabier

    2014-07-01

    Ocean warming can modify the ecophysiology and distribution of marine organisms, and relationships between species, with nonlinear interactions between ecosystem components potentially resulting in trophic amplification. Trophic amplification (or attenuation) describe the propagation of a hydroclimatic signal up the food web, causing magnification (or depression) of biomass values along one or more trophic pathways. We have employed 3-D coupled physical-biogeochemical models to explore ecosystem responses to climate change with a focus on trophic amplification. The response of phytoplankton and zooplankton to global climate-change projections, carried out with the IPSL Earth System Model by the end of the century, is analysed at global and regional basis, including European seas (NE Atlantic, Barents Sea, Baltic Sea, Black Sea, Bay of Biscay, Adriatic Sea, Aegean Sea) and the Eastern Boundary Upwelling System (Benguela). Results indicate that globally and in Atlantic Margin and North Sea, increased ocean stratification causes primary production and zooplankton biomass to decrease in response to a warming climate, whilst in the Barents, Baltic and Black Seas, primary production and zooplankton biomass increase. Projected warming characterized by an increase in sea surface temperature of 2.29 ± 0.05 °C leads to a reduction in zooplankton and phytoplankton biomasses of 11% and 6%, respectively. This suggests negative amplification of climate driven modifications of trophic level biomass through bottom-up control, leading to a reduced capacity of oceans to regulate climate through the biological carbon pump. Simulations suggest negative amplification is the dominant response across 47% of the ocean surface and prevails in the tropical oceans; whilst positive trophic amplification prevails in the Arctic and Antarctic oceans. Trophic attenuation is projected in temperate seas. Uncertainties in ocean plankton projections, associated to the use of single global and

  1. Formation of template-switching artifacts by linear amplification.

    PubMed

    Chakravarti, Dhrubajyoti; Mailander, Paula C

    2008-07-01

    Linear amplification is a method of synthesizing single-stranded DNA from either a single-stranded DNA or one strand of a double-stranded DNA. In this protocol, molecules of a single primer DNA are extended by multiple rounds of DNA synthesis at high temperature using thermostable DNA polymerases. Although linear amplification generates the intended full-length single-stranded product, it is more efficient over single-stranded templates than double-stranded templates. We analyzed linear amplification over single- or double-stranded mouse H-ras DNA (exon 1-2 region). The single-stranded H-ras template yielded only the intended product. However, when the double-stranded template was used, additional artifact products were observed. Increasing the concentration of the double-stranded template produced relatively higher amounts of these artifact products. One of the artifact DNA bands could be mapped and analyzed by sequencing. It contained three template-switching products. These DNAs were formed by incomplete DNA strand extension over the template strand, followed by switching to the complementary strand at a specific Ade nucleotide within a putative hairpin sequence, from which DNA synthesis continued over the complementary strand.

  2. RUNX1 Amplification Increases the Risk for Thrombosis in Children With B-cell Acute Lymphoblastic Leukemia.

    PubMed

    Boucher, Maria O; Smitherman, Andrew B; Pahl, Kristy S; Rao, Kathleen W; Deal, Allison M; Blatt, Julie

    2016-04-01

    RUNX1 (AML1) amplification in patients with B-cell acute lymphoblastic leukemia (B-ALL) has been associated with poor survival for unclear reasons. Our anecdotal experience suggests that children with B-ALL and RUNX1 amplification might be predisposed to thrombosis. We performed a retrospective cohort study of children with B-ALL treated from 2008 to 2014 at the North Carolina Children's Hospital. Patient demographics, cytogenetics, and diagnosis of thrombosis were extracted by blinded chart review. Analysis was performed examining the relationship between RUNX1 amplification and thrombosis. We identified 119 patients with B-ALL and a median age of 4.9 years (interquartile range, 2.9 to 8.6 y) at diagnosis. Four patients (3%) had RUNX1 amplification. The average number of RUNX1 copies among those with amplification was 5 (SD 0.81 [range, 4 to 6]). Eighteen thromboses were diagnosed within 6 months of starting treatment. These events were more likely among patients with RUNX1 amplification than in patients without amplification (75% vs. 13%; RR 5.75, 95% confidence interval, 2.75-12.01). RUNX1 amplification may predispose to early thrombotic events in children with B-ALL which could, in part, contribute to their poorer outcomes. Treatment implications, including possible prophylactic anticoagulation of patients with of RUNX1 amplification, justify larger studies to confirm these findings.

  3. FIBER OPTICS. ACOUSTOOPTICS: Amplification of semiconductor laser radiation in the wavelength range 1.24-1.3 μm by stimulated Raman scattering in an optical fiber

    NASA Astrophysics Data System (ADS)

    Belotitskiĭ, V. I.; Kuzin, E. A.; Ovsyannikov, D. V.; Petrov, Mikhail P.

    1990-07-01

    An investigation was made of the influence of weak semiconductor laser radiation on the spectrum of stimulated Raman scattering in a single-mode optical waveguide pumped by a YAG:Nd3+ laser emitting at 1.06 μm. The scattered radiation power increased by a factor exceeding 10 at the semiconductor laser wavelength. A small-signal dynamic gain reached 47 dB. Simultaneous amplification was observed of several modes of multimode semiconductor laser radiation with an intermode spectral interval of 1.3 nm.

  4. Resonant- and avalanche-ionization amplification of laser-induced plasma in air

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wu, Yue; Zhang, Zhili, E-mail: zzhang24@utk.edu; Jiang, Naibo

    2014-10-14

    Amplification of laser-induced plasma in air is demonstrated utilizing resonant laser ionization and avalanche ionization. Molecular oxygen in air is ionized by a low-energy laser pulse employing (2 + 1) resonance-enhanced multi-photon ionization (REMPI) to generate seed electrons. Subsequent avalanche ionization of molecular oxygen and nitrogen significantly amplifies the laser-induced plasma. In this plasma-amplification effect, three-body attachments to molecular oxygen dominate the electron-generation and -loss processes, while either nitrogen or argon acts as the third body with low electron affinity. Contour maps of the electron density within the plasma obtained in O₂/N₂ and O₂/Ar gas mixtures are provided to showmore » relative degrees of plasma amplification with respect to gas pressure and to verify that the seed electrons generated by O₂ 2 + 1 REMPI are selectively amplified by avalanche ionization of molecular nitrogen in a relatively low-pressure condition (≤100 Torr). Such plasma amplification occurring in air could be useful in aerospace applications at high altitude.« less

  5. Amplification in the rehabilitation of unilateral deafness: speech in noise and directional hearing effects with bone-anchored hearing and contralateral routing of signal amplification.

    PubMed

    Lin, Li-Mei; Bowditch, Stephen; Anderson, Michael J; May, Bradford; Cox, Kenneth M; Niparko, John K

    2006-02-01

    Vibromechanical stimulation with a semi-implantable bone conductor (Entific BAHA device) overcomes some of the head-shadow effects in unilateral deafness. What specific rehabilitative benefits are observed when the functional ear exhibits normal hearing versus moderate sensorineural hearing loss (SNHL)? The authors conducted a prospective trial of subjects with unilateral deafness in a tertiary care center. This study comprised adults with unilateral deafness (pure-tone average [PTA] > 90 dB; Sp.D. < 20%) and either normal monaural hearing (n = 18) or moderate SNHL (PTA = 25-50 dB: Sp.D. > 75%) in the contralateral functional ear (n = 5). Subjects were fit with contralateral routing of signal (CROS) devices for 1 month and tested before (mastoid) implantation, fitting, and testing with a bone-anchored hearing aid (BAHA). Outcome measures were: 1) subjective benefit; 2) source localization tests (Source Azimuth Identification in Noise Test [SAINT]); 3) speech discrimination in quiet and in noise assessed with Hearing In Noise Test (HINT) protocols. There was consistent satisfaction with BAHA amplification and poor acceptance of CROS amplification. General directional hearing decreased with CROS use and was unchanged by BAHA and directional microphone aids. Relative to baseline and CROS, BAHA produced significantly better speech recognition in noise. Twenty-two of 23 subjects followed up in this study continue to use their BAHA device over an average follow-up period of 30.24 months (range, 51-12 months). BAHA amplification on the side of a deaf ear yields greater benefit in subjects with monaural hearing than does CROS amplification. Advantages likely related to averting the interference of speech signals delivered to the better ear, as occurs with conventional CROS amplification, while alleviating the negative head-shadow effects of unilateral deafness. The advantages of head-shadow reduction in enhancing speech recognition with noise in the hearing ear outweigh

  6. Homogenous assay for protein detection based on proximity DNA hybridization and isothermal circular strand displacement amplification reaction.

    PubMed

    Zhang, Manjun; Li, Ruimin; Ling, Liansheng

    2017-06-01

    This work proposed a homogenous fluorescence assay for proteins, based on the target-triggered proximity DNA hybridization in combination with strand displacement amplification (SDA). It benefited from target-triggered proximity DNA hybridization to specifically recognize the target and SDA making recycling signal amplification. The system included a molecular beacon (MB), an extended probe (EP), and an assistant probe (AP), which were not self-assembly in the absence of target proteins, due to the short length of the designed complementary sequence among MB, EP, and AP. Upon addition of the target proteins, EP and AP are bound to the target proteins, which induced the occurrence of proximity hybridization between MB, EP, and AP and followed by strand displacement amplification. Through the primer extension, a tripartite complex of probes and target was displaced and recycled to hybridize with another MB, and the more opened MB enabled the detection signal to amplify. Under optimum conditions, it was used for the detection of streptavidin and thrombin. Fluorescence intensity was proportional to the concentration of streptavidin and thrombin in the range of 0.2-30 and 0.2-35 nmol/L, respectively. Furthermore, this fluorescent method has a good selectivity, in which the fluorescence intensity of thrombin was ~37-fold or even larger than that of the other proteins at the same concentration. It is a new and simple method for SDA-involved target protein detection and possesses a great potential for other protein detection in the future. Graphical abstract A homogenous assay for protein detection is based on proximity DNA hybridization and strand displacement amplification reaction.

  7. Does the Arctic Amplification peak this decade?

    NASA Astrophysics Data System (ADS)

    Martin, Torge; Haine, Thomas W. N.

    2017-04-01

    Temperatures rise faster in the Arctic than on global average, a phenomenon known as Arctic Amplification. While this is well established from observations and model simulations, projections of future climate (here: RCP8.5) with models of the Coupled Model Intercomparison Project phase 5 (CMIP5) also indicate that the Arctic Amplification has a maximum. We show this by means of an Arctic Amplification factor (AAF), which we define as the ratio of Arctic mean to global mean surface air temperature (SAT) anomalies. The SAT anomalies are referenced to the period 1960-1980 and smoothed by a 30-year running mean. For October, the multi-model ensemble-mean AAF reaches a maximum in 2017. The maximum moves however to later years as Arctic winter progresses: for the autumn mean SAT (September to November) the maximum AAF is found in 2028 and for winter (December to February) in 2060. Arctic Amplification is driven, amongst others, by the ice-albedo feedback (IAF) as part of the more general surface albedo feedback (involving clouds, snow cover, vegetation changes) and temperature effects (Planck and lapse-rate feedbacks). We note that sea ice retreat and the associated warming of the summer Arctic Ocean are not only an integral part of the IAF but are also involved in the other drivers. In the CMIP5 simulations, the timing of the AAF maximum coincides with the period of fastest ice retreat for the respective month. Presence of at least some sea ice is crucial for the IAF to be effective because of the contrast in surface albedo between ice and open water and the need to turn ocean warming into ice melt. Once large areas of the Arctic Ocean are ice-free, the IAF should be less effective. We thus hypothesize that the ice retreat significantly affects AAF variability and forces a decline of its magnitude after at least half of the Arctic Ocean is ice-free and the ice cover becomes basically seasonal.

  8. Semiquantitative Nucleic Acid Test with Simultaneous Isotachophoretic Extraction and Amplification.

    PubMed

    Bender, Andrew T; Borysiak, Mark D; Levenson, Amanda M; Lillis, Lorraine; Boyle, David S; Posner, Jonathan D

    2018-06-19

    Nucleic acid amplification tests (NAATs) provide high diagnostic accuracy for infectious diseases and quantitative results for monitoring viral infections. The majority of NAATs require complex equipment, cold chain dependent reagents, and skilled technicians to perform the tests. This largely confines NAATs to centralized laboratories and can significantly delay appropriate patient care. Low-cost, point-of-care (POC) NAATs are especially needed in low-resource settings to provide patients with diagnosis and treatment planning in a single visit to improve patient care. In this work, we present a rapid POC NAAT with integrated sample preparation and amplification using electrokinetics and paper substrates. We use simultaneous isotachophoresis (ITP) and recombinase polymerase amplification (RPA) to rapidly extract, amplify, and detect target nucleic acids from serum and whole blood in a paper-based format. We demonstrate simultaneous ITP and RPA can consistently detect 5 copies per reaction in buffer and 10 000 copies per milliliter of human serum with no intermediate user steps. We also show preliminary extraction and amplification of DNA from whole blood samples. Our test is rapid (results in less than 20 min) and made from low-cost materials, indicating its potential for detecting infectious diseases and monitoring viral infections at the POC in low resource settings.

  9. Invasive reaction assisted strand-displacement signal amplification for sensitive DNA detection.

    PubMed

    Zou, Bingjie; Song, Qinxin; Wang, Jianping; Liu, Yunlong; Zhou, Guohua

    2014-11-18

    A novel DNA detection assay was proposed by invasive reaction coupled with molecular beacon assisted strand-displacement signal amplification (IRASA). Target DNAs are firstly hybridized to two probes to initiate invasive reaction to produce amplified flaps. Then these flaps are further amplified by strand-displacement signal amplification. The detection limit was around 0.2 pM.

  10. On the amplification of magnetic fields in cosmic filaments and galaxy clusters

    NASA Astrophysics Data System (ADS)

    Vazza, F.; Brüggen, M.; Gheller, C.; Wang, P.

    2014-12-01

    The amplification of primordial magnetic fields via a small-scale turbulent dynamo during structure formation might be able to explain the observed magnetic fields in galaxy clusters. The magnetization of more tenuous large-scale structures such as cosmic filaments is more uncertain, as it is challenging for numerical simulations to achieve the required dynamical range. In this work, we present magnetohydrodynamical cosmological simulations on large uniform grids to study the amplification of primordial seed fields in the intracluster medium (ICM) and in the warm-hot-intergalactic medium (WHIM). In the ICM, we confirm that turbulence caused by structure formation can produce a significant dynamo amplification, even if the amplification is smaller than what is reported in other papers. In the WHIM inside filaments, we do not observe significant dynamo amplification, even though we achieve Reynolds numbers of Re ˜ 200-300. The maximal amplification for large filaments is of the order of ˜100 for the magnetic energy, corresponding to a typical field of a few ˜nG starting from a primordial weak field of 10-10 G (comoving). In order to start a small-scale dynamo, we found that a minimum of ˜102 resolution elements across the virial radius of galaxy clusters was necessary. In filaments we could not find a minimum resolution to set off a dynamo. This stems from the inefficiency of supersonic motions in the WHIM in triggering solenoidal modes and small-scale twisting of magnetic field structures. Magnetic fields this small will make it hard to detect filaments in radio observations.

  11. The uses and limitations of the square‐root‐impedance method for computing site amplification

    USGS Publications Warehouse

    Boore, David

    2013-01-01

    The square‐root‐impedance (SRI) method is a fast way of computing approximate site amplification that does not depend on the details from velocity models. The SRI method underestimates the peak response of models with large impedance contrasts near their base, but the amplifications for those models is often close to or equal to the root mean square of the theoretical full resonant (FR) response of the higher modes. On the other hand, for velocity models made up of gradients, with no significant impedance changes across small ranges of depth, the SRI method systematically underestimates the theoretical FR response over a wide frequency range. For commonly used gradient models for generic rock sites, the SRI method underestimates the FR response by about 20%–30%. Notwithstanding the persistent underestimation of amplifications from theoretical FR calculations, however, amplifications from the SRI method may often provide more useful estimates of amplifications than the FR method, because the SRI amplifications are not sensitive to details of the models and will not exhibit the many peaks and valleys characteristic of theoretical full resonant amplifications (jaggedness sometimes not seen in amplifications based on averages of site response from multiple recordings at a given site). The lack of sensitivity to details of the velocity models also makes the SRI method useful in comparing the response of various velocity models, in spite of any systematic underestimation of the response. The quarter‐wavelength average velocity, which is fundamental to the SRI method, is useful by itself in site characterization, and as such, is the fundamental parameter used to characterize the site response in a number of recent ground‐motion prediction equations.

  12. All-Fiber, Directly Chirped Laser Source for Chirped-Pulse-Amplification

    NASA Astrophysics Data System (ADS)

    Xin, Ran

    Chirped-pulse-amplification (CPA) technology is widely used to produce ultra-short optical pulses (sub picosecond to femtoseconds) with high pulse energy. A chirped pulse laser source with flexible dispersion control is highly desirable as a CPA seed. This thesis presents an all-fiber, directly chirped laser source (DCLS) that produces nanosecond, linearly-chirped laser pulses at 1053 nm for seeding high energy CPA systems. DCLS produces a frequency chirp on an optical pulse through direct temporal phase modulation. DCLS provides programmable control for the temporal phase of the pulse, high pulse energy and diffraction-limited beam performance, which are beneficial for CPA systems. The DCLS concept is first described. Its key enabling technologies are identified and their experimental demonstration is presented. These include high-precision temporal phase control using an arbitrary waveform generator, multi-pass phase modulation to achieve high modulation depth, regenerative amplification in a fiber ring cavity and a negative feedback system that controls the amplifier cavity dynamics. A few technical challenges that arise from the multi-pass architecture are described and their solutions are presented, such as polarization management and gain-spectrum engineering in the DCLS fiber cavity. A DCLS has been built and its integration into a high energy OPCPA system is demonstrated. DCLS produces a 1-ns chirped pulse with a 3-nm bandwidth. The temporal phase and group delay dispersion on the DCLS output pulse is measured using temporal interferometry. The measured temporal phase has an ˜1000 rad amplitude and is close to a quadratic shape. The chirped pulse is amplified from 0.9 nJ to 76 mJ in an OPCPA system. The amplified pulse is compressed to close to its Fourier transform limit, producing an intensity autocorrelation trace with a 1.5-ps width. Direct compressed-pulse duration control by adjusting the phase modulation drive amplitude is demonstrated. Limitation

  13. Single-Cell Whole-Genome Amplification and Sequencing: Methodology and Applications.

    PubMed

    Huang, Lei; Ma, Fei; Chapman, Alec; Lu, Sijia; Xie, Xiaoliang Sunney

    2015-01-01

    We present a survey of single-cell whole-genome amplification (WGA) methods, including degenerate oligonucleotide-primed polymerase chain reaction (DOP-PCR), multiple displacement amplification (MDA), and multiple annealing and looping-based amplification cycles (MALBAC). The key parameters to characterize the performance of these methods are defined, including genome coverage, uniformity, reproducibility, unmappable rates, chimera rates, allele dropout rates, false positive rates for calling single-nucleotide variations, and ability to call copy-number variations. Using these parameters, we compare five commercial WGA kits by performing deep sequencing of multiple single cells. We also discuss several major applications of single-cell genomics, including studies of whole-genome de novo mutation rates, the early evolution of cancer genomes, circulating tumor cells (CTCs), meiotic recombination of germ cells, preimplantation genetic diagnosis (PGD), and preimplantation genomic screening (PGS) for in vitro-fertilized embryos.

  14. Inefficiency of Signal Amplification by Post-selection

    NASA Astrophysics Data System (ADS)

    Tanaka, Saki; Yamamoto, Naoki

    Basing the two-state vector formalism, Aharonov, Albert and Vaidman found a measurement way such that spin 1/2 particle can turn out 100 [1]. The measurement result is called weak value and this value depends on pre-and post- selected states. The weak value becomes infinitely large when the post- selected state is orthogonal to pre-selected state. By using this feature, the weak measurement has been applied to amplification technique. However, the success of the post-selection depends on luck and this technique does not always work. We take into account of loss by post-selection, and evaluate this amplification by quantum estimation theory. As a result, we get an inequality which means that post-selection does not improve estate accuracy when the number of states is limited.

  15. Power amplification in an isolated muscle–tendon unit is load dependent

    PubMed Central

    Sawicki, Gregory S.; Sheppard, Peter; Roberts, Thomas J.

    2015-01-01

    ABSTRACT During rapid movements, tendons can act like springs, temporarily storing work done by muscles and then releasing it to power body movements. For some activities, such as frog jumping, energy is released from tendon much more rapidly than it is stored, thus amplifying muscle power output. The period during which energy is loaded into a tendon by muscle work may be aided by a catch mechanism that restricts motion, but theoretical studies indicate that power can be amplified in a muscle–tendon load system even in the absence of a catch. To explore the limits of power amplification with and without a catch, we studied the bullfrog plantaris muscle–tendon during in vitro contractions. A novel servomotor controller allowed us to measure muscle–tendon unit (MTU) mechanical behavior during contractions against a variety of simulated inertial-gravitational loads, ranging from zero to 1× the peak isometric force of the muscle. Power output of the MTU system was load dependent and power amplification occurred only at intermediate loads, reaching ∼1.3× the peak isotonic power output of the muscle. With a simulated anatomical catch mechanism in place, the highest power amplification occurred at the lowest loads, with a maximum amplification of more than 4× peak isotonic muscle power. At higher loads, the benefits of a catch for MTU performance diminished sharply, suggesting that power amplification >2.5× may come at the expense of net mechanical work delivered to the load. PMID:26449973

  16. A three-phase amplification of the cosmic magnetic field in galaxies

    NASA Astrophysics Data System (ADS)

    Martin-Alvarez, Sergio; Devriendt, Julien; Slyz, Adrianne; Teyssier, Romain

    2018-06-01

    Arguably the main challenge of galactic magnetism studies is to explain how the interstellar medium of galaxies reaches energetic equipartition despite the extremely weak cosmic primordial magnetic fields that are originally predicted to thread the inter-galactic medium. Previous numerical studies of isolated galaxies suggest that a fast dynamo amplification might suffice to bridge the gap spanning many orders of magnitude in strength between the weak early Universe magnetic fields and the ones observed in high redshift galaxies. To better understand their evolution in the cosmological context of hierarchical galaxy growth, we probe the amplification process undergone by the cosmic magnetic field within a spiral galaxy to unprecedented accuracy by means of a suite of constrained transport magnetohydrodynamical adaptive mesh refinement cosmological zoom simulations with different stellar feedback prescriptions. A galactic turbulent dynamo is found to be naturally excited in this cosmological environment, being responsible for most of the amplification of the magnetic energy. Indeed, we find that the magnetic energy spectra of simulated galaxies display telltale inverse cascades. Overall, the amplification process can be divided in three main phases, which are related to different physical mechanisms driving galaxy evolution: an initial collapse phase, an accretion-driven phase, and a feedback-driven phase. While different feedback models affect the magnetic field amplification differently, all tested models prove to be subdominant at early epochs, before the feedback-driven phase is reached. Thus the three-phase evolution paradigm is found to be quite robust vis-a-vis feedback prescriptions.

  17. Severe Early-Onset Combined Immunodeficiency due to Heterozygous Gain-of-Function Mutations in STAT1.

    PubMed

    Baris, Safa; Alroqi, Fayhan; Kiykim, Ayca; Karakoc-Aydiner, Elif; Ogulur, Ismail; Ozen, Ahmet; Charbonnier, Louis-Marie; Bakır, Mustafa; Boztug, Kaan; Chatila, Talal A; Barlan, Isil B

    2016-10-01

    Loss and gain-of-function (GOF) mutations in human signal transducer and activator of transcription 1 (STAT1) lead to distinct phenotypes. Although recurrent infections are common to both types of STAT1 mutations, GOF mutations are distinguished by chronic mucocutaneous candidiasis and autoimmunity. However, the clinical spectra of STAT1 GOF mutations continue to expand. We here describe two patients with STAT1 GOF mutations presenting early in life with combined immunodeficiency (CID). Clinical data and laboratory findings including immunophenotyping, level of interferon (IFN)-γ/IL-17(+) T cells, interferon-induced STAT1 phosphorylation, and JAK inhibitor assays were evaluated. Sequencing of STAT1 gene was performed by Sanger sequencer. Patient 1 (P1) had persistent oral candidiasis and cytomegalovirus (CMV) infection since 2 months of age and later developed cavitary lung lesions due to Mycobacterium tuberculosis. Patient 2 (P2) presented with oral candidiasis and recurrent pneumonia at 4 months of age and subsequently developed CMV pneumonitis. Both patients suffered heterozygous missense mutations in STAT1, leading to deleterious amino acid substitutions in the DNA binding domain (P1: c.1154C > T; p.T385M; P2. c.971G > T; p.C324F). Circulating CD4(+) T cells of both patients exhibited increased interferon-γ and decreased IL-17 expression as compared to controls. They also exhibited increased IFN-β and -γ-induced STAT1 phosphorylation that was reversed upon treatment with the JAK kinase inhibitor ruxolitinib. STAT1 GOF mutations may present early in life with CID, consistent with the clinical heterogeneity of the disease. JAK kinase inhibitors may potentially be useful in some patients as adjunct therapy pending definitive treatment with bone marrow transplantation.

  18. Radiation hardness of thin Low Gain Avalanche Detectors

    NASA Astrophysics Data System (ADS)

    Kramberger, G.; Carulla, M.; Cavallaro, E.; Cindro, V.; Flores, D.; Galloway, Z.; Grinstein, S.; Hidalgo, S.; Fadeyev, V.; Lange, J.; Mandić, I.; Medin, G.; Merlos, A.; McKinney-Martinez, F.; Mikuž, M.; Quirion, D.; Pellegrini, G.; Petek, M.; Sadrozinski, H. F.-W.; Seiden, A.; Zavrtanik, M.

    2018-05-01

    Low Gain Avalanche Detectors (LGAD) are based on a n++-p+-p-p++ structure where an appropriate doping of the multiplication layer (p+) leads to high enough electric fields for impact ionization. Gain factors of few tens in charge significantly improve the resolution of timing measurements, particularly for thin detectors, where the timing performance was shown to be limited by Landau fluctuations. The main obstacle for their operation is the decrease of gain with irradiation, attributed to effective acceptor removal in the gain layer. Sets of thin sensors were produced by two different producers on different substrates, with different gain layer doping profiles and thicknesses (45, 50 and 80 μm). Their performance in terms of gain/collected charge and leakage current was compared before and after irradiation with neutrons and pions up to the equivalent fluences of 5 ṡ 1015 cm-2. Transient Current Technique and charge collection measurements with LHC speed electronics were employed to characterize the detectors. The thin LGAD sensors were shown to perform much better than sensors of standard thickness (∼300 μm) and offer larger charge collection with respect to detectors without gain layer for fluences < 2 ṡ 1015 cm-2. Larger initial gain prolongs the beneficial performance of LGADs. Pions were found to be more damaging than neutrons at the same equivalent fluence, while no significant difference was found between different producers. At very high fluences and bias voltages the gain appears due to deep acceptors in the bulk, hence also in thin standard detectors.

  19. Ferrocenemonocarboxylic-HRP@Pt nanoparticles labeled RCA for multiple amplification of electro-immunosensing.

    PubMed

    Su, Huilan; Yuan, Ruo; Chai, Yaqin; Mao, Li; Zhuo, Ying

    2011-07-15

    A multiple amplification immunoassay was proposed to detect alpha-fetoprotein (AFP), which was based on ferrocenemonocarboxylic-HRP conjugated on Pt nanoparticles as labels for rolling circle amplification (RCA). Firstly, the capture antibody (anti-AFP) was immobilized on glass carbon electrode (GCE) deposited nano-sized gold particles. After a typical immuno-sandwich protocol, primary DNA was immobilized by labeling secondary antibody, which acted as a precursor to initiate RCA. The products of RCA provide large amount of sites to link detection DNAs, which were labeled by signal probes (ferrocenemonocarboxylic) and horseradish peroxidase (HRP). Moreover, the enzymatic amplification signals could be produced by the catalysis of HRP and Pt nanoparticles with the addition of H₂O₂. These lead to multiple amplification signals monitoring by electrochemical instrument and further resulted in high sensitivity of the immunoassay with the detection limit of 1.7 pg/mL. Copyright © 2011 Elsevier B.V. All rights reserved.

  20. Digital droplet multiple displacement amplification (ddMDA) for whole genome sequencing of limited DNA samples

    DOE PAGES

    Rhee, Minsoung; Light, Yooli K.; Meagher, Robert J.; ...

    2016-05-04

    Here, 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,more » 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.« less

  1. Digital droplet multiple displacement amplification (ddMDA) for whole genome sequencing of limited DNA samples

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rhee, Minsoung; Light, Yooli K.; Meagher, Robert J.

    Here, 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,more » 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.« less

  2. Development of a recombinase polymerase amplification assay for Vibrio parahaemolyticus detection with an internal amplification control.

    PubMed

    Yang, Huan-Lan; Wei, Shuang; Gooneratne, Ravi; Mutukumira, Anthony N; Ma, Xue-Jun; Tang, Shu-Ze; Wu, Xi-Yang

    2018-04-01

    A novel RPA-IAC assay using recombinase polymerase and an internal amplification control (IAC) for Vibrio parahaemolyticus detection was developed. Specific primers were designed based on the coding sequence for the toxR gene in V. parahaemolyticus. The recombinase polymerase amplification (RPA) reaction was conducted at a constant low temperature of 37 °C for 20 min. Assay specificity was validated by using 63 Vibrio strains and 10 non-Vibrio bacterial species. In addition, a competitive IAC was employed to avoid false-negative results, which co-amplified simultaneously with the target sequence. The sensitivity of the assay was determined as 3 × 10 3 CFU/mL, which is decidedly more sensitive than the established PCR method. This method was then used to test seafood samples that were collected from local markets. Seven out of 53 different raw seafoods were detected as V. parahaemolyticus-positive, which were consistent with those obtained using traditional culturing method and biochemical assay. This novel RPA-IAC assay provides a rapid, specific, sensitive, and more convenient detection method for V. parahaemolyticus.

  3. On the role of dealing with quantum coherence in amplitude amplification

    NASA Astrophysics Data System (ADS)

    Rastegin, Alexey E.

    2018-07-01

    Amplitude amplification is one of primary tools in building algorithms for quantum computers. This technique generalizes key ideas of the Grover search algorithm. Potentially useful modifications are connected with changing phases in the rotation operations and replacing the intermediate Hadamard transform with arbitrary unitary one. In addition, arbitrary initial distribution of the amplitudes may be prepared. We examine trade-off relations between measures of quantum coherence and the success probability in amplitude amplification processes. As measures of coherence, the geometric coherence and the relative entropy of coherence are considered. In terms of the relative entropy of coherence, complementarity relations with the success probability seem to be the most expository. The general relations presented are illustrated within several model scenarios of amplitude amplification processes.

  4. Hypsometric Amplification of Greenland Ice Sheet Meltwater Release

    NASA Astrophysics Data System (ADS)

    van As, D.; Hasholt, B.; Mikkelsen, A. B.; Holtegaard Nielsen, M.; Box, J.; Claesson Liljedahl, L.; Lindback, K.; Pitcher, L. H.

    2017-12-01

    Proglacial discharge monitoring provides valuable insights in Greenland ice sheet meltwater release. We use a 2006-2016 discharge time series from the Watson River draining 12000 km2 of the ice sheet in southwest Greenland to investigate the large variability in catchment-total meltwater production. An observationally-constrained reconstruction of past discharge shows that meltwater release has on average increased by a factor of 1.5 since 2003 compared to the 1949-2002 period, and that interannual variability has disproportionally increased by a factor of 2.1, suggesting that melt amplifiers are at play. We derive a hypsometric amplification factor of 1.6, which is the result of the exponential melt area increase with rising temperature. Peak meltwater discharge events such as during the July 2012 flooding are due to this and other melt amplifiers, but also require intense melting over a period exceeding the multi-day transit time for high-elevation meltwater to pass through the glacial drainage system.

  5. Tuning and amplification strategies for intravascular imaging coils.

    PubMed

    Yak, Nicolas; Anderson, Kevan J T; Wright, Graham A

    2012-11-01

    The manufacturing of intravascular imaging coils poses several challenges. Due to their size, it can be difficult to incorporate local matching networks and signal amplifiers. The goal of this study is to investigate tuning and amplification strategies for intravascular coils and to assess the signal-to-noise benefits of incorporating a matching network and/or miniature amplifier into catheter-based intravascular imaging devices at various locations in the signal chain. The results suggest that the use of a low-noise amplifier close to the receiving coil enables the use of miniature coaxial cables to be used despite being noisy. Moreover, an improvement in the signal-to-noise ratio of over 75% is presented over conventional intravascular coil configurations where the matching circuit and low-noise amplifier are placed at the proximal end. Therefore, designing devices for intravascular applications capable of generating high signal-to-noise ratio images becomes more feasible, also allowing for significant reductions in scan time. Copyright © 2011 Wiley Periodicals, Inc.

  6. Two methods for increased specificity and sensitivity in loop-mediated isothermal amplification

    USDA-ARS?s Scientific Manuscript database

    The technique of loop-mediated isothermal amplification (LAMP) utilizes 4 (or 6) primers targeting 6 (or 8) regions within a fairly small segment of a genome for amplification, with concentration higher than that used in traditional PCR methods. The high concentrations of primers used leads to an in...

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

    DOEpatents

    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.

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

    DOEpatents

    Van Antwerp, William Peter; Mastrototaro, John Joseph

    2004-10-12

    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.

  9. Amplification of intrinsic fluctuations by the Lorenz equations

    NASA Astrophysics Data System (ADS)

    Fox, Ronald F.; Elston, T. C.

    1993-07-01

    Macroscopic systems (e.g., hydrodynamics, chemical reactions, electrical circuits, etc.) manifest intrinsic fluctuations of molecular and thermal origin. When the macroscopic dynamics is deterministically chaotic, the intrinsic fluctuations may become amplified by several orders of magnitude. Numerical studies of this phenomenon are presented in detail for the Lorenz model. Amplification to macroscopic scales is exhibited, and quantitative methods (binning and a difference-norm) are presented for measuring macroscopically subliminal amplification effects. In order to test the quality of the numerical results, noise induced chaos is studied around a deterministically nonchaotic state, where the scaling law relating the Lyapunov exponent to noise strength obtained for maps is confirmed for the Lorenz model, a system of ordinary differential equations.

  10. Catechol-chitosan redox capacitor for added amplification in electrochemical immunoanalysis.

    PubMed

    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.

  11. Scalable amplification of strand subsets from chip-synthesized oligonucleotide libraries

    PubMed Central

    Schmidt, Thorsten L.; Beliveau, Brian J.; Uca, Yavuz O.; Theilmann, Mark; Da Cruz, Felipe; Wu, Chao-Ting; Shih, William M.

    2015-01-01

    Synthetic oligonucleotides are the main cost factor for studies in DNA nanotechnology, genetics and synthetic biology, which all require thousands of these at high quality. Inexpensive chip-synthesized oligonucleotide libraries can contain hundreds of thousands of distinct sequences, however only at sub-femtomole quantities per strand. Here we present a selective oligonucleotide amplification method, based on three rounds of rolling-circle amplification, that produces nanomole amounts of single-stranded oligonucleotides per millilitre reaction. In a multistep one-pot procedure, subsets of hundreds or thousands of single-stranded DNAs with different lengths can selectively be amplified and purified together. These oligonucleotides are used to fold several DNA nanostructures and as primary fluorescence in situ hybridization probes. The amplification cost is lower than other reported methods (typically around US$ 20 per nanomole total oligonucleotides produced) and is dominated by the use of commercial enzymes. PMID:26567534

  12. Geometric Effects on the Amplification of First Mode Instability Waves

    NASA Technical Reports Server (NTRS)

    Kirk, Lindsay C.; Candler, Graham V.

    2013-01-01

    The effects of geometric changes on the amplification of first mode instability waves in an external supersonic boundary layer were investigated using numerical techniques. Boundary layer stability was analyzed at Mach 6 conditions similar to freestream conditions obtained in quiet ground test facilities so that results obtained in this study may be applied to future test article design to measure first mode instability waves. The DAKOTA optimization software package was used to optimize an axisymmetric geometry to maximize the amplification of the waves at first mode frequencies as computed by the 2D STABL hypersonic boundary layer stability analysis tool. First, geometric parameters such as nose radius, cone half angle, vehicle length, and surface curvature were examined separately to determine the individual effects on the first mode amplification. Finally, all geometric parameters were allowed to vary to produce a shape optimized to maximize the amplification of first mode instability waves while minimizing the amplification of second mode instability waves. Since first mode waves are known to be most unstable in the form of oblique wave, the geometries were optimized using a broad range of wave frequencies as well as a wide range of oblique wave angles to determine the geometry that most amplifies the first mode waves. Since first mode waves are seen most often in flows with low Mach numbers at the edge of the boundary layer, the edge Mach number for each geometry was recorded to determine any relationship between edge Mach number and the stability of first mode waves. Results indicate that an axisymmetric cone with a sharp nose and a slight flare at the aft end under the Mach 6 freestream conditions used here will lower the Mach number at the edge of the boundary layer to less than 4, and the corresponding stability analysis showed maximum first mode N factors of 3.

  13. Trifunctional molecular beacon-mediated quadratic amplification for highly sensitive and rapid detection of mercury(II) ion with tunable dynamic range.

    PubMed

    Zhao, Yue; Liu, Huaqing; Chen, Feng; Bai, Min; Zhao, Junwu; Zhao, Yongxi

    2016-12-15

    Analyses of target with low abundance or concentration varying over many orders of magnitude are severe challenges faced by numerous assay methods due to their modest sensitivity and limited dynamic range. Here, we introduce a homogeneous and rapid quadratic polynomial amplification strategy through rational design of a trifunctional molecular beacon, which serves as not only a reporter molecule but also a bridge to couple two stage amplification modules without adding any reaction components or process other than basic linear amplification. As a test bed for our studies, we took mercury(II) ion as an example and obtained a high sensitivity with detection limit down to 200 pM within 30min. In order to create a tunable dynamic range, homotropic allostery is employed to modulate the target specific binding. When the number of metal binding site varies from 1 to 3, signal response is programmed accordingly with useful dynamic range spanning 50, 25 and 10 folds, respectively. Furthermore, the applicability of the proposed method in river water and biological samples are successfully verified with good recovery and reproducibility, indicating considerable potential for its practicality in complex real samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Finite Element Modelling of the Indo-Gangetic Basin to Study Site Amplification

    NASA Astrophysics Data System (ADS)

    Sivasubramonian, J.; Jaya, D.; Raghukanth, S. T. G.; Mai, P. M.

    2017-12-01

    We have developed a finite-element model of the 3D velocity structure of the Indo-Gangetic basin (IG basin) to quantify site amplifications due to seismic waves emanated from regional earthquakes. Estimating seismic wave amplifications is difficult in case of limited instrumentation, thus motivating us to propose a new simulation-based approach. The input required for the finite-element model include the spatial coordinates and the material properties (density, P-wave and S-wave velocities, Q factor) of the basin. Recent studies in the basin demarcate sediment layers of varying thickness, reaching down to a depth of 6 km and S-wave velocities ranging from 0.4-2.4 km/s (Srinivas et al., 2013). In the present study, our regional model has dimensions 900 x 900 x 80 km in x, y and z directions, discretized into 320 x 320 x 53 hexahedral elements. The top 6 km of the IG basin is divided into 8 different sediment layers with varying material properties. We use kinematic rupture models for the earthquake sources to simulate past as well as hypothetical future events. Two past earthquakes (Mw4.9, Delhi; Mw5.2, Chamoli) and two hypothetical earthquakes (Mw7.1; Mw8.5) are considered in our study. The rupture plane dimensions (L and W) and the slip distribution are estimated using the method of Mai and Beroza (2002). Based on focal-mechanism solutions and the depths of seismicity, we define the strike (580, 3090), the dip (650, 210), the rake (160, 770), and the depth of top edge of fault (5 km, 19 km) for the two large hypothetical earthquakes. Based on these parameters, the Centroid Moment Tensor (CMT) solution of the source is obtained. Ground motions are then simulated by solving the three-dimensional wave equation using the spectral element method (Komatitsch and Tromp, 1999). The key observations from our results are: 1) basin amplification factors for Peak Ground Velocity (PGV) are twice as high as Peak Ground Displacement (PGD) 2) PGV amplifications are as high as a

  15. Multiple displacement amplification on single cell and possible PGD applications.

    PubMed

    Hellani, Ali; Coskun, Serdar; Benkhalifa, Moncef; Tbakhi, Abelghani; Sakati, Nadia; Al-Odaib, Ali; Ozand, Pinar

    2004-11-01

    Multiple displacement amplification (MDA) is a technique used in the amplification of very low amounts of DNA and reported to yield large quantities of high-quality DNA. We used MDA to amplify the whole genome directly from a single cell. The most common techniques used in PGD are PCR and fluorescent in-situ hybridization (FISH). There are many limitations to these techniques including, the number of chromosomes diagnosed for FISH or the quality of DNA issued from a single cell PCR. This report shows, for the first time, use of MDA for single cell whole genome amplification. A total of 16 short tandem repeats (STRs) were amplified successfully with a similar pattern to the genomic DNA. Furthermore, allelic drop out (ADO) derived from MDA was assessed in 40 single cells by analysing (i) heterozygosity for a known beta globin mutation (IVSI-5 C-G) and by studying (ii) the heterozygous loci present in the STRs. ADO turned out to be 10.25% for the beta globin gene sequencing and 5% for the fluorescent PCR analysis of STRs. Moreover, the amplification accuracy of MDA permitted the detection of trisomy 21 on a single cell using comparative genome hybridization-array. Altogether, these data suggest that MDA can be used for single cell molecular karyotyping and the diagnosis of any single gene disorder in PGD.

  16. Amplification and Attenuation Across USArray Using Ambient Noise Wavefront Tracking

    NASA Astrophysics Data System (ADS)

    Bowden, Daniel C.; Tsai, Victor C.; Lin, Fan-Chi

    2017-12-01

    As seismic traveltime tomography continues to be refined using data from the vast USArray data set, it is advantageous to also exploit the amplitude information carried by seismic waves. We use ambient noise cross correlation to make observations of surface wave amplification and attenuation at shorter periods (8-32 s) than can be observed with only traditional teleseismic earthquake sources. We show that the wavefront tracking approach can be successfully applied to ambient noise correlations, yielding results quite similar to those from earthquake observations at periods of overlap. This consistency indicates that the wavefront tracking approach is viable for use with ambient noise correlations, despite concerns of the inhomogeneous and unknown distribution of noise sources. The resulting amplification and attenuation maps correlate well with known tectonic and crustal structure; at the shortest periods, our amplification and attenuation maps correlate well with surface geology and known sedimentary basins, while our longest period amplitudes are controlled by crustal thickness and begin to probe upper mantle materials. These amplification and attenuation observations are sensitive to crustal materials in different ways than traveltime observations and may be used to better constrain temperature or density variations. We also value them as an independent means of describing the lateral variability of observed Rayleigh wave amplitudes without the need for 3-D tomographic inversions.

  17. Clinical significance of MYCN amplification in patients with high-risk neuroblastoma.

    PubMed

    Lee, Ji Won; Son, Meong Hi; Cho, Hee Won; Ma, Young Eun; Yoo, Keon Hee; Sung, Ki Woong; Koo, Hong Hoe

    2018-05-24

    This study investigated the clinical significance of MYCN amplification within high-risk neuroblastoma (NB). Medical records of 135 patients who were diagnosed with high-risk NB from 2004 to 2016 were reviewed. Fifty-one (38%) patients had MYCN amplified tumors, and the remaining 84 (62%) had nonamplified tumors. MYCN amplification was associated with abdominal primary site, less differentiated pathology, higher levels of lactate dehydrogenase and neuron-specific enolase (NSE), lower vanillylmandelic acid level, and larger primary tumor volume at diagnosis. MYCN amplification was associated with a better early response (faster reduction of primary tumor volume and NSE level). The proportion of patients in complete response or very good partial response after induction treatment was relatively higher in MYCN amplified tumors than in nonamplified tumors; however, all progressions during induction treatment occurred only in MYCN amplified tumors (P = 0.007). The time to progression was shorter (median 1.5 years vs. 1.9 years, P = 0.037) and survival after relapse/progression was worse in MYCN amplified tumors (3 year overall survival: 7.7 ± 7.4% vs. 20.5 ± 8.8%, P = 0.046). There was no difference in event-free survival and overall survival between MYCN amplified and nonamplified tumors. MYCN amplification was associated with more aggressive features at diagnosis and a better early response, but a higher progression rate during induction treatment and lower chance of survival after relapse/progression. There was no difference in survival rates according to MYCN amplification in patients with high-risk NB. © 2018 Wiley Periodicals, Inc.

  18. New closed tube loop mediated isothermal amplification assay for prevention of product cross-contamination.

    PubMed

    Karthik, K; Rathore, Rajesh; Thomas, Prasad; Arun, T R; Viswas, K N; Dhama, Kuldeep; Agarwal, R K

    2014-01-01

    Loop mediated isothermal amplification (LAMP) assay, a promising diagnostic test, has been developed for detection of different pathogens of human as well as animals. Various positive points support its use as a field level test but the major problem is product cross contamination leading to false positive results. Different methods were adopted by various researchers to control this false positive amplification due to cross contamination but all have their own advantages and disadvantages. A new closed tube LAMP assay based on agar dye capsule was developed in the present study and this technique has some advantages over the other closed tube technique.•Agar at the concentration of 1.5% was used to sandwich SYBR green dye I with the aid of intradermal syringe. This agar dye capsule was placed over the LAMP reaction mixture before it was amplified.•To eliminate the hazardous nature of Ultra Violet (UV) light during result visualization of LAMP products, the present study demonstrates the use of Light Emitting Diode (LED) lights for result visualization.•LAMP was carried out for Brucella species detection using this modified techniques yielding good results without any cross contamination and LED showed similar fluorescence compared to UV.

  19. Coupled isothermal polynucleotide amplification and translation system

    NASA Technical Reports Server (NTRS)

    Joyce, Gerald F. (Inventor)

    1998-01-01

    A cell-free system for polynucleotide amplification and translation is disclosed. Also disclosed are methods for using the system and a composition which allows the various components of the system to function under a common set of reaction conditions.

  20. Identification of IL11RA and MELK amplification in gastric cancer by comprehensive genomic profiling of gastric cancer cell lines

    PubMed Central

    Calcagno, Danielle Queiroz; Takeno, Sylvia Santomi; Gigek, Carolina Oliveira; Leal, Mariana Ferreira; Wisnieski, Fernanda; Chen, Elizabeth Suchi; Araújo, Taíssa Maíra Thomaz; Lima, Eleonidas Moura; Melaragno, Maria Isabel; Demachki, Samia; Assumpção, Paulo Pimentel; Burbano, Rommel Rodriguez; Smith, Marília Cardoso

    2016-01-01

    AIM To identify common copy number alterations on gastric cancer cell lines. METHODS Four gastric cancer cell lines (ACP02, ACP03, AGP01 and PG100) underwent chromosomal comparative genome hybridization and array comparative genome hybridization. We also confirmed the results by fluorescence in situ hybridization analysis using the bacterial artificial chromosome clone and quantitative real time PCR analysis. RESULTS The amplification of 9p13.3 was detected in all cell lines by both methodologies. An increase in the copy number of 9p13.3 was also confirmed by fluorescence in situ hybridization analysis. Moreover, the interleukin 11 receptor alpha (IL11RA) and maternal embryonic leucine zipper kinase (MELK) genes, which are present in the 9p13.3 amplicon, revealed gains of the MELK gene in all the cell lines studied. Additionally, a gain in the copy number of IL11RA and MELK was observed in 19.1% (13/68) and 55.9% (38/68) of primary gastric adenocarcinoma samples, respectively. CONCLUSION The characterization of a small gain region at 9p13.3 in gastric cancer cell lines and primary gastric adenocarcinoma samples has revealed MELK as a candidate target gene that is possibly related to the development of gastric cancer. PMID:27920471