WorldWideScience

Sample records for strongly enhanced signals

  1. Strong electroweak symmetry breaking signals in WW scattering at TESLA

    CERN Document Server

    Chierici, R; Kobel, M

    2000-01-01

    A realistic study of the sensitivity to signals of strong electroweak symmetry breaking at TESLA energies using ee to WW nu nu and ee to ZZ nu nu processes is presented. Limits on alpha /sub 4/ and alpha /sub 5/, parameters of the electroweak chiral lagrangian, are given and discussed. (8 refs).

  2. High-Rate Strong-Signal Quantum Cryptography

    Science.gov (United States)

    Yuen, Horace P.

    1996-01-01

    Several quantum cryptosystems utilizing different kinds of nonclassical lights, which can accommodate high intensity fields and high data rate, are described. However, they are all sensitive to loss and both the high rate and the strong-signal character rapidly disappear. A squeezed light homodyne detection scheme is proposed which, with present-day technology, leads to more than two orders of magnitude data rate improvement over other current experimental systems for moderate loss.

  3. Enhanced thermal photon and dilepton production in strongly coupled = 4 SYM plasma in strong magnetic field

    Science.gov (United States)

    Mamo, Kiminad A.

    2013-08-01

    We calculate the DC conductivity tensor of strongly coupled = 4 super-Yang-Mills (SYM) plasma in a presence of a strong external magnetic field B ≫ T 2 by using its gravity dual and employing both the RG flow approach and membrane paradigm which give the same results. We find that, since the magnetic field B induces anisotropy in the plasma, different components of the DC conductivity tensor have different magnitudes depending on whether its components are in the direction of the magnetic field B. In particular, we find that a component of the DC conductivity tensor in the direction of the magnetic field B increases linearly with B while the other components (which are not in the direction of the magnetic field B) are independent of it. These results are consistent with the lattice computations of the DC conductivity tensor of the QCD plasma in an external magnetic field B. Using the DC conductivity tensor, we calculate the soft or low-frequency thermal photon and dilepton production rates of the strongly coupled = 4 SYM plasma in the presence of the strong external magnetic field B ≫ T 2. We find that the strong magnetic field B enhances both the thermal photon and dilepton production rates of the strongly coupled = 4 SYM plasma in a qualitative agreement with the experimentally observed enhancements at the heavy-ion collision experiments.

  4. Graphene Plasmonics: Guiding, Excitation and Strong SERS Enhancement

    DEFF Research Database (Denmark)

    Xiao, Sanshui

    Propagation of graphene plasmons in nanoribbon waveguides is numerically investigated and excitation of the graphene plasmons in a continuous graphene monolayer is experimentally demonstrated. Interaction between a graphene monolayer with metallic nanostructures is further experimentally studied......, and strong SERS enhancement for the graphene monolayer is observed with the aid of metallic nanostructures....

  5. Strong nuclear enhancement in intermediate mass Drell-Yan production

    CERN Document Server

    Jian Wei Qiu

    2002-01-01

    We calculate nuclear effect in Drell-Yan massive lepton-pair production in terms of parton multiple scattering in Quantum Chromodynamics (QCD). We present the nuclear modification to inclusive Drell-Yan cross sections d sigma /dQ/sup 2/ in terms of multiparton correlation functions. By extracting the size of the correlation functions from measured Drell-Yan transverse momentum broadening in nuclear media, we determine the nuclear modification at O( alpha /sub s//Q/sup 2/). We find that the nuclear modification strongly enhances the inclusive Drell-Yan cross section in the intermediate mass region (IMR): 1.5enhancement in the IMR in the Pb-Pb collisions at CERN SPS. (23 refs).

  6. Acquirement and enhancement of remote speech signals

    Science.gov (United States)

    Lü, Tao; Guo, Jin; Zhang, He-yong; Yan, Chun-hui; Wang, Can-jin

    2017-07-01

    To address the challenges of non-cooperative and remote acoustic detection, an all-fiber laser Doppler vibrometer (LDV) is established. The all-fiber LDV system can offer the advantages of smaller size, lightweight design and robust structure, hence it is a better fit for remote speech detection. In order to improve the performance and the efficiency of LDV for long-range hearing, the speech enhancement technology based on optimally modified log-spectral amplitude (OM-LSA) algorithm is used. The experimental results show that the comprehensible speech signals within the range of 150 m can be obtained by the proposed LDV. The signal-to-noise ratio ( SNR) and mean opinion score ( MOS) of the LDV speech signal can be increased by 100% and 27%, respectively, by using the speech enhancement technology. This all-fiber LDV, which combines the speech enhancement technology, can meet the practical demand in engineering.

  7. Strong Photoluminescence Enhancement of Silicon Oxycarbide through Defect Engineering

    Directory of Open Access Journals (Sweden)

    Brian Ford

    2017-04-01

    Full Text Available The following study focuses on the photoluminescence (PL enhancement of chemically synthesized silicon oxycarbide (SiCxOy thin films and nanowires through defect engineering via post-deposition passivation treatments. SiCxOy materials were deposited via thermal chemical vapor deposition (TCVD, and exhibit strong white light emission at room-temperature. Post-deposition passivation treatments were carried out using oxygen, nitrogen, and forming gas (FG, 5% H2, 95% N2 ambients, modifying the observed white light emission. The observed white luminescence was found to be inversely related to the carbonyl (C=O bond density present in the films. The peak-to-peak PL was enhanced ~18 and ~17 times for, respectively, the two SiCxOy matrices, oxygen-rich and carbon-rich SiCxOy, via post-deposition passivations. Through a combinational and systematic Fourier transform infrared spectroscopy (FTIR and PL study, it was revealed that proper tailoring of the passivations reduces the carbonyl bond density by a factor of ~2.2, corresponding to a PL enhancement of ~50 times. Furthermore, the temperature-dependent and temperature-dependent time resolved PL (TDPL and TD-TRPL behaviors of the nitrogen and forming gas passivated SiCxOy thin films were investigated to acquire further insight into the ramifications of the passivation on the carbonyl/dangling bond density and PL yield.

  8. Signal enhancement with variable span linear filters

    CERN Document Server

    Benesty, Jacob; Jensen, Jesper R

    2016-01-01

    This book introduces readers to the novel concept of variable span speech enhancement filters, and demonstrates how it can be used for effective noise reduction in various ways. Further, the book provides the accompanying Matlab code, allowing readers to easily implement the main ideas discussed. Variable span filters combine the ideas of optimal linear filters with those of subspace methods, as they involve the joint diagonalization of the correlation matrices of the desired signal and the noise. The book shows how some well-known filter designs, e.g. the minimum distortion, maximum signal-to-noise ratio, Wiener, and tradeoff filters (including their new generalizations) can be obtained using the variable span filter framework. It then illustrates how the variable span filters can be applied in various contexts, namely in single-channel STFT-based enhancement, in multichannel enhancement in both the time and STFT domains, and, lastly, in time-domain binaural enhancement. In these contexts, the properties of ...

  9. Signal Enhancement with Variable Span Linear Filters

    DEFF Research Database (Denmark)

    Benesty, Jacob; Christensen, Mads Græsbøll; Jensen, Jesper Rindom

    . Variable span filters combine the ideas of optimal linear filters with those of subspace methods, as they involve the joint diagonalization of the correlation matrices of the desired signal and the noise. The book shows how some well-known filter designs, e.g. the minimum distortion, maximum signal...... the time and STFT domains, and, lastly, in time-domain binaural enhancement. In these contexts, the properties of these filters are analyzed in terms of their noise reduction capabilities and desired signal distortion, and the analyses are validated and further explored in simulations....

  10. Concert halls with strong lateral reflections enhance musical dynamics.

    Science.gov (United States)

    Pätynen, Jukka; Tervo, Sakari; Robinson, Philip W; Lokki, Tapio

    2014-03-25

    One of the most thrilling cultural experiences is to hear live symphony-orchestra music build up from a whispering passage to a monumental fortissimo. The impact of such a crescendo has been thought to depend only on the musicians' skill, but here we show that interactions between the concert-hall acoustics and listeners' hearing also play a major role in musical dynamics. These interactions contribute to the shoebox-type concert hall's established success, but little prior research has been devoted to dynamic expression in this three-part transmission chain as a complete system. More forceful orchestral playing disproportionately excites high frequency harmonics more than those near the note's fundamental. This effect results in not only more sound energy, but also a different tone color. The concert hall transmits this sound, and the room geometry defines from which directions acoustic reflections arrive at the listener. Binaural directional hearing emphasizes high frequencies more when sound arrives from the sides of the head rather than from the median plane. Simultaneously, these same frequencies are emphasized by higher orchestral-playing dynamics. When the room geometry provides reflections from these directions, the perceived dynamic range is enhanced. Current room-acoustic evaluation methods assume linear behavior and thus neglect this effect. The hypothesis presented here is that the auditory excitation by reflections is emphasized with an orchestra forte most in concert halls with strong lateral reflections. The enhanced dynamic range provides an explanation for the success of rectangularly shaped concert-hall geometry.

  11. Signal Enhancement with Variable Span Linear Filters

    DEFF Research Database (Denmark)

    Benesty, Jacob; Christensen, Mads Græsbøll; Jensen, Jesper Rindom

    This book introduces readers to the novel concept of variable span speech enhancement filters, and demonstrates how it can be used for effective noise reduction in various ways. Further, the book provides the accompanying Matlab code, allowing readers to easily implement the main ideas discussed....... Variable span filters combine the ideas of optimal linear filters with those of subspace methods, as they involve the joint diagonalization of the correlation matrices of the desired signal and the noise. The book shows how some well-known filter designs, e.g. the minimum distortion, maximum signal......-to-noise ratio, Wiener, and tradeoff filters (including their new generalizations) can be obtained using the variable span filter framework. It then illustrates how the variable span filters can be applied in various contexts, namely in single-channel STFT-based enhancement, in multichannel enhancement in both...

  12. Enhancement of low-temperature thermometry by strong coupling

    Science.gov (United States)

    Correa, Luis A.; Perarnau-Llobet, Martí; Hovhannisyan, Karen V.; Hernández-Santana, Senaida; Mehboudi, Mohammad; Sanpera, Anna

    2017-12-01

    We consider the problem of estimating the temperature T of a very cold equilibrium sample. The temperature estimates are drawn from measurements performed on a quantum Brownian probe strongly coupled to it. We model this scenario by resorting to the canonical Caldeira-Leggett Hamiltonian and find analytically the exact stationary state of the probe for arbitrary coupling strength. In general, the probe does not reach thermal equilibrium with the sample, due to their nonperturbative interaction. We argue that this is advantageous for low-temperature thermometry, as we show in our model that (i) the thermometric precision at low T can be significantly enhanced by strengthening the probe-sampling coupling, (ii) the variance of a suitable quadrature of our Brownian thermometer can yield temperature estimates with nearly minimal statistical uncertainty, and (iii) the spectral density of the probe-sample coupling may be engineered to further improve thermometric performance. These observations may find applications in practical nanoscale thermometry at low temperatures—a regime which is particularly relevant to quantum technologies.

  13. Observation of strongly enhanced ultrashort pulses in 3-D metallic funnel-waveguide.

    Science.gov (United States)

    Lee, Dong-Hyub; Choi, Joonhee; Kim, Seungchul; Park, In-Yong; Han, Seunghwoi; Kim, Hyunwoong; Kim, Seung-Woo

    2014-07-14

    For strong field enhancement of ultrashort light pulses, a 3-D metallic funnel-waveguide is analyzed using the finite-difference time-domain (FDTD) method. Then the maximum intensity enhancement actually developed by the funnel-waveguide upon the injection of femtosecond laser pulses is observed using two-photon luminescence (TPL) microscopy. In addition, the ultrafast dephasing profile of the localized field at the hot spot of the funnel-waveguide is verified through the interferometric autocorrelation of the TPL signal. Finally it is concluded the funnel-waveguide is an effective 3-D nanostructure that is capable of boosting the peak pulse intensity of stronger than 80 TWcm(-2) by an enhancement factor of 20 dB without significant degradation of the ultrafast spatiotemporal characteristics of the original pulses.

  14. Intrinsic and enhanced biodegradation of benzene in strongly reduced aquifers

    NARCIS (Netherlands)

    Heiningen, W.N.M. van; Rijnaarts, H.H.M; Langenhoff, A.A.M.

    1999-01-01

    Laboratory microcosm studies were performed to examine intrinsic and enhanced benzene bioremediation using five different sediment and groundwater samples from three deeply anaerobic aquifers sited in northern Netherlands. The influence of addition of nitrate, sulfate, limited amounts of oxygen, and

  15. Strategic Mergers of Strong Institutions to Enhance Competitive Advantage

    Science.gov (United States)

    Harman, Grant; Harman, Kay

    2008-01-01

    Strategic mergers are formal combinations or amalgamations of higher education institutions with the aim of enhancing competitive advantage, or merging for "mutual growth". Recently, in a number of countries, there has been a decided shift from mergers initiated by governments, and dealing mainly with "problem" cases, towards…

  16. Strong enhancement of superconductivity in a nanosized Pb bridge

    OpenAIRE

    Misko, V. R.; Fomin, V. M.; Devreese, J. T.

    2000-01-01

    In recent experiments with a superconducting nanosized Pb bridge formed between a scanning tunneling microscope tip and a substrate, superconductivity has been detected at magnetic fields, which are few times larger than the third (surface) critical field. We describe the observed phenomenon on the basis of a numerical solution of the Ginzburg-Landau equations in a model structure consisting of six conoids. The spatial distribution of the superconducting phase is shown to be strongly inhomoge...

  17. Strong enhancement of magnetic anisotropy energy in alloyed nanowires

    Energy Technology Data Exchange (ETDEWEB)

    Negulyaev, Nikolay; Niebergall, Larissa; Stepanyuk, Valeri [Max-Planck-Institut fuer Mikrostrukturphysik, D-06120 Halle (Germany); Juarez Reyes, Lucila; Pastor, Gustavo [Institut fuer Theoretische Physik, Universitaet Kassel, D-34132 Kassel (Germany); Dorantes-Davila, Jesus [Instituto de Fisica, Universidad Autonoma de San Luis Potosi, 78000 San Luis Potosi (Mexico)

    2011-07-01

    One-dimensional atomic structures (monatomic wires and chains) are believed to be likely candidates for creation of nanostructures with large atomic orbital moments and hence with giant magnetic anisotropy energy (MAE) per atom. We investigate the possibility of tuning the MAE of 3d transition metal monowires alloyed with 5d elements (Ir, Pt). Our ab initio studies give clear evidence that in mixed 3d-5d atomic wires MAE is one and even two orders of magnitude more than in pure wires constructed of the corresponding 5d and 3d elements, respectively. Mechanisms responsible for the formation of such a strong MAE are revealed. The interplay between the structure of a monowire and its MAE is demonstrated. The contribution of both types of species (3d and 5d) into the MAE is discussed.

  18. Strong enhancement of superconductivity in a nanosized Pb bridge

    Science.gov (United States)

    Misko, V. R.; Fomin, V. M.; Devreese, J. T.

    2001-07-01

    In recent experiments with a superconducting nanosized Pb bridge formed between a scanning tunneling microscope tip and a substrate, superconductivity has been detected at magnetic fields, that are a few times larger than the third (surface) critical field. We describe the observed phenomenon on the basis of a numerical solution of the Ginzburg-Landau equations in a model structure consisting of six conoids. The spatial distribution of the superconducting phase is shown to be strongly inhomogeneous, with a concentration of the superconducting phase near the narrowest part (the ``neck'') of the bridge. We show that suppression of superconductivity in the bridge by applied magnetic field or by temperature first occurs near the bases and then in the neck region, what leads to a continuous superconducting-to-normal resistive transition. A position of the transition midpoint depends on temperature and, typically, is by one order of magnitude higher than the second critical field Hc2. We find that the vortex states can be realized in the bridge at low temperatures T/Tc<=0.6. The vortex states lead to a fine structure of the superconducting-to-normal resistive transition. We also analyze vortex states in the bridge that are characterized by a varying vorticity as a function of the bridge's height.

  19. Strong Static Magnetic Fields Increase the Gel Signal in Partially Hydrated DPPC/DMPC Membranes

    Directory of Open Access Journals (Sweden)

    Jennifer Tang

    2015-09-01

    Full Text Available NIt was recently reported that static magnetic fields increase lipid order in the hydrophobic membrane core of dehydrated native plant plasma membranes [Poinapen, Soft Matter 9:6804-6813, 2013]. As plasma membranes are multicomponent, highly complex structures, in order to elucidate the origin of this effect, we prepared model membranes consisting of a lipid species with low and high melting temperature. By controlling the temperature, bilayers coexisting of small gel and fluid domains were prepared as a basic model for the plasma membrane core. We studied molecular order in mixed lipid membranes made of dimyristoyl-sn-glycero-3-phosphocholine (DMPC and dipalmitoyl-sn-glycero-3-phosphocholine (DPPC using neutron diffraction in the presence of strong static magnetic fields up to 3.5 T. The contribution of the hydrophobic membrane core was highlighted through deuterium labeling the lipid acyl chains. There was no observable effect on lipid organization in fluid or gel domains at high hydration of the membranes. However, lipid order was found to be enhanced at a reduced relative humidity of 43%: a magnetic field of 3.5 T led to an increase of the gel signal in the diffraction patterns of 5%. While all biological materials have weak diamagnetic properties, the corresponding energy is too small to compete against thermal disorder or viscous effects in the case of lipid molecules. We tentatively propose that the interaction between the fatty acid chains’ electric moment and the external magnetic field is driving the lipid tails in the hydrophobic membrane core into a better ordered state.

  20. Strong Static Magnetic Fields Increase the Gel Signal in Partially Hydrated DPPC/DMPC Membranes.

    Science.gov (United States)

    Tang, Jennifer; Alsop, Richard J; Schmalzl, Karin; Epand, Richard M; Rheinstädter, Maikel C

    2015-09-29

    NIt was recently reported that static magnetic fields increase lipid order in the hydrophobic membrane core of dehydrated native plant plasma membranes [Poinapen, Soft Matter 9:6804-6813, 2013]. As plasma membranes are multicomponent, highly complex structures, in order to elucidate the origin of this effect, we prepared model membranes consisting of a lipid species with low and high melting temperature. By controlling the temperature, bilayers coexisting of small gel and fluid domains were prepared as a basic model for the plasma membrane core. We studied molecular order in mixed lipid membranes made of dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) using neutron diffraction in the presence of strong static magnetic fields up to 3.5 T. The contribution of the hydrophobic membrane core was highlighted through deuterium labeling the lipid acyl chains. There was no observable effect on lipid organization in fluid or gel domains at high hydration of the membranes. However, lipid order was found to be enhanced at a reduced relative humidity of 43%: a magnetic field of 3.5 T led to an increase of the gel signal in the diffraction patterns of 5%. While all biological materials have weak diamagnetic properties, the corresponding energy is too small to compete against thermal disorder or viscous effects in the case of lipid molecules. We tentatively propose that the interaction between the fatty acid chains' electric moment and the external magnetic field is driving the lipid tails in the hydrophobic membrane core into a better ordered state.

  1. Gold Superparticles Functionalized with Azobenzene Derivatives: SERS Nanotags with Strong Signals.

    Science.gov (United States)

    Ma, Ying; Promthaveepong, Kittithat; Li, Nan

    2017-03-29

    The surface-enhanced Raman spectroscopy (SERS) nanotag was proposed as a substitute for fluorescent dye for imaging and biosensors several decades ago. However, its weak signal and poor reproducibility has hindered its application. Here, we report a new strategy to form Au superparticles (AuSPs) with high SERS enhancement via one-pot formation and self-assembly of Au nanoparticles (NPs). An azobenzene-carrying Raman reporter was synthesized to exhibit a large Raman cross-section and multiple bands. The self-assembly of the Raman reporter on AuSPs generated SERS nanotags with intense signals. A Raman reporter carrying boronic acid and azobenzene groups displayed six distinctive bands. Its corresponding SERS nanotag demonstrated a high sensing ability toward glycoprotein through aggregation-induced SERS enhancement or as a substitute for labeled antibodies in an immunoassay of the glycoprotein.

  2. RHOA inactivation enhances Wnt signaling and promotes colorectal cancer

    Science.gov (United States)

    Rodrigues, Paulo; Macaya, Irati; Bazzocco, Sarah; Mazzolini, Rocco; Andretta, Elena; Dopeso, Higinio; Mateo-Lozano, Silvia; Bilić, Josipa; Cartón-García, Fernando; Nieto, Rocio; Suárez-López, Lucia; Afonso, Elsa; Landolfi, Stefania; Hernandez-Losa, Javier; Kobayashi, Kazuto; Cajal, Santiago Ramón y; Tabernero, Josep; Tebbutt, Niall C.; Mariadason, John M.; Schwartz, Simo; Arango, Diego

    2014-01-01

    Activation of the small GTPase RHOA has strong oncogenic effects in many tumor types, although its role in colorectal cancer remains unclear. Here we show that RHOA inactivation contributes to colorectal cancer progression/metastasis, largely through the activation of Wnt/β-catenin signaling. RhoA inactivation in the murine intestine accelerates the tumorigenic process and in human colon cancer cells leads to the redistribution of β-catenin from the membrane to the nucleus and enhanced Wnt/β-catenin signaling, resulting in increased proliferation, invasion and de-differentiation. In mice, RHOA inactivation contributes to colon cancer metastasis and reduced RHOA levels were observed at metastatic sites compared to primary human colon tumors. Therefore, we have identified a new mechanism of activation of Wnt/β-catenin signaling and characterized the role of RHOA as a novel tumor suppressor in colorectal cancer. These results constitute a shift from the current paradigm and demonstrate that RHO GTPases can suppress tumor progression and metastasis. PMID:25413277

  3. The No-Higgs Signal: Strong WW Scattering at the LHC

    Energy Technology Data Exchange (ETDEWEB)

    Michael S. Chanowitz

    2004-12-07

    Strong WW scattering at the LHC is discussed as a manifestation of electroweak symmetry breaking in the absence of a light Higgs bosom. The general framework of the Higgs mechanism--with or without a Higgs boson--is reviewed, and unitarity is shown to fix the scale of strong WW scattering. Strong WW scattering is also shown to be a possible outcome of five-dimensional models, which do not employ the usual Higgs mechanism at the TeV scale. Precision electroweak constraints are briefly discussed. Illustrative LHC signals are reviewed for models with QCD-like dynamics, stressing the complementarity of the W{sup {+-}}Z and like-charge W{sup +}W{sup +} + W{sup -}W{sup -} channels.

  4. Spectrum of absorption of a weak signal by an atom in a strong field

    International Nuclear Information System (INIS)

    Bakaev, D.S.; Vdovin, Y.A.; Ermachenko, V.M.; Yakovlenko, S.I.

    1985-01-01

    An analysis is made of the spectrum of absorption of a weak probe electromagnetic field by two-level atoms in a strong resonant laser field, undergoing collision with buffer gas atoms. The analysis is made using an approach that allows for the direct influence of a strong electromagnetic field on the dynamics of an elastic collision between an active atom and a buffer gas atom. Rate equations are analyzed for a combined ''atom--strong electromagnetic field'' system (an atom ''dressed'' by the field) allowing for spontaneous and optical collisional transitions, and also for the interaction with the probe field. In the steady-state case, an expression is derived for the electric susceptibility of the medium at the small-signal frequency. This expression contains the rates of the optical collisional transitions that depend nontrivially on the parameters of the strong electromagnetic field. The phenomenological characteristics of optical collisional transitions generally used are only valid at low intensities and for small frequency detunings of the strong electromagnetic field, i.e., in the impact limit

  5. Strongly lensed gravitational waves and electromagnetic signals as powerful cosmic rulers

    Science.gov (United States)

    Wei, Jun-Jie; Wu, Xue-Feng

    2017-12-01

    In this paper, we discuss the possibility of using strongly lensed gravitational waves (GWs) and their electromagnetic (EM) counterparts as powerful cosmic rulers. In the EM domain, it has been suggested that joint observations of the time delay (Δτ) between lensed quasar images and the velocity dispersion (σ) of the lensing galaxy (i.e. the combination Δτ/σ2) are able to constrain the cosmological parameters more strongly than Δτ or σ2 separately. Here, for the first time, we propose that this Δτ/σ2 method can be applied to the strongly lensed systems observed in both GW and EM windows. Combining the redshifts, images and σ observed in the EM domain with the very precise Δτ derived from lensed GW signals, we expect that accurate multimessenger cosmology can be achieved in the era of third-generation GW detectors. Comparing with the constraints from the Δτ method, we prove that using Δτ/σ2 can improve the discrimination between cosmological models. Furthermore, we demonstrate that with ∼50 strongly lensed GW-EM systems, we can reach a constraint on the dark energy equation of state w comparable to the 580 Union2.1 Type Ia supernovae data. Much more stringent constraints on w can be obtained when combining the Δτ and Δτ/σ2 methods.

  6. Signal-enhancement reflective pulse oximeter with Fresnel lens

    Science.gov (United States)

    Chung, Shuang-Chao; Sun, Ching-Cherng

    2016-09-01

    In this paper, a new reflective pulse oximeter is proposed and demonstrated with implanting a Fresnel lens, which enhances the reflected signal. An optical simulation model incorporated with human skin characteristics is presented to evaluate the capability of the Fresnel lens. In addition, the distance between the light emitting diode and the photodiode is optimized. Compared with the other reflective oximeters, the reflected signal light detected by the photodiode is enhanced to more than 140%.

  7. Manipulating insulin signaling to enhance mosquito reproduction

    Directory of Open Access Journals (Sweden)

    Rasgon Jason L

    2009-08-01

    Full Text Available Abstract Backgrond In the mosquito Aedes aegypti the insulin/insulin growth factor I signaling (IIS cascade is a key regulator of many physiological processes, including reproduction. Two important reproductive events, steroidogenesis in the ovary and yolk synthesis in the fat body, are regulated by the IIS cascade in mosquitoes. The signaling molecule phosphatase and tensin homolog (PTEN is a key inhibitor of the IIS cascade that helps modulate the activity of the IIS cascade. In Ae. aegypti, six unique splice variants of AaegPTEN were previously identified, but the role of these splice variants, particularly AaegPTEN3 and 6, were unknown. Results Knockdown of AaegPTEN or its specific splice variant AaegPTEN6 (the splice variant thought to regulate reproduction in the ovary and fat body using RNAi led to a 15–63% increase in egg production with no adverse effects on egg viability during the first reproductive cycle. Knockdown of AaegPTEN3, expressed predominantly in the head, had no effect on reproduction. We also characterized the protein expression patterns of these two splice variants during development and in various tissues during a reproductive cycle. Conclusion Previous studies in a range of organisms, including Drosophila melanogaster and Caenorhabditis elegans, have demonstrated that disruption of the IIS cascade leads to decreased reproduction or sterility. In this study we demonstrate that knockdown of the IIS inhibitor PTEN can actually increase reproduction in the mosquito, at least during the first reproductive cycle.

  8. Helmholtz resonator enhancement of photoacoustic signals

    Science.gov (United States)

    McClenny, W. A.; Bennett, C. A., Jr.; Russwurm, G. M.; Richmond, R.

    1981-02-01

    A Helmholtz resonator attached to a nonresonant photoacoustic cell enhances the responsivity to trace gas absorption by as much as a factor of 15.3. A simple system model based on a lumped parameter approach predicts the experimentally determined resonance frequency f sub zero within 6% for all five resonator volumes tried and gives a pressure amplitude response at resonance proportional to f sub zero to the -5/2, which is the approximate experimental dependence. Optimization of response based on the model shows a pressure amplitude dependence on a to the 1/2, the square root of the radius of the cylindrical tube connecting the cell and the resonator.

  9. Digital payloads - Enhanced performance through signal processing

    Science.gov (United States)

    Bjornstrom, G.

    A transparent signal-processing payload architecture applicable to mobile communication satellites is introduced, and its features and implementation issues are discussed. In its basic form it is characterized by the formation of a large number of narrowband beams directed at the individual users on ground, and is demonstrated to offer improved transmit power efficiency, frequency-reuse capability and traffic-routing flexibility. The processor implementation is envisaged to make extensive use of digital processing functions and ASIC technology combined with advanced SAW techniques. In addition to its inherent attractive features, this architecture provides many of the benefits of full onboard regeneration and processing while preserving most of the flexibility of conventional analog transponders. Simplified derivatives of the basic configuration that offer reduced processing complexity while preserving the essential advantages gained are also presented. Although initially conceived for FDMA/SCPC-type traffic, the concept can also be adapted to other transmission formats.

  10. Analysis of luminosity distributions of strong lensing galaxies: subtraction of diffuse lensed signal

    Science.gov (United States)

    Biernaux, J.; Magain, P.; Hauret, C.

    2017-08-01

    Context. Strong gravitational lensing gives access to the total mass distribution of galaxies. It can unveil a great deal of information about the lenses' dark matter content when combined with the study of the lenses' light profile. However, gravitational lensing galaxies, by definition, appear surrounded by lensed signal, both point-like and diffuse, that is irrelevant to the lens flux. Therefore, the observer is most often restricted to studying the innermost portions of the galaxy, where classical fitting methods show some instabilities. Aims: We aim at subtracting that lensed signal and at characterising some lenses' light profile by computing their shape parameters (half-light radius, ellipticity, and position angle). Our objective is to evaluate the total integrated flux in an aperture the size of the Einstein ring in order to obtain a robust estimate of the quantity of ordinary (luminous) matter in each system. Methods: We are expanding the work we started in a previous paper that consisted in subtracting point-like lensed images and in independently measuring each shape parameter. We improve it by designing a subtraction of the diffuse lensed signal, based only on one simple hypothesis of symmetry. We apply it to the cases where it proves to be necessary. This extra step improves our study of the shape parameters and we refine it even more by upgrading our half-light radius measurement method. We also calculate the impact of our specific image processing on the error bars. Results: The diffuse lensed signal subtraction makes it possible to study a larger portion of relevant galactic flux, as the radius of the fitting region increases by on average 17%. We retrieve new half-light radii values that are on average 11% smaller than in our previous work, although the uncertainties overlap in most cases. This shows that not taking the diffuse lensed signal into account may lead to a significant overestimate of the half-light radius. We are also able to measure

  11. Development of an Earthquake Early Warning System Using Real-Time Strong Motion Signals.

    Science.gov (United States)

    Wu, Yih-Min; Kanamori, Hiroo

    2008-01-09

    As urbanization progresses worldwide, earthquakes pose serious threat to livesand properties for urban areas near major active faults on land or subduction zonesoffshore. Earthquake Early Warning (EEW) can be a useful tool for reducing earthquakehazards, if the spatial relation between cities and earthquake sources is favorable for suchwarning and their citizens are properly trained to respond to earthquake warning messages.An EEW system forewarns an urban area of forthcoming strong shaking, normally with afew sec to a few tens of sec of warning time, i.e., before the arrival of the destructive Swavepart of the strong ground motion. Even a few second of advanced warning time willbe useful for pre-programmed emergency measures for various critical facilities, such asrapid-transit vehicles and high-speed trains to avoid potential derailment; it will be alsouseful for orderly shutoff of gas pipelines to minimize fire hazards, controlled shutdown ofhigh-technological manufacturing operations to reduce potential losses, and safe-guardingof computer facilities to avoid loss of vital databases. We explored a practical approach toEEW with the use of a ground-motion period parameter τc and a high-pass filtered verticaldisplacement amplitude parameter Pd from the initial 3 sec of the P waveforms. At a givensite, an earthquake magnitude could be determined from τ c and the peak ground-motionvelocity (PGV) could be estimated from Pd. In this method, incoming strong motion acceleration signals are recursively converted to ground velocity and displacement. A Pwavetrigger is constantly monitored. When a trigger occurs, τ c and Pd are computed. Theearthquake magnitude and the on-site ground-motion intensity could be estimated and thewarning could be issued. In an ideal situation, such warnings would be available within 10sec of the origin time of a large earthquake whose subsequent ground motion may last fortens of seconds.

  12. Development of an Earthquake Early Warning System Using Real-Time Strong Motion Signals

    Directory of Open Access Journals (Sweden)

    Hiroo Kanamori

    2008-01-01

    Full Text Available As urbanization progresses worldwide, earthquakes pose serious threat to livesand properties for urban areas near major active faults on land or subduction zonesoffshore. Earthquake Early Warning (EEW can be a useful tool for reducing earthquakehazards, if the spatial relation between cities and earthquake sources is favorable for suchwarning and their citizens are properly trained to respond to earthquake warning messages.An EEW system forewarns an urban area of forthcoming strong shaking, normally with afew sec to a few tens of sec of warning time, i.e., before the arrival of the destructive Swavepart of the strong ground motion. Even a few second of advanced warning time willbe useful for pre-programmed emergency measures for various critical facilities, such asrapid-transit vehicles and high-speed trains to avoid potential derailment; it will be alsouseful for orderly shutoff of gas pipelines to minimize fire hazards, controlled shutdown ofhigh-technological manufacturing operations to reduce potential losses, and safe-guardingof computer facilities to avoid loss of vital databases. We explored a practical approach toEEW with the use of a ground-motion period parameter τc and a high-pass filtered verticaldisplacement amplitude parameter Pd from the initial 3 sec of the P waveforms. At a givensite, an earthquake magnitude could be determined from τc and the peak ground-motionvelocity (PGV could be estimated from Pd. In this method, incoming strong motion acceleration signals are recursively converted to ground velocity and displacement. A Pwavetrigger is constantly monitored. When a trigger occurs, τc and Pd are computed. Theearthquake magnitude and the on-site ground-motion intensity could be estimated and thewarning could be issued. In an ideal situation, such warnings would be available within 10sec of the origin time of a large earthquake whose subsequent ground motion may last fortens of seconds.

  13. Low dose gamma irradiation enhances defined signaling components of intercellular reactive oxygen-mediated apoptosis induction

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, G, E-mail: georg.bauer@uniklinik-freiburg.de [Abteilung Virologie, Institut fuer Medizinische Mikrobiologie und Hygiene, Universitaet Freiburg, Freiburg (Germany)

    2011-01-01

    Transformed cells are selectively removed by intercellular ROS-mediated induction of apoptosis. Signaling is based on the HOCl and the NO/peroxynitrite pathway (major pathways) and the nitryl chloride and the metal-catalyzed Haber-Weiss pathway (minor pathways). During tumor progression, resistance against intercellular induction of apoptosis is acquired through expression of membrane-associated catalase. Low dose radiation of nontransformed cells has been shown to enhance intercellular induction of apoptosis. The present study was performed to define the signaling components which are modulated by low dose gamma irradiation. Low dose radiation induced the release of peroxidase from nontransformed, transformed and tumor cells. Extracellular superoxide anion generation was strongly enhanced in the case of transformed cells and tumor cells, but not in nontransformed cells. Enhancement of peroxidase release and superoxide anion generation either increased intercellular induction of apoptosis of transformed cells, or caused a partial protection under specific signaling conditions. In tumor cells, low dose radiation enhanced the production of major signaling components, but this had no effect on apoptosis induction, due to the strong resistance mechanism of tumor cells. Our data specify the nature of low dose radiation-induced effects on specific signaling components of intercellular induction of apoptosis at defined stages of multistep carcinogenesis.

  14. Strong enhancement of streaming current power by application of two phase flow

    NARCIS (Netherlands)

    Xie, Yanbo; Sherwood, John D.; Shui, Lingling; van den Berg, Albert; Eijkel, Jan C.T.

    2011-01-01

    We show that the performance of a streaming-potential based microfluidic energy conversion system can be strongly en-hanced by the use of two phase flow. In single-phase systems, the internal conduction current induced by the streaming poten-tial limits the output power, while in a two-phase system

  15. Adaptive optics for enhanced signal in CARS microscopy.

    Science.gov (United States)

    Wright, A J; Poland, S P; Girkin, J M; Freudiger, C W; Evans, C L; Xie, X S

    2007-12-24

    We report the use of adaptive optics with coherent anti-Stokes Raman scattering (CARS) microscopy for label-free deep tissue imaging based on molecular vibrational spectroscopy. The setup employs a deformable membrane mirror and a random search optimization algorithm to improve signal intensity and image quality at large sample depths. We demonstrate the ability to correct for both system and sample-induced aberrations in test samples as well as in muscle tissue in order to enhance the CARS signal. The combined system and sample-induced aberration correction increased the signal by an average factor of approximately 3x for the test samples at a depth of 700 microm and approximately 6x for muscle tissue at a depth of 260 microm. The enhanced signal and higher penetration depth offered by adaptive optics will augment CARS microscopy as an in vivo and in situ biomedical imaging modality.

  16. Exponential signaling gain at the receptor level enhances signal-to-noise ratio in bacterial chemotaxis.

    Directory of Open Access Journals (Sweden)

    Silke Neumann

    Full Text Available Cellular signaling systems show astonishing precision in their response to external stimuli despite strong fluctuations in the molecular components that determine pathway activity. To control the effects of noise on signaling most efficiently, living cells employ compensatory mechanisms that reach from simple negative feedback loops to robustly designed signaling architectures. Here, we report on a novel control mechanism that allows living cells to keep precision in their signaling characteristics - stationary pathway output, response amplitude, and relaxation time - in the presence of strong intracellular perturbations. The concept relies on the surprising fact that for systems showing perfect adaptation an exponential signal amplification at the receptor level suffices to eliminate slowly varying multiplicative noise. To show this mechanism at work in living systems, we quantified the response dynamics of the E. coli chemotaxis network after genetically perturbing the information flux between upstream and downstream signaling components. We give strong evidence that this signaling system results in dynamic invariance of the activated response regulator against multiplicative intracellular noise. We further demonstrate that for environmental conditions, for which precision in chemosensing is crucial, the invariant response behavior results in highest chemotactic efficiency. Our results resolve several puzzling features of the chemotaxis pathway that are widely conserved across prokaryotes but so far could not be attributed any functional role.

  17. Exponential signaling gain at the receptor level enhances signal-to-noise ratio in bacterial chemotaxis.

    Science.gov (United States)

    Neumann, Silke; Løvdok, Linda; Bentele, Kajetan; Meisig, Johannes; Ullner, Ekkehard; Paldy, Ferencz S; Sourjik, Victor; Kollmann, Markus

    2014-01-01

    Cellular signaling systems show astonishing precision in their response to external stimuli despite strong fluctuations in the molecular components that determine pathway activity. To control the effects of noise on signaling most efficiently, living cells employ compensatory mechanisms that reach from simple negative feedback loops to robustly designed signaling architectures. Here, we report on a novel control mechanism that allows living cells to keep precision in their signaling characteristics - stationary pathway output, response amplitude, and relaxation time - in the presence of strong intracellular perturbations. The concept relies on the surprising fact that for systems showing perfect adaptation an exponential signal amplification at the receptor level suffices to eliminate slowly varying multiplicative noise. To show this mechanism at work in living systems, we quantified the response dynamics of the E. coli chemotaxis network after genetically perturbing the information flux between upstream and downstream signaling components. We give strong evidence that this signaling system results in dynamic invariance of the activated response regulator against multiplicative intracellular noise. We further demonstrate that for environmental conditions, for which precision in chemosensing is crucial, the invariant response behavior results in highest chemotactic efficiency. Our results resolve several puzzling features of the chemotaxis pathway that are widely conserved across prokaryotes but so far could not be attributed any functional role.

  18. Analysis of Enhanced Velocity Signals Observed during Solar Flares ...

    Indian Academy of Sciences (India)

    2003-10-28

    Oct 28, 2003 ... close to the vicinity of the hard X-ray source regions as observed with. RHESSI. The power maps of the active region show enhancement in the frequency regime 5–6.5mHz, while there is feeble or no enhancement of these signals in 2–4 mHz frequency band. High energy particles with sufficient momentum ...

  19. Multicenter evaluation of signal enhancement algorithms for hearing aids

    NARCIS (Netherlands)

    Luts, Heleen; Eneman, Koen; Wouters, Jan; Schulte, Michael; Vormann, Matthias; Buechler, Michael; Dillier, Norbert; Houben, Rolph; Dreschler, Wouter A.; Froehlich, Matthias; Puder, Henning; Grimm, Giso; Hohmann, Volker; Leijon, Arne; Lombard, Anthony; Mauler, Dirk; Spriet, Ann

    2010-01-01

    In the framework of the European HearCom project, promising signal enhancement algorithms were developed and evaluated for future use in hearing instruments. To assess the algorithms' performance, five of the algorithms were selected and implemented on a common real-time hardware/software platform.

  20. Strong enhancement of light-matter interaction in graphene coupled to a photonic crystal nanocavity.

    Science.gov (United States)

    Gan, Xuetao; Mak, Kin Fai; Gao, Yuanda; You, Yumeng; Hatami, Fariba; Hone, James; Heinz, Tony F; Englund, Dirk

    2012-11-14

    We demonstrate a large enhancement in the interaction of light with graphene through coupling with localized modes in a photonic crystal nanocavity. Spectroscopic studies show that a single atomic layer of graphene reduces the cavity reflection by more than a factor of one hundred, while also sharply reducing the cavity quality factor. The strong interaction allows for cavity-enhanced Raman spectroscopy on subwavelength regions of a graphene sample. A coupled-mode theory model matches experimental observations and indicates significantly increased light absorption in the graphene layer. The coupled graphene-cavity system also enables precise measurements of graphene's complex refractive index.

  1. Silaffin peptides as a novel signal enhancer for gravimetric biosensors.

    Science.gov (United States)

    Nam, Dong Hyun; Lee, Jeong-O; Sang, Byoung-In; Won, Keehoon; Kim, Yong Hwan

    2013-05-01

    Application of biomimetic silica formation to gravimetric biosensors has been conducted for the first time. As a model system, silaffin peptides fused with green fluorescent protein (GFP) were immobilized on a gold quartz crystal resonator for quartz crystal microbalances using a self-assembled monolayer. When a solution of silicic acid was supplied, silica particles were successfully deposited on the Au surface, resulting in a significant change in resonance frequency (i.e., signal enhancement) with the silaffin-GFP. However, frequency was not altered when bare GFP was used as a control. The novel peptide enhancer is advantageous because it can be readily and quantitatively conjugated with sensing proteins using recombinant DNA technology. As a proof of concept, this study shows that the silaffin domains can be employed as a novel and efficient biomolecular signal enhancer for gravimetric biosensors.

  2. A Novel Blind Source Separation Algorithm and Performance Analysis of Weak Signal against Strong Interference in Passive Radar Systems

    Directory of Open Access Journals (Sweden)

    Chengjie Li

    2016-01-01

    Full Text Available In Passive Radar System, obtaining the mixed weak object signal against the super power signal (jamming is still a challenging task. In this paper, a novel framework based on Passive Radar System is designed for weak object signal separation. Firstly, we propose an Interference Cancellation algorithm (IC-algorithm to extract the mixed weak object signals from the strong jamming. Then, an improved FastICA algorithm with K-means cluster is designed to separate each weak signal from the mixed weak object signals. At last, we discuss the performance of the proposed method and verify the novel method based on several simulations. The experimental results demonstrate the effectiveness of the proposed method.

  3. Enhancing Raman signals with an interferometrically controlled AFM tip

    International Nuclear Information System (INIS)

    Oron-Carl, Matti; Krupke, Ralph

    2013-01-01

    We demonstrate the upgrade of a commercial confocal Raman microscope into a tip-enhanced Raman microscope/spectroscopy system (TERS) by integrating an interferometrically controlled atomic force microscope into the base of an existing upright microscope to provide near-field detection and thus signal enhancement. The feasibility of the system is demonstrated by measuring the Raman near-field enhancement on thin PEDOT:PSS films and on carbon nanotubes within a device geometry. An enhancement factor of 2–3 and of 5–6 is observed, respectively. Moreover, on a nanotube device we show local conductivity measurement and its correlation to Raman and topography recordings. Upgrading an existing upright confocal Raman microscope in the demonstrated way is significantly cheaper than purchasing a complete commercial TERS system. (paper)

  4. To analysis and identify various kinds of strong echo signal of ocular-perforating injury by B-scan ultrasound

    Directory of Open Access Journals (Sweden)

    Rui-Juan Wang

    2014-05-01

    Full Text Available AIM: To analysis the diagnostic value of B-scan on various kinds of strong echo signal of ocular-perforating injury.METHODS: Totally 176 patients(176 eyeswith ocular-perforating injury underwent B-scan ultrasound examination. We observed the B-scan imaging findings of the lens, vitreous cavity, eyeball wall and retrobulbar space.RESULTS: All 176 patients(176 eyesunderwent B-scan ultrasound examination had strong echo. Vitreous hemorrhage was found in 146 cases, dislocation of lens in 4 cases, intraocular foreign body in 105 cases, intravitreous bubble in 1 case, retinal detachment in 34 cases, choroidal detachment in 23 cases, posterior scleral rupture in 9 cases. Every patient had two or more signs above, and had strong echo signal. All kinds of strong echo signal of the cases were summarized as follows: thick vitreous hemorrhage; intraocular foreign body; dislocation of the lens; intravitreous bubble.CONCLUSION: Because of anterior chamber hemorrhage, cataract, vitreous hemorrhage, eyelid swelling and noncooperation of patients, we couldn't examine the posterior segment. So B-scan provides a great help to the ophthalmologist. It is very sensitive and has specific images on the detachment of retina, intraocular foreign body, posterior scleral laceration, hemorrhagic choroidal detachment. Complex perforating injury of eyeball often appears some confusing strong echo signals, but B-scan can identify those images. Thus, it is irreplaceable by other examinations.

  5. Inducible super-enhancers are organized based on canonical signal-specific transcription factor binding elements.

    Science.gov (United States)

    Bojcsuk, Dóra; Nagy, Gergely; Balint, Balint L

    2017-04-20

    Super-enhancers are established through the interactions of several enhancers and a large number of proteins, including transcription factors and co-regulators; however, the formation of these interactions is poorly understood. By re-analysing previously published estrogen receptor alpha (ERα) ChIP-seq data sets derived from the MCF-7 cell line, we observed that in the absence of stimulation, future super-enhancers are represented by one or a few transcription factor binding event(s) and these extraordinary enhancers possess a response element largely specific to the ERα dimer. Upon hormonal stimulation, these primary binding sites are surrounded by a large amount of ERα and the critical components of active enhancers, such as P300 and MED1, and together with neighbouring sites bound by newly recruited ERα, they generate the functional super-enhancers. To further validate the role of canonical elements in super-enhancer formation, we investigated some additional signal-dependent transcription factors, confirming that certain, distinguished binding elements have a general organizer function. These results suggest that certain signal-specific transcription factors guide super-enhancer formation upon binding to strong response elements. These findings may reshape the current understanding of how these regulatory units assemble, highlighting the involvement of DNA elements instead of protein-protein interactions. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  6. EELS signal enhancement by means of beam precession in the TEM

    International Nuclear Information System (INIS)

    Estradé, Sonia; Portillo, Joaquim; Yedra, Lluís; Rebled, José Manuel; Peiró, Francesca

    2012-01-01

    EELS is nowadays a most relevant characterization tool as it provides chemical and electronic information with an extraordinary spatial resolution. When a crystal is viewed in zone axis in the TEM, there is channelling of the electrons along the atom columns, which strongly reduce the EELS signal, so that it is generally advised to work slightly off the zone axis to collect EELS data, which may not always be possible or advantageous. In the present work, we demonstrate the use of precession to compensate for the reduction of EELS signal when in the zone axis. -- Highlights: ► Channelling compromises EELS signal in zone axis. ► Precession can be used to get rid of channelling effects. ► Use of precession to enhance EELS signal in the zone axis is demonstrated.

  7. Targeted activation of the hippocampal CA2 area strongly enhances social memory.

    Science.gov (United States)

    Smith, A S; Williams Avram, S K; Cymerblit-Sabba, A; Song, J; Young, W S

    2016-08-01

    Social cognition enables individuals to understand others' intentions. Social memory is a necessary component of this process, for without it, subsequent encounters are devoid of any historical information. The CA2 area of the hippocampus, particularly the vasopressin 1b receptor (Avpr1b) expressed there, is necessary for memory formation. We used optogenetics to excite vasopressin terminals, originating from the hypothalamic paraventricular nucleus, in the CA2 of mice. This markedly enhanced their social memory if the stimulation occurred during memory acquisition, but not retrieval. This effect was blocked by an Avpr1b antagonist. Finally, this enhanced memory is resistant to the social distraction of an introduced second mouse, important for socially navigating populations of individuals. Our results indicate the CA2 can increase the salience of social signals. Targeted pharmacotherapy with Avpr1b agonists or deep brain stimulation of the CA2 are potential avenues of treatment for those with declining social memory as in various dementias.

  8. Straw Formation and Enhanced Damping of Strong Density Waves in Saturn’s Rings

    Science.gov (United States)

    Stewart, Glen R.

    2017-06-01

    High resolution Cassini images of strong density waves in Saturn’s rings often show kilometer-scale structures in the wave troughs that are sometimes described as straw-like structures. These structures are likely formed by transient gravitational instabilities within the density wave and have the potential to greatly enhance the local viscous angular momentum transport and thereby limit the maximum amplitude of the density wave. A Hamiltonian theory for density waves has been developed that can describe the rate of local gravitational instabilities in the wave train. The Hamiltonian for single particle motion in the vicinity of an inner Lindblad resonance with a Saturnian satellite can be formulated such that the angle variable conjugate to the radial action is the resonant argument for the resonance. The density wave can then be derived using Hamiltonian perturbation methods to remove the satellite perturbation such that the transformed radial action and conjugate angles include the usual solution for self-gravitating density waves. Local gravitational instabilities in the density wave can now be formulated using a linearized collisionless Boltzmann equation that is expressed in terms of the transformed action-angle variables that contain the density wave solution. The gravitational potential of the linearized perturbation is found to be enhanced by a factor of ten or more in strong density waves, which likely explains the observation of kilometer-scale structures in these waves. The Hamiltonian formalism can also be used to derive an enhanced effective viscosity that results from these straw-like structures.

  9. A biological inspired fuzzy adaptive window median filter (FAWMF) for enhancing DNA signal processing.

    Science.gov (United States)

    Ahmad, Muneer; Jung, Low Tan; Bhuiyan, Al-Amin

    2017-10-01

    Digital signal processing techniques commonly employ fixed length window filters to process the signal contents. DNA signals differ in characteristics from common digital signals since they carry nucleotides as contents. The nucleotides own genetic code context and fuzzy behaviors due to their special structure and order in DNA strand. Employing conventional fixed length window filters for DNA signal processing produce spectral leakage and hence results in signal noise. A biological context aware adaptive window filter is required to process the DNA signals. This paper introduces a biological inspired fuzzy adaptive window median filter (FAWMF) which computes the fuzzy membership strength of nucleotides in each slide of window and filters nucleotides based on median filtering with a combination of s-shaped and z-shaped filters. Since coding regions cause 3-base periodicity by an unbalanced nucleotides' distribution producing a relatively high bias for nucleotides' usage, such fundamental characteristic of nucleotides has been exploited in FAWMF to suppress the signal noise. Along with adaptive response of FAWMF, a strong correlation between median nucleotides and the Π shaped filter was observed which produced enhanced discrimination between coding and non-coding regions contrary to fixed length conventional window filters. The proposed FAWMF attains a significant enhancement in coding regions identification i.e. 40% to 125% as compared to other conventional window filters tested over more than 250 benchmarked and randomly taken DNA datasets of different organisms. This study proves that conventional fixed length window filters applied to DNA signals do not achieve significant results since the nucleotides carry genetic code context. The proposed FAWMF algorithm is adaptive and outperforms significantly to process DNA signal contents. The algorithm applied to variety of DNA datasets produced noteworthy discrimination between coding and non-coding regions contrary

  10. Enhanced ULF radiation observed by DEMETER two months around the strong 2010 Haiti earthquake

    Directory of Open Access Journals (Sweden)

    M. A. Athanasiou

    2011-04-01

    Full Text Available In this paper we study the energy of ULF electromagnetic waves that were recorded by the satellite DEMETER, during its passing over Haiti before and after a destructive earthquake. This earthquake occurred on 12 January 2010, at geographic Latitude 18.46° and Longitude 287.47°, with Magnitude 7.0 R. Specifically, we are focusing on the variations of energy of Ez-electric field component concerning a time period of 100 days before and 50 days after the strong earthquake. In order to study these variations, we have developed a novel method that can be divided in two stages: first we filter the signal, keeping only the ultra low frequencies and afterwards we eliminate its trend using techniques of Singular Spectrum Analysis (SSA, combined with a third-degree polynomial filter. As it is shown, a significant increase in energy is observed for the time interval of 30 days before the earthquake. This result clearly indicates that the change in the energy of ULF electromagnetic waves could be related to strong precursory earthquake phenomena. Moreover, changes in energy associated with strong aftershock activity were also observed 25 days after the earthquake. Finally, we present results concerning the comparison between changes in energy during night and day passes of the satellite over Haiti, which showed differences in the mean energy values, but similar results as far as the rate of the energy change is concerned.

  11. Janus magneto-electric nanosphere dimers exhibiting unidirectional visible light scattering and strong electromagnetic field enhancement.

    Science.gov (United States)

    Wang, Hao; Liu, Pu; Ke, Yanlin; Su, Yunkun; Zhang, Lei; Xu, Ningsheng; Deng, Shaozhi; Chen, Huanjun

    2015-01-27

    Steering incident light into specific directions at the nanoscale is very important for future nanophotonics applications of signal transmission and detection. A prerequisite for such a purpose is the development of nanostructures with high-efficiency unidirectional light scattering properties. Here, from both theoretical and experimental sides, we conceived and demonstrated the unidirectional visible light scattering behaviors of a heterostructure, Janus dimer composed of gold and silicon nanospheres. By carefully adjusting the sizes and spacings of the two nanospheres, the Janus dimer can support both electric and magnetic dipole modes with spectral overlaps and comparable strengths. The interference of these two modes gives rise to the narrow-band unidirectional scattering behaviors with enhanced forward scattering and suppressed backward scattering. The directionality can further be improved by arranging the dimers into one-dimensional chain structures. In addition, the dimers also show remarkable electromagnetic field enhancements. These results will be important not only for applications of light emitting devices, solar cells, optical filters, and various surface enhanced spectroscopies but also for furthering our understanding on the light-matter interactions at the nanoscale.

  12. Wave failure at strong coupling in intracellular C a2 + signaling system with clustered channels

    Science.gov (United States)

    Li, Xiang; Wu, Yuning; Gao, Xuejuan; Cai, Meichun; Shuai, Jianwei

    2018-01-01

    As an important intracellular signal, C a2 + ions control diverse cellular functions. In this paper, we discuss the C a2 + signaling with a two-dimensional model in which the inositol 1,4,5-trisphosphate (I P3 ) receptor channels are distributed in clusters on the endoplasmic reticulum membrane. The wave failure at large C a2 + diffusion coupling is discussed in detail in the model. We show that with varying model parameters the wave failure is a robust behavior with either deterministic or stochastic channel dynamics. We suggest that the wave failure should be a general behavior in inhomogeneous diffusing systems with clustered excitable regions and may occur in biological C a2 + signaling systems.

  13. Security Enhancement of Wireless Sensor Networks Using Signal Intervals.

    Science.gov (United States)

    Moon, Jaegeun; Jung, Im Y; Yoo, Jaesoo

    2017-04-02

    Various wireless technologies, such as RF, Bluetooth, and Zigbee, have been applied to sensor communications. However, the applications of Bluetooth-based wireless sensor networks (WSN) have a security issue. In one pairing process during Bluetooth communication, which is known as simple secure pairing (SSP), the devices are required to specify I/O capability or user interference to prevent man-in-the-middle (MITM) attacks. This study proposes an enhanced SSP in which a nonce to be transferred is converted to a corresponding signal interval. The quantization level, which is used to interpret physical signal intervals, is renewed at every connection by the transferred nonce and applied to the next nonce exchange so that the same signal intervals can represent different numbers. Even if attackers eavesdrop on the signals, they cannot understand what is being transferred because they cannot determine the quantization level. Furthermore, the proposed model does not require exchanging passkeys as data, and the devices are secure in the case of using a fixed PIN. Subsequently, the new quantization level is calculated automatically whenever the same devices attempt to connect with each other. Therefore, the pairing process can be protected from MITM attacks and be convenient for users.

  14. Security Enhancement of Wireless Sensor Networks Using Signal Intervals

    Directory of Open Access Journals (Sweden)

    Jaegeun Moon

    2017-04-01

    Full Text Available Various wireless technologies, such as RF, Bluetooth, and Zigbee, have been applied to sensor communications. However, the applications of Bluetooth-based wireless sensor networks (WSN have a security issue. In one pairing process during Bluetooth communication, which is known as simple secure pairing (SSP, the devices are required to specify I/O capability or user interference to prevent man-in-the-middle (MITM attacks. This study proposes an enhanced SSP in which a nonce to be transferred is converted to a corresponding signal interval. The quantization level, which is used to interpret physical signal intervals, is renewed at every connection by the transferred nonce and applied to the next nonce exchange so that the same signal intervals can represent different numbers. Even if attackers eavesdrop on the signals, they cannot understand what is being transferred because they cannot determine the quantization level. Furthermore, the proposed model does not require exchanging passkeys as data, and the devices are secure in the case of using a fixed PIN. Subsequently, the new quantization level is calculated automatically whenever the same devices attempt to connect with each other. Therefore, the pairing process can be protected from MITM attacks and be convenient for users.

  15. Strong magnetic enhancement in self-assembled multiferroic-ferrimagnetic nanostructures

    Science.gov (United States)

    Chen, Ying-Jiun; Hsieh, Ying-Hui; Liao, Sheng-Chieh; Hu, Zhiwei; Huang, Meng-Jie; Kuo, Wei-Cheng; Chin, Yi-Ying; Uen, Tzeng-Ming; Juang, Jenh-Yih; Lai, Chih-Huang; Lin, Hong-Ji; Chen, Chien-Te; Chu, Ying-Hao

    2013-05-01

    In the past decade, self-assembled vertical nano-heterostructures have drawn considerable attention because a high interface-to-volume ratio can be used to tailor or create functionalities. We have systematically investigated the magnetic properties of oxide heterostructures consisting of the CoFe2O4 nanopillars embedded in the BiFeO3 matrix using macroscopic magnetization measurements and element-selective soft X-ray absorption magnetic circular dichroism (XMCD) at the Co- and Fe-L2,3 edge. The magnetization and XMCD data show that the total ordered magnetic moment of Co2+ in CoFe2O4-BiFeO3 nano-heterostructures is strongly enhanced. This study clearly indicates that the high interface-to-volume ratio vertical nanostructure creates a strong ferromagnetic and antiferromagnetic magnetic coupling via an interface. Furthermore, the magnetic coupling can be tuned in the multiferroic-ferrimagnetic self-assembled heterostructures by controlling the spacing between nanopillars.In the past decade, self-assembled vertical nano-heterostructures have drawn considerable attention because a high interface-to-volume ratio can be used to tailor or create functionalities. We have systematically investigated the magnetic properties of oxide heterostructures consisting of the CoFe2O4 nanopillars embedded in the BiFeO3 matrix using macroscopic magnetization measurements and element-selective soft X-ray absorption magnetic circular dichroism (XMCD) at the Co- and Fe-L2,3 edge. The magnetization and XMCD data show that the total ordered magnetic moment of Co2+ in CoFe2O4-BiFeO3 nano-heterostructures is strongly enhanced. This study clearly indicates that the high interface-to-volume ratio vertical nanostructure creates a strong ferromagnetic and antiferromagnetic magnetic coupling via an interface. Furthermore, the magnetic coupling can be tuned in the multiferroic-ferrimagnetic self-assembled heterostructures by controlling the spacing between nanopillars. Electronic supplementary

  16. Resonance enhancement of two photon absorption by magnetically trapped atoms in strong rf-fields

    Science.gov (United States)

    Chakraborty, A.; Mishra, S. R.

    2018-01-01

    Applying a many mode Floquet formalism for magnetically trapped atoms interacting with a polychromatic rf-field, we predict a large two photon transition probability in the atomic system of cold 87Rb atoms. The physical origin of this enormous increase in the two photon transition probability is due to the formation of avoided crossings between eigen-energy levels originating from different Floquet sub-manifolds and redistribution of population in the resonant intermediate levels to give rise to the resonance enhancement effect. Other exquisite features of the studied atom-field composite system include the splitting of the generated avoided crossings at the strong field strength limit and a periodic variation of the single and two photon transition probabilities with the mode separation frequency of the polychromatic rf-field. This work can find applications to characterize properties of cold atom clouds in the magnetic traps using rf-spectroscopy techniques.

  17. Enhancement of new physics signal sensitivity with mistagged charm quarks

    Directory of Open Access Journals (Sweden)

    Doojin Kim

    2016-07-01

    Full Text Available We investigate the potential for enhancing search sensitivity for signals having charm quarks in the final state, using the sizable bottom-mistagging rate for charm quarks at the LHC. Provided that the relevant background processes contain light quarks instead of charm quarks, the application of b-tagging on charm quark-initiated jets enables us to reject more background events than signal ones due to the relatively small mistagging rate for light quarks. The basic idea is tested with two rare top decay processes: i t→ch→cbb¯ and ii t→bH+→bb¯c where h and H+ denote the Standard Model-like higgs boson and a charged higgs boson, respectively. The major background source is a hadronic top quark decay such as t→bW+→bs¯c. We test our method with Monte Carlo simulation at the LHC 14 TeV, and find that the signal-over-background ratio can be increased by a factor of O(6–7 with a suitably designed (heavy flavor tagging algorithm and scheme.

  18. Strong photocurrent enhancements in plasmonic organic photovoltaics by biomimetic nanoarchitectures with efficient light harvesting.

    Science.gov (United States)

    Leem, Jung Woo; Kim, Sehwan; Park, Chihyun; Kim, Eunkyoung; Yu, Jae Su

    2015-04-01

    We propose the biomimetic moth-eye nanoarchitectures as a novel plasmonic light-harvesting structure for further enhancing the solar-generated photocurrents in organic photovoltaics (OPVs). The full moth-eye nanoarchitectures are composed of two-dimensional hexagonal periodic grating arrays on surfaces of both the front zinc oxide (ZnO) and rear active layers, which are prepared by a simple and cost-effective soft imprint nanopatterning technique. For the 380 nm period ZnO and 650 nm period active gratings (i.e., ZnO(P380)/Active(P650)), the poly(3-hexylthiophene-2,5-diyl):indene-C60 bis-adduct (P3HT:ICBA)-based plasmonic OPVs exhibit an improvement of the absorption spectrum compared to the pristine OPVs over a broad wavelength range of 350-750 nm, showing absorption enhancement peaks at wavelengths of ∼370, 450, and 670 nm, respectively. This leads to a considerable increase of short-circuit current density (Jsc) from 10.9 to 13.32 mA/cm(2), showing a large Jsc enhancement percentage of ∼22.2%. As a result, the strongly improved power conversion efficiency (PCE) of 6.28% is obtained compared to that (i.e., PCE = 5.12%) of the pristine OPVs. For the angle-dependent light-absorption characteristics, the plasmonic OPVs with ZnO(P380)/Active(P650) have a better absorption performance than that of the pristine OPVs at incident angles of 20-70°. For optical absorption characteristics and near-field intensity distributions of plasmonic OPVs, theoretical analyses are also performed by a rigorous coupled-wave analysis method, which gives a similar tendency with the experimentally measured data.

  19. Speed of Gravitational Waves from Strongly Lensed Gravitational Waves and Electromagnetic Signals.

    Science.gov (United States)

    Fan, Xi-Long; Liao, Kai; Biesiada, Marek; Piórkowska-Kurpas, Aleksandra; Zhu, Zong-Hong

    2017-03-03

    We propose a new model-independent measurement strategy for the propagation speed of gravitational waves (GWs) based on strongly lensed GWs and their electromagnetic (EM) counterparts. This can be done in two ways: by comparing arrival times of GWs and their EM counterparts and by comparing the time delays between images seen in GWs and their EM counterparts. The lensed GW-EM event is perhaps the best way to identify an EM counterpart. Conceptually, this method does not rely on any specific theory of massive gravitons or modified gravity. Its differential setting (i.e., measuring the difference between time delays in GW and EM domains) makes it robust against lens modeling details (photons and GWs travel in the same lensing potential) and against internal time delays between GW and EM emission acts. It requires, however, that the theory of gravity is metric and predicts gravitational lensing similar to general relativity. We expect that such a test will become possible in the era of third-generation gravitational-wave detectors, when about 10 lensed GW events would be observed each year. The power of this method is mainly limited by the timing accuracy of the EM counterpart, which for kilonovae is around 10^{4}  s. This uncertainty can be suppressed by a factor of ∼10^{10}, if strongly lensed transients of much shorter duration associated with the GW event can be identified. Candidates for such short transients include short γ-ray bursts and fast radio bursts.

  20. Microenvironmental Stiffness Enhances Glioma Cell Proliferation by Stimulating Epidermal Growth Factor Receptor Signaling

    Science.gov (United States)

    Umesh, Vaibhavi; Rape, Andrew D.; Ulrich, Theresa A.; Kumar, Sanjay

    2014-01-01

    The aggressive and rapidly lethal brain tumor glioblastoma (GBM) is associated with profound tissue stiffening and genomic lesions in key members of the epidermal growth factor receptor (EGFR) pathway. Previous studies from our laboratory have shown that increasing microenvironmental stiffness in culture can strongly enhance glioma cell behaviors relevant to tumor progression, including proliferation, yet it has remained unclear whether stiffness and EGFR regulate proliferation through common or independent signaling mechanisms. Here we test the hypothesis that microenvironmental stiffness regulates cell cycle progression and proliferation in GBM tumor cells by altering EGFR-dependent signaling. We began by performing an unbiased reverse phase protein array screen, which revealed that stiffness modulates expression and phosphorylation of a broad range of signals relevant to proliferation, including members of the EGFR pathway. We subsequently found that culturing human GBM tumor cells on progressively stiffer culture substrates both dramatically increases proliferation and facilitates passage through the G1/S checkpoint of the cell cycle, consistent with an EGFR-dependent process. Western Blots showed that increasing microenvironmental stiffness enhances the expression and phosphorylation of EGFR and its downstream effector Akt. Pharmacological loss-of-function studies revealed that the stiffness-sensitivity of proliferation is strongly blunted by inhibition of EGFR, Akt, or PI3 kinase. Finally, we observed that stiffness strongly regulates EGFR clustering, with phosphorylated EGFR condensing into vinculin-positive focal adhesions on stiff substrates and dispersing as microenvironmental stiffness falls to physiological levels. Our findings collectively support a model in which tissue stiffening promotes GBM proliferation by spatially and biochemically amplifying EGFR signaling. PMID:25000176

  1. Microenvironmental stiffness enhances glioma cell proliferation by stimulating epidermal growth factor receptor signaling.

    Directory of Open Access Journals (Sweden)

    Vaibhavi Umesh

    Full Text Available The aggressive and rapidly lethal brain tumor glioblastoma (GBM is associated with profound tissue stiffening and genomic lesions in key members of the epidermal growth factor receptor (EGFR pathway. Previous studies from our laboratory have shown that increasing microenvironmental stiffness in culture can strongly enhance glioma cell behaviors relevant to tumor progression, including proliferation, yet it has remained unclear whether stiffness and EGFR regulate proliferation through common or independent signaling mechanisms. Here we test the hypothesis that microenvironmental stiffness regulates cell cycle progression and proliferation in GBM tumor cells by altering EGFR-dependent signaling. We began by performing an unbiased reverse phase protein array screen, which revealed that stiffness modulates expression and phosphorylation of a broad range of signals relevant to proliferation, including members of the EGFR pathway. We subsequently found that culturing human GBM tumor cells on progressively stiffer culture substrates both dramatically increases proliferation and facilitates passage through the G1/S checkpoint of the cell cycle, consistent with an EGFR-dependent process. Western Blots showed that increasing microenvironmental stiffness enhances the expression and phosphorylation of EGFR and its downstream effector Akt. Pharmacological loss-of-function studies revealed that the stiffness-sensitivity of proliferation is strongly blunted by inhibition of EGFR, Akt, or PI3 kinase. Finally, we observed that stiffness strongly regulates EGFR clustering, with phosphorylated EGFR condensing into vinculin-positive focal adhesions on stiff substrates and dispersing as microenvironmental stiffness falls to physiological levels. Our findings collectively support a model in which tissue stiffening promotes GBM proliferation by spatially and biochemically amplifying EGFR signaling.

  2. Enhancement of Single-Channel Periodic Signals in the Time-Domain

    DEFF Research Database (Denmark)

    Jensen, Jesper Rindom; Benesty, Jacob; Christensen, Mads Græsbøll

    2012-01-01

    speech. That is, signal-dependent methods based on the signal statistics will introduce undesired distortion for some parts of speech compared to signal-independent methods based on the noise statistics. Since both the signal-independent and signal-dependent approaches to speech enhancement have...

  3. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia

    Science.gov (United States)

    Leweke, F M; Piomelli, D; Pahlisch, F; Muhl, D; Gerth, C W; Hoyer, C; Klosterkötter, J; Hellmich, M; Koethe, D

    2012-01-01

    Cannabidiol is a component of marijuana that does not activate cannabinoid receptors, but moderately inhibits the degradation of the endocannabinoid anandamide. We previously reported that an elevation of anandamide levels in cerebrospinal fluid inversely correlated to psychotic symptoms. Furthermore, enhanced anandamide signaling let to a lower transition rate from initial prodromal states into frank psychosis as well as postponed transition. In our translational approach, we performed a double-blind, randomized clinical trial of cannabidiol vs amisulpride, a potent antipsychotic, in acute schizophrenia to evaluate the clinical relevance of our initial findings. Either treatment was safe and led to significant clinical improvement, but cannabidiol displayed a markedly superior side-effect profile. Moreover, cannabidiol treatment was accompanied by a significant increase in serum anandamide levels, which was significantly associated with clinical improvement. The results suggest that inhibition of anandamide deactivation may contribute to the antipsychotic effects of cannabidiol potentially representing a completely new mechanism in the treatment of schizophrenia. PMID:22832859

  4. Static corrections for enhanced signal detection at IMS seismic arrays

    Science.gov (United States)

    Wilkins, Neil; Wookey, James; Selby, Neil

    2016-04-01

    Seismic monitoring forms an important part of the International Monitoring System (IMS) for verifying the Comprehensive nuclear Test Ban Treaty (CTBT). Analysis of seismic data can be used to discriminate between nuclear explosions and the tens of thousands of natural earthquakes of similar magnitude that occur every year. This is known as "forensic seismology", and techniques include measuring the P-to-S wave amplitude ratio, the body-to-surface wave magnitude ratio (mb/Ms), and source depth. Measurement of these seismic discriminants requires very high signal-to-noise ratio (SNR) data, and this has led to the development and deployment of seismic arrays as part of the IMS. Array processing methodologies such as stacking can be used, but optimum SNR improvement needs an accurate estimate of the arrival time of the particular seismic phase. To enhance the imaging capability of IMS arrays, we aim to develop site-specific static corrections to the arrival time as a function of frequency, slowness and backazimuth. Here, we present initial results for the IMS TORD array in Niger. Vespagrams are calculated for various events using the F-statistic to clearly identify seismic phases and measure their arrival times. Observed arrival times are compared with those predicted by 1D and 3D velocity models, and residuals are calculated for a range of backazimuths and slownesses. Finally, we demonstrate the improvement in signal fidelity provided by these corrections.

  5. Graphene Nanogrids FET Immunosensor: Signal to Noise Ratio Enhancement

    Directory of Open Access Journals (Sweden)

    Jayeeta Basu

    2016-10-01

    Full Text Available Recently, a reproducible and scalable chemical method for fabrication of smooth graphene nanogrids has been reported which addresses the challenges of graphene nanoribbons (GNR. These nanogrids have been found to be capable of attomolar detection of biomolecules in field effect transistor (FET mode. However, for detection of sub-femtomolar concentrations of target molecule in complex mixtures with reasonable accuracy, it is not sufficient to only explore the steady state sensitivities, but is also necessary to investigate the flicker noise which dominates at frequencies below 100 kHz. This low frequency noise is dependent on the exposure time of the graphene layer in the buffer solution and concentration of charged impurities at the surface. In this paper, the functionalization strategy of graphene nanogrids has been optimized with respect to concentration and incubation time of the cross linker for an enhancement in signal to noise ratio (SNR. It has been interestingly observed that as the sensitivity and noise power change at different rates with the functionalization parameters, SNR does not vary monotonically but is maximum corresponding to a particular parameter. The optimized parameter has improved the SNR by 50% which has enabled a detection of 0.05 fM Hep-B virus molecules with a sensitivity of around 30% and a standard deviation within 3%. Further, the SNR enhancement has resulted in improvement of quantification accuracy by five times and selectivity by two orders of magnitude.

  6. Influence of inherent parameter of stabilized UHF oscillators on autodyne response formation at a strong reflected signal

    Directory of Open Access Journals (Sweden)

    Noskov V. Ya.

    2011-08-01

    Full Text Available Results of an autodyne response analysis in UHF oscillators stabilized by the external high-Q cavity in the case of the strong signal when the reflected wave amplitude commen-surable with the own oscillation amplitude. Coupling between the basic operation cavity and the stabilizing cavity is implemented as a pass-reflecting filter with a resistive bond. Key relations are obtained, which describe the autodyne response to the own re-reflected radiation from a target. The load and oscillating system influence on autodyne response formation is fulfilled.

  7. Enhancement of a UASB-septic tank performance for decentralised treatment of strong domestic sewage.

    Science.gov (United States)

    Mahmoud, Nidal; van Lier, Jules B

    2011-01-01

    The possibility of enhancing the process performance of the UASB-septic tank for treating strong sewage in Palestine by means of inoculating the reactor with well adapted anaerobic sludge and/or adding a packing media to the upper part of the reactor, creating an anaerobic hybrid (AH)-septic tank, was investigated. To achieve these objectives, two community onsite UASB-septic tank and AH-septic tank were operated in parallel at 2 days HRT for around 8 months overlapping the cold and hot periods of the year in Palestine. The achieved removal efficiencies of CODtot in the UASB-septic tank and AH-septic tank during the first months of operation, coinciding with the cold period and the subsequent hot period, were respectively 50 (+/- 15)% and 48 (+/- 15)% and 66 (+/- 8)% and 55 (+/- 8)%. This shows that the UASB-septic tank performed significantly better (p UASB-septic tank. The removal efficiencies over the last 50 days of operation for CODtot, CODsus, CODcol and CODdis were 70, 72, 77 and 55% and 53, 54, 78 and 45% for the UASB-septic tank and AH-septic tank, respectively. Comparing the here achieved COD removal efficiencies with previously reported efficiencies of UASB-septic tanks operated in Palestine shows that the reactor performance in terms of COD removal and conversion, during the first 8 months of operation, has improved substantially by being started with well adapted anaerobic sludge, simulating and predicting long-term performance. Adding packing media did not lead to an improvement.

  8. Recent enhancements of the PMCC infrasound signal detector

    Science.gov (United States)

    Brachet, N.; Mialle, P.; Matoza, R. S.; Le Pichon, A.; Cansi, Y.; Ceranna, L.

    2010-12-01

    The Progressive Multi-Channel Correlation (PMCC) is an antenna technique that is commonly being used by the scientific community for detecting coherent signals recorded on infrasound arrays. The PMCC detector, originally developed by CEA/DASE (Cansi, 1995), was installed in 2004 in the operational environment of the International Data Centre (IDC) of the Comprehensive nuclear Test Ban Treaty Organization (CTBTO) in Vienna. During the last 5 years, several changes have been made by the IDC to enhance the PMCC source code and parameter configuration, and the detector has exhibited good performance in terms of detection sensitivity and robustness. Recent studies performed at the CEA/DASE have shown that the IDC version (DFX/Geotool-PMCC) and the DASE version (WinPMCC) of PMCC software benefit from the implementation of the adaptive processing window duration and a log-spaced frequency bands. This tested configuration enables better detection and characterization of all received signals in their wave-front parameter space (e.g., frequency-azimuth space, frequency-trace-velocity space). A new release of the WinPMCC software - running under Windows or Linux operating systems - including a fully configurable filtering and detection parameters is now available upon request. We present the results of a statistical analysis on 10 years of infrasound data recorded at the IMS stations IS26, Germany and IS22, New Caledonia. A comparison is made between the automatic detections produced by the IDC, and the reprocessed detections using the optimized filtering and detection configuration parameters. Work is also underway at the CEA/DASE to determine more rigorously the azimuth and speed uncertainties. The current algorithm estimates the uncertainties based on statistical analysis of the distribution of PMCC detection pixels in the azimuth-speed space. The new code that is being considered performs the calculation of infrasound measurement errors as a function of physical

  9. Local readout enhancement for detuned signal-recycling interferometers

    International Nuclear Information System (INIS)

    Rehbein, Henning; Mueller-Ebhardt, Helge; Schnabel, Roman; Danzmann, Karsten; Somiya, Kentaro; Chen Yanbei; Li Chao

    2007-01-01

    High power detuned signal-recycling interferometers currently planned for second-generation interferometric gravitational-wave detectors (for example Advanced LIGO) are characterized by two resonances in the detection band, an optical resonance and an optomechanical resonance which is upshifted from the suspension pendulum frequency due to the so-called optical-spring effect. The detector's sensitivity is enhanced around these two resonances. However, at frequencies below the optomechanical resonance frequency, the sensitivity of such interferometers is significantly lower than non-optical-spring configurations with comparable circulating power; such a drawback can also compromise high-frequency sensitivity, when an optimization is performed on the overall sensitivity of the interferometer to a class of sources. In this paper, we clarify the reason for such a low sensitivity, and propose a way to fix this problem. Motivated by the optical-bar scheme of Braginsky, Gorodetsky, and Khalili, we propose to add a local readout scheme which measures the motion of the arm-cavity front mirror, which at low frequencies moves together with the arm-cavity end mirror, under the influence of gravitational waves. This scheme improves the low-frequency quantum-noise-limited sensitivity of optical-spring interferometers significantly and can be considered as an incorporation of the optical-bar scheme into currently planned second-generation interferometers. On the other hand it can be regarded as an extension of the optical-bar scheme. Taking compact binary inspiral signals as an example, we illustrate how this scheme can be used to improve the sensitivity of the planned Advanced LIGO interferometer, in various scenarios, using a realistic classical-noise budget. We also discuss how this scheme can be implemented in Advanced LIGO with relative ease

  10. Enhancement of speech signals - with a focus on voiced speech models

    DEFF Research Database (Denmark)

    Nørholm, Sidsel Marie

    This thesis deals with speech enhancement, i.e., noise reduction in speech signals. This has applications in, e.g., hearing aids and teleconference systems. We consider a signal-driven approach to speech enhancement where a model of the speech is assumed and filters are generated based on this mo......This thesis deals with speech enhancement, i.e., noise reduction in speech signals. This has applications in, e.g., hearing aids and teleconference systems. We consider a signal-driven approach to speech enhancement where a model of the speech is assumed and filters are generated based...

  11. Looking for very low tectonic deformation in GNSS time series impacted by strong hydrological signal in the Okavango Delta, Botswana

    Science.gov (United States)

    Pastier, Anne-Morwenn; Dauteuil, Olivier; Murray-Hudson, Michael; Makati, Kaelo; Moreau, Frédérique; Crave, Alain; Longuevergne, Laurent; Walpersdorf, Andrea

    2017-04-01

    Located in northern Botswana, the Okavango Delta is a vast wetland, fed from the Angolan highlands and constrained by a half-graben in the Kalahari depression. Since the 70's, the Okavango graben is usually considered as the terminus of the East African Rift System. But a recent geodetic study showed there has been no extension on the tectonic structure over the past 5 years, and recent geophysical studies began to call this hypothesis into question. The deformation in the area could instead be related to far-field deformation accommodation due to the motion of the Kalahari craton relative to the rest of the Nubian plate and to the opening of the Rift Valley. Getting to the vertical deformation isn't trivial. The GNSS time series show a strong annual deformation of the ground surface (3 cm of amplitude). On the vertical component, this periodic signal is so strong that it hides the tectonic long-term deformation, while this information would give a crucial insight on the geodynamic process at play. This periodic signal is related to the seasonal loading of water due to the rainy season. This hypothesis is corroborated by the modeling of the surface deformation based on the GRACE satellites data, interpreted as the variation of groundwater amount. In the Okavango Delta, the peak of water level isn't paced with the local precipitations, but is driven by a flood pulse coming from the Angolan Highlands. The migration of this massive water body isn't visible at first order in GRACE data. Yet, local precipitations are supposed to undergo too much evapotranspiration to be significant in the hydrological balance. Thus this later water body isn't supposed to produce a mass anomaly in GRACE time series. This paradox could highlight a relationship not yet defined between groundwater and local rainfall. The wide spatial resolution of GRACE data (about 300 km) doesn't allow a modeling accurate enough to give access to the slow tectonic deformation, nor to determine the

  12. Enhanced Multistatic Active Sonar via Innovative Signal Processing

    Science.gov (United States)

    2015-09-30

    Multistatic Active Sonar Signal Processing," IEEE International Conference on Acoustics, Speech and Signal Processing (ICASSP), Vancouver, Canada, May 26-31...2015, Genoa, Italy, May 18-21. HONORS/AWARDS/PRIZES Dr. Jian Li gave a plenary talk at the IEEE Sensor Array and Multichannel Signal Processing

  13. Nanomaterial-Assisted Signal Enhancement of Hybridization for DNA Biosensors: A Review

    Directory of Open Access Journals (Sweden)

    Minqiang Li

    2009-09-01

    Full Text Available Detection of DNA sequences has received broad attention due to its potential applications in a variety of fields. As sensitivity of DNA biosensors is determined by signal variation of hybridization events, the signal enhancement is of great significance for improving the sensitivity in DNA detection, which still remains a great challenge. Nanomaterials, which possess some unique chemical and physical properties caused by nanoscale effects, provide a new opportunity for developing novel nanomaterial-based signal-enhancers for DNA biosensors. In this review, recent progress concerning this field, including some newly-developed signal enhancement approaches using quantum-dots, carbon nanotubes and their composites reported by our group and other researchers are comprehensively summarized. Reports on signal enhancement of DNA biosensors by non-nanomaterials, such as enzymes and polymer reagents, are also reviewed for comparison. Furthermore, the prospects for developing DNA biosensors using nanomaterials as signal-enhancers in future are also indicated.

  14. Enhancing Homeland Security Efforts by Building Strong Relationships between the Muslim Community and Local Law Enforcement

    National Research Council Canada - National Science Library

    Jensen, Dennis L

    2006-01-01

    ... to follow up on the incident and to prevent future attacks. It is undeniable that building a strong relationship between the local police and the Muslim community is essential in defending America against acts of terrorism...

  15. Improved stochastic resonance algorithm for enhancement of signal-to-noise ratio of high-performance liquid chromatographic signal

    Energy Technology Data Exchange (ETDEWEB)

    Xie Shaofei [Center for Instrumental Analysis, China Pharmaceutical University, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Nanjing 210009 (China); Xiang Bingren [Center for Instrumental Analysis, China Pharmaceutical University, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Nanjing 210009 (China)]. E-mail: cpuxsf@hotmail.com; Deng Haishan [Center for Instrumental Analysis, China Pharmaceutical University, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Nanjing 210009 (China); Xiang Suyun [Center for Instrumental Analysis, China Pharmaceutical University, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Nanjing 210009 (China); Lu Jun [Center for Instrumental Analysis, China Pharmaceutical University, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, Nanjing 210009 (China)

    2007-02-28

    Based on the theory of stochastic resonance, an improved stochastic resonance algorithm with a new criterion for optimizing system parameters to enhance signal-to-noise ratio (SNR) of HPLC/UV chromatographic signal for trace analysis was presented in this study. Compared with the conventional criterion in stochastic resonance, the proposed one can ensure satisfactory SNR as well as good peak shape of chromatographic peak in output signal. Application of the criterion to experimental weak signals of HPLC/UV was investigated and the results showed an excellent quantitative relationship between different concentrations and responses.

  16. Strong plasmonic enhancement of single molecule photostability in silver dimer optical antennas

    Directory of Open Access Journals (Sweden)

    Kaminska Izabela

    2018-02-01

    Full Text Available Photobleaching is an effect terminating the photon output of fluorophores, limiting the duration of fluorescence-based experiments. Plasmonic nanoparticles (NPs can increase the overall fluorophore photostability through an enhancement of the radiative rate. In this work, we use the DNA origami technique to arrange a single fluorophore in the 12-nm gap of a silver NP dimer and study the number of emitted photons at the single molecule level. Our findings yielded a 30× enhancement in the average number of photons emitted before photobleaching. Numerical simulations are employed to rationalize our results. They reveal the effect of silver oxidation on decreasing the radiative rate enhancement.

  17. Strong Coupling and Entanglement of Quantum Emitters Embedded in a Nanoantenna-Enhanced Plasmonic Cavity

    Energy Technology Data Exchange (ETDEWEB)

    Hensen, Matthias [Institut; Heilpern, Tal [Center; Gray, Stephen K. [Center; Pfeiffer, Walter [Fakultät

    2017-10-12

    Establishing strong coupling between spatially separated and thus selectively addressable quantum emitters is a key ingredient to complex quantum optical schemes in future technologies. Insofar as many plasmonic nanostructures are concerned, however, the energy transfer and mutual interaction strength between distant quantum emitters can fail to provide strong coupling. Here, based on mode hybridization, the longevity and waveguide character of an elliptical plasmon cavity are combined with intense and highly localized field modes of suitably designed nanoantennas. Based on FDTD simulations a quantum emitter-plasmon coupling strength hg = 16.7 meV is reached while simultaneously keeping a small plasmon resonance line width h gamma(s) = 33 meV. This facilitates strong coupling, and quantum dynamical simulations reveal an oscillatory exchange of excited state population arid a notable degree of entanglement between the quantum emitters spatially separated by 1.8 mu m, i.e., about twice the operating wavelength.

  18. A Method of Speech Periodicity Enhancement Using Transform-domain Signal Decomposition.

    Science.gov (United States)

    Huang, Huang; Lee, Tan; Kleijn, W Bastiaan; Kong, Ying-Yee

    2015-03-01

    Periodicity is an important property of speech signals. It is the basis of the signal's fundamental frequency and the pitch of voice, which is crucial to speech communication. This paper presents a novel framework of periodicity enhancement for noisy speech. The enhancement is applied to the linear prediction residual of speech. The residual signal goes through a constant-pitch time warping process and two sequential lapped-frequency transforms, by which the periodic component is concentrated in certain transform coefficients. By emphasizing the respective transform coefficients, periodicity enhancement of noisy residual signal is achieved. The enhanced residual signal and estimated linear prediction filter parameters are used to synthesize the output speech. An adaptive algorithm is proposed for adjusting the weights for the periodic and aperiodic components. Effectiveness of the proposed approach is demonstrated via experimental evaluation. It is observed that harmonic structure of the original speech could be properly restored to improve the perceptual quality of enhanced speech.

  19. Investigation of enhanced forward and backward anti-stokes Raman signals in lithium niobate waveguides

    Energy Technology Data Exchange (ETDEWEB)

    Li, Da; Hong, Pengda; Ding, Yujie J., E-mail: yding300@gmail.com [Department of Electrical and Computer Engineering, Lehigh University, Bethlehem, Pennsylvania 18015 (United States); Liu, Zhaojun; Wang, Lei [Department of Electrical and Computer Engineering, Lehigh University, Bethlehem, Pennsylvania 18015 (United States); School of Information Science and Engineering, Shandong University, Jinan, Shandong 250100 (China); Hua, Ping-Rang; Zhang, De-Long [School of Precision Instruments and Opto-electronics Engineering, Tianjin University, Tianjin 300072 (China)

    2015-07-07

    We have observed enhancements of the anti-Stokes Raman signals generated in lithium niobate waveguides in the forward and backward configurations by at least one order of magnitude under the pump power of the microwatt level. These output signals were measured using a single photon detector. The forward and backward propagating anti-Stokes signals exhibited different spectral features.

  20. TESTING GRAVITATIONAL LENSING AS THE SOURCE OF ENHANCED STRONG Mg II ABSORPTION TOWARD GAMMA-RAY BURSTS

    Energy Technology Data Exchange (ETDEWEB)

    Rapoport, Sharon; Onken, Christopher A.; Schmidt, Brian P.; Tucker, Brad E. [Research School of Astronomy and Astrophysics, Australian National University, Weston Creek, ACT 2611 (Australia); Wyithe, J. Stuart B. [School of Physics, University of Melbourne, Parkville, Victoria 3010 (Australia); Levan, Andrew J. [Department of Physics, University of Warwick, Coventry CV4 7AL (United Kingdom)

    2012-08-01

    Sixty percent of gamma-ray bursts (GRBs) reveal strong Mg II absorbing systems, which is a factor of {approx}2 times the rate seen along lines of sight to quasars. Previous studies argue that the discrepancy in the strong Mg II covering factor is most likely to be the result of either quasars being obscured due to dust or the consequence of many GRBs being strongly gravitationally lensed. We analyze observations of quasars that show strong foreground Mg II absorption. We find that GRB lines of sight pass closer to bright galaxies than would be expected for random lines of sight within the impact parameter expected for strong Mg II absorption. While this cannot be explained by obscuration in the GRB sample, it is a natural consequence of gravitational lensing. Upon examining the particular configurations of galaxies near a sample of GRBs with strong Mg II absorption, we find several intriguing lensing candidates. Our results suggest that lensing provides a viable contribution to the observed enhancement of strong Mg II absorption along lines of sight to GRBs, and we outline the future observations required to test this hypothesis conclusively.

  1. Traffic signal control enhancements under vehicle infrastructure integration systems.

    Science.gov (United States)

    2011-12-01

    Most current traffic signal systems are operated using a very archaic traffic-detection simple binary : logic (vehicle presence/non presence information). The logic was originally developed to provide input for old : electro-mechanical controllers th...

  2. A strong conditional mutualism limits and enhances seed dispersal and germination of a tropical palm

    Science.gov (United States)

    Klinger, R.; Rejmanek, M.

    2010-01-01

    Seed predation and seed dispersal can have strong effects on early life history stages of plants. These processes have often been studied as individual effects, but the degree to which their relative importance co-varies with seed predator abundance and how this influences seed germination rates is poorly understood. Therefore, we used a combination of observations and field experiments to determine the degree to which germination rates of the palm Astrocaryum mexicanum varied with abundance of a small mammal seed predator/disperser, Heteromysdesmarestianus, in a lowland tropical forest. Patterns of abundance of the two species were strongly related; density of H. desmarestianus was low in sites with low density of A. mexicanum and vice versa. Rates of predation and dispersal of A. mexicanum seeds depended on abundance of H. desmarestianus; sites with high densities of H. desmarestianus had the highest rates of seed predation and lowest rates of seed germination, but a greater total number of seeds were dispersed and there was greater density of seedlings, saplings, and adults of A. mexicanum in these sites. When abundance of H. desmarestianus was experimentally reduced, rates of seed predation decreased, but so did dispersal of A. mexicanum seeds. Critically, rates of germination of dispersed seeds were 5 times greater than undispersed seeds. The results suggest that the relationship between A. mexicanum and H. desmarestianus is a conditional mutualism that results in a strong local effect on the abundance of each species. However, the magnitude and direction of these effects are determined by the relative strength of opposing, but related, mechanisms. A. mexicanum nuts provide H. desmarestianus with a critical food resource, and while seed predation on A. mexicanum nuts by H. desmarestianus is very intense, A. mexicanum ultimately benefits because of the relatively high germination rates of its seeds that are dispersed by H. desmarestianus. ?? The Author(s) 2010.

  3. Entanglement-enhanced information transfer through strongly correlated systems and its application to optical lattices

    Energy Technology Data Exchange (ETDEWEB)

    Yang Song [Department of Physics and Astronomy, University College London, London WC1E 6BT (United Kingdom); Key Laboratory of Quantum Information, University of Science and Technology of China, Hefei, 230026 (China); Bayat, Abolfazl; Bose, Sougato [Department of Physics and Astronomy, University College London, London WC1E 6BT (United Kingdom)

    2011-08-15

    We show that the inherent entanglement of the ground state of strongly correlated systems can be exploited for both classical and quantum communications. Our strategy is based on a single-qubit rotation that encodes information in the entangled nature of the ground state. In classical communication, our mechanism conveys more than one bit of information in each shot, just as dense coding does, without demanding long-range entanglement. In our scheme for quantum communication, the quality is higher than the widely studied attaching scenarios. Moreover, we propose to implement this way of communication in optical lattices.

  4. Electric-field-induced strong enhancement of electroluminescence in multilayer molybdenum disulfide

    Science.gov (United States)

    Li, Dehui; Cheng, Rui; Zhou, Hailong; Wang, Chen; Yin, Anxiang; Chen, Yu; Weiss, Nathan O.; Huang, Yu; Duan, Xiangfeng

    2015-07-01

    The layered transition metal dichalcogenides have attracted considerable interest for their unique electronic and optical properties. While the monolayer MoS2 exhibits a direct bandgap, the multilayer MoS2 is an indirect bandgap semiconductor and generally optically inactive. Here we report electric-field-induced strong electroluminescence in multilayer MoS2. We show that GaN-Al2O3-MoS2 and GaN-Al2O3-MoS2-Al2O3-graphene vertical heterojunctions can be created with excellent rectification behaviour. Electroluminescence studies demonstrate prominent direct bandgap excitonic emission in multilayer MoS2 over the entire vertical junction area. Importantly, the electroluminescence efficiency observed in multilayer MoS2 is comparable to or higher than that in monolayers. This strong electroluminescence can be attributed to electric-field-induced carrier redistribution from the lowest energy points (indirect bandgap) to higher energy points (direct bandgap) in k-space. The electric-field-induced electroluminescence is general for other layered materials including WSe2 and can open up a new pathway towards transition metal dichalcogenide-based optoelectronic devices.

  5. Strongly Enhanced Free-Exciton Luminescence in Microcrystalline CsPbBr3 Films

    Science.gov (United States)

    Kondo, Shin-ichi; Kakuchi, Mitsugu; Masaki, Atsushi; Saito, Tadaaki

    2003-07-01

    The luminescence properties of CsPbBr3 films prepared via the amorphous phase by crystallization are dominated by free-exciton emission, and only a weak trace of emission due to trapped excitons was observed, in contrast to the case of bulk CsPbBr3 crystals. In particular, the films in the microcrystalline state show by more than an order of magnitude stronger free-exciton emission than in the polycrystalline state. The enhanced free-exciton emission is suggestive of excitonic superradiance.

  6. Adenovirus-induced extracellular signal-regulated kinase phosphorylation during the late phase of infection enhances viral protein levels and virus progeny

    DEFF Research Database (Denmark)

    Schümann, Michael; Dobbelstein, Matthias

    2006-01-01

    . Hence, adenovirus induces the oncogenic Raf/MEK/ERK signaling pathway to enhance viral progeny by sustaining the levels of viral proteins. Concerning therapy, our results suggest that the use of Raf/MEK/ERK inhibitors will interfere with the propagation of oncolytic adenoviruses.......The Raf/mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signaling cascade enhances tumor cell proliferation in many cases. Here, we show that adenovirus type 5, a small DNA tumor virus used in experimental cancer therapy, strongly induces ERK phosphorylation...

  7. Cadmium chloride strongly enhances cyclophosphamide-induced chromosome aberrations in mouse bone marrow cells

    Energy Technology Data Exchange (ETDEWEB)

    Pandurangarao, V.L.; Blazina, S.; Bherje, R. [Western Michigan Univ., Kalamazoo, MI (United States)] [and others

    1997-10-01

    Earlier we reported that a single 5 mg cadmium chloride (CdCl{sub 2})/kg ip dose enhanced chromosome aberrations (ca) with 50 mg/kg cyclophosphamide (CP) in mouse bone marrow cells. In this report groups of 4 mice were injected ip with saline, 0.31, 0.62, 1.25, 2.5 or 5.0 mg/kg CdCl{sub 2}, followed by saline injections at 24 h. Other mice similarly uninjected at 0 h were injected with 50 mg/kg CP at 24 h. All the mice were injected ip with 4 mg colchicine/kg at 44 h. At 48 h the bone marrow cells were processed for chromosome spreads. After dissection, visual examination revealed obvious internal hemorrhaging of the testes at 1.25 CdCl{sub 2} mg/kg and higher doses. This effect was not further increased by CP treatment. The lowest ca enhancing dose of CdCl{sub 2} on CP was 0.625 mg/kg. Our hypothesis is that Cd replaces zinc presents in numerous DNA repair enzymes and proteins resulting in diminished repair. Subsequently, the excess of unrepaired DNA damage is seen as chromatid breaks, deletions, fragments and exchanges.

  8. Signal intensity enhancement of laser ablated volume holograms

    Science.gov (United States)

    Versnel, J. M.; Williams, C.; Davidson, C. A. B.; Wilkinson, T. D.; Lowe, C. R.

    2017-11-01

    Conventional volume holographic gratings (VHGs) fabricated in photosensitive emulsions such as gelatin containing silver salts enable the facile visualization of the holographic image in ambient lighting. However, for the fabrication of holographic sensors, which require more defined and chemically-functionalised polymer matrices, laser ablation has been introduced to create the VHGs and thereby broaden their applications, although the replay signal can be challenging to detect in ambient lighting. When traditional photochemical bleaching solutions used to reduce light scattering and modulate refractive index within the VHG are applied to laser ablated volume holographic gratings, these procedures decrease the holographic peak intensity. This is postulated to occur because both light and dark fringes contain a proportion of metal particles, which upon solubilisation are converted immediately to silver iodide, yielding no net refractive index modulation. This research advances a hypothesis that the reduced intensity of holographic replay signals is linked to a gradient of different sized metal particles within the emulsion, which reduces the holographic signal and may explain why traditional bleaching processes result in a reduction in intensity. In this report, a novel experimental protocol is provided, along with simulations based on an effective medium periodic 1D stack, that offers a solution to increase peak signal intensity of holographic sensors by greater than 200%. Nitric acid is used to etch the silver nanoparticles within the polymer matrix and is thought to remove the smaller particles to generate more defined metal fringes containing a soluble metal salt. Once the grating efficiency has been increased, this salt can be converted to a silver halide, to modulate the refractive index and increase the intensity of the holographic signal. This new protocol has been tested in a range of polymer chemistries; those containing functional groups that help to

  9. Strongly enhanced temperature dependence of the chemical potential in FeSe

    Science.gov (United States)

    Rhodes, L. C.; Watson, M. D.; Haghighirad, A. A.; Eschrig, M.; Kim, T. K.

    2017-05-01

    Employing a 10-orbital tight-binding model, we present a set of hopping parameters fitted directly to our latest high-resolution angle-resolved photoemission spectroscopy (ARPES) data for the high-temperature tetragonal phase of FeSe. Using these parameters, we predict a large 10 meV shift of the chemical potential as a function of temperature. To confirm this large temperature dependence, we performed ARPES experiments on FeSe and observed a ˜25 meV rigid shift to the chemical potential between 100 and 300 K. This strong shift has important implications for theoretical models of superconductivity and of nematic order in FeSe materials.

  10. SAR image enhancement via post-correlation signal processing

    Science.gov (United States)

    Matthews, N. D.; Kaupp, V. H.; Waite, W. P.; Macdonald, H. C.

    1984-01-01

    Seventeen interpreters ranked sets of computer-generated radar imagery to assess the value of post-correlation processing on the interpretability of SAR (synthetic aperture radar) imagery. The post-correlation processing evaluated amounts to a nonlinear mapping of the signal exiting a digital correlator and allows full use of signal bandwidth for improving the spatial resolution or for noise reduction. The results indicate that it is reasonable to hypothesize an optimal SAR presentation format for specific applications even though this study was too limited to be specific.

  11. Higgs Pair Production as a Signal of Enhanced Yukawa Couplings

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, Martin [Heidelberg U.; Carena, Marcela [Chicago U., KICP; Carmona, Adrián [U. Mainz, PRISMA

    2017-12-31

    We present a non-trivial correlation between the enhancement of the Higgs-fermion couplings and the Higgs pair production cross section in two Higgs doublet models with a flavour symmetry. This symmetry suppresses flavour-changing neutral couplings of the Higgs boson and allows for a partial explanation of the hierarchy in the Yukawa sector. After taking into account the constraints from electroweak precision measurements, Higgs coupling strength measurements, and unitarity and perturbativity bounds, we identify an interesting region of parameter space leading to enhanced Yukawa couplings as well as enhanced di-Higgs gluon fusion production at the LHC reach. This effect is visible in both the resonant and non-resonant contributions to the Higgs pair production cross section. We encourage dedicated searches based on differential distributions as a novel way to indirectly probe enhanced Higgs couplings to light fermions.

  12. Joint Maximum Likelihood Time Delay Estimation of Unknown Event-Related Potential Signals for EEG Sensor Signal Quality Enhancement

    Directory of Open Access Journals (Sweden)

    Kyungsoo Kim

    2016-06-01

    Full Text Available Electroencephalograms (EEGs measure a brain signal that contains abundant information about the human brain function and health. For this reason, recent clinical brain research and brain computer interface (BCI studies use EEG signals in many applications. Due to the significant noise in EEG traces, signal processing to enhance the signal to noise power ratio (SNR is necessary for EEG analysis, especially for non-invasive EEG. A typical method to improve the SNR is averaging many trials of event related potential (ERP signal that represents a brain’s response to a particular stimulus or a task. The averaging, however, is very sensitive to variable delays. In this study, we propose two time delay estimation (TDE schemes based on a joint maximum likelihood (ML criterion to compensate the uncertain delays which may be different in each trial. We evaluate the performance for different types of signals such as random, deterministic, and real EEG signals. The results show that the proposed schemes provide better performance than other conventional schemes employing averaged signal as a reference, e.g., up to 4 dB gain at the expected delay error of 10°.

  13. Highly potent host external immunity acts as a strong selective force enhancing rapid parasite virulence evolution.

    Science.gov (United States)

    Rafaluk, Charlotte; Yang, Wentao; Mitschke, Andreas; Rosenstiel, Philip; Schulenburg, Hinrich; Joop, Gerrit

    2017-05-01

    Virulence is often under selection during host-parasite coevolution. In order to increase fitness, parasites are predicted to circumvent and overcome host immunity. A particular challenge for pathogens are external immune systems, chemical defence systems comprised of potent antimicrobial compounds released by prospective hosts into the environment. We carried out an evolution experiment, allowing for coevolution to occur, with the entomopathogenic fungus, Beauveria bassiana, and the red flour beetle, Tribolium castaneum, which has a well-documented external immune system with strong inhibitory effects against B. bassiana. After just seven transfers of experimental evolution we saw a significant increase in parasite induced host mortality, a proxy for virulence, in all B. bassiana lines. This apparent virulence increase was mainly the result of the B. bassiana lines evolving resistance to the beetles' external immune defences, not due to increased production of toxins or other harmful substances. Transcriptomic analyses of evolved B. bassiana implicated the up-regulation of oxidative stress resistance genes in the observed resistance to external immunity. It was concluded that external immunity acts as a powerful selective force for virulence evolution, with an increase in virulence being achieved apparently entirely by overcoming these defences, most likely due to elevated oxidative stress resistance. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.

  14. Strain-Induced Enhancement of the Electron Energy Relaxation in Strongly Correlated Superconductors

    Directory of Open Access Journals (Sweden)

    C. Gadermaier

    2014-03-01

    Full Text Available We use femtosecond optical spectroscopy to systematically measure the primary energy relaxation rate Γ_{1} of photoexcited carriers in cuprate and pnictide superconductors. We find that Γ_{1} increases monotonically with increased negative strain in the crystallographic a axis. Generally, the Bardeen-Shockley deformation potential theorem and, specifically, pressure-induced Raman shifts reported in the literature suggest that increased negative strain enhances electron-phonon coupling, which implies that the observed direct correspondence between a and Γ_{1} is consistent with the canonical assignment of Γ_{1} to the electron-phonon interaction. The well-known nonmonotonic dependence of the superconducting critical temperature T_{c} on the a-axis strain is also reflected in a systematic dependence T_{c} on Γ_{1}, with a distinct maximum at intermediate values (∼16  ps^{−1} at room temperature. The empirical nonmonotonic systematic variation of T_{c} with the strength of the electron-phonon interaction provides us with unique insight into the role of electron-phonon interaction in relation to the mechanism of high-T_{c} superconductivity as a crossover phenomenon.

  15. Enhanced Phosphoproteomic Profiling Workflow For Growth Factor Signaling Analysis

    DEFF Research Database (Denmark)

    Sylvester, Marc; Burbridge, Mike; Leclerc, Gregory

    2010-01-01

    A549 lung carcinoma cells were used as a model and stimulated with hepatocyte growth factor, epidermal growth factor or fibroblast growth factor. We employed a quick protein digestion workflow with spin filters without using urea. Phosphopeptides in general were enriched by sequential elution from...... transfer dissociation adds confidence in modification site assignment. The workflow is relatively simple but the integration of complementary techniques leads to a deeper insight into cellular signaling networks and the potential pharmacological intervention thereof....

  16. Strong enhancement of antioxidant activity of Aloe vera extracts by gamma irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Mi; Bai, Hyoung Woo; Lee, Seung Sik; Hong, Sung Hyun [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Cho, Jae Young; Chung, Byung Yeoup [Chonbuk National University, Jeonju (Korea, Republic of)

    2011-10-15

    The World Health Organization (WHO) has estimated that approximately 80% of individuals rely on traditional medicines. Among over 400 Aloe species, Aloe vera was the most accepted species for various medical, cosmetic and neutraceutical purposes. Aloe vera (syn.: Aloe barbadensis Miller) was a perennial succulent plant belonging to the Aloeaceae family (subfamily of the Asphodelaceae). It has been reported that Aloe vera extracts were useful in the treatment of wound and burn healing, minor skin infections, sebaceous cyst, diabetes, and elevated blood lipids in humans. Recent studies have shown that treatment with either Aloe vera crude gel or its extracts, such as acemannan, {beta}-sitosterol, and others, resulted in faster healing of wounds by stimulating fibroblast proliferation, collagen deposition, angiogenesis, and production of growth factors. Ionizing radiation technology has been developed to improve our daily life such as cancer therapy and sterilizing tool due to its unique feature that could be penetrated biomaterials leading to alter their own physical properties. More recently, many studies have attempted to apply the radiation technology to enhance their biological activities. At present, however, very little was known about whether naturally-occurring phenolic compounds of ethanolic aloe gel extracts that were altered their biological activities by ionizing radiation to serve as antioxidant in the body to reduce ROS produced by the stresses. The purpose of the current study was to investigate the influence of gamma irradiation on antioxidant activity of Aloe vera extracts, and open insight new possibilities that gamma ray could be a powerful tool for improving its own biological activities

  17. Strong enhancement of antioxidant activity of Aloe vera extracts by gamma irradiation

    International Nuclear Information System (INIS)

    Lee, Eun Mi; Bai, Hyoung Woo; Lee, Seung Sik; Hong, Sung Hyun; Cho, Jae Young; Chung, Byung Yeoup

    2011-01-01

    The World Health Organization (WHO) has estimated that approximately 80% of individuals rely on traditional medicines. Among over 400 Aloe species, Aloe vera was the most accepted species for various medical, cosmetic and neutraceutical purposes. Aloe vera (syn.: Aloe barbadensis Miller) was a perennial succulent plant belonging to the Aloeaceae family (subfamily of the Asphodelaceae). It has been reported that Aloe vera extracts were useful in the treatment of wound and burn healing, minor skin infections, sebaceous cyst, diabetes, and elevated blood lipids in humans. Recent studies have shown that treatment with either Aloe vera crude gel or its extracts, such as acemannan, β-sitosterol, and others, resulted in faster healing of wounds by stimulating fibroblast proliferation, collagen deposition, angiogenesis, and production of growth factors. Ionizing radiation technology has been developed to improve our daily life such as cancer therapy and sterilizing tool due to its unique feature that could be penetrated biomaterials leading to alter their own physical properties. More recently, many studies have attempted to apply the radiation technology to enhance their biological activities. At present, however, very little was known about whether naturally-occurring phenolic compounds of ethanolic aloe gel extracts that were altered their biological activities by ionizing radiation to serve as antioxidant in the body to reduce ROS produced by the stresses. The purpose of the current study was to investigate the influence of gamma irradiation on antioxidant activity of Aloe vera extracts, and open insight new possibilities that gamma ray could be a powerful tool for improving its own biological activities

  18. Cuckoo search based optimal mask generation for noise suppression and enhancement of speech signal

    Directory of Open Access Journals (Sweden)

    Anil Garg

    2015-07-01

    Full Text Available In this paper, an effective noise suppression technique for enhancement of speech signals using optimized mask is proposed. Initially, the noisy speech signal is broken down into various time–frequency (TF units and the features are extracted by finding out the Amplitude Magnitude Spectrogram (AMS. The signals are then classified based on quality ratio into different classes to generate the initial set of solutions. Subsequently, the optimal mask for each class is generated based on Cuckoo search algorithm. Subsequently, in the waveform synthesis stage, filtered waveforms are windowed and then multiplied by the optimal mask value and summed up to get the enhanced target signal. The experimentation of the proposed technique was carried out using various datasets and the performance is compared with the previous techniques using SNR. The results obtained proved the effectiveness of the proposed technique and its ability to suppress noise and enhance the speech signal.

  19. Cholesterol Enhances Colorectal Cancer Progression via ROS Elevation and MAPK Signaling Pathway Activation

    Directory of Open Access Journals (Sweden)

    Caihua Wang

    2017-06-01

    Full Text Available Background/Aims: Elevated serum cholesterol levels were linked to a higher risk of colorectal adenoma and colorectal cancer (CRC, while the effect of cholesterol on CRC metastasis has not been widely studied. Methods: CRC patients were enrolled to evaluate the association between low-density lipoprotein cholesterol (LDL and CRC metastases, and LDL receptor (LDLR level of the CRC tissue was assessed by immunohistochemistry. The effects of LDL on cell proliferation, migration and stemness were assessed in CRC cells in vitro, and the effects of high fat diet (HFD on tumor growth and intestinal tumorigenicity were investigated in vivo. ROS assays, gene expression array analysis and western blot were used to explore the mechanisms of LDL in CRC progression. Results: The level of LDL was positively correlated with liver metastases, and a higher level of LDL receptor (LDLR expression was associated with advanced N and M stages of CRC. In vitro, LDL promoted the migration and sphere formation of CRC cells and induced upregulated expression of “stemness” genes including Sox2, Oct4, Nanog and Bmi 1. High-fat diet (HFD significantly enhanced tumor growth in vivo, and was associated with a shorter intestinal length in azoxymethane/dextran sodium sulfate (AOM/DSS-treated mice. Furthermore, LDL significantly elevated reactive oxygen species (ROS levels and Whole Human Genome Microarray found 87 differentially expressed genes between LDL-treated CRC cells and controls, which were largely clustered in the MAP kinase (MAPK signaling pathway. Conclusions: LDL enhances intestinal inflammation and CRC progression via activation of ROS and signaling pathways including the MAPK pathway. Inflammation is strongly associated with cancer initiation, and the role of LDL in intestinal tumorigenicity should be further explored.

  20. Different Signal Enhancement Pathways of Attention and Consciousness Underlie Perception in Humans.

    Science.gov (United States)

    van Boxtel, Jeroen J A

    2017-06-14

    It is not yet known whether attention and consciousness operate through similar or largely different mechanisms. Visual processing mechanisms are routinely characterized by measuring contrast response functions (CRFs). In this report, behavioral CRFs were obtained in humans (both males and females) by measuring afterimage durations over the entire range of inducer stimulus contrasts to reveal visual mechanisms behind attention and consciousness. Deviations relative to the standard CRF, i.e., gain functions, describe the strength of signal enhancement, which were assessed for both changes due to attentional task and conscious perception. It was found that attention displayed a response-gain function, whereas consciousness displayed a contrast-gain function. Through model comparisons, which only included contrast-gain modulations, both contrast-gain and response-gain effects can be explained with a two-level normalization model, in which consciousness affects only the first level and attention affects only the second level. These results demonstrate that attention and consciousness can effectively show different gain functions because they operate through different signal enhancement mechanisms. SIGNIFICANCE STATEMENT The relationship between attention and consciousness is still debated. Mapping contrast response functions (CRFs) has allowed (neuro)scientists to gain important insights into the mechanistic underpinnings of visual processing. Here, the influence of both attention and consciousness on these functions were measured and they displayed a strong dissociation. First, attention lowered CRFs, whereas consciousness raised them. Second, attention manifests itself as a response-gain function, whereas consciousness manifests itself as a contrast-gain function. Extensive model comparisons show that these results are best explained in a two-level normalization model in which consciousness affects only the first level, whereas attention affects only the second level

  1. Wheel running eliminates high-fat preference and enhances leptin signaling in the ventral tegmental area.

    Science.gov (United States)

    Scarpace, P J; Matheny, M; Zhang, Y

    2010-05-11

    Voluntary wheel running (WR) is a form of physical activity in rodents that influences ingestive behavior. This study examined the effects of WR on dietary preference and the potential role of leptin in mediating these effects. In a two-diet choice paradigm in which both palatable high-fat (HF) food and standard laboratory chow were provided ad libitum, rats displayed a strong preference for the former and chose to eat almost exclusively the HF diet over chow in sedentary conditions. With free access to running wheels, however, rats exhibited no preference for the HF food and consumed equal gram amounts of both chow and HF diets. The total daily caloric consumption during WR in the dietary choice protocol was equivalent to the amount of calories consumed daily by WR rats with only chow or only HF diet available, yet significantly less than sedentary chow caloric consumption. Two days after initiating WR, leptin signal transduction was examined in multiple selected brain sites following leptin injection into the third cerebral ventricle. The maximal leptin-stimulated STAT3 phosphorylation was enhanced only in the ventral tegmental area (VTA), but not in the arcuate nucleus, lateral hypothalamus, dorsal medial or ventral medial hypothalamus, or substantia nigra. In conclusion, wheel running appears to act either as an independent reinforcing factor or as a more favored activity to substitute for the consumption of a palatable HF diet, thus eliminating the preference for the HF food. Moreover, WR enhances leptin signaling specifically in the VTA, suggestive of a WR-evoked mechanism of heightened leptin function in the VTA to curb the drive to consume palatable HF foods. Copyright 2010 Elsevier Inc. All rights reserved.

  2. Secondary ion mass spectrometric signal enhancement of phosphatidylcholine dioleoyl on enlarged nanoparticles surface

    Science.gov (United States)

    Gulin, A.; Mochalova, M.; Denisov, N.; Nadtochenko, V.

    2014-10-01

    A silicon wafer surface coverage of nanoparticles (NPs) can enhance the L-α-phosphatidylcholine dioleoyl (DOPC) signal intensity in time-of-flight secondary ion mass spectrometry (TOF-SIMS). A ToF-SIMS mass spectrometer was used with a pulsed primary beam of focused 30 keV Bi3+ ions. The signal enhancing effect has been studied for metallic (Ag, Au, Pb), semiconductor (TiO2), dielectric (SiO2) and hybrid (Au/TiO2NPs, core-shell Au/SiO2) nanoparticles. Ag NPs can attenuate secondary ions signal, whereas all other studied NPs show the signal enhancement. The emission of DOPC lipid secondary ions immobilized on core-shell Au/SiO2NPs was enhanced up to 42 times. This technique is a simple preparatory method enabling an overall increase in molecular lipid ions.

  3. Expanded research and development of an enhanced rear signaling system for commercial motor vehicles.

    Science.gov (United States)

    2014-04-01

    The purpose of the current study was to further develop and refine the prototype Enhanced Rear Signaling (ERS) : system that was developed during the previous Phase III effort. Expanded development efforts for the ERS system : included modification o...

  4. Method for separation of a weak background signal from at the presence of a strong one in the Fourier spectroscopy

    International Nuclear Information System (INIS)

    Lib, Yu.N.; Zhukov, M.S.

    1985-01-01

    A method for solving a big signal problem in the nmr Fourier spectroscopy is described. Thus the digital filtration of a big signal is carried out, where from the droop of induced signal accumulated before the moment of memory content overflow, subtracted is a model interferogram, corresponding only to removed big signals (the model interferogram is the result of perocessing of an initial interferogram). Calculating formulae and dependences haracterizing the accumulation-subtraction process and minimal gain as compared with a common technique with scaling are given. Experimental results which confirm the method efficiency are stated

  5. Parametric Adaptive Radar Detector with Enhanced Mismatched Signals Rejection Capabilities

    Directory of Open Access Journals (Sweden)

    Liu Bin

    2010-01-01

    Full Text Available We consider the problem of adaptive signal detection in the presence of Gaussian noise with unknown covariance matrix. We propose a parametric radar detector by introducing a design parameter to trade off the target sensitivity with sidelobes energy rejection. The resulting detector merges the statistics of Kelly's GLRT and of the Rao test and so covers Kelly's GLRT and the Rao test as special cases. Both invariance properties and constant false alarm rate (CFAR behavior for this detector are studied. At the analysis stage, the performance of the new receiver is assessed and compared with several traditional adaptive detectors. The results highlight better rejection capabilities of this proposed detector for mismatched signals. Further, we develop two two-stage detectors, one of which consists of an adaptive matched filter (AMF followed by the aforementioned detector, and the other is obtained by cascading a GLRT-based Subspace Detector (SD and the proposed adaptive detector. We show that the former two-stage detector outperforms traditional two-stage detectors in terms of selectivity, and the latter yields more robustness.

  6. Disorder in convergent floral nanostructures enhances signalling to bees

    Science.gov (United States)

    Moyroud, Edwige; Wenzel, Tobias; Middleton, Rox; Rudall, Paula J.; Banks, Hannah; Reed, Alison; Mellers, Greg; Killoran, Patrick; Westwood, M. Murphy; Steiner, Ullrich; Vignolini, Silvia; Glover, Beverley J.

    2017-10-01

    Diverse forms of nanoscale architecture generate structural colour and perform signalling functions within and between species. Structural colour is the result of the interference of light from approximately regular periodic structures; some structural disorder is, however, inevitable in biological organisms. Is this disorder functional and subject to evolutionary selection, or is it simply an unavoidable outcome of biological developmental processes? Here we show that disordered nanostructures enable flowers to produce visual signals that are salient to bees. These disordered nanostructures (identified in most major lineages of angiosperms) have distinct anatomies but convergent optical properties; they all produce angle-dependent scattered light, predominantly at short wavelengths (ultraviolet and blue). We manufactured artificial flowers with nanoscale structures that possessed tailored levels of disorder in order to investigate how foraging bumblebees respond to this optical effect. We conclude that floral nanostructures have evolved, on multiple independent occasions, an effective degree of relative spatial disorder that generates a photonic signature that is highly salient to insect pollinators.

  7. Enhancement of MS Signal Processing For Improved Cancer Biomarker Discovery

    Science.gov (United States)

    Si, Qian

    Technological advances in proteomics have shown great potential in detecting cancer at the earliest stages. One way is to use the time of flight mass spectroscopy to identify biomarkers, or early disease indicators related to the cancer. Pattern analysis of time of flight mass spectra data from blood and tissue samples gives great hope for the identification of potential biomarkers among the complex mixture of biological and chemical samples for the early cancer detection. One of the keys issues is the pre-processing of raw mass spectra data. A lot of challenges need to be addressed: unknown noise character associated with the large volume of data, high variability in the mass spectroscopy measurements, and poorly understood signal background and so on. This dissertation focuses on developing statistical algorithms and creating data mining tools for computationally improved signal processing for mass spectrometry data. I have introduced an advanced accurate estimate of the noise model and a half-supervised method of mass spectrum data processing which requires little knowledge about the data.

  8. MR imaging signal enhancement of normal intracranial and extracranial structures

    International Nuclear Information System (INIS)

    Muraki, A.S.; Carvlin, M.J.; Francisco, J.; Rocklage, S.M.; Quay, S.

    1988-01-01

    The authors report their initial experience using a paramagnetic manganese chelate complex as a contrast agent for magnetic resonance (MR) imaging of the central nervous system. Five female cats weighing 2-4 kg were used, and anesthesia was induced and maintained with intravenous nembutal (15-25 mg/kg). This contrast agent, manganese (II) N, N'-bis(pyridoxal-5-phosphate) ethylenediamine-N,N'-diacetic acid, or Mn(DPDP)(Salutar), has previously shown efficacy for MR imaging of the hepatobiliary axis but has not been employed in neuroradiologic imaging. T1-weighted (repetition time, 400 msec, echo time, 15, 26 msec; 4-mm sections) spin-echo images were acquired before and after intravenous administration (100 μmol/kg) of the contrast agent. On post-contrast images, the pituitary gland, infundibulum and portohypophyseal system of the hypothalamus and choroid lexus demonstrated signal increase at t=0-30 minutes after injection

  9. Crosstalk between pathways enhances the controllability of signalling networks.

    Science.gov (United States)

    Wang, Dingjie; Jin, Suoqin; Zou, Xiufen

    2016-02-01

    The control of complex networks is one of the most challenging problems in the fields of biology and engineering. In this study, the authors explored the controllability and control energy of several signalling networks, which consisted of many interconnected pathways, including networks with a bow-tie architecture. On the basis of the theory of structure controllability, they revealed that biological mechanisms, such as cross-pathway interactions, compartmentalisation and so on make the networks easier to fully control. Furthermore, using numerical simulations for two realistic examples, they demonstrated that the control energy of normal networks with crosstalk is lower than in networks without crosstalk. These results indicate that the biological networks are optimally designed to achieve their normal functions from the viewpoint of the control theory. The authors' work provides a comprehensive understanding of the impact of network structures and properties on controllability.

  10. Electrochemical-signal enhanced information storage device composed of cytochrome c/SNP bilayer.

    Science.gov (United States)

    Yoon, Jinho; Chung, Yong-Ho; Yoo, Si-Youl; Min, Junhong; Choi, Jeong-Woo

    2014-03-01

    The films organized with biomolecules and organic materials are important elements for developing bioelectronic devices according to their electron transfer property. Until now, several concepts of techniques have been accomplished to be used for developing biomemory devices. However it is difficult to detect the current signal from the electron transfer between biomolecules and the substrate in these fabricated films. To enhance the current signal, the silver nanoparticle was introduced to the cytochrome c in this present study. The surface morphology of the fabricated film was investigated by atomic force microscopy. The current signal enhancement was investigated by cyclic voltammetry. As a result, we could obtain the redox potentials. Moreover, by chronoamperometry, we validated that this proposed layer showed the signal-enhanced memory property for biomemory devices. This new film composed of the cytochrome c and the silver nanoparticle showed the signal enhancement. Using chronoamperometry, the areas under the graphs between 0 s and 50 ms were calculated. The calculated result showed that the areas under the cytochrome c/SNP graph and cytochrome c graph were 6.93 x 10(-7) C and 4.54 x 10(-7) C, respectively. This numerical value verified that the cytochrome c/silver nanoparticle hetero-layer film showed better electron charged biomemory performance compared to the cytochrome c monolayer. This signal-enhanced film can be applied to the bioelectronic devices which are able to replace existing electronic devices in the near future.

  11. Mine detection using SF-GPR: A signal processing approach for resolution enhancement and clutter reduction

    DEFF Research Database (Denmark)

    Karlsen, Brian; Jakobsen, Kaj Bjarne; Larsen, Jan

    2001-01-01

    is presented, and the effects of combining clutter reduction with resolution enhancement are examined using simulated SF-GPR data examples. The resolution enhancement method is based on methods from optical signal processing and is largely carried out in the frequency domain to reduce the computational burden......Proper clutter reduction is essential for Ground Penetrating Radar data since low signal-to-clutter ratio prevent correct detection of mine objects. A signal processing approach for resolution enhancement and clutter reduction used on Stepped-Frequency Ground Penetrating Radar (SF-GPR) data....... The clutter reduction method is based on basis function decomposition of the SF-GPR time-series from which the clutter and the signal are separated....

  12. Supramolecular Nanofibers Enhance Growth Factor Signaling by Increasing Lipid Raft Mobility

    Energy Technology Data Exchange (ETDEWEB)

    Newcomb, Christina J.; Sur, Shantanu; Lee, Sungsoo S.; Yu, Jeong Min; Zhou, Yan; Snead, Malcolm L.; Stupp, Samuel I. (NWU); (USC)

    2016-04-12

    The nanostructures of self-assembling biomaterials have been previously designed to tune the release of growth factors in order to optimize biological repair and regeneration. We report here on the discovery that weakly cohesive peptide nanostructures in terms of intermolecular hydrogen bonding, when combined with low concentrations of osteogenic growth factor, enhance both BMP-2 and Wnt mediated signaling in myoblasts and bone marrow stromal cells, respectively. Conversely, analogous nanostructures with enhanced levels of internal hydrogen bonding and cohesion lead to an overall reduction in BMP-2 signaling. We propose that the mechanism for enhanced growth factor signaling by the nanostructures is related to their ability to increase diffusion within membrane lipid rafts. The phenomenon reported here could lead to new nanomedicine strategies to mediate growth factor signaling for translational targets.

  13. Measles Virus Mutants Possessing the Fusion Protein with Enhanced Fusion Activity Spread Effectively in Neuronal Cells, but Not in Other Cells, without Causing Strong Cytopathology

    Science.gov (United States)

    Ohno, Shinji; Shirogane, Yuta; Suzuki, Satoshi O.; Koga, Ritsuko

    2014-01-01

    ABSTRACT Subacute sclerosing panencephalitis (SSPE) is caused by persistent measles virus (MV) infection in the central nervous system (CNS). Since human neurons, its main target cells, do not express known MV receptors (signaling lymphocyte activation molecule [SLAM] and nectin 4), it remains to be understood how MV infects and spreads in them. We have recently reported that fusion-enhancing substitutions in the extracellular domain of the MV fusion (F) protein (T461I and S103I/N462S/N465S), which are found in multiple SSPE virus isolates, promote MV spread in human neuroblastoma cell lines and brains of suckling hamsters. In this study, we show that hyperfusogenic viruses with these substitutions also spread efficiently in human primary neuron cultures without inducing syncytia. These substitutions were found to destabilize the prefusion conformation of the F protein trimer, thereby enhancing fusion activity. However, these hyperfusogenic viruses exhibited stronger cytopathology and produced lower titers at later time points in SLAM- or nectin 4-expressing cells compared to the wild-type MV. Although these viruses spread efficiently in the brains of SLAM knock-in mice, they did not in the spleens. Taken together, the results suggest that enhanced fusion activity is beneficial for MV to spread in neuronal cells where no cytopathology occurs, but detrimental to other types of cells due to strong cytopathology. Acquisition of enhanced fusion activity through substitutions in the extracellular domain of the F protein may be crucial for MV's extensive spread in the CNS and development of SSPE. IMPORTANCE Subacute sclerosing panencephalitis (SSPE) is a fatal disease caused by persistent measles virus (MV) infection in the central nervous system (CNS). Its cause is not well understood, and no effective therapy is currently available. Recently, we have reported that enhanced fusion activity of MV through the mutations in its fusion protein is a major determinant of

  14. GA(3) enhances root responsiveness to exogenous IAA by modulating auxin transport and signalling in Arabidopsis.

    Science.gov (United States)

    Li, Guijun; Zhu, Changhua; Gan, Lijun; Ng, Denny; Xia, Kai

    2015-03-01

    We used auxin-signalling mutants, auxin transport mutants, and auxin-related marker lines to show that exogenously applied GA enhances auxin-induced root inhibition by affecting auxin signalling and transport. Variation in root elongation is valuable when studying the interactions of phytohormones. Auxins influence the biosynthesis and signalling of gibberellins (GAs), but the influence of GAs on auxins in root elongation is poorly understood. This study was conducted to investigate the effect of GA3 on Arabidopsis root elongation in the presence of auxin. Root elongation was inhibited in roots treated with both IAA and GA3, compared to IAA alone, and the effect was dose dependent. Further experiments showed that GA3 could modulate auxin signalling based on root elongation in auxin-signalling mutants and the expression of auxin-responsive reporters. The GA3-enhanced inhibition of root elongation observed in the wild type was not found in the auxin-signalling mutants tir1-1 and axr1-3. GA3 increased DR5::GUS expression in the root meristem and elongation zones, and IAA2::GUS in the columella. The DR5rev::GFP signal was enhanced in columella cells of the root caps and in the elongation zone in GA3-treated seedling roots. A reduction was observed in the stele of PAC-treated roots. We also examined the effect of GA3 on auxin transport. The enhanced responsiveness caused by GA3 was not observed in the auxin influx mutant aux1-7 or the efflux mutant eir1-1. Additional molecular data demonstrated that GA3 could promote auxin transport via AUX1 and PIN proteins. However, GA3-induced PIN gene expression did not fully explain GA-enhanced PIN protein accumulation. These results suggest that GA3 is involved in auxin-mediated primary root elongation by modulating auxin signalling and transport, and thus enhances root responsiveness to exogenous IAA.

  15. Noise-enhanced nonlinear response and the role of modular structure for signal detection in neuronal networks.

    Science.gov (United States)

    Lopes, M A; Lee, K-E; Goltsev, A V; Mendes, J F F

    2014-11-01

    We show that sensory noise can enhance the nonlinear response of neuronal networks, and when delivered together with a weak signal, it improves the signal detection by the network. We reveal this phenomenon in neuronal networks that are in a dynamical state preceding a saddle-node bifurcation corresponding to the appearance of sustained network oscillations. In this state, even a weak subthreshold pulse can evoke a large-amplitude oscillation of neuronal activity. The signal-to-noise ratio reaches a maximum at an optimum level of sensory noise, manifesting stochastic resonance (SR) at the population level. We demonstrate SR by use of simulations and numerical integration of rate equations in a cortical model. Using this model, we mimic the experiments of Gluckman et al. [Phys. Rev. Lett. 77, 4098 (1996)PRLTAO0031-900710.1103/PhysRevLett.77.4098] that have given evidence of SR in mammalian brain. We also study neuronal networks in which neurons are grouped in modules and every module works in the regime of SR. We find that even a few modules can strongly enhance the reliability of signal detection in comparison with the case when a modular organization is absent.

  16. Use and Protection of GPS Sidelobe Signals for Enhanced Navigation Performance in High Earth Orbit

    Science.gov (United States)

    Parker, Joel J. K.; Valdez, Jennifer E.; Bauer, Frank H.; Moreau, Michael C.

    2016-01-01

    GPS (Global Positioning System) Space Service Volume (SSV) signal environment is from 3,000-36,000 kilometers altitude. Current SSV specifications only capture performance provided by signals transmitted within 23.5(L1) or 26(L2-L5) off-nadir angle. Recent on-orbit data lessons learned show significant PNT (Positioning, Navigation and Timing) performance improvements when the full aggregate signal is used. Numerous military civil operational missions in High Geosynchronous Earth Orbit (HEOGEO) utilize the full signal to enhance vehicle PNT performance

  17. Enhancement of endocannabinoid signaling protects against cocaine-induced neurotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Vilela, Luciano R. [Graduate Program in Neuroscience, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Gobira, Pedro H.; Viana, Thercia G. [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Medeiros, Daniel C.; Ferreira-Vieira, Talita H. [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Doria, Juliana G. [Graduate Program in Neuroscience, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Rodrigues, Flávia [Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Aguiar, Daniele C. [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Pereira, Grace S.; Massessini, André R. [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Ribeiro, Fabíola M. [Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Oliveira, Antonio Carlos P. de [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Moraes, Marcio F.D., E-mail: mfdm@icb.ufmg.br [Department of Physiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil); Moreira, Fabricio A., E-mail: fabriciomoreira@icb.ufmg.br [Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil)

    2015-08-01

    Cocaine is an addictive substance with a potential to cause deleterious effects in the brain. The strategies for treating its neurotoxicity, however, are limited. Evidence suggests that the endocannabinoid system exerts neuroprotective functions against various stimuli. Thus, we hypothesized that inhibition of fatty acid amide hydrolase (FAAH), the main enzyme responsible for terminating the actions of the endocannabinoid anandamide, reduces seizures and cell death in the hippocampus in a model of cocaine intoxication. Male Swiss mice received injections of endocannabinoid-related compounds followed by the lowest dose of cocaine that induces seizures, electroencephalographic activity and cell death in the hippocampus. The molecular mechanisms were studied in primary cell culture of this structure. The FAAH inhibitor, URB597, reduced cocaine-induced seizures and epileptiform electroencephalographic activity. The cannabinoid CB{sub 1} receptor selective agonist, ACEA, mimicked these effects, whereas the antagonist, AM251, prevented them. URB597 also inhibited cocaine-induced activation and death of hippocampal neurons, both in animals and in primary cell culture. Finally, we investigated if the PI3K/Akt/ERK intracellular pathway, a cell surviving mechanism coupled to CB{sub 1} receptor, mediated these neuroprotective effects. Accordingly, URB597 injection increased ERK and Akt phosphorylation in the hippocampus. Moreover, the neuroprotective effect of this compound was reversed by the PI3K inhibitor, LY294002. In conclusion, the pharmacological facilitation of the anandamide/CB1/PI3K signaling protects the brain against cocaine intoxication in experimental models. This strategy may be further explored in the development of treatments for drug-induced neurotoxicity. - Highlights: • Cocaine toxicity is characterized by seizures and hippocampal cell death. • The endocannabinoid anandamide acts as a brain protective mechanism. • Inhibition of anandamide hydrolysis

  18. Enhancement of endocannabinoid signaling protects against cocaine-induced neurotoxicity

    International Nuclear Information System (INIS)

    Vilela, Luciano R.; Gobira, Pedro H.; Viana, Thercia G.; Medeiros, Daniel C.; Ferreira-Vieira, Talita H.; Doria, Juliana G.; Rodrigues, Flávia; Aguiar, Daniele C.; Pereira, Grace S.; Massessini, André R.; Ribeiro, Fabíola M.; Oliveira, Antonio Carlos P. de; Moraes, Marcio F.D.; Moreira, Fabricio A.

    2015-01-01

    Cocaine is an addictive substance with a potential to cause deleterious effects in the brain. The strategies for treating its neurotoxicity, however, are limited. Evidence suggests that the endocannabinoid system exerts neuroprotective functions against various stimuli. Thus, we hypothesized that inhibition of fatty acid amide hydrolase (FAAH), the main enzyme responsible for terminating the actions of the endocannabinoid anandamide, reduces seizures and cell death in the hippocampus in a model of cocaine intoxication. Male Swiss mice received injections of endocannabinoid-related compounds followed by the lowest dose of cocaine that induces seizures, electroencephalographic activity and cell death in the hippocampus. The molecular mechanisms were studied in primary cell culture of this structure. The FAAH inhibitor, URB597, reduced cocaine-induced seizures and epileptiform electroencephalographic activity. The cannabinoid CB 1 receptor selective agonist, ACEA, mimicked these effects, whereas the antagonist, AM251, prevented them. URB597 also inhibited cocaine-induced activation and death of hippocampal neurons, both in animals and in primary cell culture. Finally, we investigated if the PI3K/Akt/ERK intracellular pathway, a cell surviving mechanism coupled to CB 1 receptor, mediated these neuroprotective effects. Accordingly, URB597 injection increased ERK and Akt phosphorylation in the hippocampus. Moreover, the neuroprotective effect of this compound was reversed by the PI3K inhibitor, LY294002. In conclusion, the pharmacological facilitation of the anandamide/CB1/PI3K signaling protects the brain against cocaine intoxication in experimental models. This strategy may be further explored in the development of treatments for drug-induced neurotoxicity. - Highlights: • Cocaine toxicity is characterized by seizures and hippocampal cell death. • The endocannabinoid anandamide acts as a brain protective mechanism. • Inhibition of anandamide hydrolysis attenuates

  19. METHODS FOR QUALITY ENHANCEMENT OF USER VOICE SIGNAL IN VOICE AUTHENTICATION SYSTEMS

    Directory of Open Access Journals (Sweden)

    O. N. Faizulaieva

    2014-03-01

    Full Text Available The reasonability for the usage of computer systems user voice in the authentication process is proved. The scientific task for improving the signal/noise ratio of the user voice signal in the authentication system is considered. The object of study is the process of input and output of the voice signal of authentication system user in computer systems and networks. Methods and means for input and extraction of voice signal against external interference signals are researched. Methods for quality enhancement of user voice signal in voice authentication systems are suggested. As modern computer facilities, including mobile ones, have two-channel audio card, the usage of two microphones is proposed in the voice signal input system of authentication system. Meanwhile, the task of forming a lobe of microphone array in a desired area of voice signal registration (100 Hz to 8 kHz is solved. The usage of directional properties of the proposed microphone array gives the possibility to have the influence of external interference signals two or three times less in the frequency range from 4 to 8 kHz. The possibilities for implementation of space-time processing of the recorded signals using constant and adaptive weighting factors are investigated. The simulation results of the proposed system for input and extraction of signals during digital processing of narrowband signals are presented. The proposed solutions make it possible to improve the value of the signal/noise ratio of the useful signals recorded up to 10, ..., 20 dB under the influence of external interference signals in the frequency range from 4 to 8 kHz. The results may be useful to specialists working in the field of voice recognition and speaker’s discrimination.

  20. Secondary ion mass spectrometric signal enhancement of phosphatidylcholine dioleoyl on enlarged nanoparticles surface

    Energy Technology Data Exchange (ETDEWEB)

    Gulin, A. [N.N. Semenov Institute of Chemical Physics, RAS, Kosigin str. 4, Moscow 119991 (Russian Federation); Mochalova, M. [Moscow Institute of Physics and Technology, Institutskii per. 9, Dolgoprudny, Moscow 141700 (Russian Federation); Denisov, N. [Institute of Problem of Chemical Physics, RAS, Semenov av. 1, Chernogolovka, 142432 (Russian Federation); Nadtochenko, V., E-mail: nadtochenko@gmail.com [N.N. Semenov Institute of Chemical Physics, RAS, Kosigin str. 4, Moscow 119991 (Russian Federation); Moscow Institute of Physics and Technology, Institutskii per. 9, Dolgoprudny, Moscow 141700 (Russian Federation); Institute of Problem of Chemical Physics, RAS, Semenov av. 1, Chernogolovka, 142432 (Russian Federation)

    2014-10-15

    Graphical abstract: - Highlights: • TOF-SIMS mass-spectra of DOPC lipid on enlarged nanoparticles surface were studied. • Metallic, semiconductor, dielectric and hybrid nanoparticles were examined. • Effect of nanoparticles on mass-spectral peaks intensity was investigated. • The highest signal enhancement of 42 times was found for hybrid core–shell Au/SiO{sub 2} nanoparticles. - Abstract: A silicon wafer surface coverage of nanoparticles (NPs) can enhance the L-α-phosphatidylcholine dioleoyl (DOPC) signal intensity in time-of-flight secondary ion mass spectrometry (TOF-SIMS). A ToF-SIMS mass spectrometer was used with a pulsed primary beam of focused 30 keV Bi{sub 3}{sup +} ions. The signal enhancing effect has been studied for metallic (Ag, Au, Pb), semiconductor (TiO{sub 2}), dielectric (SiO{sub 2}) and hybrid (Au/TiO{sub 2}NPs, core–shell Au/SiO{sub 2}) nanoparticles. Ag NPs can attenuate secondary ions signal, whereas all other studied NPs show the signal enhancement. The emission of DOPC lipid secondary ions immobilized on core–shell Au/SiO{sub 2}NPs was enhanced up to 42 times. This technique is a simple preparatory method enabling an overall increase in molecular lipid ions.

  1. Secondary ion mass spectrometric signal enhancement of phosphatidylcholine dioleoyl on enlarged nanoparticles surface

    International Nuclear Information System (INIS)

    Gulin, A.; Mochalova, M.; Denisov, N.; Nadtochenko, V.

    2014-01-01

    Graphical abstract: - Highlights: • TOF-SIMS mass-spectra of DOPC lipid on enlarged nanoparticles surface were studied. • Metallic, semiconductor, dielectric and hybrid nanoparticles were examined. • Effect of nanoparticles on mass-spectral peaks intensity was investigated. • The highest signal enhancement of 42 times was found for hybrid core–shell Au/SiO 2 nanoparticles. - Abstract: A silicon wafer surface coverage of nanoparticles (NPs) can enhance the L-α-phosphatidylcholine dioleoyl (DOPC) signal intensity in time-of-flight secondary ion mass spectrometry (TOF-SIMS). A ToF-SIMS mass spectrometer was used with a pulsed primary beam of focused 30 keV Bi 3 + ions. The signal enhancing effect has been studied for metallic (Ag, Au, Pb), semiconductor (TiO 2 ), dielectric (SiO 2 ) and hybrid (Au/TiO 2 NPs, core–shell Au/SiO 2 ) nanoparticles. Ag NPs can attenuate secondary ions signal, whereas all other studied NPs show the signal enhancement. The emission of DOPC lipid secondary ions immobilized on core–shell Au/SiO 2 NPs was enhanced up to 42 times. This technique is a simple preparatory method enabling an overall increase in molecular lipid ions

  2. Thy-1/CD3 coengagement promotes TCR signaling and enhances particularly tyrosine phosphorylation of the raft molecule LAT.

    Science.gov (United States)

    Leyton, L; Quest, A F; Bron, C

    1999-08-01

    Clustering of the glycosyl-phosphatidylinositol (GPI)-anchored protein Thy-1 on the cell surface leads to T cell activation. However, despite the similarity to TCR-mediated events, cell signaling triggered by Thy-1 crosslinking, reportedly occurs in a manner independent of the TCR/CD3 complex. To investigate the relationship between responses resulting from Thy-1 or TCR engagement, a biochemically well defined system employing only affinity purified antibodies was used to crosslink these surface molecules and activation was assessed by monitoring tyrosine phosphorylation, intracellular calcium influx and IL-2 production. By these criteria, anti-CD3 mAbs moderately activated EL-4 thymoma or 2B4 hybridoma cell lines, while costimulation with anti-Thy-1-mAb strongly enhanced TCR signaling. Furthermore, a Thy-1 loss mutant cell line, did not respond to stimulation through CD3 despite expressing all essential signaling molecules. Together these results emphasized the existence of a poorly appreciated mutual interdependence between Thy-1 and CD3 for efficient cellular signaling. Thy-1/CD3-mediated activation enhanced mostly tyrosine phosphorylation of a 40 kDa protein which was identified as a transmembrane protein lacking N-linked oligosaccharides. These biochemical properties are identical to those described for a recently cloned adaptor protein called 'Linker for Activation of T cells' (LAT). Indeed, polyclonal Abs raised against a LAT-peptide (amino acids 103-131) specifically recognized the 40 kDa protein. LAT is present in microdomains of the plasma membrane enriched in sphingolipids, cholesterol, GPI-anchored proteins and a variety of signaling molecules. By contrast, the TCR/CD3 complex is excluded from these domains at least until stimulation takes place. Hence, we propose that Thy-1 promotes TCR/CD3 dependent signaling by facilitating LAT phosphorylation on tyrosine and the subsequent recruitment of downstream effector molecules.

  3. Enhanced dispersion stability and mobility of carboxyl-functionalized carbon nanotubes in aqueous solutions through strong hydrogen bonds

    International Nuclear Information System (INIS)

    Bahk, Yeon Kyoung; He, Xu; Gitsis, Emmanouil; Kuo, Yu-Ying; Kim, Nayoung; Wang, Jing

    2015-01-01

    Dispersion of carbon nanotubes has been heavily studied due to its importance for their technical applications, toxic effects, and environmental impacts. Common electrolytes, such as sodium chloride and potassium chloride, promote agglomeration of nanoparticles in aqueous solutions. On the contrary, we discovered that acetic electrolytes enhanced the dispersion of multi-walled carbon nanotubes (MWCNTs) with carboxyl functional group through the strong hydrogen bond, which was confirmed by UV–Vis spectrometry, dispersion observations and aerosolization-quantification method. When concentrations of acetate electrolytes such as ammonium acetate (CH 3 CO 2 NH 4 ) and sodium acetate (CH 3 CO 2 Na) were lower than 0.03 mol per liter, MWCNT suspensions showed better dispersion and had higher mobility in porous media. The effects by the acetic environment are also applicable to other nanoparticles with the carboxyl functional group, which was demonstrated with polystyrene latex particles as an example

  4. Both Autocrine Signaling and Paracrine Signaling of HB-EGF Enhance Ocular Neovascularization.

    Science.gov (United States)

    Inoue, Yuki; Shimazawa, Masamitsu; Nakamura, Shinsuke; Takata, Shinsuke; Hashimoto, Yuhei; Izawa, Hiroshi; Masuda, Tomomi; Tsuruma, Kazuhiro; Sakaue, Tomohisa; Nakayama, Hironao; Higashiyama, Shigeki; Hara, Hideaki

    2018-01-01

    The incidence of blindness is increasing because of the increase in abnormal ocular neovascularization. Anti-VEGF (vascular endothelial growth factor) therapies have led to good results, although they are not a cure for the blindness. The purpose of this study was to determine what role HB-EGF (heparin-binding epidermal growth factor-like growth factor) plays in ocular angiogenesis. We examined the role played by HB-EGF in ocular neovascularization in 2 animal models of neovascularization: laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy. We also studied human retinal microvascular endothelial cells in culture. Our results showed that the neovascularization was decreased in both the CNV and oxygen-induced retinopathy models in HB-EGF conditional knockout mice compared with that in wild-type mice. Moreover, the expressions of HB-EGF and VEGF were increased after laser-induced CNV and oxygen-induced retinopathy, and their expression sites were located around the neovascular areas. Exposure of human retinal microvascular endothelial cells to HB-EGF and VEGF increased their proliferation and migration, and CRM-197 (cross-reactive material-197), an HB-EGF inhibitor, decreased the HB-EGF-induced and VEGF-induced cell proliferation and migration. VEGF increased the expression of HB-EGF mRNA. VEGF-dependent activation of EGFR (epidermal growth factor receptor)/ERK1/2 (extracellular signal-regulated kinase 1/2) signaling and cell proliferation of endothelial cells required stimulation of the ADAM17 (a disintegrin and metalloprotease) and ADAM12. CRM-197 decreased the grades of the fluorescein angiograms and size of the CNV areas in marmoset monkeys. These findings suggest that HB-EGF plays an important role in the development of CNV. Therefore, further investigations of HB-EGF are needed as a potential therapeutic target in the treatment of exudative age-related macular degeneration. © 2017 American Heart Association, Inc.

  5. Multichannel Signal Enhancement using Non-Causal, Time-Domain Filters

    DEFF Research Database (Denmark)

    Jensen, Jesper Rindom; Christensen, Mads Græsbøll; Benesty, Jacob

    2013-01-01

    In the vast amount of time-domain filtering methods for speech enhancement, the filters are designed to be causal. Recently, however, it was shown that the noise reduction and signal distortion capabilities of such single-channel filters can be improved by allowing the filters to be non-causal. W......In the vast amount of time-domain filtering methods for speech enhancement, the filters are designed to be causal. Recently, however, it was shown that the noise reduction and signal distortion capabilities of such single-channel filters can be improved by allowing the filters to be non......-causal, multichannel filters for enhancement based on an orthogonal decomposition is proposed. The evaluation shows that there is a potential gain in noise reduction and signal distortion by introducing non-causality. Moreover, experiments on real-life speech show that we can improve the perceptual quality....

  6. Enhancement of Chiroptical Signals by Circular Differential Mie Scattering of Nanoparticles.

    Science.gov (United States)

    Yoo, SeokJae; Park, Q-Han

    2015-09-25

    We enhance the weak optical signals of small chiral molecules via circular differential Mie scattering (CDMS) of nanoparticles immersed in them. CDMS is the preferential Mie scattering of left- and right-handed circularly polarized light by nanoparticles whose sizes are about the same as the wavelength of light. Solving the Mie scattering theory for chiral media, we find that the CDMS signal of the particle is linearly proportional to the chirality parameter κ of the molecules. This linear amplitude enhancement by CDMS of the particle holds, even for large particles, which have a retardation effect. We also demonstrate that the CDMS of a nanoparticle is sensitive to changes of molecular concentration, and that the nanoparticle can be utilized as a chiroptical biosensor detecting the concentration of analyte. We expect that the enhancement of molecular chiroptical signals by CDMS will pave the way for novel chiroptical spectroscopy using nanostructures.

  7. Mutant p53 shapes the enhancer landscape of cancer cells in response to chronic immune signaling.

    Science.gov (United States)

    Rahnamoun, Homa; Lu, Hanbin; Duttke, Sascha H; Benner, Christopher; Glass, Christopher K; Lauberth, Shannon M

    2017-09-29

    Inflammation influences cancer development, progression, and the efficacy of cancer treatments, yet the mechanisms by which immune signaling drives alterations in the cancer cell transcriptome remain unclear. Using ChIP-seq, RNA-seq, and GRO-seq, here we demonstrate a global overlap in the binding of tumor-promoting p53 mutants and the master proinflammatory regulator NFκB that drives alterations in enhancer and gene activation in response to chronic TNF-α signaling. We show that p53 mutants interact directly with NFκB and that both factors impact the other's binding at diverse sets of active enhancers. In turn, the simultaneous and cooperative binding of these factors is required to regulate RNAPII recruitment, the synthesis of enhancer RNAs, and the activation of tumor-promoting genes. Collectively, these findings establish a mechanism by which chronic TNF-α signaling orchestrates a functional interplay between mutant p53 and NFκB that underlies altered patterns of cancer-promoting gene expression.Inflammation is known to affect cancer development, yet the mechanisms by which immune signaling drives transformation remain unclear. Here, the authors provide evidence that chronic TNF-α signaling promotes the enhancer binding and transcriptional interplay between mutant p53 and NFκB.

  8. Enhanced summer warming reduces fungal decomposer diversity and litter mass loss more strongly in dry than in wet tundra.

    Science.gov (United States)

    Christiansen, Casper T; Haugwitz, Merian S; Priemé, Anders; Nielsen, Cecilie S; Elberling, Bo; Michelsen, Anders; Grogan, Paul; Blok, Daan

    2017-01-01

    Many Arctic regions are currently experiencing substantial summer and winter climate changes. Litter decomposition is a fundamental component of ecosystem carbon and nutrient cycles, with fungi being among the primary decomposers. To assess the impacts of seasonal climatic changes on litter fungal communities and their functioning, Betula glandulosa leaf litter was surface-incubated in two adjacent low Arctic sites with contrasting soil moisture regimes: dry shrub heath and wet sedge tundra at Disko Island, Greenland. At both sites, we investigated the impacts of factorial combinations of enhanced summer warming (using open-top chambers; OTCs) and deepened snow (using snow fences) on surface litter mass loss, chemistry and fungal decomposer communities after approximately 1 year. Enhanced summer warming significantly restricted litter mass loss by 32% in the dry and 17% in the wet site. Litter moisture content was significantly reduced by summer warming in the dry, but not in the wet site. Likewise, fungal total abundance and diversity were reduced by OTC warming at the dry site, while comparatively modest warming effects were observed in the wet site. These results suggest that increased evapotranspiration in the OTC plots lowered litter moisture content to the point where fungal decomposition activities became inhibited. In contrast, snow addition enhanced fungal abundance in both sites but did not significantly affect litter mass loss rates. Across sites, control plots only shared 15% of their fungal phylotypes, suggesting strong local controls on fungal decomposer community composition. Nevertheless, fungal community functioning (litter decomposition) was negatively affected by warming in both sites. We conclude that although buried soil organic matter decomposition is widely expected to increase with future summer warming, surface litter decay and nutrient turnover rates in both xeric and relatively moist tundra are likely to be significantly restricted by

  9. Wood properties in a long-lived conifer reveal strong climate signals where ring-width series do not.

    Science.gov (United States)

    Drew, David M; Allen, Kathryn; Downes, Geoffrey M; Evans, Robert; Battaglia, Michael; Baker, Patrick

    2013-01-01

    Although tree-ring-width chronologies have been widely used for temperature reconstructions, there are many sites around the world at which there is little evidence of a clear climate signal in the ring-width chronologies. This is the case with the long-lived conifer Huon pine (Lagarostrobos franklinii (Hook. F.) Quinn), endemic to Tasmania, Australia, when the species grows at low elevation. In this study, we developed chronologies of several wood properties (e.g., tracheid radial diameter, microfibril angle) from Huon pine growing at a low-elevation site. We found that despite the absence of a climate signal in the ring-width chronologies, there were significant correlations between wood density, tracheid radial diameter and microfibril angle and temperature, stream flow and a drought index, enabling the development of robust chronologies. This novel finding suggests that chronologies based on these wood properties may have important potential for climate reconstructions from sites and species that have not yet been realized. In particular, a relatively extensive resource of ancient, low-elevation Huon pine in western Tasmania, in which climate signals have not been found using ring widths, may now be useful as part of the broader effort to reconstruct Southern Hemisphere climate.

  10. Detection of a Low Power Communication Signal in the Presence of a Strong Co-Channel TV Broadcast Interference Using a Kalman Filter

    Science.gov (United States)

    2014-12-01

    Television Systems Committee AWGN additive white Gaussian noise BCH Bose-Chaudhuri-Hocquengham bps bits per second CIR channel impulse response... impulse responses (CIRs) are used both for equalization in the respective DVB-T2 receivers and in the KF to estimate the state of the DVB-T2 signal...if a communication system can operate reliably in the presence of a strong, co-channel interference, then there is no need to buy spectrum, an

  11. Transmission Property of Directly Modulated Signals Enhanced by a Micro-ring Resonator

    DEFF Research Database (Denmark)

    An, Yi; Lorences Riesgo, Abel; Seoane, Jorge

    2012-01-01

    A silicon micro-ring resonator is used to enhance the modulation speed of a 10-Gbit/s directly modulated laser to 40 Gbit/s. The generated signal is transmitted error free over 4.5 km SSMF. Dispersion tolerance is also studied....

  12. Laser induced breakdown spectroscopy based on single beam splitting and geometric configuration for effective signal enhancement.

    Science.gov (United States)

    Yang, Guang; Lin, Qingyu; Ding, Yu; Tian, Di; Duan, Yixiang

    2015-01-05

    A new laser induced breakdown spectroscopy (LIBS) based on single-beam-splitting (SBS) and proper optical geometric configuration has been initially explored in this work for effective signal enhancement. In order to improve the interaction efficiency of laser energy with the ablated material, a laser beam operated in pulse mode was divided into two streams to ablate/excite the target sample in different directions instead of the conventional one beam excitation in single pulse LIBS (SP-LIBS). In spatial configuration, the laser beam geometry plays an important role in the emission signal enhancement. Thus, an adjustable geometric configuration with variable incident angle between the two splitted laser beams was constructed for achieving maximum signal enhancement. With the optimized angles of 60° and 70° for Al and Cu atomic emission lines at 396.15 nm and 324.75 nm respectively, about 5.6- and 4.8-folds signal enhancements were achieved for aluminum alloy and copper alloy samples compared to SP-LIBS. Furthermore, the temporal analysis, in which the intensity of atomic lines in SP-LIBS decayed at least ten times faster than the SBS-LIBS, proved that the energy coupling efficiency of SBS-LIBS was significantly higher than that of SP-LIBS.

  13. Laser Induced Breakdown Spectroscopy Based on Single Beam Splitting and Geometric Configuration for Effective Signal Enhancement

    Science.gov (United States)

    Yang, Guang; Lin, Qingyu; Ding, Yu; Tian, Di; Duan, Yixiang

    2015-01-01

    A new laser induced breakdown spectroscopy (LIBS) based on single-beam-splitting (SBS) and proper optical geometric configuration has been initially explored in this work for effective signal enhancement. In order to improve the interaction efficiency of laser energy with the ablated material, a laser beam operated in pulse mode was divided into two streams to ablate/excite the target sample in different directions instead of the conventional one beam excitation in single pulse LIBS (SP-LIBS). In spatial configuration, the laser beam geometry plays an important role in the emission signal enhancement. Thus, an adjustable geometric configuration with variable incident angle between the two splitted laser beams was constructed for achieving maximum signal enhancement. With the optimized angles of 60° and 70° for Al and Cu atomic emission lines at 396.15 nm and 324.75 nm respectively, about 5.6- and 4.8-folds signal enhancements were achieved for aluminum alloy and copper alloy samples compared to SP-LIBS. Furthermore, the temporal analysis, in which the intensity of atomic lines in SP-LIBS decayed at least ten times faster than the SBS-LIBS, proved that the energy coupling efficiency of SBS-LIBS was significantly higher than that of SP-LIBS. PMID:25557721

  14. Novel nano-sized MR contrast agent mediates strong tumor contrast enhancement in an oncogene-driven breast cancer model.

    Directory of Open Access Journals (Sweden)

    Per-Olof Eriksson

    Full Text Available The current study was carried out to test the potential of a new nanomaterial (Spago Pix as a macromolecular magnetic MR contrast agent for tumor detection and to verify the presence of nanomaterial in tumor tissue. Spago Pix, synthesized by Spago Nanomedical AB, is a nanomaterial with a globular shape, an average hydrodynamic diameter of 5 nm, and a relaxivity (r1 of approximately 30 (mM Mn-1 s-1 (60 MHz. The material consists of an organophosphosilane hydrogel with strongly chelated manganese (II ions and a covalently attached PEG surface layer. In vivo MRI of the MMTV-PyMT breast cancer model was performed on a 3 T clinical scanner. Tissues were thereafter analyzed for manganese and silicon content using inductively coupled plasma-atomic emission spectroscopy (ICP-AES. The presence of nanomaterial in tumor and muscle tissue was assessed using an anti-PEG monoclonal antibody. MR imaging of tumor-bearing mice (n = 7 showed a contrast enhancement factor of 1.8 (tumor versus muscle at 30 minutes post-administration. Contrast was retained and further increased 2-4 hours after administration. ICP-AES and immunohistochemistry confirmed selective accumulation of nanomaterial in tumor tissue. A blood pharmacokinetics analysis showed that the concentration of Spago Pix gradually decreased over the first hour, which was in good agreement with the time frame in which the accumulation in tumor occurred. In summary, we demonstrate that Spago Pix selectively enhances MR tumor contrast in a clinically relevant animal model. Based on the generally higher vascular leakiness in malignant compared to benign tissue lesions, Spago Pix has the potential to significantly improve cancer diagnosis and characterization by MRI.

  15. Changes in gadolinium-DTPA enhanced magnetic resonance signal intensity ratio in hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Tsukihashi, Hironori; Ishibashi, Yutaka; Shimada, Toshio; Hatano, Jun; Tanabe, Kazuaki; Ooyake, Nobuyuki; Morioka, Shigefumi; Moriyama, Katsutoshi (Shimane Medical Univ., Izumo (Japan))

    Serial gadolinium-diethylene-triamine-pentaacetic acid (Gd-DTPA) enhanced magnetic resonance (MR) signal intensity ratios were measured in 6 normal subjects and 20 hypertrophic cardiomyopathy (HCM) patients to try to differentiate normal from disorganized myocardial tissue. Images were obtained at 10-minute intervals 5-60 minutes after Gd-DTPA (0.1 mmol/kg) injection. The signal intensity ratio (myocardial signal intensity/skeletal muscle signal intensity) was measured at both hypertrophic and non-hypertrophic regions in each image at the apex and mid-ventricular levels. The signal intensity ratio was standardized to compare each case. Hypertrophic myocardium was classified into two types. Type I in 11 of 20 patients was visualized as a homogeneous image, while type II in the other 9 patients was revealed as a mixed isointensity and high intensity area. The peak value of the standardized signal intensity ratio at the apex level was 1.28[+-]0.09 in HCM patients and 1.23[+-]0.06 in normal subjects, and at the mid ventricular level was 1.26[+-]0.07 in hypertrophic regions, 1.17[+-]0.12 in non-hypertrophic regions, and 1.16[+-]0.07 in normal subjects. Thirty minutes after Gd injection, the standardized signal intensity ratio at the apex level was 1.21[+-]0.08 in HCM patients and 1.07[+-]0.08 in normal subjects, and those at the mid ventricular level was 1.20[+-]0.09 in hypertrophic regions, 1.11[+-]0.11 in non-hypertrophic regions, and 1.04[+-]0.06 in normal subjects. The delayed decay of the signal intensity ratio and high signal intensity ratio in Gd-DTPA enhanced MR images are useful in myocardial tissue characterization in hypertrophic cardiomyopathy. (author).

  16. Data-Driven Iterative Vibration Signal Enhancement Strategy Using Alpha Stable Distribution

    Directory of Open Access Journals (Sweden)

    Grzegorz Żak

    2017-01-01

    Full Text Available The authors propose a novel procedure for enhancement of the signal to noise ratio in vibration data acquired from machines working in mining industry environment. Proposed method allows performing data-driven reduction of the deterministic, high energy, and low frequency components. Furthermore, it provides a way to enhance signal of interest. Procedure incorporates application of the time-frequency decomposition, α-stable distribution based signal modeling, and stability parameter in the time domain as a stoppage criterion for iterative part of the procedure. An advantage of the proposed algorithm is data-driven, automative detection of the informative frequency band as well as band with high energy due to the properties of the used distribution. Furthermore, there is no need to have knowledge regarding kinematics, speed, and so on. The proposed algorithm is applied towards real data acquired from the belt conveyor pulley drive’s gearbox.

  17. Traveltime dispersion in an isotropic elastic mantle: strong lower-mantle signal in differential-frequency residuals

    Science.gov (United States)

    Schuberth, Bernhard S. A.; Zaroli, Christophe; Nolet, Guust

    2015-12-01

    We study wavefield effects of direct P- and S-waves in elastic and isotropic 3-D seismic structures derived from the temperature field of a high-resolution mantle circulation model. More specifically, we quantify the dispersion of traveltime residuals caused by diffraction in structures with dynamically constrained length scales and magnitudes of the lateral variations in seismic velocities and density. 3-D global wave propagation is simulated using a spectral element method. Intrinsic attenuation (i.e. dissipation of seismic energy) is deliberately neglected, so that any variation of traveltimes with frequency can be attributed to structural effects. Traveltime residuals are measured at 15, 22.5, 34 and 51 s dominant periods by cross-correlation of 3-D and 1-D synthetic waveforms. Additional simulations are performed for a model in which 3-D structure is removed in the upper 800 km to isolate the dispersion signal of the lower mantle. We find that the structural length scales inherent to a vigorously convecting mantle give rise to significant diffraction-induced body-wave traveltime dispersion. For both P- and S-waves, the difference between long-period and short-period residuals for a given source-receiver pair can reach up to several seconds for the period bands considered here. In general, these `differential-frequency' residuals tend to increase in magnitude with increasing short-period delay. Furthermore, the long-period signal typically is smaller in magnitude than the short-period one; that is, wave-front healing is efficient independent of the sign of the residuals. Unlike the single-frequency residuals, the differential-frequency residuals are surprisingly similar between the `lower-mantle' and the `whole-mantle' model for corresponding source-receiver pairs. The similarity is more pronounced in case of S-waves and varies between different combinations of period bands. The traveltime delay acquired in the upper mantle seems to cancel in these differential

  18. Downhole microseismic signal-to-noise ratio enhancement via strip matching shearlet transform

    Science.gov (United States)

    Li, Juan; Ji, Shuo; Li, Yue; Qian, Zhihong; Lu, Weili

    2018-04-01

    Shearlet transform has been proved effective in noise attenuation. However, because of the low magnitude and high frequency of downhole microseismic signals, the coefficient values of valid signals and noise are similar in the shearlet domain. As a result, it is hard to suppress the noise. In this paper, we present a novel signal-to-noise ratio enhancement scheme called strip matching shearlet transform. The method takes into account the directivity of microseismic events and shearlets. Through strip matching, the matching degree in direction between them has been promoted. Then the coefficient values of valid signals are much larger than those of the noise. Consequently, we can separate them well with the help of thresholding. The experimental results on both synthetic records and field data illustrate that our proposed method preserves the useful components and attenuates the noise well.

  19. The MsPRP2 promoter enables strong heterologous gene expression in a root-specific manner and is enhanced by overexpression of Alfin 1.

    Science.gov (United States)

    Winicov, Ilga; Valliyodan, Babu; Xue, Lingru; Hoober, J Kenneth

    2004-10-01

    Promoter specificity and efficiency of utilization are essential for endogenous and transgene expression. Selective root expression remains to be defined in terms of both promoter elements and transcription factors that provide high levels of ubiquitous expression. We characterized expression from the MsPRP2 promoter with the green fluorescent protein (GFP) reporter transgene in alfalfa (Medicago sativa) and found that a promoter fragment (+1 to -652 bp) retained the root and callus specificity of the endogenous MsPRP2 gene and hence this promoter fragment contains elements necessary for root-specific expression. The strong ubiquitous expression obtained from this promoter was comparable to that of the CaMV 35S promoter in roots and was enhanced by transgenic overexpression of Alfin 1, a root- and callus-specific transcription factor in alfalfa. No transgenic expression was obtained in leaves with this promoter in the presence or absence of Alfin 1. The increased expression of GFP in alfalfa containing the Alfin 1 transgene confirms the function of Alfin 1 binding sites in the MsPRP2 promoter fragment and also indicates that Alfin 1 concentrations are limiting for maximal expression in calli and roots. These findings characterize the MsPRP2 promoter as a novel root- and callus-specific promoter of plant origin that can be used as an effective tool for strong root-directed gene expression. In addition, we have demonstrated that the signal sequence of MsPRP2 can be used for efficient secretion of transgene products from callus and roots.

  20. A new goniothalamin N-acylated aza-derivative strongly downregulates mediators of signaling transduction associated with pancreatic cancer aggressiveness.

    Science.gov (United States)

    Barcelos, Rosimeire Coura; Pelizzaro-Rocha, Karin Juliane; Pastre, Julio Cezar; Dias, Marina Pereira; Ferreira-Halder, Carmen Veríssima; Pilli, Ronaldo Aloise

    2014-11-24

    In this study, a novel concise series of molecules based on the structure of goniothalamin (1) was synthesized and evaluated against a highly metastatic human pancreatic cancer cell line (Panc-1). Among them, derivative 8 displayed a low IC50 value (2.7 μM) and its concentration for decreasing colony formation was 20-fold lower than goniothalamin (1). Both compounds reduced the levels of the receptor tyrosine kinase (AXL) and cyclin D1 which are known to be overexpressed in pancreatic cancer cells. Importantly, despite the fact that goniothalamin (1) and derivative 8 caused pancreatic cancer cell cycle arrest and cell death, only derivative 8 was able to downregulate pro-survival and proliferation pathways mediated by mitogen activated protein kinase ERK1/2. Another interesting finding was that Panc-1 cells treated with derivative 8 displayed a strong decrease in the transcription factor (c-Myc), hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) protein levels. Notably, the molecular effects caused by derivative 8 might not be related to ROS generation, since no significant production of ROS was observed in low concentrations of this compound (from 1.5 up to 3 μM). Therefore, the downregulation of important mediators of pancreatic cancer aggressiveness by derivative 8 reveals its great potential for the development of new chemotherapeutic agents for pancreatic cancer treatment. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  1. RpoD promoters in Campylobacter jejuni exhibit a strong periodic signal instead of a-35 box

    DEFF Research Database (Denmark)

    Petersen, Lise; Larsen, Thomas Schou; Ussery, David

    2003-01-01

    We have used a hidden Markov model (HMM) to identify the consensus sequence of the RpoD promoters in the genome of Campylobacter jejuni. The identified promoter consensus sequence is unusual compared to other bacteria, in that the region upstream of the TATA-box does not contain a conserved -35...... region, but shows a very strong periodic variation in the AT-content and semi-conserved T-stretches, with a period of 10-11 nucleotides. The TATA-box is in some, but not all cases, preceded by a TGx, similar to an extended -10 promoter. We predicted a total of 764 presumed RpoD promoters in the C...... with a training set of 175 genes. This leads to the conclusion that the remaining genes (354) are more rarely preceded by a (RpoD) promoter, and consequently that operon structure may be more widespread in C.jejuni than has been assumed by others. Structural predictions of the regions upstream of the TATA...

  2. Strong enhancement of Penning ionization for asymmetric atom pairs in cold Rydberg gases: the Tom and Jerry effect

    KAUST Repository

    Efimov, D K

    2016-05-18

    We consider Penning ionization of Rydberg atom pairs as an Auger-type process induced by the dipole-dipole interaction and employ semiclassical formulae for dipole transitions to calculate the autoionization width as a function of the principal quantum numbers, n d, n i, of both atoms. While for symmetric atom pairs with the well-known increase of the autoionization width with increasing n 0 is obtained, the result for asymmetric pairs is counterintuitive - for a fixed n i of the ionizing atom of the pair, the autoionization width strongly increases with decreasing n d of the de-excited atom. For H Rydberg atoms this increase reaches two orders of magnitude at the maximum of the n d dependence, and the same type of counterintuitive behavior is exhibited also by Na, Rb and Cs atoms. This is a purely quantum-mechanical effect, which points towards existence of optimal (we call them \\'Tom\\' and \\'Jerry\\' for \\'big\\' and \\'small\\') pairs of Rydberg atoms with respect to autoionization efficiency. Building on the model of population redistribution in cold Rydberg gases proposed in [1], we demonstrate that population evolution following the initial laser excitation of Rydberg atoms in state n 0 would eventually lead to the formation of such Tom-Jerry pairs with which feature autoionization widths that are enhanced by several orders of magnitude compared to that of two atoms in the initial laser-excited state n 0. We also show that in the high-density regime of cold Rydberg gas experiments the ionization rate of Tom-Jerry pairs can be substantially larger than the blackbody radiation-induced photoionization rate. © 2016 IOP Publishing Ltd.

  3. Enhancement of the automatic ultrasonic signal processing system using digital technology

    International Nuclear Information System (INIS)

    Koo, In Soo; Park, H. Y.; Suh, Y. S.; Kim, D. Hoon; Huh, S.; Sung, S. H.; Jang, G. S.; Ryoo, S. G.; Choi, J. H.; Kim, Y. H.; Lee, J. C.; Kim, D. Hyun; Park, H. J.; Kim, Y. C.; Lee, J. P.; Park, C. H.; Kim, M. S.

    1999-12-01

    The objective of this study is to develop the automatic ultrasonic signal processing system which can be used in the inspection equipment to assess the integrity of the reactor vessel by enhancing the performance of the ultrasonic signal processing system. Main activities of this study divided into three categories such as the development of the circuits for generating ultrasonic signal and receiving the signal from the inspection equipment, the development of signal processing algorithm and H/W of the data processing system, and the development of the specification for application programs and system S/W for the analysis and evaluation computer. The results of main activities are as follows 1) the design of the ultrasonic detector and the automatic ultrasonic signal processing system by using the investigation of the state-of-the-art technology in the inside and outside of the country. 2) the development of H/W and S/W of the data processing system based on the results. Especially, the H/W of the data processing system, which have both advantages of digital and analog controls through the real-time digital signal processing, was developed using the DSP which can process the digital signal in the real-time, and was developed not only firmware of the data processing system in order for the peripherals but also the test algorithm of specimen for the calibration. The application programs and the system S/W of the analysis/evaluation computer were developed. Developed equipment was verified by the performance test. Based on developed prototype for the automatic ultrasonic signal processing system, the localization of the overall ultrasonic inspection equipment for nuclear industries would be expected through the further studies of the H/W establishment of real applications, developing the S/W specification of the analysis computer. (author)

  4. Parametrized tests of the strong-field dynamics of general relativity using gravitational wave signals from coalescing binary black holes: Fast likelihood calculations and sensitivity of the method

    Science.gov (United States)

    Meidam, Jeroen; Tsang, Ka Wa; Goldstein, Janna; Agathos, Michalis; Ghosh, Archisman; Haster, Carl-Johan; Raymond, Vivien; Samajdar, Anuradha; Schmidt, Patricia; Smith, Rory; Blackburn, Kent; Del Pozzo, Walter; Field, Scott E.; Li, Tjonnie; Pürrer, Michael; Van Den Broeck, Chris; Veitch, John; Vitale, Salvatore

    2018-02-01

    Thanks to the recent discoveries of gravitational wave signals from binary black hole mergers by Advanced Laser Interferometer Gravitational Wave Observatory and Advanced Virgo, the genuinely strong-field dynamics of spacetime can now be probed, allowing for stringent tests of general relativity (GR). One set of tests consists of allowing for parametrized deformations away from GR in the template waveform models and then constraining the size of the deviations, as was done for the detected signals in previous work. In this paper, we construct reduced-order quadratures so as to speed up likelihood calculations for parameter estimation on future events. Next, we explicitly demonstrate the robustness of the parametrized tests by showing that they will correctly indicate consistency with GR if the theory is valid. We also check to what extent deviations from GR can be constrained as information from an increasing number of detections is combined. Finally, we evaluate the sensitivity of the method to possible violations of GR.

  5. Efficient Techniques of Sparse Signal Analysis for Enhanced Recovery of Information in Biomedical Engineering and Geosciences

    KAUST Repository

    Sana, Furrukh

    2016-11-01

    Sparse signals are abundant among both natural and man-made signals. Sparsity implies that the signal essentially resides in a small dimensional subspace. The sparsity of the signal can be exploited to improve its recovery from limited and noisy observations. Traditional estimation algorithms generally lack the ability to take advantage of signal sparsity. This dissertation considers several problems in the areas of biomedical engineering and geosciences with the aim of enhancing the recovery of information by exploiting the underlying sparsity in the problem. The objective is to overcome the fundamental bottlenecks, both in terms of estimation accuracies and required computational resources. In the first part of dissertation, we present a high precision technique for the monitoring of human respiratory movements by exploiting the sparsity of wireless ultra-wideband signals. The proposed technique provides a novel methodology of overcoming the Nyquist sampling constraint and enables robust performance in the presence of noise and interferences. We also present a comprehensive framework for the important problem of extracting the fetal electrocardiogram (ECG) signals from abdominal ECG recordings of pregnant women. The multiple measurement vectors approach utilized for this purpose provides an efficient mechanism of exploiting the common structure of ECG signals, when represented in sparse transform domains, and allows leveraging information from multiple ECG electrodes under a joint estimation formulation. In the second part of dissertation, we adopt sparse signal processing principles for improved information recovery in large-scale subsurface reservoir characterization problems. We propose multiple new algorithms for sparse representation of the subsurface geological structures, incorporation of useful prior information in the estimation process, and for reducing computational complexities of the problem. The techniques presented here enable significantly

  6. Canonical Wnt signaling transiently stimulates proliferation and enhances neurogenesis in neonatal neural progenitor cultures

    International Nuclear Information System (INIS)

    Hirsch, Cordula; Campano, Louise M.; Woehrle, Simon; Hecht, Andreas

    2007-01-01

    Canonical Wnt signaling triggers the formation of heterodimeric transcription factor complexes consisting of β-catenin and T cell factors, and thereby controls the execution of specific genetic programs. During the expansion and neurogenic phases of embryonic neural development canonical Wnt signaling initially controls proliferation of neural progenitor cells, and later neuronal differentiation. Whether Wnt growth factors affect neural progenitor cells postnatally is not known. Therefore, we have analyzed the impact of Wnt signaling on neural progenitors isolated from cerebral cortices of newborn mice. Expression profiling of pathway components revealed that these cells are fully equipped to respond to Wnt signals. However, Wnt pathway activation affected only a subset of neonatal progenitors and elicited a limited increase in proliferation and neuronal differentiation in distinct subsets of cells. Moreover, Wnt pathway activation only transiently stimulated S-phase entry but did not support long-term proliferation of progenitor cultures. The dampened nature of the Wnt response correlates with the predominant expression of inhibitory pathway components and the rapid actuation of negative feedback mechanisms. Interestingly, in differentiating cell cultures activation of canonical Wnt signaling reduced Hes1 and Hes5 expression suggesting that during postnatal neural development, Wnt/β-catenin signaling enhances neurogenesis from progenitor cells by interfering with Notch pathway activity

  7. Secondary ions mass spectrometric signal enhancement of peptides on enlarged-gold nanoparticle surfaces.

    Science.gov (United States)

    Kim, Young-Pil; Lee, Tae Geol

    2012-06-05

    A high surface coverage of gold nanoparticles (AuNPs) is a prerequisite for enhancing the peptide signal intensity in time-of-flight secondary ion mass spectrometry (TOF-SIMS). Here, we demonstrate the TOF-SIMS signal amplification of peptides on a surface by enlarging surface-confined AuNPs using the NH(2)OH/Au(3+) seeding method. Because of the increased surface area and spherical structure of the Au, the SIMS intensity of the peptides became significantly enhanced on the enlarged-AuNPs surface, especially at high concentrations of peptide solution (>10 μM), compared to that of the bare gold surface or submonolyer of AuNPs. We are confident that this will be a useful method for diagnosis and bioassay with high sensitivity in a label-free manner.

  8. Laser Induced Breakdown Spectroscopy Based on Single Beam Splitting and Geometric Configuration for Effective Signal Enhancement

    OpenAIRE

    Yang, Guang; Lin, Qingyu; Ding, Yu; Tian, Di; Duan, Yixiang

    2015-01-01

    A new laser induced breakdown spectroscopy (LIBS) based on single-beam-splitting (SBS) and proper optical geometric configuration has been initially explored in this work for effective signal enhancement. In order to improve the interaction efficiency of laser energy with the ablated material, a laser beam operated in pulse mode was divided into two streams to ablate/excite the target sample in different directions instead of the conventional one beam excitation in single pulse LIBS (SP-LIBS)...

  9. Enhanced Schottky signals from electron-cooled, coasting beams in a heavy-ion storage ring

    Energy Technology Data Exchange (ETDEWEB)

    Krantz, C., E-mail: claude.krantz@mpi-hd.mpg.d [Max-Planck-Institut fuer Kernphysik, Saupfercheckweg 1, D-69117 Heidelberg (Germany); Blaum, K.; Grieser, M. [Max-Planck-Institut fuer Kernphysik, Saupfercheckweg 1, D-69117 Heidelberg (Germany); Litvinov, Yu.A. [Max-Planck-Institut fuer Kernphysik, Saupfercheckweg 1, D-69117 Heidelberg (Germany); GSI Helmholtzzentrum fuer Schwerionenforschung, Planckstrasse 1, D-64291 Darmstadt (Germany); Repnow, R.; Wolf, A. [Max-Planck-Institut fuer Kernphysik, Saupfercheckweg 1, D-69117 Heidelberg (Germany)

    2011-02-11

    Measurements at the Test Storage Ring of the Max-Planck-Institut fuer Kernphysik in Heidelberg (Germany) have shown that the signal amplitude induced in a Schottky-noise pickup electrode by a coasting electron-cooled ion beam can be greatly enhanced by exposure of the latter to a perturbing radiofrequency signal which is detuned from the true beam revolution frequency. The centre frequencies obtained from harmonic analysis of the observed pickup signal closely follow those imposed on the ions by the electron cooling force. The phenomenon can be exploited to measure the true revolution frequency of ion beams of very low intensity, whose pure Schottky noise is too weak to be measurable under normal circumstances.

  10. Blueberry supplementation enhances signaling and prevents behavioral deficits in an Alzheimer disease model.

    Science.gov (United States)

    Joseph, J A; Denisova, N A; Arendash, G; Gordon, M; Diamond, D; Shukitt-Hale, B; Morgan, D

    2003-06-01

    Previously, we showed that blueberry (BB) supplementation reversed the deleterious effects of aging on motor behavior and neuronal signaling in senescent rodents. We now report that BB-fed (from 4 months of age) APP + PS1 transgenic mice showed no deficits in Y-maze performance (at 12 months of age) with no alterations in amyloid beta burden. It appeared that the protective mechanisms are derived from BB-induced enhancement of memory-associated neuronal signaling (e.g. extracellular signal-regulated kinase) and alterations in neutral sphingomyelin-specific phospholipase C activity. Thus, our data indicate for the first time that it may be possible to overcome genetic predispositions to Alzheimer disease through diet.

  11. Wnt signaling in ovarian development inhibits Sf1 activation of Sox9 via the Tesco enhancer.

    Science.gov (United States)

    Bernard, Pascal; Ryan, Janelle; Sim, Helena; Czech, Daniel P; Sinclair, Andrew H; Koopman, Peter; Harley, Vincent R

    2012-02-01

    Genome analysis of patients with disorders of sex development, and gain- and loss-of-function studies in mice indicate that gonadal development is regulated by opposing signals. In females, the Wnt/β-catenin canonical pathway blocks testicular differentiation by repressing the expression of the Sertoli cell-specific gene Sox9 by an unknown mechanism. Using cell and embryonic gonad culture models, we show that activation of the Wnt/β-catenin pathway inhibits the expression of Sox9 and Amh, whereas mRNA and protein levels of Sry and steroidogenic factor 1 (Sf1), two key transcriptional regulators of Sox9, are not altered. Ectopic activation of Wnt/β-catenin signaling in male gonads led to a loss of Sf1 binding to the Tesco enhancer and absent Sox9 expression that we also observed in wild-type ovaries. Moreover, ectopic Wnt/β-catenin signaling induced the expression of the female somatic cell markers, Bmp2 and Rspo1, as a likely consequence of Sox9 loss. Wnt/β-catenin signaling in XY gonads did not, however, affect gene expression of the steroidogenic Leydig cell Sf1 target gene, Cyp11a1, or Sf1 binding to the Cyp11a1 promoter. Our data support a model in ovary development whereby activation of β-catenin prevents Sf1 binding to the Sox9 enhancer, thereby inhibiting Sox9 expression and Sertoli cell differentiation.

  12. Fusarium oxysporum volatiles enhance plant growth via affecting auxin transport and signaling

    Directory of Open Access Journals (Sweden)

    Vasileios eBitas

    2015-11-01

    Full Text Available Volatile organic compounds (VOCs have well-documented roles in plant-plant communication and directing animal behavior. In this study, we examine the less understood roles of VOCs in plant-fungal relationships. Phylogenetically and ecologically diverse strains of Fusarium oxysporum, a fungal species complex that often resides in the rhizosphere of assorted plants, produce volatile compounds that augment shoot and root growth of Arabidopsis thaliana and tobacco. Growth responses of A. thaliana hormone signaling mutants and expression patterns of a GUS reporter gene under the auxin-responsive DR5 promoter supported the involvement of auxin signaling in F. oxysporum volatile-mediated growth enhancement. In addition, 1-naphthylthalamic acid, an inhibitor of auxin efflux, negated F. oxysporum volatile-mediated growth enhancement in both plants. Comparison of the profiles of volatile compounds produced by F. oxysporum strains that differentially affected plant growth suggests that the relative compositions of both growth inhibitory and stimulatory compounds may determine the degree of plant growth enhancement. Volatile-mediated signaling between fungi and plants may represent a potentially conserved, yet mostly overlooked, mechanism underpinning plant-fungus interactions and fungal niche adaption.

  13. Enhancement of the conductivity detection signal in capillary electrophoresis systems using neutral cyclodextrins as sweeping agents.

    Science.gov (United States)

    Boublík, Milan; Riesová, Martina; Dubský, Pavel; Gaš, Bohuslav

    2018-02-16

    Conductivity detection is a universal detection technique often encountered in electrophoretic separation systems, especially in modern chip-electrophoresis based devices. On the other hand, it is sparsely combined with another contemporary trend of enhancing limits of detection by means of various preconcentration strategies. This can be attributed to the fact that a preconcentration experimental setup usually brings about disturbances in a conductivity baseline. Sweeping with a neutral sweeping agent seems a good candidate for overcoming this problem. A neutral sweeping agent does not hinder the conductivity detection while a charged analyte may preconcentrate on its boundary due to a decrease in its effective mobility. This study investigates such sweeping systems theoretically, by means of computer simulations, and experimentally. A formula is provided for the reliable estimation of the preconcentration factor. Additionally, it is demonstrated that the conductivity signal can significantly benefit from slowing down the analyte and thus the overall signal enhancement can easily overweight amplification caused solely by the sweeping process. The overall enhancement factor can be deduced a priori from the linearized theory of electrophoresis implemented in the PeakMaster freeware. Sweeping by neutral cyclodextrin is demonstrated on an amplification of a conductivity signal of flurbiprofen in a real drug sample. Finally, a possible formation of unexpected system peaks in systems with a neutral sweeping agent is revealed by the computer simulation and confirmed experimentally. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Novel Signal-Enhancing Approaches for Optical Detection of Nucleic Acids—Going beyond Target Amplification

    Directory of Open Access Journals (Sweden)

    Laura Miotke

    2015-09-01

    Full Text Available Detection of low-abundance nucleic acids is a challenging task, which over the last two decades has been solved using enzymatic target amplification. Enzymatic synthesis enhances the signal so that diverse, scientifically and clinically relevant molecules can be identified and studied, including cancer DNA, viral nucleic acids, and regulatory RNAs. However, using enzymes increases the detection time and cost, not to mention the high risk of mistakes with amplification and data alignment. These limitations have stimulated a growing interest in enzyme-free methods within researchers and industry. In this review we discuss recent advances in signal-enhancing approaches aimed at nucleic acid diagnostics that do not require target amplification. Regardless of enzyme usage, signal enhancement is crucial for the reliable detection of nucleic acids at low concentrations. We pay special attention to novel nanomaterials, fluorescence microscopy, and technical advances in detectors for optical assessment. We summarize sensitivity parameters of the currently available assays and devices which makes this review relevant to the broad spectrum of researchers working in fields from biophysics, to engineering, to synthetic biology and bioorganic chemistry.

  15. Lenalidomide induces lipid raft assembly to enhance erythropoietin receptor signaling in myelodysplastic syndrome progenitors.

    Directory of Open Access Journals (Sweden)

    Kathy L McGraw

    Full Text Available Anemia remains the principal management challenge for patients with lower risk Myelodysplastic Syndromes (MDS. Despite appropriate cytokine production and cellular receptor display, erythropoietin receptor (EpoR signaling is impaired. We reported that EpoR signaling is dependent upon receptor localization within lipid raft microdomains, and that disruption of raft integrity abolishes signaling capacity. Here, we show that MDS erythroid progenitors display markedly diminished raft assembly and smaller raft aggregates compared to normal controls (p = 0.005, raft number; p = 0.023, raft size. Because lenalidomide triggers raft coalescence in T-lymphocytes promoting immune synapse formation, we assessed effects of lenalidomide on raft assembly in MDS erythroid precursors and UT7 cells. Lenalidomide treatment rapidly induced lipid raft formation accompanied by EpoR recruitment into raft fractions together with STAT5, JAK2, and Lyn kinase. The JAK2 phosphatase, CD45, a key negative regulator of EpoR signaling, was displaced from raft fractions. Lenalidomide treatment prior to Epo stimulation enhanced both JAK2 and STAT5 phosphorylation in UT7 and primary MDS erythroid progenitors, accompanied by increased STAT5 DNA binding in UT7 cells, and increased erythroid colony forming capacity in both UT7 and primary cells. Raft induction was associated with F-actin polymerization, which was blocked by Rho kinase inhibition. These data indicate that deficient raft integrity impairs EpoR signaling, and provides a novel strategy to enhance EpoR signal fidelity in non-del(5q MDS.

  16. Optimizing signal intensity correction during evaluation of hepatic parenchymal enhancement on gadoxetate disodium-enhanced MRI: Comparison of three methods

    Energy Technology Data Exchange (ETDEWEB)

    Onoda, Minori, E-mail: onoda@radt.med.kindai.ac.jp [Department of Radiological Technology, Kinki University Hospital, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 920-0942 (Japan); Hyodo, Tomoko, E-mail: neneth@m.ehime-u.ac.jp [Department of Radiology, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Murakami, Takamichi, E-mail: murakami@med.kindai.ac.jp [Department of Radiology, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Okada, Masahiro, E-mail: okada777@med.u-ryukyu.ac.jp [Department of Radiology, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Uto, Tatsuro, E-mail: chuho@med.kindai.ac.jp [Department of Radiological Technology, Kinki University Hospital, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511 (Japan); Hori, Masatoshi, E-mail: mhori@radiol.med.osaka-u.ac.jp [Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Miyati, Tosiaki, E-mail: ramiyati@mhs.mp.kanazawa-u.ac.jp [Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, 5-11-80 Kodatsuno, Kanazawa, Ishikawa 920-0942 (Japan)

    2015-03-15

    Highlights: •Signal intensity is often used to evaluate hepatic enhancement with Gd-EOB-DTPA in the hepatobiliary phase. •Comparison of uncorrected signal intensity with T{sub 1} value revealed signal intensity instability. •Measurement of uncorrected liver SI or SNR often yields erroneous results on late-phase gadoxetate MRI due to shimming and other optimization techniques. •Signal intensity corrected by scale and rescale slope from DICOM data gave comparable results. -- Abstract: Objective: To compare signal intensity (SI) correction using scale and rescale slopes with SI correction using SIs of spleen and muscle for quantifying multiphase hepatic contrast enhancement with Gd-EOB-DTPA by assessing their correlation with T{sub 1} values generated from Look-Locker turbo-field-echo (LL-TFE) sequence data (ER-T{sub 1}). Materials and methods: Thirty patients underwent Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) in this prospective clinical study. For each patient, breath-hold T{sub 1}-weighted fat-suppressed three-dimensional (3D) gradient echo sequences (e-THRIVE) were acquired before and 2 (first phase), 10 (second phase), and 20 min (third phase) after intravenous Gd-EOB-DTPA. Look-Locker turbo-field-echo (LL-TFE) sequences were acquired before and 1.5 (first phase), 8 (second phase), and 18 min (third phase) postcontrast. The liver parenchyma enhancement ratios (ER) of each phase were calculated using the SI from e-THRIVE sequences (ER-SI) and the T{sub 1} values generated from LL-TFE sequence data (ER-T{sub 1}) respectively. ER-SIs were calculated in three ways: (1) comparing with splenic SI (ER-SI-s), (2) comparing with muscle SI (ER-SI-m), (3) using scale and rescale slopes obtained from DICOM headers (ER-SI-c), to eliminate the effects of receiver gain and scaling. For each of the first, second and third phases, correlation and agreement were assessed between each ER-SI and ER-T{sub 1}. Results: In the first phase, all ER-SIs correlated

  17. Age dependence of spleen- and muscle-corrected hepatic signal enhancement on hepatobiliary phase gadoxetate MRI

    Energy Technology Data Exchange (ETDEWEB)

    Matoori, Simon [Paracelsus Medical University Salzburg, Department of Radiology, Salzburg (Austria); Hirslanden Clinic St. Anna, Clinical Research Group, Lucerne (Switzerland); Froehlich, Johannes M. [Hirslanden Clinic St. Anna, Clinical Research Group, Lucerne (Switzerland); ETH Zurich, Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, Zurich (Switzerland); Cantonal Hospital Winterthur, Department of Radiology, Winterthur (Switzerland); Breitenstein, Stefan [Cantonal Hospital Winterthur, Department of Surgery, Clinic for Visceral and Thoracic Surgery, Winterthur (Switzerland); Doert, Aleksis [Cantonal Hospital Winterthur, Department of Radiology, Winterthur (Switzerland); Pozdniakova, Viktoria [Stavanger University Hospital, Department of Radiology, Stavanger (Norway); Koh, Dow-Mu [Royal Marsden Hospital, Department of Radiology, Surrey, England (United Kingdom); Gutzeit, Andreas [Paracelsus Medical University Salzburg, Department of Radiology, Salzburg (Austria); Hirslanden Clinic St. Anna, Clinical Research Group, Lucerne (Switzerland); Cantonal Hospital Winterthur, Department of Radiology, Winterthur (Switzerland)

    2016-06-15

    To identify correlations of signal enhancements (SE) and SE normalized to reference tissues of the spleen, kidney, liver, musculus erector spinae (MES) and ductus hepatocholedochus (DHC) on hepatobiliary phase gadoxetate-enhanced MRI with patient age in non-cirrhotic patients. A heterogeneous cohort of 131 patients with different clinical backgrounds underwent a standardized 3.0-T gadoxetate-enhanced liver MRI between November 2008 and June 2013. After exclusion of cirrhotic patients, a cohort of 75 patients with no diagnosed diffuse liver disease was selected. The ratio of signal intensity 20 min post- to pre-contrast administration (SE) in the spleen, kidney, liver, MES and DHC, and the SE of the kidney, liver and DHC normalized to the reference tissues spleen or MES were compared to patient age. Patient age was inversely correlated with the liver SE normalized to the spleen and MES SE (both p < 0.001) and proportionally with the SE of the spleen (p = 0.043), the MES (p = 0.030) and the kidney (p = 0.022). No significant correlations were observed for the DHC (p = 0.347) and liver SE (p = 0.606). The age dependence of hepatic SE normalized to the enhancement in the spleen and MES calls for a cautious interpretation of these quantification methods. (orig.)

  18. Phenotypic Consequences of a Genetic Predisposition to Enhanced Nitric Oxide Signaling.

    Science.gov (United States)

    Emdin, Connor A; Khera, Amit V; Klarin, Derek; Natarajan, Pradeep; Zekavat, Seyedeh M; Nomura, Akihiro; Haas, Mary; Aragam, Krishna; Ardissino, Diego; Wilson, James G; Schunkert, Heribert; McPherson, Ruth; Watkins, Hugh; Elosua, Roberto; Bown, Matthew J; Samani, Nilesh J; Baber, Usman; Erdmann, Jeanette; Gormley, Padhraig; Palotie, Aarno; Stitziel, Nathan O; Gupta, Namrata; Danesh, John; Saleheen, Danish; Gabriel, Stacey; Kathiresan, Sekar

    2018-01-16

    Nitric oxide signaling plays a key role in the regulation of vascular tone and platelet activation. Here, we seek to understand the impact of a genetic predisposition to enhanced nitric oxide signaling on risk for cardiovascular diseases, thus informing the potential utility of pharmacological stimulation of the nitric oxide pathway as a therapeutic strategy. We analyzed the association of common and rare genetic variants in 2 genes that mediate nitric oxide signaling (Nitric Oxide Synthase 3 [ NOS3 ] and Guanylate Cyclase 1, Soluble, Alpha 3 [ GUCY1A3 ]) with a range of human phenotypes. We selected 2 common variants (rs3918226 in NOS3 and rs7692387 in GUCY1A3 ) known to associate with increased NOS3 and GUCY1A3 expression and reduced mean arterial pressure, combined them into a genetic score, and standardized this exposure to a 5 mm Hg reduction in mean arterial pressure. Using individual-level data from 335 464 participants in the UK Biobank and summary association results from 7 large-scale genome-wide association studies, we examined the effect of this nitric oxide signaling score on cardiometabolic and other diseases. We also examined whether rare loss-of-function mutations in NOS3 and GUCY1A3 were associated with coronary heart disease using gene sequencing data from the Myocardial Infarction Genetics Consortium (n=27 815). A genetic predisposition to enhanced nitric oxide signaling was associated with reduced risks of coronary heart disease (odds ratio, 0.37; 95% confidence interval [CI], 0.31-0.45; P =5.5*10 -26 ], peripheral arterial disease (odds ratio 0.42; 95% CI, 0.26-0.68; P =0.0005), and stroke (odds ratio, 0.53; 95% CI, 0.37-0.76; P =0.0006). In a mediation analysis, the effect of the genetic score on decreased coronary heart disease risk extended beyond its effect on blood pressure. Conversely, rare variants that inactivate the NOS3 or GUCY1A3 genes were associated with a 23 mm Hg higher systolic blood pressure (95% CI, 12-34; P =5.6*10 -5

  19. Epsin 1 Promotes Synaptic Growth by Enhancing BMP Signal Levels in Motoneuron Nuclei.

    Directory of Open Access Journals (Sweden)

    Phillip A Vanlandingham

    Full Text Available Bone morphogenetic protein (BMP retrograde signaling is crucial for neuronal development and synaptic plasticity. However, how the BMP effector phospho-Mother against decapentaplegic (pMad is processed following receptor activation remains poorly understood. Here we show that Drosophila Epsin1/Liquid facets (Lqf positively regulates synaptic growth through post-endocytotic processing of pMad signaling complex. Lqf and the BMP receptor Wishful thinking (Wit interact genetically and biochemically. lqf loss of function (LOF reduces bouton number whereas overexpression of lqf stimulates bouton growth. Lqf-stimulated synaptic overgrowth is suppressed by genetic reduction of wit. Further, synaptic pMad fails to accumulate inside the motoneuron nuclei in lqf mutants and lqf suppresses synaptic overgrowth in spinster (spin mutants with enhanced BMP signaling by reducing accumulation of nuclear pMad. Interestingly, lqf mutations reduce nuclear pMad levels without causing an apparent blockage of axonal transport itself. Finally, overexpression of Lqf significantly increases the number of multivesicular bodies (MVBs in the synapse whereas lqf LOF reduces MVB formation, indicating that Lqf may function in signaling endosome recycling or maturation. Based on these observations, we propose that Lqf plays a novel endosomal role to ensure efficient retrograde transport of BMP signaling endosomes into motoneuron nuclei.

  20. The application of empirical mode decomposition for the enhancement of cardiotocograph signals

    International Nuclear Information System (INIS)

    Krupa, B N; Mohd Ali, M A; Zahedi, E

    2009-01-01

    Cardiotocograph (CTG) is widely used in everyday clinical practice for fetal surveillance, where it is used to record fetal heart rate (FHR) and uterine activity (UA). These two biosignals can be used for antepartum and intrapartum fetal monitoring and are, in fact, nonlinear and non-stationary. CTG recordings are often corrupted by artifacts such as missing beats in FHR, high-frequency noise in FHR and UA signals. In this paper, an empirical mode decomposition (EMD) method is applied on CTG signals. A recursive algorithm is first utilized to eliminate missing beats. High-frequency noise is reduced using EMD followed by the partial reconstruction (PAR) method, where the noise order is identified by a statistical method. The obtained signal enhancement from the proposed method is validated by comparing the resulting traces with the output obtained by applying classical signal processing methods such as Butterworth low-pass filtering, linear interpolation and a moving average filter on 12 CTG signals. Three obstetricians evaluated all 12 sets of traces and rated the proposed method, on average, 3.8 out of 5 on a scale of 1(lowest) to 5 (highest)

  1. MAPK/ERK signaling pathway-induced hyper-O-GlcNAcylation enhances cancer malignancy.

    Science.gov (United States)

    Zhang, Xinling; Ma, Leina; Qi, Jieqiong; Shan, Hui; Yu, Wengong; Gu, Yuchao

    2015-12-01

    Dysregulated MAPK/ERK signaling is implicated in one-third of human tumors and represents an attractive target for the development of anticancer drugs. Similarly, elevated protein O-GlcNAcylation and O-GlcNAc transferase (OGT) are detected in various cancers and serve as attractive novel cancer-specific therapeutic targets. However, the potential connection between them remains unexplored. Here, a positive correlation was found between the activated MAPK/ERK signaling and hyper-O-GlcNAcylation in various cancer types and inhibition of the MAPK/ERK signaling by 10 µM U0126 significantly decreased the expression of OGT and O-GlcNAcylation in H1299, BPH-1 and DU145 cells; then, the pathway analysis of the potential regulators of OGT obtained from the UCSC Genome Browser was done, and ten downstream targets of ERK pathway were uncovered; the following results showed that ELK1, one of the ten targets of ERK pathway, mediated ERK signaling-induced OGT upregulation; finally, the MTT assay and the soft agar assay showed that the inhibition of MAPK/ERK signaling reduced the promotion effect of hyper-O-GlcNAcylation on cancer cell proliferation and anchorage-independent growth. Taken together, our data originally provided evidence for the regulatory mechanism of hyper-O-GlcNAcylation in tumors, which will be helpful for the development of anticancer drugs targeting to hyper-O-GlcNAcylation. This study also provided a new mechanism by which MAPK/ERK signaling-enhanced cancer malignancy. Altogether, the recently discovered oncogenic factor O-GlcNAc was linked to the classical MAPK/ERK signaling which is essential for the maintenance of malignant phenotype of cancers.

  2. Enhancement of the Signal-to-Noise Ratio in Sonic Logging Waveforms by Seismic Interferometry

    KAUST Repository

    Aldawood, Ali

    2012-04-01

    Sonic logs are essential tools for reliably identifying interval velocities which, in turn, are used in many seismic processes. One problem that arises, while logging, is irregularities due to washout zones along the borehole surfaces that scatters the transmitted energy and hence weakens the signal recorded at the receivers. To alleviate this problem, I have extended the theory of super-virtual refraction interferometry to enhance the signal-to-noise ratio (SNR) sonic waveforms. Tests on synthetic and real data show noticeable signal-to-noise ratio (SNR) enhancements of refracted P-wave arrivals in the sonic waveforms. The theory of super-virtual interferometric stacking is composed of two redatuming steps followed by a stacking procedure. The first redatuming procedure is of correlation type, where traces are correlated together to get virtual traces with the sources datumed to the refractor. The second datuming step is of convolution type, where traces are convolved together to dedatum the sources back to their original positions. The stacking procedure following each step enhances the signal to noise ratio of the refracted P-wave first arrivals. Datuming with correlation and convolution of traces introduces severe artifacts denoted as correlation artifacts in super-virtual data. To overcome this problem, I replace the datuming with correlation step by datuming with deconvolution. Although the former datuming method is more robust, the latter one reduces the artifacts significantly. Moreover, deconvolution can be a noise amplifier which is why a regularization term is utilized, rendering the datuming with deconvolution more stable. Tests of datuming with deconvolution instead of correlation with synthetic and real data examples show significant reduction of these artifacts. This is especially true when compared with the conventional way of applying the super-virtual refraction interferometry method.

  3. Inhibition of apoptosis signal-regulating kinase 1 enhances endochondral bone formation by increasing chondrocyte survival

    Science.gov (United States)

    Eaton, G J; Zhang, Q-S; Diallo, C; Matsuzawa, A; Ichijo, H; Steinbeck, M J; Freeman, T A

    2014-01-01

    Endochondral ossification is the result of chondrocyte differentiation, hypertrophy, death and replacement by bone. The careful timing and progression of this process is important for normal skeletal bone growth and development, as well as fracture repair. Apoptosis Signal-Regulating Kinase 1 (ASK1) is a mitogen-activated protein kinase (MAPK), which is activated by reactive oxygen species and other cellular stress events. Activation of ASK1 initiates a signaling cascade known to regulate diverse cellular events including cytokine and growth factor signaling, cell cycle regulation, cellular differentiation, hypertrophy, survival and apoptosis. ASK1 is highly expressed in hypertrophic chondrocytes, but the role of ASK1 in skeletal tissues has not been investigated. Herein, we report that ASK1 knockout (KO) mice display alterations in normal growth plate morphology, which include a shorter proliferative zone and a lengthened hypertrophic zone. These changes in growth plate dynamics result in accelerated long bone mineralization and an increased formation of trabecular bone, which can be attributed to an increased resistance of terminally differentiated chondrocytes to undergo cell death. Interestingly, under normal cell culture conditions, mouse embryonic fibroblasts (MEFs) derived from ASK1 KO mice show no differences in either MAPK signaling or osteogenic or chondrogenic differentiation when compared with wild-type (WT) MEFs. However, when cultured with stress activators, H2O2 or staurosporine, the KO cells show enhanced survival, an associated decrease in the activation of proteins involved in death signaling pathways and a reduction in markers of terminal differentiation. Furthermore, in both WT mice treated with the ASK1 inhibitor, NQDI-1, and ASK1 KO mice endochondral bone formation was increased in an ectopic ossification model. These findings highlight a previously unrealized role for ASK1 in regulating endochondral bone formation. Inhibition of ASK1 has

  4. Real-time implementations of acoustic signal enhancement techniques for aerial based surveillance and rescue applications

    Science.gov (United States)

    Ramos, Antonio L. L.; Shao, Zhili; Holthe, Aleksander; Sandli, Mathias F.

    2017-05-01

    The introduction of the System-on-Chip (SoC) technology has brought exciting new opportunities for the development of smart low cost embedded systems spanning a wide range of applications. Currently available SoC devices are capable of performing high speed digital signal processing tasks in software while featuring relatively low development costs and reduced time-to-market. Unmanned aerial vehicles (UAV) are an application example that has shown tremendous potential in an increasing number of scenarios, ranging from leisure to surveillance as well as in search and rescue missions. Video capturing from UAV platforms is a relatively straightforward task that requires almost no preprocessing. However, that does not apply to audio signals, especially in cases where the data is to be used to support real-time decision making. In fact, the enormous amount of acoustic interference from the surroundings, including the noise from the UAVs propellers, becomes a huge problem. This paper discusses a real-time implementation of the NLMS adaptive filtering algorithm applied to enhancing acoustic signals captured from UAV platforms. The model relies on a combination of acoustic sensors and a computational inexpensive algorithm running on a digital signal processor. Given its simplicity, this solution can be incorporated into the main processing system of an UAV using the SoC technology, and run concurrently with other required tasks, such as flight control and communications. Simulations and real-time DSP-based implementations have shown significant signal enhancement results by efficiently mitigating the interference from the noise generated by the UAVs propellers as well as from other external noise sources.

  5. Wayside acoustic diagnosis of defective train bearings based on signal resampling and information enhancement

    Science.gov (United States)

    He, Qingbo; Wang, Jun; Hu, Fei; Kong, Fanrang

    2013-10-01

    The diagnosis of train bearing defects plays a significant role to maintain the safety of railway transport. Among various defect detection techniques, acoustic diagnosis is capable of detecting incipient defects of a train bearing as well as being suitable for wayside monitoring. However, the wayside acoustic signal will be corrupted by the Doppler effect and surrounding heavy noise. This paper proposes a solution to overcome these two difficulties in wayside acoustic diagnosis. In the solution, a dynamically resampling method is firstly presented to reduce the Doppler effect, and then an adaptive stochastic resonance (ASR) method is proposed to enhance the defective characteristic frequency automatically by the aid of noise. The resampling method is based on a frequency variation curve extracted from the time-frequency distribution (TFD) of an acoustic signal by dynamically minimizing the local cost functions. For the ASR method, the genetic algorithm is introduced to adaptively select the optimal parameter of the multiscale noise tuning (MST)-based stochastic resonance (SR) method. The proposed wayside acoustic diagnostic scheme combines signal resampling and information enhancement, and thus is expected to be effective in wayside defective bearing detection. The experimental study verifies the effectiveness of the proposed solution.

  6. A Review of Signal Subspace Speech Enhancement and Its Application to Noise Robust Speech Recognition

    Directory of Open Access Journals (Sweden)

    Hermus Kris

    2007-01-01

    Full Text Available The objective of this paper is threefold: (1 to provide an extensive review of signal subspace speech enhancement, (2 to derive an upper bound for the performance of these techniques, and (3 to present a comprehensive study of the potential of subspace filtering to increase the robustness of automatic speech recognisers against stationary additive noise distortions. Subspace filtering methods are based on the orthogonal decomposition of the noisy speech observation space into a signal subspace and a noise subspace. This decomposition is possible under the assumption of a low-rank model for speech, and on the availability of an estimate of the noise correlation matrix. We present an extensive overview of the available estimators, and derive a theoretical estimator to experimentally assess an upper bound to the performance that can be achieved by any subspace-based method. Automatic speech recognition experiments with noisy data demonstrate that subspace-based speech enhancement can significantly increase the robustness of these systems in additive coloured noise environments. Optimal performance is obtained only if no explicit rank reduction of the noisy Hankel matrix is performed. Although this strategy might increase the level of the residual noise, it reduces the risk of removing essential signal information for the recogniser's back end. Finally, it is also shown that subspace filtering compares favourably to the well-known spectral subtraction technique.

  7. Genistein attenuates hypoxic pulmonary hypertension via enhanced nitric oxide signaling and the erythropoietin system.

    Science.gov (United States)

    Kuriyama, Sachiko; Morio, Yoshiteru; Toba, Michie; Nagaoka, Tetsutaro; Takahashi, Fumiyuki; Iwakami, Shin-Ichiro; Seyama, Kuniaki; Takahashi, Kazuhisa

    2014-06-01

    Upregulation of the erythropoietin (EPO)/EPO receptor (EPOR) system plays a protective role against chronic hypoxia-induced pulmonary hypertension (hypoxic PH) through enhancement of endothelial nitric oxide (NO)-mediated signaling. Genistein (Gen), a phytoestrogen, is considered to ameliorate NO-mediated signaling. We hypothesized that Gen attenuates and prevents hypoxic PH. In vivo, Sprague-Dawley rats raised in a hypobaric chamber were treated with Gen (60 mkg/kg) for 21 days. Pulmonary hemodynamics and vascular remodeling were ameliorated in Gen-treated hypoxic PH rats. Gen also restored cGMP levels and phosphorylated endothelial NO synthase (p-eNOS) at Ser(1177) and p-Akt at Ser(473) expression in the lungs. Additionally, Gen potentiated plasma EPO concentration and EPOR-positive endothelial cell counts. In experiments with hypoxic PH rats' isolated perfused lungs, Gen caused NO- and phosphatidylinositol 3-kinase (PI3K)/Akt-dependent vasodilation that reversed abnormal vasoconstriction. In vitro, a combination of EPO and Gen increased the p-eNOS and the EPOR expression in human umbilical vein endothelial cells under a hypoxic environment. Moreover, Gen potentiated the hypoxic increase in EPO production from human hepatoma cells. We conclude that Gen may be effective for the prevention of hypoxic PH through the improvement of PI3K/Akt-dependent, NO-mediated signaling in association with enhancement of the EPO/EPOR system. Copyright © 2014 the American Physiological Society.

  8. Correlation dynamics and enhanced signals for the identification of serial biomolecules and DNA bases

    International Nuclear Information System (INIS)

    Ahmed, Towfiq; Haraldsen, Jason T; Balatsky, Alexander V; Rehr, John J; Di Ventra, Massimiliano; Schuller, Ivan

    2014-01-01

    Nanopore-based sequencing has demonstrated a significant potential for the development of fast, accurate, and cost-efficient fingerprinting techniques for next generation molecular detection and sequencing. We propose a specific multilayered graphene-based nanopore device architecture for the recognition of single biomolecules. Molecular detection and analysis can be accomplished through the detection of transverse currents as the molecule or DNA base translocates through the nanopore. To increase the overall signal-to-noise ratio and the accuracy, we implement a new ‘multi-point cross-correlation’ technique for identification of DNA bases or other molecules on the single molecular level. We demonstrate that the cross-correlations between each nanopore will greatly enhance the transverse current signal for each molecule. We implement first-principles transport calculations for DNA bases surveyed across a multilayered graphene nanopore system to illustrate the advantages of the proposed geometry. A time-series analysis of the cross-correlation functions illustrates the potential of this method for enhancing the signal-to-noise ratio. This work constitutes a significant step forward in facilitating fingerprinting of single biomolecules using solid state technology. (paper)

  9. Correlation dynamics and enhanced signals for the identification of serial biomolecules and DNA bases

    Science.gov (United States)

    Ahmed, Towfiq; Haraldsen, Jason T.; Rehr, John J.; Di Ventra, Massimiliano; Schuller, Ivan; Balatsky, Alexander V.

    2014-03-01

    Nanopore-based sequencing has demonstrated a significant potential for the development of fast, accurate, and cost-efficient fingerprinting techniques for next generation molecular detection and sequencing. We propose a specific multilayered graphene-based nanopore device architecture for the recognition of single biomolecules. Molecular detection and analysis can be accomplished through the detection of transverse currents as the molecule or DNA base translocates through the nanopore. To increase the overall signal-to-noise ratio and the accuracy, we implement a new ‘multi-point cross-correlation’ technique for identification of DNA bases or other molecules on the single molecular level. We demonstrate that the cross-correlations between each nanopore will greatly enhance the transverse current signal for each molecule. We implement first-principles transport calculations for DNA bases surveyed across a multilayered graphene nanopore system to illustrate the advantages of the proposed geometry. A time-series analysis of the cross-correlation functions illustrates the potential of this method for enhancing the signal-to-noise ratio. This work constitutes a significant step forward in facilitating fingerprinting of single biomolecules using solid state technology.

  10. Sulforaphane epigenetically enhances neuronal BDNF expression and TrkB signaling pathways.

    Science.gov (United States)

    Kim, Jisung; Lee, Siyoung; Choi, Bo-Ryoung; Yang, Hee; Hwang, Youjin; Park, Jung Han Yoon; LaFerla, Frank M; Han, Jung-Soo; Lee, Ki Won; Kim, Jiyoung

    2017-02-01

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin that supports the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses. We investigated the effect of sulforaphane, a hydrolysis product of glucoraphanin present in Brassica vegetables, on neuronal BDNF expression and its synaptic signaling pathways. Mouse primary cortical neurons and a triple-transgenic mouse model of Alzheimer's disease (3 × Tg-AD) were used to study the effect of sulforaphane. Sulforaphane enhanced neuronal BDNF expression and increased levels of neuronal and synaptic molecules such as MAP2, synaptophysin, and PSD-95 in primary cortical neurons and 3 × Tg-AD mice. Sulforaphane elevated levels of synaptic TrkB signaling pathway components, including CREB, CaMKII, ERK, and Akt in both primary cortical neurons and 3 × Tg-AD mice. Sulforaphane increased global acetylation of histone 3 (H3) and H4, inhibited HDAC activity, and decreased the level of HDAC2 in primary cortical neurons. Chromatin immunoprecipitation analysis revealed that sulforaphane increased acetylated H3 and H4 at BDNF promoters, suggesting that sulforaphane regulates BDNF expression via HDAC inhibition. These findings suggest that sulforaphane has the potential to prevent neuronal disorders such as Alzheimer's disease by epigenetically enhancing neuronal BDNF expression and its TrkB signaling pathways. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Signal enhancement ratio (SER) quantified from breast DCE-MRI and breast cancer risk

    Science.gov (United States)

    Wu, Shandong; Kurland, Brenda F.; Berg, Wendie A.; Zuley, Margarita L.; Jankowitz, Rachel C.; Sumkin, Jules; Gur, David

    2015-03-01

    Breast magnetic resonance imaging (MRI) is recommended as an adjunct to mammography for women who are considered at elevated risk of developing breast cancer. As a key component of breast MRI, dynamic contrast-enhanced MRI (DCE-MRI) uses a contrast agent to provide high intensity contrast between breast tissues, making it sensitive to tissue composition and vascularity. Breast DCE-MRI characterizes certain physiologic properties of breast tissue that are potentially related to breast cancer risk. Studies have shown that increased background parenchymal enhancement (BPE), which is the contrast enhancement occurring in normal cancer-unaffected breast tissues in post-contrast sequences, predicts increased breast cancer risk. Signal enhancement ratio (SER) computed from pre-contrast and post-contrast sequences in DCE-MRI measures change in signal intensity due to contrast uptake over time and is a measure of contrast enhancement kinetics. SER quantified in breast tumor has been shown potential as a biomarker for characterizing tumor response to treatments. In this work we investigated the relationship between quantitative measures of SER and breast cancer risk. A pilot retrospective case-control study was performed using a cohort of 102 women, consisting of 51 women who had diagnosed with unilateral breast cancer and 51 matched controls (by age and MRI date) with a unilateral biopsy-proven benign lesion. SER was quantified using fully-automated computerized algorithms and three SER-derived quantitative volume measures were compared between the cancer cases and controls using logistic regression analysis. Our preliminary results showed that SER is associated with breast cancer risk, after adjustment for the Breast Imaging Reporting and Data System (BI-RADS)-based mammographic breast density measures. This pilot study indicated that SER has potential for use as a risk factor for breast cancer risk assessment in women at elevated risk of developing breast cancer.

  12. Hippo Signaling Influences HNF4A and FOXA2 Enhancer Switching during Hepatocyte Differentiation

    Directory of Open Access Journals (Sweden)

    Olivia Alder

    2014-10-01

    Full Text Available Cell fate acquisition is heavily influenced by direct interactions between master regulators and tissue-specific enhancers. However, it remains unclear how lineage-specifying transcription factors, which are often expressed in both progenitor and mature cell populations, influence cell differentiation. Using in vivo mouse liver development as a model, we identified thousands of enhancers that are bound by the master regulators HNF4A and FOXA2 in a differentiation-dependent manner, subject to chromatin remodeling, and associated with differentially expressed target genes. Enhancers exclusively occupied in the embryo were found to be responsive to developmentally regulated TEAD2 and coactivator YAP1. Our data suggest that Hippo signaling may affect hepatocyte differentiation by influencing HNF4A and FOXA2 interactions with temporal enhancers. In summary, transcription factor-enhancer interactions are not only tissue specific but also differentiation dependent, which is an important consideration for researchers studying cancer biology or mammalian development and/or using transformed cell lines.

  13. Temporal dependence of in vivo USPIO-enhanced MRI signal changes in human carotid atheromatous plaques

    Energy Technology Data Exchange (ETDEWEB)

    Tang, T.Y.; Sadat, U. [Cambridge University Hospitals NHS Foundation Trust, University Department of Radiology, Cambridge (United Kingdom); Cambridge University Hospitals NHS Foundation Trust, Cambridge Vascular Unit, Cambridge (United Kingdom); Patterson, A.J.; Graves, M.J.; Howarth, S.P.S.; U-King-Im, J.M.; Li, Z.Y.; Young, V.E.; Gillard, J.H. [Cambridge University Hospitals NHS Foundation Trust, University Department of Radiology, Cambridge (United Kingdom); Miller, S.R. [GlaxoSmithKline, Biostatistics and Data Sciences, Harlow (United Kingdom); Walsh, S.R.; Boyle, J.R.; Gaunt, M.E. [Cambridge University Hospitals NHS Foundation Trust, Cambridge Vascular Unit, Cambridge (United Kingdom)

    2009-07-15

    Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced MRI has been shown to be a useful modality to image activated macrophages in vivo, which are principally responsible for plaque inflammation. This study determined the optimum imaging time-window to detect maximal signal change post-USPIO infusion using T{sub 1}-weighted (T{sub 1}w), T{sub 2}*-weighted (T{sub 2}*w) and quantitative T{sub 2}* (qT{sub 2}*) imaging. Six patients with an asymptomatic carotid stenosis underwent high resolution T{sub 1}w, T{sub 2}*w and qT{sub 2}* MR imaging of their carotid arteries at 1.5 T. Imaging was performed before and at 24, 36, 48, 72 and 96 h after USPIO (Sinerem trademark, Guerbet, France) infusion. Each slice showing atherosclerotic plaque was manually segmented into quadrants and signal changes in each quadrant were fitted to an exponential power function to model the optimum time for post-infusion imaging. The power function determining the mean time to convergence for all patients was 46, 41 and 39 h for the T{sub 1}w, T{sub 2}*w and qT{sub 2}* sequences, respectively. When modelling each patient individually, 90% of the maximum signal intensity change was observed at 36 h for three, four and six patients on T{sub 1}w, T{sub 2}*w and qT{sub 2}*, respectively. The rates of signal change decrease after this period but signal change was still evident up to 96 h. This study showed that a suitable imaging window for T{sub 1}w, T{sub 2}*w and qT{sub 2}* signal changes post-USPIO infusion was between 36 and 48 h. Logistically, this would be convenient in bringing patients back for one post-contrast MRI, but validation is required in a larger cohort of patients. (orig.)

  14. Enhanced NMDA receptor-mediated intracellular calcium signaling in magnocellular neurosecretory neurons in heart failure rats.

    Science.gov (United States)

    Stern, Javier E; Potapenko, Evgeniy S

    2013-08-15

    An enhanced glutamate excitatory function within the hypothalamic supraoptic and paraventricluar nuclei is known to contribute to increased neurosecretory and presympathetic neuronal activity, and hence, neurohumoral activation, during heart failure (HF). Still, the precise mechanisms underlying enhanced glutamate-driven neuronal activity in HF remain to be elucidated. Here, we performed simultaneous electrophysiology and fast confocal Ca²⁺ imaging to determine whether altered N-methyl-d-aspartate (NMDA) receptor-mediated changes in intracellular Ca²⁺ levels (NMDA-ΔCa²⁺) occurred in hypothalamic magnocellular neurosecretory cells (MNCs) in HF rats. We found that activation of NMDA receptors resulted in a larger ΔCa²⁺ in MNCs from HF when compared with sham rats. The enhanced NMDA-ΔCa²⁺ was neither dependent on the magnitude of the NMDA-mediated current (voltage clamp) nor on the degree of membrane depolarization or firing activity evoked by NMDA (current clamp). Differently from NMDA receptor activation, firing activity evoked by direct membrane depolarization resulted in similar changes in intracellular Ca²⁺ in sham and HF rats. Taken together, our results support a relatively selective alteration of intracellular Ca²⁺ homeostasis and signaling following activation of NMDA receptors in MNCs during HF. The downstream functional consequences of such altered ΔCa²⁺ signaling during HF are discussed.

  15. BAMBI Promotes C2C12 Myogenic Differentiation by Enhancing Wnt/β-Catenin Signaling

    Directory of Open Access Journals (Sweden)

    Qiangling Zhang

    2015-08-01

    Full Text Available Bone morphogenic protein and activin membrane-bound inhibitor (BAMBI is regarded as an essential regulator of cell proliferation and differentiation that represses transforming growth factor-β and enhances Wnt/β-catenin signaling in various cell types. However, its role in skeletal muscle remains largely unknown. In the current study, we found that the expression level of BAMBI peaked in the early differentiation phase of the C2C12 rodent myoblast cell line. Knockdown of BAMBI via siRNA inhibited C2C12 differentiation, indicated by repressed MyoD, MyoG, and MyHC expression as well as reductions in the differentiation and fusion indices. BAMBI knockdown reduced the activity of Wnt/β-catenin signaling, as characterized by the decreased nuclear translocation of β-catenin and the lowered transcription of Axin2, which is a well-documented target gene of the Wnt/β-catenin signaling pathway. Furthermore, treatment with LiCl, an activator of Wnt/β-catenin signaling, rescued the reduction in C2C12 differentiation caused by BAMBI siRNA. Taken together, our data suggest that BAMBI is required for normal C2C12 differentiation, and that its role in myogenesis is mediated by the Wnt/β-catenin pathway.

  16. Caenorhabditis elegans SMA-10/LRIG is a conserved transmembrane protein that enhances bone morphogenetic protein signaling.

    Directory of Open Access Journals (Sweden)

    Tina L Gumienny

    2010-05-01

    Full Text Available Bone morphogenetic protein (BMP pathways control an array of developmental and homeostatic events, and must themselves be exquisitely controlled. Here, we identify Caenorhabditis elegans SMA-10 as a positive extracellular regulator of BMP-like receptor signaling. SMA-10 acts genetically in a BMP-like (Sma/Mab pathway between the ligand DBL-1 and its receptors SMA-6 and DAF-4. We cloned sma-10 and show that it has fifteen leucine-rich repeats and three immunoglobulin-like domains, hallmarks of an LRIG subfamily of transmembrane proteins. SMA-10 is required in the hypodermis, where the core Sma/Mab signaling components function. We demonstrate functional conservation of LRIGs by rescuing sma-10(lf animals with the Drosophila ortholog lambik, showing that SMA-10 physically binds the DBL-1 receptors SMA-6 and DAF-4 and enhances signaling in vitro. This interaction is evolutionarily conserved, evidenced by LRIG1 binding to vertebrate receptors. We propose a new role for LRIG family members: the positive regulation of BMP signaling by binding both Type I and Type II receptors.

  17. Homocysteine enhances MMP-9 production in murine macrophages via ERK and Akt signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Jin; Lee, Yi Sle; Seo, Kyo Won; Bae, Jin Ung; Kim, Gyu Hee; Park, So Youn; Kim, Chi Dae, E-mail: chidkim@pusan.ac.kr

    2012-04-01

    Homocysteine (Hcy) at elevated levels is an independent risk factor of cardiovascular diseases, including atherosclerosis. In the present study, we investigated the effect of Hcy on the production of matrix metalloproteinases (MMP) in murine macrophages. Among the MMP known to regulate the activities of collagenase and gelatinase, Hcy exclusively increased the gelatinolytic activity of MMP-9 in J774A.1 cells as well as in mouse peritoneal macrophages. Furthermore, this activity was found to be correlated with Western blot findings in J774A.1 cells, which showed that MMP-9 expression was concentration- and time-dependently increased by Hcy. Inhibition of the ERK and Akt pathways led to a significant decrease in Hcy-induced MMP-9 expression, and combined treatment with inhibitors of the ERK and Akt pathways showed an additive effects. Activity assays for ERK and Akt showed that Hcy increased the phosphorylation of both, but these phosphorylation were not affected by inhibitors of the Akt and ERK pathways. In line with these findings, the molecular inhibition of ERK and Akt using siRNA did not affect the Hcy-induced phosphorylation of Akt and ERK, respectively. Taken together, these findings suggest that Hcy enhances MMP-9 production in murine macrophages by separately activating the ERK and Akt signaling pathways. -- Highlights: ► Homocysteine (Hcy) induced MMP-9 production in murine macrophages. ► Hcy induced MMP-9 production through ERK and Akt signaling pathways. ► ERK and Akt signaling pathways were activated by Hcy in murine macrophages. ► ERK and Akt pathways were additively act on Hcy-induced MMP-9 production. ► Hcy enhances MMP-9 production in macrophages via activation of ERK and Akt signaling pathways in an independent manner.

  18. PTP1B Inhibition Causes Rac1 Activation by Enhancing Receptor Tyrosine Kinase Signaling

    Directory of Open Access Journals (Sweden)

    Ayako Tsuchiya

    2014-04-01

    Full Text Available Background/Aims: The present study investigated the signaling pathway underlying Rac1 activation induced by the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl-cyclopropyl]-octanoic acid (DCP-LA. Methods: Activity of protein tyrosine phosphatase 1B (PTP1B was assayed under cell-free conditions. Western blot was carried out to quantify phosphorylation of insulin receptor substrate-1 (IRS-1 and Akt in PC-12 cells. Rac1 activity was monitored in the föerster resonance energy transfer (FRET analysis using living and fixed PC-12 cells. Results: DCP-LA markedly suppressed PTP1B activity in a concentration (100 pM-100 µM-dependent manner. In the DCP-LA binding assay, fluorescein-conjugated DCP-LA produced a single fluorescent signal band at 60 kDa, corresponding to the molecule of PTP1B, and the signal was attenuated or abolished by co-treatment or pretreatment with non-conjugated DCP-LA. DCP-LA significantly enhanced nerve growth factor (NGF-stimulated phosphorylation of IRS-1 at Tyr1222 and Akt1/2 at Thr308/309 and Ser473/474 in PC-12 cells. In the FRET analysis, DCP-LA significantly enhanced NGF-stimulated Rac1 activation, which is abrogated by the phosphatidylinositol 3 kinase (PI3K inhibitor wortmannin, the 3-phosphoinositide-dependent protein kinase-1 (PDK1 inhibitor BX912, or the Akt inhibitor MK2206. Conclusion: The results of the present study show that DCP-LA-induced PTP1B inhibition, possibly through its direct binding, causes Rac1 activation by enhancing a pathway along a receptor tyrosine kinase (RTK/IRS-1/PI3K/Akt/Rac1 axis.

  19. TRH receptor mobility in the plasma membrane is strongly affected by agonist binding and by interaction with some cognate signaling proteins.

    Science.gov (United States)

    Moravcova, Radka; Melkes, Barbora; Novotny, Jiri

    2018-02-01

    Extensive research has been dedicated to elucidating the mechanisms of signal transduction through different G protein-coupled receptors (GPCRs). However, relatively little is known about the regulation of receptor movement within the cell membrane upon ligand binding. In this study we focused our attention on the thyrotropin-releasing hormone (TRH) receptor that typically couples to G q/11 proteins. We monitored receptor diffusion in the plasma membrane of HEK293 cells stably expressing yellow fluorescent protein (YFP)-tagged TRH receptor (TRHR-YFP) by fluorescence recovery after photobleaching (FRAP). FRAP analysis indicated that the lateral movement of the TRH receptor was markedly reduced upon TRH binding as the value of its diffusion coefficient fell down by 55%. This effect was prevented by the addition of the TRH receptor antagonist midazolam. We also found that siRNA-mediated knockdown of G q/11 α, Gβ, β-arrestin2 and phospholipase Cβ1, but not of G i α1, β-arrestin1 or G protein-coupled receptor kinase 2, resulted in a significant decrease in the rate of TRHR-YFP diffusion, indicating the involvement of the former proteins in the regulation of TRH receptor behavior. The observed partial reduction of the TRHR-YFP mobile fraction caused by down-regulation of G i α1 and β-arrestin1 suggests that these proteins may also play distinct roles in THR receptor-mediated signaling. These results demonstrate for the first time that not only agonist binding but also abundance of some signaling proteins may strongly affect TRH receptor dynamics in the plasma membrane.

  20. Proton detection for signal enhancement in solid-state NMR experiments on mobile species in membrane proteins

    Energy Technology Data Exchange (ETDEWEB)

    Ward, Meaghan E.; Ritz, Emily [University of Guelph, Department of Physics (Canada); Ahmed, Mumdooh A. M. [Suez University, The Department of Physics, Faculty of Science (Egypt); Bamm, Vladimir V.; Harauz, George [University of Guelph, Biophysics Interdepartmental Group (Canada); Brown, Leonid S.; Ladizhansky, Vladimir, E-mail: vladizha@uoguelph.ca [University of Guelph, Department of Physics (Canada)

    2015-12-15

    Direct proton detection is becoming an increasingly popular method for enhancing sensitivity in solid-state nuclear magnetic resonance spectroscopy. Generally, these experiments require extensive deuteration of the protein, fast magic angle spinning (MAS), or a combination of both. Here, we implement direct proton detection to selectively observe the mobile entities in fully-protonated membrane proteins at moderate MAS frequencies. We demonstrate this method on two proteins that exhibit different motional regimes. Myelin basic protein is an intrinsically-disordered, peripherally membrane-associated protein that is highly flexible, whereas Anabaena sensory rhodopsin is composed of seven rigid transmembrane α-helices connected by mobile loop regions. In both cases, we observe narrow proton linewidths and, on average, a 10× increase in sensitivity in 2D insensitive nuclear enhancement of polarization transfer-based HSQC experiments when proton detection is compared to carbon detection. We further show that our proton-detected experiments can be easily extended to three dimensions and used to build complete amino acid systems, including sidechain protons, and obtain inter-residue correlations. Additionally, we detect signals which do not correspond to amino acids, but rather to lipids and/or carbohydrates which interact strongly with membrane proteins.

  1. Digital passband processing of wideband-modulated optical signals for enhanced underwater imaging.

    Science.gov (United States)

    Mullen, Linda; Lee, Robert; Nash, Justin

    2016-11-01

    Radar modulation, demodulation, and signal processing techniques have been merged with laser imaging to enhance visibility in murky underwater environments. The modulation provides a way to reject multiple scattered light that would otherwise reduce image contrast and resolution. Recent work has focused on the use of wideband modulation schemes and digital passband processing to resolve range details of an underwater scene. Use of the CLEAN algorithm has also been investigated to extract object features that are obscured by scattered light. Results from controlled laboratory experiments show an improvement in the range resolution and accuracy of underwater imagery relative to data collected with a conventional short pulse system.

  2. Enhancing the GLP-1 receptor signaling pathway leads to proliferation and neuroprotection in human neuroblastoma cells

    OpenAIRE

    Li, Yazhou; Tweedie, David; Mattson, Mark P.; Holloway, Harold W.; Greig, Nigel H.

    2010-01-01

    Increasing evidence suggests that glucagon-like peptide-1 (GLP-1), an incretin hormone of current interest in type 2 diabetes, is neuroprotective in both cell culture and animal models. To characterize the neuroprotective properties of GLP-1 and associated underlying mechanisms, we over-expressed the GLP-1 receptor (R) on human neuroblastoma SH-SY5Y cells to generate a neuronal culture system featuring enhanced GLP-1R signaling. In GLP-1R over-expressing SH-SY5Y (SH-hGLP-1R#9) cells, GLP-1 an...

  3. The enhanced greenhouse signal versus natural variations in observed climate time series: a statistical approach

    Energy Technology Data Exchange (ETDEWEB)

    Schoenwiese, C.D. [J.W. Goethe Univ., Frankfurt (Germany). Inst. for Meteorology and Geophysics

    1995-12-31

    It is a well-known fact that human activities lead to an atmospheric concentration increase of some IR-active trace gases (greenhouse gases GHG) and that this influence enhances the `greenhouse effect`. However, there are major quantitative and regional uncertainties in the related climate model projections and the observational data reflect the whole complex of both anthropogenic and natural forcing of the climate system. This contribution aims at the separation of the anthropogenic enhanced greenhouse signal in observed global surface air temperature data versus other forcing using statistical methods such as multiple (multiforced) regressions and neural networks. The competitive natural forcing considered are volcanic and solar activity, in addition the ENSO (El Nino/Southern Oscillation) mechanism. This analysis will be extended also to the NAO (North Atlantic Oscillation) and anthropogenic sulfate formation in the troposphere

  4. Enhanced insulin signaling in human skeletal muscle and adipose tissue following gastric bypass surgery

    DEFF Research Database (Denmark)

    Albers, Peter Hjorth; Bojsen-Moller, Kirstine N; Dirksen, Carsten

    2015-01-01

    Roux-en-Y gastric bypass (RYGB) leads to increased peripheral insulin sensitivity. The aim of this study was to investigate the effect of RYGB on expression and regulation of proteins involved in regulation of peripheral glucose metabolism. Skeletal muscle and adipose tissue biopsies from glucose......-surgery when major weight loss was evident and occurred concomitantly with alterations in plasma adiponectin and in protein expression/signaling in peripheral tissues. In skeletal muscle, protein expression of GLUT4, phosphorylated levels of TBC1D4 as well as insulin-induced changes in phosphorylation of Akt...... and glycogen synthase activity were enhanced 12 months post-surgery. In adipose tissue, protein expression of GLUT4, Akt2, TBC1D4 and acetyl-CoA carboxylase (ACC), phosphorylated levels of AMP-activated protein kinase and ACC as well as insulin-induced changes in phosphorylation of Akt and TBC1D4 were enhanced...

  5. 5′ and 3′ Untranslated Regions Strongly Enhance Performance of Geminiviral Replicons in Nicotiana benthamiana Leaves

    Science.gov (United States)

    Diamos, Andrew G.; Rosenthal, Sun H.; Mason, Hugh S.

    2016-01-01

    We previously reported a recombinant protein production system based on a geminivirus replicon that yields high levels of vaccine antigens and monoclonal antibodies in plants. The bean yellow dwarf virus (BeYDV) replicon generates massive amounts of DNA copies, which engage the plant transcription machinery. However, we noticed a disparity between transcript level and protein production, suggesting that mRNAs could be more efficiently utilized. In this study, we systematically evaluated genetic elements from human, viral, and plant sources for their potential to improve the BeYDV system. The tobacco extensin terminator enhanced transcript accumulation and protein production compared to other commonly used terminators, indicating that efficient transcript processing plays an important role in recombinant protein production. Evaluation of human-derived 5′ untranslated regions (UTRs) indicated that many provided high levels of protein production, supporting their cross-kingdom function. Among the viral 5′ UTRs tested, we found the greatest enhancement with the tobacco mosaic virus omega leader. An analysis of the 5′ UTRs from the Arabidopsis thaliana and Nicotinana benthamiana photosystem I K genes found that they were highly active when truncated to include only the near upstream region, providing a dramatic enhancement of transgene production that exceeded that of the tobacco mosaic virus omega leader. The tobacco Rb7 matrix attachment region inserted downstream from the gene of interest provided significant enhancement, which was correlated with a reduction in plant cell death. Evaluation of Agrobacterium strains found that EHA105 enhanced protein production and reduced cell death compared to LBA4301 and GV3101. We used these improvements to produce Norwalk virus capsid protein at >20% total soluble protein, corresponding to 1.8 mg/g leaf fresh weight, more than twice the highest level ever reported in a plant system. We also produced the monoclonal antibody

  6. 8-Port Homodyne Detection of EIT-Enhanced Cross-Phase Modulation Using Broadband Signal Pulses

    Science.gov (United States)

    Dmochowski, Grzegorz

    This thesis summarizes my work on the interactions between light and matter in the context of optical quantum information processing. I have designed and implemented a phase-sensitive detection scheme for optical-frequency electromagnetic fields, which has been used to measure murad phase shifts on nanosecond timescales. This phase measurement was developed for the express purpose of detecting cross-phase modulation (XPM), a key ingredient in the construction of optical logic gates. I have implemented the 'N-scheme', a form of XPM which exploits electromagnetically-induced transparency (EIT) and which was promised to yield 'giant' optical nonlinearities sufficient for all-optical quantum information processing. Using a cloud of laser-cooled 85Rb atoms as the nonlinear medium, I present the first ever experimental study of EIT-enhanced XPM in the controversial regime of broadband signal pulses and spectrally narrow EIT windows. The results of this experiment constitute a breakdown of the original proposal for EIT-enhanced XPM. In light of these findings, I conclude with a theoretical analysis of the feasibility of using N-scheme as implemented in our lab to perform a non-demolition measurement of a single photon (a crucial step when using XPM to generate a universal optical logic gate). While possible in principle, the experimental conditions necessary to achieve a signal-to-noise ratio above unity are found to be practically unrealistic, suggesting a more sophisticated scheme is necessary.

  7. Enhancement of strong-field multiple ionization in the vicinity of the conical intersection in 1,3-cyclohexadiene ring opening

    International Nuclear Information System (INIS)

    Petrovic, Vladimir S.; Kim, Jaehee; Schorb, Sebastian; White, James; Cryan, James P.; Zipp, Lucas; Glownia, J. Michael; Broege, Douglas; Miyabe, Shungo; Tao, Hongli; Martinez, Todd; Bucksbaum, Philip H.

    2013-01-01

    Nonradiative energy dissipation in electronically excited polyatomic molecules proceeds through conical intersections, loci of degeneracy between electronic states. We observe a marked enhancement of laser-induced double ionization in the vicinity of a conical intersection during a non-radiative transition. We measured double ionization by detecting the kinetic energy of ions released by laser-induced strong-field fragmentation during the ring-opening transition between 1,3-cyclohexadiene and 1,3,5-hexatriene. The enhancement of the double ionization correlates with the conical intersection between the HOMO and LUMO orbitals

  8. Circumvention of regulatory CD4(+) T cell activity during cross-priming strongly enhances T cell-mediated immunity.

    Science.gov (United States)

    Heit, Antje; Gebhardt, Friedemann; Lahl, Katharina; Neuenhahn, Michael; Schmitz, Frank; Anderl, Florian; Wagner, Hermann; Sparwasser, Tim; Busch, Dirk H; Kastenmüller, Kathrin

    2008-06-01

    Immunization with purified antigens is a safe and practical vaccination strategy but is generally unable to induce sustained CD8(+) T cell-mediated protection against intracellular pathogens. Most efforts to improve the CD8(+) T cell immunogenicity of these vaccines have focused on co-administration of adjuvant to support cross-presentation and dendritic cell maturation. In addition, it has been shown that CD4(+) T cell help during the priming phase contributes to the generation of protective CD8(+) memory T cells. In this report we demonstrate that the depletion of CD4(+) T cells paradoxically enhances long-lasting CD8-mediated protective immunity upon protein vaccination. Functional and genetic in vivo inactivation experiments attribute this enhancement primarily to MHC class II-restricted CD4(+) regulatory T cells (Treg), which appear to physiologically suppress the differentiation process towards long-living effector memory T cells. Since, in functional terms, this suppression by Treg largely exceeds the positive effects of conventional CD4(+) T cell help, even the absence of all CD4(+) T cells or lack of MHC class II-mediated interactions on priming dendritic cells result in enhanced CD8(+) T cell immunogenicity. These findings have important implications for the improvement of vaccines against intracellular pathogens or tumors, especially in patients with highly active Treg.

  9. Enhancing dopaminergic signaling and histone acetylation promotes long-term rescue of deficient fear extinction

    Science.gov (United States)

    Whittle, N; Maurer, V; Murphy, C; Rainer, J; Bindreither, D; Hauschild, M; Scharinger, A; Oberhauser, M; Keil, T; Brehm, C; Valovka, T; Striessnig, J; Singewald, N

    2016-01-01

    Extinction-based exposure therapy is used to treat anxiety- and trauma-related disorders; however, there is the need to improve its limited efficacy in individuals with impaired fear extinction learning and to promote greater protection against return-of-fear phenomena. Here, using 129S1/SvImJ mice, which display impaired fear extinction acquisition and extinction consolidation, we revealed that persistent and context-independent rescue of deficient fear extinction in these mice was associated with enhanced expression of dopamine-related genes, such as dopamine D1 (Drd1a) and -D2 (Drd2) receptor genes in the medial prefrontal cortex (mPFC) and amygdala, but not hippocampus. Moreover, enhanced histone acetylation was observed in the promoter of the extinction-regulated Drd2 gene in the mPFC, revealing a potential gene-regulatory mechanism. Although enhancing histone acetylation, via administering the histone deacetylase (HDAC) inhibitor MS-275, does not induce fear reduction during extinction training, it promoted enduring and context-independent rescue of deficient fear extinction consolidation/retrieval once extinction learning was initiated as shown following a mild conditioning protocol. This was associated with enhanced histone acetylation in neurons of the mPFC and amygdala. Finally, as a proof-of-principle, mimicking enhanced dopaminergic signaling by L-dopa treatment rescued deficient fear extinction and co-administration of MS-275 rendered this effect enduring and context-independent. In summary, current data reveal that combining dopaminergic and epigenetic mechanisms is a promising strategy to improve exposure-based behavior therapy in extinction-impaired individuals by initiating the formation of an enduring and context-independent fear-inhibitory memory. PMID:27922638

  10. Strongly enhanced irreversibility fields and Bose-glass behaviour in bulk YBCO with discontinuous columnar irradiation defects

    International Nuclear Information System (INIS)

    Fuchs, G; Nenkov, K; Krabbes, G; Weinstein, R; Gandini, A; Sawh, R; Mayes, B; Parks, D

    2007-01-01

    Flux pinning properties and irreversibility fields B irr (T) of melt-textured YBCO with discontinuous or multiple-in-line-damage (MILD) columnar defects produced by irradiation with high-energy U 238 ions were studied at a constant matching field of B φ = 10 T and for several energy losses between S e = 1.67 and 2.4 keV A -1 . With increasing S e and increasing length of the MILD pins, the critical current density j c (H,T) strongly increases and B irr (T) for fields along the c axis progressively shifts upwards reaching 9 T at 77 K. For S e = 2.4 keV A -1 , a pronounced kink is observed in B irr (T) at 8 T which is a strong indication of Bose-glass behaviour. The j c (H) dependence of this sample shows a peak at a low applied field B p . This peak effect is explained by the entanglement of vortices. It is argued that for MILD pins single vortices interact simultaneously with many short columnar defects in neighbouring ion trails resulting in an automatic splay in the vortex orientation. The observed decrease of B p with increasing temperature is estimated taking the increasing thermal fluctuations into account

  11. Evaluation of the impact of higher-order energy enhancement characteristics of solitons in strongly dispersion-managed optical fibers

    International Nuclear Information System (INIS)

    Diaz-Otero, Francisco J.; Guillán-Lorenzo, Omar; Pedrosa-Rodríguez, Laura

    2017-01-01

    Highlights: • Empirical model describing the pulse energy enhancement required to obtain stable pulses to higher-order polynomial equations • An improvement in the accuracy is obtained through the addition of a new quartic addend dependent on the map strength. • This conclusion is validated through a comparison in a commercial DM soliton submarine network. • The error in the interaction distance for two adjacent pulses in the same channel is of the same order as the energy error - Abstract: We study the propagation properties of nonlinear pulses with periodic evolution in a dispersion-managed transmission link by means of a variational approach. We fit the energy enhancement required for stable propagation of a single soliton in a prototypical commercial link to a polynomial approximation that describes the dependence of the energy on the map strength of the normalized unit cell. We present an improvement of a relatively old and essential result, namely, the dependence of the energy-enhancement factor of dispersion-management solitons with the square of the map strength of the fiber link. We find that adding additional corrections to the conventional quadratic formula up to the fourth order results in an improvement in the accuracy of the description of the numerical results obtained with the variational approximation. Even a small error in the energy is found to introduce large deviations in the pulse parameters during its evolution. The error in the evaluation of the interaction distance between two adjacent time division multiplexed pulses propagating in the same channel in a prototypical submarine link is of the same order as the error in the energy.

  12. Strong enhancement of piezoelectric constants in ScxAl1−xN: First-principles calculations

    Directory of Open Access Journals (Sweden)

    Hiroyoshi Momida

    2016-06-01

    Full Text Available We theoretically investigate the piezoelectricity of ScxAl1−xN in the entire range of x by first-principles calculations. We find that the piezoelectric constants of wurtzite-type ScxAl1−xN significantly enhance as x increases from 0 to 0.75. However, the energy stability analyses between structure phases show that the cubic-type phases become more stable than the wurtzite-type phases at x of approximately 0.5 and higher, interfering with the ability of wurtzite-type ScxAl1−xN to realize the maximum piezoelectricity. Moreover, our study on element combination dependences on piezoelectricity in A0.5B0.5N (A = Sc, Y, La and B = Al, Ga, In indicates that Sc, Y, and La have the strongest effect on the enhancement of piezoelectric constants in AlN, GaN, and InN, respectively.

  13. Subversion of innate defenses by the interplay between DENV and pre-existing enhancing antibodies: TLRs signaling collapse.

    Science.gov (United States)

    Modhiran, Naphak; Kalayanarooj, Siripen; Ubol, Sukathida

    2010-12-21

    The phenomenon of antibody dependent enhancement as a major determinant that exacerbates disease severity in DENV infections is well accepted. While the detailed mechanism of antibody enhanced disease severity is unclear, evidence suggests that it is associated with both increased DENV infectivity and suppression of the type I IFN and pro-inflammatory cytokine responses. Therefore, it is imperative for us to understand the intracellular mechanisms altered during ADE infection to decipher the mechanism of severe pathogenesis. In this present work, qRT-PCR, immunoblotting and gene array analysis were conducted to determine whether DENV-antibody complex infection exerts a suppressive effect on the expression and/or function of the pathogen recognition patterns, focusing on the TLR-signaling pathway. We show here that FcγRI and FcγRIIa synergistically facilitated entry of DENV-antibody complexes into monocytic THP-1 cells. Ligation between DENV-antibody complexes and FcR not only down regulated TLRs gene expression but also up regulated SARM, TANK, and negative regulators of the NF-κB pathway, resulting in suppression of innate responses but increased viral production. These results were confirmed by blocking with anti-FcγRI or anti-FcγRIIa antibodies which reduced viral production, up-regulated IFN-β synthesis, and increased gene expression in the TLR-dependent signaling pathway. The negative impact of DENV-ADE infection on the TLR-dependent pathway was strongly supported by gene array screening which revealed that both MyD88-dependent and -independent signaling molecules were down regulated during DENV-ADE infection. Importantly, the same phenomenon was seen in PBMC of secondary DHF/DSS patients but not in PBMC of DF patients. Our present work demonstrates the mechanism by which DENV uses pre-existing immune mediators to defeat the principal activating pathway of innate defense resulting in suppression of an array of innate immune responses. Interestingly, this

  14. Enhanced hot-electron production and strong-shock generation in hydrogen-rich ablators for shock ignition

    Science.gov (United States)

    Theobald, W.; Bose, A.; Yan, R.; Betti, R.; Lafon, M.; Mangino, D.; Christopherson, A. R.; Stoeckl, C.; Seka, W.; Shang, W.; Michel, D. T.; Ren, C.; Nora, R. C.; Casner, A.; Peebles, J.; Beg, F. N.; Ribeyre, X.; Llor Aisa, E.; Colaïtis, A.; Tikhonchuk, V.; Wei, M. S.

    2017-12-01

    Experiments were performed with CH, Be, C, and SiO2 ablators interacting with high-intensity UV laser radiation (5 × 1015 W/cm2, λ = 351 nm) to determine the optimum material for hot-electron production and strong-shock generation. Significantly more hot electrons are produced in CH (up to ˜13% instantaneous conversion efficiency), while the amount is a factor of ˜2 to 3 lower in the other ablators. A larger hot-electron fraction is correlated with a higher effective ablation pressure. The higher conversion efficiency in CH is attributed to stronger damping of ion-acoustic waves because of the presence of light H ions.

  15. "X-Map 2.0" for Edema Signal Enhancement for Acute Ischemic Stroke Using Non-Contrast-Enhanced Dual-Energy Computed Tomography.

    Science.gov (United States)

    Taguchi, Katsuyuki; Itoh, Toshihide; Fuld, Matthew K; Fournie, Eric; Lee, Okkyun; Noguchi, Kyo

    2018-03-14

    A novel imaging technique ("X-map") has been developed to identify acute ischemic lesions for stroke patients using non-contrast-enhanced dual-energy computed tomography (NE-DE-CT). Using the 3-material decomposition technique, the original X-map ("X-map 1.0") eliminates fat and bone from the images, suppresses the gray matter (GM)-white matter (WM) tissue contrast, and makes signals of edema induced by severe ischemia easier to detect. The aim of this study was to address the following 2 problems with the X-map 1.0: (1) biases in CT numbers (or artifacts) near the skull of NE-DE-CT images and (2) large intrapatient and interpatient variations in X-map 1.0 values. We improved both an iterative beam-hardening correction (iBHC) method and the X-map algorithm. The new iBHC (iBHC2) modeled x-ray physics more accurately. The new X-map ("X-map 2.0") estimated regional GM values-thus, maximizing the ability to suppress the GM-WM contrast, make edema signals quantitative, and enhance the edema signals that denote an increased water density for each pixel. We performed a retrospective study of 11 patients (3 men, 8 women; mean age, 76.3 years; range, 68-90 years) who presented to the emergency department with symptoms of acute stroke. Images were reconstructed with the old iBHC (iBHC1) and the iBHC2, and biases in CT numbers near the skull were measured. Both X-map 2.0 maps and X-map 1.0 maps were computed from iBHC2 images, both with and without a material decomposition-based edema signal enhancement (ESE) process. X-map values were measured at 5 to 9 locations on GM without infarct per patient; the mean value was calculated for each patient (we call it the patient-mean X-map value) and subtracted from the measured X-map values to generate zero-mean X-map values. The standard deviation of the patient-mean X-map values over multiple patients denotes the interpatient variation; the standard deviation over multiple zero-mean X-map values denotes the intrapatient variation

  16. Dark exposure of petunia cuttings strongly improves adventitious root formation and enhances carbohydrate availability during rooting in the light.

    Science.gov (United States)

    Klopotek, Yvonne; Haensch, Klaus-Thomas; Hause, Bettina; Hajirezaei, Mohammad-Reza; Druege, Uwe

    2010-05-01

    The effect of temporary dark exposure on adventitious root formation (ARF) in Petuniaxhybrida 'Mitchell' cuttings was investigated. Histological and metabolic changes in the cuttings during the dark treatment and subsequent rooting in the light were recorded. Excised cuttings were exposed to the dark for seven days at 10 degrees C followed by a nine-day rooting period in perlite or were rooted immediately for 16 days in a climate chamber at 22/20 degrees C (day/night) and a photosynthetic photon flux density (PPFD) of 100micromolm(-2)s(-1). Dark exposure prior to rooting increased, accelerated and synchronized ARF. The rooting period was reduced from 16 days (non-treated cuttings) to 9 days (treated cuttings). Under optimum conditions, despite the reduced rooting period, dark-exposed cuttings produced a higher number and length of roots than non-treated cuttings. An increase in temperature to 20 degrees C during the dark treatment or extending the cold dark exposure to 14 days caused a similar enhancement of root development compared to non-treated cuttings. Root meristem formation had already started during the dark treatment and was enhanced during the subsequent rooting period. Levels of soluble sugars (glucose, fructose and sucrose) and starch in leaf and basal stem tissues significantly decreased during the seven days of dark exposure. This depletion was, however, compensated during rooting after 6 and 24h for soluble sugars in leaves and the basal stem, respectively, whereas the sucrose level in the basal stem was already increased at 6h. The association of higher carbohydrate levels with improved rooting in previously dark-exposed versus non-treated cuttings indicates that increased post-darkness carbohydrate availability and allocation towards the stem base contribute to ARF under the influence of dark treatment and provide energy for cell growth subject to a rising sink intensity in the base of the cutting. Copyright 2009 Elsevier GmbH. All rights reserved.

  17. Prolactin signaling enhances colon cancer stemness by modulating Notch signaling in a Jak2-STAT3/ERK manner

    Science.gov (United States)

    Anant, Shrikant

    2014-01-01

    Prolactin (PRL) is a secretory cytokine produced by various tissues. Binding to the cognate PRL receptor (PRLR), it activates intracellular signaling via janus kinase (JAK), extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription (STAT) proteins. PRL regulates diverse activities under normal and abnormal conditions, including malignancies. Previous clinical data suggest serum PRL levels are elevated in colorectal cancer (CRC) patients. In this study, we first determined the expression of PRL and PRLR in colon cancer tissue and cell lines. Higher levels of PRLR expression were observed in the cancer cells and cell lines compared with normal colonic epithelial cells. Incubation of colon cancer cells with PRL-induced JAK2, STAT3 and ERK1/2 phosphorylation and increased expression of Jagged 1, which is a Notch-1 receptor ligand. Notch signaling regulates CRC stem cell population. We observed increased accumulation of the cleaved/active form of Notch-1 receptor (Notch intracellular domain) and increased expression of Notch responsive genes HEY1, HES1 and stem cell marker genes DCLK1, LGR5, ALDH1 and CD44. Finally, inhibiting PRL induced JAK2-STAT3 and JAK2-ERK1/2 using AG490 and PD98059, respectively, leads to complete abrogation of Notch signaling, suggesting a role for this pathway in regulating CRC stem cells. Together, our results demonstrate that cytokine signaling induced by PRL is active in colorectal cancers and may provide a novel target for therapeutic intervention. PMID:24265293

  18. Enhanced signaling scheme with admission control in the hybrid optical wireless (HOW) networks

    DEFF Research Database (Denmark)

    Yan, Ying; Yu, Hao; Wessing, Henrik

    2009-01-01

    that it can support stringent Quality of Service (QoS) requirements. In this paper, we describe and evaluate a resource management framework designed for the HOW networks. There are two parts in the resource management framework The first part is the Enhanced MPCP (E-MPCP) scheme aiming at improving signaling......The hybrid optical wireless (HOW) network has been viewed as a promising solution to meet the increasing user bandwidth and mobility demands. Due to the basic differences in the optical and wireless technologies, a challenging problem lies in the Media Access Control (MAC) protocol design so...... dropping probability depend on several factors. These factors include the frame duration, the traffic load and the total number of shared users. The results also highlight that our proposed system achieves significant improvements over the traditional approach in terms of user QoS guarantee and network...

  19. Enhancement of arachidonic acid signaling pathway by nicotinic acid receptor HM74A

    International Nuclear Information System (INIS)

    Tang, Yuting; Zhou, Lubing; Gunnet, Joseph W.; Wines, Pamela G.; Cryan, Ellen V.; Demarest, Keith T.

    2006-01-01

    HM74A is a G protein-coupled receptor for nicotinic acid (niacin), which has been used clinically to treat dyslipidemia for decades. The molecular mechanisms whereby niacin exerts its pleiotropic effects on lipid metabolism remain largely unknown. In addition, the most common side effect in niacin therapy is skin flushing that is caused by prostaglandin release, suggesting that the phospholipase A 2 (PLA 2 )/arachidonic acid (AA) pathway is involved. Various eicosanoids have been shown to activate peroxisome-proliferator activated receptors (PPAR) that play a diverse array of roles in lipid metabolism. To further elucidate the potential roles of HM74A in mediating the therapeutic effects and/or side effects of niacin, we sought to explore the signaling events upon HM74A activation. Here we demonstrated that HM74A synergistically enhanced UTP- and bradykinin-mediated AA release in a pertussis toxin-sensitive manner in A431 cells. Activation of HM74A also led to Ca 2+ -mobilization and enhanced bradykinin-promoted Ca 2+ -mobilization through Gi protein. While HM74A increased ERK1/2 activation by the bradykinin receptor, it had no effects on UTP-promoted ERK1/2 activation.Furthermore, UTP- and bradykinin-mediated AA release was significantly decreased in the presence of both MAPK kinase inhibitor PD 098059 and PKC inhibitor GF 109203X. However, the synergistic effects of HM74A were not dramatically affected by co-treatment with both inhibitors, indicating the cross-talk occurred at the receptor level. Finally, stimulation of A431 cells transiently transfected with PPRE-luciferase with AA significantly induced luciferase activity, mimicking the effects of PPARγ agonist rosiglitazone, suggesting that alteration of AA signaling pathway can regulate gene expression via endogenous PPARs

  20. The expression of a recombinant glycolate dehydrogenase polyprotein in potato (Solanum tuberosum) plastids strongly enhances photosynthesis and tuber yield.

    Science.gov (United States)

    Nölke, Greta; Houdelet, Marcel; Kreuzaler, Fritz; Peterhänsel, Christoph; Schillberg, Stefan

    2014-08-01

    We have increased the productivity and yield of potato (Solanum tuberosum) by developing a novel method to enhance photosynthetic carbon fixation based on expression of a polyprotein (DEFp) comprising all three subunits (D, E and F) of Escherichia coli glycolate dehydrogenase (GlcDH). The engineered polyprotein retained the functionality of the native GlcDH complex when expressed in E. coli and was able to complement mutants deficient for the D, E and F subunits. Transgenic plants accumulated DEFp in the plastids, and the recombinant protein was active in planta, reducing photorespiration and improving CO2 uptake with a significant impact on carbon metabolism. Transgenic lines with the highest DEFp levels and GlcDH activity produced significantly higher levels of glucose (5.8-fold), fructose (3.8-fold), sucrose (1.6-fold) and transitory starch (threefold), resulting in a substantial increase in shoot and leaf biomass. The higher carbohydrate levels produced in potato leaves were utilized by the sink capacity of the tubers, increasing the tuber yield by 2.3-fold. This novel approach therefore has the potential to increase the biomass and yield of diverse crops. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  1. Enhanced crystal-field splitting and orbital-selective coherence induced by strong correlations in V2O3

    Science.gov (United States)

    Poteryaev, Alexander I.; Tomczak, Jan M.; Biermann, Silke; Georges, Antoine; Lichtenstein, Alexander I.; Rubtsov, Alexey N.; Saha-Dasgupta, Tanusri; Andersen, Ole K.

    2007-08-01

    We present a study of the paramagnetic metallic and insulating phases of vanadium sesquioxide by means of the Nth order muffin-tin orbital implementation of density functional theory combined with dynamical mean-field theory. The transition is shown to be driven by a correlation-induced enhancement of the crystal-field splitting within the t2g manifold, which results in a suppression of the hybridization between the a1g and egπ bands. We discuss the changes in the effective quasiparticle band structure caused by the correlations and the corresponding self-energies. At temperatures of about 400K , we find the a1g orbital displays coherent quasiparticle behavior, while a large imaginary part of the self-energy and broad features in the spectral function indicate that the egπ orbitals are still far above their coherence temperature. The local spectral functions are in excellent agreement with recent bulk sensitive photoemission data. Finally, we also make a prediction for angle-resolved photoemission experiments by calculating momentum-resolved spectral functions.

  2. Generation and tunable enhancement of a sum-frequency signal in lithium niobate nanowires

    Science.gov (United States)

    Sergeyev, Anton; Reig Escalé, Marc; Grange, Rachel

    2017-02-01

    Recent developments in the fabrication of lithium niobate (LiNbO3) structures down to the nanoscale opens up novel applications of this versatile material in nonlinear optics. Current nonlinear optical studies in sub-micron waveguides are mainly restricted to the generation of second and third harmonics. In this work, we demonstrate the generation and waveguiding of the sum-frequency generation (SFG) signal in a single LiNbO3 nanowire with a cross-section of 517 nm  ×  654 nm. Furthermore, we enhance the guided SFG signal 17.9 times by means of modal phase matching. We also display tuning of the phase-matched wavelength by varying the nanowire cross-section and changing the polarization of the incident laser. The results prove that LiNbO3 nanowires can be successfully used for nonlinear wave-mixing applications and assisting the miniaturization of optical devices. , which features invited work from the best early-career researchers working within the scope of J Phys D. This project is part of the Journal of Physics series’ 50th anniversary celebrations in 2017. Rachel Grange was selected by the Editorial Board of J Phys D as an Emerging Leader.

  3. Sigma-1 receptor enhances neurite elongation of cerebellar granule neurons via TrkB signaling.

    Science.gov (United States)

    Kimura, Yuriko; Fujita, Yuki; Shibata, Kumi; Mori, Megumi; Yamashita, Toshihide

    2013-01-01

    Sigma-1 receptor (Sig-1R) is an integral membrane protein predominantly expressed in the endoplasmic reticulum. Sig-1R demonstrates a high affinity to various synthetic compounds including well-known psychotherapeutic drugs in the central nervous system (CNS). For that, it is considered as an alternative target for psychotherapeutic drugs. On the cellular level, when Sig-1R is activated, it is known to play a role in neuroprotection and neurite elongation. These effects are suggested to be mediated by its ligand-operated molecular chaperone activity, and/or upregulation of various Ca(2+) signaling. In addition, recent studies show that Sig-1R activation induces neurite outgrowth via neurotrophin signaling. Here, we tested the hypothesis that Sig-1R activation promotes neurite elongation through activation of tropomyosin receptor kinase (Trk), a family of neurotrophin receptors. We found that 2-(4-morpholinethyl)1-phenylcyclohexanecarboxylate (PRE-084), a selective Sig-1R agonist, significantly promoted neurite outgrowth, and K252a, a Trk inhibitor, attenuated Sig-1R-mediated neurite elongation in cerebellar granule neurons (CGNs). Moreover, we revealed that Sig-1R interacts with TrkB, and PRE-084 treatment enhances phosphorylation of Y515, but not Y706. Thus, our results indicate that Sig-1R activation promotes neurite outgrowth in CGNs through Y515 phosphorylation of TrkB.

  4. High glucose induces podocyte injury via enhanced (prorenin receptor-Wnt-β-catenin-snail signaling pathway.

    Directory of Open Access Journals (Sweden)

    Caixia Li

    Full Text Available (Prorenin receptor (PRR expression is upregulated in diabetes. We hypothesized that PRR contributes to podocyte injury via activation of Wnt-β-catenin-snail signaling pathway. Mouse podocytes were cultured in normal (5 mM or high (25 mM D-glucose for 3 days. Compared to normal glucose, high glucose significantly decreased mRNA and protein expressions of podocin and nephrin, and increased mRNA and protein expressions of PRR, Wnt3a, β-catenin, and snail, respectively. Confocal microscopy studies showed significant reduction in expression and reorganization of podocyte cytoskeleton protein, F-actin, in response to high glucose. Transwell functional permeability studies demonstrated significant increase in albumin flux through podocytes monolayer with high glucose. Cells treated with high glucose and PRR siRNA demonstrated significantly attenuated mRNA and protein expressions of PRR, Wnt3a, β-catenin, and snail; enhanced expressions of podocin mRNA and protein, improved expression and reorganization of F-actin, and reduced transwell albumin flux. We conclude that high glucose induces podocyte injury via PRR-Wnt-β-catenin-snail signaling pathway.

  5. A set of enhanced green fluorescent protein concatemers for quantitative determination of nuclear localization signal strength.

    Science.gov (United States)

    Böhm, Jennifer; Thavaraja, Ramya; Giehler, Susanne; Nalaskowski, Marcus M

    2017-09-15

    Regulated transport of proteins between nucleus and cytoplasm is an important process in the eukaryotic cell. In most cases, active nucleo-cytoplasmic protein transport is mediated by nuclear localization signal (NLS) and/or nuclear export signal (NES) motifs. In this study, we developed a set of vectors expressing enhanced GFP (EGFP) concatemers ranging from 2 to 12 subunits (2xEGFP to 12xEGFP) for analysis of NLS strength. As shown by in gel GFP fluorescence analysis and αGFP Western blotting, EGFP concatemers are expressed as fluorescent full-length proteins in eukaryotic cells. As expected, nuclear localization of concatemeric EGFPs decreases with increasing molecular weight. By oligonucleotide ligation this set of EGFP concatemers can be easily fused to NLS motifs. After determination of intracellular localization of EGFP concatemers alone and fused to different NLS motifs we calculated the size of a hypothetic EGFP concatemer showing a defined distribution of EGFP fluorescence between nucleus and cytoplasm (n/c ratio = 2). Clear differences of the size of the hypothetic EGFP concatemer depending on the fused NLS motif were observed. Therefore, we propose to use the size of this hypothetic concatemer as quantitative indicator for comparing strength of different NLS motifs. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Spatial covert attention increases contrast sensitivity across the CSF: support for signal enhancement

    Science.gov (United States)

    Carrasco, M.; Penpeci-Talgar, C.; Eckstein, M.

    2000-01-01

    This study is the first to report the benefits of spatial covert attention on contrast sensitivity in a wide range of spatial frequencies when a target alone was presented in the absence of a local post-mask. We used a peripheral precue (a small circle indicating the target location) to explore the effects of covert spatial attention on contrast sensitivity as assessed by orientation discrimination (Experiments 1-4), detection (Experiments 2 and 3) and localization (Experiment 3) tasks. In all four experiments the target (a Gabor patch ranging in spatial frequency from 0.5 to 10 cpd) was presented alone in one of eight possible locations equidistant from fixation. Contrast sensitivity was consistently higher for peripherally- than for neutrally-cued trials, even though we eliminated variables (distracters, global masks, local masks, and location uncertainty) that are known to contribute to an external noise reduction explanation of attention. When observers were presented with vertical and horizontal Gabor patches an external noise reduction signal detection model accounted for the cueing benefit in a discrimination task (Experiment 1). However, such a model could not account for this benefit when location uncertainty was reduced, either by: (a) Increasing overall performance level (Experiment 2); (b) increasing stimulus contrast to enable fine discriminations of slightly tilted suprathreshold stimuli (Experiment 3); and (c) presenting a local post-mask (Experiment 4). Given that attentional benefits occurred under conditions that exclude all variables predicted by the external noise reduction model, these results support the signal enhancement model of attention.

  7. Antibody-mediated delivery of interleukin-2 to the stroma of breast cancer strongly enhances the potency of chemotherapy.

    Science.gov (United States)

    Mårlind, Jessica; Kaspar, Manuela; Trachsel, Eveline; Sommavilla, Roberto; Hindle, Stuart; Bacci, Camilla; Giovannoni, Leonardo; Neri, Dario

    2008-10-15

    There is an interest in the discovery of biopharmaceuticals, which are well tolerated and which potentiate the action of anthracyclines and taxanes in breast cancer therapy. We have produced a recombinant fusion protein, composed of the human antibody fragment scFv(F16) fused to human interleukin-2 (F16-IL2), and tested its therapeutic performance in the MDA-MB-231 xenograft model of human breast cancer. The F16 antibody is specific to the alternatively spliced A1 domain of tenascin-C, which is virtually undetectable in normal tissues but is strongly expressed in the neovasculature and stroma of breast cancer. When used as monotherapy, F16-IL2 displayed a strikingly superior therapeutic benefit compared with unconjugated recombinant IL-2. The administration of doxorubicin either before (8 days, 24 h, or 2 h) or simultaneously with the injection of F16-IL2 did not decrease the accumulation of immunocytokine in the tumor as measured by quantitative biodistribution analysis. Therapy experiments, featuring five once per week coadministrations of 20 mug F16-IL2 and doxorubicin, showed a statistically significant reduction of tumor growth rate and prolongation of survival at a 4 mg/kg doxorubicin dose but not at a 1 mg/kg dose. By contrast, combination of F16-IL2 with paclitaxel (5 and 1 mg/kg) exhibited a significant therapeutic benefit compared with paclitaxel alone at both dose levels. F16-IL2, alone or in combination with doxorubicin, was well tolerated in cynomolgus monkeys at doses equivalent to the ones now used in clinical studies. F16-IL2 may represent a new useful biopharmaceutical for the treatment of breast cancer.

  8. The Targeted SMAC Mimetic SW IV-134 is a strong enhancer of standard chemotherapy in pancreatic cancer.

    Science.gov (United States)

    Hashim, Yassar M; Vangveravong, Suwanna; Sankpal, Narendra V; Binder, Pratibha S; Liu, Jingxia; Goedegebuure, S Peter; Mach, Robert H; Spitzer, Dirk; Hawkins, William G

    2017-01-17

    Pancreatic cancer is a lethal malignancy that frequently acquires resistance to conventional chemotherapies often associated with overexpression of inhibitors of apoptosis proteins (IAPs). We have recently described a novel means to deliver second mitochondria-derived activator of caspases (SMAC) mimetics selectively to cancer cells employing the sigma-2 ligand/receptor interaction. The intrinsic death pathway agonist SMAC offers an excellent opportunity to counteract the anti-apoptotic activity of IAPs. SMAC mimetics have been used to sensitize several cancer types to chemotherapeutic agents but cancer-selective delivery and appropriate cellular localization have not yet been considered. In our current study, we tested the ability of the sigma-2/SMAC drug conjugate SW IV-134 to sensitize pancreatic cancer cells to gemcitabine. Using the targeted SMAC mimetic SW IV-134, inhibition of the X-linked inhibitor of apoptosis proteins (XIAP) was induced pharmacologically and its impact on cell viability was studied alone and in combination with gemcitabine. Pathway analyses were performed by assessing caspase activation, PARP cleavage and membrane blebbing (Annexin-V), key components of apoptotic cell death. Single-agent treatment regimens were compared with combination therapy in a preclinical mouse model of pancreatic cancer. The sensitizing effect of XIAP interference toward gemcitabine was confirmed via pharmacological intervention using our recently designed, targeted SMAC mimetic SW IV-134 across a wide range of commonly used pancreatic cancer cell lines at concentrations where the individual drugs showed only minimal activity. On a mechanistic level, we identified involvement of key components of the apoptosis machinery during cell death execution. Furthermore, combination therapy proved superior in decreasing the tumor burden and extending the lives of the animals in a preclinical mouse model of pancreatic cancer. We believe that the strong sensitizing capacity of

  9. Resolution enhancement by subtraction of confocal signals taken at different pinhole sizes.

    Science.gov (United States)

    Heintzmann, Rainer; Sarafis, Vassilios; Munroe, Paul; Nailon, John; Hanley, Quentin S; Jovin, Thomas M

    2003-01-01

    Subtractive imaging in confocal fluorescence light microscopy is based on the subtraction of a suitably weighted widefield image from a confocal image. An approximation to a widefield image can be obtained by detection with an opened confocal pinhole. The subtraction of images enhances the resolution in-plane as well as along the optic axis. Due to the linearity of the approach, the effect of subtractive imaging in Fourier-space corresponds to a reduction of low spatial frequency contributions leading to a relative enhancement of the high frequencies. Along the direction of the optic axis this also results in an improved sectioning. Image processing can achieve a similar effect. However, a 3D volume dataset must be acquired and processed, yielding a result essentially identical to subtractive imaging but superior in signal-to-noise ratio. The latter can be increased further with the technique of weighted averaging in Fourier-space. A comparison of 2D and 3D experimental data analysed with subtractive imaging, the equivalent Fourier-space processing of the confocal data only, and Fourier-space weighted averaging is presented.

  10. Enhanced anandamide signaling reduces flight behavior elicited by an approaching robo-beetle.

    Science.gov (United States)

    Heinz, Daniel E; Genewsky, Andreas; Wotjak, Carsten T

    2017-11-01

    Our current knowledge of the implications of endocannabinoids in fear and anxiety is largely based on fear conditioning paradigms and approach-avoidance conflicts. Here we establish the ethobehavioral beetle mania task (BMT), which confronts mice with an erratically moving robo-beetle. With the help of this task we demonstrate decreased tolerance yet increased avoidance responses to an approaching beetle in high-anxiety behavior (HAB) and BALBc mice compared to C57BL/6N, CD1 and normal-anxiety behavior (NAB) mice. Also DBA/2N mice showed decreased passive and increased active behavior, but followed the robo-beetle more often than HAB and BALBc mice. Treatment with diazepam (1 mg/kg) increased tolerance without affecting avoidance behavior in HAB mice. Treatment with the MAGL inhibitor JZL184 (8 mg/kg) increased flight behavior, but did not affect tolerance. The FAAH inhibitor URB597 (0.3 mg/kg), however, reduced flight behavior and enhanced tolerance to the robo-beetle. The latter effects were blocked by co-treatment with the CB1 receptor antagonist SR141716A (3 mg/kg), which failed to affect the behavior by itself. Taken together, we validate the BMT as a novel test for studying endocannabinoids beyond traditional paradigms and for assessing active fear responses in mice. Furthermore, we demonstrate panicolytic consequences of pharmacological enhancement of anandamide, but not 2-AG signaling. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Tobacco randomly inserted tt8 differenly enhance light signals and flavonoid accumulation

    International Nuclear Information System (INIS)

    Sompornpailin, K.; Kanthang, S.

    2015-01-01

    The individual lines of tobacco over-expressing TT8, a bHLH gene, were constructed and cultured under tissue culture condition radiating with photosynthetically activation radiation (PAR) or PAR+UVA. They were compared to wild type (WT). Leaf of treated plants was extracted and analyzed for flavonoid accumulations using a spectrophotometer. The extract of TT8 plants significantly contained flavone, flavonol and anthocyanin level, higher than the WT extract did. The petal extracts of mature transgenic under PAR had a similar absorbance profile of each substance, but these extracts had higher flavonoid contents than the leaf extracts did. All flavonoid subgroups and p-coumaric acid biosynthesis were significantly enhanced after the additional UVA radiation to plant. This UVA condition slightly stimulated an accumulation of these substances in normal plant. Some transgenic greatly increased flavonoid accumulation in responding to PAR+UVA, but the others were slightly different compared to WT. The distinct insertion site is directly affected TT8 gene expression. Transgenic seeds had a dark brown color more than WT seed, which indicated high content of polymer flavonoids (proanthocyanins). This over-expressing TT8 in transgenic tobacco may directly or indirectly enhance the signal transductions of PAR and UVA and raise up flavonoid accumulation. (author)

  12. Enhancing Linearity of Voltage Controlled Oscillator Thermistor Signal Conditioning Circuit Using Linear Search

    Science.gov (United States)

    Rana, K. P. S.; Kumar, Vineet; Prasad, Tapan

    2018-02-01

    Temperature to Frequency Converters (TFCs) are potential signal conditioning circuits (SCCs) usually employed in temperature measurements using thermistors. A NE/SE-566 based SCC has been recently used in several reported works as TFC. Application of NE/SE-566 based SCC requires a mechanism for finding the optimal values of SCC parameters yielding the optimal linearity and desired sensitivity performances. Two classical methods, namely, inflection point and three point have been employed for this task. In this work, the application of these two methods, on NE/SE-566 based SCC in TFC, is investigated in detail and the conditions for its effective usage are developed. Further, since these classical methods offer an approximate linearization of temperature and frequency relationship an application of a linear search based technique is proposed to further enhance the linearity. The implemented linear search method used results obtained from the above mentioned classical methods. The presented simulation studies, for three different industrial grade thermistors, revealed that the linearity enhancements of 21.7, 18.3 and 17.8% can be achieved over the inflection point method and 4.9, 4.7 and 4.7% over the three point method, for an input temperature range of 0-100 °C.

  13. Enhancement of Twins Fetal ECG Signal Extraction Based on Hybrid Blind Extraction Techniques

    Directory of Open Access Journals (Sweden)

    Ahmed Kareem Abdullah

    2017-07-01

    Full Text Available ECG machines are noninvasive system used to measure the heartbeat signal. It’s very important to monitor the fetus ECG signals during pregnancy to check the heat activity and to detect any problem early before born, therefore the monitoring of ECG signals have clinical significance and importance. For multi-fetal pregnancy case the classical filtering algorithms are not sufficient to separate the ECG signals between mother and fetal. In this paper the mixture consists of mixing from three ECG signals, the first signal is the mother ECG (M-ECG signal, second signal the Fetal-1 ECG (F1-ECG, and third signal is the Fetal-2 ECG (F2-ECG, these signals are extracted based on modified blind source extraction (BSE techniques. The proposed work based on hybridization between two BSE techniques to ensure that the extracted signals separated well. The results demonstrate that the proposed work very efficiently to extract the useful ECG signals

  14. Polarization-based enhancement of ocean color signal for estimating suspended particulate matter: radiative transfer simulations and laboratory measurements.

    Science.gov (United States)

    Liu, Jia; He, Xianqiang; Liu, Jiahang; Bai, Yan; Wang, Difeng; Chen, Tieqiao; Wang, Yihao; Zhu, Feng

    2017-04-17

    Absorption and scattering by molecules, aerosols and hydrosols, and the reflection and transmission over the sea surface can modify the original polarization state of sunlight. However, water-leaving radiance polarization, containing embedded water constituent information, has largely been neglected. Here, the efficiency of the parallel polarization radiance (PPR) for enhancing ocean color signal of suspended particulate matter is examined via vector radiative transfer simulations and laboratory experiments. The simulation results demonstrate that the PPR has a slightly higher ocean color signal at the top-of-atmosphere as compared with that of the total radiance. Moreover, both the simulations and laboratory measurements reveal that, compared with total radiance, PPR can effectively enhance the normalized ocean color signal for a large range of observation geometries, wavelengths, and suspended particle concentrations. Thus, PPR has great potential for improving the ocean color signal detection from satellite.

  15. Strong light-extraction enhancement in GaInN light-emitting diodes patterned with TiO2 micro-pillars with tapered sidewalls

    Science.gov (United States)

    Ma, Ming; Cho, Jaehee; Fred Schubert, E.; Park, Yongjo; Bum Kim, Gi; Sone, Cheolsoo

    2012-10-01

    An effective method to enhance the light extraction for GaInN light-emitting diodes (LEDs) is reported. The method employs TiO2 micro-pillars with tapered sidewalls, which are refractive-index-matched to the underlying GaN. The tapered micro-pillars are fabricated by using reflowed photoresist as mask during CHF3-based dry etch, with O2 added in order to precisely control the taper angle. LEDs patterned with TiO2 micro-pillars with tapered sidewalls show a 100% enhancement in light-output power over planar reference LEDs. The measured results are in good agreement with ray-tracing simulations, showing strong potential of optical surfaces that are controlled in terms of refractive index and lateral structure.

  16. Molecular cloning and expression of mouse and human cDNA encoding AES and ESG proteins with strong similarity to Drosophila enhancer of split groucho protein.

    Science.gov (United States)

    Miyasaka, H; Choudhury, B K; Hou, E W; Li, S S

    1993-08-15

    Mouse and human cDNA encoding AES (amino-terminal enhancer of split) and ESG (enhancer of split groucho) proteins with strong similarity to Drosophila enhancer of split groucho protein were isolated and sequenced. Mouse AES-1 and AES-2 proteins, probably resulting from alternative splicing, contain 202 and 196 amino acids, respectively, while mouse ESG protein consists of 771 amino acids. The amino acid sequences of mouse and human AES proteins were found to exhibit approximately 50% identity to the amino-terminal region of Drosophila groucho, mouse ESG and human transducin-like enhancer of split (TLE) proteins. Mouse AES transcripts of 1.5 kb and 1.2 kb were abundantly expressed in muscle, heart and brain. Human AES transcripts of 1.6 kb and 1.4 kb were predominantly present in muscle, heart and placenta. Mouse ESG (homolog of human TLE 3) transcripts of 3.3 kb and 4.0 kb were found only in testis, while human TLE 1 transcripts of 4.5 kb was more abundant in muscle and placenta compared to heart, brain, lung, liver, kidney and pancreas. Human AES, TLE 1 and TLE 3 genes were mapped to chromosomes 19, 9 and 15, respectively, using human and Chinese hamster hybrid cell lines.

  17. Arctigenin enhances chemosensitivity of cancer cells to cisplatin through inhibition of the STAT3 signaling pathway.

    Science.gov (United States)

    Yao, Xiangyang; Zhu, Fenfen; Zhao, Zhihui; Liu, Chang; Luo, Lan; Yin, Zhimin

    2011-10-01

    Arctigenin is a dibenzylbutyrolactone lignan isolated from Bardanae fructus, Arctium lappa L, Saussureamedusa, Torreya nucifera, and Ipomea cairica. It has been reported to exhibit anti-inflammatory activities, which is mainly mediated through its inhibitory effect on nuclear transcription factor-kappaB (NF-κB). But the role of arctigenin in JAK-STAT3 signaling pathways is still unclear. In present study, we investigated the effect of arctigenin on signal transducer and activator of transcription 3 (STAT3) pathway and evaluated whether suppression of STAT3 activity by arctigenin could sensitize cancer cells to a chemotherapeutic drug cisplatin. Our results show that arctigenin significantly suppressed both constitutively activated and IL-6-induced STAT3 phosphorylation and subsequent nuclear translocation in cancer cells. Inhibition of STAT3 tyrosine phosphorylation was found to be achieved through suppression of Src, JAK1, and JAK2, while suppression of STAT3 serine phosphorylation was mediated by inhibition of ERK activation. Pervanadate reversed the arctigenin-induced downregulation of STAT3 activation, suggesting the involvement of a protein tyrosine phosphatase. Indeed, arctigenin can obviously induce the expression of the PTP SHP-2. Furthermore, the constitutive activation level of STAT3 was found to be correlated to the resistance of cancer cells to cisplatin-induced apoptosis. Arctigenin dramatically promoted cisplatin-induced cell death in cancer cells, indicating that arctigenin enhanced the sensitivity of cancer cells to cisplatin mainly via STAT3 suppression. These observations suggest a novel anticancer function of arctigenin and a potential therapeutic strategy of using arctigenin in combination with chemotherapeutic agents for cancer treatment. Copyright © 2011 Wiley-Liss, Inc.

  18. CD70 reverse signaling enhances NK cell function and immunosurveillance in CD27-expressing B-cell malignancies.

    Science.gov (United States)

    Al Sayed, Mohamad F; Ruckstuhl, Carla A; Hilmenyuk, Tamara; Claus, Christina; Bourquin, Jean-Pierre; Bornhauser, Beat C; Radpour, Ramin; Riether, Carsten; Ochsenbein, Adrian F

    2017-07-20

    The interaction of the tumor necrosis factor receptor (TNFR) CD27 with its ligand CD70 is an emerging target to treat cancer. CD27 signaling provides costimulatory signals to cytotoxic T cells but also increases the frequency of regulatory T cells. Similar to other TNFR ligands, CD70 has been shown to initiate intracellular signaling pathways (CD70 reverse signaling). CD27 is expressed on a majority of B-cell non-Hodgkin lymphoma, but its role in the immune control of lymphoma and leukemia is unknown. We therefore generated a cytoplasmic deletion mutant of CD27 (CD27-trunc) to study the role of CD70 reverse signaling in the immunosurveillance of B-cell malignancies in vivo. Expression of CD27-trunc on malignant cells increased the number of tumor-infiltrating interferon γ-producing natural killer (NK) cells. In contrast, the antitumoral T-cell response remained largely unchanged. CD70 reverse signaling in NK cells was mediated via the AKT signaling pathway and increased NK cell survival and effector function. The improved immune control by activated NK cells prolonged survival of CD27-trunc-expressing lymphoma-bearing mice. Finally, CD70 reverse signaling enhanced survival and effector function of human NK cells in a B-cell acute lymphoblastic leukemia xenotransplants model. Therefore, CD70 reverse signaling in NK cells contributes to the immune control of CD27-expressing B-cell lymphoma and leukemia. © 2017 by The American Society of Hematology.

  19. Expression of Caveolin 1 is enhanced by DNA demethylation during adipocyte differentiation. status of insulin signaling.

    Science.gov (United States)

    Palacios-Ortega, Sara; Varela-Guruceaga, Maider; Milagro, Fermín Ignacio; Martínez, José Alfredo; de Miguel, Carlos

    2014-01-01

    Caveolin 1 (Cav-1) is an essential constituent of adipocyte caveolae which binds the beta subunit of the insulin receptor (IR) and is implicated in the regulation of insulin signaling. We have found that, during adipocyte differentiation of 3T3-L1 cells the promoter, exon 1 and first intron of the Cav-1 gene undergo a demethylation process that is accompanied by a strong induction of Cav-1 expression, indicating that epigenetic mechanisms must have a pivotal role in this differentiation process. Furthermore, IR, PKB-Akt and Glut-4 expression are also increased during the differentiation process suggesting a coordinated regulation with Cav-1. Activation of Cav-1 protein by phosphorylation arises during the differentiation process, yet in fully mature adipocytes insulin is no longer able to significantly increase Cav-1 phosphorylation. However, these long-term differentiated cells are still able to respond adequately to insulin, increasing IR and PKB-Akt phosphorylation and glucose uptake. The activation of Cav-1 during the adipocyte differentiation process could facilitate the maintenance of insulin sensitivity by these fully mature adipocytes isolated from additional external stimuli. However, under the influence of physiological conditions associated to obesity, such as chronic inflammation and hypoxia, insulin sensitivity would finally be compromised.

  20. Dietary fiber enhances TGF-β signaling and growth inhibition in the gut.

    Science.gov (United States)

    Cao, Yanna; Gao, Xuxia; Zhang, Weili; Zhang, Guohua; Nguyen, Anthony K; Liu, Xianghua; Jimenez, Fernando; Cox, Charles S; Townsend, Courtney M; Ko, Tien C

    2011-07-01

    Dietary fiber intake links to decreased risk of colorectal cancers. The underlying mechanisms remain unclear. Recently, we found that butyrate, a short-chain fatty acid produced in gut by bacterial fermentation of dietary fiber, enhances TGF-β signaling in rat intestinal epithelial cells (RIE-1). Furthermore, TGF-β represses inhibitors of differentiation (Ids), leading to apoptosis. We hypothesized that dietary fiber enhances TGF-β's growth inhibitory effects on gut epithelium via inhibition of Id2. In this study, Balb/c and DBA/2N mice were fed with a regular rodent chow or supplemented with a dietary fiber (20% pectin) and Smad3 level in gut epithelium was measured. In vitro, RIE-1 cells were treated with butyrate and TGF-β(1), and cell functions were evaluated. Furthermore, the role of Ids in butyrate- and TGF-β-induced growth inhibition was investigated. We found that pectin feeding increased Smad3 protein levels in the jejunum (1.47 ± 0.26-fold, P = 0.045, in Balb/c mice; 1.49 ± 0.19-fold, P = 0.016, in DBA/2N mice), and phospho-Smad3 levels (1.92 ± 0.27-fold, P = 0.009, in Balb/c mice; 1.83 ± 0.28-fold, P = 0.022, in DBA/2N mice). Butyrate or TGF-β alone inhibited cell growth and induced cell cycle arrest. The combined treatment of butyrate and TGF-β synergistically induced cell cycle arrest and apoptosis in RIE-1 cells and repressed Id2 and Id3 levels. Furthermore, knockdown of Id2 gene expression by use of small interfering RNA caused cell cycle arrest and apoptosis. We conclude that dietary fiber pectin enhanced Smad3 expression and activation in the gut. Butyrate and TGF-β induced cell cycle arrest and apoptosis, which may be mediated by repression of Id2. Our results implicate a novel mechanism of dietary fiber in reducing the risk of colorectal cancer development.

  1. Controlled Growth of Gold Nanostars: Effect of Spike Length on SERS Signal Enhancement.

    Science.gov (United States)

    Sheen Mers, S V; Umadevi, S; Ganesh, V

    2017-05-19

    Two different types of gold nanostars (Au NS), namely, short-spiked nanostars (SSNS) and long-spiked nanostars (LSNS), are prepared by using a hexagonal lyotropic liquid-crystalline (LLC) phase as a template. The formation, size and length of spikes or arms of the resultant Au NS are controlled by preparation in either a hexagonal LLC phase or an isotropic phase. These NS are anchored onto indium tin oxide (ITO) electrodes through a self-assembled monolayer of 3-mercaptopropyltrimethoxysilane, which acts as a linker molecule. Structural and morphological characterisations of SSNS- and LSNS-anchored ITO electrodes are performed by means of microscopic and spectroscopic analyses. Further electrochemical techniques, namely, cyclic voltammetry and electrochemical impedance spectroscopy, are also used to confirm the immobilisation of these Au NS on ITO electrodes and to study the electrochemical characteristics. These studies clearly reveal the formation of star-shaped, branched, anisotropic nanostructures of gold during the template preparation method and these Au NS are successfully anchored onto ITO electrodes through a covalent immobilisation strategy. Furthermore, the SERS activity of these Au NS is analysed by using glutathione and crystal violet as analytes and by employing glass and ITO as substrates. It is interesting to note that SSNS show a significant enhancement in SERS signals relative to those of LSNS. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Glycer-AGEs-RAGE signaling enhances the angiogenic potential of hepatocellular carcinoma by upregulating VEGF expression.

    Science.gov (United States)

    Takino, Junichi; Yamagishi, Shoichi; Takeuchi, Masayoshi

    2012-04-21

    To investigate the effect of glyceraldehyde-derived advanced glycation end-products (Glycer-AGEs) on hepatocellular carcinoma (HCC) cells. Two HCC cell lines (Hep3B and HepG2 cells) and human umbilical vein endothelial cells (HUVEC) were used. Cell viability was determined using the WST-8 assay. Western blotting, enzyme linked immunosorbent assay, and real-time reverse transcription-polymerase chain reactions were used to detect protein and mRNA. Angiogenesis was evaluated by assessing the proliferation, migration, and tube formation of HUVEC. The receptor for AGEs (RAGE) protein was detected in Hep3B and HepG2 cells. HepG2 cells were not affected by the addition of Glycer-AGEs. Glycer-AGEs markedly increased vascular endothelial growth factor (VEGF) mRNA and protein expression, which is one of the most potent angiogenic factors. Compared with the control unglycated bovine serum albumin (BSA) treatment, VEGF mRNA expression levels induced by the Glycer-AGEs treatment were 1.00 ± 0.10 vs 1.92 ± 0.09 (P RAGE signaling enhances the angiogenic potential of HCC cells by upregulating VEGF expression.

  3. Immersive audiomotor game play enhances neural and perceptual salience of weak signals in noise.

    Science.gov (United States)

    Whitton, Jonathon P; Hancock, Kenneth E; Polley, Daniel B

    2014-06-24

    All sensory systems face the fundamental challenge of encoding weak signals in noisy backgrounds. Although discrimination abilities can improve with practice, these benefits rarely generalize to untrained stimulus dimensions. Inspired by recent findings that action video game training can impart a broader spectrum of benefits than traditional perceptual learning paradigms, we trained adult humans and mice in an immersive audio game that challenged them to forage for hidden auditory targets in a 2D soundscape. Both species learned to modulate their angular search vectors and target approach velocities based on real-time changes in the level of a weak tone embedded in broadband noise. In humans, mastery of this tone in noise task generalized to an improved ability to comprehend spoken sentences in speech babble noise. Neural plasticity in the auditory cortex of trained mice supported improved decoding of low-intensity sounds at the training frequency and an enhanced resistance to interference from background masking noise. These findings highlight the potential to improve the neural and perceptual salience of degraded sensory stimuli through immersive computerized games.

  4. Dengue vaccine safety signal: Immune enhancement, waning immunity, or chance occurrence?

    Science.gov (United States)

    Gessner, Bradford D; Halsey, Neal

    2017-06-14

    A new dengue vaccine was associated with increased risk of hospitalized virologically-confirmed disease during year 3 of follow-up among children age 2-5years. Among hypotheses to explain this finding, we could not distinguish definitively between antibody dependent enhancement, waning immunity, or chance occurrence. However, any theory must account for the following: (a) the signal occurred mainly because of decreased dengue among controls rather than increased dengue among vaccinees; (b) among 48 data points, a statistically significant increase in hospitalization among vaccinated children occurred for only one age group, during one year, and in one region; (c) cumulative risk was similar for vaccinated vs. control children age 2-5years at the end of year 5 and lower for vaccinated vs. control children among older age groups; (d) the protective effect of vaccine against hospitalization decreased from years 1-2 to years 3-5 of follow-up for all age groups and regions. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  5. Enhancement of signal sensitivity in a heterogeneous neural network refined from synaptic plasticity

    Energy Technology Data Exchange (ETDEWEB)

    Li Xiumin; Small, Michael, E-mail: ensmall@polyu.edu.h, E-mail: 07901216r@eie.polyu.edu.h [Department of Electronic and Information Engineering, Hong Kong Polytechnic University, Hung Hom, Kowloon (Hong Kong)

    2010-08-15

    Long-term synaptic plasticity induced by neural activity is of great importance in informing the formation of neural connectivity and the development of the nervous system. It is reasonable to consider self-organized neural networks instead of prior imposition of a specific topology. In this paper, we propose a novel network evolved from two stages of the learning process, which are respectively guided by two experimentally observed synaptic plasticity rules, i.e. the spike-timing-dependent plasticity (STDP) mechanism and the burst-timing-dependent plasticity (BTDP) mechanism. Due to the existence of heterogeneity in neurons that exhibit different degrees of excitability, a two-level hierarchical structure is obtained after the synaptic refinement. This self-organized network shows higher sensitivity to afferent current injection compared with alternative archetypal networks with different neural connectivity. Statistical analysis also demonstrates that it has the small-world properties of small shortest path length and high clustering coefficients. Thus the selectively refined connectivity enhances the ability of neuronal communications and improves the efficiency of signal transmission in the network.

  6. Performance Analysis and Enhancements for the Music Subspace Direction-Finding Algorithm in the Presence of Wideband Signals

    Science.gov (United States)

    2014-12-01

    signals classification ( MUSIC ) subspace direction-finding algorithm are evaluated in this thesis. Additionally, two performance enhancements are...presented: one that reduces the MUSIC computational load and one that provides a method of utilizing collector motion to resolve DOA ambiguities.

  7. Strong enhancement of emission efficiency in GaN light-emitting diodes by plasmon-coupled light amplification of graphene

    Science.gov (United States)

    Kim, Jong Min; Kim, Sung; Hwang, Sung Won; Kim, Chang Oh; Shin, Dong Hee; Kim, Ju Hwan; Jang, Chan Wook; Kang, Soo Seok; Hwang, Euyheon; Choi, Suk-Ho; El-Gohary, Sherif H.; Byun, Kyung Min

    2018-02-01

    Recently, we have demonstrated that excitation of plasmon-polaritons in a mechanically-derived graphene sheet on the top of a ZnO semiconductor considerably enhances its light emission efficiency. If this scheme is also applied to device structures, it is then expected that the energy efficiency of light-emitting diodes (LEDs) increases substantially and the commercial potential will be enormous. Here, we report that the plasmon-induced light coupling amplifies emitted light by ∼1.6 times in doped large-area chemical-vapor-deposition-grown graphene, which is useful for practical applications. This coupling behavior also appears in GaN-based LEDs. With AuCl3-doped graphene on Ga-doped ZnO films that is used as transparent conducting electrodes for the LEDs, the average electroluminescence intensity is 1.2–1.7 times enhanced depending on the injection current. The chemical doping of graphene may produce the inhomogeneity in charge densities (i.e., electron/hole puddles) or roughness, which can play a role as grating couplers, resulting in such strong plasmon-enhanced light amplification. Based on theoretical calculations, the plasmon-coupled behavior is rigorously explained and a method of controlling its resonance condition is proposed.

  8. Wavelet transform of signal for enhancement of SNR in wire rope inspection

    Science.gov (United States)

    Lunin, V.; Barat, V.

    2002-05-01

    In magnetic testing of steel wire rope the MFL signals of broken wires may be corrupted by background noise arising from the probe lift-off, vibration and white noise, resulting in unreliable detection and inaccurate characterization of rope weakness. In this paper, a signal processing technique is presented to reduce this background noise by the use of a wavelet transform. The results of processing signals from testing rope pieces show that proposed technique is effective for extracting defect signals.

  9. Viral double-strand RNA-binding proteins can enhance innate immune signaling by toll-like Receptor 3.

    Directory of Open Access Journals (Sweden)

    Yvonne Lai

    Full Text Available Toll-like Receptor 3 (TLR3 detects double-stranded (ds RNAs to activate innate immune responses. While poly(I:C is an excellent agonist for TLR3 in several cell lines and in human peripheral blood mononuclear cells, viral dsRNAs tend to be poor agonists, leading to the hypothesis that additional factor(s are likely required to allow TLR3 to respond to viral dsRNAs. TLR3 signaling was examined in a lung epithelial cell line by quantifying cytokine production and in human embryonic kidney cells by quantifying luciferase reporter levels. Recombinant 1b hepatitis C virus polymerase was found to enhance TLR3 signaling in the lung epithelial BEAS-2B cells when added to the media along with either poly(I:C or viral dsRNAs. The polymerase from the genotype 2a JFH-1 HCV was a poor enhancer of TLR3 signaling until it was mutated to favor a conformation that could bind better to a partially duplexed RNA. The 1b polymerase also co-localizes with TLR3 in endosomes. RNA-binding capsid proteins (CPs from two positive-strand RNA viruses and the hepadenavirus hepatitis B virus (HBV were also potent enhancers of TLR3 signaling by poly(I:C or viral dsRNAs. A truncated version of the HBV CP that lacked an arginine-rich RNA-binding domain was unable to enhance TLR3 signaling. These results demonstrate that several viral RNA-binding proteins can enhance the dsRNA-dependent innate immune response initiated by TLR3.

  10. Melatonin Enhances Phenolics Accumulation Partially via Ethylene Signaling and Resulted in High Antioxidant Capacity in Grape Berries

    Directory of Open Access Journals (Sweden)

    Lili Xu

    2017-08-01

    Full Text Available This study assessed the primary impacts of exogenous melatonin (MT treatment on grape berry metabolism. Exogenous MT treatment increased the endogenous MT content and modified berry ripening. Transcriptomic analysis revealed that the processes of polyphenol metabolism, carbohydrate metabolism and ethylene biosynthesis and signaling were the three most significantly altered biological processes upon MT treatment. Further experiments verified that MT treatment increased the contents of total anthocyanins, phenols, flavonoids and proanthocyanidins in berries. Additionally, the contents of 18 of the 22 detected individual phenolic compounds were enhanced by MT treatment; particularly, the resveratrol content was largely increased concomitantly with the up-regulation of STS gene expression. Meanwhile, MT treatment enhanced the antioxidant capacity of berries. On the other hand, it was indicated that ethylene participated in the regulation of polyphenol metabolism and antioxidant capacity under MT treatment in grape berries. In summary, MT enhances the polyphenol content and antioxidant capacity of grape berries partially via ethylene signaling.

  11. Enhanced signal dispersion in saturation transfer difference experiments by conversion to a 1D-STD-homodecoupled spectrum

    International Nuclear Information System (INIS)

    Martin-Pastor, Manuel; Vega-Vazquez, Marino; Capua, Antonia De; Canales, Angeles; Andre, Sabine; Gabius, Hans-Joachim; Jimenez-Barbero, Jesus

    2006-01-01

    The saturation transfer difference (STD) experiment is a rich source of information on topological aspects of ligand binding to a receptor. The epitope mapping is based on a magnetization transfer after signal saturation from the receptor to the ligand, where interproton distances permit this process. Signal overlap in the STD spectrum can cause difficulties to correctly assign and/or quantitate the measured enhancements. To address this issue we report here a modified version of the routine experiment and a processing scheme that provides a 1D-STD homodecoupled spectrum (i.e. an experiment in which all STD signals appear as singlets) with line widths similar to those in original STD spectrum. These refinements contribute to alleviate problems of signal overlap. The experiment is based on 2D-J-resolved spectroscopy, one of the fastest 2D experiments under conventional data sampling in the indirect dimension, and provides excellent sensitivity, a key factor for the difference experiments

  12. Enhanced signal dispersion in saturation transfer difference experiments by conversion to a 1D-STD-homodecoupled spectrum

    Energy Technology Data Exchange (ETDEWEB)

    Martin-Pastor, Manuel; Vega-Vazquez, Marino [Universidade de Santiago de Compostela, Laboratorio Integral de Dinamica e Estructura de Biomoleculas Jose R. Carracido, Unidade de Resonancia Magnetica, Edificio CACTUS, RIAIDT (Spain); Capua, Antonia De [Seconda Universita degli Studi di Napoli, Dipartimento di Scienze Ambientali (Italy); Canales, Angeles [Centro de Investigaciones Biologicas, CSIC, Departamento de Estructura y funcion de proteinas (Spain); Andre, Sabine; Gabius, Hans-Joachim [Ludwig-Maximilians-Universitaet, Institut fuer Physiologische Chemie, Tieraerztliche Fakultaet (Germany); Jimenez-Barbero, Jesus [Centro de Investigaciones Biologicas, CSIC, Departamento de Estructura y funcion de proteinas (Spain)], E-mail: JJbarbero@cib.csic.es

    2006-10-15

    The saturation transfer difference (STD) experiment is a rich source of information on topological aspects of ligand binding to a receptor. The epitope mapping is based on a magnetization transfer after signal saturation from the receptor to the ligand, where interproton distances permit this process. Signal overlap in the STD spectrum can cause difficulties to correctly assign and/or quantitate the measured enhancements. To address this issue we report here a modified version of the routine experiment and a processing scheme that provides a 1D-STD homodecoupled spectrum (i.e. an experiment in which all STD signals appear as singlets) with line widths similar to those in original STD spectrum. These refinements contribute to alleviate problems of signal overlap. The experiment is based on 2D-J-resolved spectroscopy, one of the fastest 2D experiments under conventional data sampling in the indirect dimension, and provides excellent sensitivity, a key factor for the difference experiments.

  13. A p38 Mitogen-Activated Protein Kinase-Regulated Myocyte Enhancer Factor 2–β-Catenin Interaction Enhances Canonical Wnt Signaling

    Science.gov (United States)

    Ehyai, Saviz; Dionyssiou, Mathew G.; Gordon, Joseph W.; Williams, Declan; Siu, K. W. Michael

    2015-01-01

    Canonical Wnt/β-catenin signaling plays a major role in various biological contexts, such as embryonic development, cell proliferation, and cancer progression. Previously, a connection between p38 mitogen-activated protein kinase (MAPK) signaling and Wnt-mediated activation of β-catenin was implied but poorly understood. In the present study, we investigated potential cross talk between p38 MAPK and Wnt/β-catenin signaling. Here we show that a loss of p38 MAPK α/β function reduces β-catenin nuclear accumulation in Wnt3a-stimulated primary vascular smooth muscle cells (VSMCs). Conversely, active p38 MAPK signaling increases β-catenin nuclear localization and target gene activity in multiple cell types. Furthermore, the effect of p38 MAPK α/β on β-catenin activity is mediated through phosphorylation of a key p38 MAPK target, myocyte enhancer factor 2 (MEF2). Here we report a p38 MAPK-mediated, phosphorylation-dependent interaction between MEF2 and β-catenin in multiple cell types and primary VSMCs that results in (i) increased β-catenin nuclear retention, which is reversed by small interfering RNA (siRNA)-mediated MEF2 gene silencing; (ii) increased activation of MEF2 and Wnt/β-catenin target genes; and (iii) increased Wnt-stimulated cell proliferation. These observations provide mechanistic insight into a fundamental level of cross talk between p38 MAPK/MEF2 signaling and canonical Wnt signaling. PMID:26552705

  14. Caffeic acid phenethylester increases stress resistance and enhances lifespan in Caenorhabditis elegans by modulation of the insulin-like DAF-16 signalling pathway.

    Science.gov (United States)

    Havermann, Susannah; Chovolou, Yvonni; Humpf, Hans-Ulrich; Wätjen, Wim

    2014-01-01

    CAPE is an active constituent of propolis which is widely used in traditional medicine. This hydroxycinnamic acid derivate is a known activator of the redox-active Nrf2 signalling pathway in mammalian cells. We used C. elegans to investigate the effects of this compound on accumulation of reactive oxygen species and the modulation of the pivotal redox-active pathways SKN-1 and DAF-16 (homologues of Nrf2 and FoxO, respectively) in this model organism; these results were compared to the effects in Hct116 human colon carcinoma cells. CAPE exerts a strong antioxidative effect in C. elegans: The increase of reactive oxygen species induced by thermal stress was diminished by about 50%. CAPE caused a nuclear translocation of DAF-16, but not SKN-1. CAPE increased stress resistance of the nematode against thermal stress and finally a prolongation of the median and maximum lifespan by 9 and 17%, respectively. This increase in stress resistance and lifespan was dependent on DAF-16 as shown in experiments using a DAF-16 loss of function mutant strain. Life prolongation was retained under SKN-1 RNAi conditions showing that the effect is SKN-1 independent. The results of CAPE obtained in C. elegans differed from the results obtained in Hct116 colon carcinoma cells: CAPE also caused strong antioxidative effects in the mammalian cells, but no activation of the FoxO4 signalling pathway was detectable. Instead, an activation of the Nrf2 signalling pathway was shown by luciferase assay and western blots. CAPE activates the insulin-like DAF-16, but not the SKN-1 signalling pathway in C. elegans and therefore enhances the stress resistance and lifespan of this organism. Since modulation of the DAF-16 pathway was found to be a pivotal effect of CAPE in C. elegans, this has to be taken into account for the investigation of the molecular mechanisms of the traditional use of propolis.

  15. Strong evidence for enhanced multiple electron capture from surfaces in 46 MeV/u Pb81+ collisions with thin carbon foils.

    Science.gov (United States)

    Bräuning, H; Mokler, P H; Liesen, D; Bosch, F; Franzke, B; Krämer, A; Kozhuharov, C; Ludziejewski, T; Ma, X; Nolden, F; Steck, M; Stöhlker, T; Dunford, R W; Kanter, E P; Bednarz, G; Warczak, A; Stachura, Z; Tribedi, L; Kambara, T; Dauvergne, D; Kirsch, R; Cohen, C

    2001-02-05

    Strong evidence has been found for enhanced multiple electron capture into 46 MeV/u Pb81+ with a significant contribution from the entrance surface of thin carbon foils. Capture of up to five electrons has been observed. The multiple electron capture yield is found to increase with decreasing target thickness for thin targets. A simple model describing the data and showing the importance of capture from surfaces is discussed. Further evidence is found for a pronounced asymmetry between electron capture at the entrance and the exit surfaces. Absolute yields for multiple electron capture and projectile ionization are presented. The experimental total cross sections for single capture and ionization agree well with theory.

  16. Extreme enhancement of blocking temperature by strong magnetic dipoles interaction of α-Fe nanoparticle-based high-density agglomerate

    International Nuclear Information System (INIS)

    Kura, H; Takahashi, M; Ogawa, T

    2011-01-01

    High-volume fraction α-Fe nanoparticle (NP) agglomerates were prepared using chemically synthesized NPs. In the agglomerate, NPs are separated by surfactant and NP superlattice with a hexagonal close-packed structure is locally realized. Volume fractions of NPs at 20% and 42% were obtained in agglomerates consisting of 2.9 nm and 8.2 nm diameter NPs, respectively. The high saturation magnetization of α-Fe NPs and high volume fraction of NPs in the agglomerate provide strong magnetic dipole-dipole interaction. The interaction energy of the agglomerate became much larger than the anisotropic energy of individual NPs. As a result, the blocking temperature of the 8.2 nm NP agglomerate was significantly enhanced from 52.2 K to around 500 K. (fast track communication)

  17. Detection of aflatoxin B₁ with immunochromatographic test strips: Enhanced signal sensitivity using gold nanoflowers.

    Science.gov (United States)

    Ji, Yanwei; Ren, Meiling; Li, Yanping; Huang, Zhibing; Shu, Mei; Yang, Hongwei; Xiong, Yonghua; Xu, Yang

    2015-09-01

    Immunochromatographic test strips (ICTS) are commonly limited to higher concentrations of analytes. This limitation stems from the relatively low sensitivity of conventional gold nanospheres (AuNSs with a diameter of 20 nm) to emit detectable brightness values. The larger multi-branched gold nanoflowers (AuNFs) with a higher optical brightness as well as good colloidal stability exhibit significant improvements over conventional AuNSs for enhanced sensitivity of ICTS. In this study, blue AuNFs with an average diameter of 75±5 nm were synthetized and employed as a signal amplification probe for ultrasensitive and quantitative detection of aflatoxin B1 (AFB1) in rice. A portable optical strip reader was used to record the optical densities of test and control lines of the strip. Under the optimal conditions, the AuNF based ICTS system accurately detected AFB1 linearly and dynamically over the range of 0.5-25 pg/mL with a half maximal inhibitory concentration at 4.17 pg/mL. The inhibitory concentration was achieved 10 times lower than that of the traditional AuNS based ICTS systems (41.25 pg/mL). The limit of detection for AFB1 in rice extract was achieved at 0.32 pg/mL. In summary, AuNFs are a novel probe that exhibited excellent sensitivity in the ICTS system and could be used for ultrasensitive detection of other analytes in food safety monitoring, and even medical diagnostics. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Severe Dermatomyositis Triggered by Interferon Beta-1a Therapy and Associated With Enhanced Type I Interferon Signaling

    Science.gov (United States)

    Somani, Ally-Khan; Swick, Alan R.; Cooper, Kevin D.; McCormick, Thomas S.

    2013-01-01

    Background Type I interferons (IFNs) are common therapeutics for several diseases, including viral infections and multiple sclerosis (MS). Although numerous studies have implicated type I INFs with the production of autoantibodies and the development of certain autoimmune disorders, interferon beta has not previously been described in association with dermatomyositis, to our knowledge. Previous microarray studies of muscle biopsy specimens from patients with dermatomyositis disclosed a type I IFN–induced gene expression profile. The central role of plasmacytoid dendritic cell precursors, together with increased type IIFN production, suggests a pivotal role for type I IFNs in dermatomyositis. We report a case of dermatomyositis exacerbated or induced by interferon beta therapy for MS and provide evidence that demonstrates enhanced type I IFN signaling in this patient. Observations We observed new-onset dermatomyositis in a 57-year-old patient treated with interferon beta for MS. His symptoms were exacerbated temporally by interferon beta injections. Immunohistochemical staining of skin biopsy specimens for myxovirus-resistance protein A (a surrogate marker for cutaneous type I IFN signaling) showed increased staining that correlated temporally with interferon beta treatment and subsequent disease activity. In vitro treatment with interferon beta of peripheral blood mononuclear cells isolated from our patient revealed enhanced type I IFN signaling assessed by interferon-induced gene expression profiles. Conclusions To our knowledge, this is the first description of dermatomyositis exacerbated or induced by interferon beta treatment. Our results demonstrate enhanced type I IFN signaling following interferon beta treatment in our patient with dermatomyositis. PMID:18936398

  19. Enhancing Brassinosteroid Signaling via Overexpression of Tomato (Solanum lycopersicum SlBRI1 Improves Major Agronomic Traits

    Directory of Open Access Journals (Sweden)

    Shuming Nie

    2017-08-01

    Full Text Available Brassinosteroids (BRs play important roles in plant growth, development, and stress responses through the receptor, Brassinosteroid-insensitive 1 (BRI1, which perceives BRs and initiates BR signaling. There is considerable potential agricultural value in regulating BR signaling in crops. In this study, we investigated the effects of overexpressing the tomato (Solanum lycopersicum BRI1 gene, SlBRI1, on major agronomic traits, such as seed germination, vegetative growth, fruit ethylene production, carotenoid accumulation, yield, and quality attributes. SlBRI1 overexpression enhanced the endogenous BR signaling intensity thereby increasing the seed germination rate, lateral root number, hypocotyl length, CO2 assimilation, plant height, and flower size. The transgenic plants also showed an increase in fruit yield and fruit number per plant, although the mean weight of individual fruit was reduced, compared with wild type. SlBRI1 overexpression also promoted fruit ripening and ethylene production, and caused an increase in levels of carotenoids, ascorbic acid, soluble solids, and soluble sugars during fruit ripening. An increased BR signaling intensity mediated by SlBRI1 overexpression was therefore positively correlated with carotenoid accumulation and fruit nutritional quality. Our results indicate that enhancing BR signaling by overexpression of SlBRI1 in tomato has the potential to improve multiple major agronomic traits.

  20. Active elimination of radio frequency interference for improved signal-to-noise ratio for in-situ NMR experiments in strong magnetic field gradients

    Science.gov (United States)

    Ibrahim, M.; Pardi, C. I.; Brown, T. W. C.; McDonald, P. J.

    2018-02-01

    Improvement in the signal-to-noise ratio of Nuclear Magnetic Resonance (NMR) systems may be achieved either by increasing the signal amplitude or by decreasing the noise. The noise has multiple origins - not all of which are strictly "noise": incoherent thermal noise originating in the probe and pre-amplifiers, probe ring down or acoustic noise and coherent externally broadcast radio frequency transmissions. The last cannot always be shielded in open access experiments. In this paper, we show that pulsed, low radio-frequency data communications are a significant source of broadcast interference. We explore two signal processing methods of de-noising short T2∗ NMR experiments corrupted by these communications: Linear Predictive Coding (LPC) and the Discrete Wavelet Transform (DWT). Results are shown for numerical simulations and experiments conducted under controlled conditions with pseudo radio frequency interference. We show that both the LPC and DWT methods have merit.

  1. Mapping one strong 'Ohana: using network analysis and GIS to enhance the effectiveness of a statewide coalition to prevent child abuse and neglect.

    Science.gov (United States)

    Cardazone, Gina; U Sy, Angela; Chik, Ivan; Corlew, Laura Kate

    2014-06-01

    Network analysis and GIS enable the presentation of meaningful data about organizational relationships and community characteristics, respectively. Together, these tools can provide a concrete representation of the ecological context in which coalitions operate, and may help coalitions identify opportunities for growth and enhanced effectiveness. This study uses network analysis and GIS mapping as part of an evaluation of the One Strong 'Ohana (OSO) campaign. The OSO campaign was launched in 2012 via a partnership between the Hawai'i Children's Trust Fund (HCTF) and the Joyful Heart Foundation. The OSO campaign uses a collaborative approach aimed at increasing public awareness of child maltreatment and protective factors that can prevent maltreatment, as well as enhancing the effectiveness of the HCTF Coalition. This study focuses on three elements of the OSO campaign evaluation: (1) Network analysis exploring the relationships between 24 active Coalition member organizations, (2) GIS mapping of responses to a randomized statewide phone survey (n = 1,450) assessing awareness of factors contributing to child maltreatment, and (3) Combined GIS maps and network data, illustrating opportunities for geographically-targeted coalition building and public awareness activities.

  2. Jun and Fos related gene products bind to and modulate the GPE I, a strong enhancer element of the rat glutathione transferase P gene.

    Science.gov (United States)

    Oridate, N; Nishi, S; Inuyama, Y; Sakai, M

    1994-10-18

    The rat glutathione transferase P gene has a strong enhancer element, termed GPE I, which is composed of a dyad of palindromicly oriented TPA (phorbol 12-O-tetradecanoate 13-acetate) responsive element (TRE)-like sequences. TRE is a binding sequence of the transcription factor AP-1, which consists of several closely related proteins belonging to the Jun and Fos family. The gel retardation experiments show that all the heterodimers formed between the Jun and Fos related gene products bind to the GPE I as well as to the TRE. In spite of the fact that the GPE I has a stronger activity than the TRE, the binding affinities of these heterodimers to the GPE I are much lower than to the TRE. Co-transfection studies of the reporter construct containing the GPE I and expression constructs of each of the Jun and Fos family cDNAs indicate that FosB and delta FosB repress transcription through the GPE I enhancer. These results suggests that some of Jun/Fos family may regulate the rat GST-P gene expression through the GPE I in vivo.

  3. Volatile anaesthetics enhance the metastasis related cellular signalling including CXCR2 of ovarian cancer cells.

    Science.gov (United States)

    Iwasaki, Masae; Zhao, Hailin; Jaffer, Tanweer; Unwith, Sandeep; Benzonana, Laura; Lian, Qingquan; Sakamoto, Atsuhiro; Ma, Daqing

    2016-05-03

    The majority of ovarian cancer patients relapse after surgical resection. Evidence is accumulating regarding the role of surgery in disseminating cancer cells; in particular anaesthesia may have an impact on cancer re-occurrence. Here, we have investigated the metastatic potential of volatile anaesthetics isoflurane, sevoflurane and desflurane on ovarian cancer cells. Human ovarian carcinoma cells (SKOV3) were exposed to isoflurane (2%), sevoflurane (3.6%) or desflurane (10.3%) for 2 hours. Metastatic related gene expression profiles were measured using the Tumour Metastasis PCR Array and qRT-PCR. Subsequently vascular endothelial growth factor A (VEGF-A), matrix metalloproteinase 11 (MMP11), transforming growth factor beta-1 (TGF-β1) and chemokine (C-X-C motif) receptor 2 (CXCR2) proteins expression were determined using immunofluorescent staining. The migratory capacities of SK-OV3 cells were assessed with a scratch assay and the potential role of CXCR2 in mediating the effects of volatile anaesthetics on cancer cell biology were further investigated with CXCR2 knockdown by siRNA. All three volatile anaesthetics altered expression of 70 out of 81 metastasic related genes with significant increases in VEGF-A, MMP-11, CXCR2 and TGF-β genes and protein expression with a magnitude order of desflurane (greatest), sevoflurane and isoflurane. Scratch analysis revealed that exposure to these anesthetics increased migration, which was abolished by CXCR2 knockdown. Volatile anaesthetics at clinically relevant concentrations have strong effects on cancer cell biology which in turn could enhance ovarian cancer metastatic potential. This work raises the urgency for further in vivo studies and clinical trials before any conclusions can be made in term of the alteration of clinical practice.

  4. Enhanced endogenous bone morphogenetic protein signaling protects against bleomycin induced pulmonary fibrosis.

    Science.gov (United States)

    De Langhe, Ellen; Cailotto, Frederic; De Vooght, Vanessa; Aznar-Lopez, Carolina; Vanoirbeek, Jeroen Alfons; Luyten, Frank Prosper; Lories, Rik Jozef Urbain

    2015-03-15

    Effective treatments for fibrotic diseases such as idiopathic pulmonary fibrosis are largely lacking. Transforming growth factor beta (TGFβ) plays a central role in the pathophysiology of fibrosis. We hypothesized that bone morphogenetic proteins (BMP), another family within the TGFβ superfamily of growth factors, modulate fibrogenesis driven by TGFβ. We therefore studied the role of endogenous BMP signaling in bleomycin induced lung fibrosis. Lung fibrosis was induced in wild-type or noggin haploinsufficient (Nog +/LacZ ) mice by intratracheal instillation of bleomycin, or phosphate buffered saline as a control. Invasive pulmonary function tests were performed using the flexiVent® SCIREQ system. The mice were sacrificed and lung tissue was collected for analysis using histopathology, collagen quantification, immunohistochemistry and gene expression analysis. Nog +/LacZ mice are a known model of increased BMP signaling and were partially protected from bleomycin-induced lung fibrosis with reduced Ashcroft score, reduced collagen content and preservation of pulmonary compliance. In bleomycin-induced lung fibrosis, TGFβ and BMP signaling followed an inverse course, with dynamic activation of TGFβ signaling and repression of BMP signaling activity. Upon bleomycin exposure, active BMP signaling is decreased. Derepression of BMP signaling in Nog +/LacZ mice protects against bleomycin-induced pulmonary fibrosis. Modulating the balance between BMP and TGFβ, in particular increasing endogenous BMP signals, may therefore be a therapeutic target in fibrotic lung disease.

  5. Application of adaptive digital signal processing to speech enhancement for the hearing impaired.

    Science.gov (United States)

    Chabries, D M; Christiansen, R W; Brey, R H; Robinette, M S; Harris, R W

    1987-01-01

    A major complaint of individuals with normal hearing and hearing impairments is a reduced ability to understand speech in a noisy environment. This paper describes the concept of adaptive noise cancelling for removing noise from corrupted speech signals. Application of adaptive digital signal processing has long been known and is described from a historical as well as technical perspective. The Widrow-Hoff LMS (least mean square) algorithm developed in 1959 forms the introduction to modern adaptive signal processing. This method uses a "primary" input which consists of the desired speech signal corrupted with noise and a second "reference" signal which is used to estimate the primary noise signal. By subtracting the adaptively filtered estimate of the noise, the desired speech signal is obtained. Recent developments in the field as they relate to noise cancellation are described. These developments include more computationally efficient algorithms as well as algorithms that exhibit improved learning performance. A second method for removing noise from speech, for use when no independent reference for the noise exists, is referred to as single channel noise suppression. Both adaptive and spectral subtraction techniques have been applied to this problem--often with the result of decreased speech intelligibility. Current techniques applied to this problem are described, including signal processing techniques that offer promise in the noise suppression application.

  6. A novel strategy for signal denoising using reweighted SVD and its applications to weak fault feature enhancement of rotating machinery

    Science.gov (United States)

    Zhao, Ming; Jia, Xiaodong

    2017-09-01

    Singular value decomposition (SVD), as an effective signal denoising tool, has been attracting considerable attention in recent years. The basic idea behind SVD denoising is to preserve the singular components (SCs) with significant singular values. However, it is shown that the singular values mainly reflect the energy of decomposed SCs, therefore traditional SVD denoising approaches are essentially energy-based, which tend to highlight the high-energy regular components in the measured signal, while ignoring the weak feature caused by early fault. To overcome this issue, a reweighted singular value decomposition (RSVD) strategy is proposed for signal denoising and weak feature enhancement. In this work, a novel information index called periodic modulation intensity is introduced to quantify the diagnostic information in a mechanical signal. With this index, the decomposed SCs can be evaluated and sorted according to their information levels, rather than energy. Based on that, a truncated linear weighting function is proposed to control the contribution of each SC in the reconstruction of the denoised signal. In this way, some weak but informative SCs could be highlighted effectively. The advantages of RSVD over traditional approaches are demonstrated by both simulated signals and real vibration/acoustic data from a two-stage gearbox as well as train bearings. The results demonstrate that the proposed method can successfully extract the weak fault feature even in the presence of heavy noise and ambient interferences.

  7. Table-moving contrast-enhanced MR angiography. Evaluation of imaging methods and its vascular signal characters

    Energy Technology Data Exchange (ETDEWEB)

    Amanuma, Makoto; Yoshida, Tadashi; Hirata, Hisashi; Kozawa, Eito; Enomoto, Kyoko; Watabe, Tsuneya; Heshiki, Atsuko [Saitama Medical School, Moroyama (Japan)

    1999-10-01

    Signal characteristics of table-moving contrast enhanced MR angiography (MRA) were analyzed in 31 consecutive patients. Imaging was performed at four different stations continuously before and after Gd-DTPA infusion and subtracted MRA were processed. Signal to noise ratio (SNR) of the main arteries was measured at 11 different points and their distribution pattern was compared relative to its position and dose of Gd-DTPA. Degree of arterial and venous demonstration was also scored by two radiologists. Arterial signal in the proximal stations showed significantly higher value than that in distal stations. In a single station, the proximal part of arterial main stem also had higher signal value than did distal part. The signal difference was largest in the proximal station. Although higher dose of contrast medium provided higher vascular signal, image quality was also clinically acceptable in the nearly single dose (0.10-0.15 mmol/kg). By optimizing imaging parameters, high quality whole-body MRA was possible even with single dose of contrast medium. (author)

  8. Analytical signal normalization in laser-enhanced ionization spectrometry with laser ablation of solid samples into a flame

    International Nuclear Information System (INIS)

    Labutin, T.A.; Popov, A.M.; Gorbatenko, A.A.; Zorov, N.B.

    2005-01-01

    The characteristics of analytical and reference signals (RS) were studied in laser-enhanced ionization (LEI) spectrometry combined with laser ablation of solid samples into a flame. Optoacoustic (OA) and atomic emission (AE) signals have been considered as possible RS. An algorithm of RS selection has been developed. Correlations between LEI signals and RS, which carry information on sample evaporation processes, have been explored. OA (the 1st minimum) and AE (AlI, λ = 396.1 nm) signals were found to be useful as RS (the correlation coefficients were 0.992 and 0.993, respectively). Both RS did not depend on the analyte (Li) content in the sample. It has been shown that the slope of the correlation plots (LEI vs. RS) depends on the Li content in the solid sample. This slope may be used as a novel type of normalized analytical signal, which does not depend on the ablation pulse energy. The influence of both ablating laser radiation characteristics and sample matrix composition on the analytical signal is eliminated (or at least diminished) when using this normalization

  9. Weak signal acquisition enhancement in software GPS receivers – Pre-filtering combined post-correlation detection approach

    Directory of Open Access Journals (Sweden)

    G. Arul Elango

    2017-01-01

    Full Text Available The Civilian Global Positioning System (GPS receivers often encounter problems of interference and noise which degrade the receiver performance. The conventional methods of parallel code phase search acquisition with coherent, non-coherent and differential coherent detection for weak signal acquisition fail to enhance the signal for all conditions especially, when the Carrier to Noise ratio (C/N0 falls below 15 dB-Hz. Hence, the GPS receiver has to employ sophisticated techniques to excise the noise and to improve the Signal-to-Noise Ratio (SNR of the signal for further processing. In this paper, a pre-filtering technique of reduced rank Singular Spectral Analysis (SSA is proposed for noise excision and is processed through coherent, non-coherent and differential detection postcorrelation methods to retrieve the signal embedded in noise. Monte Carlo simulations carried out to examine the acquisition sensitivity at various power levels with the different postcorrelation approaches indicate that the SSA combined with differential detection approach provides a significant performance improvement with lesser mean acquisition time. It has 96% probability of detection at a worst signal power level of −159 dBm (i.e. C/N0 15 dB-Hz, compared to other conventional methods.

  10. SIM-DSP: A DSP-Enhanced CAD Platform for Signal Integrity Macromodeling and Simulation

    Directory of Open Access Journals (Sweden)

    Chi-Un Lei

    2014-12-01

    Full Text Available Macromodeling-Simulation process for signal integrity verifications has become necessary for the high speed circuit system design. This paper aims to introduce a “VLSI Signal Integrity Macromodeling and Simulation via Digital Signal Processing Techniques” framework (known as SIM-DSP framework, which applies digital signal processing techniques to facilitate the SI verification process in the pre-layout design phase. Core identification modules and peripheral (pre-/post-processing modules have been developed and assembled to form a verification flow. In particular, a single-step discrete cosine transform truncation (DCTT module has been developed for modeling-simulation process. In DCTT, the response modeling problem is classified as a signal compression problem, wherein the system response can be represented by a truncated set of non-pole based DCT bases, and error can be analyzed through Parseval’s theorem. Practical examples are given to show the applicability of our proposed framework.

  11. Electrochemical immunoassay for thyroxine detection using cascade catalysis as signal amplified enhancer and multi-functionalized magnetic graphene sphere as signal tag.

    Science.gov (United States)

    Han, Jing; Zhuo, Ying; Chai, Yaqin; Yu, Yanqing; Liao, Ni; Yuan, Ruo

    2013-08-06

    This paper constructed a reusable electrochemical immunosensor for the detection of thyroxine at an ultralow concentration using cascade catalysis of cytochrome c (Cyt c) and glucose oxidase (GOx) as signal amplified enhancer. It is worth pointing out that numerous Cyt c and GOx were firstly carried onto the double-stranded DNA polymers based on hybridization chain reaction (HCR), and then the amplified responses could be achieved by cascade catalysis of Cyt c and GOx recycling with the help of glucose. Moreover, multi-functionalized magnetic graphene sphere was synthesized and used as signal tag, which not only exhibited good mechanical properties, large surface area and an excellent electron transfer rate of graphene, but also possessed excellent redox activity and desirable magnetic property. With a sandwich-type immunoreaction, the proposed cascade catalysis amplification strategy could greatly enhance the sensitivity for the detection of thyroxine. Under the optimal conditions, the immunosensor showed a wide linear ranged from 0.05pg mL(-1) to 5ng mL(-1) and a low detection limit down to 15fg mL(-1). Importantly, the proposed method offers promise for reproducible and cost-effective analysis of biological samples. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Enhanced sensory re-learning after nerve repair using 3D audio-visual signals and kinaesthesia--preliminary results.

    Science.gov (United States)

    Schmidhammer, R; Hausner, T; Kröpfl, A; Huber, W; Hopf, R; Leixnering, M; Herz, H; Redl, H

    2007-01-01

    Sensory re-learning methods and basics on cortical reorganization after peripheral nerve lesion are well documented. The aim of enhanced sensory re-learning using 3D audio-visual signals and kinaesthetic training is the augmentation of cognitive memory (visual and acoustic sensory memory) and cognitive function for the improvement of cerebral plasticity processes and starts as soon as possible after nerve repair. Preliminary results are shown.

  13. Polyclonal immune responses to antigens associated with cancer signaling pathways and new strategies to enhance cancer vaccines.

    Science.gov (United States)

    Clay, Timothy M; Osada, Takuya; Hartman, Zachary C; Hobeika, Amy; Devi, Gayathri; Morse, Michael A; Lyerly, H Kim

    2011-04-01

    Aberrant signaling pathways are a hallmark of cancer. A variety of strategies for inhibiting signaling pathways have been developed, but monoclonal antibodies against receptor tyrosine kinases have been among the most successful. A challenge for these therapies is therapeutic unresponsiveness and acquired resistance due to mutations in the receptors, upregulation of alternate growth and survival pathways, or inadequate function of the monoclonal antibodies. Vaccines are able to induce polyclonal responses that can have a multitude of affects against the target molecule. We began to explore therapeutic vaccine development to antigens associated with these signaling pathways. We provide an illustrative example in developing therapeutic cancer vaccines inducing polyclonal adaptive immune responses targeting the ErbB family member HER2. Further, we will discuss new strategies to augment the clinical efficacy of cancer vaccines by enhancing vaccine immunogenicity and reversing the immunosuppressive tumor microenvironment.

  14. HER2 signaling pathway activation and response of breast cancer cells to HER2-targeting agents is dependent strongly on the 3D microenvironment

    Energy Technology Data Exchange (ETDEWEB)

    Weigelt, Britta; Lo, Alvin T; Park, Catherine C; Gray, Joe W; Bissell, Mina J

    2009-07-27

    Development of effective and durable breast cancer treatment strategies requires a mechanistic understanding of the influence of the microenvironment on response. Previous work has shown that cellular signaling pathways and cell morphology are dramatically influenced by three-dimensional (3D) cultures as opposed to traditional two-dimensional (2D) monolayers. Here, we compared 2D and 3D culture models to determine the impact of 3D architecture and extracellular matrix (ECM) on HER2 signaling and on the response of HER2-amplified breast cancer cell lines to the HER2-targeting agents Trastuzumab, Pertuzumab and Lapatinib. We show that the response of the HER2-amplified AU565, SKBR3 and HCC1569 cells to these anti-HER2 agents was highly dependent on whether the cells were cultured in 2D monolayer or 3D laminin-rich ECM gels. Inhibition of {beta}1 integrin, a major cell-ECM receptor subunit, significantly increased the sensitivity of the HER2-amplified breast cancer cell lines to the humanized monoclonal antibodies Trastuzumab and Pertuzumab when grown in a 3D environment. Finally, in the absence of inhibitors, 3D cultures had substantial impact on HER2 downstream signaling and induced a switch between PI3K-AKT- and RAS-MAPKpathway activation in all cell lines studied, including cells lacking HER2 amplification and overexpression. Our data provide direct evidence that breast cancer cells are able to rapidly adapt to different environments and signaling cues by activating alternative pathways that regulate proliferation and cell survival, events that may play a significant role in the acquisition of resistance to targeted therapies.

  15. HER2 signaling pathway activation and response of breast cancer cells to HER2-targeting agents is dependent strongly on the 3D microenvironment.

    Science.gov (United States)

    Weigelt, Britta; Lo, Alvin T; Park, Catherine C; Gray, Joe W; Bissell, Mina J

    2010-07-01

    Development of effective and durable breast cancer treatment strategies requires a mechanistic understanding of the influence of the microenvironment on response. Previous work has shown that cellular signaling pathways and cell morphology are dramatically influenced by three-dimensional (3D) cultures as opposed to traditional two-dimensional (2D) monolayers. Here, we compared 2D and 3D culture models to determine the impact of 3D architecture and extracellular matrix (ECM) on HER2 signaling and on the response of HER2-amplified breast cancer cell lines to the HER2-targeting agents Trastuzumab, Pertuzumab and Lapatinib. We show that the response of the HER2-amplified AU565, SKBR3 and HCC1569 cells to these anti-HER2 agents was highly dependent on whether the cells were cultured in 2D monolayer or 3D laminin-rich ECM gels. Inhibition of beta1 integrin, a major cell-ECM receptor subunit, significantly increased the sensitivity of the HER2-amplified breast cancer cell lines to the humanized monoclonal antibodies Trastuzumab and Pertuzumab when grown in a 3D environment. Finally, in the absence of inhibitors, 3D cultures had substantial impact on HER2 downstream signaling and induced a switch between PI3K-AKT- and RAS-MAPK-pathway activation in all cell lines studied, including cells lacking HER2 amplification and overexpression. Our data provide direct evidence that breast cancer cells are able to rapidly adapt to different environments and signaling cues by activating alternative pathways that regulate proliferation and cell survival, events that may play a significant role in the acquisition of resistance to targeted therapies.

  16. Enhancing weak transient signals in SEVIRI false color imagery: Application to dust source detection in southern Africa

    Science.gov (United States)

    Murray, J. E.; Brindley, H. E.; Bryant, R. G.; Russell, J. E.; Jenkins, K. F.; Washington, R.

    2016-09-01

    A method is described to significantly enhance the signature of dust events using observations from the Spinning Enhanced Visible and InfraRed Imager (SEVIRI). The approach involves the derivation of a composite clear-sky signal for selected channels on an individual time step and pixel basis. These composite signals are subtracted from each observation in the relevant channels to enhance weak transient signals associated with either (a) low levels of dust emission or (b) dust emissions with high salt or low quartz content. Different channel combinations, of the differenced data from the steps above, are then rendered in false color imagery for the purpose of improved identification of dust source locations and activity. We have applied this clear-sky difference (CSD) algorithm over three (globally significant) source regions in southern Africa: the Makgadikgadi Basin, Etosha Pan, and the Namibian and western South African coast. Case study analyses indicate three notable advantages associated with the CSD approach over established image rendering methods: (i) an improved ability to detect dust plumes, (ii) the observation of source activation earlier in the diurnal cycle, and (iii) an improved ability to resolve and pinpoint dust plume source locations.

  17. Consequences of a dark disk for the Fermi and PAMELA signals in theories with a Sommerfeld enhancement

    International Nuclear Information System (INIS)

    Cholis, Ilias; Goodenough, Lisa

    2010-01-01

    Much attention has been given to dark matter explanations of the PAMELA positron fraction and Fermi electronic excesses. For those theories with a TeV-scale WIMP annihilating through a light force-carrier, the associated Sommerfeld enhancement provides a natural explanation of the large boost factor needed to explain the signals, and the light force-carrier naturally gives rise to hard cosmic ray spectra without excess π 0 -gamma rays or anti-protons. The Sommerfeld enhancement of the annihilation rate, which at low relative velocities v rel scales as 1/v rel , relies on the comparatively low velocity dispersion of the dark matter particles in the smooth halo. Dark matter substructures in which the velocity dispersion is smaller than in the smooth halo have even larger annihilation rates. N-body simulations containing only dark matter predict the existence of such structures, for example subhalos and caustics, and the effects of these substructures on dark matter indirect detection signals have been studied extensively. The addition of baryons into cosmological simulations of disk-dominated galaxies gives rise to an additional substructure component, a dark disk. The disk has a lower velocity dispersion than the spherical halo component by a factor ∼ 6, so the contributions to dark matter signals from the disk can be more significant in Sommerfeld models than for WIMPs without such low-velocity ehancements. We consider the consequences of a dark disk on the observed signals of e + e − , p p-bar and γ-rays as measured by Fermi and PAMELA in models where the WIMP annihilations are into a light boson. We find that both the PAMELA and Fermi results are easily accomodated by scenarios in which a disk signal is included with the standard spherical halo signal. If contributions from the dark disk are important, limits from extrapolations to the center of the galaxy contain significant uncertainties beyond those from the spherical halo profile alone

  18. AFCo1, a meningococcal B-derived cochleate adjuvant, strongly enhances antibody and T-cell immunity against Plasmodium falciparum merozoite surface protein 4 and 5

    Directory of Open Access Journals (Sweden)

    Pérez Oliver

    2009-02-01

    Full Text Available Abstract Background Whilst a large number of malaria antigens are being tested as candidate malaria vaccines, a major barrier to the development of an effective vaccine is the lack of a suitable human adjuvant capable of inducing a strong and long lasting immune response. In this study, the ability of AFCo1, a potent T and B cell adjuvant based on cochleate structures derived from meningococcal B outer membrane proteoliposomes (MBOMP, to boost the immune response against two Plasmodium falciparum antigens, merozoite surface protein 4 (MSP4 and 5 (MSP5, was evaluated. Methods Complete Freund's adjuvant (CFA, which is able to confer protection against malaria in animal MSP4/5 vaccine challenge models, was used as positive control adjuvant. MSP4 and 5-specific IgG, delayed-type hypersensitivity (DTH, T-cell proliferation, and cytokine production were evaluated in parallel in mice immunized three times intramuscularly with MSP4 or MSP5 incorporated into AFCo1, synthetic cochleate structures, CFA or phosphate buffered saline. Results AFCo1 significantly enhanced the IgG and T-cell response against MSP4 and MSP5, with a potency equivalent to CFA, with the response being characterized by both IgG1 and IgG2a isotypes, increased interferon gamma production and a strong DTH response, consistent with the ability of AFCo1 to induce Th1-like immune responses. Conclusion Given the proven safety of MBOMP, which is already in use in a licensed human vaccine, AFCo1 could assist the development of human malaria vaccines that require a potent and safe adjuvant.

  19. AFCo1, a meningococcal B-derived cochleate adjuvant, strongly enhances antibody and T-cell immunity against Plasmodium falciparum merozoite surface protein 4 and 5.

    Science.gov (United States)

    Bracho, Gustavo; Zayas, Caridad; Wang, Lina; Coppel, Ross; Pérez, Oliver; Petrovsky, Nikolai

    2009-02-27

    Whilst a large number of malaria antigens are being tested as candidate malaria vaccines, a major barrier to the development of an effective vaccine is the lack of a suitable human adjuvant capable of inducing a strong and long lasting immune response. In this study, the ability of AFCo1, a potent T and B cell adjuvant based on cochleate structures derived from meningococcal B outer membrane proteoliposomes (MBOMP), to boost the immune response against two Plasmodium falciparum antigens, merozoite surface protein 4 (MSP4) and 5 (MSP5), was evaluated. Complete Freund's adjuvant (CFA), which is able to confer protection against malaria in animal MSP4/5 vaccine challenge models, was used as positive control adjuvant. MSP4 and 5-specific IgG, delayed-type hypersensitivity (DTH), T-cell proliferation, and cytokine production were evaluated in parallel in mice immunized three times intramuscularly with MSP4 or MSP5 incorporated into AFCo1, synthetic cochleate structures, CFA or phosphate buffered saline. AFCo1 significantly enhanced the IgG and T-cell response against MSP4 and MSP5, with a potency equivalent to CFA, with the response being characterized by both IgG1 and IgG2a isotypes, increased interferon gamma production and a strong DTH response, consistent with the ability of AFCo1 to induce Th1-like immune responses. Given the proven safety of MBOMP, which is already in use in a licensed human vaccine, AFCo1 could assist the development of human malaria vaccines that require a potent and safe adjuvant.

  20. P-Code-Enhanced Encryption-Mode Processing of GPS Signals

    Science.gov (United States)

    Young, Lawrence; Meehan, Thomas; Thomas, Jess B.

    2003-01-01

    A method of processing signals in a Global Positioning System (GPS) receiver has been invented to enable the receiver to recover some of the information that is otherwise lost when GPS signals are encrypted at the transmitters. The need for this method arises because, at the option of the military, precision GPS code (P-code) is sometimes encrypted by a secret binary code, denoted the A code. Authorized users can recover the full signal with knowledge of the A-code. However, even in the absence of knowledge of the A-code, one can track the encrypted signal by use of an estimate of the A-code. The present invention is a method of making and using such an estimate. In comparison with prior such methods, this method makes it possible to recover more of the lost information and obtain greater accuracy.

  1. Receptor protein tyrosine phosphatase alpha enhances rheumatoid synovial fibroblast signaling and promotes arthritis in mice

    NARCIS (Netherlands)

    Stanford, Stephanie M; Svensson, Mattias N D; Sacchetti, Cristiano; Pilo, Caila A; Wu, Dennis J; Kiosses, William B; Hellvard, Annelie; Bergum, Brith; Aleman Muench, German R; Elly, Christian; Liu, Yun-Cai; den Hertog, Jeroen; Elson, Ari; Sap, Jan; Mydel, Piotr; Boyle, David L; Corr, Maripat; Firestein, Gary S; Bottini, Nunzio

    2016-01-01

    OBJECTIVE: During rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) critically promote disease pathogenesis by aggressively invading the joint extracellular matrix. The focal adhesion kinase (FAK) signaling pathway is emerging as a contributor to RA FLS anomalous behavior. The receptor

  2. Enhancing the blue shift of SHG signal in GaSe:B/Ce crystal

    Science.gov (United States)

    Karatay, Ahmet; Yuksek, Mustafa; Ertap, Hüseyin; Elmali, Ayhan; Karabulut, Mevlut

    2018-02-01

    The influence of Ce3+ on the wavelength of second harmonic generation (SHG) signal in boron doped GaSe crystals have been investigated. We found that by substitution of Ce3+ with B3+, SHG signal shifted to lower wavelength. In addition, the nonlinear absorption (NA) properties and ultrafast dynamics of pure, 1 at.% B3+ and 0.5 at.% B3++ 0.5 at.% Ce3+ doped GaSe crystals have been studied by open aperture Z-scan and ultrafast pump probe spectroscopy techniques. From the open aperture Z-scan experiments we observed that all of the crystals showed nonlinear absorption (NA). However, pump-probe experiments revealed that when GaSe crystal is doped, the NA signal turns into a bleaching signal with different lifetimes depending on the type and concentration of the dopant atoms.

  3. Dynamic Range Enhancement of High-Speed Electrical Signal Data via Non-Linear Compression

    Science.gov (United States)

    Laun, Matthew C. (Inventor)

    2016-01-01

    Systems and methods for high-speed compression of dynamic electrical signal waveforms to extend the measuring capabilities of conventional measuring devices such as oscilloscopes and high-speed data acquisition systems are discussed. Transfer function components and algorithmic transfer functions can be used to accurately measure signals that are within the frequency bandwidth but beyond the voltage range and voltage resolution capabilities of the measuring device.

  4. Enhanced Toll-like receptor responses in the absence of signaling adaptor DAP12.

    OpenAIRE

    Hamerman, Jessica A; Tchao, Nadia K; Lowell, Clifford A; Lanier, Lewis L

    2005-01-01

    DAP12 is a signaling adaptor containing an immunoreceptor tyrosine-based activation motif (ITAM) that pairs with receptors on myeloid cells and natural killer cells. We examine here the responses of mice lacking DAP12 to stimulation through Toll-like receptors (TLRs). Unexpectedly, DAP12-deficient macrophages produced higher concentrations of inflammatory cytokines in response to a variety of pathogenic stimuli. Additionally, macrophages deficient in spleen tyrosine kinase (Syk), which signal...

  5. Real-Time EEG Signal Enhancement Using Canonical Correlation Analysis and Gaussian Mixture Clustering

    Directory of Open Access Journals (Sweden)

    Chin-Teng Lin

    2018-01-01

    Full Text Available Electroencephalogram (EEG signals are usually contaminated with various artifacts, such as signal associated with muscle activity, eye movement, and body motion, which have a noncerebral origin. The amplitude of such artifacts is larger than that of the electrical activity of the brain, so they mask the cortical signals of interest, resulting in biased analysis and interpretation. Several blind source separation methods have been developed to remove artifacts from the EEG recordings. However, the iterative process for measuring separation within multichannel recordings is computationally intractable. Moreover, manually excluding the artifact components requires a time-consuming offline process. This work proposes a real-time artifact removal algorithm that is based on canonical correlation analysis (CCA, feature extraction, and the Gaussian mixture model (GMM to improve the quality of EEG signals. The CCA was used to decompose EEG signals into components followed by feature extraction to extract representative features and GMM to cluster these features into groups to recognize and remove artifacts. The feasibility of the proposed algorithm was demonstrated by effectively removing artifacts caused by blinks, head/body movement, and chewing from EEG recordings while preserving the temporal and spectral characteristics of the signals that are important to cognitive research.

  6. Investigations of the signal production in liquid-ionization-chambers by the passage of strongly ionizing particles and a now theoretical description of recombination

    International Nuclear Information System (INIS)

    Supper, R.

    1991-12-01

    Starting from the original Onsager-theory an extended theory is presented describing the recombination of charge carriers and of signal production in TMS (tetramethylsilane) liquid ionization chambers. The shielding by the impurities of the liquid is explicitly taken into account. By dedicated measurements various parameter dependencies of the theory are checked and the parameter values are experimentally determined. The studies comprise test procedures of the TMS chamber operation and are in context of a hadron calorimeter set up of the cosmic ray experiment KASCADE. (orig.) [de

  7. Multinuclear giant cell formation is enhanced by down-regulation of Wnt signaling in gastric cancer cell line, AGS

    International Nuclear Information System (INIS)

    Kim, Shi-Mun; Kim, Rockki; Ryu, Jae-Hyun; Jho, Eek-Hoon; Song, Ki-Joon; Jang, Shyh-Ing; Kee, Sun-Ho

    2005-01-01

    AGS cells, which were derived from malignant gastric adenocarcinoma tissue, lack E-cadherin-mediated cell adhesion but have a high level of nuclear β-catenin, which suggests altered Wnt signal. In addition, approximately 5% of AGS cells form multinuclear giant cells in the routine culture conditions, while taxol treatment causes most AGS cells to become giant cells. The observation of reduced nuclear β-catenin levels in giant cells induced by taxol treatment prompted us to investigate the relationship between Wnt signaling and giant cell formation. After overnight serum starvation, the shape of AGS cells became flattened, and this morphological change was accompanied by decrease in Myc expression and an increase in the giant cell population. Lithium chloride treatment, which inhibits GSK3β activity, reversed these serum starvation effects, which suggests an inverse relationship between Wnt signaling and giant cell formation. Furthermore, the down-regulation of Wnt signaling caused by the over-expression of ICAT, E-cadherin, and Axin enhanced giant cell formation. Therefore, down-regulation of Wnt signaling may be related to giant cell formation, which is considered to be a survival mechanism against induced cell death

  8. β-Integrin de-phosphorylation by the Density-Enhanced Phosphatase DEP-1 attenuates EGFR signaling in C. elegans.

    Directory of Open Access Journals (Sweden)

    Michael Walser

    2017-01-01

    Full Text Available Density-Enhanced Phosphatase-1 (DEP-1 de-phosphorylates various growth factor receptors and adhesion proteins to regulate cell proliferation, adhesion and migration. Moreover, dep-1/scc1 mutations have been detected in various types of human cancers, indicating a broad tumor suppressor activity. During C. elegans development, DEP-1 mediates binary cell fate decisions by negatively regulating EGFR signaling. Using a substrate-trapping DEP-1 mutant in a proteomics approach, we have identified the C. elegans β-integrin subunit PAT-3 as a specific DEP-1 substrate. DEP-1 selectively de-phosphorylates tyrosine 792 in the membrane-proximal NPXY motif to promote integrin activation via talin recruitment. The non-phosphorylatable β-integrin mutant pat-3(Y792F partially suppresses the hyperactive EGFR signaling phenotype caused by loss of dep-1 function. Thus, DEP-1 attenuates EGFR signaling in part by de-phosphorylating Y792 in the β-integrin cytoplasmic tail, besides the direct de-phosphorylation of the EGFR. Furthermore, in vivo FRAP analysis indicates that the αβ-integrin/talin complex attenuates EGFR signaling by restricting receptor mobility on the basolateral plasma membrane. We propose that DEP-1 regulates EGFR signaling via two parallel mechanisms, by direct receptor de-phosphorylation and by restricting receptor mobility through αβ-integrin activation.

  9. Contrast microsphere enhancement of the tricuspid regurgitant spectral Doppler signal - Is it still necessary with contemporary scanners?

    Science.gov (United States)

    Platts, David G; Vaishnav, Manan; Burstow, Darryl J; Craig, Christian Hamilton; Chan, Jonathan; Sedgwick, John L; Scalia, Gregory M

    2017-12-01

    Accurate evaluation of the tricuspid regurgitant (TR) spectral Doppler signal is important during transthoracic echocardiographic (TTE) evaluation for pulmonary hypertension (PHT). Contrast enhancement improves Doppler backscatter. However, its incremental benefit with contemporary scanners is less well established. The aim of this study was to assess whether the TR spectral Doppler signal using contemporary scanners was improved using a second generation contrast agent, Definity® (CE), compared to unenhanced TTE (UE). Analysis of patients who underwent UE then CE TR interrogation was performed. TR signal was evaluated by an experienced reader and graded 1 (clear-high level of confidence of interpretation and complete spectral Doppler envelope), 2 (suboptimal with medium-low level of confidence of interpretation and incomplete envelope), 3 (poor-absent and no measurable spectral Doppler signal). Maximal TR velocity (TRV) was defined as peak velocity that could be clearly identified. An inexperienced sonographer read 30 randomly selected studies. 176 TTE were performed in 173 patients (mean age 57 ± 14.8 years). Wilcoxon signed rank test demonstrated significant improvement (p contemporary scanners, CE improved the ability to detect and measure TRV, except in those with clear unenhanced TR spectral Doppler signals or greater than mild tricuspid regurgitation.

  10. A multivariate analysis of variation in genome size and endoreduplication in angiosperms reveals strong phylogenetic signal and association with phenotypic traits.

    Science.gov (United States)

    Bainard, Jillian D; Bainard, Luke D; Henry, Thomas A; Fazekas, Aron J; Newmaster, Steven G

    2012-12-01

    Genome size (C-value) and endopolyploidy (endoreduplication index, EI) are known to correlate with various morphological and ecological traits, in addition to phylogenetic placement. A phylogenetically controlled multivariate analysis was used to explore the relationships between DNA content and phenotype in angiosperms. Seeds from 41 angiosperm species (17 families) were grown in a common glasshouse experiment. Genome size (2C-value and 1Cx-value) and EI (in four tissues: leaf, stem, root, petal) were determined using flow cytometry. The phylogenetic signal was calculated for each measure of DNA content, and phylogenetic canonical correlation analysis (PCCA) explored how the variation in genome size and EI was correlated with 18 morphological and ecological traits. Phylogenetic signal (λ) was strongest for EI in all tissues, and λ was stronger for the 2C-value than the 1Cx-value. PCCA revealed that EI was correlated with pollen length, stem height, seed mass, dispersal mechanism, arbuscular mycorrhizal association, life history and flowering time, and EI and genome size were both correlated with stem height and life history. PCCA provided an effective way to explore multiple factors of DNA content variation and phenotypic traits in a phylogenetic context. Traits that were correlated significantly with DNA content were linked to plant competitive ability. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

  11. Naringin enhances osteogenic differentiation through the activation of ERK signaling in human bone marrow mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Huichao Wang

    2017-04-01

    Full Text Available Objective(s: Naringin has been reported to regulate bone metabolism. However, its effect on osteogenesis remains unclear. The aim was to investigate the effect of naringin on osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs through the activation of the ERK signaling pathway in osteogenic differentiation. Materials and Methods: Annexin V-FITC assay and MTT assay were used to measure the effect of naringin on cytotoxicity and proliferation of hBMSCs, respectively. Alkaline phosphatase activity analysis, Alizarin Red S staining, Western blotting, and real-time PCR assay were used to evaluate both the potential effect of naringin on osteogenic differentiation and the role of ERK signaling pathway in osteogenic differentiation. Results: Our results showed that naringin had no obvious toxicity on hBMSCs, and could significantly promote the proliferation of hBMSCs. Naringin also enhanced the osteogenic differentiation of hBMSCs and increased the protein and mRNA expression levels of osteogenic markers such as Runx-2, OXS, OCN, and Col1 in a dose-dependent manner. In addition, we found that the enhancing effect of naringin on osteogenic differentiation was related to the activation of phosphor-ERK, with an increase in duration of activity from 30 min to 120 min. More importantly, both the enhancing effect of naringin on osteogenic differentiation and the activity effect of naringin on ERK signaling pathway were reversed by U0126 addition. Conclusion: Our findings demonstrated that naringin promoted proliferation and osteogenesis of hBMSCs by activating the ERK signaling pathway and it might be a potential therapeutic agent for treating or preventing osteoporosis.

  12. Coherent response of a two-level atom to a signal field with account of suppression of phase relaxation by a strong field

    International Nuclear Information System (INIS)

    Grishanin, B.A.; Shatalova, G.G.

    1984-01-01

    Calculation is made of a coherent part of response to a weak test field of an atom located in a strong resonance field. The latter bads to a suppression of phase relaxation. This response is shown to appear both at a test field freq uency ω and at a combination frequency 2ωsub(l)-ω, where ωsub(l) is a resona nce field frequency. The spectrum of test field absorption by such a system has a symmetric form and consist of two parts, one of which corresponds to a test f ield absorption and another - to its amplification

  13. Phosphoproteomics Reveals MAPK Inhibitors Enhance MET- and EGFR-Driven AKT Signaling in KRAS-Mutant Lung Cancer.

    Science.gov (United States)

    Kim, Jae-Young; Welsh, Eric A; Fang, Bin; Bai, Yun; Kinose, Fumi; Eschrich, Steven A; Koomen, John M; Haura, Eric B

    2016-10-01

    Pathway inhibition of the RAS-driven MAPK pathway using small-molecule kinase inhibitors has been a key focus for treating cancers driven by oncogenic RAS, yet significant clinical responses are lacking. Feedback reactivation of ERK driven by drug-induced RAF activity has been suggested as one of the major drug resistance mechanisms, especially in the context of oncogenic RAS. To determine whether additional adaptive resistance mechanisms may coexist, we characterized global phosphoproteomic changes after MEK inhibitor selumetinib (AZD6244) treatment in KRAS-mutant A427 and A549 lung adenocarcinoma cell lines employing mass spectrometry-based phosphoproteomics. We identified 9,075 quantifiable unique phosphosites (corresponding to 3,346 unique phosphoproteins), of which 567 phosphosites were more abundant and 512 phosphosites were less abundant after MEK inhibition. Selumetinib increased phosphorylation of KSR-1, a scaffolding protein required for assembly of MAPK signaling complex, as well as altered phosphorylation of GEF-H1, a novel regulator of KSR-1 and implicated in RAS-driven MAPK activation. Moreover, selumetinib reduced inhibitory serine phosphorylation of MET at Ser985 and potentiated HGF- and EGF-induced AKT phosphorylation. These results were recapitulated by pan-RAF (LY3009120), MEK (GDC0623), and ERK (SCH772984) inhibitors, which are currently under early-phase clinical development against RAS-mutant cancers. Our results highlight the unique adaptive changes in MAPK scaffolding proteins (KSR-1, GEF-H1) and in RTK signaling, leading to enhanced PI3K-AKT signaling when the MAPK pathway is inhibited. This study highlights the unique adaptive changes in MAPK scaffolding proteins (KSR-1, GEF-H1) and in RTK signaling, leading to enhanced PI3K/AKT signaling when the MAPK pathway is inhibited. Mol Cancer Res; 14(10); 1019-29. ©2016 AACR. ©2016 American Association for Cancer Research.

  14. Testin, a novel binding partner of the calcium-sensing receptor, enhances receptor-mediated Rho-kinase signalling

    International Nuclear Information System (INIS)

    Magno, Aaron L.; Ingley, Evan; Brown, Suzanne J.; Conigrave, Arthur D.; Ratajczak, Thomas; Ward, Bryan K.

    2011-01-01

    Highlights: → A yeast two-hybrid screen revealed testin bound to the calcium-sensing receptor. → The second zinc finger of LIM domain 1 of testin is critical for interaction. → Testin bound to a region of the receptor tail important for cell signalling. → Testin and receptor interaction was confirmed in mammalian (HEK293) cells. → Overexpression of testin enhanced receptor-mediated Rho signalling in HEK293 cells. -- Abstract: The calcium-sensing receptor (CaR) plays an integral role in calcium homeostasis and the regulation of other cellular functions including cell proliferation and cytoskeletal organisation. The multifunctional nature of the CaR is manifested through ligand-dependent stimulation of different signalling pathways that are also regulated by partner binding proteins. Following a yeast two-hybrid library screen using the intracellular tail of the CaR as bait, we identified several novel binding partners including the focal adhesion protein, testin. Testin has not previously been shown to interact with cell surface receptors. The sites of interaction between the CaR and testin were mapped to the membrane proximal region of the receptor tail and the second zinc-finger of LIM domain 1 of testin, the integrity of which was found to be critical for the CaR-testin interaction. The CaR-testin association was confirmed in HEK293 cells by coimmunoprecipitation and confocal microscopy studies. Ectopic expression of testin in HEK293 cells stably expressing the CaR enhanced CaR-stimulated Rho activity but had no effect on CaR-stimulated ERK signalling. These results suggest an interplay between the CaR and testin in the regulation of CaR-mediated Rho signalling with possible effects on the cytoskeleton.

  15. Microwave assisted in situ synthesis of Ag–NaCMC films and their reproducible surface-enhanced Raman scattering signals

    International Nuclear Information System (INIS)

    Jiang, Tao; Li, Junpeng; Zhang, Li; Wang, Binbing; Zhou, Jun

    2014-01-01

    Graphical abstract: Two kinds of Ag–NaCMC films for surface-enhanced Raman scattering (SERS) were prepared by conventional heating and microwave assisted in situ reduction methods without any additional capping or reducing agents. A relatively narrow and symmetric surface plasmon resonance band was observed in the absorption spectra of the films fabricated by the microwave assisted in situ reduction method. More uniform silver nanoparticles (NPs) implied by the symmetric absorption spectrum were further confirmed by the scanning electron microscopy images. After the simulation of the E-field intensity distribution around the silver NPs in NaCMC film, the Raman scattering enhancement factors (EFs) of these films were then investigated with 4-mercaptobenzoic acid molecule as a SERS reporter. Improved reproducibility of SERS signal was obtained in the microwave assisted synthesized Ag–NaCMC film, although it maintained an EF as only 1.11 × 10 8 . The reproducible SERS signal of the Ag–NaCMC film is particularly attractive and this microwave assisted in situ reduction method is suitable for the production of excellent substrate for biosensor application. - Highlights: • The synthesis of Ag–NaCMC films was successfully fulfilled by a low-cost microwave method. • More uniform silver nanoparticles were observed in Ag–NaCMC film synthesized by microwave. • Improved reproducibility of SERS signal was obtained in microwave synthesized Ag–NaCMC film. - Abstract: Two kinds of Ag–NaCMC films for surface-enhanced Raman scattering (SERS) were prepared by conventional heating and microwave assisted in situ reduction methods without any additional capping or reducing agents. A relatively narrow and symmetric surface plasmon resonance band was observed in the absorption spectra of the films fabricated by the microwave assisted in situ reduction method. More uniform silver nanoparticles (NPs) implied by the symmetric absorption spectrum were further confirmed by

  16. Demonstration of a squeezed-light-enhanced power- and signal-recycled Michelson interferometer.

    Science.gov (United States)

    Vahlbruch, Henning; Chelkowski, Simon; Hage, Boris; Franzen, Alexander; Danzmann, Karsten; Schnabel, Roman

    2005-11-18

    We report on the experimental combination of three advanced interferometer techniques for gravitational wave detection, namely, power recycling, detuned signal recycling, and squeezed field injection. For the first time, we experimentally prove the compatibility of especially the latter two. To achieve a broadband nonclassical sensitivity improvement, we applied a filter cavity for compensation of quadrature rotation. The signal-to-noise ratio was improved by up to 2.8 dB beyond the coherent state's shot noise. The complete setup was stably locked for arbitrary times and characterized by injected single-sideband modulation fields.

  17. Prognosis prediction of non-enhancing T2 high signal intensity lesions in glioblastoma patients after standard treatment: application of dynamic contrast-enhanced MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Rihyeon; Yun, Tae Jin; Kim, Ji-Hoon; Sohn, Chul-Ho [Seoul National University Hospital, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Choi, Seung Hong [Seoul National University Hospital, Department of Radiology, 101 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Seoul National University Medical Research Center, Department of Radiology, Seoul National University College of Medicine, and Institute of Radiation Medicine, 103 Daehak-ro, Jongno-gu, Seoul (Korea, Republic of); Seoul National University, Center for Nanoparticle Research, Institute for Basic Science (IBS), Daehak-dong, Gwanak-gu, Seoul (Korea, Republic of); Seoul National University, School of Chemical and Biological Engineering, Daehak-dong, Gwanak-gu, Seoul (Korea, Republic of); Lee, Soon-Tae [Seoul National University Hospital, Department of Neurology, Seoul (Korea, Republic of); Park, Chul-Kee [Seoul National University Hospital, Department of Neurosurgery, Seoul (Korea, Republic of); Kim, Tae Min [Seoul National University Hospital, Department of Internal Medicine, Seoul (Korea, Republic of); Park, Sun-Won [Seoul National University College of Medicine, Department of Radiology, SMG-SNU Boramae Medical Center, Seoul (Korea, Republic of); Park, Sung-Hye [Seoul National University Hospital, Department of Pathology, Seoul (Korea, Republic of); Kim, Il Han [Seoul National University Hospital, Department of Radiation Oncology, Seoul (Korea, Republic of)

    2017-03-15

    To identify candidate imaging biomarkers for early disease progression in glioblastoma multiforme (GBM) patients by analysis of dynamic contrast-enhanced (DCE) MR parameters of non-enhancing T2 high signal intensity (SI) lesions. Forty-nine GBM patients who had undergone preoperative DCE MR imaging and received standard treatment were retrospectively included. According to the Response Assessment in Neuro-Oncology criteria, patients were classified into progression (n = 21) or non-progression (n = 28) groups. We analysed the pharmacokinetic parameters of Ktrans, Ve and Vp within non-enhancing T2 high SI lesions of each tumour. The best percentiles of each parameter from cumulative histograms were identified by the area under the receiver operating characteristic curve (AUC) and were compared using multivariate stepwise logistic regression. For the differentiation of early disease progression, the highest AUC values were found in the 99th percentile of Ktrans (AUC 0.954), the 97th percentile of Ve (AUC 0.815) and the 94th percentile of Vp (AUC 0.786) (all p < 0.05). The 99th percentile of Ktrans was the only significant independent variable from the multivariate stepwise logistic regression (p = 0.002). We found that the Ktrans of non-enhancing T2 high SI lesions in GBM patients holds potential as a candidate prognostic marker in future prospective studies. (orig.)

  18. Appearance of high signal intensity and gadolinium-DTPA contrast enhancement in hypertrophied myocardium by magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, Tsunehiko; Yamada, Naoaki; Nagata, Seiki (National Cardiovascular Center, Suita, Osaka (Japan))

    1989-11-01

    This study was undertaken to examine the potential role of magnetic resonance imaging (MRI) for evaluating myocardial tissue characterization in hypertrophic cardiomyopathy (HCM). ECG-gated MRI images were acquired in 32 HCM patients and 30 patients with hypertensive heart disease (HHD), using a 1.5 T superconducting magnet system. The thickened areas were depicted as high signal intensities in the septum of 12 HCM patients (38%) and the endocardium of 5 HHD patients (17%). Echocardiography revealed that MRI appearance of high signal intensity was associated with more thickened myocardial wall. For evaluable 16 patients receiving i.v. injection of Gd-DTPA in a dose of 0.1 mM/kg, enhancement effects were observed in 10 patients (63%). High signal intensity appearing in the hypertrophied myocardium, as well as contrast enhancement, may not be characteristic of HCM, but reflect the likelihood of myocardial degeneration associated with the hypertrophied myocardium. Although MRI may not be capable of differentiating tissue characterization in HCM from that in HHD, it may provide different information about tissue characterization in the hypertrophied myocardium from that obtained by other techniques. (N.K.).

  19. Oxidative stress enhances cephalosporin resistance of Enterococcus faecalis through activation of a two-component signaling system.

    Science.gov (United States)

    Djorić, Dušanka; Kristich, Christopher J

    2015-01-01

    Enterococcus faecalis is a low-GC Gram-positive bacterium, a normal resident of the gastrointestinal (GI) tract, and an important hospital-acquired pathogen. An important risk factor for hospital-acquired enterococcal infections is prior therapy with broad-spectrum cephalosporins, antibiotics that impair cell wall biosynthesis by inhibiting peptidoglycan cross-linking. Enterococci are intrinsically resistant to cephalosporins; however, environmental factors that modulate cephalosporin resistance have not been described. While searching for the genetic determinants of cephalosporin resistance in E. faecalis, we unexpectedly discovered that oxidative stress, whether from external sources or derived from endogenous metabolism, drives enhanced intrinsic resistance to cephalosporins. A particular source of oxidative stress, H2O2, activates signaling through the CroR-CroS two-component signaling system, a known determinant of cephalosporin resistance in E. faecalis. We find that CroR-CroS is required for adaptation to H2O2 stress and that H2O2 potentiates the activities of cephalosporins against E. faecalis when the CroR-CroS signaling system is nonfunctional. Rather than directly detecting H2O2, our data suggest that the CroR-CroS system responds to cell envelope damage caused by H2O2 exposure in order to promote cell envelope repair and enhanced cephalosporin resistance. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  20. Helicobacter pylori-derived Heat shock protein 60 enhances angiogenesis via a CXCR2-mediated signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chen-Si [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China); School of Veterinary Medicine, National Taiwan University, Taipei, Taiwan (China); He, Pei-Juin; Hsu, Wei-Tung [Department of Biological Science and Technology, National Chiao-Tung University, Hsin-Chu, Taiwan (China); Wu, Ming-Shiang [Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Wu, Chang-Jer [Department of Food Science, National Taiwan Ocean University, Keelung, Taiwan (China); Shen, Hsiao-Wei [Institute of Molecular Medicine and Bioengineering, National Chiao-Tung University, Hsin-Chu, Taiwan (China); Hwang, Chia-Hsiang [Yung-Shin Pharmaceutical Industry Co., Ltd., Tachia, Taichung, Taiwan (China); Lai, Yiu-Kay [Department of Life Science, Institute of Biotechnology, National Tsing Hua University, Hsin-Chu, Taiwan (China); Tsai, Nu-Man [School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China); Liao, Kuang-Wen, E-mail: kitchhen@yahoo.com.tw [Institute of Molecular Medicine and Bioengineering, National Chiao-Tung University, Hsin-Chu, Taiwan (China)

    2010-06-25

    Helicobacter pylori is a potent carcinogen associated with gastric cancer malignancy. Recently, H. pylori Heat shock protein 60 (HpHSP60) has been reported to promote cancer development by inducing chronic inflammation and promoting tumor cell migration. This study demonstrates a role for HpHSP60 in angiogenesis, a necessary precursor to tumor growth. We showed that HpHSP60 enhanced cell migration and tube formation, but not cell proliferation, in human umbilical vein endothelial cells (HUVECs). HpHSP60 also indirectly promoted HUVEC proliferation when HUVECs were co-cultured with supernatants collected from HpHSP60-treated AGS or THP-1 cells. The angiogenic array showed that HpHSP60 dramatically induced THP-1 cells and HUVECs to produce the chemotactic factors IL-8 and GRO. Inhibition of CXCR2, the receptor for IL-8 and GRO, or downstream PLC{beta}2/Ca2+-mediated signaling, significantly abolished HpHSP60-induced tube formation. In contrast, suppression of MAP K or PI3 K signaling did not affect HpHSP60-mediated tubulogenesis. These data suggest that HpHSP60 enhances angiogenesis via CXCR2/PLC{beta}2/Ca2+ signal transduction in endothelial cells.

  1. In contrast to BOLD: signal enhancement by extravascular water protons as an alternative mechanism of endogenous fMRI signal change.

    Science.gov (United States)

    Figley, Chase R; Leitch, Jordan K; Stroman, Patrick W

    2010-10-01

    Despite the popularity and widespread application of functional magnetic resonance imaging (fMRI) in recent years, the physiological bases of signal change are not yet fully understood. Blood oxygen level-dependant (BOLD) contrast - attributed to local changes in blood flow and oxygenation, and therefore magnetic susceptibility - has become the most prevalent means of functional neuroimaging. However, at short echo times, spin-echo sequences show considerable deviations from the BOLD model, implying a second, non-BOLD component of signal change. This has been dubbed "signal enhancement by extravascular water protons" (SEEP) and is proposed to result from proton-density changes associated with cellular swelling. Given that such changes are independent of magnetic susceptibility, SEEP may offer new and improved opportunities for carrying out fMRI in regions with close proximity to air-tissue and/or bone-tissue interfaces (e.g., the prefrontal cortex and spinal cord), as well as regions close to large blood vessels, which may not be ideally suited for BOLD imaging. However, because of the interdisciplinary nature of the literature, there has yet to be a thorough synthesis, tying together the various and sometimes disparate aspects of SEEP theory. As such, we aim to provide a concise yet comprehensive overview of SEEP, including recent and compelling evidence for its validity, its current applications and its future relevance to the rapidly expanding field of functional neuroimaging. Before presenting the evidence for a non-BOLD component of endogenous functional contrast, and to enable a more critical review for the nonexpert reader, we begin by reviewing the fundamental principles underlying BOLD theory. Copyright © 2010 Elsevier Inc. All rights reserved.

  2. Relationship between Length and Surface-Enhanced Raman Spectroscopy Signal Strength in Metal Nanoparticle Chains: Ideal Models versus Nanofabrication

    Directory of Open Access Journals (Sweden)

    Kristen D. Alexander

    2012-01-01

    Full Text Available We have employed capillary force deposition on ion beam patterned substrates to fabricate chains of 60 nm gold nanospheres ranging in length from 1 to 9 nanoparticles. Measurements of the surface-averaged SERS enhancement factor strength for these chains were then compared to the numerical predictions. The SERS enhancement conformed to theoretical predictions in the case of only a few chains, with the vast majority of chains tested not matching such behavior. Although all of the nanoparticle chains appear identical under electron microscope observation, the extreme sensitivity of the SERS enhancement to nanoscale morphology renders current nanofabrication methods insufficient for consistent production of coupled nanoparticle chains. Notwithstanding this fact, the aggregate data also confirmed that nanoparticle dimers offer a large improvement over the monomer enhancement while conclusively showing that, within the limitations imposed by current state-of-the-art nanofabrication techniques, chains comprising more than two nanoparticles provide only a marginal signal boost over the already considerable dimer enhancement.

  3. A bacterial signal peptidase enhances processing of a recombinant single chain antibody fragment in insect cells

    NARCIS (Netherlands)

    Ailor, E; Pathmanathan, J; Jongbloed, JDH; Betenbaugh, MJ

    1999-01-01

    The production of an antibody single chain fragment (scFv) in insect cells was accompanied by the formation of an insoluble intracellular precursor even with the inclusion of the bee melittin signal peptide. The presence of the precursor polypeptide suggests a limitation in the processing of the

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

    DEFF Research Database (Denmark)

    1998-01-01

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

  5. A capillary-based probe for in situ detection of enhanced fluorescence signals

    Science.gov (United States)

    Long, F.; Xiao, R.; Zhu, A. N.; Shi, H. C.; Wang, S. Q.

    2013-07-01

    A simple, compact, and high sensitivity capillary-based probe for the in situ detection of fluorescence signals with high sensitivity is demonstrated. A home-made single-multi-mode fiber coupler that is coaxially aligned with the capillary-based probe provides for the transmission of excitation light and the collection and transmission of fluorescence. We propose a conceptually straightforward theoretical model to optimize the factors affecting the fluorescence-capture capability of the capillary-based probe. The fluorescence signal detected by fiber-optic spectroscopy non-linearly increases with the length of the capillary-based probe. In addition, the thicker the capillary tube wall is, the less the fluorescence signals determined are. The performance of the proposed probe is evaluated experimentally by measuring the fluorescence spectra of Cy5.5 dye and blue-green algae. The experimental results show that the proposed probe provides more than a ten-fold increase in fluorescence signal compared with direct measurements by a flat-tipped multi-mode fiber probe. The advantages of the capillary-based probe, which include its simple and compact structure, excellent light collection efficiency, requirement of small sample volume, and recoverability of samples, allow its wide application to in situ detection in the medical, forensic, biological, geological, and environmental fields with high sensitivity.

  6. Calmodulin physically interacts with the erythropoietin receptor and enhances Jak2-mediated signaling

    International Nuclear Information System (INIS)

    Kakihana, Kazuhiko; Yamamoto, Masahide; Iiyama, Mitsuko; Miura, Osamu

    2005-01-01

    Stimulation of the erythropoietin receptor (EpoR) induces a transient increase in intracellular Ca 2+ level as well as activation of the Jak2 tyrosine kinase to stimulate various downstream signaling pathways. Here, we demonstrate that the universal Ca 2+ receptor calmodulin (CaM) binds EpoR in a Ca 2+ -dependent manner in vitro. Binding studies using various EpoR mutants in hematopoietic cells showed that CaM binds the membrane-proximal 65-amino-acid cytoplasmic region (amino acids 258-312) of EpoR that is critical for activation of Jak2-mediated EpoR signaling. Structurally unrelated CaM antagonists, W-13 and CMZ, inhibited activation of Jak2-mediated EpoR signaling pathways, whereas W-12, a W-13 analog, did not show any significant inhibitory effect. Moreover, overexpression of CaM augmented Epo-induced tyrosine phosphorylation of the EpoR. W-13, but not W-12, also inhibited Epo-induced proliferation and survival. Together, these results indicate that CaM binds to the membrane-proximal EpoR cytoplasmic region and plays an essential role in activation of Jak2-mediated EpoR signaling

  7. Bacillus licheniformis Isolated from Traditional Korean Food Resources Enhances the Longevity of Caenorhabditis elegans through Serotonin Signaling.

    Science.gov (United States)

    Park, Mi Ri; Oh, Sangnam; Son, Seok Jun; Park, Dong-June; Oh, Sejong; Kim, Sae Hun; Jeong, Do-Youn; Oh, Nam Su; Lee, Youngbok; Song, Minho; Kim, Younghoon

    2015-12-02

    In this study, we investigated potentially probiotic Bacillus licheniformis strains isolated from traditional Korean food sources for ability to enhance longevity using the nematode Caenorhabditis elegans as a simple in vivo animal model. We first investigated whether B. licheniformis strains were capable of modulating the lifespan of C. elegans. Among the tested strains, preconditioning with four B. licheniformis strains significantly enhanced the longevity of C. elegans. Unexpectedly, plate counting and transmission electron microscopy (TEM) results indicated that B. licheniformis strains were not more highly attached to the C. elegans intestine compared with Escherichia coli OP50 or Lactobacillus rhamnosus GG controls. In addition, qRT-PCR and an aging assay with mutant worms showed that the conditioning of B. licheniformis strain 141 directly influenced genes associated with serotonin signaling in nematodes, including tph-1 (tryptophan hydroxylase), bas-1 (serotonin- and dopamine-synthetic aromatic amino acid decarboxylase), mod-1 (serotonin-gated chloride channel), ser-1, and ser-7 (serotonin receptors) during C. elegans aging. Our findings suggest that B. licheniformis strain 141, which is isolated from traditional Korean foods, is a probiotic generally recognized as safe (GRAS) strain that enhances the lifespan of C. elegans via host serotonin signaling.

  8. Signal enhancement in nano-Raman spectroscopy by gold caps on silicon nanowires obtained by vapour-liquid-solid growth

    International Nuclear Information System (INIS)

    Christiansen, S H; Becker, M; Fahlbusch, S; Michler, J; Sivakov, V; Andrae, G; Geiger, R

    2007-01-01

    Silicon nanowires grown by the vapour-liquid-solid growth mechanism with gold as the catalyst show gold caps ∼50-400 nm in diameter with an almost ideal hemispherical shape atop a silicon column. These gold caps are extremely well suited for exploiting the tip or surface enhanced Raman scattering effects since they assume the right size on the nanometre scale and a reproducible, almost ideal hemispherical shape. On attaching a nanowire with a gold cap to an atomic force microscopy (AFM) tip, the signal enhancement by the gold nanoparticle can be used to spatially resolve a Raman signal. Applications of this novel nanowire based technical tip enhanced Raman scattering solution are widespread and lie in the fields of biomedical and life sciences as well as security (e.g. detection of bacteria and explosives) and in the field of solid state research, e.g. in silicon technology where the material composition, doping, crystal orientation and lattice strain can be probed by Raman spectroscopy. A prerequisite for obtaining this spatial resolution in nano-Raman spectroscopy is the attachment of a nanowire with a gold cap to an AFM tip. This attachment by welding a nanowire in a scanning electron microscope to an AFM tip is demonstrated in this paper

  9. Signal enhancement in nano-Raman spectroscopy by gold caps on silicon nanowires obtained by vapour liquid solid growth

    Science.gov (United States)

    Christiansen, S. H.; Becker, M.; Fahlbusch, S.; Michler, J.; Sivakov, V.; Andrä, G.; Geiger, R.

    2007-01-01

    Silicon nanowires grown by the vapour-liquid-solid growth mechanism with gold as the catalyst show gold caps ~50-400 nm in diameter with an almost ideal hemispherical shape atop a silicon column. These gold caps are extremely well suited for exploiting the tip or surface enhanced Raman scattering effects since they assume the right size on the nanometre scale and a reproducible, almost ideal hemispherical shape. On attaching a nanowire with a gold cap to an atomic force microscopy (AFM) tip, the signal enhancement by the gold nanoparticle can be used to spatially resolve a Raman signal. Applications of this novel nanowire based technical tip enhanced Raman scattering solution are widespread and lie in the fields of biomedical and life sciences as well as security (e.g. detection of bacteria and explosives) and in the field of solid state research, e.g. in silicon technology where the material composition, doping, crystal orientation and lattice strain can be probed by Raman spectroscopy. A prerequisite for obtaining this spatial resolution in nano-Raman spectroscopy is the attachment of a nanowire with a gold cap to an AFM tip. This attachment by welding a nanowire in a scanning electron microscope to an AFM tip is demonstrated in this paper.

  10. Signal enhancement in nano-Raman spectroscopy by gold caps on silicon nanowires obtained by vapour-liquid-solid growth.

    Science.gov (United States)

    Christiansen, S H; Becker, M; Fahlbusch, S; Michler, J; Sivakov, V; Andrä, G; Geiger, R

    2007-01-24

    Silicon nanowires grown by the vapour-liquid-solid growth mechanism with gold as the catalyst show gold caps approximately 50-400 nm in diameter with an almost ideal hemispherical shape atop a silicon column. These gold caps are extremely well suited for exploiting the tip or surface enhanced Raman scattering effects since they assume the right size on the nanometre scale and a reproducible, almost ideal hemispherical shape. On attaching a nanowire with a gold cap to an atomic force microscopy (AFM) tip, the signal enhancement by the gold nanoparticle can be used to spatially resolve a Raman signal. Applications of this novel nanowire based technical tip enhanced Raman scattering solution are widespread and lie in the fields of biomedical and life sciences as well as security (e.g. detection of bacteria and explosives) and in the field of solid state research, e.g. in silicon technology where the material composition, doping, crystal orientation and lattice strain can be probed by Raman spectroscopy. A prerequisite for obtaining this spatial resolution in nano-Raman spectroscopy is the attachment of a nanowire with a gold cap to an AFM tip. This attachment by welding a nanowire in a scanning electron microscope to an AFM tip is demonstrated in this paper.

  11. Metagenome-based diversity analyses suggest a strong locality signal for bacterial communities associated with oyster aquaculture farms in Ofunato Bay

    KAUST Repository

    Kobiyama, Atsushi

    2018-04-30

    Ofunato Bay, in Japan, is the home of buoy-and-rope-type oyster aquaculture activities. Since the oysters filter suspended materials and excrete organic matter into the seawater, bacterial communities residing in its vicinity may show dynamic changes depending on the oyster culture activities. We employed a shotgun metagenomic technique to study bacterial communities near oyster aquaculture facilities at the center of the bay (KSt. 2) and compared the results with those of two other localities far from the station, one to the northeast (innermost bay, KSt. 1) and the other to the southwest (bay entrance, KSt. 3). Seawater samples were collected every month from January to December 2015 from the surface (1 m) and deeper (8 or 10 m) layers of the three locations, and the sequentially filtered fraction on 0.2-μm membranes was sequenced on an Illumina MiSeq system. The acquired reads were uploaded to MG-RAST for KEGG functional abundance analysis, while taxonomic analyses at the phylum and genus levels were performed using MEGAN after parsing the BLAST output. Discrimination analyses were then performed using the ROC-AUC value of the cross validation, targeting the depth (shallow or deep), locality [(KSt. 1 + KSt. 2) vs. KSt 3; (KSt. 1 + KSt. 3) vs. KSt. 2 or the (KSt. 2 + KSt. 3) vs. KSt. 1] and seasonality (12 months). The matrix discrimination analysis on the adjacent 2 continuous seasons by ROC-AUC, which was based on the datasets that originated from different depths, localities and months, showed the strongest discrimination signal on the taxonomy matrix at the phylum level for the datasets from July to August compared with those from September to June, while the KEGG matrix showed the strongest signal for the datasets from March to June compared with those from July to February. Then, the locality combination was subjected to the same ROC-AUC discrimination analysis, resulting in significant differences between KSt. 2 and KSt. 1 + KSt. 3

  12. Sustained Persistence of IL2 Signaling Enhances the Antitumor Effect of Peptide Vaccines through T-cell Expansion and Preventing PD-1 Inhibition.

    Science.gov (United States)

    Sultan, Hussein; Kumai, Takumi; Fesenkova, Valentyna I; Fan, Aaron E; Wu, Juan; Cho, Hyun-Il; Kobayashi, Hiroya; Harabuchi, Yasuaki; Celis, Esteban

    2018-02-26

    Peptide vaccines can be a successful and cost-effective way of generating T-cell responses against defined tumor antigens, especially when combined with immune adjuvants such as poly-IC. However, strong immune adjuvants can induce a collateral increase in numbers of irrelevant, nonspecific T cells, which limits the effectiveness of the peptide vaccines. Here, we report that providing prolonged IL2 signaling in the form of either IL2/anti-IL2 complexes or pegylated IL2 overcomes the competitive suppressive effect of irrelevant T cells, allowing the preferential expansion of antigen-specific T cells. In addition to increasing the number of tumor-reactive T cells, sustained IL2 enhanced the ability of T cells to resist PD-1-induced negative signals, increasing the therapeutic effectiveness of the vaccines against established tumors. This vaccination strategy using peptides and sustained IL2 could be taken into the clinic for the treatment of cancer. Cancer Immunol Res; 6(5); 1-11. ©2018 AACR. ©2018 American Association for Cancer Research.

  13. EGFR signaling enhances aerobic glycolysis in triple negative breast cancer cells to promote tumor growth and immune escape

    Science.gov (United States)

    Lim, Seung-Oe; Li, Chia-Wei; Xia, Weiya; Lee, Heng-Huan; Chang, Shih-Shin; Shen, Jia; Hsu, Jennifer L.; Raftery, Dan; Djukovic, Danijel; Gu, Haiwei; Chang, Wei-Chao; Wang, Hung-Ling; Chen, Mong-Liang; Huo, Longfei; Chen, Chung-Hsuan; Wu, Yun; Sahin, Aysegul; Hanash, Samir M.; Hortobagyi, Gabriel N.; Hung, Mien-Chie

    2016-01-01

    Oncogenic signaling reprograms cancer cell metabolism to augment the production of glycolytic metabolites in favor of tumor growth. The ability of cancer cells to evade immunosurveillance and the role of metabolic regulators in T cell functions suggest that oncogene-induced metabolic reprogramming may be linked to immune escape. Epidermal growth factor (EGF) signaling, frequently dysregulated in triple-negative breast cancer (TNBC), is also associated with increased glycolysis. Here, we demonstrated in TNBC cells that EGF signaling activates the first step in glycolysis, but impedes the last step, leading to an accumulation of metabolic intermediates in this pathway. Furthermore, we showed that one of these intermediates, fructose 1,6 bisphosphate (F1,6BP), directly binds to and enhances the activity of the EGF receptor (EGFR), thereby increasing lactate excretion which leads to inhibition of local cytotoxic T cell activity. Notably, combining the glycolysis inhibitor 2-deoxy-D-glucose (2-DG) with the EGFR inhibitor gefitinib effectively suppressed TNBC cell proliferation and tumor growth. Our results illustrate how jointly targeting the EGFR/F1,6BP signaling axis may offer an immediately applicable therapeutic strategy to treat TNBC. PMID:26759242

  14. An investigation of signal performance enhancements achieved through innovative pixel design across several generations of indirect detection, active matrix, flat-panel arrays

    International Nuclear Information System (INIS)

    Antonuk, Larry E.; Zhao Qihua; El-Mohri, Youcef; Du Hong; Wang Yi; Street, Robert A.; Ho, Jackson; Weisfield, Richard; Yao, William

    2009-01-01

    Active matrix flat-panel imager (AMFPI) technology is being employed for an increasing variety of imaging applications. An important element in the adoption of this technology has been significant ongoing improvements in optical signal collection achieved through innovations in indirect detection array pixel design. Such improvements have a particularly beneficial effect on performance in applications involving low exposures and/or high spatial frequencies, where detective quantum efficiency is strongly reduced due to the relatively high level of additive electronic noise compared to signal levels of AMFPI devices. In this article, an examination of various signal properties, as determined through measurements and calculations related to novel array designs, is reported in the context of the evolution of AMFPI pixel design. For these studies, dark, optical, and radiation signal measurements were performed on prototype imagers incorporating a variety of increasingly sophisticated array designs, with pixel pitches ranging from 75 to 127 μm. For each design, detailed measurements of fundamental pixel-level properties conducted under radiographic and fluoroscopic operating conditions are reported and the results are compared. A series of 127 μm pitch arrays employing discrete photodiodes culminated in a novel design providing an optical fill factor of ∼80% (thereby assuring improved x-ray sensitivity), and demonstrating low dark current, very low charge trapping and charge release, and a large range of linear signal response. In two of the designs having 75 and 90 μm pitches, a novel continuous photodiode structure was found to provide fill factors that approach the theoretical maximum of 100%. Both sets of novel designs achieved large fill factors by employing architectures in which some, or all of the photodiode structure was elevated above the plane of the pixel addressing transistor. Generally, enhancement of the fill factor in either discrete or continuous

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

    Science.gov (United States)

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

    1997-07-01

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

  16. Attenuating GABA(A) receptor signaling in dopamine neurons selectively enhances reward learning and alters risk preference in mice.

    Science.gov (United States)

    Parker, Jones G; Wanat, Matthew J; Soden, Marta E; Ahmad, Kinza; Zweifel, Larry S; Bamford, Nigel S; Palmiter, Richard D

    2011-11-23

    Phasic dopamine (DA) transmission encodes the value of reward-predictive stimuli and influences both learning and decision-making. Altered DA signaling is associated with psychiatric conditions characterized by risky choices such as pathological gambling. These observations highlight the importance of understanding how DA neuron activity is modulated. While excitatory drive onto DA neurons is critical for generating phasic DA responses, emerging evidence suggests that inhibitory signaling also modulates these responses. To address the functional importance of inhibitory signaling in DA neurons, we generated mice lacking the β3 subunit of the GABA(A) receptor specifically in DA neurons (β3-KO mice) and examined their behavior in tasks that assessed appetitive learning, aversive learning, and risk preference. DA neurons in midbrain slices from β3-KO mice exhibited attenuated GABA-evoked IPSCs. Furthermore, electrical stimulation of excitatory afferents to DA neurons elicited more DA release in the nucleus accumbens of β3-KO mice as measured by fast-scan cyclic voltammetry. β3-KO mice were more active than controls when given morphine, which correlated with potential compensatory upregulation of GABAergic tone onto DA neurons. β3-KO mice learned faster in two food-reinforced learning paradigms, but extinguished their learned behavior normally. Enhanced learning was specific for appetitive tasks, as aversive learning was unaffected in β3-KO mice. Finally, we found that β3-KO mice had enhanced risk preference in a probabilistic selection task that required mice to choose between a small certain reward and a larger uncertain reward. Collectively, these findings identify a selective role for GABA(A) signaling in DA neurons in appetitive learning and decision-making.

  17. Sphingosine-1-phosphate enhances satellite cell activation in dystrophic muscles through a S1PR2/STAT3 signaling pathway.

    Directory of Open Access Journals (Sweden)

    Kenneth C Loh

    Full Text Available Sphingosine-1-phosphate (S1P activates a widely expressed family of G protein-coupled receptors, serves as a muscle trophic factor and activates muscle stem cells called satellite cells (SCs through unknown mechanisms. Here we show that muscle injury induces dynamic changes in S1P signaling and metabolism in vivo. These changes include early and profound induction of the gene encoding the S1P biosynthetic enzyme SphK1, followed by induction of the catabolic enzyme sphingosine phosphate lyase (SPL 3 days later. These changes correlate with a transient increase in circulating S1P levels after muscle injury. We show a specific requirement for SphK1 to support efficient muscle regeneration and SC proliferation and differentiation. Mdx mice, which serve as a model for muscular dystrophy (MD, were found to be S1P-deficient and exhibited muscle SPL upregulation, suggesting that S1P catabolism is enhanced in dystrophic muscle. Pharmacological SPL inhibition increased muscle S1P levels, improved mdx muscle regeneration and enhanced SC proliferation via S1P receptor 2 (S1PR2-dependent inhibition of Rac1, thereby activating Signal Transducer and Activator of Transcription 3 (STAT3, a central player in inflammatory signaling. STAT3 activation resulted in p21 and p27 downregulation in a S1PR2-dependent fashion in myoblasts. Our findings suggest that S1P promotes SC progression through the cell cycle by repression of cell cycle inhibitors via S1PR2/STAT3-dependent signaling and that SPL inhibition may provide a therapeutic strategy for MD.

  18. Solid and liquid 129Xe NMR signals enhanced by spin-exchange optical pumping under flow

    International Nuclear Information System (INIS)

    Zhou Xin; Luo Jun; Sun Xianping; Zeng Xizhi; Liu Maili; Liu Wuyang

    2002-01-01

    Laser-polarized 129 Xe gas was produced by spin-exchange with Cs atom optically pumped with diode laser array in a low field under flow. The nuclear spin polarizations of the solid and liquid 129 Xe frozen from the laser-polarized 129 Xe gas were 2.16% and 1.45% respectively in the SY-80M NMR spectrometer, which corresponded to the enhancements of 6000 and 5000 compared to those without optical pumping under the same conditions. It could provide the base and possibility for quantum computers using laser-enhanced solid and liquid 129 Xe. Polarization loss of transport and state change was also discussed

  19. Two Methods of Automatic Evaluation of Speech Signal Enhancement Recorded in the Open-Air MRI Environment

    Science.gov (United States)

    Přibil, Jiří; Přibilová, Anna; Frollo, Ivan

    2017-12-01

    The paper focuses on two methods of evaluation of successfulness of speech signal enhancement recorded in the open-air magnetic resonance imager during phonation for the 3D human vocal tract modeling. The first approach enables to obtain a comparison based on statistical analysis by ANOVA and hypothesis tests. The second method is based on classification by Gaussian mixture models (GMM). The performed experiments have confirmed that the proposed ANOVA and GMM classifiers for automatic evaluation of the speech quality are functional and produce fully comparable results with the standard evaluation based on the listening test method.

  20. WaterControl: self-diffusion based solvent signal suppression enhanced by selective inversion.

    Science.gov (United States)

    Zheng, Gang; Torres, Allan M; Price, William S

    2017-05-01

    Selective inversion/excitation based solvent signal suppression techniques are widely used in various NMR experiments because of their high efficiency and general applicability. However, these techniques generate a 'null'/suppression region containing (non-quantitatively) degraded solvent and desired resonances because of their reliance on the rejection of the coherence transfer pathway corresponding to all the resonances within the suppression region. To address this issue, the WaterControl technique was developed by inserting a (pulsed gradient - selective inversion pulse - pulsed gradient) unit into each 'transverse' period of a standard stimulated echo pulse sequence so that the coherence transfer pathways corresponding to both the suppression and non-suppression regions can be selected in one transient. The new sequence affords a diffusion based and quantifiable solvent signal suppression with no or minimal loss of features of interest. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  1. Influence of multi-microphone signal enhancement algorithms on auditory movement detection in acoustically complex situations

    DEFF Research Database (Denmark)

    Lundbeck, Micha; Hartog, Laura; Grimm, Giso

    2017-01-01

    The influence of hearing aid (HA) signal processing on the perception of spatially dynamic sounds has not been systematically investigated so far. Previously, we observed that interfering sounds impaired the detectability of left-right source movements and reverberation that of near-far source...... movements for elderly hearing-impaired (EHI) listeners (Lundbeck et al., 2017). Here, we explored potential ways of improving these deficits with HAs. To that end, we carried out acoustic analyses to examine the impact of two beamforming algorithms and a binaural coherence-based noise reduction scheme...... on the cues underlying movement perception. While binaural cues remained mostly unchanged, there were greater monaural spectral changes and increases in signal-to-noise ratio and direct-to-reverberant sound ratio as a result of the applied processing. Based on these findings, we conducted a listening test...

  2. Influence of multi-microphone signal enhancement algorithms on auditory movement detection in acoustically complex situations

    DEFF Research Database (Denmark)

    Lundbeck, Micha; Hartog, Laura; Grimm, Giso

    The influence of hearing aid (HA) signal processing on the perception of spatially dynamic sounds has not been systematically investigated so far. Previously, we observed that for elderly hearing-impaired (EHI) listeners concurrent distractor sounds impaired the detectability of left-right source...... movements, and reverberation that of near-far source movements (Lundbeck et al, Trends Hear 2017). Here, we explored potential ways of improving these deficits with HAs. To that end, we carried out detailed acoustic analyses on the stimuli used previously to examine the impact of two beamforming algorithms...... and a binaural coherence-based noise reduction scheme on the cues underlying movement perception. While the binaural cues remained mostly unchanged, the applied processing led to greater monaural spectral changes, as well as increases in signal-to-noise ratio and direct-to-reverberant sound ratio. Based...

  3. Enhanced insulin receptor, but not PI3K, signalling protects podocytes from ER stress.

    Science.gov (United States)

    Garner, Kathryn L; Betin, Virginie M S; Pinto, Vanda; Graham, Mark; Abgueguen, Emmanuelle; Barnes, Matt; Bedford, David C; McArdle, Craig A; Coward, Richard J M

    2018-03-02

    Disruption of the insulin-PI3K-Akt signalling pathway in kidney podocytes causes endoplasmic reticulum (ER) stress, leading to podocyte apoptosis and proteinuria in diabetic nephropathy. We hypothesised that by improving insulin sensitivity we could protect podocytes from ER stress. Here we use established activating transcription factor 6 (ATF6)- and ER stress element (ERSE)-luciferase assays alongside a novel high throughput imaging-based C/EBP homologous protein (CHOP) assay to examine three models of improved insulin sensitivity. We find that by improving insulin sensitivity at the level of the insulin receptor (IR), either by IR over-expression or by knocking down the negative regulator of IR activity, protein tyrosine-phosphatase 1B (PTP1B), podocytes are protected from ER stress caused by fatty acids or diabetic media containing high glucose, high insulin and inflammatory cytokines TNFα and IL-6. However, contrary to this, knockdown of the negative regulator of PI3K-Akt signalling, phosphatase and tensin homolog deleted from chromosome 10 (PTEN), sensitizes podocytes to ER stress and apoptosis, despite increasing Akt phosphorylation. This indicates that protection from ER stress is conferred through not just the PI3K-Akt pathway, and indeed we find that inhibiting the MEK/ERK signalling pathway rescues PTEN knockdown podocytes from ER stress.

  4. An Enhanced Data Visualization Method for Diesel Engine Malfunction Classification Using Multi-Sensor Signals

    Directory of Open Access Journals (Sweden)

    Yiqing Li

    2015-10-01

    Full Text Available The various multi-sensor signal features from a diesel engine constitute a complex high-dimensional dataset. The non-linear dimensionality reduction method, t-distributed stochastic neighbor embedding (t-SNE, provides an effective way to implement data visualization for complex high-dimensional data. However, irrelevant features can deteriorate the performance of data visualization, and thus, should be eliminated a priori. This paper proposes a feature subset score based t-SNE (FSS-t-SNE data visualization method to deal with the high-dimensional data that are collected from multi-sensor signals. In this method, the optimal feature subset is constructed by a feature subset score criterion. Then the high-dimensional data are visualized in 2-dimension space. According to the UCI dataset test, FSS-t-SNE can effectively improve the classification accuracy. An experiment was performed with a large power marine diesel engine to validate the proposed method for diesel engine malfunction classification. Multi-sensor signals were collected by a cylinder vibration sensor and a cylinder pressure sensor. Compared with other conventional data visualization methods, the proposed method shows good visualization performance and high classification accuracy in multi-malfunction classification of a diesel engine.

  5. An enhanced data visualization method for diesel engine malfunction classification using multi-sensor signals.

    Science.gov (United States)

    Li, Yiqing; Wang, Yu; Zi, Yanyang; Zhang, Mingquan

    2015-10-21

    The various multi-sensor signal features from a diesel engine constitute a complex high-dimensional dataset. The non-linear dimensionality reduction method, t-distributed stochastic neighbor embedding (t-SNE), provides an effective way to implement data visualization for complex high-dimensional data. However, irrelevant features can deteriorate the performance of data visualization, and thus, should be eliminated a priori. This paper proposes a feature subset score based t-SNE (FSS-t-SNE) data visualization method to deal with the high-dimensional data that are collected from multi-sensor signals. In this method, the optimal feature subset is constructed by a feature subset score criterion. Then the high-dimensional data are visualized in 2-dimension space. According to the UCI dataset test, FSS-t-SNE can effectively improve the classification accuracy. An experiment was performed with a large power marine diesel engine to validate the proposed method for diesel engine malfunction classification. Multi-sensor signals were collected by a cylinder vibration sensor and a cylinder pressure sensor. Compared with other conventional data visualization methods, the proposed method shows good visualization performance and high classification accuracy in multi-malfunction classification of a diesel engine.

  6. Immobilization Techniques and Integrated Signal Enhancement for POC Nanocolor Microfluidic Devices

    Directory of Open Access Journals (Sweden)

    Marlies Schlauf

    2015-01-01

    Full Text Available Resonance enhanced absorption (REA nanocolor microfluidic devices are new promising bioassay platforms, which employ nanoparticle- (NP- protein conjugates for the immunodetection of medically relevant markers in biologic samples such as blood, urine, and saliva. The core component of a REA test device is a PET chip coated with aluminum and SiO2 thin layers, onto which biorecognitive molecules are immobilized. Upon addition of a sample containing the analyte of interest, a NP-protein-analyte complex is formed in the test device that is captured on the REA chip, for example, via streptavidin-biotin interaction. Thereby, a colored symbol is generated, which allows optical readout. Silver enhancement of the bound nanoparticles may be used to increase the sensitivity of the assay. Herein, we demonstrate that adsorptive immobilization via a cationic polymeric interlayer is a competitive and fast technique for the binding of the capture protein streptavidin onto planar SiO2 surfaces such as REA biochips. Moreover, we report the development of a silver enhancement technology that operates even in the presence of high chloride concentrations as may be encountered in biologic samples. The silver enhancement reagents may be integrated into the microfluidic assay platform to be released upon sample addition. Hereby, a highly sensitive one-step assay can be realized.

  7. Black ginseng activates Akt signaling, thereby enhancing myoblast differentiation and myotube growth

    Directory of Open Access Journals (Sweden)

    Soo-Yeon Lee

    2018-01-01

    Conclusion: BG enhances myoblast differentiation and myotube hypertrophy by activating Akt/mTOR/p70S6k axis. Thus, our study demonstrates that BG has promising potential to treat or prevent muscle loss related to aging or other pathological conditions, such as diabetes.

  8. Mathematical model for biomolecular quantification using surface-enhanced Raman spectroscopy based signal intensity distributions

    DEFF Research Database (Denmark)

    Palla, Mirko; Bosco, Filippo Giacomo; Yang, Jaeyoung

    2015-01-01

    This paper presents the development of a novel statistical method for quantifying trace amounts of biomolecules by surface-enhanced Raman spectroscopy (SERS) using a rigorous, single molecule (SM) theory based mathematical derivation. Our quantification framework could be generalized for planar...

  9. Enhanced signal-to-noise ratio estimation for tropospheric lidar channels

    Science.gov (United States)

    Saeed, Umar; Barragan, Rubén; Rocadenbosch, Francesc

    2016-04-01

    This works combines the fields of tropospheric lidar remote sensing and signal processing to come up with a robust signal-to-noise ratio (SNR) estimator apt for elastic and Raman channels. The estimator uses a combined low-pass / high-pass filtering scheme along with high-order statistics (kurtosis) to estimate the range-dependent signal and noise components with minimum distortion. While low-pass filtering is used to estimate the range-dependent signal level, high-pass filtering is used to estimate the noise component with minimum distortion. From this noise component estimate (a random realization) the noise level (e.g., variance) is computed as a function of range along with error bars. The minimum-distortion specification determines the optimal cut-off de-noising filter frequency and, in turn, the spatial resolution of the SNR estimation algorithm. The proposed SNR estimator has a much wider dynamic range of operation than well-known classic SNR estimation techniques, in which the SNR is directly computed from the mean and standard deviation of the measured noise-corrupted lidar signal along successive adjacent range intervals and where the spatial resolution is just a subjective input from the user's side. Aligned with ACTRIS (http://www.actris.net) WP on "optimization of the processing chain and Single-Calculus Chain (SCC)" the proposed topic is of application to assess lidar reception channel performance and confidence on the detected atmospheric morphology (e.g., cloud base and top, and location of aerosol layers). The SNR algorithm is tested against the classic SNR estimation approach using test-bed synthetic lidar data modelling the UPC multi-spectral lidar. Towards this end, the Nd:YAG UPC elastic-Raman lidar provides aerosol channels in the near-infrared (1064 nm), visible (532 nm), and ultra-violet (355 nm) as well as aerosol Raman and water-vapour channels with fairly varying SNR levels. The SNR estimator is also used to compare SNR levels between

  10. Trypanosoma cruzi infection is a potent risk factor for non-alcoholic steatohepatitis enhancing local and systemic inflammation associated with strong oxidative stress and metabolic disorders.

    Directory of Open Access Journals (Sweden)

    Luisina I Onofrio

    2015-02-01

    Full Text Available The immune mechanisms underlying experimental non-alcoholic steatohepatitis (NASH, and more interestingly, the effect of T. cruzi chronic infection on the pathogenesis of this metabolic disorder are not completely understood.We evaluated immunological parameters in male C57BL/6 wild type and TLR4 deficient mice fed with a standard, low fat diet, LFD (3% fat as control group, or a medium fat diet, MFD (14% fat in order to induce NASH, or mice infected intraperitoneally with 100 blood-derived trypomastigotes of Tulahuen strain and also fed with LFD (I+LFD or MFD (I+MFD for 24 weeks. We demonstrated that MFD by itself was able to induce NASH in WT mice and that parasitic infection induced marked metabolic changes with reduction of body weight and steatosis revealed by histological studies. The I+MFD group also improved insulin resistance, demonstrated by homeostasis model assessment of insulin resistance (HOMA-IR analysis; although parasitic infection increased the triglycerides and cholesterol plasma levels. In addition, hepatic M1 inflammatory macrophages and cytotoxic T cells showed intracellular inflammatory cytokines which were associated with high levels of IL6, IFNγ and IL17 plasmatic cytokines and CCL2 chemokine. These findings correlated with an increase in hepatic parasite load in I+MFD group demonstrated by qPCR assays. The recruitment of hepatic B lymphocytes, NK and dendritic cells was enhanced by MFD, and it was intensified by parasitic infection. These results were TLR4 signaling dependent. Flow cytometry and confocal microscopy analysis demonstrated that the reactive oxygen species and peroxinitrites produced by liver inflammatory leukocytes of MFD group were also exacerbated by parasitic infection in our NASH model.We highlight that a medium fat diet by itself is able to induce steatohepatitis. Our results also suggest a synergic effect between damage associated with molecular patterns generated during NASH and parasitic infection

  11. miR-19a: an effective regulator of SOCS3 and enhancer of JAK-STAT signalling.

    Directory of Open Access Journals (Sweden)

    Aideen S Collins

    Full Text Available Suppressors of cytokine signalling (SOCS proteins are classic inhibitors of the Janus kinase-signal transducer and activator of transcription (JAK-STAT pathway. Many cytokines and pathogenic mediators induce expression of SOCS, which act in a negative feedback loop to inhibit further signal transduction. SOCS mRNA expression is regulated by DNA binding of STAT proteins, however, their post-transcriptional regulation is poorly understood. microRNAs (miRNAs are small non-coding RNAs that bind to complementary sequences on target mRNAs, often silencing gene expression. miR-19a has been shown to regulate SOCS1 expression during mutiple myeloma and be induced by the anti-viral cytokine interferon-(IFN-α, suggesting a role in the regulation of the JAK-STAT pathway. This study aimed to identify targets of miR-19a in the JAK-STAT pathway and elucidate the functional consequences. Bioinformatic analysis identified highly conserved 3'UTR miR-19a target sequences in several JAK-STAT associated genes, including SOCS1, SOCS3, SOCS5 and Cullin (Cul 5. Functional studies revealed that miR-19a significantly decreased SOCS3 mRNA and protein, while a miR-19a antagomir specifically reversed its inhibitory effect. Furthermore, miR-19a-mediated reduction of SOCS3 enhanced IFN-α and interleukin (IL-6 signal transduction through STAT3. These results reveal a novel mechanism by which miR-19a may augment JAK-STAT signal transduction via control of SOCS3 expression and are fundamental to the understanding of inflammatory regulation.

  12. Glycine enhances muscle protein mass associated with maintaining Akt-mTOR-FOXO1 signaling and suppressing TLR4 and NOD2 signaling in piglets challenged with LPS.

    Science.gov (United States)

    Liu, Yulan; Wang, Xiuying; Wu, Huanting; Chen, Shaokui; Zhu, Huiling; Zhang, Jing; Hou, Yongqing; Hu, Chien-An Andy; Zhang, Guolong

    2016-08-01

    Pro-inflammatory cytokines play a critical role in the pathophysiology of muscle atrophy. We hypothesized that glycine exerted an anti-inflammatory effect and alleviated lipopolysaccharide (LPS)-induced muscle atrophy in piglets. Pigs were assigned to four treatments including the following: 1) nonchallenged control, 2) LPS-challenged control, 3) LPS+1.0% glycine, and 4) LPS+2.0% glycine. After receiving the control, 1.0 or 2.0% glycine-supplemented diets, piglets were treated with either saline or LPS. At 4 h after treatment with saline or LPS, blood and muscle samples were harvested. We found that 1.0 or 2.0% glycine increased protein/DNA ratio, protein content, and RNA/DNA ratio in gastrocnemius or longissimus dorsi (LD) muscles. Glycine also resulted in decreased mRNA expression of muscle atrophy F-box (MAFbx) and muscle RING finger 1 (MuRF1) in gastrocnemius muscle. In addition, glycine restored the phosphorylation of Akt, mammalian target of rapamycin (mTOR), eukaryotic initiation factor 4E binding protein 1 (4E-BP1), and Forkhead Box O 1 (FOXO1) in gastrocnemius or LD muscles. Furthermore, glycine resulted in decreased plasma tumor necrosis factor-α (TNF-α) concentration and muscle TNF-α mRNA abundance. Moreover, glycine resulted in decreased mRNA expresson of Toll-like receptor 4 (TLR4), nucleotide-binding oligomerization domain protein 2 (NOD2), and their respective downstream molecules in gastrocnemius or LD muscles. These results indicate glycine enhances muscle protein mass under an inflammatory condition. The beneficial roles of glycine on the muscle are closely associated with maintaining Akt-mTOR-FOXO1 signaling and suppressing the activation of TLR4 and/or NOD2 signaling pathways. Copyright © 2016 the American Physiological Society.

  13. Enhancing scatterometry CD signal-to-noise ratio for 1x logic and memory challenges

    Science.gov (United States)

    Shaughnessy, Derrick; Krishnan, Shankar; Wei, Lanhua; Shchegrov, Andrei V.

    2013-04-01

    The ongoing transition from 2D to 3D structures in logic and memory has led to an increased adoption of scatterometry CD (SCD) for inline metrology. However, shrinking device dimensions in logic and high aspect ratios in memory represent primary challenges for SCD and require a significant breakthrough in improving signal-to-noise performance. We present a report on the new generation of SCD technology, enabled by a new laser-driven plasma source. The developed light source provides several key advantages over conventional arc lamps typically used in SCD applications. The plasma color temperature of the laser driven source is considerably higher than available with arc lamps resulting in >5X increase in radiance in the visible and >10X increase in radiance in the DUV when compared to sources on previous generation SCD tools while maintaining or improving source intensity noise. This high radiance across such a broad spectrum allows for the use of a single light source from 190-1700nm. When combined with other optical design changes, the higher source radiance enables reduction of measurement box size of our spectroscopic ellipsometer from 45×45um box to 25×25um box without compromising signal to noise ratio. The benefits for 1×nm SCD metrology of the additional photons across the DUV to IR spectrum have been found to be greater than the increase in source signal to noise ratio would suggest. Better light penetration in Si and poly-Si has resulted in improved sensitivity and correlation breaking for critical parameters in 1xnm FinFET and HAR flash memory structures.

  14. Sortilin Associates with Trk Receptors to Enhance Anterograde Transport and Signaling by Neurotrophins

    DEFF Research Database (Denmark)

    Vægter, Christian Bjerggaard

      Neurotrophins (NT) are neuronal growth factors essential for development and maintenance of the nervous system. They are released in two forms with opposing biological functions. The proforms induce apoptosis by engaging a death signaling complex comprising the p75NTR neurotrophin receptor...... and survival has been extensively studied in knockout mouse models. We recently generated a Sortilin knockout mouse model (Sort1-/-) and showed that the receptor is essential for p75NTR to induce death of neurons during certain stages of development and aging and upon brain injury (Jansen et al, Nat. Neurosci...

  15. MYB and bHLH transcription factor transgenes increase anthocyanin pigmentation in petunia and lisianthus plants, and the petunia phenotypes are strongly enhanced under field conditions

    Directory of Open Access Journals (Sweden)

    Kathy E Schwinn

    2014-11-01

    Full Text Available Petunia line Mitchell [MP, Petunia axillaris × (P. axillaris × P. hybrida] and Eustoma grandiflorum (lisianthus plants were produced containing a transgene for over-expression of the R2R3-MYB transcription factor (ROSEA1 that up-regulates flavonoid biosynthesis in Antirrhinum majus. The petunia lines were also crossed with previously produced MP lines containing a Zea mays flavonoid-related bHLH transcription factor transgene (LEAF COLOR, LC, which induces strong vegetative pigmentation when these 35S:LC plants are exposed to high light levels. 35S:ROS1 lisianthus transgenics had limited changes in anthocyanin pigmentation, specifically, precocious pigmentation of flower petals and increased pigmentation of sepals. RNA transcript levels for two anthocyanin biosynthetic genes, chalcone synthase and anthocyanidin synthase, were increased in the 35S:ROS1 lisianthus petals compared to those of control lines. With MP, the 35S:ROS1 calli showed novel red pigmentation in culture, but this was generally not seen in tissue culture plantlets regenerated from the calli or young plants transferred to soil in the greenhouse. Anthocyanin pigmentation was enhanced in the stems of mature 35S:ROS1 MP plants, but the MP white-flower phenotype was not complemented. Progeny from a 35S:ROS1×35S:LC cross had novel pigmentation phenotypes that were not present in either parental line or MP. In particular, there was increased pigment accumulation in the petal throat region, and the anthers changed from yellow to purple colour. An outdoor field trial was conducted with the 35S:ROS1, 35S:LC, 35S:ROS1×35S:LC and control MP lines. Field conditions rapidly induced intense foliage pigmentation in 35S:LC plants, a phenotype not observed in control MP or equivalent 35S:LC plants maintained in a greenhouse. No difference in plant stature, seed germination, or plant survival was observed between transgenic and control plants.

  16. Enhancement of molecular NMR signal induced by polarization transfer from laser-polarized 129Xe

    International Nuclear Information System (INIS)

    Sun Xianping

    2001-01-01

    There is a large non-equilibrium nuclear polarization and a longer relaxation time in the laser-polarized 129 Xe produced by means of optical pumping and spin exchange. The characteristics of the laser-polarized 129 Xe permit the transfer of the polarization to enhance the atomic nuclear spin in liquid, solid and surface of solid molecules. Therefore, the sensitivity in nuclear magnetic resonance measurements for the molecules is enhanced and applications in the investigations of materials and surface sciences are expanded. The progress in the investigations of materials and surface sciences are expanded. The progress in the investigations of the polarization transfer between laser-polarized 129 Xe and the atomic nuclei in the molecules, the relative physics and the measurement of some parameters are introduced

  17. Double pulse laser ablation and plasma: Laser induced breakdown spectroscopy signal enhancement

    International Nuclear Information System (INIS)

    Babushok, V.I.; DeLucia, F.C.; Gottfried, J.L.; Munson, C.A.; Miziolek, A.W.

    2006-01-01

    A review of recent results of the studies of double laser pulse plasma and ablation for laser induced breakdown spectroscopy applications is presented. The double pulse laser induced breakdown spectroscopy configuration was suggested with the aim of overcoming the sensitivity shortcomings of the conventional single pulse laser induced breakdown spectroscopy technique. Several configurations have been suggested for the realization of the double pulse laser induced breakdown spectroscopy technique: collinear, orthogonal pre-spark, orthogonal pre-heating and dual pulse crossed beam modes. In addition, combinations of laser pulses with different wavelengths, different energies and durations were studied, thus providing flexibility in the choice of wavelength, pulse width, energy and pulse sequence. The double pulse laser induced breakdown spectroscopy approach provides a significant enhancement in the intensity of laser induced breakdown spectroscopy emission lines up to two orders of magnitude greater than a conventional single pulse laser induced breakdown spectroscopy. The double pulse technique leads to a better coupling of the laser beam with the plasma plume and target material, thus providing a more temporally effective energy delivery to the plasma and target. The experimental results demonstrate that the maximum effect is obtained at some optimum separation delay time between pulses. The optimum value of the interpulse delay depends on several factors, such as the target material, the energy level of excited states responsible for the emission, and the type of enhancement process considered. Depending on the specified parameter, the enhancement effects were observed on different time scales ranging from the picosecond time level (e.g., ion yield, ablation mass) up to the hundred microsecond level (e.g., increased emission intensity for laser induced breakdown spectroscopy of submerged metal target in water). Several suggestions have been proposed to explain

  18. Hardware-efficient signal generation of layered/enhanced ACO-OFDM for short-haul fiber-optic links.

    Science.gov (United States)

    Wang, Qibing; Song, Binhuang; Corcoran, Bill; Boland, David; Zhu, Chen; Zhuang, Leimeng; Lowery, Arthur J

    2017-06-12

    Layered/enhanced ACO-OFDM is a promising candidate for intensity modulation and direct-detection based short-haul fiber-optic links due to its both power and spectral efficiency. In this paper, we firstly demonstrate a hardware-efficient real-time 9.375 Gb/s QPSK-encoded layered/enhanced asymmetrical clipped optical OFDM (L/E-ACO-OFDM) transmitter using a Virtex-6 FPGA. This L/E-ACO-OFDM signal is successfully transmitted over 20-km uncompensated standard single-mode fiber (S-SMF) using a directly modulated laser. Several methods are explored to reduce the FPGA's logic resource utilization by taking advantage of the L/E-ACO-OFDM's signal characteristics. We show that the logic resource occupation of L/E-ACO-OFDM transmitter is almost the same as that of DC-biased OFDM transmitter when they achieve the same spectral efficiency, proving its great potential to be used in a real-time short-haul optical transmission link.

  19. PAF enhances MMP-2 production in rat aortic VSMCs via a β-arrestin2-dependent ERK signaling pathway.

    Science.gov (United States)

    Kim, Yun H; Lee, Seung J; Seo, Kyo W; Bae, Jin U; Park, So Y; Kim, Eun K; Bae, Sun S; Kim, Jae H; Kim, Chi D

    2013-10-01

    Platelet-activating factor (PAF), 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine, is a potent phospholipid mediator and has been reported to be localized in atherosclerotic plaque. However, its role in the progression of atherosclerosis remains unclear. In the present study, we investigated the role of PAF in the production of matrix metalloproteinase (MMP) in primary vascular smooth muscle cells (VSMCs). When rat aortic primary VSMCs were stimulated with PAF (1 nmol/l), the expressions of MMP-2 mRNA and protein, but not of MMP-9, were significantly increased, and these upregulations were markedly attenuated by inhibiting extracellular signal-regulated kinases (ERKs) using molecular and pharmacological inhibitors, but not by using inhibitors of p38 mitogen-activated protein kinase or c-Jun N-terminal kinase. Likewise, ERK phosphorylation was markedly enhanced in PAF-stimulated VSMCs, and this was attenuated by WEB2086, but not by EGF receptor inhibitor, demonstrating the specificity of PAF receptor (PAFR) in PAF-induced ERK phosphorylation. In immunofluorescence studies, β-arrestin2 in PAF-stimulated VSMCs colocalized with PAFR and phosphorylated ERK (P-ERK). Coimmunoprecipitation results suggest that β-arrestin2-bound PAFRs existed as a complex with P-ERK. In addition, PAF-induced ERK phosphorylation and MMP-2 production were significantly attenuated by β-arrestin2 depletion. Taken together, the study shows that PAF enhances MMP-2 production in VSMCs via a β-arrestin2-dependent ERK signaling pathway.

  20. Deficiency of thioredoxin binding protein-2 (TBP-2 enhances TGF-β signaling and promotes epithelial to mesenchymal transition.

    Directory of Open Access Journals (Sweden)

    So Masaki

    Full Text Available Transforming growth factor beta (TGF-β has critical roles in regulating cell growth, differentiation, apoptosis, invasion and epithelial-mesenchymal transition (EMT of various cancer cells. TGF-β-induced EMT is an important step during carcinoma progression to invasion state. Thioredoxin binding protein-2 (TBP-2, also called Txnip or VDUP1 is downregulated in various types of human cancer, and its deficiency results in the earlier onset of cancer. However, it remains unclear how TBP-2 suppresses the invasion and metastasis of cancer.In this study, we demonstrated that TBP-2 deficiency increases the transcriptional activity in response to TGF-β and also enhances TGF-β-induced Smad2 phosphorylation levels. Knockdown of TBP-2 augmented the TGF-β-responsive expression of Snail and Slug, transcriptional factors related to TGF-β-mediated induction of EMT, and promoted TGF-β-induced spindle-like morphology consistent with the depletion of E-Cadherin in A549 cells.Our results indicate that TBP-2 deficiency enhances TGF-β signaling and promotes TGF-β-induced EMT. The control of TGF-β-induced EMT is critical for the inhibition of the invasion and metastasis. Thus TBP-2, as a novel regulatory molecule of TGF-β signaling, is likely to be a prognostic indicator or a potential therapeutic target for preventing tumor progression.

  1. Transient metals enhance cytotoxicity of curcumin: potential involvement of the NF-kappaB and mTOR signaling pathways.

    Science.gov (United States)

    Lou, Jessica R; Zhang, Xiao-Xi; Zheng, Jie; Ding, Wei-Qun

    2010-09-01

    Curcumin has been recognized as a metal-binding compound and an anticancer agent, yet the involvement of metals in the anticancer action of curcumin remains unclear. The present study examined the role of transient metals in curcumin-induced cytotoxicity in cancer cells. Metal-binding activity and cytotoxicity of curcumin were examined in human cancer lines with cell viability assay, confocal microscopy, Western blot, and measurement of hydrogen peroxide generation. It was found that Cu (II) most significantly potentiated the cytotoxicity of curcumin among the metals tested. The combination of curcumin and Cu (II) did not generate reactive oxygen species and vitamin E did not block the cytotoxicity. Curcumin plus Cu (II) enhanced intracellular copper levels and potentiated curcumin-induced suppression of the nuclear factor kappa B (NF-κB) pathway, as well as alterations of mammalian target of rapamycin-raptor (mTOR) signaling. Transient metals enhance the cytotoxicity of curcumin, likely through targeting of the NF-κB and mTOR signaling pathways.

  2. Modulation of Wnt Signaling Enhances Inner Ear Organoid Development in 3D Culture.

    Directory of Open Access Journals (Sweden)

    Rachel E DeJonge

    Full Text Available Stem cell-derived inner ear sensory epithelia are a promising source of tissues for treating patients with hearing loss and dizziness. We recently demonstrated how to generate inner ear sensory epithelia, designated as inner ear organoids, from mouse embryonic stem cells (ESCs in a self-organizing 3D culture. Here we improve the efficiency of this culture system by elucidating how Wnt signaling activity can drive the induction of otic tissue. We found that a carefully timed treatment with the potent Wnt agonist CHIR99021 promotes induction of otic vesicles-a process that was previously self-organized by unknown mechanisms. The resulting otic-like vesicles have a larger lumen size and contain a greater number of Pax8/Pax2-positive otic progenitor cells than organoids derived without the Wnt agonist. Additionally, these otic-like vesicles give rise to large inner ear organoids with hair cells whose morphological, biochemical and functional properties are indistinguishable from those of vestibular hair cells in the postnatal mouse inner ear. We conclude that Wnt signaling plays a similar role during inner ear organoid formation as it does during inner ear development in the embryo.

  3. Ganglionic GFAP + glial Gq-GPCR signaling enhances heart functions in vivo.

    Science.gov (United States)

    Xie, Alison Xiaoqiao; Lee, Jakovin J; McCarthy, Ken D

    2017-01-26

    The sympathetic nervous system (SNS) accelerates heart rate, increases cardiac contractility, and constricts resistance vessels. The activity of SNS efferent nerves is generated by a complex neural network containing neurons and glia. Gq G protein-coupled receptor (Gq-GPCR) signaling in glial fibrillary acidic protein-expressing (GFAP + ) glia in the central nervous system supports neuronal function and regulates neuronal activity. It is unclear how Gq-GPCR signaling in GFAP + glia affects the activity of sympathetic neurons or contributes to SNS-regulated cardiovascular functions. In this study, we investigated whether Gq-GPCR activation in GFAP + glia modulates the regulatory effect of the SNS on the heart; transgenic mice expressing Gq-coupled DREADD (designer receptors exclusively activated by designer drugs) (hM3Dq) selectively in GFAP + glia were used to address this question in vivo. We found that acute Gq-GPCR activation in peripheral GFAP + glia significantly accelerated heart rate and increased left ventricle contraction. Pharmacological experiments suggest that the glial-induced cardiac changes were due to Gq-GPCR activation in satellite glial cells within the sympathetic ganglion; this activation led to increased norepinephrine (NE) release and beta-1 adrenergic receptor activation within the heart. Chronic glial Gq-GPCR activation led to hypotension in female Gfap -hM3Dq mice. This study provides direct evidence that Gq-GPCR activation in peripheral GFAP + glia regulates cardiovascular functions in vivo.

  4. Inactivation of EGFR/AKT signaling enhances TSA-induced ovarian cancer cell differentiation.

    Science.gov (United States)

    Shao, Genbao; Lai, Wensheng; Wan, Xiaolei; Xue, Jing; Wei, Ye; Jin, Jie; Zhang, Liuping; Lin, Qiong; Shao, Qixiang; Zou, Shengqiang

    2017-05-01

    Ovarian tumor is one of the most lethal gynecologic cancers, but differentiation therapy for this cancer is poorly characterized. Here, we show that thrichostatin A (TSA), the well known inhibitor of histone deacetylases (HDACs), can induce cell differentiation in HO8910 ovarian cancer cells. TSA-induced cell differentiation is characterized by typical morphological change, increased expression of the differentiation marker FOXA2, decreased expression of the pluripotency markers SOX2 and OCT4, suppressing cell proliferation, and cell cycle arrest in the G1 phase. TSA also induces an elevated expression of cell cycle inhibitory protein p21Cip1 along with a decrease in cell cycle regulatory protein cyclin D1. Significantly, blockage of epidermal growth factor receptor (EGFR) signaling pathway with specific inhibitors of this signaling cascade promotes the TSA-induced differentiation of HO8910 cells. These results imply that the EGFR cascade inhibitors in combination with TSA may represent a promising differentiation therapy strategy for ovarian cancer.

  5. Activation of stress signalling pathways enhances tolerance of fungi to chemical fungicides and antifungal proteins.

    Science.gov (United States)

    Hayes, Brigitte M E; Anderson, Marilyn A; Traven, Ana; van der Weerden, Nicole L; Bleackley, Mark R

    2014-07-01

    Fungal disease is an increasing problem in both agriculture and human health. Treatment of human fungal disease involves the use of chemical fungicides, which generally target the integrity of the fungal plasma membrane or cell wall. Chemical fungicides used for the treatment of plant disease, have more diverse mechanisms of action including inhibition of sterol biosynthesis, microtubule assembly and the mitochondrial respiratory chain. However, these treatments have limitations, including toxicity and the emergence of resistance. This has led to increased interest in the use of antimicrobial peptides for the treatment of fungal disease in both plants and humans. Antimicrobial peptides are a diverse group of molecules with differing mechanisms of action, many of which remain poorly understood. Furthermore, it is becoming increasingly apparent that stress response pathways are involved in the tolerance of fungi to both chemical fungicides and antimicrobial peptides. These signalling pathways such as the cell wall integrity and high-osmolarity glycerol pathway are triggered by stimuli, such as cell wall instability, changes in osmolarity and production of reactive oxygen species. Here we review stress signalling induced by treatment of fungi with chemical fungicides and antifungal peptides. Study of these pathways gives insight into how these molecules exert their antifungal effect and also into the mechanisms used by fungi to tolerate sub-lethal treatment by these molecules. Inactivation of stress response pathways represents a potential method of increasing the efficacy of antifungal molecules.

  6. Female scent signals enhance the resistance of male mice to influenza.

    Directory of Open Access Journals (Sweden)

    Ekaterina A Litvinova

    Full Text Available BACKGROUND: The scent from receptive female mice functions as a signal, which stimulates male mice to search for potential mating partners. This searching behavior is coupled with infection risk due to sniffing both scent marks as well as nasal and anogenital areas of females, which harbor bacteria and viruses. Consideration of host evolution under unavoidable parasitic pressures, including helminthes, bacteria, viruses, etc., predicts adaptations that help protect hosts against the parasites associated with mating. METHODS AND FINDINGS: We propose that the perception of female signals by BALB/c male mice leads to adaptive redistribution of the immune defense directed to protection against respiratory infection risks. Our results demonstrate migration of macrophages and neutrophils to the upper airways upon exposure to female odor stimuli, which results in an increased resistance of the males to experimental influenza virus infection. This moderate leukocyte intervention had no negative effect on the aerobic performance in male mice. CONCLUSIONS: Our data provide the first demonstration of the adaptive immunological response to female odor stimuli through induction of nonspecific immune responses in the upper respiratory tract.

  7. Using Differential Evolution to Optimize Learning from Signals and Enhance Network Security

    Energy Technology Data Exchange (ETDEWEB)

    Harmer, Paul K [Air Force Institute of Technology; Temple, Michael A [Air Force Institute of Technology; Buckner, Mark A [ORNL; Farquhar, Ethan [ORNL

    2011-01-01

    Computer and communication network attacks are commonly orchestrated through Wireless Access Points (WAPs). This paper summarizes proof-of-concept research activity aimed at developing a physical layer Radio Frequency (RF) air monitoring capability to limit unauthorizedWAP access and mprove network security. This is done using Differential Evolution (DE) to optimize the performance of a Learning from Signals (LFS) classifier implemented with RF Distinct Native Attribute (RF-DNA) fingerprints. Performance of the resultant DE-optimized LFS classifier is demonstrated using 802.11a WiFi devices under the most challenging conditions of intra-manufacturer classification, i.e., using emissions of like-model devices that only differ in serial number. Using identical classifier input features, performance of the DE-optimized LFS classifier is assessed relative to a Multiple Discriminant Analysis / Maximum Likelihood (MDA/ML) classifier that has been used for previous demonstrations. The comparative assessment is made using both Time Domain (TD) and Spectral Domain (SD) fingerprint features. For all combinations of classifier type, feature type, and signal-to-noise ratio considered, results show that the DEoptimized LFS classifier with TD features is uperior and provides up to 20% improvement in classification accuracy with proper selection of DE parameters.

  8. Romantic love is associated with enhanced inhibitory control in an emotional stop-signal task

    Directory of Open Access Journals (Sweden)

    Sensen Song

    2016-10-01

    Full Text Available Purpose: This study explored whether romantic lovers differ in emotion-related inhibitory control capacity from those who are single. Methods: 88 healthy undergraduate college students participated in the study. Half were currently in love and in a romantic relationship (love group, LG, and half were single and had never been in a romantic relationship (single group, SG. Based on duration of romantic relationship (i.e., love duration, the LG were further divided into two subgroups: early stage love and longer periods of love. All participants completed an emotional Stop Signal Task (eSST, which consisted of a variety of human face stimuli representing sadness (a negative emotion, as well as neutral emotions. Results: Results found that relative to SG, lovers showed greater inhibitory control [shorter stop-signal reaction time (SSRT] during negative emotion condition trials. Furthermore, in early stages of love, SSRT for negative emotion condition trials was significantly shorter compared to that in longer periods of love or SG individuals, with no significant differences between the latter two groups. Conclusions: Compared with individuals who were single, early-stage lovers showed greater capacity for inhibiting action during presentation of negative emotional stimuli. Within a greater social context, greater inhibitory control capacity during early stages of love may be related to the successful formation of romantic relationships, particularly to the ability to persevere in goal-directed action despite negative emotional contexts such as that of sadness.

  9. The serum of dysautonomia patients enhances proliferation and signaling in Schwann cells.

    Science.gov (United States)

    Lambrecht, Rein H; Pollard, Katherine A; Alshekhlee, Amer; Chelimsky, Thomas C; Berti-Mattera, Liliana N

    2010-01-04

    Disorders of the autonomic nervous system, or dysautonomias, affect a large segment of the population, especially women, and represent a diagnostic challenge. Identification of biomarkers for autonomic disorders, and the subsequent development of screening methods, would benefit diagnosis and symptom management. We studied the effect of sera from fifteen well-characterized dysautonomia patients (mean age 49+/-16 years, 10 females, 5 males) and ten control subjects (mean age 31+/-14 years, 5 females, 5 males) on the proliferation of cultured Schwann cells and activity of mitogen-activated protein kinases (MAPKs) in these cells. We correlated characteristics of patients with the effects on cell proliferation and signaling. Overall, we observed a significant increase in proliferation when Schwann cells were incubated with sera from female dysautonomia patients when compared to control subjects and male patients. Interestingly, removal of IgGs significantly reduced the proliferative effect of patient sera. We also observed significant activation of p38 MAPK following incubation with both male and female patient sera. These results suggest that patient sera contain factors that contribute to aberrant Schwann cell proliferation and signaling and may ultimately lead to autonomic nerve dysfunction. Our observations represent a promising first step in the identification of dysautonomia biomarkers.

  10. Romantic Love Is Associated with Enhanced Inhibitory Control in an Emotional Stop-Signal Task.

    Science.gov (United States)

    Song, Sensen; Zou, Zhiling; Song, Hongwen; Wang, Yongming; d'Oleire Uquillas, Federico; Wang, Huijun; Chen, Hong

    2016-01-01

    Purpose: This study explored whether romantic lovers differ in emotion-related inhibitory control capacity from those who are single. Methods: 88 healthy undergraduate college students participated in the study. Half were currently in love and in a romantic relationship (love group, LG), and half were single and had never been in a romantic relationship (single group, SG). Based on duration of romantic relationship (i.e., love duration), the LG were further divided into two subgroups: "early stage love" and "longer periods of love". All participants completed an emotional Stop Signal Task, consisting of a variety of human face stimuli displaying either sad or neutral affect. Results: Results found that relative to SG, lovers showed greater inhibitory control [shorter stop-signal reaction time (SSRT)] during negative emotion condition trials. Furthermore, in early stages of love, SSRT for negative emotion condition trials was significantly shorter compared to that in "longer periods of love" or SG individuals, with no significant differences between the two latter groups. Conclusion: Compared with individuals who were single, early stage lovers showed greater capacity for inhibiting action during presentation of negative emotional stimuli. Within a greater social context, greater inhibitory control capacity during early stages of love may be related to the successful formation of romantic relationships, particularly to the ability to persevere in goal-directed action despite negative emotional contexts such as that of sadness.

  11. Romantic Love Is Associated with Enhanced Inhibitory Control in an Emotional Stop-Signal Task

    Science.gov (United States)

    Song, Sensen; Zou, Zhiling; Song, Hongwen; Wang, Yongming; d’Oleire Uquillas, Federico; Wang, Huijun; Chen, Hong

    2016-01-01

    Purpose: This study explored whether romantic lovers differ in emotion-related inhibitory control capacity from those who are single. Methods: 88 healthy undergraduate college students participated in the study. Half were currently in love and in a romantic relationship (love group, LG), and half were single and had never been in a romantic relationship (single group, SG). Based on duration of romantic relationship (i.e., love duration), the LG were further divided into two subgroups: “early stage love” and “longer periods of love”. All participants completed an emotional Stop Signal Task, consisting of a variety of human face stimuli displaying either sad or neutral affect. Results: Results found that relative to SG, lovers showed greater inhibitory control [shorter stop-signal reaction time (SSRT)] during negative emotion condition trials. Furthermore, in early stages of love, SSRT for negative emotion condition trials was significantly shorter compared to that in “longer periods of love” or SG individuals, with no significant differences between the two latter groups. Conclusion: Compared with individuals who were single, early stage lovers showed greater capacity for inhibiting action during presentation of negative emotional stimuli. Within a greater social context, greater inhibitory control capacity during early stages of love may be related to the successful formation of romantic relationships, particularly to the ability to persevere in goal-directed action despite negative emotional contexts such as that of sadness. PMID:27826260

  12. Signal enhancement in a lateral flow immunoassay based on dual gold nanoparticle conjugates.

    Science.gov (United States)

    Shen, Guangyu; Zhang, Songbai; Hu, Xia

    2013-11-01

    In order to amplify signal of lateral flow immunoassay for specific detection of thrombin. A new, simple method of amplifying signals using two gold nanoparticle conjugates (GNP) in gold-nanoparticle-based lateral flow immunoassay without an additional step was developed. The first conjugates were prepared by labeling DNA1 with 30 nm GNPs, and the second conjugates were prepared by immobilizing both DNA2 and thrombin aptamer on the surfaces of 16 nm GNPs. The detection limit was improved 30 times. The lateral flow immunoassay developed in this study was applied to detect thrombin concentration in the range of 0.5-120 nM with a detection limit of 0.25 nM. The lateral flow immunoassay developed in this study was used to detect thrombin concentrations within a range of 0.5-120 nM with a detection limit of 0.25 nM. This assay is very versatile and can be easily extended to other proteins. © 2013.

  13. Insulin resistance enhances the mitogen-activated protein kinase signaling pathway in ovarian granulosa cells.

    Directory of Open Access Journals (Sweden)

    Linghui Kong

    Full Text Available The ovary is the main regulator of female fertility. Granulosa cell dysfunction may be involved in various reproductive endocrine disorders. Here we investigated the effect of insulin resistance on the metabolism and function of ovarian granulosa cells, and dissected the functional status of the mitogen-activated protein kinase signaling pathway in these cells. Our data showed that dexamethasone-induced insulin resistance in mouse granulosa cells reduced insulin sensitivity, accompanied with an increase in phosphorylation of p44/42 mitogen-activated protein kinase. Furthermore, up-regulation of cytochrome P450 subfamily 17 and testosterone and down-regulation of progesterone were observed in insulin-resistant mouse granulosa cells. Inhibition of p44/42 mitogen-activated protein kinase after induction of insulin resistance in mouse granulosa cells decreased phosphorylation of p44/42 mitogen-activated protein kinase, downregulated cytochrome P450 subfamily 17 and lowered progesterone production. This insulin resistance cell model can successfully demonstrate certain mechanisms such as hyperandrogenism, which may inspire a new strategy for treating reproductive endocrine disorders by regulating cell signaling pathways.

  14. Definition of an Enhanced Map-Matching Algorithm for Urban Environments with Poor GNSS Signal Quality.

    Science.gov (United States)

    Jiménez, Felipe; Monzón, Sergio; Naranjo, Jose Eugenio

    2016-02-04

    Vehicle positioning is a key factor for numerous information and assistance applications that are included in vehicles and for which satellite positioning is mainly used. However, this positioning process can result in errors and lead to measurement uncertainties. These errors come mainly from two sources: errors and simplifications of digital maps and errors in locating the vehicle. From that inaccurate data, the task of assigning the vehicle's location to a link on the digital map at every instant is carried out by map-matching algorithms. These algorithms have been developed to fulfil that need and attempt to amend these errors to offer the user a suitable positioning. In this research; an algorithm is developed that attempts to solve the errors in positioning when the Global Navigation Satellite System (GNSS) signal reception is frequently lost. The algorithm has been tested with satisfactory results in a complex urban environment of narrow streets and tall buildings where errors and signal reception losses of the GPS receiver are frequent.

  15. Brain-generated estradiol drives long-term optimization of auditory coding to enhance the discrimination of communication signals.

    Science.gov (United States)

    Tremere, Liisa A; Pinaud, Raphael

    2011-03-02

    Auditory processing and hearing-related pathologies are heavily influenced by steroid hormones in a variety of vertebrate species, including humans. The hormone estradiol has been recently shown to directly modulate the gain of central auditory neurons, in real time, by controlling the strength of inhibitory transmission via a nongenomic mechanism. The functional relevance of this modulation, however, remains unknown. Here we show that estradiol generated in the songbird homolog of the mammalian auditory association cortex, rapidly enhances the effectiveness of the neural coding of complex, learned acoustic signals in awake zebra finches. Specifically, estradiol increases mutual information rates, coding efficiency, and the neural discrimination of songs. These effects are mediated by estradiol's modulation of both the rate and temporal coding of auditory signals. Interference with the local action or production of estradiol in the auditory forebrain of freely behaving animals disrupts behavioral responses to songs, but not to other behaviorally relevant communication signals. Our findings directly show that estradiol is a key regulator of auditory function in the adult vertebrate brain.

  16. Light finger contact concurrently reduces postural sway and enhances signal detection performance in children with developmental coordination disorder.

    Science.gov (United States)

    Chen, Fu-Chen; Tsai, Chia-Liang

    2016-03-01

    The current study examined the effects of light finger touch on postural sway and signal detection performance in children with developmental coordination disorder (DCD). Children with DCD (n=30; 18 boys, 12 girls; age=11.87 ± 0.48 years) and typically developing children (n=30; 14 boys, 16 girls; age=11.73 ± 0.52 years) were recruited from schools in Pintung County, Taiwan. Participants completed a signal detection task under no finger touch (NT) and light finger touch (LT) conditions, while postural sway in both anteroposterior (AP) and mediolateral (ML) axes was recorded. In both conditions, children with DCD exhibited significantly higher levels of postural sway (pTDC. Additionally, both groups significantly reduced postural sway (pTDC relative to children with DCD (pTDC (p<0.05). These results suggest that light finger touch is effective in concurrently reducing postural sway and enhancing signal detection in both groups. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Application of power functions to chromatographic data for the enhancement of signal to noise ratios and separation resolution.

    Science.gov (United States)

    Shalliker, R A; Stevenson, P G; Shock, D; Mnatsakanyan, M; Dasgupta, P K; Guiochon, G

    2010-09-03

    Chromatographic detection responses are recorded digitally. A peak is represented ideally by a Guassian distribution. Raising a Guassian distribution to the power 'n' increases the height of the peak to that power, but decreases the standard deviation by radicaln. Hence there is an increasing disparity in detection responses as the signal moves from low level noise, with a corresponding decrease in peak width. This increases the S/N ratio and increases peak to peak resolution. The ramifications of these factors are that poor resolution in complex chromatographic data can be improved, and low signal responses embedded at near noise levels can be enhanced. The application of this data treatment process is potentially very useful in 2D-HPLC where sample dilution occurs between dimension, reducing signal response, and in the application of post-reaction detection methods, where band broadening is increased by virtue of reaction coils. In this work power functions applied to chromatographic data are discussed in the context of (a) complex separation problems, (b) 2D-HPLC separations, and (c) post-column reaction detectors. 2010 Elsevier B.V. All rights reserved.

  18. Resistin Enhances Inflammatory Cytokine Production in Coronary Artery Tissues by Activating the NF-κB Signaling

    Directory of Open Access Journals (Sweden)

    Fang Gao

    2016-01-01

    Full Text Available Purpose. Kawasaki disease (KD is a systemic vasculitis and is a leading cause of coronary artery lesions (CALs in childhood. Our previous study has shown higher levels of serum Resistin in KD patients with coronary aneurysm. This study aimed at examining the association of Resistin with inflammatory cytokine expression in mouse model of coronary arteritis and determining the potential mechanisms. Methods. C57BL/6 mice were injected with Lactobacillus cell wall extract (LCWE to induce coronary arteritis. The relative levels of Resistin, TNF-α, IL-1β, and MMP-9 expression and inflammatory infiltrates in the coronary arteries were determined longitudinally by quantitative RT-PCR, ELISA, and histology. The effect of TLR4 and NF-κB activation on Resistin-induced TNF-α and IL-1β expression in human coronary artery endothelium cells (HCAECs was examined by quantitative RT-PCR. Results. Higher levels of Resistin, TNF-α, IL-1β, and MMP-9 expression were associated with the degrees of inflammatory infiltrates in the coronary artery walls of the LCWE-injected mice. Resistin enhanced TNF-α and IL-1β expression in HCAECs at 18 or 24 hours after stimulation. Pretreatment with anti-TLR4 attenuated Resistin-enhanced IL-1β, but not TNF-α, expression and pretreatment with parthenolide or QNZ demolished Resistin-enhanced TNF-α expression in HACECs. Pretreatment with parthenolide, but not QNZ, blocked Resistin-enhanced IL-1β expression in HCAECs. Conclusion. Resistin may enhance inflammation by cross-talking with TLR4/NF-κB signaling during the development of coronary arteritis in mice.

  19. Plasmon-Coupled Whispering Gallery Modes on Nanodisk Arrays for Signal Enhancements.

    Science.gov (United States)

    Kang, Tae Young; Lee, Wonju; Ahn, Heesang; Shin, Dong-Myeong; Kim, Chang-Seok; Oh, Jin-Woo; Kim, Donghyun; Kim, Kyujung

    2017-09-15

    Metallic nanostructures including single and double nanodisks are successfully used to enhance the localized electric field in vicinity of microcavity in whispering gallery mode (WGM) sensor. We demonstrate numerical calculations of plasmonic coupling of WGMs to single and double nanodisk arrays on a planar substrate. We then experimentally confirmed that the resonance wavelength of WGM sensor was dramatically shifted by adoption of single and double nanodisks on the surface of microcavity in the WGM sensor. Thus, our approach provides the tunable sensitivity of WGM sensor, and has a great potential to be used in numerous areas where the single biomolecule, protein-protein folding and biomolecular interactions are involved.

  20. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    International Nuclear Information System (INIS)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy; Pillai, Ayyappan Harikrishna; Harikumar, Sankaran Kutty; Mishra, Santosh Kumar; Sarkar, Souvendra Nath

    2014-01-01

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  1. Atorvastatin ameliorates arsenic-induced hypertension and enhancement of vascular redox signaling in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sarath, Thengumpallil Sasindran; Waghe, Prashantkumar; Gupta, Priyanka; Choudhury, Soumen; Kannan, Kandasamy [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Pillai, Ayyappan Harikrishna [Division of Animal Biochemistry, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Harikumar, Sankaran Kutty; Mishra, Santosh Kumar [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India); Sarkar, Souvendra Nath, E-mail: snsarkar1911@rediffmail.com [Division of Pharmacology and Toxicology, Indian Veterinary Research Institute, Izatnagar, 243122 Bareilly, Uttar Pradesh (India)

    2014-11-01

    Chronic arsenic exposure has been linked to elevated blood pressure and cardiovascular diseases, while statins reduce the incidence of cardiovascular disease predominantly by their low density lipoprotein-lowering effect. Besides, statins have other beneficial effects, including antioxidant and anti-inflammatory activities. We evaluated whether atorvastatin, a widely used statin, can ameliorate arsenic-induced increase in blood pressure and alteration in lipid profile and also whether the amelioration could relate to altered NO and ROS signaling. Rats were exposed to sodium arsenite (100 ppm) through drinking water for 90 consecutive days. Atorvastatin (10 mg/kg bw, orally) was administered once daily during the last 30 days of arsenic exposure. On the 91st day, blood was collected for lipid profile. Western blot of iNOS and eNOS protein, NO and 3-nitrotyrosine production, Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation, lipid peroxidation and antioxidants were evaluated in thoracic aorta. Arsenic increased systolic, diastolic and mean arterial blood pressure, while it decreased HDL-C and increased LDL-C, total cholesterol and triglycerides in serum. Arsenic down-regulated eNOS and up-regulated iNOS protein expression and increased basal NO and 3-nitrotyrosine level. Arsenic increased aortic Nox-4 and p22Phox mRNA expression, Nox activity, ROS generation and lipid peroxidation. Further, arsenic decreased the activities of superoxide dismutase, catalase, and glutathione peroxidase and depleted aortic GSH content. Atorvastatin regularized blood pressure, improved lipid profile and attenuated arsenic-mediated redox alterations. The results demonstrate that atorvastatin has the potential to ameliorate arsenic-induced hypertension by improving lipid profile, aortic NO signaling and restoring vascular redox homeostasis. - Highlights: • Arsenic increased systolic, diastolic and mean arterial blood pressure and caused dyslipidemia. • Arsenic increased

  2. A new oxovanadium complex enhances renal function by improving insulin signaling pathway in diabetic mice.

    Science.gov (United States)

    Liu, Y; Chen, D D; Xing, Y H; Ge, N; Zhang, Y; Liu, J; Zou, W

    2014-01-01

    Since vanadium complexes have insulin-mimetic effects and can be used to treat complications of diabetes, we aimed to screen a new oxovanadium complex with a low toxicity, and investigate its insulin-mimetic effects, as well as the mechanism of improvement to diabetic mouse renal function. Cells were treated with oxovanadium complexes, and viability was assessed by MTT assay. Diabetic mouse model was established using alloxan. Blood urea nitrogen (BUN) and serum creatinine (SCr) in the mice were measured using an automatic biochemical analyzer, and blood glucose was measured using a Glucoval Compact meter. Expression of proteins related to the insulin signaling pathway in the renal cortex of mice was measured by Western blot analysis. Diabetic mice developed high blood glucose, BUN and SCr levels compared with control mice. The new oxovanadium complex with 3,5-dimethyl-pyrazolyl ligand, VO(HB(3,5-Me2pz)3)(3,5-Me2pz)(SCN)(SCNH)2, showed low toxicity and significantly reduced blood glucose, BUN and SCr levels in the diabetic mice. Additionally, p42/p44MAPK and Akt phosphorylation was markedly increased in diabetic mice and was decreased by treatment with the new oxovanadium complex. Caveolin-1 (Cav-1) expression was greatly decreased in diabetic mice and significantly increased after treatment with the new oxovanadium complex. The new oxovanadium complex, with 3,5-dimethyl-pyrazolyl ligand, improves kidney function in diabetic mice, and its mechanism may involve regulation of the insulin signaling pathway. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Metformin exerts glucose-lowering action in high-fat fed mice via attenuating endotoxemia and enhancing insulin signaling

    Science.gov (United States)

    Zhou, Zi-yu; Ren, Li-wei; Zhan, Ping; Yang, Han-yan; Chai, Dan-dan; Yu, Zhi-wen

    2016-01-01

    Aim: Accumulating evidence shows that lipopolysaccharides (LPS) derived from gut gram-negative bacteria can be absorbed, leading to endotoxemia that triggers systemic inflammation and insulin resistance. In this study we examined whether metformin attenuated endotoxemia, thus improving insulin signaling in high-fat diet fed mice. Methods: Mice were fed a high-fat diet for 18 weeks to induce insulin resistance. One group of the mice was treated with oral metformin (100 mg·kg−1·d−1) for 4 weeks. Another group was treated with LPS (50 μg·kg−1·d−1, sc) for 5 days followed by the oral metformin for 10 d. Other two groups received a combination of antibiotics for 7 d or a combination of antibiotics for 7 d followed by the oral metformin for 4 weeks, respectively. Glucose metabolism and insulin signaling in liver and muscle were evaluated, the abundance of gut bacteria, gut permeability and serum LPS levels were measured. Results: In high-fat fed mice, metformin restored the tight junction protein occludin-1 levels in gut, reversed the elevated gut permeability and serum LPS levels, and increased the abundance of beneficial bacteria Lactobacillus and Akkermansia muciniphila. Metformin also increased PKB Ser473 and AMPK T172 phosphorylation, decreased MDA contents and redox-sensitive PTEN protein levels, activated the anti-oxidative Nrf2 system, and increased IκBα in liver and muscle of the mice. Treatment with exogenous LPS abolished the beneficial effects of metformin on glucose metabolism, insulin signaling and oxidative stress in liver and muscle of the mice. Treatment with antibiotics alone produced similar effects as metformin did. Furthermore, the beneficial effects of antibiotics were addictive to those of metformin. Conclusion: Metformin administration attenuates endotoxemia and enhances insulin signaling in high-fat fed mice, which contributes to its anti-diabetic effects. PMID:27180982

  4. FGF23 activates injury-primed renal fibroblasts via FGFR4-dependent signalling and enhancement of TGF-β autoinduction.

    Science.gov (United States)

    Smith, Edward R; Holt, Stephen G; Hewitson, Tim D

    2017-11-01

    Bone-derived fibroblast growth factor 23 (FGF23) is an important endocrine regulator of mineral homeostasis with effects transduced by cognate FGF receptor (FGFR)1-α-Klotho complexes. Circulating FGF23 levels rise precipitously in patients with kidney disease and portend worse renal and cardiovascular outcomes. De novo expression of FGF23 has been found in the heart and kidney following injury but its significance remains unclear. Studies showing that exposure to chronically high FGF23 concentrations activates hypertrophic gene programs in the cardiomyocyte has spawned intense interest in other pathological off-target effects of FGF23 excess. In the kidney, observational evidence points to a concordance of ectopic renal FGF23 expression and the activation of local transforming growth factor (TGF)-β signalling. Although we have previously shown that FGF23 activates injury-primed renal fibroblasts in vitro, our understanding of the mechanism underpinning these effects was incomplete. Here we show that in the absence of α-Klotho, FGF23 augments pro-fibrotic signalling cascades in injury-primed renal fibroblasts via activation of FGFR4 and upregulation of the calcium transporter, transient receptor potential cation channel 6. The resultant rise in intracellular calcium and production of mitochondrial reactive oxygen species induced expression of NFAT responsive-genes and enhanced TGF-β1 autoinduction through non-canonical JNK-dependent pathways. Reconstitution with transmembrane α-Klotho, or its soluble ectodomain, restored classical Egr signalling and antagonised FGF23-driven myofibroblast differentiation. Thus, renal FGF23 may amplify local myofibroblast activation in injury and perpetuate pro-fibrotic signalling. These findings strengthen the rationale for exploring therapeutic inhibition of FGFR4 or restoration of α-Klotho as upstream regulators of off-target FGF23 effects. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  5. Osteoblast-secreted collagen upregulates paracrine Sonic hedgehog signaling by prostate cancer cells and enhances osteoblast differentiation

    Directory of Open Access Journals (Sweden)

    Zunich Samantha M

    2012-07-01

    Full Text Available Abstract Background Induction of osteoblast differentiation by paracrine Sonic hedgehog (Shh signaling may be a mechanism through which Shh-expressing prostate cancer cells initiate changes in the bone microenvironment and promote metastases. A hallmark of osteoblast differentiation is the formation of matrix whose predominant protein is type 1 collagen. We investigated the formation of a collagen matrix by osteoblasts cultured with prostate cancer cells, and its effects on interactions between prostate cancer cells and osteoblasts. Results In the presence of exogenous ascorbic acid (AA, a co-factor in collagen synthesis, mouse MC3T3 pre-osteoblasts in mixed cultures with human LNCaP prostate cancer cells or LNCaP cells modified to overexpress Shh (LNShh cells formed collagen matrix with distinct fibril ultrastructural characteristics. AA increased the activity of alkaline phosphatase and the expression of the alkaline phosphatase gene Akp2, markers of osteoblast differentiation, in MC3T3 pre-osteoblasts cultured with LNCaP or LNShh cells. However, the AA-stimulated increase in Akp2 expression in MC3T3 pre-osteoblasts cultured with LNShh cells far exceeded the levels observed in MC3T3 cells cultured with either LNCaP cells with AA or LNShh cells without AA. Therefore, AA and Shh exert a synergistic effect on osteoblast differentiation. We determined whether the effect of AA on LNShh cell-induced osteoblast differentiation was mediated by Shh signaling. AA increased the expression of Gli1 and Ptc1, target genes of the Shh pathway, in MC3T3 pre-osteoblasts cultured with LNShh cells to at least twice their levels without AA. The ability of AA to upregulate Shh signaling and enhance alkaline phosphatase activity was blocked in MC3T3 cells that expressed a dominant negative form of the transcription factor GLI1. The AA-stimulated increase in Shh signaling and Shh-induced osteoblast differentiation was also inhibited by the specific collagen synthesis

  6. Seismic switch for strong motion measurement

    Science.gov (United States)

    Harben, P.E.; Rodgers, P.W.; Ewert, D.W.

    1995-05-30

    A seismic switching device is described that has an input signal from an existing microseismic station seismometer and a signal from a strong motion measuring instrument. The seismic switch monitors the signal level of the strong motion instrument and passes the seismometer signal to the station data telemetry and recording systems. When the strong motion instrument signal level exceeds a user set threshold level, the seismometer signal is switched out and the strong motion signal is passed to the telemetry system. The amount of time the strong motion signal is passed before switching back to the seismometer signal is user controlled between 1 and 15 seconds. If the threshold level is exceeded during a switch time period, the length of time is extended from that instant by one user set time period. 11 figs.

  7. Bell's palsy: what is the prognostic value of measurements of signal intensity increases with contrast enhancement on MRI?

    International Nuclear Information System (INIS)

    Kress, B.P.J.; Efinger, K.; Solbach, T.; Gottschalk, A.; Baehren, W.; Griesbeck, F.; Kornhuber, A.W.

    2002-01-01

    Our objective was to assess the prognostic value of measurements of the degree of contrast enhancement of the intratemporal segments of the facial nerve. We prospectively obtained MRI, slice thickness <1 mm of 20 patients with a facial palsy on the first day of inpatient treatment, and measured contrast enhancement of the nerve. The data were compared with compound muscle action potential (CMAP) measurements and the clinical course. Analysis of the initial enabled differentiation of three patients whose palsy was to show no improvement from 17 whose palsy was to resolve as expected. No patient with a poor outcome showed lesser increase in signal in the internal auditory canal, pars tympanica and pars mastoidea than patients who fully recovered. In no patient who had been diagnosed on the basis of the initial MRI as having a ''normal'' palsy was the amplitude of the (CMAP) reduced to less than 20% that of the normal side. Measurement of contrast enhancement was thus shown to be a prognostic indicator and may provide a basis for a differential treatment of facial palsy. (orig.)

  8. Knockdown of MALAT1 enhances chemosensitivity of ovarian cancer cells to cisplatin through inhibiting the Notch1 signaling pathway.

    Science.gov (United States)

    Bai, Lin; Wang, Aihua; Zhang, Yali; Xu, Xiaofeng; Zhang, Xiao

    2018-05-15

    Long non-coding RNAs (lncRNAs) are critical regulators in chemoresistance of various tumors including ovarian cancer. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been reported to be upregulated and contributed to ovarian cancer tumorigenesis. The aim of this study was to explore the roles of MALAT1 and the underlying molecular regulatory mechanism in the chemoresistance of ovarian cancer cells. Our data demonstrated that MALAT1 and Notch1 mRNA were upregulated in ovarian cancer tissues, as well as cisplatin (CDDP)-resistant ovarian cancer cells. A positive correlation between MALAT1 and Notch1 mRNA expression was observed. MALAT1 knockdown significantly attenuated CDDP resistance, and enhanced CDDP-induced apoptosis in CDDP-resistant ovarian cancer cells. MALAT1 knockdown enhanced CDDP-induced apoptosis in vivo, as indicated by upregulation of Bax protein expression and downregulation of Bcl-2 protein expression. Additionally, MALAT1 knockdown inhibited the Notch1 pathway and ABCC1 expression in CDDP-resistant ovarian cancer cells. MALAT1 was demonstrated to interact with Notch1. Notch1 knockdown attenuated CDDP resistance, and downregulated the protein expression of ABCC1 in ovarian cancer cells. Taken together, our findings suggested that knockdown of MALAT-1 enhanced chemosensitivity of ovarian cancer cells to CDDP through inhibiting Notch1 signaling pathway. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Overexpression of PeHA1 enhances hydrogen peroxide signaling in salt-stressed Arabidopsis.

    Science.gov (United States)

    Wang, Meijuan; Wang, Yang; Sun, Jian; Ding, Mingquan; Deng, Shurong; Hou, Peichen; Ma, Xujun; Zhang, Yuhong; Wang, Feifei; Sa, Gang; Tan, Yeqing; Lang, Tao; Li, Jinke; Shen, Xin; Chen, Shaoliang

    2013-10-01

    The plant plasma membrane (PM) H(+)-ATPase plays a crucial role in controlling K(+)/Na(+) homeostasis under salt stress. Our previous microarray analysis indicated that Populus euphratica retained a higher abundance of PM H(+)-ATPase transcript versus a salt-sensitive poplar. To clarify the roles of the PM H(+)-ATPase in salt sensing and adaptation, we isolated the PM H(+)-ATPase gene PeHA1 from P. euphratica and introduced it into Arabidopsis thaliana. Compared to wild-type, PeHA1-transgenic Arabidopsis had a greater germination rate, root length, and biomass under NaCl stress (50-150 mM). Ectopic expression of PeHA1 remarkably enhanced the capacity to control the homeostasis of ions and reactive oxygen species in salinized Arabidopsis. Flux data from salinized roots showed that transgenic plants exhibited a more pronounced Na(+)/H(+) antiport and less reduction of K(+) influx versus wild-type. Enhanced PM ATP hydrolytic activity, proton pumping, and Na(+)/H(+) antiport in PeHA1-transgenic plants, were consistent to those observed in vivo, i.e., H(+) extrusion, external acidification, and Na(+) efflux. Activities of the antioxidant enzymes ascorbate peroxidase and catalase were typically higher in transgenic seedlings irrespective of salt concentration. In transgenic Arabidopsis roots, H2O2 production was higher under control conditions and increased more rapidly than wild-type when plants were subjected to NaCl treatment. Interestingly, transgenic plants were unable to control K(+)/Na(+) homeostasis when salt-induced H2O2 production was inhibited by diphenylene iodonium, an inhibitor of NADPH oxidase. These observations suggest that PeHA1 accelerates salt tolerance partially through rapid H2O2 production upon salt treatment, which triggers adjustments in K(+)/Na(+) homeostasis and antioxidant defense in Arabidopsis. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  10. Progress of performance of MOEMS micro spectrometers through enhanced signal processing, detectors and system setup

    Science.gov (United States)

    Grüger, Heinrich; Egloff, Thomas; Messerschmidt, Matthias; Scholles, Michael

    2008-09-01

    Micro spectrometers have been realized by the use of MEMS based scanning grating chips several years ago. The main advantage is the requirement of a single detector instead of a detector array for micro spectrometers applying fixed gratings. Especially in the near infrared range beyond the detection limit of silicon detectors, this can help to reduce the system costs significantly. First measurements for test application have been performed successfully. Industrial applications require wide spectral range, high long term stability and sufficient computation power in the system itself to realize intelligent sensor heads for process monitoring and quality control. Through the recent time, many details have been improved. Extended InGaAs detectors have been used to extend the spectral range up to 2500nm. Improvements of the grating position readout improved the wavelength stability of the system even under tough operation conditions. The integration of faster digital signal processors opens the possibility to implement spectral evaluation algorithms into the system itself. Besides simple applications shown earlier like the selection of different kinds of plastic waste, now a more quantitative analysis can be achieved. For example the ethanol content of liquor samples has been measured and evaluated quantitatively.

  11. Local synaptic signaling enhances the stochastic transport of motor-driven cargo in neurons

    KAUST Repository

    Newby, Jay

    2010-08-23

    The tug-of-war model of motor-driven cargo transport is formulated as an intermittent trapping process. An immobile trap, representing the cellular machinery that sequesters a motor-driven cargo for eventual use, is located somewhere within a microtubule track. A particle representing a motor-driven cargo that moves randomly with a forward bias is introduced at the beginning of the track. The particle switches randomly between a fast moving phase and a slow moving phase. When in the slow moving phase, the particle can be captured by the trap. To account for the possibility that the particle avoids the trap, an absorbing boundary is placed at the end of the track. Two local signaling mechanisms-intended to improve the chances of capturing the target-are considered by allowing the trap to affect the tug-of-war parameters within a small region around itself. The first is based on a localized adenosine triphosphate (ATP) concentration gradient surrounding a synapse, and the second is based on a concentration of tau-a microtubule-associated protein involved in Alzheimer\\'s disease-coating the microtubule near the synapse. It is shown that both mechanisms can lead to dramatic improvements in the capture probability, with a minimal increase in the mean capture time. The analysis also shows that tau can cause a cargo to undergo random oscillations, which could explain some experimental observations. © 2010 IOP Publishing Ltd.

  12. DHX36 enhances RIG-I signaling by facilitating PKR-mediated antiviral stress granule formation.

    Science.gov (United States)

    Yoo, Ji-Seung; Takahasi, Kiyohiro; Ng, Chen Seng; Ouda, Ryota; Onomoto, Koji; Yoneyama, Mitsutoshi; Lai, Janice Ching; Lattmann, Simon; Nagamine, Yoshikuni; Matsui, Tadashi; Iwabuchi, Kuniyoshi; Kato, Hiroki; Fujita, Takashi

    2014-03-01

    RIG-I is a DExD/H-box RNA helicase and functions as a critical cytoplasmic sensor for RNA viruses to initiate antiviral interferon (IFN) responses. Here we demonstrate that another DExD/H-box RNA helicase DHX36 is a key molecule for RIG-I signaling by regulating double-stranded RNA (dsRNA)-dependent protein kinase (PKR) activation, which has been shown to be essential for the formation of antiviral stress granule (avSG). We found that DHX36 and PKR form a complex in a dsRNA-dependent manner. By forming this complex, DHX36 facilitates dsRNA binding and phosphorylation of PKR through its ATPase/helicase activity. Using DHX36 KO-inducible MEF cells, we demonstrated that DHX36 deficient cells showed defect in IFN production and higher susceptibility in RNA virus infection, indicating the physiological importance of this complex in host defense. In summary, we identify a novel function of DHX36 as a critical regulator of PKR-dependent avSG to facilitate viral RNA recognition by RIG-I-like receptor (RLR).

  13. DHX36 enhances RIG-I signaling by facilitating PKR-mediated antiviral stress granule formation.

    Directory of Open Access Journals (Sweden)

    Ji-Seung Yoo

    2014-03-01

    Full Text Available RIG-I is a DExD/H-box RNA helicase and functions as a critical cytoplasmic sensor for RNA viruses to initiate antiviral interferon (IFN responses. Here we demonstrate that another DExD/H-box RNA helicase DHX36 is a key molecule for RIG-I signaling by regulating double-stranded RNA (dsRNA-dependent protein kinase (PKR activation, which has been shown to be essential for the formation of antiviral stress granule (avSG. We found that DHX36 and PKR form a complex in a dsRNA-dependent manner. By forming this complex, DHX36 facilitates dsRNA binding and phosphorylation of PKR through its ATPase/helicase activity. Using DHX36 KO-inducible MEF cells, we demonstrated that DHX36 deficient cells showed defect in IFN production and higher susceptibility in RNA virus infection, indicating the physiological importance of this complex in host defense. In summary, we identify a novel function of DHX36 as a critical regulator of PKR-dependent avSG to facilitate viral RNA recognition by RIG-I-like receptor (RLR.

  14. Estrogen enhanced cell-cell signalling in breast cancer cells exposed to targeted irradiation

    International Nuclear Information System (INIS)

    Shao, Chunlin; Folkard, Melvyn; Held, Kathryn D; Prise, Kevin M

    2008-01-01

    Radiation-induced bystander responses, where cells respond to their neighbours being irradiated are being extensively studied. Although evidence shows that bystander responses can be induced in many types of cells, it is not known whether there is a radiation-induced bystander effect in breast cancer cells, where the radiosensitivity may be dependent on the role of the cellular estrogen receptor (ER). This study investigated radiation-induced bystander responses in estrogen receptor-positive MCF-7 and estrogen receptor-negative MDA-MB-231 breast cancer cells. The influence of estrogen and anti-estrogen treatments on the bystander response was determined by individually irradiating a fraction of cells within the population with a precise number of helium-3 using a charged particle microbeam. Damage was scored as chromosomal damage measured as micronucleus formation. A bystander response measured as increased yield of micronucleated cells was triggered in both MCF-7 and MDA-MB-231 cells. The contribution of the bystander response to total cell damage in MCF-7 cells was higher than that in MDA-MB-231 cells although the radiosensitivity of MDA-MB-231 was higher than MCF-7. Treatment of cells with 17β-estradiol (E2) increased the radiosensitivity and the bystander response in MCF-7 cells, and the effect was diminished by anti-estrogen tamoxifen (TAM). E2 also increased the level of intracellular reactive oxygen species (ROS) in MCF-7 cells in the absence of radiation. In contrast, E2 and TAM had no influence on the bystander response and ROS levels in MDA-MB-231 cells. Moreover, the treatment of MCF-7 cells with antioxidants eliminated both the E2-induced ROS increase and E2-enhanced bystander response triggered by the microbeam irradiation, which indicates that ROS are involved in the E2-enhanced bystander micronuclei formation after microbeam irradiation. The observation of bystander responses in breast tumour cells may offer new potential targets for radiation

  15. Signal enhancement in amperometric peroxide detection by using graphene materials with low number of defects

    International Nuclear Information System (INIS)

    Zöpfl, Alexander; Matysik, Frank-Michael; Hirsch, Thomas; Sisakthi, Masoumeh; Eroms, Jonathan; Strunk, Christoph

    2016-01-01

    Two-dimensional carbon nanomaterials ranging from single-layer graphene to defective structures such as chemically reduced graphene oxide were studied with respect to their use in electrodes and sensors. Their electrochemical properties and utility in terms of fabrication of sensing devices are compared. Specifically, the electrodes have been applied to reductive amperometric determination of hydrogen peroxide. Low-defect graphene (SG) was obtained through mechanical exfoliation of natural graphite, while higher-defect graphenes were produced by chemical vapor deposition (CVDG) and by chemical oxidation of graphite and subsequent reduction (rGO). The carbonaceous materials were mainly characterized by Raman microscopy. They were applied as electrode material and the electrochemical behavior was investigated by chronocoulometry, cyclic voltammetry, electrochemical impedance spectroscopy and amperometry and compared to a carbon disc electrode. It is shown that the quality of the graphene has an enormous impact on the amperometric performance. The use of carbon materials with many defects (like rGO) does not result in a significant improvement in signal compared to a plain carbon disc electrode. The sensitivity is 173 mA · M −1  · cm −2 in case of using CVDG which is about 50 times better than that of a plain carbon disc electrode and about 7 times better than that of rGO. The limit of detection for hydrogen peroxide is 15.1 μM (at a working potential of −0.3 V vs SCE) for CVDG. It is concluded that the application of two-dimensional carbon nanomaterials offers large perspectives in amperometric detection systems due to electrocatalytic effects that result in highly sensitive detection. (author)

  16. Exercise training improves blood flow to contracting skeletal muscle of older men via enhanced cGMP signaling

    DEFF Research Database (Denmark)

    Piil, Peter Bergmann; Smith Jørgensen, Tue; Egelund, Jon

    2018-01-01

    -induced adaptations in the regulation of skeletal muscle blood flow and oxidative metabolism during exercise in aging humans. We measured leg hemodynamics and oxidative metabolism during exercise engaging the knee-extensor muscles in young (n=15, 25 ± 1 years) and older (n=15, 72 ± 1 years) subjects before and after...... group; however, these effects of PDE5 inhibition were not detected after training. These findings suggest a role for enhanced cGMP signaling in the training-induced improvement of regulation of blood flow in contracting skeletal muscle of older men.......Physical activity has the potential to offset age-related impairments in the regulation of blood flow and O2 delivery to the exercising muscles; however, the mechanisms underlying this effect of physical activity remain poorly understood. The present study examined the role of cGMP in training...

  17. Basal forebrain motivational salience signal enhances cortical processing and decision speed

    Directory of Open Access Journals (Sweden)

    Sylvina M Raver

    2015-10-01

    Full Text Available The basal forebrain (BF contains major projections to the cerebral cortex, and plays a well-documented role in arousal, attention, decision-making, and in modulating cortical activity. BF neuronal degeneration is an early event in Alzheimer’s disease and dementias, and occurs in normal cognitive aging. While the BF is best known for its population of cortically projecting cholinergic neurons, the region is anatomically and neurochemically diverse, and also contains prominent populations of non-cholinergic projection neurons. In recent years, increasing attention has been dedicated to these non-cholinergic BF neurons in order to better understand how non-cholinergic BF circuits control cortical processing and behavioral performance. In this review, we focus on a unique population of putative non-cholinergic BF neurons that encodes the motivational salience of stimuli with a robust ensemble bursting response. We review recent studies that describe the specific physiological and functional characteristics of these BF salience-encoding neurons in behaving animals. These studies support the unifying hypothesis whereby BF salience-encoding neurons act as a gain modulation mechanism of the decision-making process to enhance cortical processing of behaviorally relevant stimuli, and thereby facilitate faster and more precise behavioral responses. This function of BF salience-encoding neurons represents a critical component in determining which incoming stimuli warrant an animal’s attention, and is therefore a fundamental and early requirement of behavioral flexibility.

  18. Multiuser receiver for DS-CDMA signals in multipath channels: an enhanced multisurface method.

    Science.gov (United States)

    Mahendra, Chetan; Puthusserypady, Sadasivan

    2006-11-01

    This paper deals with the problem of multiuser detection in direct-sequence code-division multiple-access (DS-CDMA) systems in multipath environments. The existing multiuser detectors can be divided into two categories: (1) low-complexity poor-performance linear detectors and (2) high-complexity good-performance nonlinear detectors. In particular, in channels where the orthogonality of the code sequences is destroyed by multipath, detectors with linear complexity perform much worse than the nonlinear detectors. In this paper, we propose an enhanced multisurface method (EMSM) for multiuser detection in multipath channels. EMSM is an intermediate piecewise linear detection scheme with a run-time complexity linear in the number of users. Its bit error rate performance is compared with existing linear detectors, a nonlinear radial basis function detector trained by the new support vector learning algorithm, and Verdu's optimal detector. Simulations in multipath channels, for both synchronous and asynchronous cases, indicate that it always outperforms all other linear detectors, performing nearly as well as nonlinear detectors.

  19. Erythropoietin enhances mitochondrial biogenesis in cardiomyocytes exposed to chronic hypoxia through Akt/eNOS signalling pathway.

    Science.gov (United States)

    Qin, Chuan; Zhou, Shengkai; Xiao, Yingbin; Chen, Lin

    2014-03-01

    Adaptation of cardiomyocytes to chronic hypoxia in cyanotic patients remains unclear. Mitochondrial biogenesis is enhanced in myocardium from cyanotic patients, which is possibly an adaptive response. Erythropoietin (EPO) in blood and its receptor (EPOR) on cardiomyocytes are upregulated by chronic hypoxia, suggesting that EPO-EPOR interaction is increased, which is inferred to positively regulate mitochondrial biogenesis through protein kinase B (Akt)/endothelial nitric oxide synthase (eNOS) signalling pathway. H9c2 cardiomyocytes were exposed to hypoxia (1% O(2)) for 1 week and treated with different doses of recombinant human erythropoietin (rhEPO). Mitochondrial number, mitochondrial DNA (mtDNA) copy number and peroxisome proliferator activated receptor gamma coactivator alpha (PGC-1α) mRNA expression increased in a dose-dependent manner induced by rhEPO. Akt and eNOS were significantly phosphorylated by rhEPO. Both blocking Akt with Wortmannin and silencing eNOS expression with shRNA plasmid decreased the mtDNA copy number and PGC-1α mRNA expression induced by rhEPO. Blocking Akt was associated with the decreased phosphorylation of Akt and eNOS. RNA interference led to a reduction in the total and phosphorylated proteins of eNOS. Thus EPO enhances mitochondrial biogenesis in cardiomyocytes exposed to chronic hypoxia, at least partly through Akt/eNOS signalling, which might be an adaptive mechanism of cardiomyocytes associated with the increased EPO-EPOR interaction in patients with cyanotic congenital heart disease (CCHD). © 2013 International Federation for Cell Biology.

  20. Estrogen deficiency results in enhanced expression of Smoothened of the Hedgehog signaling in the thymus and affects thymocyte development.

    Science.gov (United States)

    Li, Chun-Lin; Toda, Katsumi; Saibara, Toshiji; Zhang, Ting; Ono, Masafumi; Iwasaki, Shinji; Maeda, Takashi; Okada, Teruhiko; Hayashi, Yoshihiro; Enzan, Hideaki; Shizuta, Yutaka; Onishi, Saburo

    2002-05-01

    Aromatase is an essential enzyme for estrogen synthesis. We investigated the role of estrogen in thymocyte development using aromatase-deficient (ArKO) mice. Like its role as a regulator of bone metabolism through regulating osteoprotegerin (OPG) production, estrogen is involved in the processes of thymocyte development although aromatase mRNA was not detectable in the thymus. Thymic regression and reduced cellularity were evident in ArKO mice. The major difficulties in thymocyte development of ArKO mice were observed during the CD44+ CD25- stage at the cortico-medullary junction and during the CD44- CD25- stage at the subcapsular region where the estrogen receptor was expressed in the stromal cells. The proportion of thymocytes during the CD44+ CD25- stage was reduced. The progression of CD44- CD25+ cells to the CD44- CD25- stage was accelerated in ArKO mice possibly due to insufficient osteoprotegerin production in estrogen-deficiency. However, the expression of Smoothened of the Hedgehog signaling was enhanced in CD4- CD8- double negative cells. This enhancement may result in impaired progression of CD44- CD25- cells to the CD4+ CD8+ double positive stage and impaired proliferation of CD4+ CD8+ double positive cells since Smoothened (Smo) is known to arrest cells as non-proliferating cells. This could be the reason why the proportion of CD3+ TCRbeta(high) cells during the late phase of thymocyte maturation was reduced in ArKO mice. From these observations, we propose that estrogen supports thymocyte development and maturation at many stages through many regulatory pathways including the sonic hedgehog- and the osteoprotegerin ligand (OPGL)-mediated signaling.

  1. CYP2S1 depletion enhances colorectal cell proliferation is associated with PGE2-mediated activation of β-catenin signaling

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Chao [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030 (China); College of Life Science, Anhui Normal University, Wuhu 241000, Anhui (China); Li, Changyuan [College of Life Science, Anhui Normal University, Wuhu 241000, Anhui (China); Li, Minle; Tong, Xuemei [Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai 200025 (China); Hu, Xiaowen; Yang, Xuhan [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030 (China); Yan, Xiaomei [School of Life Sciences & Biotechnology, Shanghai JiaoTong University, Shanghai 200240 (China); He, Lin, E-mail: helinhelin@gmail.com [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030 (China); Wan, Chunling, E-mail: clwan@sjtu.edu.cn [Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030 (China)

    2015-02-15

    Colorectal epithelial cancer is one of the most common cancers in the world and its 5-year survival rate is still relatively low. Cytochrome P450 (CYP) enzymes in epithelial cells lining the alimentary tract play an important role in the oxidative metabolism of a wide range of xenobiotics, including (pro-)carcinogens and endogenous compounds. Although CYP2S1, a member of CYP family, strongly expressed in many extrahepatic tissues, the role of CYP2S1 in cancer remains unclear. To investigate whether CYP2S1 involves in colorectal carcinogenesis, cell proliferation was analyzed in HCT116 cells depleted of CYP2S1 using small hairpin interfering RNA. Our data show that CYP2S1 knockdown promotes cell proliferation through increasing the level of endogenous prostaglandin E2(PGE2). PGE2, in turn, reduces phosphorylation of β-catenin and activates β-catenin signaling, which contributes to the cell proliferation. Furthermore, CYP2S1 knockdown increase tumor growth in xenograft mouse model. In brief, these results demonstrate that CYP2S1 regulates colorectal cancer growth through associated with PGE2-mediated activation of β-catenin signaling. - Highlights: • Knockdown of CYP2S1 expression improve HCT116 cell proliferation in vitro and in vivo. • Elevate PGE2 production in CYP2S1 knockdown cell is associated with its proliferation. • Elevate PGE2 level in CYP2S1 knockdown cells enhance β-catenin accumulation. • β-catenin activate TCF/LEF and target gene expression thus promote cell proliferation.

  2. Hyaluronic acid enhances proliferation of human amniotic mesenchymal stem cells through activation of Wnt/β-catenin signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ru-Ming; Sun, Ren-Gang; Zhang, Ling-Tao; Zhang, Qing-Fang; Chen, Dai-Xiong [Guizhou Center for Translational Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi 563000 (China); Zhong, Jian-Jiang, E-mail: jjzhong@sjtu.edu.cn [State Key Laboratory of Microbial Metabolism, and School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai 200240 (China); Xiao, Jian-Hui, E-mail: jhxiao@yahoo.com [Guizhou Center for Translational Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Zunyi 563000 (China)

    2016-07-15

    This study investigated the pro-proliferative effect of hyaluronic acid (HA) on human amniotic mesenchymal stem cells (hAMSCs) and the underlying mechanisms. Treatment with HA increased cell population growth in a dose- and time-dependent manner. Analyses by flow cytometry and immunocytochemistry revealed that HA did not change the cytophenotypes of hAMSCs. Additionally, the osteogenic, chondrogenic, and adipogenic differentiation capabilities of these hAMSCs were retained after HA treatment. Moreover, HA increased the mRNA expressions of wnt1, wnt3a, wnt8a, cyclin D1, Ki-67, and β-catenin as well as the protein level of β-catenin and cyclin D1 in hAMSCs; and the nuclear localization of β-catenin was also enhanced. Furthermore, the pro-proliferative effect of HA and up-regulated expression of Wnt/β-catenin pathway-associated proteins - wnt3a, β-catenin and cyclin D1 in hAMSCs were significantly inhibited upon pre-treatment with Wnt-C59, an inhibitor of the Wnt/β-catenin pathway. These results suggest that HA may positively regulate hAMSCs proliferation through regulation of the Wnt/β-catenin signaling pathway. - Highlights: • Hyaluronic acid (HA) could promote the proliferation of hAMSCs. • HA treatment dose not affect the pluripotency of hAMSCs. • HA increases hAMSCs proliferation through activation of Wnt/β-catenin signaling.

  3. A TOTP-Based Enhanced Route Optimization Procedure for Mobile IPv6 to Reduce Handover Delay and Signalling Overhead

    Science.gov (United States)

    Shah, Peer Azmat; Hasbullah, Halabi B.; Lawal, Ibrahim A.; Aminu Mu'azu, Abubakar; Tang Jung, Low

    2014-01-01

    Due to the proliferation of handheld mobile devices, multimedia applications like Voice over IP (VoIP), video conferencing, network music, and online gaming are gaining popularity in recent years. These applications are well known to be delay sensitive and resource demanding. The mobility of mobile devices, running these applications, across different networks causes delay and service disruption. Mobile IPv6 was proposed to provide mobility support to IPv6-based mobile nodes for continuous communication when they roam across different networks. However, the Route Optimization procedure in Mobile IPv6 involves the verification of mobile node's reachability at the home address and at the care-of address (home test and care-of test) that results in higher handover delays and signalling overhead. This paper presents an enhanced procedure, time-based one-time password Route Optimization (TOTP-RO), for Mobile IPv6 Route Optimization that uses the concepts of shared secret Token, time based one-time password (TOTP) along with verification of the mobile node via direct communication and maintaining the status of correspondent node's compatibility. The TOTP-RO was implemented in network simulator (NS-2) and an analytical analysis was also made. Analysis showed that TOTP-RO has lower handover delays, packet loss, and signalling overhead with an increased level of security as compared to the standard Mobile IPv6's Return-Routability-based Route Optimization (RR-RO). PMID:24688398

  4. A TOTP-Based Enhanced Route Optimization Procedure for Mobile IPv6 to Reduce Handover Delay and Signalling Overhead

    Directory of Open Access Journals (Sweden)

    Peer Azmat Shah

    2014-01-01

    Full Text Available Due to the proliferation of handheld mobile devices, multimedia applications like Voice over IP (VoIP, video conferencing, network music, and online gaming are gaining popularity in recent years. These applications are well known to be delay sensitive and resource demanding. The mobility of mobile devices, running these applications, across different networks causes delay and service disruption. Mobile IPv6 was proposed to provide mobility support to IPv6-based mobile nodes for continuous communication when they roam across different networks. However, the Route Optimization procedure in Mobile IPv6 involves the verification of mobile node’s reachability at the home address and at the care-of address (home test and care-of test that results in higher handover delays and signalling overhead. This paper presents an enhanced procedure, time-based one-time password Route Optimization (TOTP-RO, for Mobile IPv6 Route Optimization that uses the concepts of shared secret Token, time based one-time password (TOTP along with verification of the mobile node via direct communication and maintaining the status of correspondent node’s compatibility. The TOTP-RO was implemented in network simulator (NS-2 and an analytical analysis was also made. Analysis showed that TOTP-RO has lower handover delays, packet loss, and signalling overhead with an increased level of security as compared to the standard Mobile IPv6’s Return-Routability-based Route Optimization (RR-RO.

  5. A TOTP-based enhanced route optimization procedure for mobile IPv6 to reduce handover delay and signalling overhead.

    Science.gov (United States)

    Shah, Peer Azmat; Hasbullah, Halabi B; Lawal, Ibrahim A; Aminu Mu'azu, Abubakar; Tang Jung, Low

    2014-01-01

    Due to the proliferation of handheld mobile devices, multimedia applications like Voice over IP (VoIP), video conferencing, network music, and online gaming are gaining popularity in recent years. These applications are well known to be delay sensitive and resource demanding. The mobility of mobile devices, running these applications, across different networks causes delay and service disruption. Mobile IPv6 was proposed to provide mobility support to IPv6-based mobile nodes for continuous communication when they roam across different networks. However, the Route Optimization procedure in Mobile IPv6 involves the verification of mobile node's reachability at the home address and at the care-of address (home test and care-of test) that results in higher handover delays and signalling overhead. This paper presents an enhanced procedure, time-based one-time password Route Optimization (TOTP-RO), for Mobile IPv6 Route Optimization that uses the concepts of shared secret Token, time based one-time password (TOTP) along with verification of the mobile node via direct communication and maintaining the status of correspondent node's compatibility. The TOTP-RO was implemented in network simulator (NS-2) and an analytical analysis was also made. Analysis showed that TOTP-RO has lower handover delays, packet loss, and signalling overhead with an increased level of security as compared to the standard Mobile IPv6's Return-Routability-based Route Optimization (RR-RO).

  6. Sensitive electrochemical immunoassay with signal enhancement based on nanogold-encapsulated poly(amidoamine) dendrimer-stimulated hydrogen evolution reaction.

    Science.gov (United States)

    Sun, Ai-Li

    2015-12-07

    A new electrochemical immunosensor with signal enhancement was designed for sensitive detection of disease-related protein (human carbohydrate antigen 19-9, CA 19-9 used in this case). The assay was carried out on a capture antibody-modified screen-printed carbon electrode with a sandwich-type mode by using detection antibody-functionalized nanogold-encapsulated poly(amidoamine) dendrimer (AuNP-PAAD). The AuNP-PAAD was first synthesized through the in situ reduction method and functionalized with the polyclonal rabbit anti-human CA 19-9 antibody. Upon target CA 19-9 introduction, a sandwiched immunocomplex could be formed between the capture antibody and detection antibody. Accompanying the AuNP-PAAD, the electrocatalytic activity of the carried gold nanoparticles toward the hydrogen evolution reaction (HER) allowed the rapid quantification of the target analyte on the electrode. The amplified electrochemical signal mainly derived from AuNP-catalyzed HER in an acidic medium. Under optimal conditions, the immuno-HER assay displayed a wide dynamic concentration range from 0.01 to 300 U mL(-1) toward target CA 19-9 with a detection limit (LOD) of 6.3 mU mL(-1). The reproducibility, precision, specificity and stability of our strategy were acceptable. Additionally, the system was further validated by assaying 13 human serum specimens, giving well matched results obtained from the commercialized enzyme-linked immunosorbent assay (ELISA) method.

  7. Decreased abundance of type III secretion system-inducing signals in Arabidopsis mkp1 enhances resistance against Pseudomonas syringae

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Jeffrey C.; Wan, Ying; Kim, Young-Mo; Pasa-Tolic, Ljiljana; Metz, Thomas O.; Peck, Scott C.

    2014-04-21

    Many phytopathogenic bacteria use a type III secretion system (T3SS) to inject defense-suppressing effector proteins into host cells. Genes encoding the T3SS are induced at the start of infection, yet host signals that initiate T3SS gene expression are poorly understood. Here we identify several plant-derived metabolites that induce the T3SS in the bacterial pathogen Pseudomonas syringae pv tomato DC3000. In addition, we report that mkp1 (mapk phosphatase 1), an Arabidopsis mutant that is more resistant to bacterial infection, produces decreased levels of these T3SS-inducing metabolites. Consistent with the observed decrease in these metabolites, T3SS effector delivery by DC3000 was impaired in mkp1. Addition of the bioactive metabolites to the mkp1-DC3000 interaction fully restored T3SS effector delivery and suppressed enhanced resistance in mkp1. Together, these results demonstrate that DC3000 perceives multiple signals derived from plants to initiate their virulence program, and reveal a new layer of molecular communication between plants and these pathogenic bacteria.

  8. Improving the arterial input function in dynamic contrast enhanced MRI by fitting the signal in the complex plane.

    Science.gov (United States)

    Simonis, Frank F J; Sbrizzi, Alessandro; Beld, Ellis; Lagendijk, Jan J W; van den Berg, Cornelis A T

    2016-10-01

    Dynamic contrast enhanced (DCE) imaging is a widely used technique in oncologic imaging. An essential prerequisite for obtaining quantitative values from DCE-MRI is the determination of the arterial input function (AIF). However, it is very challenging to accurately estimate the AIF using MR. A comprehensive model, which uses complex data instead of either magnitude or phase, was developed to improve AIF estimation. The model was first applied to simulated data. Subsequently, the accuracy of the estimated contrast agent concentration was validated in a phantom. Finally the method was applied to existing DCE scans of 13 prostate cancer patients. The complex signal method combines the complementary strengths of the magnitude and phase method, increasing the precision and accuracy of concentration estimation in simulated and phantom data. The in vivo AIFs show a good agreement between arterial voxels (standard deviation in the peak and tail equal 0.4 mM and 0.12 mM, respectively). Furthermore, the dynamic behavior closely followed the AIF obtained with DCE-CT in the same patients (mean correlation coefficient: 0.92). By using the complex signal, the AIF estimation becomes more accurate and precise. This might enable patient specific AIFs, thereby improving the quantitative values obtained from DCE-MRI. Magn Reson Med 76:1236-1245, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  9. Thiazolidinediones enhance sodium-coupled bicarbonate absorption from renal proximal tubules via PPARγ-dependent nongenomic signaling.

    Science.gov (United States)

    Endo, Yoko; Suzuki, Masashi; Yamada, Hideomi; Horita, Shoko; Kunimi, Motoei; Yamazaki, Osamu; Shirai, Ayumi; Nakamura, Motonobu; Iso-O, Naoyuki; Li, Yuehong; Hara, Masumi; Tsukamoto, Kazuhisa; Moriyama, Nobuo; Kudo, Akihiko; Kawakami, Hayato; Yamauchi, Toshimasa; Kubota, Naoto; Kadowaki, Takashi; Kume, Haruki; Enomoto, Yutaka; Homma, Yukio; Seki, George; Fujita, Toshiro

    2011-05-04

    Thiazolidinediones (TZDs) improve insulin resistance by activating a nuclear hormone receptor, peroxisome proliferator-activated receptor γ (PPARγ). However, the use of TZDs is associated with plasma volume expansion through a mechanism that remains to be clarified. Here we showed that TZDs rapidly stimulate sodium-coupled bicarbonate absorption from the renal proximal tubule in vitro and in vivo. TZD-induced transport stimulation is dependent on PPARγ-Src-EGFR-ERK and observed in rat, rabbit and human, but not in mouse proximal tubules where Src-EGFR is constitutively activated. The existence of PPARγ-Src-dependent nongenomic signaling, which requires the ligand-binding ability, but not the transcriptional activity of PPARγ, is confirmed in mouse embryonic fibroblast cells. The enhancement of the association between PPARγ and Src by TZDs supports an indispensable role of Src in this signaling. These results suggest that the PPARγ-dependent nongenomic stimulation of renal proximal transport is also involved in TZD-induced volume expansion. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Enhanced Inhibition of ERK Signaling by a Novel Allosteric MEK Inhibitor, CH5126766, That Suppresses Feedback Reactivation of RAF Activity

    Science.gov (United States)

    Joseph, Eric W.; Ohara, Kazuhiro; Miura, Takaaki; Sakamoto, Hiroshi; Matsuda, Yutaka; Tomii, Yasushi; Tachibana-Kondo, Yukako; Iikura, Hitoshi; Aoki, Toshihiro; Shimma, Nobuo; Arisawa, Mikio; Sowa, Yoshihiro; Poulikakos, Poulikos I.; Rosen, Neal; Aoki, Yuko; Sakai, Toshiyuki

    2014-01-01

    Tumors with mutant RAS are often dependent on extracellular signal–regulated kinase (ERK) signaling for growth; however, MEK inhibitors have only marginal antitumor activity in these tumors. MEK inhibitors relieve ERK-dependent feedback inhibition of RAF and cause induction of MEK phosphorylation. We have now identified a MEK inhibitor, CH5126766 (RO5126766), that has the unique property of inhibiting RAF kinase as well. CH5126766 binding causes MEK to adopt a conformation in which it cannot be phosphorylated by and released from RAF. This results in formation of a stable MEK/RAF complex and inhibition of RAF kinase. Consistent with this mechanism, this drug does not induce MEK phosphorylation. CH5126766 inhibits ERK signaling output more effectively than a standard MEK inhibitor that induces MEK phosphorylation and has potent antitumor activity as well. These results suggest that relief of RAF feedback limits pathway inhibition by standard MEK inhibitors. CH5126766 represents a new type of MEK inhibitor that causes MEK to become a dominant-negative inhibitor of RAF and that, in doing so, may have enhanced therapeutic activity in ERK-dependent tumors with mutant RAS. PMID:23667175

  11. AVE 3085, a novel endothelial nitric oxide synthase enhancer, attenuates cardiac remodeling in mice through the Smad signaling pathway.

    Science.gov (United States)

    Chen, Yili; Chen, Cong; Feng, Cong; Tang, Anli; Ma, Yuedong; He, Xin; Li, Yanhui; He, Jiangui; Dong, Yugang

    2015-03-15

    AVE 3085 is a novel endothelial nitric oxide synthase enhancer. Although AVE 3085 treatment has been shown to be effective in spontaneously restoring endothelial function in hypertensive rats, little is known about the effects and mechanisms of AVE 3085 with respect to cardiac remodeling. The present study was designed to examine the effects of AVE 3085 on cardiac remodeling and the mechanisms underlying the effects of this compound. Mice were subjected to aortic banding to induce cardiac remodeling and were then administered AVE 3085 (10 mg kg day(-1), orally) for 4 weeks. At the end of the treatment, the aortic banding-treated mice exhibited significant elevations in cardiac remodeling, characterized by an increase in left ventricular weight relative to body weight, an increase in the area of collagen deposition, an increase in the mean myocyte diameter, and increases in the gene expressions of the hypertrophic markers atrial natriuretic peptide (ANP) and β-MHC. These indexes were significantly decreased in the AVE 3085-treated mice. Furthermore, AVE 3085 treatment reduced the expression and activation of the Smad signaling pathway in the aortic banding-treated mice. Our data showed that AVE 3085 attenuated cardiac remodeling, and this effect was possibly mediated through the inhibition of Smad signaling. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Coconut oil protects cortical neurons from amyloid beta toxicity by enhancing signaling of cell survival pathways.

    Science.gov (United States)

    Nafar, F; Clarke, J P; Mearow, K M

    2017-05-01

    Alzheimer's disease is a progressive neurodegenerative disease that has links with other conditions that can often be modified by dietary and life-style interventions. In particular, coconut oil has received attention as having potentially having benefits in lessening the cognitive deficits associated with Alzheimer's disease. In a recent report, we showed that neuron survival in cultures co-treated with coconut oil and Aβ was rescued compared to cultures exposed only to Aβ. Here we investigated treatment with Aβ for 1, 6 or 24 h followed by addition of coconut oil for a further 24 h, or treatment with coconut oil for 24 h followed by Aβ exposure for various periods. Neuronal survival and several cellular parameters (cleaved caspase 3, synaptophysin labeling and ROS) were assessed. In addition, the influence of these treatments on relevant signaling pathways was investigated with Western blotting. In terms of the treatment timing, our data indicated that coconut oil rescues cells pre-exposed to Aβ for 1 or 6 h, but is less effective when the pre-exposure has been 24 h. However, pretreatment with coconut oil prior to Aβ exposure showed the best outcomes. Treatment with octanoic or lauric acid also provided protection against Aβ, but was not as effective as the complete oil. The coconut oil treatment reduced the number of cells with cleaved caspase and ROS labeling, as well as rescuing the loss of synaptophysin labeling observed with Aβ treatment. Treatment with coconut oil, as well as octanoic, decanoic and lauric acids, resulted in a modest increase in ketone bodies compared to controls. The biochemical data suggest that Akt and ERK activation may contribute to the survival promoting influence of coconut oil. This was supported by observations that a PI3-Kinase inhibitor blocked the rescue effect of CoOil on Aβ amyloid toxicity. Further studies into the mechanisms of action of coconut oil and its constituent medium chain fatty acids are warranted

  13. Enhanced Wnt signaling improves bone mass and strength, but not brittleness, in the Col1a1(+/mov13) mouse model of type I Osteogenesis Imperfecta.

    Science.gov (United States)

    Jacobsen, Christina M; Schwartz, Marissa A; Roberts, Heather J; Lim, Kyung-Eun; Spevak, Lyudmila; Boskey, Adele L; Zurakowski, David; Robling, Alexander G; Warman, Matthew L

    2016-09-01

    Osteogenesis Imperfecta (OI) comprises a group of genetic skeletal fragility disorders. The mildest form of OI, Osteogenesis Imperfecta type I, is frequently caused by haploinsufficiency mutations in COL1A1, the gene encoding the α1(I) chain of type 1 collagen. Children with OI type I have a 95-fold higher fracture rate compared to unaffected children. Therapies for OI type I in the pediatric population are limited to anti-catabolic agents. In adults with osteoporosis, anabolic therapies that enhance Wnt signaling in bone improve bone mass, and ongoing clinical trials are determining if these therapies also reduce fracture risk. We performed a proof-of-principle experiment in mice to determine whether enhancing Wnt signaling in bone could benefit children with OI type I. We crossed a mouse model of OI type I (Col1a1(+/Mov13)) with a high bone mass (HBM) mouse (Lrp5(+/p.A214V)) that has increased bone strength from enhanced Wnt signaling. Offspring that inherited the OI and HBM alleles had higher bone mass and strength than mice that inherited the OI allele alone. However, OI+HBM and OI mice still had bones with lower ductility compared to wild-type mice. We conclude that enhancing Wnt signaling does not make OI bone normal, but does improve bone properties that could reduce fracture risk. Therefore, agents that enhance Wnt signaling are likely to benefit children and adults with OI type 1. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Contrast-enhanced MRI after neoadjuvant chemotherapy of breast cancer: lesion-to-background parenchymal signal enhancement ratio for discriminating pathological complete response from minimal residual tumour.

    Science.gov (United States)

    Kim, Soo-Yeon; Cho, Nariya; Shin, Sung Ui; Lee, Han-Byoel; Han, Wonshik; Park, In Ae; Kwon, Bo Ra; Kim, Soo Yeon; Lee, Su Hyun; Chang, Jung Min; Moon, Woo Kyung

    2018-01-29

    To retrospectively investigate whether the lesion-to-background parenchymal signal enhancement ratio (SER) on breast MRI can distinguish pathological complete response (pCR) from minimal residual cancer following neoadjuvant chemotherapy (NAT), and compare its performance with the conventional criterion. 216 breast cancer patients who had undergone NAT and MRI and achieved pCR or minimal residual cancer on surgical histopathology were included. Clinical-pathological features, SER and lesion size on MR images were analysed. Multivariate logistic regression, ROC curve and McNemar's test were performed. SER on early-phase MR images was independently associated with pCR (odds ratio [OR], 0.286 [95% CI: 0.113-0.725], p = .008 for Reader 1; OR, 0.306 [95% CI: 0.111-0.841], p = .022 for Reader 2). Compared with the conventional criterion, SER ≤1.6 increased AUC (0.585-0.599 vs. 0.709-0.771, p=.001-.033) and specificity (21.9-27.4% vs. 80.8-86.3%, p highest specificity of 90.4%. SER on early-phase MR images was independently associated with pCR, and showed improved AUC and specificity compared to the conventional criterion. The combined criterion of SER and size could be used to select candidates to avoid surgery in a future study. • Compared with conventional criterion, SER ≤ 1.6 criterion increased AUC and specificity. • Simple measurement of signal intensity could differentiate pCR from minimal residual cancer. • SER ≤1.6 and/or size≤0.2cm criterion showed the highest specificity of 90.4 %. • The combined criterion could be used for a study to avoid surgery.

  15. A Mouse Monoclonal Antibody against Dengue Virus Type 1 Mochizuki Strain Targeting Envelope Protein Domain II and Displaying Strongly Neutralizing but Not Enhancing Activity

    Science.gov (United States)

    Kotaki, Tomohiro; Konishi, Eiji

    2013-01-01

    Dengue fever and its more severe form, dengue hemorrhagic fever, are major global concerns. Infection-enhancing antibodies are major factors hypothetically contributing to increased disease severity. In this study, we generated 26 monoclonal antibodies (MAbs) against the dengue virus type 1 Mochizuki strain. We selected this strain because a relatively large number of unique and rare amino acids were found on its envelope protein. Although most MAbs showing neutralizing activities exhibited enhancing activities at subneutralizing doses, one MAb (D1-IV-7F4 [7F4]) displayed neutralizing activities without showing enhancing activities at lower concentrations. In contrast, another MAb (D1-V-3H12 [3H12]) exhibited only enhancing activities, which were suppressed by pretreatment of cells with anti-FcγRIIa. Although antibody engineering revealed that antibody subclass significantly affected 7F4 (IgG3) and 3H12 (IgG1) activities, neutralizing/enhancing activities were also dependent on the epitope targeted by the antibody. 7F4 recognized an epitope on the envelope protein containing E118 (domain II) and had a neutralizing activity 10- to 1,000-fold stronger than the neutralizing activity of previously reported human or humanized neutralizing MAbs targeting domain I and/or domain II. An epitope-blocking enzyme-linked immunosorbent assay (ELISA) indicated that a dengue virus-immune population possessed antibodies sharing an epitope with 7F4. Our results demonstrating induction of these antibody species (7F4 and 3H12) in Mochizuki-immunized mice may have implications for dengue vaccine strategies designed to minimize induction of enhancing antibodies in vaccinated humans. PMID:24049185

  16. LIGO: The strong belief

    CERN Multimedia

    Antonella Del Rosso

    2016-01-01

    Twenty years of designing, building and testing a number of innovative technologies, with the strong belief that the endeavour would lead to a historic breakthrough. The Bulletin publishes an abstract of the Courier’s interview with Barry Barish, one of the founding fathers of LIGO.   The plots show the signals of gravitational waves detected by the twin LIGO observatories at Livingston, Louisiana, and Hanford, Washington. (Image: Caltech/MIT/LIGO Lab) On 11 February, the Laser Interferometer Gravitational-Wave Observatory (LIGO) and Virgo collaborations published a historic paper in which they showed a gravitational signal emitted by the merger of two black holes. These results come after 20 years of hard work by a large collaboration of scientists operating the two LIGO observatories in the US. Barry Barish, Linde Professor of Physics, Emeritus at the California Institute of Technology and former Director of the Global Design Effort for the Internat...

  17. GITR signaling potentiates airway hyperresponsiveness by enhancing Th2 cell activity in a mouse model of asthma

    Directory of Open Access Journals (Sweden)

    Van Oosterhout Antoon JM

    2009-10-01

    Full Text Available Abstract Background Allergic asthma is characterized by airway hyperresponsiveness (AHR and allergic inflammation of the airways, driven by allergen-specific Th2 cells. The asthma phenotypes and especially AHR are sensitive to the presence and activity of regulatory T (Treg cells in the lung. Glucocorticoid-induced tumor necrosis factor receptor (GITR is known to have a co-stimulatory function on effector CD4+ T cells, rendering these cells insensitive to Treg suppression. However, the effects of GITR signaling on polarized Th1 and Th2 cell effector functions are not well-established. We sought to evaluate the effect of GITR signaling on fully differentiated Th1 and Th2 cells and to determine the effects of GITR activation at the time of allergen provocation on AHR and airway inflammation in a Th2-driven mouse model of asthma. Methods CD4+CD25- cells were polarized in vitro into Th1 and Th2 effector cells, and re-stimulated in the presence of GITR agonistic antibodies to assess the effect on IFNγ and IL-4 production. To evaluate the effects of GITR stimulation on AHR and allergic inflammation in a mouse asthma model, BALB/c mice were sensitized to OVA followed by airway challenges in the presence or absence of GITR agonist antibodies. Results GITR engagement potentiated cytokine release from CD3/CD28-stimulated Th2 but not Th1 cells in vitro. In the mouse asthma model, GITR triggering at the time of challenge induced enhanced airway hyperresponsiveness, serum IgE and ex vivo Th2 cytokine release, but did not increase BAL eosinophilia. Conclusion GITR exerts a differential effect on cytokine release of fully differentiated Th1 and Th2 cells in vitro, potentiating Th2 but not Th1 cytokine production. This effect on Th2 effector functions was also observed in vivo in our mouse model of asthma, resulting in enhanced AHR, serum IgE responses and Th2 cytokine production. This is the first report showing the effects of GITR activation on cytokine

  18. Inhibition of apoptosis signal-regulating kinase 1 alters the wound epidermis and enhances auricular cartilage regeneration.

    Science.gov (United States)

    Zhang, Qian-Shi; Kurpad, Deepa S; Mahoney, My G; Steinbeck, Marla J; Freeman, Theresa A

    2017-01-01

    Why regeneration does not occur in mammals remains elusive. In lower vertebrates, epimorphic regeneration of the limb is directed by the wound epidermis, which controls blastema formation to promote regrowth of the appendage. Herein, we report that knockout (KO) or inhibition of Apoptosis Signal-regulated Kinase-1 (ASK1), also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5), after full thickness ear punch in mice prolongs keratinocyte activation within the wound epidermis and promotes regeneration of auricular cartilage. Histological analysis showed the ASK1 KO ears displayed enhanced protein markers associated with blastema formation, hole closure and regeneration of auricular cartilage. At seven days after punch, the wound epidermis morphology was markedly different in the KO, showing a thickened stratum corneum with rounded cell morphology and a reduction of both the granular cell layer and decreased expression of filament aggregating protein. In addition, cytokeratin 6 was expressed in the stratum spinosum and granulosum. Topical application of inhibitors of ASK1 (NQDI-1), the upstream ASK1 activator, calcium activated mitogen kinase 2 (KN93), or the downstream target, c-Jun N-terminal kinase (SP600125) also resulted in enhanced regeneration; whereas inhibition of the other downstream target, the p38 α/β isoforms, (SB203580) had no effect. The results of this investigation indicate ASK1 inhibition prolongs keratinocyte and blastemal cell activation leading to ear regeneration.

  19. Inhibition of apoptosis signal-regulating kinase 1 alters the wound epidermis and enhances auricular cartilage regeneration.

    Directory of Open Access Journals (Sweden)

    Qian-Shi Zhang

    Full Text Available Why regeneration does not occur in mammals remains elusive. In lower vertebrates, epimorphic regeneration of the limb is directed by the wound epidermis, which controls blastema formation to promote regrowth of the appendage. Herein, we report that knockout (KO or inhibition of Apoptosis Signal-regulated Kinase-1 (ASK1, also known as mitogen-activated protein kinase kinase kinase 5 (MAP3K5, after full thickness ear punch in mice prolongs keratinocyte activation within the wound epidermis and promotes regeneration of auricular cartilage. Histological analysis showed the ASK1 KO ears displayed enhanced protein markers associated with blastema formation, hole closure and regeneration of auricular cartilage. At seven days after punch, the wound epidermis morphology was markedly different in the KO, showing a thickened stratum corneum with rounded cell morphology and a reduction of both the granular cell layer and decreased expression of filament aggregating protein. In addition, cytokeratin 6 was expressed in the stratum spinosum and granulosum. Topical application of inhibitors of ASK1 (NQDI-1, the upstream ASK1 activator, calcium activated mitogen kinase 2 (KN93, or the downstream target, c-Jun N-terminal kinase (SP600125 also resulted in enhanced regeneration; whereas inhibition of the other downstream target, the p38 α/β isoforms, (SB203580 had no effect. The results of this investigation indicate ASK1 inhibition prolongs keratinocyte and blastemal cell activation leading to ear regeneration.

  20. Dipalmitoleoylphosphoethanolamine as a PP2A enhancer obstructs insulin signaling by promoting Ser/Thr dephosphorylation of Akt.

    Science.gov (United States)

    Tsuchiya, Ayako; Kanno, Takeshi; Nishizaki, Tomoyuki

    2014-01-01

    The phospholipid phosphatidylethanolamine is implicated in the regulation of a variety of cellular processes. The present study investigated the effect of phosphatidylethanolamines such as 1,2-diarachidonoyl-sn-glycero-3-phosphoethanolamine (DAPE), 1,2-dilinoleoyl-sn-glycero-3-phosphoethanolamine (DLPE), 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), and 1,2-dipalmitoleoyl-sn-glycero-3-phosphoethanolamine (DPPE) on protein phosphatases, Akt1/2 activity, GLUT4 mobilizations, and glucose uptake into cells. Activity of protein phosphatase 2A (PP2A) was assayed under the cell-free conditions, and Western blotting, intracellular GLUT4 trafficking, and glucose uptake into cells were monitored using differentiated 3T3-L1-GLUT4myc adipocytes. Of the investigated phosphatidylethanolamines, DLPE and DPPE significantly enhanced PP2A activity. DPPE inhibited insulin-induced phosphorylation of Akt1/2 at Thr308/309 and Ser473/474 in differentiated 3T3-L1-GLUT4myc adipocytes. DPPE also inhibited insulin-stimulated GLUT4 translocation to the cell surface and reduced insulin-stimulated glucose uptake into adipocytes. The results of the present study indicate that the PP2A enhancer DPPE obstructs insulin signaling by promoting serine/threonine dephosphorylation of Akt1/2, resulting in the suppression of GLUT4 translocation to the cell surface and glucose uptake into adipocytes. © 2014 S. Karger AG, Basel.

  1. Dipalmitoleoylphosphoethanolamine as a PP2A Enhancer Obstructs Insulin Signaling by Promoting Ser/Thr Dephosphorylation of Akt

    Directory of Open Access Journals (Sweden)

    Ayako Tsuchiya

    2014-08-01

    Full Text Available Background/Aims: The phospholipid phosphatidylethanolamine is implicated in the regulation of a variety of cellular processes. The present study investigated the effect of phosphatidylethanolamines such as 1,2-diarachidonoyl-sn-glycero-3-phosphoethanolamine (DAPE, 1,2-dilinoleoyl-sn-glycero-3-phosphoethanolamine (DLPE, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE, and 1,2-dipalmitoleoyl-sn-glycero-3-phosphoethanolamine (DPPE on protein phosphatases, Akt1/2 activity, GLUT4 mobilizations, and glucose uptake into cells. Methods: Activity of protein phosphatase 2A (PP2A was assayed under the cell-free conditions, and Western blotting, intracellular GLUT4 trafficking, and glucose uptake into cells were monitored using differentiated 3T3-L1-GLUT4myc adipocytes. Results: Of the investigated phosphatidylethanolamines, DLPE and DPPE significantly enhanced PP2A activity. DPPE inhibited insulin-induced phosphorylation of Akt1/2 at Thr308/309 and Ser473/474 in differentiated 3T3-L1-GLUT4myc adipocytes. DPPE also inhibited insulin-stimulated GLUT4 translocation to the cell surface and reduced insulin-stimulated glucose uptake into adipocytes. Conclusion: The results of the present study indicate that the PP2A enhancer DPPE obstructs insulin signaling by promoting serine/threonine dephosphorylation of Akt1/2, resulting in the suppression of GLUT4 translocation to the cell surface and glucose uptake into adipocytes.

  2. Adiponectin enhances osteogenic differentiation in human adipose-derived stem cells by activating the APPL1-AMPK signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Tong; Wu, Yu-wei; Lu, Hui; Guo, Yuan [Second Dental Center, Peking University School and Hospital of Stomatology, Beijing (China); National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing (China); Tang, Zhi-hui, E-mail: tang_zhihui@live.cn [Second Dental Center, Peking University School and Hospital of Stomatology, Beijing (China); National Engineering Laboratory for Digital and Material Technology of Stomatology, Peking University School and Hospital of Stomatology, Beijing (China)

    2015-05-29

    Human adipose-derived stem cells (hASCs) are multipotent progenitor cells with multi-lineage differentiation potential including osteogenesis and adipogenesis. While significant progress has been made in understanding the transcriptional control of hASC fate, little is known about how hASC differentiation is regulated by the autocrine loop. The most abundant adipocytokine secreted by adipocytes, adiponectin (APN) plays a pivotal role in glucose metabolism and energy homeostasis. Growing evidence suggests a positive association between APN and bone formation yet little is known regarding the direct effects of APN on hASC osteogenesis. Therefore, this study was designed to investigate the varied osteogenic effects and regulatory mechanisms of APN in the osteogenic commitment of hASCs. We found that APN enhanced the expression of osteoblast-related genes in hASCs, such as osteocalcin, alkaline phosphatase, and runt-related transcription factor-2 (Runx2, also known as CBFa1), in a dose- and time-dependent manner. This was further confirmed by the higher expression levels of alkaline phosphatase and increased formation of mineralization nodules, along with the absence of inhibition of cell proliferation. Importantly, APN at 1 μg/ml was the optimal concentration, resulting in maximum deposition of calcium nodules, and was significant superior to bone morphogenetic protein 2. Mechanistically, we found for the first time that APN increased nuclear translocation of the leucine zipper motif (APPL)-1 as well as AMP-activated protein kinase (AMPK) phosphorylation, which were reversed by pretreatment with APPL1 siRNA. Our results indicate that APN promotes the osteogenic differentiation of hASCs by activating APPL1-AMPK signaling, suggesting that manipulation of APN is a novel therapeutic target for controlling hASC fate. - Highlights: • Adiponectin enhances osteogenic differentiation in human adipose-derived stem cells. • The knock-down of APPL1 block the enhancement of

  3. Predicting local recurrence following breast-conserving treatment: parenchymal signal enhancement ratio (SER) around the tumor on preoperative MRI

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mi Young; Cho, Nariya; Koo, Hye Ryoung; Yun, Bo La; Bae, Min Sun; Moon, Woo Kyung [Dept. of Radiology, Seoul National Univ. Coll. of Medicine, Seoul National Univ. Hospital, Seoul (Korea, Republic of)], e-mail: river7774@gmail.com; Chie, Eui Kyu [Dept. of Radiation Oncology, Seoul National Univ. Coll. of Medicine, Seoul National Univ. Hospital, Seoul (Korea, Republic of)

    2013-09-15

    Background: The level of background parenchymal enhancement around tumor is known to be associated with breast cancer risk. However, there is no study investigating predictive power of parenchymal signal enhancement ratio (SER) around tumor for ipsilateral breast tumor recurrence (IBTR). Purpose: To investigate whether the breast parenchymal SER around the tumor on preoperative dynamic contrast-enhanced magnetic resonance imaging (MRI) is associated with subsequent IBTR in breast cancer patients who had undergone breast-conserving treatment. Material and Methods: Nineteen consecutive women (mean age, 44 years; range, 34-63 years) with breast cancer who developed IBTR following breast-conserving treatment and 114 control women matched for age, as well as T and N stages were included. We compared the clinicopathologic features of the two groups including nuclear grade, histologic grade, hormonal receptor status, human epidermal growth factor receptor-2 (HER-2) status, lymphovascular invasion, negative margin width, use of adjuvant therapy, and parenchymal SER around the tumor on preoperative DCE-MRI. The SER was measured on a slice showing the largest dimension of the tumor. Multivariate conditional logistic regression analysis was used to identify independent factors associated with IBTR. Results: In univariate analysis, ER negativity (odds ratio [OR] = 4.7; P = 0.040), PR negativity (OR = 4.0; P = 0.013), HER-2 positivity (OR = 3.6; P = 0.026), and a parenchymal SER greater than 0.53 (OR = 23.3; P = 0.011) were associated with IBTR. In multivariate analysis, ER negativity (OR = 3.8; P = 0.015) and a parenchymal SER greater than 0.53 (OR = 13.2; P = 0.040) on preoperative MRI were independent factors associated with IBTR. Conclusion: In addition to ER negativity, a higher parenchymal SER on preoperative MRI was an independent factor associated with subsequent IBTR in patients with breast cancer who had undergone breast-conserving treatment.

  4. Dietary iron enhances colonic inflammation and IL-6/IL-11-Stat3 signaling promoting colonic tumor development in mice.

    Directory of Open Access Journals (Sweden)

    Anita C G Chua

    Full Text Available Chronic intestinal inflammation and high dietary iron are associated with colorectal cancer development. The role of Stat3 activation in iron-induced colonic inflammation and tumorigenesis was investigated in a mouse model of inflammation-associated colorectal cancer. Mice, fed either an iron-supplemented or control diet, were treated with azoxymethane and dextran sodium sulfate (DSS. Intestinal inflammation and tumor development were assessed by endoscopy and histology, gene expression by real-time PCR, Stat3 phosphorylation by immunoblot, cytokines by ELISA and apoptosis by TUNEL assay. Colonic inflammation was more severe in mice fed an iron-supplemented compared with a control diet one week post-DSS treatment, with enhanced colonic IL-6 and IL-11 release and Stat3 phosphorylation. Both IL-6 and ferritin, the iron storage protein, co-localized with macrophages suggesting iron may act directly on IL-6 producing-macrophages. Iron increased DSS-induced colonic epithelial cell proliferation and apoptosis consistent with enhanced mucosal damage. DSS-treated mice developed anemia that was not alleviated by dietary iron supplementation. Six weeks post-DSS treatment, iron-supplemented mice developed more and larger colonic tumors compared with control mice. Intratumoral IL-6 and IL-11 expression increased in DSS-treated mice and IL-6, and possibly IL-11, were enhanced by dietary iron. Gene expression of iron importers, divalent metal transporter 1 and transferrin receptor 1, increased and iron exporter, ferroportin, decreased in colonic tumors suggesting increased iron uptake. Dietary iron and colonic inflammation synergistically activated colonic IL-6/IL-11-Stat3 signaling promoting tumorigenesis. Oral iron therapy may be detrimental in inflammatory bowel disease since it may exacerbate colonic inflammation and increase colorectal cancer risk.

  5. TRAF1 Coordinates Polyubiquitin Signaling to Enhance Epstein-Barr Virus LMP1-Mediated Growth and Survival Pathway Activation.

    Directory of Open Access Journals (Sweden)

    Hannah Greenfeld

    2015-05-01

    Full Text Available The Epstein-Barr virus (EBV encoded oncoprotein Latent Membrane Protein 1 (LMP1 signals through two C-terminal tail domains to drive cell growth, survival and transformation. The LMP1 membrane-proximal TES1/CTAR1 domain recruits TRAFs to activate MAP kinase, non-canonical and canonical NF-kB pathways, and is critical for EBV-mediated B-cell transformation. TRAF1 is amongst the most highly TES1-induced target genes and is abundantly expressed in EBV-associated lymphoproliferative disorders. We found that TRAF1 expression enhanced LMP1 TES1 domain-mediated activation of the p38, JNK, ERK and canonical NF-kB pathways, but not non-canonical NF-kB pathway activity. To gain insights into how TRAF1 amplifies LMP1 TES1 MAP kinase and canonical NF-kB pathways, we performed proteomic analysis of TRAF1 complexes immuno-purified from cells uninduced or induced for LMP1 TES1 signaling. Unexpectedly, we found that LMP1 TES1 domain signaling induced an association between TRAF1 and the linear ubiquitin chain assembly complex (LUBAC, and stimulated linear (M1-linked polyubiquitin chain attachment to TRAF1 complexes. LMP1 or TRAF1 complexes isolated from EBV-transformed lymphoblastoid B cell lines (LCLs were highly modified by M1-linked polyubiqutin chains. The M1-ubiquitin binding proteins IKK-gamma/NEMO, A20 and ABIN1 each associate with TRAF1 in cells that express LMP1. TRAF2, but not the cIAP1 or cIAP2 ubiquitin ligases, plays a key role in LUBAC recruitment and M1-chain attachment to TRAF1 complexes, implicating the TRAF1:TRAF2 heterotrimer in LMP1 TES1-dependent LUBAC activation. Depletion of either TRAF1, or the LUBAC ubiquitin E3 ligase subunit HOIP, markedly impaired LCL growth. Likewise, LMP1 or TRAF1 complexes purified from LCLs were decorated by lysine 63 (K63-linked polyubiqutin chains. LMP1 TES1 signaling induced K63-polyubiquitin chain attachment to TRAF1 complexes, and TRAF2 was identified as K63-Ub chain target. Co-localization of M1- and K63

  6. Strong Enhancement of Photoelectric Conversion Efficiency of Co-hybridized Polymer Solar Cell by Silver Nanoplates and Core-Shell Nanoparticles.

    Science.gov (United States)

    Shen, Wenfei; Tang, Jianguo; Wang, Yao; Liu, Jixian; Huang, Linjun; Chen, Weichao; Yang, Lanlan; Wang, Wei; Wang, Yanxin; Yang, Renqiang; Yun, Jungheum; Belfiore, Laurence A

    2017-02-15

    A new way was meticulously designed to utilize the localized surface plasmon resonance (LSPR) effect and the light scattering effect of silver nanoplate (Ag-nPl) and core-shell Ag@SiO 2 nanoparticles (Ag@SiO 2 -NPs) to enhance the photovoltaic performances of polymer solar cells (PSCs). To prevent direct contact between silver nanoparticles (Ag-NPs) and photoactive materials which will cause electrons quenching, bare Ag-nPl were spin-coated on indium tin oxide and silica capsulated Ag-NPs were incorporated to a PBDTTT-C-T:PC 71 BM active layer. As a result, the devices incorporated with Ag-nPl and Ag@SiO 2 -NPs showed great enhancements. With the dual effects of Ag-nPl and Ag@SiO 2 -NPs in devices, all wavelength sensitization in the visible range was realized; therefore, the power conversion efficiency (PCE) of PSCs showed a great enhancement of 14.0% to 8.46%, with an increased short-circuit current density of 17.23 mA·cm -2 . The improved photovoltaic performances of the devices were ascribed to the LSPR effect and the light scattering effect of metallic nanoparticles. Apart from optical effects, the charge collection efficiency of PSCs was improved after the incorporation of Ag-nPl.

  7. Enhancing weak transient signals in SEVIRI false colour imagery: application to dust source detection in southern Africa

    Science.gov (United States)

    Murray, Jon E.; Brindley, Helen E.; Bryant, Robert G.; Russell, Jacqui E.; Jenkins, Katherine F.

    2013-04-01

    Understanding the processes governing the availability and entrainment of mineral dust into the atmosphere requires dust sources to be identified and the evolution of dust events to be monitored. To achieve this aim a wide range of approaches have been developed utilising observations from a variety of different satellite sensors. Global maps of source regions and their relative strengths have been derived from instruments in low Earth orbit (e.g. Total Ozone Monitoring Spectrometer (TOMS) (Prospero et al., 2002), MODerate resolution Imaging Spectrometer (MODIS) (Ginoux et al., 2012)). Instruments such as MODIS can also be used to improve precise source location (Baddock et al., 2009) but the information available is restricted to the satellite overpass times which may not be coincident with active dust emission from the source. Hence, at a regional scale, some of the more successful approaches used to characterise the activity of different sources use high temporal resolution data available from instruments in geostationary orbit. For example, the widely used red-green-blue (RGB) dust scheme developed by Lensky and Rosenfeld (2008) (hereafter LR2008) makes use of observations from selected thermal channels of the Spinning Enhanced Visible and InfraRed Imager (SEVIRI) in a false colour rendering scheme in which dust appears pink. This scheme has provided the basis for numerous studies of north African dust sources and factors governing their activation (e.g. Schepanski et al., 2007, 2009, 2012). However, the LR2008 imagery can fail to identify dust events due to the effects of atmospheric moisture, variations in dust layer height and optical properties, and surface conditions (Brindley et al., 2012). Here we introduce a new method designed to circumvent some of these issues and enhance the signature of dust events using observations from SEVIRI. The approach involves the derivation of a composite clear-sky signal for selected channels on an individual time-step and

  8. Quality assurance in MRI breast screening: comparing signal-to-noise ratio in dynamic contrast-enhanced imaging protocols

    Science.gov (United States)

    Kousi, Evanthia; Borri, Marco; Dean, Jamie; Panek, Rafal; Scurr, Erica; Leach, Martin O.; Schmidt, Maria A.

    2016-01-01

    MRI has been extensively used in breast cancer staging, management and high risk screening. Detection sensitivity is paramount in breast screening, but variations of signal-to-noise ratio (SNR) as a function of position are often overlooked. We propose and demonstrate practical methods to assess spatial SNR variations in dynamic contrast-enhanced (DCE) breast examinations and apply those methods to different protocols and systems. Four different protocols in three different MRI systems (1.5 and 3.0 T) with receiver coils of different design were employed on oil-filled test objects with and without uniformity filters. Twenty 3D datasets were acquired with each protocol; each dataset was acquired in under 60 s, thus complying with current breast DCE guidelines. In addition to the standard SNR calculated on a pixel-by-pixel basis, we propose other regional indices considering the mean and standard deviation of the signal over a small sub-region centred on each pixel. These regional indices include effects of the spatial variation of coil sensitivity and other structured artefacts. The proposed regional SNR indices demonstrate spatial variations in SNR as well as the presence of artefacts and sensitivity variations, which are otherwise difficult to quantify and might be overlooked in a clinical setting. Spatial variations in SNR depend on protocol choice and hardware characteristics. The use of uniformity filters was shown to lead to a rise of SNR values, altering the noise distribution. Correlation between noise in adjacent pixels was associated with data truncation along the phase encoding direction. Methods to characterise spatial SNR variations using regional information were demonstrated, with implications for quality assurance in breast screening and multi-centre trials.

  9. Asymmetric thermal-relic dark matter: Sommerfeld-enhanced freeze-out, annihilation signals and unitarity bounds

    International Nuclear Information System (INIS)

    Baldes, Iason; Petraki, Kalliopi

    2017-01-01

    Dark matter that possesses a particle-antiparticle asymmetry and has thermalised in the early universe, requires a larger annihilation cross-section compared to symmetric dark matter, in order to deplete the dark antiparticles and account for the observed dark matter density. The annihilation cross-section determines the residual symmetric component of dark matter, which may give rise to annihilation signals during CMB and inside haloes today. We consider dark matter with long-range interactions, in particular dark matter coupled to a light vector or scalar force mediator. We compute the couplings required to attain a final antiparticle-to-particle ratio after the thermal freeze-out of the annihilation processes in the early universe, and then estimate the late-time annihilation signals. We show that, due to the Sommerfeld enhancement, highly asymmetric dark matter with long-range interactions can have a significant annihilation rate, potentially larger than symmetric dark matter of the same mass with contact interactions. We discuss caveats in this estimation, relating to the formation of stable bound states. Finally, we consider the non-relativistic partial-wave unitarity bound on the inelastic cross-section, we discuss why it can be realised only by long-range interactions, and showcase the importance of higher partial waves in this regime of large inelasticity. We derive upper bounds on the mass of symmetric and asymmetric thermal-relic dark matter for s -wave and p -wave annihilation, and exhibit how these bounds strengthen as the dark asymmetry increases.

  10. Afferent signalling from the acid-challenged rat stomach is inhibited and gastric acid elimination is enhanced by lafutidine.

    Science.gov (United States)

    Edelsbrunner, Martin E; Nakano, Motoko; Holzer, Peter

    2009-06-02

    Lafutidine is a histamine H2 receptor antagonist, the gastroprotective effect of which is related to its antisecretory activity and its ability to activate a sensory neuron-dependent mechanism of defence. The present study investigated whether intragastric administration of lafutidine (10 and 30 mg/kg) modifies vagal afferent signalling, mucosal injury, intragastric acidity and gastric emptying after gastric acid challenge. Adult rats were treated with vehicle, lafutidine (10 - 30 mg/kg) or cimetidine (10 mg/kg), and 30 min later their stomachs were exposed to exogenous HCl (0.25 M). During the period of 2 h post-HCl, intragastric pH, gastric volume, gastric acidity and extent of macroscopic gastric mucosal injury were determined and the activation of neurons in the brainstem was visualized by c-Fos immunocytochemistry. Gastric acid challenge enhanced the expression of c-Fos in the nucleus tractus solitarii but caused only minimal damage to the gastric mucosa. Lafutidine reduced the HCl-evoked expression of c-Fos in the NTS and elevated the intragastric pH following intragastric administration of excess HCl. Further analysis showed that the gastroprotective effect of lafutidine against excess acid was delayed and went in parallel with facilitation of gastric emptying, measured indirectly via gastric volume changes, and a reduction of gastric acidity. The H2 receptor antagonist cimetidine had similar but weaker effects. These observations indicate that lafutidine inhibits the vagal afferent signalling of a gastric acid insult, which may reflect an inhibitory action on acid-induced gastric pain. The ability of lafutidine to decrease intragastric acidity following exposure to excess HCl cannot be explained by its antisecretory activity but appears to reflect dilution and/or emptying of the acid load into the duodenum. This profile of actions emphasizes the notion that H2 receptor antagonists can protect the gastric mucosa from acid injury independently of their

  11. Afferent signalling from the acid-challenged rat stomach is inhibited and gastric acid elimination is enhanced by lafutidine

    Directory of Open Access Journals (Sweden)

    Holzer Peter

    2009-06-01

    Full Text Available Abstract Background Lafutidine is a histamine H2 receptor antagonist, the gastroprotective effect of which is related to its antisecretory activity and its ability to activate a sensory neuron-dependent mechanism of defence. The present study investigated whether intragastric administration of lafutidine (10 and 30 mg/kg modifies vagal afferent signalling, mucosal injury, intragastric acidity and gastric emptying after gastric acid challenge. Methods Adult rats were treated with vehicle, lafutidine (10 – 30 mg/kg or cimetidine (10 mg/kg, and 30 min later their stomachs were exposed to exogenous HCl (0.25 M. During the period of 2 h post-HCl, intragastric pH, gastric volume, gastric acidity and extent of macroscopic gastric mucosal injury were determined and the activation of neurons in the brainstem was visualized by c-Fos immunocytochemistry. Results Gastric acid challenge enhanced the expression of c-Fos in the nucleus tractus solitarii but caused only minimal damage to the gastric mucosa. Lafutidine reduced the HCl-evoked expression of c-Fos in the NTS and elevated the intragastric pH following intragastric administration of excess HCl. Further analysis showed that the gastroprotective effect of lafutidine against excess acid was delayed and went in parallel with facilitation of gastric emptying, measured indirectly via gastric volume changes, and a reduction of gastric acidity. The H2 receptor antagonist cimetidine had similar but weaker effects. Conclusion These observations indicate that lafutidine inhibits the vagal afferent signalling of a gastric acid insult, which may reflect an inhibitory action on acid-induced gastric pain. The ability of lafutidine to decrease intragastric acidity following exposure to excess HCl cannot be explained by its antisecretory activity but appears to reflect dilution and/or emptying of the acid load into the duodenum. This profile of actions emphasizes the notion that H2 receptor antagonists can protect

  12. Pharmacological Inhibition of Protein Kinase G1 Enhances Bone Formation by Human Skeletal Stem Cells Through Activation of RhoA-Akt Signaling

    DEFF Research Database (Denmark)

    Kermani, Abbas Jafari; Siersbaek, Majken S; Chen, Li

    2015-01-01

    Development of novel approaches to enhance bone regeneration is needed for efficient treatment of bone defects. Protein kinases play a key role in regulation of intracellular signal transduction pathways, and pharmacological targeting of protein kinases has led to development of novel treatments...... that pharmacological inhibition of PRKG1 in hMSC implanted at the site of bone defect can enhance bone regeneration. Stem Cells 2015....

  13. 3’-Deoxyadenosine (Cordycepin) Produces a Rapid and Robust Antidepressant Effect via Enhancing Prefrontal AMPA Receptor Signaling Pathway

    Science.gov (United States)

    Li, Bai; Hou, Yangyang; Zhu, Ming; Bao, Hongkun; Nie, Jun; Zhang, Grace Y.; Shan, Liping; Yao, Yao; Du, Kai; Yang, Hongju; Li, Meizhang; Zheng, Bingrong; Xu, Xiufeng; Xiao, Chunjie; Du, Jing

    2016-01-01

    Background: The development of rapid and safe antidepressants for the treatment of major depression is in urgent demand. Converging evidence suggests that glutamatergic signaling seems to play important roles in the pathophysiology of depression. Methods: We studied the antidepressant effects of 3’-deoxyadenosine (3’-dA, Cordycepin) and the critical role of the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor in male CD-1 mice via behavioral and biochemical experiments. After 3’-dA treatment, the phosphorylation and synaptic localization of the AMPA receptors GluR1 and GluR2 were determined in the prefrontal cortex (PFC) and hippocampus (HIP). The traditional antidepressant imipramine was applied as a positive control. Results: We found that an injection of 3’-dA led to a rapid and robust antidepressant effect, which was significantly faster and stronger than imipramine, after 45min in tail suspension and forced swim tests. This antidepressant effect remained after 5 days of treatment with 3’-dA. Unlike the psycho-stimulants, 3’-dA did not show a hyperactive effect in the open field test. After 45min or 5 days of treatment, 3’-dA enhanced GluR1 S845 phosphorylation in both the PFC and HIP. In addition, after 45min of treatment, 3’-dA significantly up-regulated GluR1 S845 phosphorylation and GluR1, but not GluR2 levels, at the synapses in the PFC. After 5 days of treatment, 3’-dA significantly enhanced GluR1 S845 phosphorylation and GluR1, but not GluR2, at the synapses in the PFC and HIP. Moreover, the AMPA-specific antagonist GYKI 52466 was able to block the rapid antidepressant effects of 3’-dA. Conclusion: This study identified 3’-dA as a novel rapid antidepressant with clinical potential and multiple beneficial mechanisms, particularly in regulating the prefrontal AMPA receptor signaling pathway. PMID:26443809

  14. Thromboxane A{sub 2} receptor signaling promotes liver tissue repair after toxic injury through the enhancement of macrophage recruitment

    Energy Technology Data Exchange (ETDEWEB)

    Minamino, Tsutomu [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Ito, Yoshiya [Departments of Surgery, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Ohkubo, Hirotoki [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Departments of Surgery, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Hosono, Kanako; Suzuki, Tatsunori [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Sato, Takehito [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Ae, Takako; Shibuya, Akitaka [Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Sakagami, Hiroyuki [Departments of Anatomy, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Narumiya, Shuh [Department of Pharmacology, Kyoto University School of Medicine, Kyoto, 606-8315 (Japan); Koizumi, Wasaburo [Departments of Gastroenterology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan); Majima, Masataka, E-mail: mmajima@med.kitasato-u.ac.jp [Departments of Pharmacology, Kitasato University School of Medicine, Kanagawa 252-0374 (Japan)

    2012-02-15

    It is thought that thromboxane A{sub 2} (TxA{sub 2}) contributes to the progression of inflammation during acute hepatic injury; however, it is still unknown whether TxA{sub 2} is involved in liver repair. The objective of the present study was to examine the role of TxA{sub 2} receptor (TP) signaling in liver injury and repair in response to toxic injury. Carbon tetrachloride (CCl{sub 4}) was used to induce liver injury in TP knockout (TP{sup −/−}) mice and wild-type (WT) mice. In WT mice, serum levels of alanine aminotransferase (ALT) and the size of the necrotic area peaked at 24 and 48 h, respectively, and then declined. In TP{sup −/−} mice, the changes in ALT levels were similar to WT mice, but liver regeneration was impaired as evidenced by remained elevated levels of hepatic necrosis and by delayed hepatocyte proliferation, which was associated with the reduced expression of growth factors including interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and hepatocyte growth factor (HGF). In TP{sup −/−} mice, the accumulation of hepatic CD11b{sup +}/F4/80{sup +} macrophages in injured livers was attenuated, and the hepatic expression of monocyte chemoattractant protein-1 (MCP-1/CCL2) and its receptor, the C―C chemokine receptor (CCR2), was reduced compared to WT. Additionally, the application of the TP receptor agonist, U-46619, enhanced the expression of MCP-1/CCL2 and CCR2 in peritoneal macrophages, which was associated with increased levels of IL-6, TNFα and HGF. These results suggested that TP receptor signaling facilitates liver recovery following CCl{sub 4}-induced hepatotoxicity by affecting the expression of hepatotrophic growth factors, and through the recruitment of macrophages mediated by MCP-1/CCL2-CCR2 expression. -- Highlights: ► TP enhances liver regeneration by CCl{sub 4}. ► TP accumulates macrophages. ► TP up-regulates MCP-1.

  15. A Relativity Enhanced, Medium-Strong Au(I)···H-N Hydrogen Bond in a Protonated Phenylpyridine-Gold(I) Thiolate.

    Science.gov (United States)

    Berger, Raphael J F; Schoiber, Jürgen; Monkowius, Uwe

    2017-01-17

    Gold is an electron-rich metal with a high electronegativity comparable to that of sulfur. Hence, hydrogen bonds of the Au(I)···H-E (E = electronegative element) type should be possible, but their existence is still under debate. Experimental results are scarce and often contradictory. As guidance for possible preparative work, we have theoretically investigated (ppyH)Au(SPh) (ppy = 2-phenylpyridine) bearing two monoanionic ligands which are not strongly electronegative at the same time to further increase the charge density on the gold(I) atom. The protonated pyridine nitrogen atom in ppy is geometrically ideally suited to place a proton in close proximity to the gold atom in a favorable geometry for a classical hydrogen bond arrangement. Indeed, the results of the calculations indicate that the hydrogen bonded conformation of (ppyH)Au(SPh) represents a minimum geometry with bond metrics in the expected range for medium-strong hydrogen bonds [r(N-H) = 1.043 Å, r(H···Au) = 2.060 Å, a(N-H···Au) = 141.4°]. The energy difference between the conformer containing the H···Au bond and another conformer without a hydrogen bond amounts to 7.8 kcal mol -1 , which might serve as an estimate of the hydrogen bond strength. Spectroscopic properties were calculated, yielding further characteristics of such hydrogen bonded gold species.

  16. The many shades of enhancement: timing of post-gadolinium images strongly influences the scoring of juvenile idiopathic arthritis wrist involvement on MRI

    Energy Technology Data Exchange (ETDEWEB)

    Rieter, Jasper F.M.M.; Nusman, Charlotte M.; Hemke, Robert; Maas, Mario [University of Amsterdam, Department of Radiology, Academic Medical Center, Amsterdam (Netherlands); Tanturri de Horatio, Laura [Ospedale Pediatrico Bambino Gesu, Department of Radiology, Rome (Italy); Ording Mueller, Lil-Sofie [Oslo University Hospital, Department of Radiology, Oslo (Norway); Avenarius, Derk F.M. [Faculty of Health Sciences at the University of Tromsoe, Tromsoe (Norway); Rossum, Marion A.J. van [University of Amsterdam, Department of Radiology, Academic Medical Center, Amsterdam (Netherlands); Emma Children' s Hospital, Amsterdam (Netherlands); Malattia, Clara [Ospedale Pediatrico Gaslini, Department of Paediatrics, Genoa (Italy); Rosendahl, Karen [Haukeland University Hospital, Radiology Department, Section of Pediatric Radiology, Bergen (Norway); University of Bergen, Department of Clinical Medicine, K1, Bergen (Norway)

    2016-10-15

    Potential long-term side effects of treatment for juvenile idiopathic arthritis are concerning. This has necessitated accurate tools, such as MRI, to monitor treatment response and allow for personalized therapy. To examine the extent to which timing of post-contrast MR images influences the scoring of inflammatory change in the wrist in children with juvenile idiopathic arthritis. We studied two sets of post-contrast 3-D gradient echo MRI series of the wrist in 34 children with juvenile idiopathic arthritis. These images were obtained immediately after administration of intravenous contrast material and again after approximately 10 min. The dataset was drawn from a prospective multicenter project conducted 2006-2010. We assessed five wrist locations for synovial enhancement, effusion and overall inflammation. Examinations were scored by one radiologist in two sessions - the first was based on the early post-contrast images, and the later session, for which the previous findings were masked, was based on the later post-contrast images. Fifty-two of the 170 locations (30.6%) received a higher synovial enhancement score based on the late post-contrast images as compared to the early images. Sixty of the 170 (35%) locations received a higher total inflammation score. The mean scores of synovial enhancement and total inflammation were significantly higher when based on the late post-contrast images as compared to the early post-contrast images. An MRI-based scoring system for the presence and degree of synovitis should be based on a standardized MR-protocol with a fixed interval between intravenous contrast injection and post-contrast images. (orig.)

  17. Modest human immunodeficiency virus coreceptor function of CXCR3 is strongly enhanced by mimicking the CXCR4 ligand binding pocket in the CXCR3 receptor

    DEFF Research Database (Denmark)

    Hatse, Sigrid; Huskens, Dana; Princen, Katrien

    2007-01-01

    The chemokine receptor CXCR3 can exhibit weak coreceptor function for several human immunodeficiency virus type 1 (HIV-1) and HIV-2 strains and clinical isolates. These viruses produced microscopically visible cytopathicity in U87.CD4.CXCR3 cell cultures, whereas untransfected (CXCR3-negative) U87...... at positions 300 and 304 of the CXCR3 receptor. This mutant receptor (CXCR3[K300A, S304E]) showed markedly enhanced HIV coreceptor function compared to the wild-type receptor (CXCR3[WT]). Moreover, the CXCR4 antagonist AMD3100 exhibited antagonistic and anti-HIV activities in U87.CD4.CXCR3[K300A, S304E] cells...

  18. Enhancement of Near-IR Photoelectric Conversion in Dye-Sensitized Solar Cells Using an Osmium Sensitizer with Strong Spin-Forbidden Transition.

    Science.gov (United States)

    Kinoshita, Takumi; Fujisawa, Jun-Ichi; Nakazaki, Jotaro; Uchida, Satoshi; Kubo, Takaya; Segawa, Hiroshi

    2012-02-02

    A new osmium (Os) complex of the [Os(tcterpy)-(4,4'-bis(p-butoxystyryl)-2,2'-bipyridine)Cl]PF6 (Os-stbpy) has been synthesized and characterized for dye-sensitized solar cells (DSSCs). The Os-stbpy dye shows enhanced spin-forbidden absorptions around 900 nm. The DSSCs with Os-stbpy show a wide-band spectral response up to 1100 nm with high overall conversion efficiency of 6.1% under standard solar illumination.

  19. Dopamine modulates persistent synaptic activity and enhances the signal-to-noise ratio in the prefrontal cortex.

    Directory of Open Access Journals (Sweden)

    Sven Kroener

    2009-08-01

    Full Text Available The importance of dopamine (DA for prefrontal cortical (PFC cognitive functions is widely recognized, but its mechanisms of action remain controversial. DA is thought to increase signal gain in active networks according to an inverted U dose-response curve, and these effects may depend on both tonic and phasic release of DA from midbrain ventral tegmental area (VTA neurons.We used patch-clamp recordings in organotypic co-cultures of the PFC, hippocampus and VTA to study DA modulation of spontaneous network activity in the form of Up-states and signals in the form of synchronous EPSP trains. These cultures possessed a tonic DA level and stimulation of the VTA evoked DA transients within the PFC. The addition of high (> or = 1 microM concentrations of exogenous DA to the cultures reduced Up-states and diminished excitatory synaptic inputs (EPSPs evoked during the Down-state. Increasing endogenous DA via bath application of cocaine also reduced Up-states. Lower concentrations of exogenous DA (0.1 microM had no effect on the up-state itself, but they selectively increased the efficiency of a train of EPSPs to evoke spikes during the Up-state. When the background DA was eliminated by depleting DA with reserpine and alpha-methyl-p-tyrosine, or by preparing corticolimbic co-cultures without the VTA slice, Up-states could be enhanced by low concentrations (0.1-1 microM of DA that had no effect in the VTA containing cultures. Finally, in spite of the concentration-dependent effects on Up-states, exogenous DA at all but the lowest concentrations increased intracellular current-pulse evoked firing in all cultures underlining the complexity of DA's effects in an active network.Taken together, these data show concentration-dependent effects of DA on global PFC network activity and they demonstrate a mechanism through which optimal levels of DA can modulate signal gain to support cognitive functioning.

  20. Diclofenac enhances proinflammatory cytokine-induced nitric oxide production through NF-κB signaling in cultured astrocytes

    International Nuclear Information System (INIS)

    Kakita, Hiroki; Aoyama, Mineyoshi; Hussein, Mohamed Hamed; Kato, Shin; Suzuki, Satoshi; Ito, Tetsuya; Togari, Hajime; Asai, Kiyofumi

    2009-01-01

    Recently, the number of reports of encephalitis/encephalopathy associated with influenza virus has increased. In addition, the use of a non-steroidal anti-inflammatory drug, diclofenac sodium (DCF), is associated with a significant increase in the mortality rate of influenza-associated encephalopathy. Activated astrocytes are a source of nitric oxide (NO), which is largely produced by inducible NO synthase (iNOS) in response to proinflammatory cytokines. Therefore, we investigated whether DCF enhances nitric oxide production in astrocytes stimulated with proinflammatory cytokines. We stimulated cultured rat astrocytes with three cytokines, interleukin-1β, tumor necrosis factor-α and interferon-γ, and then treated the astrocytes with DCF or acetaminophen (N-acetyl-p-aminophenol: APAP). iNOS and NO production in astrocyte cultures were induced by proinflammatory cytokines. The addition of DCF augmented NO production, but the addition of APAP did not. NF-κB inhibitors SN50 and MG132 inhibited iNOS gene expression in cytokine-stimulated astrocytes with or without DCF. Similarly, NF-κB p65 Stealth small interfering RNA suppressed iNOS gene expression in cytokine-stimulated astrocytes with or without DCF. LDH activity and DAPI staining showed that DCF induces cell damage in cytokine-stimulated astrocytes. An iNOS inhibitor, L-NMMA, inhibited the cytokine- and DCF-induced cell damage. In conclusion, this study demonstrates that iNOS and NO are induced in astrocyte cultures by proinflammatory cytokines. Addition of DCF further augments NO production. This effect is mediated via NF-κB signaling and leads to cell damage. The enhancement of DCF on NO production may explain the significant increase in the mortality rate of influenza-associated encephalopathy in patients treated with DCF.

  1. RAD001 enhances the potency of BEZ235 to inhibit mTOR signaling and tumor growth.

    Directory of Open Access Journals (Sweden)

    Beat Nyfeler

    Full Text Available The mammalian target of rapamycin (mTOR is regulated by oncogenic growth factor signals and plays a pivotal role in controlling cellular metabolism, growth and survival. Everolimus (RAD001 is an allosteric mTOR inhibitor that has shown marked efficacy in certain cancers but is unable to completely inhibit mTOR activity. ATP-competitive mTOR inhibitors such as NVP-BEZ235 can block rapamycin-insensitive mTOR readouts and have entered clinical development as anti-cancer agents. Here, we show the degree to which RAD001 and BEZ235 can be synergistically combined to inhibit mTOR pathway activation, cell proliferation and tumor growth, both in vitro and in vivo. RAD001 and BEZ235 synergized in cancer lines representing different lineages and genetic backgrounds. Strong synergy is seen in neuronal, renal, breast, lung, and haematopoietic cancer cells harboring abnormalities in PTEN, VHL, LKB1, Her2, or KRAS. Critically, in the presence of RAD001, the mTOR-4EBP1 pathway and tumorigenesis can be fully inhibited using lower doses of BEZ235. This is relevant since RAD001 is relatively well tolerated in patients while the toxicity profiles of ATP-competitive mTOR inhibitors are currently unknown.

  2. Sub-lethal irradiation of human colorectal tumor cells imparts enhanced and sustained susceptibility to multiple death receptor signaling pathways.

    Directory of Open Access Journals (Sweden)

    Victoria Ifeadi

    Full Text Available BACKGROUND: Death receptors (DR of the TNF family function as anti-tumor immune effector molecules. Tumor cells, however, often exhibit DR-signaling resistance. Previous studies indicate that radiation can modify gene expression within tumor cells and increase tumor cell sensitivity to immune attack. The aim of this study is to investigate the synergistic effect of sub-lethal doses of ionizing radiation in sensitizing colorectal carcinoma cells to death receptor-mediated apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: The ability of radiation to modulate the expression of multiple death receptors (Fas/CD95, TRAILR1/DR4, TRAILR2/DR5, TNF-R1 and LTβR was examined in colorectal tumor cells. The functional significance of sub-lethal doses of radiation in enhancing tumor cell susceptibility to DR-induced apoptosis was determined by in vitro functional sensitivity assays. The longevity of these changes and the underlying molecular mechanism of irradiation in sensitizing diverse colorectal carcinoma cells to death receptor-mediated apoptosis were also examined. We found that radiation increased surface expression of Fas, DR4 and DR5 but not LTβR or TNF-R1 in these cells. Increased expression of DRs was observed 2 days post-irradiation and remained elevated 7-days post irradiation. Sub-lethal tumor cell irradiation alone exhibited minimal cell death, but effectively sensitized three of three colorectal carcinoma cells to both TRAIL and Fas-induced apoptosis, but not LTβR-induced death. Furthermore, radiation-enhanced Fas and TRAIL-induced cell death lasted as long as 5-days post-irradiation. Specific analysis of intracellular sensitizers to apoptosis indicated that while radiation did reduce Bcl-X(L and c-FLIP protein expression, this reduction did not correlate with the radiation-enhanced sensitivity to Fas and/or TRAIL mediated apoptosis among the three cell types. CONCLUSIONS/SIGNIFICANCE: Irradiation of tumor cells can overcome Fas and TRAIL

  3. [Signal intensity-time curve and quantitative dynamic contrast-enhanced magnetic resonance imaging in differentiating neoplasms of uterus].

    Science.gov (United States)

    Guo, Yongmei; Jiang, Xinqing; Liu, Guoshun; Huang, Yunhai; Xu, Xiangdong

    2015-12-01

    To evaluate signal intensity-time (SI-Time) curve and quantitative dynamic contrast-enhanced 3.0T magnetic resonance imaging in diagnosis and differentiating neoplasm of uterus.
 A total of 42 cases of uterine neoplasm (20 were malignant and 22 were benign) were evaluated in our study. All cases received dynamic contrast-enhanced scanning on 3.0T MRI. The raw data was processed by Siemens Tissue 4D software and the SI-Time curve was obtained and analyzed. Pharmacokinetic modeling of Tofts with a modeled vascular input function was used for calculating volume parameters: volume transfer constant (Ktrans), reverse volume transfer constant (Kep), the extravascular extracellular space volume per unit volume of tissue (Ve). The correlation of these parameters at each groups were investigated. The SI-Time curve and the data of perfusion parameters between the 2 groups were compared by T test.
 Among 20 malignant tumors, 12 were cervical carcinoma and 8 were endometrial cancer. Among the benign tumors, 13 were leiomyomas, 3 were endometrial polyp, 3 were endometrial hyperplasia, and 3 were adenomyosis. 59.1% cases of benign tumors belong to Type I curve and 65% cases of malignant tumors belong to Type II curve. There was significant difference in SI-Time curve between benign and malignant tumors (P=0.011). If Type I curve was used as diagnostic criteria for benign tumors, and Type II and III curve were for malignant tumors, the diagnostic sensitivity, specificity, positive predictive value, negative predictive value were 90.0%, 59.1%, 66.7%, and 86.7%, respectively. Ve was 0.477 ± 0.143 in malignant and 0.614 ± 0.146 in control group with significant difference (P=0.004). Ve was 0.477 ± 0.143 in malignant and 0.589 0.176 in benign group with significant difference (P=0.004). Ktrans was (0.178 ± 0.067) min⁻¹ in malignant and (0.263 ± 0.111) min⁻¹ in control group with significant difference (P=0.003). Ktrans was (0.182 ± 0.096) min⁻¹ in benign and (0

  4. Myocardial tissue characterization in hypertrophic cardiomyopathy. Comparison between Gd-DTPA enhanced MR signal intensity ratio and myocardial biopsy

    Energy Technology Data Exchange (ETDEWEB)

    Tsukihashi, Hironori; Shimada, Toshio; Ishibashi, Yutaka [Shimane Medical Univ., Izumo (Japan)] [and others

    1995-09-01

    The aim of this study is to demonstrate whether Gd-DTPA enhanced magnetic resonance imaging (Gd-EMRI) can be used to evaluate myocardial tissue characterization. We performed Gd-EMRI in 20 patients with hypertrophic cardiomyopathy (HCM) and 6 normal controls. Ventricular myocardial biopsy was performed in 7 patients. Gd-EMRI was obtained every 10 minutes from 5 to 50 minutes after intravenous Gd-DTPA (0.1 mmol/kg) injection. Signal intensity (SI) in hypertrophic region of myocardium was measured from LV short axis image. We standardized the data according to following equations. IR (intensity ratio) =SI (myocardium) /SI (skeletal muscle). SIR=IR (in time course) /IR (before Gd-DTPA injection). SIR in HCM was delayed in time course compared with that in normal controls. Interstitial fibrosis was prominent when SIR (peak) minus SIR (40min. after) /SIR (peak) was small. The delayed decay of IR in HCM was closely related to the grade of interstitial fibrosis rather than the edema of interstitial tissue or the myocardial cell diameter. We conclude that the decay analysis with Gd-EMRI is useful to evaluate myocardial tissue characterization closely related to myocardial fibrosis in comparison with cardiac histology. (author).

  5. A general approach to search for supersymmetry at the LHC by combining signal enhanced kinematic regions using the ATLAS detector

    CERN Document Server

    Schneider, Basil; Weber, Michele

    The Standard Model of particle physics is a very successful theory, but it cannot describe e.g. gravity or explain the hierarchy problem. Supersymmetry is a proposed extension to the Standard Model that would solve some of its shortcomings by introducing a relation between fermions and bosons through the existence of a supersymmetric partner to every particle in the Standard Model. Since it is a broken symmetry, supersymmetric particles are heavier than their Standard Model counterparts. No supersymmetric particle has been observed to date. The ATLAS experiment at the Large Hadron Collider is a multi-purpose detector to measure parameters in the Standard Model and conduct searches for new particles. Searching for supersymmetric particles is one of the main goals of the experiment. In 2012, 20.3~fb$^{-1}$ of data at a centre-of-mass energy of $\\sqrt{s}$ = 8 TeV was collected by ATLAS. In this thesis, I analyzed the ATLAS data and developed a novel statistical approach that bins a signal enhanced region in pha...

  6. Beyond negative valence: 2-week administration of a serotonergic antidepressant enhances both reward and effort learning signals.

    Directory of Open Access Journals (Sweden)

    Jacqueline Scholl

    2017-02-01

    Full Text Available To make good decisions, humans need to learn about and integrate different sources of appetitive and aversive information. While serotonin has been linked to value-based decision-making, its role in learning is less clear, with acute manipulations often producing inconsistent results. Here, we show that when the effects of a selective serotonin reuptake inhibitor (SSRI, citalopram are studied over longer timescales, learning is robustly improved. We measured brain activity with functional magnetic resonance imaging (fMRI in volunteers as they performed a concurrent appetitive (money and aversive (effort learning task. We found that 2 weeks of citalopram enhanced reward and effort learning signals in a widespread network of brain regions, including ventromedial prefrontal and anterior cingulate cortex. At a behavioral level, this was accompanied by more robust reward learning. This suggests that serotonin can modulate the ability to learn via a mechanism that is independent of stimulus valence. Such effects may partly underlie SSRIs' impact in treating psychological illnesses. Our results highlight both a specific function in learning for serotonin and the importance of studying its role across longer timescales.

  7. Switch Enhancers Interpret TGF-β and Hippo Signaling to Control Cell Fate in Human Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    Tobias A. Beyer

    2013-12-01

    Full Text Available A small toolkit of morphogens is used repeatedly to direct development, raising the question of how context dictates interpretation of the same cue. One example is the transforming growth factor β (TGF-β pathway that in human embryonic stem cells fulfills two opposite functions: pluripotency maintenance and mesendoderm (ME specification. Using proteomics coupled to analysis of genome occupancy, we uncover a regulatory complex composed of transcriptional effectors of the Hippo pathway (TAZ/YAP/TEAD, the TGF-β pathway (SMAD2/3, and the pluripotency regulator OCT4 (TSO. TSO collaborates with NuRD repressor complexes to buffer pluripotency gene expression while suppressing ME genes. Importantly, the SMAD DNA binding partner FOXH1, a major specifier of ME, is found near TSO elements, and upon fate specification we show that TSO is disrupted with subsequent SMAD-FOXH1 induction of ME. These studies define switch-enhancer elements and provide a framework to understand how cellular context dictates interpretation of the same morphogen signal in development.

  8. Anthropogenic enhancement of moderate-to-strong El Niño events likely contributed to drought and poor harvests in southern Africa during 2016

    Science.gov (United States)

    Funk, Chris; Davenport, Frank; Harrison, Laura; Magadzire, Tamuka; Galu, Gideon; Artan, Guleid A.; Shukla, Shraddhanand; Korecha, Diriba; Indeje, Matayo; Pomposi, Catherine; Macharia, Denis; Husak, Gregory; Dieudonne Nsadisa, Faka

    2018-01-01

    In December–February (DJF) of 2015/16, a strong El Niño (Niño‑3.4 SST >29°C) contributed to a severe drought over southern Africa (SA; Funk et al. 2016). A 9-million ton cereal deficit resulted in 26 mil‑ lion people in need of humanitarian assistance (SADC 2016). While SA rainfall has a well-documented nega‑ tive teleconnection with Niño‑3.4 SSTs (Hoell et al. 2015, 2017; Jury et al. 1994; Lindesay 1988; Misra 2003; Nicholson and Entekhabi 1987; Nicholson and Kim 1997; Reason et al. 2000; Rocha and Simmonds 1997), the link between climate change and El Niño remains unclear (Christensen et al. 2013) due to the large natural variability of ENSO SSTs (Wittenberg 2009), uncertainties surrounding measurements and trends (Solomon and Newman 2012), intermodel differences in ENSO representation and feedbacks (Guilyardi et al. 2012; Kim et al. 2014), and difficulties associated with quantifying ENSO strength (Cai et al. 2015).

  9. Strongly coupled CeO2/Co3O4/poly(3,4-ethylenedioxythiophene) nanofibers with enhanced nanozyme activity for highly sensitive colorimetric detection

    Science.gov (United States)

    Chi, Maoqiang; Zhu, Yun; Yang, Zezhou; Gao, Mu; Chen, Sihui; Song, Na; Wang, Ce; Lu, Xiaofeng

    2017-07-01

    In this work, we have prepared CeO2/Co3O4 composite nanofibers via an electrospinning technique followed by a calcination process. Then core-shell structured CeO2/Co3O4/poly(3,4-ethylenedioxythiophene) (PEDOT) composite nanofibers were fabricated through a redox reaction between the 3,4-ethylenedioxythiophene (EDOT) monomer and Co3O4 on the surface of CeO2/Co3O4 composite nanofibers. The morphology and composition of the two composite nanofibers were confirmed by field-emission scanning electron microscopy, transmission electron microscopy, x-ray diffraction, Fourier transform infrared spectroscopy, and x-ray photoelectron spectra measurements. Due to the synergistic effect between CeO2 and Co3O4, the catalytic activity was enhanced compared to that of independent oxide nanofibers. After the growth of PEDOT, the catalytic activity process was further improved, having achieved a secondary synergistic effect. Application of the two prepared composite nanofibers as peroxidase-like catalysts for the colorimetric detection of H2O2 was investigated. It is anticipated that this work can inspire researchers to develop various novel functional nanocomposites for applications in biosensing and environmental monitoring.

  10. A novel energy transfer inducing strong enhancement of electric dipole transition in Na3Mo12PO40:xEu3+ phosphors

    Science.gov (United States)

    Long, Jinqiao; Wang, Tianman; Luo, Zhirong; Gao, Yong; Song, Baoling; Liang, Jing; Liao, Sen; Huang, Yingheng; Zhang, Huaxin

    2017-08-01

    A series of Na3Mo12PO40:xEu3+ phosphors have been successfully synthesized by a solid-state method, and characterized by powder x-ray diffraction (PXRD). The PXRD results confirm that the samples have crystal phases of Na3Mo12PO40. For PL spectra of Na3Mo12PO40:2.0Eu3+ excited by 394 and 465 nm, R (R is the peak area ratio of 5D0  →  7F2 to 5D0  →  7F1) is only 1.46 with an excitation of 394 nm, but increases to 3.03 with an excitation of 465 nm. Furthermore, a new enhancement of electric dipole transition is observed. Emission spectrum (PL) intensity at 617 nm excited by 465 nm is 1.95 times as high as the excitation spectrum (PLE) intensity at 465 nm. Thus, cooperative energy transfers from the magnetic dipole (MD) Eu3+ center to the electric dipole (ED) Eu3+ center when excited by 465 nm is demonstrated for the new fluorescent behavior.

  11. Complementary roles of benzylpiperazine and iodine 'vapor' in the strong enhancement of orange photoluminescence from CuI(1 1 1) thin film.

    Science.gov (United States)

    Rawal, Takat B; Turkowski, Volodymyr; Rahman, Talat S

    2014-05-07

    We have employed density functional theory, corrected by the on-site electron-electron repulsion energy U, to clarify the mechanism behind the enhanced orange photoluminescence (PL) of a CuI(1 1 1) thin film conjugated with a benzylpiperazine (BZP) molecule in the presence of an iodine 'vapor' atom. Our results demonstrated that the adsorbed molecule and the 'vapor' atom play complementary roles in producing the PL. The latter, in attaching to the film surface, creates a hole-trapping surface state located ~0.25 eV above the valence band-edge of the film, in good agreement with ~0.2 eV reported in experiments. Upon photo-excitation of the BZP/CuI(1 1 1) system in the presence of surface iodine 'vapor' atoms, excited electrons are transferred into the conduction band of CuI, and holes are trapped by the 'vapor' atoms. These holes, in turn, quickly relax into the HOMO state of the BZP molecule, owing to the fact that the molecule adsorbs on the film surface in the immediate vicinity of a 'vapor' atom. Relaxed holes subsequently recombine with excited electrons in the conduction band of the CuI film, thereby producing a luminescence peak at ~2.1 eV, in qualitative agreement with experimental findings.

  12. Incorporating Functional Genomic Information to Enhance Polygenic Signal and Identify Variants Involved in Gene-by-Environment Interaction for Young Adult Alcohol Problems.

    Science.gov (United States)

    Salvatore, Jessica E; Savage, Jeanne E; Barr, Peter; Wolen, Aaron R; Aliev, Fazil; Vuoksimaa, Eero; Latvala, Antti; Pulkkinen, Lea; Rose, Richard J; Kaprio, Jaakko; Dick, Danielle M

    2018-02-01

    Characterizing aggregate genetic risk for alcohol misuse and identifying variants involved in gene-by-environment (G × E) interaction effects has so far been a major challenge. We hypothesized that functional genomic information could be used to enhance detection of polygenic signal underlying alcohol misuse and to prioritize identification of single nucleotide polymorphisms (SNPs) most likely to exhibit G × E effects. We examined these questions in the young adult FinnTwin12 sample (n = 1,170). We used genomewide association estimates from an independent sample to derive 2 types of polygenic scores for alcohol problems in FinnTwin12. Genomewide polygenic scores included all SNPs surpassing a designated p-value threshold. DNase polygenic scores were a subset of the genomewide polygenic scores including only variants in DNase I hypersensitive sites (DHSs), which are open chromatin marks likely to index regions with a regulatory function. We conducted parallel analyses using height as a nonpsychiatric model phenotype to evaluate the consistency of effects. For the G × E analyses, we examined whether SNPs in DHSs were overrepresented among SNPs demonstrating significant G × E effects in an interaction between romantic relationship status and intoxication frequency. Contrary to our expectations, we found that DNase polygenic scores were not more strongly predictive of alcohol problems than conventional polygenic scores. However, variants in DNase polygenic scores had per-SNP effects that were up to 1.4 times larger than variants in conventional polygenic scores. This same pattern of effects was also observed in supplementary analyses with height. In G × E models, SNPs in DHSs were modestly overrepresented among SNPs with significant interaction effects for intoxication frequency. These findings highlight the potential utility of integrating functional genomic annotation information to increase the signal-to-noise ratio in polygenic scores and identify

  13. Gastric Metaplasia Induced by Helicobacter pylori Is Associated with Enhanced SOX9 Expression via Interleukin-1 Signaling.

    Science.gov (United States)

    Serizawa, Takako; Hirata, Yoshihiro; Hayakawa, Yoku; Suzuki, Nobumi; Sakitani, Kosuke; Hikiba, Yohko; Ihara, Sozaburo; Kinoshita, Hiroto; Nakagawa, Hayato; Tateishi, Keisuke; Koike, Kazuhiko

    2016-02-01

    Histopathological changes of the gastric mucosa after Helicobacter pylori infection, such as atrophy, metaplasia, and dysplasia, are considered to be precursors of gastric cancer, yet the mechanisms of histological progression are unknown. The aim of this study was to analyze the histopathological features of the gastric mucosa in mice infected with H. pylori strain PMSS1 in relation to gastric stem cell marker expression. C57BL/6J mice infected with PMSS1 were examined for histopathological changes, levels of proinflammatory cytokines, and expression of stem cell markers. Histopathological gastritis scores, such as atrophy and metaplasia, and levels of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β), were increased after PMSS1 infection. Expression levels of the cell proliferation and stem cell markers CD44 and SOX9 were also significantly increased in PMSS1-infected mice. Importantly, almost all metaplastic cells induced by PMSS1 infection expressed SOX9. When IL-1 receptor (IL-1R) knockout mice were infected with PMSS1, metaplastic changes and expression levels of stem cell markers were significantly decreased compared with those in wild-type (WT) mice. In conclusion, H. pylori infection induced the expression of cytokines and stem cell markers and histopathological metaplasia in the mouse gastric mucosa. SOX9 expression, in particular, was strongly associated with metaplastic changes, and these changes were dependent on IL-1 signaling. The results suggested the importance of SOX9 in gastric carcinogenesis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  14. Hyaluronan esters drive Smad gene expression and signaling enhancing cardiogenesis in mouse embryonic and human mesenchymal stem cells.

    Directory of Open Access Journals (Sweden)

    Margherita Maioli

    Full Text Available BACKGROUND: Development of molecules chemically modifying the expression of crucial orchestrator(s of stem cell commitment may have significant biomedical impact. We have recently developed hyaluronan mixed esters of butyric and retinoic acids (HBR, turning cardiovascular stem cell fate into a high-yield process. The HBR mechanism(s remain still largely undefined. METHODOLOGY/PRINCIPAL FINDINGS: We show that in both mouse embryonic stem (ES cells and human mesenchymal stem cells from fetal membranes of term placenta (FMhMSCs, HBR differentially affected the patterning of Smad proteins, one of the major conductors of stem cell cardiogenesis. Real-time RT-PCR and Western blot analyses revealed that in both cell types HBR enhanced gene and protein expression of Smad1,3, and 4, while down-regulating Smad7. HBR acted at the transcriptional level, as shown by nuclear run-off experiments in isolated nuclei. Immunofluorescence analysis indicated that HBR increased the fluorescent staining for Smad1,3, and 4, confirming that the transcriptional action of HBR encompassed the upregulation of the encoded Smad proteins. Chromatin immune precipitation and transcriptional analyses showed that HBR increased the transcription of the cardiogenic gene Nkx-2.5 through Smad4 binding to its own consensus Smad site. Treatment of mouse ES cells and FMhMSCs with HBR led to the concomitant overexpression of both Smad4 and α-sarcomeric actinin. Smad4 silencing by the aid of lentiviral-mediated Smad4 shRNA confirmed a dominant role of Smad4 in HBR-induced cardiogenesis. CONCLUSIONS/SIGNIFICANCE: The use of HBR may pave the way to novel combinatorial strategies of molecular and stem cell therapy based on fine tuning of targeted Smad transciption and signaling leading to a high-throughput of cardiogenesis without the needs of gene transfer technologies.

  15. Loss of C9orf72 Enhances Autophagic Activity via Deregulated mTOR and TFEB Signaling.

    Directory of Open Access Journals (Sweden)

    Janet Ugolino

    2016-11-01

    Full Text Available The most common cause of the neurodegenerative diseases amyotrophic lateral sclerosis and frontotemporal dementia is a hexanucleotide repeat expansion in C9orf72. Here we report a study of the C9orf72 protein by examining the consequences of loss of C9orf72 functions. Deletion of one or both alleles of the C9orf72 gene in mice causes age-dependent lethality phenotypes. We demonstrate that C9orf72 regulates nutrient sensing as the loss of C9orf72 decreases phosphorylation of the mTOR substrate S6K1. The transcription factor EB (TFEB, a master regulator of lysosomal and autophagy genes, which is negatively regulated by mTOR, is substantially up-regulated in C9orf72 loss-of-function animal and cellular models. Consistent with reduced mTOR activity and increased TFEB levels, loss of C9orf72 enhances autophagic flux, suggesting that C9orf72 is a negative regulator of autophagy. We identified a protein complex consisting of C9orf72 and SMCR8, both of which are homologous to DENN-like proteins. The depletion of C9orf72 or SMCR8 leads to significant down-regulation of each other's protein level. Loss of SMCR8 alters mTOR signaling and autophagy. These results demonstrate that the C9orf72-SMCR8 protein complex functions in the regulation of metabolism and provide evidence that loss of C9orf72 function may contribute to the pathogenesis of relevant diseases.

  16. Acute food deprivation enhances fear extinction but inhibits long-term depression in the lateral amygdala via ghrelin signaling.

    Science.gov (United States)

    Huang, Chiung-Chun; Chou, Dylan; Yeh, Che-Ming; Hsu, Kuei-Sen

    2016-02-01

    Fear memory-encoding thalamic input synapses to the lateral amygdala (T-LA) exhibit dynamic efficacy changes that are tightly correlated with fear memory strength. Previous studies have shown that auditory fear conditioning involves strengthening of synaptic strength, and conversely, fear extinction training leads to T-LA synaptic weakening and occlusion of long-term depression (LTD) induction. These findings suggest that the mechanisms governing LTD at T-LA synapses may determine the behavioral outcomes of extinction training. Here, we explored this hypothesis by implementing food deprivation (FD) stress in mice to determine its effects on fear extinction and LTD induction at T-LA synapses. We found that FD increased plasma acylated ghrelin levels and enhanced fear extinction and its retention. Augmentation of fear extinction by FD was blocked by pretreatment with growth hormone secretagogue receptor type-1a antagonist D-Lys(3)-GHRP-6, suggesting an involvement of ghrelin signaling. Confirming previous findings, two distinct forms of LTD coexist at thalamic inputs to LA pyramidal neurons that can be induced by low-frequency stimulation (LFS) or paired-pulse LFS (PP-LFS) paired with postsynaptic depolarization, respectively. Unexpectedly, we found that FD impaired the induction of PP-LFS- and group I metabotropic glutamate receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG)-induced LTD, but not LFS-induced LTD. Ghrelin mimicked the effects of FD to impair the induction of PP-LFS- and DHPG-induced LTD at T-LA synapses, which were blocked by co-application of D-Lys(3)-GHRP-6. The sensitivity of synaptic transmission to 1-naphthyl acetyl spermine was not altered by either FD or ghrelin treatment. These results highlight distinct features of fear extinction and LTD at T-LA synapses. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Over-expression of mitochondrial antiviral signaling protein inhibits coxsackievirus B3 infection by enhancing type-I interferons production

    Directory of Open Access Journals (Sweden)

    Zhang Qing-Meng

    2012-12-01

    Full Text Available Abstract Background Recent studies have revealed that Mitochondrial Antiviral Signaling (MAVS protein plays an essential role in the inhibition of viral infection through type I interferon (IFN pathway. It has been shown that 3C (pro cysteine protease of coxsackievirus B3 (CVB3 cleaves MAVS to inhibit type I IFNs induction. Other workers also found that MAVS knock-out mice suffered CVB3 susceptibility and severe histopathological change. Accordingly,our experiments were designed to explore the protection of over-expressing MAVS against CVB3 infection and the possible mechanism. Results In this study, HeLa cells (transfected with MAVS constructs pre- or post- exposure to CVB3 were used to analyze the function of exogenous MAVS on CVB3 infection. The results revealed that though CVB3 infection induced production of type I IFNs, viral replication and cell death were not effectively inhibited. Similarly, exogenous MAVS increased type I IFNs moderately. Morever, we observed robust production of type I IFNs in CVB3 post-infected HeLa cells thereby successfully inhibiting CVB3 infection, as well formation of cytopathic effect (CPE and cell death. Finally, introduction of exogenous MAVS into CVB3 pre-infected cells also restricted viral infection efficiently by greatly up-regulating IFNs. Conclusions In summary, exogenous MAVS effectively prevents and controls CVB3 infection by modulating and promoting the production of type I IFNs. The IFNs level in MAVS over-expressing cells is still tightly regulated by CVB3 infection. Thus, the factors that up-regulate MAVS might be an alternative prescription in CVB3-related syndromes by enhancing IFNs production.

  18. Icariin Inhibits Pulmonary Hypertension Induced by Monocrotaline through Enhancement of NO/cGMP Signaling Pathway in Rats

    Directory of Open Access Journals (Sweden)

    Li-sheng Li

    2016-01-01

    Full Text Available It has been reported that icariin (ICA increased contents of nitric oxide (NO and cyclic guanosine monophosphate (cGMP by improving expression of endothelial nitric oxide synthase (eNOS and inhibition of phosphodiesterase type 5 (PDE5. In addition, dysfunction of the NO/cGMP pathway may play a crucial role in the pathogenesis of pulmonary hypertension (PH. In this study, the potential protective effects of ICA on PH induced by monocrotaline (MCT, 50 mg/kg singly subcutaneous injection were investigated and the possible mechanisms involved in NO/cGMP pathway were explored in male Sprague Dawley rats. The results showed that ICA (20, 40, and 80 mg/kg/d treatment by intragastric administration could significantly ameliorate PH and upregulate the expression of eNOS gene and downregulate the expression of PDE5 gene in MCT-treated rats. Both ICA (40 mg/kg/d and L-arginine (200 mg/kg/d, a precursor of NO as positive control, notably increased the contents of NO and cGMP in lung tissue homogenate, which were inversed by treatment with GN-nitro-L-arginine-methyl ester (L-NAME, a NOS inhibitor, and L-NAME-treatment could also inhibit the protective effects of ICA (40 mg/kg/d on mean pulmonary artery pressure and artery remodeling and tends to inhibit right ventricle hypertrophy index. In summary, ICA is effective in protecting against MCT-induced PH in rats through enhancement of NO/cGMP signaling pathway in rats.

  19. Clinical significance of abnormal high signal intensity of left ventricular myocardium by gadolinium-diethylenetriaminepenta-acetic acid enhanced magnetic resonance imaging in hypertrophic cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Koito, Hitoshi; Suzuki, Junichi; Nakamori, Hisato; Ohkubo, Naohiko; Wakayama, Yuka; Iwasaka, Toshiji; Inada, Mitsuo; Katoh, Tsumotu [Kansai Medical Univ., Moriguchi, Osaka (Japan)

    1995-04-01

    The significance of abnormal high signal intensity observed in left ventricular myocardium by gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) enhanced magnetic resonance (MR) imaging in hypertrophic cardiomyopathy (HCM) patients was assessed by comparison with T{sub 1}-weighted MR imaging, thallium-201 ({sup 201}Tl) myocardial scintigraphy, radionuclide angiocardiography, M-mode echocardiography, electrocardiography, and chest radiography. The 16 patients were divided into three groups: 8 patients (group I) with abnormal high signal intensity before and after Gd-DTPA enhancement, 4 (group II) with abnormal high signal intensity only after enhancement and 4 (group III) without abnormal high signal intensity. Thallium-201 myocardial single photon emission computed tomography (SPECT) showed abnormalities of regional {sup 201}Tl uptake in the left ventricular myocardium in 4 patients in Group I, 3 in group II, and one in Group III. No significant difference in left ventricular ejection fraction (LVEF) was seen between groups I, II, and III (64{+-}13%, 67{+-}17% and 71{+-}7%) although 3 patients in group I had LVEF of less than 55%. Left ventricular peak filling rates (PFR) of groups I and II were significantly lower than group III (1.90{+-}0.44, 2.41{+-}0.43 and 3.37{+-}0.48 EDV/sec). Group I had larger end-diastolic left ventricular dimension (LVDd), significantly larger end-systolic left ventricular dimension (LVDs), and smaller % fractional shortening (%FS) than group III (49{+-}4 vs 42{+-}6 mm, 31{+-}5 vs 22{+-}4 mm, and 38{+-}8 vs 49{+-}4%). Abnormal high signal intensity in left ventricular myocardium in HCM seems to reflect myocardial ischemia and fibrosis due to small vessel disease, or myocardial degeneration and necrosis. We conclude that Gd-DTPA enhanced MR imaging may detect the early process of the dilated phase of HCM. (J.P.N.).

  20. Rice Dwarf Virus P2 Protein Hijacks Auxin Signaling by Directly Targeting the Rice OsIAA10 Protein, Enhancing Viral Infection and Disease Development.

    Directory of Open Access Journals (Sweden)

    Lian Jin

    2016-09-01

    Full Text Available The phytohormone auxin plays critical roles in regulating myriads of plant growth and developmental processes. Microbe infection can disturb auxin signaling resulting in defects in these processes, but the underlying mechanisms are poorly understood. Auxin signaling begins with perception of auxin by a transient co-receptor complex consisting of an F-box transport inhibitor response 1/auxin signaling F-box (TIR1/AFB protein and an auxin/indole-3-acetic acid (Aux/IAA protein. Auxin binding to the co-receptor triggers ubiquitination and 26S proteasome degradation of the Aux/IAA proteins, leading to subsequent events, including expression of auxin-responsive genes. Here we report that Rice dwarf virus (RDV, a devastating pathogen of rice, causes disease symptoms including dwarfing, increased tiller number and short crown roots in infected rice as a result of reduced sensitivity to auxin signaling. The RDV capsid protein P2 binds OsIAA10, blocking the interaction between OsIAA10 and OsTIR1 and inhibiting 26S proteasome-mediated OsIAA10 degradation. Transgenic rice plants overexpressing wild-type or a dominant-negative (degradation-resistant mutant of OsIAA10 phenocopy RDV symptoms are more susceptible to RDV infection; however, knockdown of OsIAA10 enhances the resistance of rice to RDV infection. Our findings reveal a previously unknown mechanism of viral protein reprogramming of a key step in auxin signaling initiation that enhances viral infection and pathogenesis.

  1. Relationship between signal intensity on hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MR imaging and prognosis of borderline lesions of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Satoshi, E-mail: satoshik@staff.kanazawa-u.ac.jp [Department of Radiology, Kanazawa University School of Medicine, 13-1, Takara Machi, Kanazawa 920-8641 (Japan); Matsui, Osamu, E-mail: matsuio@med.kanazawa-u.ac.jp [Department of Radiology, Kanazawa University School of Medicine, 13-1, Takara Machi, Kanazawa 920-8641 (Japan); Gabata, Toshifumi, E-mail: gabata@med.kanazawa-u.ac.jp [Department of Radiology, Kanazawa University School of Medicine, 13-1, Takara Machi, Kanazawa 920-8641 (Japan); Koda, Wataru, E-mail: wkoda@staff.kanazawa-u.ac.jp [Department of Radiology, Kanazawa University School of Medicine, 13-1, Takara Machi, Kanazawa 920-8641 (Japan); Minami, Tetsuya, E-mail: tminami@staff.kanazawa-u.ac.jp [Department of Radiology, Kanazawa University School of Medicine, 13-1, Takara Machi, Kanazawa 920-8641 (Japan); Ryu, Yasuji, E-mail: yryu-kanazawa@umin.ac.jp [Department of Radiology, Kanazawa University School of Medicine, 13-1, Takara Machi, Kanazawa 920-8641 (Japan); Kozaka, Kazuto, E-mail: k-kozaka@staff.kanazawa-u.ac.jp [Department of Radiology, Kanazawa University School of Medicine, 13-1, Takara Machi, Kanazawa 920-8641 (Japan); Kitao, Azusa, E-mail: azusa@med.kanazawa-u.ac.jp [Department of Radiology, Kanazawa University School of Medicine, 13-1, Takara Machi, Kanazawa 920-8641 (Japan)

    2012-11-15

    Purpose: To elucidate the incidence of signal intensity patterns of borderline lesions of hepatocellular carcinoma (HCC) on hepatobiliary phase Gd-EOB-DTPA (EOB) enhanced MRI and clarify the natural histories of these lesions. Materials and methods: Total 99 borderline lesions of HCC were identified by angiography-assisted CT. The signal intensity of borderline lesions on hepatobiliary phase of EOB-enhanced MRI was analyzed. Progress rate from borderline lesions to hypervascular HCC was calculated with the Kaplan-Meier method among each signal intensity groups of nodules. Results: On hepatobiliary phase of EOB-enhanced MRI, 41.4% of the borderline lesions showed hypo-, 42.4% showed iso-, and 16.2% showed hyperintense, compared to background liver. Overall progress rates from borderline lesions to HCC were 10% in 1-year, 14% in 2-year and 20% in 3-year follow-up period. Progress rates to HCC in hypointense borderline lesions were 17% in 1-year, 28% in 2-year and 41% in 3-year follow-up period, and in isointense borderline lesions were 7% in 1-year, 7% in 2-year and 7% in 3-year follow-up period. No hyperintense borderline lesions progressed to HCC in follow-up period. Conclusion: Although borderline lesions of HCC may show hypo-, iso- and hyperintensity on hepatobiliary phase of EOB-enhanced MRI, hypointense borderline lesions are high risk to progress HCC.

  2. Gdf11/Smad signalling and Cdx proteins cooperate to activate the Hoxc8 early enhancer in HepG2 cells.

    Science.gov (United States)

    Gaunt, Stephen J

    2017-01-01

    Developing anatomy along the head-tail axis of bilaterian embryos is specified, to a large extent, by the overlapping patterns of expression of the Hox genes. Hox gene enhancers respond to a variety of signals in order to regulate these discreet domains of expression. For mouse Hoxc8, the 399bp "early enhancer" plays a major role. Activation of this enhancer is now examined using luciferase expression constructs transfected into HepG2 cells. Constructs are activated by the combined actions of Gdf11/Smad and Cdx protein signalling pathways, both of which are functional in early embryos. Each of these pathways alone has little stimulatory effect. Stimulation by the two pathways together exceeds the sum of the effects of each pathway alone, indicating synergistic activity. By mutation analysis, two Smad binding motifs are identified as mediators of the Gdf11 effect and two Cdx binding motifs mediate the Cdx effect. The two Smad motifs and one of the Cdx sites are conserved from fish to mammals. Gdf11 stimulation is partially inhibited by Specific Inhibitor of Smad3, suggesting that Smad3 plays a part in signal transduction. Fgf2 increases luciferase activation by the Hoxc8 enhancer, but not, apparently, by specific interactions with either Gdf11 or Cdx effects.

  3. Differentiation of mass-forming focal pancreatitis from pancreatic ductal adenocarcinoma: value of characterizing dynamic enhancement patterns on contrast-enhanced MR images by adding signal intensity color mapping

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Mimi [Hanyang University College of Medicine, Department of Radiology, Hanyang Medical Center, Seoul (Korea, Republic of); Jang, Kyung Mi [Sungkyunkwan University School of Medicine, Department of Radiology, Samsung Medical Center, Seoul (Korea, Republic of); Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea, Republic of); Kim, Jae-Hun; Jeong, Woo Kyoung; Kim, Seong Hyun; Kang, Tae Wook; Kim, Young Kon; Cha, Dong Ik [Sungkyunkwan University School of Medicine, Department of Radiology, Samsung Medical Center, Seoul (Korea, Republic of); Kim, Kyunga [Samsung Medical Center, Biostatics and Clinical Epidemiology Center, Research Institute for Future Medicine, Seoul (Korea, Republic of)

    2017-04-15

    To evaluate the value of dynamic enhancement patterns on contrast-enhanced MR images by adding signal intensity colour mapping (SICM) to differentiate mass-forming focal pancreatitis (MFFP) from pancreatic ductal adenocarcinoma (PDAC). Forty-one clinicopathologically proven MFFPs and 144 surgically confirmed PDACs were enrolled. Laboratory and MR imaging parameters were used to differentiate MFFP from PDAC. In particular, enhancement patterns on MR images adding SICM were evaluated. By using classification tree analysis (CTA), we determined the predictors for the differentiation of MFFP from PDAC. In the CTA, with all parameters except enhancement pattern on SICM images, ductal obstruction grade and T1 hypointensity grade of the pancreatic lesion were the first and second splitting predictor for differentiation of MFFP from PDAC, in order. By adding an enhancement pattern on the SICM images to CTA, the enhancement pattern was the only splitting predictor to differentiate MFFP from PDAC. The CTA model including enhancement pattern on SICM images has sensitivity of 78.0 %, specificity of 99.3 %, and accuracy of 94.6 % for differentiating MFFP from PDAC. The characterization of enhancement pattern for pancreatic lesions on contrast-enhanced MR images adding SICM would be helpful to differentiate MFFP from PDAC. (orig.)

  4. A Class of Optimal Rectangular Filtering Matrices for Single-Channel Signal Enhancement in the Time Domain

    DEFF Research Database (Denmark)

    Jensen, Jesper Rindom; Benesty, Jacob; Christensen, Mads Græsbøll

    2013-01-01

    in the filters, that are otherwise reserved for preserving the signal subspace, can be used for achieving an improved output signal-to-noise ratio (SNR). Moreover, the filters allow for explicit control of the tradeoff between noise reduction and speech distortion via the chosen rank of the signal subspace...... and real signals. The results show a number of interesting things. Firstly, they show how speech distortion can be traded for noise reduction and vice versa in a seamless manner. Moreover, the introduced filter designs are capable of achieving both the upper and lower bounds for the output SNR via...

  5. Assessing the osteoblast transcriptome in a model of enhanced bone formation due to constitutive G{sub s}–G protein signaling in osteoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Wattanachanya, Lalita, E-mail: lalita_md@yahoo.com [Endocrine Research Unit, Veterans Affairs Medical Center and Departments of Medicine and Physiology, University of California, San Francisco, CA (United States); Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok (Thailand); Wang, Liping, E-mail: lipingwang05@yahoo.com [Endocrine Research Unit, Veterans Affairs Medical Center and Departments of Medicine and Physiology, University of California, San Francisco, CA (United States); Millard, Susan M., E-mail: susan.millard@mater.uq.edu.au [Endocrine Research Unit, Veterans Affairs Medical Center and Departments of Medicine and Physiology, University of California, San Francisco, CA (United States); Lu, Wei-Dar, E-mail: weidar_lu@yahoo.com [Endocrine Research Unit, Veterans Affairs Medical Center and Departments of Medicine and Physiology, University of California, San Francisco, CA (United States); O’Carroll, Dylan, E-mail: dylancocarroll@gmail.com [Endocrine Research Unit, Veterans Affairs Medical Center and Departments of Medicine and Physiology, University of California, San Francisco, CA (United States); Hsiao, Edward C., E-mail: Edward.Hsiao@ucsf.edu [Division of Endocrinology and Metabolism, Department of Medicine, University of California, San Francisco, CA (United States); Conklin, Bruce R., E-mail: bconklin@gladstone.ucsf.edu [Gladstone Institute of Cardiovascular Disease, San Francisco, CA (United States); Department of Medicine, University of California, San Francisco, CA (United States); Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA (United States); Nissenson, Robert A., E-mail: Robert.Nissenson@ucsf.edu [Endocrine Research Unit, Veterans Affairs Medical Center and Departments of Medicine and Physiology, University of California, San Francisco, CA (United States)

    2015-05-01

    G protein-coupled receptor (GPCR) signaling in osteoblasts (OBs) is an important regulator of bone formation. We previously described a mouse model expressing Rs1, an engineered constitutively active G{sub s}-coupled GPCR, under the control of the 2.3 kb Col I promoter. These mice showed a dramatic age-dependent increase in trabecular bone of femurs. Here, we further evaluated the effects of enhanced G{sub s} signaling in OBs on intramembranous bone formation by examining calvariae of 1- and 9-week-old Col1(2.3)/Rs1 mice and characterized the in vivo gene expression specifically occurring in osteoblasts with activated G{sub s} G protein-coupled receptor signaling, at the cellular level rather than in a whole bone. Rs1 calvariae displayed a dramatic increase in bone volume with partial loss of cortical structure. By immunohistochemistry, Osterix was detected in cells throughout the inter-trabecular space while Osteocalcin was expressed predominantly in cells along bone surfaces, suggesting the role of paracrine mediators secreted from OBs driven by 2.3 kb Col I promoter could influence early OB commitment, differentiation, and/or proliferation. Gene expression analysis of calvarial OBs revealed that genes affected by Rs1 signaling include those encoding proteins important for cell differentiation, cytokines and growth factors, angiogenesis, coagulation, and energy metabolism. The set of G{sub s}-GPCRs and other GPCRs that may contribute to the observed skeletal phenotype and candidate paracrine mediators of the effect of G{sub s} signaling in OBs were also determined. Our results identify novel detailed in vivo cellular changes of the anabolic response of the skeleton to G{sub s} signaling in mature OBs. - Highlights: • OB expression of an engineered G{sub s}-coupled receptor dramatically increases bone mass. • We investigated the changes in gene expression in vivo in enhanced OB G{sub s} signaling. • Genes in cell cycle and transcription were increased in

  6. Precursory strong-signal characteristics of the convective clouds of the Central Tibetan Plateau detected by radar echoes with respect to the evolutionary processes of an eastward-moving heavy rainstorm belt in the Yangtze River Basin

    Science.gov (United States)

    Zhao, Yang; Xu, Xiangde; Ruan, Zheng; Chen, Bin; Wang, Fang

    2018-03-01

    The integrated analysis of the data from a C-band frequency-modulated continuous-wave (C-FMCW) radar site in Naqu obtained during a rainstorm over the middle and lower reaches of the Yangtze River and the data concerning the three-dimensional structure of the circulation of the precipitation system that occurred over the lower reaches of the Yangtze River Basin during the Third Tibetan Plateau (TP) Atmospheric Experiment from August 15th to 19th, 2014, was carried out. The changes in the echo intensity at the C-FMCW radar site in Naqu were of regional indicative significance for the characteristics of the whole-layer apparent heat source Q1 in local areas and the region of the adjacent river source area, including the Yangtze River, Yellow River, and Lancang River (hereinafter referred to as the "source area of three rivers"), as well as to the vertical speeds due to the development of convection. This study indicates that the C-FMCW radar echo intensity of the plateau convection zone and the related power structures of the coupled dipole circulations in the middle layer of the atmosphere, as well as in the upper atmospheric level divergence and lower atmospheric level convergence, are important stimuli for convective clouds in this region. Furthermore, these radar data provided a physical image of the development and maintenance mechanisms of an eastward-moving heavy rainstorm belt. This study also shows that changes in the echo intensities at the C-FMCW radar site of Naqu can provide strong signals related to heavy rainstorm processes in the upper reaches of the Yangtze River.

  7. Study on the Thick-Walled Pipe Ultrasonic Signal Enhancement of Modified S-Transform and Singular Value Decomposition

    Directory of Open Access Journals (Sweden)

    Haichao Cai

    2015-01-01

    Full Text Available When detecting the ultrasonic flaw of thick-walled pipe, the flaw echo signals are often interrupted by scanning system frequency and background noise. In particular when the thick-walled pipe defect is small, echo signal amplitude is often drowned in noise signal and affects the extraction of defect signal and the position determination accuracy. This paper presents the modified S-transform domain singular value decomposition method for the analysis of ultrasonic flaw echo signals. By changing the scale rule of Gaussian window functions with S-transform to improve the time-frequency resolution. And the paper tries to decompose the singular value decomposition of time-frequency matrix after the S-transform to determine the singular entropy of effective echo signal and realize the adaptive filter. Experiments show that, using this method can not only remove high frequency noise but also remove the low frequency noise and improve the signal-to-noise ratio of echo signal.

  8. Broadband Signal Enhancement of Seismic Array Data: Application to Long-Period Surface Waves & High Frequency Wavefields

    National Research Council Canada - National Science Library

    Vernon, Frank

    1998-01-01

    .... "Dual-frequency" coherence is useful in identifying overtones and frequency shifts between signals, features which are undetectable by standard coherence measures. We construct a filter to extract only the coherent frequencies from a waveform and show that it significantly increases the signal-noise-ratio for dispersive waveforms.

  9. Enhanced effect of nuclear localization signal peptide during ultrasound‑targeted microbubble destruction‑mediated gene transfection.

    Science.gov (United States)

    Cao, Sheng; Zhou, Qing; Chen, Jin-Ling; Jiang, Nan; Wang, Yi-Jia; Deng, Qing; Hu, Bo; Guo, Rui-Qiang

    2017-07-01

    Ultrasound‑targeted microbubble destruction (UTMD) can promote the entry of plasmid DNA (pDNA) into the cell cytoplasm, by increasing the permeability of the cell membrane. But the transfection efficiency remains low due to inability of the pDNA to enter the nucleus. Various methods have been explored to improve the UTMD transfection efficiency, but with little success. In cells, the classic nuclear localization signal (cNLS) peptide is an amino acid sequence that signals proteins that are due for nuclear transport. The present study aimed to investigate whether binding of a cNLS peptide to the pDNA may improve the transfection efficiency of UTMD. Four experimental groups were analyzed: Control group (UTMD + pDNA), group with cNLS (UTMD + pDNA + cNLS), group with mutated NLS (mNLS; UTMD + pDNA + mNLS), and group with cNLS and the nuclear import blocker, wheat germ agglutinin (WGA; UTMD + pDNA + cNLS + WGA). The NLS was labeled by fluorescein isothiocyanate, whereas pDNA was labeled with Cy3. Different molar ratios were tested for the NLS and pDNA combination in order to achieve optimal binding of the two molecules. Human umbilical vein endothelial cells were then transfected using the optimum ultrasonic irradiation parameters and NLS/pDNA molar ratio. At 6 h post‑transfection, the rates of Cy3‑labeled pDNA inside the cells and their nuclei were detected by flow cytometry and laser confocal microscopy, and the cellular vs. nuclear uptake of pDNA was calculated. In order to further evaluate the effect of NLS on UTMD‑mediated gene transfection, the transfection efficiency and relative expression levels of mRNA and protein were detected at 48 h post‑transfection. The results demonstrated that the optimal molar ratio of NLS with pDNA was 104:1. The rates of pDNA successful entry into the cell and nucleus were significantly higher in the cNLS group compared with the control group. The transfection efficiency, and relative expression levels of mRNA and protein

  10. Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic enzymes and insulin signaling molecules in streptozotocin–cadmium induced diabetic nephrotoxic rats

    Energy Technology Data Exchange (ETDEWEB)

    Kandasamy, Neelamegam; Ashokkumar, Natarajan, E-mail: npashokkumar1@gmail.com

    2014-09-01

    Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. The present study was aimed to evaluate the therapeutic potential of myricetin by assaying the activities of key enzymes of carbohydrate metabolism, insulin signaling molecules and renal function markers in streptozotocin (STZ)–cadmium (Cd) induced diabetic nephrotoxic rats. After myricetin treatment schedule, blood and tissue samples were collected to determine plasma glucose, insulin, hemoglobin, glycosylated hemoglobin and renal function markers, carbohydrate metabolic enzymes in the liver and insulin signaling molecules in the pancreas and skeletal muscle. A significant increase of plasma glucose, glycosylated hemoglobin, urea, uric acid, creatinine, blood urea nitrogen (BUN), urinary albumin, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase and a significant decrease of plasma insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase, glycogen and glycogen synthase with insulin signaling molecule expression were found in the STZ–Cd induced diabetic nephrotoxic rats. The administration of myricetin significantly normalizes the carbohydrate metabolic products like glucose, glycated hemoglobin, glycogen phosphorylase and gluconeogenic enzymes and renal function markers with increase insulin, glycogen, glycogen synthase and insulin signaling molecule expression like glucose transporter-2 (GLUT-2), glucose transporter-4 (GLUT-4), insulin receptor-1 (IRS-1), insulin receptor-2 (IRS-2) and protein kinase B (PKB). Based on the data, the protective effect of myricetin was confirmed by its histological annotation of the pancreas, liver and kidney tissues. These findings suggest that myricetin improved carbohydrate metabolism which subsequently enhances glucose utilization and renal function in STZ–Cd induced diabetic nephrotoxic rats. - Highlights: • Diabetic rats are more susceptible to cadmium nephrotoxicity. • Cadmium plays as a cumulative

  11. Protective effect of bioflavonoid myricetin enhances carbohydrate metabolic enzymes and insulin signaling molecules in streptozotocin–cadmium induced diabetic nephrotoxic rats

    International Nuclear Information System (INIS)

    Kandasamy, Neelamegam; Ashokkumar, Natarajan

    2014-01-01

    Diabetic nephropathy is the kidney disease that occurs as a result of diabetes. The present study was aimed to evaluate the therapeutic potential of myricetin by assaying the activities of key enzymes of carbohydrate metabolism, insulin signaling molecules and renal function markers in streptozotocin (STZ)–cadmium (Cd) induced diabetic nephrotoxic rats. After myricetin treatment schedule, blood and tissue samples were collected to determine plasma glucose, insulin, hemoglobin, glycosylated hemoglobin and renal function markers, carbohydrate metabolic enzymes in the liver and insulin signaling molecules in the pancreas and skeletal muscle. A significant increase of plasma glucose, glycosylated hemoglobin, urea, uric acid, creatinine, blood urea nitrogen (BUN), urinary albumin, glycogen phosphorylase, glucose-6-phosphatase, and fructose-1,6-bisphosphatase and a significant decrease of plasma insulin, hemoglobin, hexokinase, glucose-6-phosphate dehydrogenase, glycogen and glycogen synthase with insulin signaling molecule expression were found in the STZ–Cd induced diabetic nephrotoxic rats. The administration of myricetin significantly normalizes the carbohydrate metabolic products like glucose, glycated hemoglobin, glycogen phosphorylase and gluconeogenic enzymes and renal function markers with increase insulin, glycogen, glycogen synthase and insulin signaling molecule expression like glucose transporter-2 (GLUT-2), glucose transporter-4 (GLUT-4), insulin receptor-1 (IRS-1), insulin receptor-2 (IRS-2) and protein kinase B (PKB). Based on the data, the protective effect of myricetin was confirmed by its histological annotation of the pancreas, liver and kidney tissues. These findings suggest that myricetin improved carbohydrate metabolism which subsequently enhances glucose utilization and renal function in STZ–Cd induced diabetic nephrotoxic rats. - Highlights: • Diabetic rats are more susceptible to cadmium nephrotoxicity. • Cadmium plays as a cumulative

  12. Exploiting LBL-assembled Au nanoparticles to enhance Raman signals for point-of-care testing of osteoporosis with excreta sample

    Science.gov (United States)

    Sun, Jian F.; Liu, Xuan; Guo, Zhi R.; Dong, Jian; Huang, Yawen; Zhang, Jie; Jin, Hui; Gu, Ning

    2017-02-01

    Due to the intrinsic lack of specific biomarkers, there is an increasing demand for degenerative diseases to develop a testing method independent upon the targeting biomolecules. In this paper, we proposed a novel idea for this issue which was to analyze the characteristic information of metabolites with Raman spectrum. First, we achieved the fabrication of stable, uniform and reproducible substrate to enhance the Raman signals, which is crucial to the following analysis of information. This idea was confirmed with the osteoporosis-modeled mice. Furthermore, the testing results with clinical samples also preliminarily exhibited the feasibility of this strategy. The substrate to enhance Raman signal was fabricated by the layer-by-layer assembly of Au nanoparticles. The osteoporosis modeling was made by bilateral ovariectomy. Ten female mice were randomly divided into two groups. The urine and dejecta samples of mice were collected every week. Clinic urine samples were collected from patients with osteoporosis while the controlled samples were from the young students in our university. The LBL-assembled substrate of Au nanoparticles was uniform, stable and reproducible to significantly enhance the Raman signals from tiny amount of samples. With a simple data processing technique, the Raman signal-based method can effectively reflect the development of osteoporosis by comparison with micro-CT characterization. Moreover, the Raman signal from samples of clinic patients also showed the obvious difference with that of the control. Raman spectrum may be a good tool to convey the pathological information of metabolites in molecular level. Our results manifested that the information-based testing is possibly feasible and promising. Our strategy utilizes the characteristic information rather than the biological recognition to test the diseases which are difficult to find specific biomarkers. This will be greatly beneficial to the prevention and diagnosis of degenerative

  13. Standardized processing of MALDI imaging raw data for enhancement of weak analyte signals in mouse models of gastric cancer and Alzheimer's disease.

    Science.gov (United States)

    Schwartz, Matthias; Meyer, Björn; Wirnitzer, Bernhard; Hopf, Carsten

    2015-03-01

    Conventional mass spectrometry image preprocessing methods used for denoising, such as the Savitzky-Golay smoothing or discrete wavelet transformation, typically do not only remove noise but also weak signals. Recently, memory-efficient principal component analysis (PCA) in conjunction with random projections (RP) has been proposed for reversible compression and analysis of large mass spectrometry imaging datasets. It considers single-pixel spectra in their local context and consequently offers the prospect of using information from the spectra of adjacent pixels for denoising or signal enhancement. However, little systematic analysis of key RP-PCA parameters has been reported so far, and the utility and validity of this method for context-dependent enhancement of known medically or pharmacologically relevant weak analyte signals in linear-mode matrix-assisted laser desorption/ionization (MALDI) mass spectra has not been explored yet. Here, we investigate MALDI imaging datasets from mouse models of Alzheimer's disease and gastric cancer to systematically assess the importance of selecting the right number of random projections k and of principal components (PCs) L for reconstructing reproducibly denoised images after compression. We provide detailed quantitative data for comparison of RP-PCA-denoising with the Savitzky-Golay and wavelet-based denoising in these mouse models as a resource for the mass spectrometry imaging community. Most importantly, we demonstrate that RP-PCA preprocessing can enhance signals of low-intensity amyloid-β peptide isoforms such as Aβ1-26 even in sparsely distributed Alzheimer's β-amyloid plaques and that it enables enhanced imaging of multiply acetylated histone H4 isoforms in response to pharmacological histone deacetylase inhibition in vivo. We conclude that RP-PCA denoising may be a useful preprocessing step in biomarker discovery workflows.

  14. Bioinert Anodic Alumina Nanotubes for Targeting of Endoplasmic Reticulum Stress and Autophagic Signaling: A Combinatorial Nanotube-Based Drug Delivery System for Enhancing Cancer Therapy.

    Science.gov (United States)

    Wang, Ye; Kaur, Gagandeep; Chen, Yuting; Santos, Abel; Losic, Dusan; Evdokiou, Andreas

    2015-12-16

    Although nanoparticle-based targeted delivery systems have gained promising achievements for cancer therapy, the development of sophisticated strategies with effective combinatorial therapies remains an enduring challenge. Herein, we report the fabrication of a novel nanomaterial, so-called anodic alumina nanotubes (AANTs) for proof-of-concept cancer therapy by targeting cell signaling networks. This strategy is to target autophagic and endoplasmic reticulum (ER) stress signaling by using thapsigargin (TG)-loaded AANTs cotreated with an autophagy inhibitor 3-methyladenine (3-MA). We first show that AANTs are nontoxic and can activate autophagy in different cell types including human fibroblast cells (HFF), human monocyte cells (THP-1), and human breast cancer cells (MDA-MB 231-TXSA). Treatment with 3-MA at a nontoxic dose reduced the level of autophagy induced by AANTs, and consequently sensitized breast cancer cells to AANTs-induced cellular stresses. To target autophagic and ER stress signaling networking, breast cancer cells were treated with 3-MA together with AANTs loaded with the prototype ER stress inducer TG. We demonstrated that 3-MA enhanced the cancer cell killing effect of AANTs loaded with TG. This effect was associated with enhanced ER stress signaling due to the combination effect of TG and 3-MA. These findings not only demonstrate the excellent biocompatibility of AANTs as novel biomaterials but also provide new opportunities for developing ER- and autophagy-targeted delivery systems for future clinical cancer therapy.

  15. Statins induce apoptosis through inhibition of Ras signaling pathways and enhancement of Bim and p27 expression in human hematopoietic tumor cells.

    Science.gov (United States)

    Fujiwara, Daichiro; Tsubaki, Masanobu; Takeda, Tomoya; Tomonari, Yoshika; Koumoto, Yu-Ichi; Sakaguchi, Katsuhiko; Nishida, Shozo

    2017-10-01

    Recently, statins have been demonstrated to improve cancer-related mortality or prognosis in patients of various cancers. However, the details of the apoptosis-inducing mechanisms remain unknown. This study showed that the induction of apoptosis by statins in hematopoietic tumor cells is mediated by mitochondrial apoptotic signaling pathways, which are activated by the suppression of mevalonate or geranylgeranyl pyrophosphate biosynthesis. In addition, statins decreased the levels of phosphorylated extracellular signal-regulated kinase 1/2 and mammalian target of rapamycin through suppressing Ras prenylation. Furthermore, inhibition of extracellular signal-regulated kinase 1/2 and mammalian target of rapamycin by statins induced Bim expression via inhibition of Bim phosphorylation and ubiquitination and cell-cycle arrest at G1 phase via enhancement of p27 expression. Moreover, combined treatment of U0126, a mitogen-activated protein kinase kinase 1/2 inhibitor, and rapamycin, a mammalian target of rapamycin inhibitor, induced Bim and p27 expressions. The present results suggested that statins induce apoptosis by decreasing the mitochondrial transmembrane potential, increasing the activation of caspase-9 and caspase-3, enhancing Bim expression, and inducing cell-cycle arrest at G1 phase through inhibition of Ras/extracellular signal-regulated kinase and Ras/mammalian target of rapamycin pathways. Therefore, our findings support the use of statins as potential anticancer agents or concomitant drugs of adjuvant therapy.

  16. Rac1 augments Wnt signaling by stimulating β-catenin–lymphoid enhancer factor-1 complex assembly independent of β-catenin nuclear import

    Science.gov (United States)

    Jamieson, Cara; Lui, Christina; Brocardo, Mariana G.; Martino-Echarri, Estefania; Henderson, Beric R.

    2015-01-01

    ABSTRACT β-Catenin transduces the Wnt signaling pathway and its nuclear accumulation leads to gene transactivation and cancer. Rac1 GTPase is known to stimulate β-catenin-dependent transcription of Wnt target genes and we confirmed this activity. Here we tested the recent hypothesis that Rac1 augments Wnt signaling by enhancing β-catenin nuclear import; however, we found that silencing/inhibition or up-regulation of Rac1 had no influence on nuclear accumulation of β-catenin. To better define the role of Rac1, we employed proximity ligation assays (PLA) and discovered that a significant pool of Rac1–β-catenin protein complexes redistribute from the plasma membrane to the nucleus upon Wnt or Rac1 activation. More importantly, active Rac1 was shown to stimulate the formation of nuclear β-catenin–lymphoid enhancer factor 1 (LEF-1) complexes. This regulation required Rac1-dependent phosphorylation of β-catenin at specific serines, which when mutated (S191A and S605A) reduced β-catenin binding to LEF-1 by up to 50%, as revealed by PLA and immunoprecipitation experiments. We propose that Rac1-mediated phosphorylation of β-catenin stimulates Wnt-dependent gene transactivation by enhancing β-catenin–LEF-1 complex assembly, providing new insight into the mechanism of cross-talk between Rac1 and canonical Wnt/β-catenin signaling. PMID:26403202

  17. The insulin response integrates increased TGF-β signaling through Akt-induced enhancement of cell surface delivery of TGF-β receptors

    Science.gov (United States)

    Budi, Erine H.; Muthusamy, Baby Periyanayaki; Derynck, Rik

    2015-01-01

    Increased activity of transforming growth factor β (TGF-β), which binds to and stimulates cell surface receptors, contributes to cancer progression and fibrosis by driving epithelial cells toward a migratory mesenchymal phenotype and increasing the abundance of extracellular matrix proteins. The abundance of TGF-β receptors at the cell surface determines cellular responsiveness to TGF-β, which is often produced by the same cells that have the receptors, and thus serves as an autocrine signal. We found that Akt-mediated phosphorylation of AS160, a RabGAP [guanosine triphosphatase (GTPase)-activating protein] promoted the translocation of TGF-β receptors from intracellular stores to the plasma membrane of mouse embryonic fibroblasts (MEFs) and NMuMG epithelial cells. Consequently, insulin, which is commonly used to treat hyperglycemia and activates Akt signaling, increased the amount of TGF-β receptors at the cell surface, thereby enhancing TGF-β responsiveness. This insulin-induced increase in autocrine TGF-β signaling contributed to insulin-induced gene expression responses, attenuated the epithelial phenotype, and promoted the migration of NMuMG cells. Furthermore, the enhanced delivery of TGF-β receptors at the cell surface enabled insulin to increase TGF-β-induced gene responses. The enhancement of TGF-β responsiveness in response to Akt activation may help to explain the biological effects of insulin, the progression of cancers in which Akt is activated, and the increased incidence of fibroses in diabetes. PMID:26420907

  18. Anomalous enhancement in daytime 40-kHz signal amplitude accompanied by geomagnetic storms, earthquakes and meteor showers

    Directory of Open Access Journals (Sweden)

    B. K. De

    1995-10-01

    Full Text Available Anomalous propagational characteristics, daytime signal levels greater than night-time, were observed. The amplitude records of a 40-kHz signal propagated over a distance of 5100 km from Sanwa, Japan to Calcutta along a low-latitude path show higher signal strength at midday compared to the midnight level on days preceded by principal geomagnetic storms, earthquakes and major meteor showers. This is explained by the increased ionization in the D-region following geophysical events. The storm after-effects only have a duration of a single day in this low-latitude path.

  19. Effects of chemical synapses on the enhancement of signal propagation in coupled neurons near the canard regime

    Science.gov (United States)

    Li, Xiumin; Wang, Jiang; Hu, Wuhua

    2007-10-01

    The response of three coupled FitzHugh-Nagumo neurons, under Gaussian white noise, to a subthreshold periodic signal is studied in this paper. By combining the canard dynamics, chemical coupling, and stochastic resonance together, the information transfer in this neural system is investigated. We find that chemical synaptic coupling is more efficient than the well-known linear coupling (gap junction) for local signal input, i.e., only one of the three neurons is subject to the periodic signal. This weak and local input is common in biological systems for the sake of low energy consumption.

  20. HSP72 protects cells from ER stress-induced apoptosis via enhancement of IRE1alpha-XBP1 signaling through a physical interaction.

    Directory of Open Access Journals (Sweden)

    Sanjeev Gupta

    2010-07-01

    Full Text Available Endoplasmic reticulum (ER stress is a feature of secretory cells and of many diseases including cancer, neurodegeneration, and diabetes. Adaptation to ER stress depends on the activation of a signal transduction pathway known as the unfolded protein response (UPR. Enhanced expression of Hsp72 has been shown to reduce tissue injury in response to stress stimuli and improve cell survival in experimental models of stroke, sepsis, renal failure, and myocardial ischemia. Hsp72 inhibits several features of the intrinsic apoptotic pathway. However, the molecular mechanisms by which Hsp72 expression inhibits ER stress-induced apoptosis are not clearly understood. Here we show that Hsp72 enhances cell survival under ER stress conditions. The UPR signals through the sensor IRE1alpha, which controls the splicing of the mRNA encoding the transcription factor XBP1. We show that Hsp72 enhances XBP1 mRNA splicing and expression of its target genes, associated with attenuated apoptosis under ER stress conditions. Inhibition of XBP1 mRNA splicing either by dominant negative IRE1alpha or by knocking down XBP1 specifically abrogated the inhibition of ER stress-induced apoptosis by Hsp72. Regulation of the UPR was associated with the formation of a stable protein complex between Hsp72 and the cytosolic domain of IRE1alpha. Finally, Hsp72 enhanced the RNase activity of recombinant IRE1alpha in vitro, suggesting a direct regulation. Our data show that binding of Hsp72 to IRE1alpha enhances IRE1alpha/XBP1 signaling at the ER and inhibits ER stress-induced apoptosis. These results provide a physical connection between cytosolic chaperones and the ER stress response.

  1. HSP72 protects cells from ER stress-induced apoptosis via enhancement of IRE1alpha-XBP1 signaling through a physical interaction.

    LENUS (Irish Health Repository)

    Gupta, Sanjeev

    2010-01-01

    Endoplasmic reticulum (ER) stress is a feature of secretory cells and of many diseases including cancer, neurodegeneration, and diabetes. Adaptation to ER stress depends on the activation of a signal transduction pathway known as the unfolded protein response (UPR). Enhanced expression of Hsp72 has been shown to reduce tissue injury in response to stress stimuli and improve cell survival in experimental models of stroke, sepsis, renal failure, and myocardial ischemia. Hsp72 inhibits several features of the intrinsic apoptotic pathway. However, the molecular mechanisms by which Hsp72 expression inhibits ER stress-induced apoptosis are not clearly understood. Here we show that Hsp72 enhances cell survival under ER stress conditions. The UPR signals through the sensor IRE1alpha, which controls the splicing of the mRNA encoding the transcription factor XBP1. We show that Hsp72 enhances XBP1 mRNA splicing and expression of its target genes, associated with attenuated apoptosis under ER stress conditions. Inhibition of XBP1 mRNA splicing either by dominant negative IRE1alpha or by knocking down XBP1 specifically abrogated the inhibition of ER stress-induced apoptosis by Hsp72. Regulation of the UPR was associated with the formation of a stable protein complex between Hsp72 and the cytosolic domain of IRE1alpha. Finally, Hsp72 enhanced the RNase activity of recombinant IRE1alpha in vitro, suggesting a direct regulation. Our data show that binding of Hsp72 to IRE1alpha enhances IRE1alpha\\/XBP1 signaling at the ER and inhibits ER stress-induced apoptosis. These results provide a physical connection between cytosolic chaperones and the ER stress response.

  2. Enhanced Androgen Signaling With Androgen Receptor Overexpression in the Osteoblast Lineage Controls Skeletal Turnover, Matrix Quality and Bone Architecture

    National Research Council Canada - National Science Library

    Wiren, Kristine M; Jepsen, Karl

    2006-01-01

    .... We genetically engineered transgenic mice in which androgen receptor (AR) overexpression is skeletally targeted in two separate models to better understand the role of androgen signaling directly in bone...

  3. Contrast microsphere enhancement of the tricuspid regurgitant spectral Doppler signal - Is it still necessary with contemporary scanners?

    Directory of Open Access Journals (Sweden)

    David G. Platts

    2017-12-01

    Conclusion: In the era of contemporary scanners, CE improved the ability to detect and measure TRV, except in those with clear unenhanced TR spectral Doppler signals or greater than mild tricuspid regurgitation.

  4. Prosystemin Overexpression in Tomato Enhances Resistance to Different Biotic Stresses by Activating Genes of Multiple Signaling Pathways

    OpenAIRE

    Coppola, Mariangela; Corrado, Giandomenico; Coppola, Valentina; Cascone, Pasquale; Martinelli, Rosanna; Digilio, Maria Cristina; Pennacchio, Francesco; Rao, Rosa

    2014-01-01

    Systemin is a signal peptide that promotes the response to wounding and herbivore attack in tomato. This 18-amino acid peptide is released from a larger precursor, prosystemin. To study the role of systemin as a modulator of defense signaling, we generated tomato (Solanum lycopersicum) transgenic plants that overexpress the prosystemin cDNA. We carried out a transcriptomic analysis comparing two different transgenic events with the untransformed control. The Gene Ontology categories of the 50...

  5. An Internet of Things based physiological signal monitoring and receiving system for virtual enhanced health care network.

    Science.gov (United States)

    Rajan, J Pandia; Rajan, S Edward

    2018-01-01

    Wireless physiological signal monitoring system designing with secured data communication in the health care system is an important and dynamic process. We propose a signal monitoring system using NI myRIO connected with the wireless body sensor network through multi-channel signal acquisition method. Based on the server side validation of the signal, the data connected to the local server is updated in the cloud. The Internet of Things (IoT) architecture is used to get the mobility and fast access of patient data to healthcare service providers. This research work proposes a novel architecture for wireless physiological signal monitoring system using ubiquitous healthcare services by virtual Internet of Things. We showed an improvement in method of access and real time dynamic monitoring of physiological signal of this remote monitoring system using virtual Internet of thing approach. This remote monitoring and access system is evaluated in conventional value. This proposed system is envisioned to modern smart health care system by high utility and user friendly in clinical applications. We claim that the proposed scheme significantly improves the accuracy of the remote monitoring system compared to the other wireless communication methods in clinical system.

  6. Coculture with endothelial cells enhances osteogenic differentiation of periodontal ligament stem cells via cyclooxygenase-2/prostaglandin E2/vascular endothelial growth factor signaling under hypoxia.

    Science.gov (United States)

    Zhao, Lixing; Wu, Yeke; Tan, Lijun; Xu, Zhenrui; Wang, Jun; Zhao, Zhihe; Li, Xiaoyu; Li, Yu; Yang, Pu; Tang, Tian

    2013-12-01

    During periodontitis and orthodontic tooth movement, periodontal vasculature is severely impaired, leading to a hypoxic microenvironment of periodontal cells. However, the impact of hypoxia on periodontal cells is poorly defined. The present study investigates responses of cocultured endothelial cells (ECs) and periodontal ligament stem cells (PDLSCs) to hypoxia. Osteogenic differentiation, molecular characterization, and various behaviors of PDLSCs and human umbilical venous ECs under hypoxia were assessed by quantitative real-time reverse-transcription polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay. Moreover, the effect of ECs on PDLSC osteogenic differentiation was tested using NS398 (cyclooxygenase 2 blocker), SU5416 (vascular endothelial growth factor [VEGF] receptor inhibitor), AH6809, L-798106, and L-161982 (EP1/2/3/4 antagonists). First, hypoxia promoted osteogenic differentiation in PDLSCs and enhanced EC migration, whereas PD98059 (extracellular signal-regulated protein kinase [ERK] inhibitor) blocked, and cocultured ECs further enhanced, hypoxia-induced osteogenic differentiation. Second, NS398 impaired EC migration and prostaglandin E2 (PGE2)/VEGF release, whereas cocultured PDLSCs and exogenous PGE2 partially reversed it. Third, NS398 (pretreated ECs) decreased PGE2/VEGF concentrations. NS398-treated ECs and AH6809/SU5416-treated PDLSCs impaired cocultured EC-induced enhancement of PDLSC osteogenic differentiation. Hypoxia enhances ERK-mediated osteogenic differentiation in PDLSCs. Coculture with EC further augments PDLSC osteogenic differentiation via cyclooxygenase-2/PGE2/VEGF signaling.

  7. Enhancement of β-amyloid oligomer accumulation after intracerebroventricular injection of streptozotocin, which involves central insulin signaling in a transgenic mouse model.

    Science.gov (United States)

    Lin, Fangju; Jia, Jianping; Qin, Wei

    2014-11-12

    The β-amyloid (Aβ) oligomer rather than fibrillar Aβ has become the important focus of recent studies on the pathogenesis of Alzheimer's disease (AD). Insulin signaling plays important roles in cognitive disease, such as AD. However, in-vivo evidence for the link between central insulin signaling and the Aβ oligomer are lacking, and the mechanisms underlying the effect of central insulin signaling on AD are still elusive. Our team has established the Presenilin-1 Val97Leu mutant transgenic (PS1V97L) AD mouse model with the intraneuronal Aβ oligomer as the potential initiator for other pathologies, but without extracellular amyloid plaque formation. Using this model, we investigated the roles of disturbed central insulin signaling induced by intracerebroventricular injection of streptozotocin (STZ) in the progression of AD. We observed that PS1V97L mice after intracerebroventricular injection of STZ showed increased Aβ oligomer accumulation and aggravated spatial learning and memory deficit in the absence of diabetes symptoms. Furthermore, STZ administration inhibited the activation of the insulin receptor and enhanced the activation of c-Jun NH2-terminal kinase, which was accompanied by increased production of carboxy-terminal fragments from the amyloid precursor protein, in the brain of PS1V97L mice. Overall, our study provided in-vivo evidence for a role of central insulin signaling in AD progression.

  8. Changes in signal-to-noise ratios and contrast-to-noise ratios of hypervascular hepatocellular carcinomas on ferucarbotran-enhanced dynamic MR imaging

    International Nuclear Information System (INIS)

    Park, Yulri; Choi, Dongil; Kim, Seong Hyun; Kim, Seung Hoon; Kim, Min Ju; Lee, Jongmee; Lim, Jae Hoon; Lee, Won Jae; Lim, Hyo K.

    2006-01-01

    Purpose: To verify changes in the signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) of hypervascular hepatocellular carcinomas (HCCs) on ferucarbotran-enhanced dynamic T1-weighted MR imaging. Materials and methods: Fifty-two patients with 61 hypervascular HCCs underwent ferucarbotran-enhanced dynamic MR imaging, and then hepatic resection. Hypervascular HCCs were identified when definite enhancement was noted during the arterial dominant phase of three-phase MDCT. Dynamic MR Images with T1-weighted fast multiplanar spoiled gradient-recalled echo sequence (TR200/TE4.2) were obtained before and 20 s, and 1, 3, 5, and 10 min, after bolus injection of ferucarbotran. We estimated the signal intensities of tumors and livers, and calculated the SNRs and CNRs of the tumors. Results: On ferucarbotran-enhanced dynamic MR imaging, SNR measurements showed a fluctuating pattern, namely, an increase in SNR followed by a decrease and a subsequent increase (or a decrease in SNR followed by a increase and a subsequent decrease) in 50 (82.0%) of 61 tumors, a single-peak SNR pattern (highest SNR on 20 s, 1, 3, or 5 min delayed images followed by a decrease) in seven (11.5%), and a decrease in SNR followed by an increase in four (6.6%). Maximum absolute CNRs with positive value were noted on 10 min delayed images in 41 (67.2%) tumors, and maximum absolute CNRs with negative value were observed on 20 s delayed images in 12 (19.7%) and on 1 min delayed images in eight (13.1%). Conclusion: Despite showing various SNR and CNR changes, the majority of hypervascular HCCs demonstrated a fluctuating SNR pattern on ferucarbotran-enhanced dynamic MR imaging and a highest CNR on 10 min delayed image, which differed from the classic enhancement pattern on multiphasic CT

  9. Triglyceride synthesis in hepatocytes isolated from rats fed a low-protein diet is enhanced independently of upregulation of insulin signaling.

    Science.gov (United States)

    Taguchi, Yusuke; Toyoshima, Yuka; Tokita, Reiko; Kato, Hisanori; Takahashi, Shin-Ichiro; Minami, Shiro

    2017-08-26

    It is known that protein malnutrition develops fatty liver in rats. However, the mechanisms by which protein malnutrition enhances lipid accumulation in the liver are not fully understood. Our previous studies have demonstrated that protein malnutrition upregulates insulin signaling with an increase in TG levels in rat livers. Here, we examined whether the upregulated insulin signaling contributes to an enhancement of TG accumulation under protein malnutrition. As it is difficult to analyze insulin-induced hepatic TG synthesis in vivo, the isolated hepatocytes derived from rats fed a low-protein diet were used. The hepatocytes were isolated from rats fed a 15% casein diet (15C) as a control diet or a 5% casein diet (5C) as a low-protein diet and then treated with insulin. As shown in vivo, insulin signaling was upregulated in isolated hepatocytes from 5C-fed rats (5C hepatocytes). However, the insulin-induced increase in the mRNA levels of lipogenic enzymes, including acetyl-CoA carboxylase 1 (ACC1) and fatty acid synthase (FAS), was similar in both groups. The amounts of TG synthesized from both glucose and palmitate, as well as ACC1 and FAS protein levels, were increased at the basal state in 5C hepatocytes, but were not further increased by insulin. These results indicate that TG synthesis via both de novo fatty acid synthesis and esterification is enhanced in 5C hepatocytes, which is independent of the upregulation of insulin signaling. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Prosystemin Overexpression in Tomato Enhances Resistance to Different Biotic Stresses by Activating Genes of Multiple Signaling Pathways.

    Science.gov (United States)

    Coppola, Mariangela; Corrado, Giandomenico; Coppola, Valentina; Cascone, Pasquale; Martinelli, Rosanna; Digilio, Maria Cristina; Pennacchio, Francesco; Rao, Rosa

    Systemin is a signal peptide that promotes the response to wounding and herbivore attack in tomato. This 18-amino acid peptide is released from a larger precursor, prosystemin. To study the role of systemin as a modulator of defense signaling, we generated tomato ( Solanum lycopersicum ) transgenic plants that overexpress the prosystemin cDNA. We carried out a transcriptomic analysis comparing two different transgenic events with the untransformed control. The Gene Ontology categories of the 503 differentially expressed genes indicated that several biological functions were affected. Systemin promotes the expression of an array of defense genes that are dependent on different signaling pathways and it downregulates genes connected with carbon fixation and carbohydrate metabolism. These alterations present a degree of overlap with the response programs that are classically associated to pathogen defense or abiotic stress protection, implying that end products of the systemin signaling pathway may be more diverse than expected. We show also that the observed transcriptional modifications have a relevant functional outcome, since transgenic lines were more resistant against very different biotic stressors such as aphids ( Macrosiphum euphorbiae ), phytopathogenic fungi ( Botrytis cinerea and Alternaria alternata ) and phytophagous larvae ( Spodoptera littoralis ). Our work demonstrated that in tomato the modulation of a single gene is sufficient to provide a wide resistance against stress by boosting endogenous defense pathways. Overall, the data provided evidence that the systemin peptide might serve as DAMP signal in tomato, acting as a broad indicator of tissue integrity.

  11. A Data-Driven Noise Reduction Method and Its Application for the Enhancement of Stress Wave Signals

    Directory of Open Access Journals (Sweden)

    Hai-Lin Feng

    2012-01-01

    Full Text Available Ensemble empirical mode decomposition (EEMD has been recently used to recover a signal from observed noisy data. Typically this is performed by partial reconstruction or thresholding operation. In this paper we describe an efficient noise reduction method. EEMD is used to decompose a signal into several intrinsic mode functions (IMFs. The time intervals between two adjacent zero-crossings within the IMF, called instantaneous half period (IHP, are used as a criterion to detect and classify the noise oscillations. The undesirable waveforms with a larger IHP are set to zero. Furthermore, the optimum threshold in this approach can be derived from the signal itself using the consecutive mean square error (CMSE. The method is fully data driven, and it requires no prior knowledge of the target signals. This method can be verified with the simulative program by using Matlab. The denoising results are proper. In comparison with other EEMD based methods, it is concluded that the means adopted in this paper is suitable to preprocess the stress wave signals in the wood nondestructive testing.

  12. RPS3a over-expressed in HBV-associated hepatocellular carcinoma enhances the HBx-induced NF-κB signaling via its novel chaperoning function.

    Directory of Open Access Journals (Sweden)

    Keo-Heun Lim

    Full Text Available Hepatitis B virus (HBV infection is one of the major causes of hepatocellular carcinoma (HCC development. Hepatitis B virus X protein (HBx is known to play a key role in the development of hepatocellular carcinoma (HCC. Several cellular proteins have been reported to be over-expressed in HBV-associated HCC tissues, but their role in the HBV-mediated oncogenesis remains largely unknown. Here, we explored the effect of the over-expressed cellular protein, a ribosomal protein S3a (RPS3a, on the HBx-induced NF-κB signaling as a critical step for HCC development. The enhancement of HBx-induced NF-κB signaling by RPS3a was investigated by its ability to translocate NF-κB (p65 into the nucleus and the knock-down analysis of RPS3a. Notably, further study revealed that the enhancement of NF-κB by RPS3a is mediated by its novel chaperoning activity toward physiological HBx. The over-expression of RPS3a significantly increased the solubility of highly aggregation-prone HBx. This chaperoning function of RPS3a for HBx is closely correlated with the enhanced NF-κB activity by RPS3a. In addition, the mutational study of RPS3a showed that its N-terminal domain (1-50 amino acids is important for the chaperoning function and interaction with HBx. The results suggest that RPS3a, via extra-ribosomal chaperoning function for HBx, contributes to virally induced oncogenesis by enhancing HBx-induced NF-κB signaling pathway.

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

    Directory of Open Access Journals (Sweden)

    Pavel V. Bakharev

    2015-06-01

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

  14. Measurement of absorption spectrum of deuterium oxide (D2O) and its application to signal enhancement in multiphoton microscopy at the 1700-nm window

    International Nuclear Information System (INIS)

    Wang, Yuxin; Wen, Wenhui; Wang, Kai; Wang, Ke; Zhai, Peng; Qiu, Ping

    2016-01-01

    1700-nm window has been demonstrated to be a promising excitation window for deep-tissue multiphoton microscopy (MPM). Long working-distance water immersion objective lenses are typically used for deep-tissue imaging. However, absorption due to immersion water at 1700 nm is still high and leads to dramatic decrease in signals. In this paper, we demonstrate measurement of absorption spectrum of deuterium oxide (D 2 O) from 1200 nm to 2600 nm, covering the three low water-absorption windows potentially applicable for deep-tissue imaging (1300 nm, 1700 nm, and 2200 nm). We apply this measured result to signal enhancement in MPM at the 1700-nm window. Compared with water immersion, D 2 O immersion enhances signal levels in second-harmonic generation imaging, 3-photon fluorescence imaging, and third-harmonic generation imaging by 8.1, 24.8, and 24.7 times with 1662-nm excitation, in good agreement with theoretical calculation based on our absorption measurement. This suggests D 2 O a promising immersion medium for deep-tissue imaging

  15. The adaptor protein NTAL enhances proximal signaling and potentiates corticosteroid-induced apoptosis in T-ALL

    Czech Academy of Sciences Publication Activity Database

    Svojgr, K.; Kalina, T.; Kanderová, V.; Skopcová, Tereza; Brdička, Tomáš; Zuna, J.

    2012-01-01

    Roč. 40, č. 5 (2012), s. 379-385 ISSN 0301-472X R&D Projects: GA MŠk 2B06064 Institutional support: RVO:68378050 Keywords : acute lymphoblastic leukemia * TCR signaling * NTAL * ERK Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.907, year: 2012

  16. Long-Term Expansion, Enhanced Chondrogenic Potential, and Suppression of Endochondral Ossification of Adult Human MSCs via WNT Signaling Modulation

    Directory of Open Access Journals (Sweden)

    Roberto Narcisi

    2015-03-01

    Full Text Available Mesenchymal stem cells (MSCs are a potential source of chondrogenic cells for the treatment of cartilage disorders, but loss of chondrogenic potential during in vitro expansion and the propensity of cartilage to undergo hypertrophic maturation impede their therapeutic application. Here we report that the signaling protein WNT3A, in combination with FGF2, supports long-term expansion of human bone marrow-derived MSCs. The cells retained their chondrogenic potential and other phenotypic and functional properties of multipotent MSCs, which were gradually lost in the absence of WNT3A. Moreover, we discovered that endogenous WNT signals are the main drivers of the hypertrophic maturation that follows chondrogenic differentiation. Inhibition of WNT signals during differentiation prevented calcification and maintained cartilage properties following implantation in a mouse model. By maintaining potency during expansion and preventing hypertrophic maturation following differentiation, the modulation of WNT signaling removes two major obstacles that impede the clinical application of MSCs in cartilage repair.

  17. Receptor Protein Tyrosine Phosphatase α-Mediated Enhancement of Rheumatoid Synovial Fibroblast Signaling and Promotion of Arthritis in Mice

    NARCIS (Netherlands)

    Stanford, Stephanie M; Svensson, Mattias N D; Sacchetti, Cristiano; Pilo, Caila A; Wu, Dennis J; Kiosses, William B; Hellvard, Annelie; Bergum, Brith; Muench, German R Aleman; Elly, Christian; Liu, Yun-Cai; den Hertog, Jeroen; Elson, Ari; Sap, Jan; Mydel, Piotr; Boyle, David L; Corr, Maripat; Firestein, Gary S; Bottini, Nunzio

    OBJECTIVE: During rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) critically promote disease pathogenesis by aggressively invading the extracellular matrix of the joint. The focal adhesion kinase (FAK) signaling pathway is emerging as a contributor to the anomalous behavior of RA FLS.

  18. Strong enhancement of the chemiluminescence of the Cu(II)-H2O2 system on addition of carbon nitride quantum dots, and its application to the detection of H2O2 and glucose.

    Science.gov (United States)

    Hallaj, Tooba; Amjadi, Mohammad; Song, Zhenlun; Bagheri, Robabeh

    2017-12-19

    The authors report that carbon nitride quantum dots (CN QDs) exert a strong enhancing effect on the Cu(II)/H 2 O 2 chemiluminescent system. Chemiluminescence (CL) intensity is enhanced by CN QDs by a factor of ~75, while other carbon nanomaterials have a much weaker effect. The possible mechanism of the effect was evaluated by recording fluorescence and CL spectra and by examining the effect of various radical scavengers. Emitting species was found to be excited-state CN QDs that produce green CL peaking at 515 nm. The new CL system was applied to the sensitive detection of H 2 O 2 and glucose (via glucose oxidase-catalyzed formation of H 2 O 2 ) with detection limits (3σ) of 10 nM for H 2 O 2 and 100 nM for glucose. The probe was employed for glucose determination in human plasma samples with satisfactory results. Graphical abstract The effect of carbon nitride quantum dots (CN QDs) on Cu(II)-H 2 O 2 chemiluminescence reaction was studied and the new CL system was applied for sensitive detection of glucose based on the glucose oxidase (GOx)-catalyzed formation of H 2 O 2 .

  19. Fcγ-receptor IIa-mediated Src Signaling Pathway Is Essential for the Antibody-Dependent Enhancement of Ebola Virus Infection.

    Directory of Open Access Journals (Sweden)

    Wakako Furuyama

    2016-12-01

    Full Text Available Antibody-dependent enhancement (ADE of Ebola virus (EBOV infection has been demonstrated in vitro, raising concerns about the detrimental potential of some anti-EBOV antibodies. ADE has been described for many viruses and mostly depends on the cross-linking of virus-antibody complexes to cell surface Fc receptors, leading to enhanced infection. However, little is known about the molecular mechanisms underlying this phenomenon. Here we show that Fcγ-receptor IIa (FcγRIIa-mediated intracellular signaling through Src family protein tyrosine kinases (PTKs is required for ADE of EBOV infection. We found that deletion of the FcγRIIa cytoplasmic tail abolished EBOV ADE due to decreased virus uptake into cellular endosomes. Furthermore, EBOV ADE, but not non-ADE infection, was significantly reduced by inhibition of the Src family protein PTK pathway, which was also found to be important to promote phagocytosis/macropinocytosis for viral uptake into endosomes. We further confirmed a significant increase of the Src phosphorylation mediated by ADE. These data suggest that antibody-EBOV complexes bound to the cell surface FcγRIIa activate the Src signaling pathway that leads to enhanced viral entry into cells, providing a novel perspective for the general understanding of ADE of virus infection.

  20. Fibroblast growth factor-4 enhances proliferation of mouse embryonic stem cells via activation of c-Jun signaling.

    Directory of Open Access Journals (Sweden)

    Sung-Ho Kook

    Full Text Available Fibroblast growth factor-4 (FGF4 is expressed in embryonic stages and in adult tissues, where it plays critical roles in modulating multiple cellular functions. However, the exact roles of FGF4 on proliferation and differentiation of embryonic stem cells (ESCs are not completely understood. Exogenous addition of FGF4 stimulated proliferation of mouse ESCs (mESCs, as proven by the increases in DNA synthesis and cell cycle regulatory protein induction. These increases were almost completely inhibited by pre-treating cells with anti-FGF4 antibody. FGF4 also activated c-Jun N-terminal kinase (JNK and extracellular-signal regulated kinase (ERK signaling, but not p38 kinase. Blockage of JNK signaling by SP600125 or by transfection with its specific siRNA significantly inhibited FGF4-stimulated cell proliferation through the suppression of c-Jun induction and activator protein-1 (AP-1 activity. However, ERK or p38 kinase inhibitor did not affect FGF4-stimulated proliferation in mESCs. FGF4 suppressed osteogenic differentiation of mESCs by inhibiting expression of transcription factors involved in bone formation. Further, exogenous FGF4 addition stimulated proliferation of human periodontal ligament stem cells (hPDLSCs and bone marrow mesenchymal stem cells (BMMSCs via activation of ERK signaling. FGF4 also augmented mineralization of hPDLSCs, but not of BMMSCs. Collectively, it is suggested that FGF4 triggers proliferation of stem cells by activating MAPK-mediated signaling, while it affects differently osteogenic differentiation according to the origins of stem cells.