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Sample records for early vlf signal

  1. VLF signal anomalies dues to TS and Hurricanes

    Science.gov (United States)

    Nait Amor, Samir

    2017-04-01

    VLF signal propagates by multiples reflection in the Earth-Ionosphere wave guide. It constitutes a powerful tool to study the lower region of the ionosphere, the D region. This technique was applied to study perturbations related to the solar flares effect, TGF, the connection between TLEs and Early events.... In this contribution I will present a new results on the evidence of signal perturbations associated with TS and Hurricanes. A wavelet spectral analysis is applied to the signal amplitude to search for eventual Atmospheric Gravity wave which may be the origin of the signal perturbations.

  2. Transionospheric Propagation of VLF Transmitter Signals

    Science.gov (United States)

    Cohen, M.; Inan, U. S.; Lehtinen, N. G.

    2012-12-01

    Ground based Very Low Frequency (VLF, 3-30 kHz) radio transmitters may play a significant role in precipitation of inner belt (L<2.5) energetic Van Allen electrons. Initial analyses of the total contribution of VLF transmitters utilized models of transionospheric propagation, but some recent studies have suggested that those models may overestimate (by 20-100 dB) the VLF energy reaching the magnetosphere. One possible cause of this discrepancy was suggested to be conversion of wave energy into electrostatic modes in the D, E, and F regions, from ionospheric density irregularities, either natural or generated by the transmitter heating itself. The DEMETER satellite built a six year history of continuous and global survey mode data which, when combined, yields detailed pictures of the radiation pattern from many transmitters into space at 680 km, with 25 km resolution, and clear features like the interference pattern on the ground mapped upwards. With both E and B survey mode data, we can also directly approximate the total power injected into the magnetosphere from each transmitter, separately for day and night, as well as the power arriving at the conjugate region. We find no detectable variation of signal intensity with geomagnetic conditions. We find evidence of transmitter heating affecting the transionospheric propagation of other transmitters. We find that the power reaching the conjugate region is a large fraction of the power injected above the transmitter. We then employ a full wave model to simulate VLF transmitter transionospheric propagation, calculating the electromagnetic fields and power flux injected into the magnetosphere. Although the model does not include ionospheric irregularities, the radiation pattern largely matches the observed one, and the total power calculated is within 6 dB of observations for every transmitter, both day and night, and across a range of low to middle latitudes and transmitter powers. We thus conclude that the effect of

  3. Possibility of Earthquake-prediction by analyzing VLF signals

    Science.gov (United States)

    Ray, Suman; Chakrabarti, Sandip Kumar; Sasmal, Sudipta

    2016-07-01

    Prediction of seismic events is one of the most challenging jobs for the scientific community. Conventional ways for prediction of earthquakes are to monitor crustal structure movements, though this method has not yet yield satisfactory results. Furthermore, this method fails to give any short-term prediction. Recently, it is noticed that prior to any seismic event a huge amount of energy is released which may create disturbances in the lower part of D-layer/E-layer of the ionosphere. This ionospheric disturbance may be used as a precursor of earthquakes. Since VLF radio waves propagate inside the wave-guide formed by lower ionosphere and Earth's surface, this signal may be used to identify ionospheric disturbances due to seismic activity. We have analyzed VLF signals to find out the correlations, if any, between the VLF signal anomalies and seismic activities. We have done both the case by case study and also the statistical analysis using a whole year data. In both the methods we found that the night time amplitude of VLF signals fluctuated anomalously three days before the seismic events. Also we found that the terminator time of the VLF signals shifted anomalously towards night time before few days of any major seismic events. We calculate the D-layer preparation time and D-layer disappearance time from the VLF signals. We have observed that this D-layer preparation time and D-layer disappearance time become anomalously high 1-2 days before seismic events. Also we found some strong evidences which indicate that it may possible to predict the location of epicenters of earthquakes in future by analyzing VLF signals for multiple propagation paths.

  4. The VLF fingerprint of elves: Step-like and long-recovery early VLF perturbations caused by powerful ±CG lightning EM pulses

    Science.gov (United States)

    Haldoupis, Christos; Cohen, Morris; Arnone, Enrico; Cotts, Benjamin; Dietrich, Stefano

    2013-08-01

    Subionospheric VLF recordings are investigated in relation with intense cloud-to-ground (CG) lightning data. Lightning impacts the lower ionosphere via heating and ionization changes which produce VLF signal perturbations known as early VLF events. Typically, early events recover in about 100 s, but a small subclass does not recover for many minutes, known as long-recovery early events (LORE). In this study, we identify LORE as a distinct category of early VLF events, whose signature may occur either on its own or alongside the short-lived typical early VLF event. Since LORE onsets coincide with powerful lightning strokes of either polarity (±), we infer that they are due to long-lasting ionization changes in the uppermost D region ionosphere caused by electromagnetic pulses emitted by strong ± CG lightning peak currents of typically > 250 kA, which are also known to generate elves. The LORE perturbations are detected when the discharge is located within ~250 km from the great circle path of a VLF transmitter-receiver link. The probability of occurrence increases with stroke intensity and approaches unity for discharges with peak currents ≥ ~300 kA. LOREs are nighttime phenomena that occur preferentially, at least in the present regional data set, during winter when strong ± CG discharges are more frequent and intense. The evidence suggests LORE as a distinct signature representing the VLF fingerprint of elves, a fact which, although was predicted by theory, it escaped identification in the long-going VLF research of lightning effects in the lower ionosphere.

  5. TLEs and early VLF events: Simulating the important impact of transmitter-disturbance-receiver geometry

    Science.gov (United States)

    NaitAmor, S.; Ghalila, H.; Cohen, M. B.

    2017-01-01

    Early very low frequency (VLF) events are perturbations to subionospherically propagating VLF radio transmitters which sometimes occur when lightning activity is near the transmitter-receiver path. They are often correlated to Transient Luminous Events (TLEs). Recent analysis have focused on a new type of early events whose recovery time persists for many minutes, called LOng Recovery Events (LOREs). The underlying cause of these events is still unclear. Curiously, LOREs sometimes appear on only one path, while the same event observed on a different transmitter-receiver path does not indicate a LORE. In this paper we observe and simulate two cases of early signal perturbations: The first is a typical early VLF event, and the second is a LORE. Both were recorded by two AWESOME VLF receivers in North Africa on 12 December 2009, during the EuroSprite campaign. We combine observations with theoretical modeling to infer the electron density change that most closely reproduces the observed perturbation. Our results explain the cases where LOREs are detected on only one path as resulting from transmitter-receiver geometry significantly which impacts the modal content and therefore the observed VLF recovery time.

  6. Multi Station Frequency Response and Polarization of ELF/VLF Signals Generated via Ionospheric Modification

    Science.gov (United States)

    Maxworth, Ashanthi; Golkowski, Mark; University of Colorado Denver Team

    2013-10-01

    ELF/VLF wave generation via HF modulated ionospheric heating has been practiced for many years as a unique way to generate waves in the ELF/VLF band (3 Hz - 30 kHz). This paper presents experimental results and associated theoretical modeling from work performed at the High Frequency Active Auroral Research Program (HAARP) facility in Alaska, USA. An experiment was designed to investigate the modulation frequency dependence of the generated ELF/VLF signal amplitudes and polarization at multiple sites at distances of 37 km, 50 km and 99 km from the facility. While no difference is observed for X mode versus O mode modulation of the heating wave, it is found that ELF/VLF amplitude and polarization as a function of modulated ELF/VLF frequency is different for each site. An ionospheric heating code is used to determine the primary current sources leading to the observations.

  7. Decrease of VLF transmitter signal and Chorus-whistler waves before l'Aquila earthquake occurrence

    Directory of Open Access Journals (Sweden)

    M. Y. Boudjada

    2010-07-01

    Full Text Available We investigate the VLF emissions observed by the Instrument Champ Electrique (ICE experiment onboard the DEMETER micro-satellite. We analyze intensity level variation 10 days before and after the occurrence of l'Aquila earthquake (EQ. We found a clear decrease of the VLF received signal related to ionospheric whistler mode (mainly Chorus emission and to signal transmitted by the DFY VLF station in Germany, few days (more than one week before the earthquake. The VLF power spectral density decreases of more than two orders of magnitude until the EQ, and it recovers to normal levels just after the EQ occurrence. The geomagnetic activity is principally weak four days before EQ and increases again one day before l'Aquila seismic event. Our results are discussed in the frame of short- and long-terms earthquakes prediction focusing on the crucial role of the magnetic field of the Earth.

  8. More evidence for a one-to-one correlation between Sprites and Early VLF perturbations

    DEFF Research Database (Denmark)

    Haldoupis, C.; Amvrosiadi, N.; Cotts, B. R. T.;

    2010-01-01

    Past studies have shown a correlation between sprites and early VLF perturbations, but the reported correlation varies widely from ∼50% to 100%. The present study resolves these large discrepancies by analyzing several case studies of sprite and narrowband VLF observations, in which multiple...... for this option to be resolved we need more studies using highly sensitive optical systems capable of detecting weaker sprites, sprite halos and elves....

  9. Study of latitudinal effects on VLF transmitter signals recorded by DEMETER/ICE experiment

    Science.gov (United States)

    Boudjada, M. Y.; Schwingenschuh, K.; Berthelier, J. J.; Döller, R.; Galopeau, P. H. M.; Parrot, M.; Stangl, G.; Biernat, H.; Voller, W.; Besser, B.

    2010-05-01

    We report on VLF transmitter signals observed by the ‘Instrument Capteur Electrique' (ICE) experiment onboard the DEMETER micro-satellite. The DEMETER polar and circular sun-synchronous orbits lead to cover an invariant latitude range between -65° and +65° where up- and down-going half-orbits correspond to night-time (22:00 LT) and day-time (10:00 LT), respectively. The DEMETER orbit features permit to record signals emitted by some VLF ground-stations and detected by ICE experiment. We consider three transmitter signals emitted by stations in Europe (Germany, DFY, 16.58 kHz), in Asia (Japan, JP, 17.8 kHz) and in Australia (Australia, NWC, 19.8 kHz). We study the variation of these VLF signals taking into consideration the DEMETER satellite latitudes .We emphasis on latitudes where the satellite is close to the Earth's sub-auroral regions. We discuss particularly the presence, or not, of auroral magnetic activity effect on the VLF transmitter signals.

  10. Comparative Analysis of VLF Signal Variation along Trajectory Induced by X-ray Solar Flares

    Indian Academy of Sciences (India)

    A. Kolarski; D. Grubor

    2015-12-01

    Comparative qualitative analysis of amplitude and phase delay variations was carried out along the trajectory of GQD/22.1 kHz and NAA/24.0 kHz VLF signal traces, propagating from Skelton (UK) and Maine (USA) toward Belgrade, induced by four isolated solar X-ray flare events occurred during the period from September 2005 to December 2006. For monitoring, recording and for storage of VLF data at the Institute of Physics in Belgrade, Serbia, the AbsPAL system was used. For modeling purposes of propagating conditions along GQD and NAA signal propagation paths, LWPCv21 program code was used. Occurred solar flare events induced lower ionosphere electron density height profile changes, causing perturbations in VLF wave propagation within Earth-ionosphere waveguides. As analyzed VLF signals characterize by different propagation parameters along trajectories from their transmitters to the Belgrade receiver site, their propagation is affected in different ways for different solar flare events and also for the same solar flare events.

  11. Comparative Analysis of VLF Signal Variation along Trajectory Induced by X-ray Solar Flares

    Science.gov (United States)

    Kolarski, A.; Grubor, D.

    2015-12-01

    Comparative qualitative analysis of amplitude and phase delay variations was carried out along the trajectory of GQD/22.1 kHz and NAA/24.0 kHz VLF signal traces, propagating from Skelton (UK) and Maine (USA) toward Belgrade, induced by four isolated solar X-ray flare events occurred during the period from September 2005 to December 2006. For monitoring, recording and for storage of VLF data at the Institute of Physics in Belgrade, Serbia, the AbsPAL system was used. For modeling purposes of propagating conditions along GQD and NAA signal propagation paths, LWPCv21 program code was used. Occurred solar flare events induced lower ionosphere electron density height profile changes, causing perturbations in VLF wave propagation within Earth-ionosphere waveguides. As analyzed VLF signals characterize by different propagation parameters along trajectories from their transmitters to the Belgrade receiver site, their propagation is affected in different ways for different solar flare events and also for the same solar flare events.

  12. Cluster observations of ELF/VLF signals generated by modulated heating of the lower ionosphere with the HAARP HF transmitter

    Directory of Open Access Journals (Sweden)

    M. Platino

    2004-07-01

    Full Text Available It is now well known that amplitude modulated HF transmissions into the ionosphere can be used to generate ELF/VLF signals using the so-called "electrojet antenna". Although most observations of the generated ELF/VLF signals have been made on the ground, several low and high-altitude satellite observations have also been reported (James et al., 1990. One of the important unknowns in the physics of ELF/VLF wave generation by ionospheric heating is the volume of the magnetosphere illuminated by the ELF/VLF waves. In an attempt to investigate this question further, ground-satellite conjunction experiments have recently been conducted using the four Cluster satellites and the HF heater of the High-Frequency Active Auroral Research Program (HAARP facility in Gakona, Alaska. Being located on largely closed field lines at L≈4.9, HAARP is currently also being used for ground-to-ground type of ELF/VLF wave-injection experiments, and will be increasingly used for this purpose as it is now being upgraded for higher power operation. In this paper, we describe the HAARP installation and present recent results of the HAARP-Cluster experiments. We give an overview of the detected ELF/VLF signals at Cluster, and a possible explanation of the spectral signature detected, as well as the determination of the location of the point of injection of the HAARP ELF/VLF signals into the magnetosphere using ray tracing.

  13. Cluster observations of ELF/VLF signals generated by modulated heating of the lower ionosphere with the HAARP HF transmitter

    OpenAIRE

    Platino, M.; Inan, U.S.; Bell, T. F.; Pickett, J; Kennedy, E J; Trotignon, J. G.; Rauch, J. L.; Canu, P.

    2004-01-01

    It is now well known that amplitude modulated HF transmissions into the ionosphere can be used to generate ELF/VLF signals using the so-called "electrojet antenna". Although most observations of the generated ELF/VLF signals have been made on the ground, several low and high-altitude satellite observations have also been reported (James et al., 1990). One of the important unknowns in the physics of ELF/VLF wave generation by ionospheric heating is the volume of the magnetosphere ill...

  14. Cluster observations of ELF/VLF signals generated by modulated heating of the lower ionosphere with the HAARP HF transmitter

    OpenAIRE

    Platino, M.; U. S. Inan; Bell, T.F.; Pickett, J.; Kennedy, E.J.; J. G. Trotignon; Rauch, J.L.; P. Canu

    2004-01-01

    It is now well known that amplitude modulated HF transmissions into the ionosphere can be used to generate ELF/VLF signals using the so-called "electrojet antenna". Although most observations of the generated ELF/VLF signals have been made on the ground, several low and high-altitude satellite observations have also been reported (James et al., 1990). One of the important unknowns in the physics of ELF/VLF wave generation by ionospheric heating is the volume of the magnetosphere ill...

  15. Study of long path VLF signal propagation characteristics as observed from Indian Antarctic station, Maitri

    Science.gov (United States)

    Sasmal, Sudipta; Pal, Sujay; Chakrabarti, Sandip K.

    2014-10-01

    To examine the quality and propagation characteristics of the Very Low Frequency (VLF) radio waves in a very long propagation path, Indian Centre for Space Physics, Kolkata, participated in the 27th Indian scientific expedition to Antarctica during 2007-2008. One Stanford University made AWESOME VLF receiving system was installed at the Indian Antarctic station Maitri and about five weeks of data were recorded successfully from the Indian transmitter VTX and several other transmitting stations worldwide. The quality of the signal from the VTX transmitter was found to be very good, consistent and highly stable in day and night. The signal shows the evidences of the presence of the 24 h solar radiation in the Antarctic region during local summer. Here we report the both narrow band and broadband VLF observations from this site. The diurnal variations of VTX signal (18.2 kHz) are presented systematically for Antarctica path and also compared the same with the variations for a short propagation path (VTX-Kolkata). We compute the spatial distribution of the VTX signal along the VTX-Antarctica path using the most well-known LWPC model for an all-day and all-night propagation conditions. The calculated signal amplitudes corresponding to those conditions relatively corroborate the observations. We also present the attenuation rate of the dominant waveguide modes corresponding to those propagation conditions where the effects of the Antarctic polar ice on the attenuation of different propagating waveguide modes are visible.

  16. Study of the effect of solar flares on VLF signals during D-layer preparation or disappearance time

    Science.gov (United States)

    Ray, Suman; Chakrabarti, Sandip Kumar; Palit, Sourav

    2016-07-01

    "Very Low Frequency" (VLF) is one of the bands of the Radio waves having frequency 3-30 KHz, which propagates through the Earth-ionosphere wave-guide. In relation to propagation of radio waves through ionosphere, low mass and high mobility cause electrons to play a vital role. Electrons are not distributed uniformly in the ionosphere and depending on this factor, ionosphere has different layers namely D, E and F. Different ionospheric layers generally exist during day and night time. During day-time when the main source of the ionization of the ionosphere is Sun, the lower most layer of ionosphere is D-layer. But during the night-time when Sun is absent and cosmic ray is the main source of the ionization of the ionosphere, this D-layer disappears and E-layer becomes the lower most region of the ionosphere. Normally, patterns of VLF signal depend on regular solar flux variations. However, during solar flares extra energetic particles are released from Sun, which makes the changes in the ionization of the ionosphere and these changes can perturb VLF signal amplitude. Usually if a solar flare occurs during any time of day, it only affects the amplitude and phase of the VLF signals. But in the present work, we found the if the flare occurs during D-layer preparation / disappearance time, then it will not only affect to amplitude and phase of the VLF signals but also to terminator times of VLF signals. We have observed that the sun set terminator time of the VLF signals shifted towards night time due to the effect of a M-class solar flare which occurred during the D-layer disappearance time. The shift is so high that it crossed 5σ level. We are now trying to a make model using the ion-chemistry and LWPC code to explain this observed effect.

  17. A comparative study of measured amplitude and phase perturbations of VLF and LF radio signals induced by solar flares

    Directory of Open Access Journals (Sweden)

    Šulić D.M.

    2014-01-01

    Full Text Available Very Low Frequency (VLF and Low Frequency (LF signal perturbations were examined to study ionospheric disturbances induced by solar X-ray flares in order to understand processes involved in propagation of VLF/LF radio signals over short paths and to estimate specific characteristics of each short path. The receiver at the Belgrade station is constantly monitoring the amplitude and phase of a coherent and subionospherically propagating LF signal operated in Sicily NSC at 45.90 kHz, and a VLF signal operated in Isola di Tavolara ICV at 20.27 kHz, with the great circle distances of 953 km and 976 km, respectively. A significant number of similarities between these short paths is a direct result of both transmitters and the receiver’s geographic location. The main difference is in transmitter frequencies. From July 2008 to February 2014 there were about 200 events that were chosen for further examination. All selected examples showed that the amplitude and phase of VLF and LF signals were perturbed by solar X-ray flares occurrence. This six-year period covers both minimum and maximum of solar activity. Simultaneous measurement of amplitude and phase of the VLF/LF signals during a solar flare occurrence was applied to evaluate the electron density profile versus altitude, to carry out the function of time over the middle Europe. [Projekat Ministarstva nauke Republike Srbije, br. 176002 i br. III4402

  18. SNR changes of VLF radio signals detected onboard the DEMETER satellite and their possible relationship to the Wenchuan earthquake

    Institute of Scientific and Technical Information of China (English)

    M.; Parrot

    2009-01-01

    Here we used the VLF signal data received by the DEMETER satellite, transmitted from various ground VLF transmitters which are located around China, to study the changes in the signal to noise ratio (SNR) before and after the Wenchuan earthquake, which had a magnitude of 8.0. We also found that the SNRs of different frequency signals decreased significantly over the epicenter region before the earthquake, and reverted to their original levels after the earthquake. This phenomenon may be related to the earthquake.

  19. Statistical correlation of spectral broadening in VLF transmitter signal and low-frequency ionospheric turbulence from observation on DEMETER satellite

    Directory of Open Access Journals (Sweden)

    A. Rozhnoi

    2008-10-01

    Full Text Available In our earlier papers we have found the effect of VLF transmitter signal depression over epicenters of the large earthquakes from observation on the French DEMETER satellite that can be considered as new method of global diagnostics of seismic influence on the ionosphere. At present paper we investigate a possibility VLF signal-ionospheric turbulence interaction using additional characteristic of VLF signal-spectrum broadening. This characteristic is important for estimation of the interaction type: linear or nonlinear scattering. Our main results are the following:
    – There are two zones of increased spectrum broadening, which are centered near magnetic latitudes Φ=±10° and Φ=±40°. Basing on the previous case study research and ground ionosonde registrations, probably it is evidence of nonlinear (active scattering of VLF signal on the ionospheric turbulence. However occurrence rate of spectrum broadening in the middle-latitude area is higher than in the near-equatorial zone (~15–20% in comparison with ~100% in former area that is probably coincides with the rate of ionospheric turbulence.
    – From two years statistics of observation in the selected 3 low-latitude regions and 1 middle-latitude region inside reception area of VLF signal from NWC transmitter we find a correlation of spectrum broadening neither with ion-cyclotron noise (f=150–500 Hz, which possibly means poor representation of the turbulence by the noise due to its mixture with natural ELF emission (which correlates with whistler, nor with magnetic storm activity.
    – We find rather evident correlation of ion-cyclotron frequency noise, VLF signal depression and weak correlation of spectrum broadening with seismicity in the middle-latitude region over Japan. But in the low-latitude regions we do not find such a correlation. Statistical decrease of VLF signal supports our previous case study results. However rather weak spectrum broadening

  20. Multifractal variability of Very Low Frequency (VLF) signal during Earthquakes (M greater than 5) occurred at Greece during the year 2011-2012

    Science.gov (United States)

    Sondhiya, Deepak Kumar; Gwal, Ashok Kumar; Verma, Shivali; Kasde, Satish Kumar; Sonakia, Anjana

    In this work Wavelet Transform Modulus Maxima (WTMM) based multifractal analysis method is used to extracts the earthquake precursory signatures from scaling characteristics of subionospheric Very Low Frequency (VLF) signals. We found specific dynamics of their fractal characteristics before the earthquake, appearance of the spike in the signal and increase of the fractal dimension. We analyze VLF signals of famous Turkey Bafa transmitter (N 370 24’, E 27019’) recorded by sudden Ionospheric Disturbance (SID) monitoring station located at South of France during the Earthquake occurred at Greece during the year 2011-2012. The analysis of VLF signal during some days before and after the occurrence of earthquake has been done. Keywords: Multifractal analysis, VLF signal, Sudden Ionospheric disturbances

  1. Modeling of the lower ionospheric response and VLF signal modulation during a total solar eclipse using ionospheric chemistry and LWPC

    Science.gov (United States)

    Chakraborty, Suman; Palit, Sourav; Ray, Suman; Chakrabarti, Sandip K.

    2016-02-01

    The variation in the solar Extreme Ultraviolet (EUV) radiation flux by any measure is the most dominant natural source to produce perturbations or modulations in the ionospheric chemical and plasma properties. A solar eclipse, though a very rare phenomenon, is similarly bound to produce a significant short time effect on the local ionospheric properties. The influence of the ionizing solar flux reduction during a solar eclipse on the lower ionosphere or, more precisely, the D-region, can be studied with the observation of Very Low Frequency (VLF) radio wave signal modulation. The interpretation of such an effect on VLF signals requires a knowledge of the D-region ion chemistry, which is not well studied till date. Dominant parameters which govern the ion chemistry, such as the recombination coefficients, are poorly known. The occurrence of events such as a solar eclipse provides us with an excellent opportunity to investigate the accuracy of our knowledge of the chemical condition in this part of Earth's atmosphere and the properties which control the ionospheric stability under such disturbances. In this paper, using existing knowledge of the lower ionospheric chemical and physical properties we carry out an interpretation of the effects obtained during the total solar eclipse of 22 of July 2009 on the VLF signal. Data obtained from a week long campaign conducted by the Indian Centre for Space Physics (ICSP) over the Indian subcontinent has been used for this purpose. Both positive and negative amplitude changes during the eclipse were observed along various receiver locations. In this paper, data for a propagation path between a Indian Navy VLF transmitter named VTX3 and a pair of receivers in India are used. We start from the observed solar flux during the eclipse and calculate the ionization during the whole time span over most of the influenced region in a range of height. We incorporate a D-region ion-chemistry model to find the equilibrium ion density over

  2. Tilt - ellips and rho - phase modelling of VLF EM and VLF R in Candi Umbul Magelang

    Science.gov (United States)

    Affanti, Adella Putri; Niasari, Sintia Windhi

    2017-07-01

    A research for geothermal energy is increased due to the need of green energy. The presence of geothermal manifestations indicate the existence of geothermal system. One of the geothermal manifestations is warm spring. CandiUmbul area which located in Telomoyo, Magelang has warm spring as the geothermal manifestation. Very Low Frequency (VLF) is one of geophysical method that can be used to map the subsurface in Candi Umbul, Telomoyo. VLF is a method using electromagnetic field that powered and transferred by the transmitter. The receiver read the electromagnetic signal which induce the rock and give information about the conductivity as the physical property measurred. In this research, after collecting and processing data, we modeled tilt-ellips data of VLF-EM and rho-phase data of VLF-R to explain the geothermal system of Candi Umbul. Both VLF-EM and VLF-R model were correlated for the interpretation. The model showed an anomalous conductive feature beneath the research area. The result of this research showed that the anomaly is oriented in NW-SE direction. This direction is assumed as a fluid path way of Candi Umbul which became the outflow of Telomoyo geothermal system. To prove the early deduction this research is still on going.

  3. A study of VLF signals variations associated with the changes of ionization level in the D-region in consequence of solar conditions

    CERN Document Server

    Sulic, D M; Mihajlov, A A

    2016-01-01

    In this paper we confine our attention to the analysis of amplitude and phase data acquired by monitoring VLF/LF radio signals emitted by four European transmitters during a seven-year period (2008-2014). All the data were recorded at a Belgrade site (44.85$^{0}$ N, 20.38$^{0}$ E) by the Stanford University ELF/VLF receiver AWESOME. Propagation of VLF/LF radio signal takes place in the Earth-ionosphere waveguide and strongly depends on ionization level of the D-region, which means that it is mainly controlled by solar conditions. Some results of amplitude and phase variations on GQD/22.10 kHz, DHO/23.40 kHz, ICV/20.27 kHz and NSC/45.90 kHz radio signals measurements at short distances ($D < 2$ Mm) over Central Europe and their interpretation are summarized in this paper. Attention is restricted to regular diurnal, seasonal and solar variations including sunrise and sunset effects on propagation characteristics of four VLF/LF radio signals. We study VLF/LF propagation over short path as a superposition of d...

  4. A Probe of magnetosphere-ionosphere coupling using Very Low Frequency (VLF) Radio Signal from North-West Cape (Australia) to Kolkata (India)

    Science.gov (United States)

    Nwankwo, Victor U. J.; Chakrabarti, Sandip Kumar

    Very low frequency (VLF) radio waves has been employed for the detection and study of various terrestrial and extra-terrestrial high energy phenomena such as solar flares, solar eclipse, gamma ray burst, lightning induced electron precipitation etc., and the subsequent variations in the lower ionosphere driven by these events. In this study, we exploit the propagation characteristics of VLF signal through the Earth-ionosphere waveguide, to probe changes in ionospheric signatures, induced by solar driven variations in magnetospheric conditions. Our study is based on the VLF signal (amplitude and phase) received at the Ionospheric and Earthquake Research Centre (IERC), Sitapur, under Indian Centre for Space Physics (ICSP), which is transmitted by the Australian NWC station at about 19.8kHz.

  5. Modeling of very low frequency (VLF radio wave signal profile due to solar flares using the GEANT4 Monte Carlo simulation coupled with ionospheric chemistry

    Directory of Open Access Journals (Sweden)

    S. Palit

    2013-09-01

    Full Text Available X-ray photons emitted during solar flares cause ionization in the lower ionosphere (~60 to 100 km in excess of what is expected to occur due to a quiet sun. Very low frequency (VLF radio wave signals reflected from the D-region of the ionosphere are affected by this excess ionization. In this paper, we reproduce the deviation in VLF signal strength during solar flares by numerical modeling. We use GEANT4 Monte Carlo simulation code to compute the rate of ionization due to a M-class flare and a X-class flare. The output of the simulation is then used in a simplified ionospheric chemistry model to calculate the time variation of electron density at different altitudes in the D-region of the ionosphere. The resulting electron density variation profile is then self-consistently used in the LWPC code to obtain the time variation of the change in VLF signal. We did the modeling of the VLF signal along the NWC (Australia to IERC/ICSP (India propagation path and compared the results with observations. The agreement is found to be very satisfactory.

  6. VLF signal perturbation due to the total solar eclipse of March 2015

    Science.gov (United States)

    Nait Amor, Samir; Bouderba, Yasmina

    2016-07-01

    On March 20 2015 a total Solar eclipse occurred and covered several regions in north America, Greenland, west of Europe and north Africa with different occultation rates. During this event, many VLF paths recorded at Algiers receiver were perturbed. In this contribution, we will present a qualitative analysis of two paths (GQD and DHO) which were disturbed differently since the occultation rate at the transmitter locations was different. In addition to the qualitative study, we determined the newly formed reference height and β values at different times during the eclipse transit. From these determined parameters the time profile of the electron density is then deduced. The results showed that the new reference height, β and the electron density are different from one transmitter analysis to other due to the occultation rate difference.

  7. Solution uniquity of an inverse VLF problem: A case-study of the polar, ground-based, VLF radio signal disturbances caused by the ultra-energetic relativistic electron precipitations and of their southern boundaries

    Science.gov (United States)

    Remenets, G. F.; Astafiev, A. M.

    2016-09-01

    Here we present the results of a case study of the rare, abnormal, qualitatively specific behavior of Aldra (northern Norway) and GBR (UK) VLF transmitter signals (10-16 kHz) received at Kola Peninsula. The abnormal amplitude and the phase disturbances of signals were used as a proxy for ultra-energetic relativistic (solar?) electron precipitation (URE, ∼100 MeV) into the middle polar atmosphere. The disturbances have been observed under quiet or moderately disturbed geomagnetic activity. Based on bearing results, it was established that the abnormal variations of the electric conductivity of ionized middle atmosphere (of a sporadic Ds layer under the regular ionosphere D layer) were characterized by the following: (i) the time function of height h(t) of an effective spherical waveguide between the Earth surface and the sporadic Ds layer shows a minimum value equal to ∼30 km and (ii) the reflection coefficient R(t) of radio wave with a grazing angle of incidence from a virtual boundary with height h(t) has a minimum value equal to ∼0.4. The southern boundaries of the ultra-energetic relativistic electron precipitations have been found as well. They turned out to be not southerly than 61 degree of magnetic latitude and similar to the ones obtained in our previous study of the events for other dates under the similar geophysical conditions although we do not know anything definite about the rigidity and density of the electron fluxes. A used calculation method of analysis is based on a necessary condition that a number n of input data should be greater than a number m of output parameter-functions. We have stated by numerical testing that a decrease of n from 6 to 4 generates a lack of uniqueness of an inverse VLF problem solution for m = 2. It is important for future VLF ground-based monitoring of the URE precipitation events.

  8. A Study On The Final Phase Of The Bardarbunga Volcano Of 2015 Using Vlf Wave Of Nrk Signal Of Iceland Received At Kiel Longwave Monitor

    Directory of Open Access Journals (Sweden)

    Govinda Sharma

    2015-08-01

    Full Text Available Seismo-ionospheric changes often affect the VLF waves resulting in possible changes in the terminator times and often lead to night time fluctuations. The Bardarbunga volcano which started on 2014 ended on the last days of February of 2015. In this paper we present the results of the VLF analysis of the first three months of 2015 using a signal of 37.50 KHz where an analysis on the sunset terminator time D-layer dissipation time daytime fluctuation and night time fluctuation of the VLF amplitude was done. We contrasted the values of these parameters for the first two months of 2015 where the volcano was active with third month of 2015 when the volcano had completely subsided. The Sunset terminator time and the daytime fluctuations in the VLF amplitude for the first two months showed no major anomalies. The anomaly in the D-layer disappearance time and night time fluctuation count reached its peak values for the volcanically active months.

  9. VLF signal modulations during the total solar eclipse of 22nd July, 2009: model using D region ion chemistry and LWPC

    Science.gov (United States)

    Chakraborty, Suman; Chakrabarti, Sandip Kumar; Palit, Sourav; Ray, Suman

    2016-07-01

    One of the major sources of ionospheric perturbations is variations in solar Extreme Ultraviolet (EUV) radiation flux. Solar eclipse is a phenomenon which is capable of producing significant effects on the physical and chemical properties of the ionospheric plasma. During a solar eclipse, the solar radiation flux reduces considerably for a limited period of time over specific locations on the Earth. This induces certain changes within the ionosphere or more precisely, in the D-region which can be studied with the observation of Very Low Frequency (VLF) radio signal modulations. The parameters which mainly govern the ion-chemistry, such as the recombination coefficients are poorly known till date. Solar eclipse provides us with an excellent opportunity to study these parameters as its time of occurrence is known beforehand and thus we can equip ourselves accordingly. In the present study we considered the Total Solar Eclipse (TSE) that occurred on 22nd July, 2009 within the Indian subcontinent. Indian Centre for Space Physics (ICSP) conducted a week long campaign during the eclipse and data were recorded from dozens of places within India and abroad. Both positive and negative changes in VLF signal amplitude were observed. In this paper, data for a propagation path between Indian Navy VLF transmitter named VTX3 and a pair of receivers in India, namely Malda and Kolkata are used. We start with calculating the obscuration function for these two places to find the variations in ionization flux within the period of the eclipse. After this, we incorporated the D region ion chemistry model to find the equilibrium ion density over the region and employ the LWPC code to find the VLF signal amplitude. We varied the values of recombination coefficients to achieve desired accuracy in our results. In doing so, we achieved two goals: First, we have been able to reproduce the trend of variation in VLF signal amplitude (both positive and negative) at both the receiving locations

  10. ELF and VLF radio waves

    Science.gov (United States)

    Barr, R.; Jones, D. L.; Rodger, C. J.

    2000-11-01

    This review covers developments in ELF and VLF radio-wave propagation research over the last 50 years of the Journal of Atmospheric and Solar-Terrestrial Physics. A review of such a large field, over such a long period, cannot be fully comprehensive and the authors have therefore covered important areas which have they themselves have found interesting. The survey begins with a review of work on natural and man made sources of ELF and VLF radiation. This is followed by sections on experimental and theoretical studies of unperturbed (ambient) ELF and VLF radio propagation. Schumann resonance research, which is currently undergoing a renaissance, is then reviewed. A review of research into transient perturbations of ELF and VLF propagation follows, extending from the early work on nuclear explosions up to the current work on sprites. The review concludes with a brief summary of the VLF navigation systems of the USSR and USA, (Alpha and Omega) whose development and life-span covered most of the last 50 years.

  11. Ionosperic anomaly due to seismic activities – Part 1: Calibration of the VLF signal of VTX 18.2 KHz station from Kolkata and deviation during seismic events

    OpenAIRE

    Sasmal, S.; Chakrabarti, S. K.

    2009-01-01

    VLF signals are long thought to give away important information about the lithosphere-ionosphere coupling. In order to establish co-relations, if any, between the ionospheric activities and the earthquakes, we need to understand what the reference signals are, throughout the year. The best opportunity to do this is during the period of solar minimum where the number of flares and sunspots are negligible and the data would be primarily affected by the sun and variation would be due to normal s...

  12. Ionospheric perturbations related to the earthquake in Vrancea area on November 22, 2014, as detected by electromagnetic VLF/LF frequency signals

    Directory of Open Access Journals (Sweden)

    Maria Solovieva

    2015-11-01

    Full Text Available Data from the European network of very low/ low frequency (VLF/LF receivers has been used to study the response of the lower ionosphere to the earthquake of magnitude 5.5 in Vrancea area on November 22, 2014. Negative amplitude anomalies have been observed during 3 days before the earthquake and two days after, on the LF (45.9 kHz signal passed above the seismic area. No perturbations have been found for the same signal in control paths during this period. Other possible influences both from above and below which can produce perturbations in the ionosphere have been taken into consideration.

  13. Prediction of the Nighttime VLF Subionospheric Signal Amplitude by Using Nonlinear Autoregressive with Exogenous Input Neural Network Model

    Science.gov (United States)

    Santosa, H.; Hobara, Y.; Balikhin, M. A.

    2015-12-01

    Very Low Frequency (VLF) waves have been proposed as an approach to study and monitor the lower ionospheric conditions. The ionospheric perturbations are identified in relation with thunderstorm activity, geomagnetic storm and other factors. The temporal dependence of VLF amplitude has a complicated and large daily variabilities in general due to combinations of both effects from above (space weather effect) and below (atmospheric and crustal processes) of the ionosphere. Quantitative contributions from different external sources are not known well yet. Thus the modelling and prediction of VLF wave amplitude are important issues to study the lower ionospheric responses from various external parameters and to also detect the anomalies of the ionosphere. The purpose of the study is to model and predict nighttime average amplitude of VLF wave propagation from the VLF transmitter in Hawaii (NPM) to receiver in Chofu (CHO) Tokyo, Japan path using NARX neural network. The constructed model was trained for the target parameter of nighttime average amplitude of NPM-CHO path. The NARX model, which was built based on daily input variables of various physical parameters such as stratosphere temperature, cosmic rays and total column ozone, possessed good accuracies. As a result, the constructed models are capable of performing accurate multistep ahead predictions, while maintaining acceptable one step ahead prediction accuracy. The results of the predicted daily VLF amplitude are in good agreement with observed (true) value for one step ahead prediction (r = 0.92, RMSE = 1.99), multi-step ahead 5 days prediction (r = 0.91, RMSE = 1.14) and multi-step ahead 10 days prediction (r = 0.75, RMSE = 1.74). The developed model indicates the feasibility and reliability of predicting lower ionospheric properties by the NARX neural network approach, and provides physical insights on the responses of lower ionosphere due to various external forcing.

  14. Building and Testing a Portable VLF Receiver

    Science.gov (United States)

    McLaughlin, Robert; Krause, L.

    2014-01-01

    Unwanted emissions or signal noise is a major problem for VLF radio receivers. These can occur from man made sources such as power line hum, which can be prevalent for many harmonics after the fundamental 50 or 60 Hz AC source or from VLF radio transmissions such as LORAN, used for navigation and communications. Natural emissions can also be detrimental to the quality of recordings as some of the more interesting natural emissions such as whistlers or auroral chorus may be drowned out by the more common sferic emissions. VLF receivers must selectively filter out unwanted emissions and amplify the filtered signal to a record-able level without degrading the quality.

  15. Effects of a Solar Eclipse on the Propagation of VLF-LF Signals: Observations and Results

    Directory of Open Access Journals (Sweden)

    Barin Kumar De

    2011-01-01

    Full Text Available The results from the measurements of some of the fundamental parameters (amplitude of sferics and transmitted signal, conductivity of lower ionosphere of the ionospheric responses to the 22 July 2009 solar eclipse (partial: 91.7% are shown. This study summarizes our results from sferics signals at 81 kHz and subionospheric transmitted signals at 19.8 and 40 kHz recorded at Agartala, Tripura (latitude: 23¢XN, longitude: 91.4¢XE. We observed significant absorption in amplitude of these signals during the eclipse period compared to their ambient values for the same period during the adjacent 7 days. The signal strength along their propagation paths was controlled by the eclipse associated decrease in ionization in the D-region of the ionosphere. Waveguide mode theory calculations show that the elevation of the height of lower ionosphere boundary of the Earth-ionosphere waveguide to a value where the conductivity parameter was 106 unit. The absorption in 81 kHz sferics amplitude is high compared to the absorption in the amplitude of 40 kHz signal transmitted from Japan. The simultaneous changes in the amplitudes of sferics and in the amplitude of transmitted signals assert some sort of coupling between the upper atmosphere and the Earth¡¦s near-surface atmosphere prevailing clouds during solar eclipse.

  16. Ranking of Sudden Ionospheric Disturbances by Means of the Duration of Vlf Perturbed Signal in Agreement with Satellite X-Ray Flux Classification

    Directory of Open Access Journals (Sweden)

    Ammar Ahmed

    2016-12-01

    Full Text Available Ionosphere undergoes permanently solar flares that quickly change its properties inducing sometime unwanted effects. These changes, or events, are known as Sudden Ionospheric Disturbances (SIDs and the knowledge of their magnitude may be of great interest to anticipate probable damages. Currently, there does not exist any classification of these ionospheric changes based on their amplitude due to the wide variability of its responses. The only way to surmise their importance is to study them indirectly, throughout the classification of the X-ray flux intensity recorded by satellites. An attempt of classification based on their duration was proposed by the American Association of Variable Star Observers (AAVSO but it is not very accurate because SID’s duration is measured directly from the raw signal of the Very Low Frequency (VLF signal and/or the Low Frequency (LF signal. The aim of this work is to investigate, through a set of simple mathematical techniques applied to VLF/LF signals recorded by ground based receivers, the best method to estimate SIDs durations and then propose a new classification based on these durations.

  17. Ionospheric turbulence from ground-based and satellite VLF/LF transmitter signal observations for the Simushir earthquake (November 15, 2006

    Directory of Open Access Journals (Sweden)

    Pier Francesco Biagi

    2012-04-01

    Full Text Available

    Signals from very low frequency (VLF/ low frequency (LF transmitters recorded on the ground station at Petropavlovsk-Kamchatsky and on board the French DEMETER satellite were analyzed for the Simushir earthquake (M 8.3; November 15, 2006. The period of analysis was from October 1, 2006, to January 31, 2007. The ground and satellite data were processed by a method based on the difference between the real signal at night-time and the model signal. The model for the ground observations was the monthly averaged signal amplitudes and phases, as calculated for the quiet days of every month. For the satellite data, a two-dimensional model of the signal distribution over the selected area was constructed. Preseismic effects were found several days before the earthquake, in both the ground and satellite observations.

     

  18. Correlation of Solar X-ray Flux and SID Modified VLF Signal Strength

    Science.gov (United States)

    2015-03-26

    plotted using software provided with the SID monitors. An ideal signal during a quiescent day will be stronger at night, variable during sunrise and... software and tools to calibrate the SID monitor and connect it to a Linux- or 2-33 Windows- based computer [Loudet 2013]. Whether privately...South Africa S-0090-FB-0090 1 Hamilton Amateur Astronomers, Ancaster, Ontario, Canada S-0091 1 Instituto Geofisico Universidad Javeriana, Bogota

  19. Bispectrum Analysis of Non-linear wave-wave Interaction between VLF Transmitter signal and ELF emission on the Basis of DEMETER satellite observations

    Science.gov (United States)

    Sondhiya, Deepak Kumar; Gwal, Ashok Kumar; Kasde, Satish Kumar

    2016-07-01

    Symmetric sidebands are observed in the ionosphere by the DEMETER (Detection of Electromagnetic Radiation Transmitted through Earthquake Region) satellite, when it passes above the Indian VLF transmitter, named VTX (18.2 kHz), located near Kanyakumari, India. The spectral boarding phenomena may be divided into two types: (1) spectrally broadened components occurring without any association with ELF/VLF emissions under disturbed ionospheric condition, (2) Spectrally broadened components with predominant side band structure in association with ELF emission. Generally spectral analysis at second order (Power spectrum) is used to analyze the frequency component of signal, but it losses the phase information among the different Fourier components. To retain this information the bispectrum (third order) and/or the bicoherence (normalized bispectrum) are used. Results suggest a non-linear mode coupling between the transmitter signal and ELF emission which produces sidebands that are quasi-electrostatic in nature. However, faint spectral broadened components in both types 1 and 2 may be connected with Doppler shift of quasi-electrostatic, whistler mode waves with a broad spectrum near resonance cone, due to scattering of the transmitter signals from ionospheric irregularities in the F-region. Keywords: spectral boarding, wave-wave Interaction, whistler mode waves and Doppler shift

  20. Subionospheric VLF signatures and their association with sprites observed during EuroSprite 2003

    DEFF Research Database (Denmark)

    Mika, A.; Haldoupis, C.; Marshall, R.A.

    2005-01-01

    to sprites. Bandpass filtering of the broadband VLF signal revealed that only about 5% of the sprites were escorted by early VLF perturbations, possibly due to backscatter. Finally, by using all 131 sprites captured during EuroSprite-2003, the time lags of the sprites to the preceding +/- CG discharges were...... computed and analyzed. The time-lag distribution had a well defined tail suggesting that at least one third of the sprites observed were lagging the +/- CG discharges by more than 30 up to 300 ms. In addition these "long-delayed" sprites were not accompanied by any radio-sferics during the sprite...

  1. Ionospheric turbulence from TEC variations and VLF/LF transmitter signal observations before and during the destructive seismic activity of August and October 2016 in Central Italy

    Science.gov (United States)

    Contadakis, Michael E.; Arabelos, Demetrios N.; Vergos, George; Spatala, Spyrous; Skeberis, Christos; Xenos, Tomas D.; Biagi, Pierfrancesco; Scordilis, Emmanuel M.

    2017-04-01

    In this paper we investigate the ionospheric turbulence from TEC variations and VLF/LF transmitter signal observations before and during the disastrous seismic activity of August and October 2016 in Central Italy . The Total Electron Content (TEC) data of 8 Global Positioning System (GPS) stations of the EUREF network, which are being provided by IONOLAB (Turkey), were analysed using Discrete Fourier Analysis in order to investigate the TEC variations (Contadakis et al. 2009, Contadakis et al. 2012, Contadakis et al. 2015). The data acquired for VLF/LF signal observations are from the receiver of Thessaloniki(40.59N, 22,78E), Greece (Skeberis et al. 2015) which monitor the VLF/LF transmitters of the International Network for Frontier Research on Earthquake Precursors (INFREP). A method of normalization according to the distance between the receiver and the transmitter is applied on the above data and then they are processed by the Hilbert Huang Transform (HHT) to produce the corresponding spectra for visual analysis. The results of this investigation indicate that the High- Frequency limit fo, of the ionospheric turbulence content, increases as the site and the moment of the earthquake occurrence is approaching, pointing to the earthquake locus. In accordence ,the analyzed data from the receiver of INFREP network in Thessaloniki, Greece show that the signals from the two VLF European transmitters, Tavolara ( Italy) and Le Blanc (France), for wich the transmission path crosses the epicentral zones, indicate enhanced high frequency variations, the last ten days before the moment of the earthquake occurrence. We conclude that the LAIC mechanism through acoustic or gravity wave could explain this phenomenology. Reference Contadakis, M.E., Arabelos, D.N., Asteriadis, G., Spatalas, S.D., Pikridas, C. TEC variations over the Mediterranean during the seismic activity period of the last quarter of 2005 in the area of Greece, Nat. Hazards and Earth Syst. Sci., 8, 1267

  2. Application of an Automated System for the Processing of VLF signals to Detect, Analyze and Classify Seismic-Ionospheric Precursor Phenomena

    Science.gov (United States)

    Skeberis, Christos; Xenos, Thomas; Contadakis, Michael; Arabelos, Dimitrios; Biagi, Pier Francesco; Maggipinto, Tommaso

    2013-04-01

    This paper studies the development and application of an automated system based on Predictive Modular Neural Networks (PREMONNs) and Self Organizing Maps (SOMs) along with the necessary backend development of database classification required to provide a fully integrated system for detecting disturbances that can be attributed to seismic-ionospheric precursor phenomena using VLF radio signals. The aforementioned system can analyze all the relevant data and bring forth and adaptively discriminate different characteristics in the received signals, in real time in order to provide data segments of interest that can be correlated to subsequent seismic phenomena and can be classified with respect to pre-recorded samples of previous points of interest (POIs). PREMONNs as it was demonstrated in previous studies can be used for time-series switching detection and can be applied to the detection of POIs , whereas SOMs have been extensively used in unsupervised pattern recognition and classification of datasets. For the purpose of this paper, data acquired in Thessaloniki (40.59N, 22,78E) from the VLF station in Tavolara, Italy (ICV station Lat 40.923, Lon. 9.731) for over two years (December 2010 - December 2012) are used. The receiver was developed by Elettronika Srl, and is part of the International Network for Frontier Research on Earthquake Precursors (INFREP). The received VLF signal is normalized and then processed using the Empirical Mode Decomposition Method (EMD). The resulting data are passed to an Artificial Neural Network (ANN) based on PREMONNs trained specifically for this purpose and the output from that stage is passed onto a classifier based on SOMs to compare and classify points of interest based on a current database of received signals and identifying and storing new ones for future reference. The efficacy of the detection and the results of the aforementioned process is then discussed and results are presented. Therefore, based on the results it may be

  3. Variations of VLF/LF signals observed on the ground and satellite during a seismic activity in Japan region in May–June 2008

    Directory of Open Access Journals (Sweden)

    A. Rozhnoi

    2010-03-01

    Full Text Available Signals of two Japanese transmitters (22.2 kHz and 40 kHz recorded on the ground VLF/LF station in Petropavlovsk-Kamchatsky and on board the DEMETER French satellite have been analyzed during a seismic activity in Japan in May–June 2008. The period of analysis was from 18 April to 27 June. During this time two rather large earthquakes occurred in the north part of Honshu Island – 7 May (M=6.8 and 13 June (M=6.9. The ground and satellite data were processed by a method based on the difference between the real signal in nighttime and the model one. For ground observations a clear decrease in both signals has been found several days before the first earthquake. For the second earthquake anomalies were detected only in JJI signal. The epicenters of earthquakes were in reliable reception zone of 40 kHz signal on board the DEMETER. Signal enhancement above the seismic active region and significant signal intensity depletion in the magnetically conjugate area has been found for satellite observation before the first earthquake. Anomalies in satellite data coincide in time with those in the ground-based observation.

  4. The development of the International Network for Frontier Research on Earthquake Precursors (INFREP) by designing new analysing software and by setting up new recording locations of radio VLF/LF signals in Romania

    Science.gov (United States)

    Moldovan, Iren-Adelina; Petruta Constantin, Angela; Emilian Toader, Victorin; Toma-Danila, Dragos; Biagi, Pier Francesco; Maggipinto, Tommaso; Dolea, Paul; Septimiu Moldovan, Adrian

    2014-05-01

    Based on scientific evidences supporting the causality between earthquake preparatory stages, space weather and solar activity and different types of electromagnetic (EM) disturbances together with the benefit of having full access at ground and space based EM data, INFREP proposes a complex and cross correlated investigation of phenomena that occur in the coupled system Lithosphere-Atmosphere-Ionsophere in order to identify possible causes responsible for anomalous effects observed in the propagation characteristics of radio waves, especially at low (LF) and very low frequency (VLF). INFREP, a network of VLF (20-60 kHz) and LF (150-300 kHz) radio receivers, was put into operation in Europe in 2009, having as principal goal, the study of disturbances produced by the earthquakes on the propagation properties of these signals. The Romanian NIEP VLF / LF monitoring system consisting in a radio receiver -made by Elettronika S.R.L. (Italy) and provided by the Bari University- and the infrastructure that is necessary to record and transmit the collected data, is a part of the international initiative INFREP. The NIEP VLF / LF receiver installed in Romania was put into operation in February 2009 in Bucharest and relocated to the Black-Sea shore (Dobruja Seismologic Observatory) in December 2009. The first development of the Romanian EM monitoring system was needed because after changing the receiving site from Bucharest to Eforie we obtained unsatisfactory monitoring data, characterized by large fluctuations of the received signals' intensities. Trying to understand this behavior has led to the conclusion that the electric component of the electromagnetic field was possibly influenced by the local conditions. Starting from this observation we have run some tests and changed the vertical antenna with a loop-type antenna that is more appropriate in highly electric-field polluted environments. Since the amount of recorded data is huge, for streamlining the research process

  5. Ionosperic anomaly due to seismic activities – Part 1: Calibration of the VLF signal of VTX 18.2 KHz station from Kolkata and deviation during seismic events

    Directory of Open Access Journals (Sweden)

    S. Sasmal

    2009-08-01

    Full Text Available VLF signals are long thought to give away important information about the lithosphere-ionosphere coupling. In order to establish co-relations, if any, between the ionospheric activities and the earthquakes, we need to understand what the reference signals are, throughout the year. The best opportunity to do this is during the period of solar minimum where the number of flares and sunspots are negligible and the data would be primarily affected by the sun and variation would be due to normal sunset and sunrise effects. In this paper, we present the result of the sunrise and sunset terminators as a function of the day of the year for a period of four years, viz, 2005–2008 when the solar activity was very low. The terminators are for the 18.2 KHz VTX signal of the Indian Navy as observed from Indian Centre for Space Physics receiving station located in Kolkata. A total of 624 days of data have been used to obtain the mean plot. Any deviation of observations from this so-called the standardized calibration curve would point to influences by terrestrial (such as earthquakes and extra-terrestrial events (such as solar activities. We present examples of deviations which occur in a period of 16 months and show that the correlation with seismic events is significant and typically the highest deviation takes place up to a couple of days prior to the seismic event. Simultaneous observations of such deviations from more than one station could improve the predictability of earthquakes.

  6. Ionosperic anomaly due to seismic activities - Part 1: Calibration of the VLF signal of VTX 18.2 KHz station from Kolkata and deviation during seismic events

    Science.gov (United States)

    Sasmal, S.; Chakrabarti, S. K.

    2009-08-01

    VLF signals are long thought to give away important information about the lithosphere-ionosphere coupling. In order to establish co-relations, if any, between the ionospheric activities and the earthquakes, we need to understand what the reference signals are, throughout the year. The best opportunity to do this is during the period of solar minimum where the number of flares and sunspots are negligible and the data would be primarily affected by the sun and variation would be due to normal sunset and sunrise effects. In this paper, we present the result of the sunrise and sunset terminators as a function of the day of the year for a period of four years, viz, 2005-2008 when the solar activity was very low. The terminators are for the 18.2 KHz VTX signal of the Indian Navy as observed from Indian Centre for Space Physics receiving station located in Kolkata. A total of 624 days of data have been used to obtain the mean plot. Any deviation of observations from this so-called the standardized calibration curve would point to influences by terrestrial (such as earthquakes) and extra-terrestrial events (such as solar activities). We present examples of deviations which occur in a period of 16 months and show that the correlation with seismic events is significant and typically the highest deviation takes place up to a couple of days prior to the seismic event. Simultaneous observations of such deviations from more than one station could improve the predictability of earthquakes.

  7. VLF observations of ionospheric disturbances in association with TLEs from the EuroSprite-2007 campaign

    DEFF Research Database (Denmark)

    NaitAmor, S.; AlAbdoadaim, M. A.; Cohen, M. B.

    2010-01-01

    Two Very Low Frequency (VLF) AWESOME remote sensing systems located at Algiers, Algeria (36.45°N, 3.28°E) and Sebha, Libya (27.02°N, 14.26°E) monitor VLF signal perturbations for evidence of ionospheric disturbances. During the EuroSprite-2007 campaign a number of Transient Luminous Events (TLEs...

  8. VLF Science at Indian Centre for Space Physics

    Science.gov (United States)

    Chakrabarti, Sandip Kumar

    2016-07-01

    Indian Centre for Space Physics has been monitoring VLF signals from stations around the world at its laboratories at Kolkata and Sitapur (Ionospheric and Earthquake Research Centre) as well as at several places throughout India when in a campaign mode. We have been interested to study high energy events from space, such as solar flares and gamma ray bursts. We have made studies during multiple solar eclipses and most importantly made substantial progress in the problem of lithosphere-ionosphere coupling while understanding various types of anomalies prior to major earthquakes. Other effects such as AGWs and LEPs are being studied. We have experience of two antarctic expedition and obtained VLF data from both Maitri and Bharati stations of India, which revealed, among other things, how the signal attenuation can indicate the extent of ice mass in Antarctica. We have been able to reproduce various VLF perturbation events using Atmospheric Chemical evolution model coupled with LWPC code. For instance we have reproduced solar flare induced VLF amplitude perturbation pattern by completely ab initio calculation. We also targeted the inverse problem, namely, deduction of the injected radiation spectra from space from the VLF signal alone, thereby establishing that the Earth can be used as a gigantic detector. These interesting results would be presented in my review talk.

  9. Optimizing an ELF/VLF Phased Array at HAARP

    Science.gov (United States)

    Fujimaru, S.; Moore, R. C.

    2013-12-01

    The goal of this study is to maximize the amplitude of 1-5 kHz ELF/VLF waves generated by ionospheric HF heating and measured at a ground-based ELF/VLF receiver. The optimization makes use of experimental observations performed during ELF/VLF wave generation experiments at the High-frequency Active Auroral Research Program (HAARP) Observatory in Gakona, Alaska. During these experiments, the amplitude, phase, and propagation delay of the ELF/VLF waves were carefully measured. The HF beam was aimed at 15 degrees zenith angle in 8 different azimuthal directions, equally spaced in a circle, while broadcasting a 3.25 MHz (X-mode) signal that was amplitude modulated (square wave) with a linear frequency-time chirp between 1 and 5 kHz. The experimental observations are used to provide reference amplitudes, phases, and propagation delays for ELF/VLF waves generated at these specific locations. The presented optimization accounts for the trade-off between duty cycle, heated area, and the distributed nature of the source region in order to construct a "most efficient" phased array. The amplitudes and phases generated by modulated heating at each location are combined in post-processing to find an optimal combination of duty cycle, heating location, and heating order.

  10. Seismo-electromagnetic VLF link calibration in Europe

    Science.gov (United States)

    Eichelberger, Hans; Schwingenschuh, Konrad; Wolbang, Daniel; Besser, Bruno P.; Rozhnoi, Alexander; Solovieva, Maria; Biagi, Pier Francesco; Stachel, Manfred; Prattes, Gustav; Boudjada, Mohammed Y.; Aydogar, Özer; Zehetleitner, Sigrid; Grill, Claudia; Jernej, Irmgard

    2015-04-01

    The general background is the investigation of seismic activity with electromagnetic signals, i.e. to disentangle amplitude and phase modifications from a variety of sources. This work focus on characterisation of very low frequency (VLF) radio links between several transmitters and the Graz receiver in the current active solar cycle. Particular emphasis is on solar flares related disturbances in the Earth-ionosphere waveguide, an important dayside non-seismic influence on the VLF paths. These variations can serve as a calibration tool of the facility even for nighttime periods when different seismo-electromagnetic (SEM) methods are applied, e.g. terminator time or nighttime amplitude. Supporting data are the GOES X-ray flux measurements. As immediate objective we study individual C/M/X-class solar flare events in the sub-ionospheric VLF waveguide (amplitude fluctuations) and calculate statistical parameters with the C-class population. The used system, which is part of a broader network of receiving stations, is primarily dedicated to investigate earthquake related phenomena and associated lithospheric atmospheric ionospheric coupling mechanisms. We receive simultaneously 12 VLF transmitters (amplitude and phase measurements) from the northern hemisphere with a selected temporal resolution of 20 seconds. We conclude that the numerous C/M/X-class solar flare events, together with the the high signal-to-noise ratio of the facility, are a valuable combination for short-term VLF path characterisation in a robust manner. As outlook, due to the steady VLF measurements, a monitoring service for certain lower atmospheric variations can be envisaged.

  11. Catalogue of x-ray solar flare induced variations in sub-ionospheric very low frequency (VLF) waveguides

    Science.gov (United States)

    Eichelberger, Hans; Schwingenschuh, Konrad; Boudjada, Mohammed Y.; Besser, Bruno P.; Wolbang, Daniel; Rozhnoi, Alexander; Solovieva, Maria; Biagi, Pier F.; Stachel, Manfred; Prattes, Gustav; Aydogar, Özer; Muck, Cosima; Grill, Claudia; Jernej, Irmgard; Stachel, Thomas; Moro, Florian

    2017-04-01

    In this study we present a catalogue of solar flare induced very low frequency (VLF) variations along sub-ionospheric paths between several transmitters and the Graz seismo-electromagnetic UltraMSK receiving station. These measurements of non-seismic disturbances are important in order to carefully characterise the Earth-ionosphere VLF waveguide and disentangle possible earthquake related phenomena from natural and man-made ambient VLF amplitude and phase modifications. The period of investigation is from Jan. 2010 to April 2016, i.e. largely covers the sunspot cycle 24. In total we've 373 VLF amplitude and phase fluctuations related with C/M/X-class solar flare events (the data are from NOAA GOES x-ray flux measurements). We obtain the statistics (dependence on VLF signal vs. x-ray flux variations) for high signal-to-noise ratio VLF links under consideration of the zenith angle. We conclude, that with the mid-latitude Graz VLF knot, a part of the European receiver network, a reliable service for solar flare induced variations of the VLF waveguide can be established. In addition to complementary region-wide network multi-parameter observations this could be a crucial step towards a full characterisation of the behaviour of sub-ionospheric VLF paths including modifications related to seismic activity.

  12. The European VLF/LF radio network: current status

    Science.gov (United States)

    Biagi, Pier Francesco; Maggipinto, Tommaso; Ermini, A.

    2014-11-01

    For several years researches about correlation between seismicity and disturbances in radio broadcasting are being carried out: in particular, the Japanese Pacific VLF radio network and the European VLF-LF radio network have been developed during the last years. The European network has been developed starting from two LF receivers located in central Italy in 1996. Up to now, 11 receivers of a new type, able to sample the VLF and LF intensity of ten radio signals, are being into operation in different European countries. The daily updating of data is effective and the data bank is located at the Department of Physics of the University of Bari (Italy) which is the central node of the network. In order to discover anomalies, the software able to carry out automatically a daily data analysis by the Wavelet spectra method has been planned and realized. At the moment, the software operates on four signals (two LF and two VLF) collected by one of the receiver located in Italy. If the anomaly is particularly strong a warning system gives an advise on the work station into operation in the central node of the Network. In any case, before assuming an anomaly as a seismic anomaly, geomagnetic and meteorological data must be checked as well as any possible instrumental malfunction. At present these controls are carried out only discontinuously by the researchers of the Bari Team.

  13. ELF/VLF wave generation from the beating of two HF ionospheric heating sources

    Science.gov (United States)

    Cohen, M. B.; Moore, R. C.; Golkowski, M.; Lehtinen, N. G.

    2012-12-01

    It is well established that Extremely Low Frequency (ELF, 0.3-3 kHz) and Very Low Frequency (VLF, 3-30 kHz) radio waves can be generated via modulated High Frequency (HF, 3-10 MHz) heating of the lower ionosphere (60-100 km). The ionospheric absorption of HF power modifies the conductivity of the lower ionosphere, which in the presence of natural currents such as the auroral electrojet, creates an `antenna in the sky.' We utilize a theoretical model of the HF to ELF/VLF conversion and the ELF/VLF propagation, and calculate the amplitudes of the generated ELF/VLF waves when two HF heating waves, separated by the ELF/VLF frequency, are transmitted from two adjacent locations. The resulting ELF/VLF radiation pattern exhibits a strong directional dependence (as much as 15 dB) that depends on the physical spacing of the two HF sources. This beat wave source can produce signals 10-20 dB stronger than those generated using amplitude modulation, particularly for frequencies greater than 5-10 kHz. We evaluate recent suggestions that beating two HF waves generates ELF/VLF waves in the F-region (>150 km), and conclude that those experimental results may have misinterpreted, and can be explained strictly by the much more well established D region mechanism.

  14. VLF wave injection experiments from Siple Station, Antarctica

    OpenAIRE

    R.A., Helliwell

    1987-01-01

    The background of VLF wave-particle experiments from Siple Station, Antarctica, including wave-induced precipitation is briefly reviewed. Single frequency ducted signals that exceed a certain 'threshold' intensity are observed at the conjugate point (Roberval, Quebec) to be amplified 30-50dB, with temporal growth rates of 30-200dB/s. Following saturation, variable frequency emissions are triggered. When a second signal is added to the first, with a frequency spacing Df

  15. Models of ionospheric VLF absorption of powerful ground based transmitters

    Science.gov (United States)

    Cohen, M. B.; Lehtinen, N. G.; Inan, U. S.

    2012-12-01

    Ground based Very Low Frequency (VLF, 3-30 kHz) radio transmitters play a role in precipitation of energetic Van Allen electrons. Initial analyses of the contribution of VLF transmitters to radiation belt losses were based on early models of trans-ionospheric propagation known as the Helliwell absorption curves, but some recent studies have found that the model overestimates (by 20-100 dB) the VLF energy reaching the magnetosphere. It was subsequently suggested that conversion of wave energy into electrostatic modes may be responsible for the error. We utilize a newly available extensive record of VLF transmitter energy reaching the magnetosphere, taken from the DEMETER satellite, and perform a direct comparison with a sophisticated full wave model of trans-ionospheric propagation. Although the model does not include the effect of ionospheric irregularities, it correctly predicts the average total power injected into the magnetosphere within several dB. The results, particularly at nighttime, appear to be robust against the variability of the ionospheric electron density. We conclude that the global effect of irregularity scattering on whistler mode conversion to quasi-electrostatic may be no larger than 6 dB.

  16. The Early ULF Signal of the Gigantic Jets Revealed By Hilbert-Huang Transform

    Science.gov (United States)

    Huang, Po-Hsun; Bing-Chih Chen, Alfred

    2015-04-01

    The conventional Fourier analysis on the sferics in ULF and VLF bandpasses has been done for years. Several phenomena e.g. whistler and Schumann resonance have been well studied by the Fourier spectrum comprehensively. But the Fourier analysis is computed by an integration over time, therefore, the temporal resolution is smoothed, and limited not only by the sampling rate but also the size of the integration window. The instantaneous frequency can't be obtained through this conventional approach. We introduce the Hilbert-Huang transform (HHT) instead of Fourier transform to analyze the sferics of TLEs recorded at Lulin observatory. The Hilbert-Huang transform decomposes a signal into so-called intrinsic mode functions (IMF), and derive instantaneous frequency data by differentiating the phase angle yielded by Hilbert transform. Our analysis of HHT on several gigantic jets recorded by ground observation surprisingly revealed an early signal of frequency-change during the phase of the leading jet, and this early signal can not be identified by Fourier analysis. In the phase of leading jet, the amplitude of the sferics remains a constant and no significant features are recognized in the recorded waveform, but an obvious frequency change about 100-200 millisecond prior to the main discharge of the full development jets (FDJs), which can be clearly recognized in the HHT spectra of all observed gigantic jets. From a further simulation, this frequency change is confirmed to come from the nature of the discharge, not an alias or a false signal generated by the analysis method. This early signal may implies an in-cloud discharge process which is suggested by Krehbiel et al. [2008

  17. Observations of the impenetrable barrier, the plasmapause, and the VLF bubble during the 17 March 2015 storm

    Science.gov (United States)

    Foster, J. C.; Erickson, P. J.; Baker, D. N.; Jaynes, A. N.; Mishin, E. V.; Fennel, J. F.; Li, X.; Henderson, M. G.; Kanekal, S. G.

    2016-06-01

    Van Allen Probes observations during the 17 March 2015 major geomagnetic storm strongly suggest that VLF transmitter-induced waves play an important role in sculpting the earthward extent of outer zone MeV electrons. A magnetically confined bubble of very low frequency (VLF) wave emissions of terrestrial, human-produced origin surrounds the Earth. The outer limit of the VLF bubble closely matches the position of an apparent barrier to the inward extent of multi-MeV radiation belt electrons near 2.8 Earth radii. When the VLF transmitter signals extend beyond the eroded plasmapause, electron loss processes set up near the outer extent of the VLF bubble create an earthward limit to the region of local acceleration near L = 2.8 as MeV electrons are scattered into the atmospheric loss cone.

  18. A Global Survey of ELF/VLF Radio Noise

    Science.gov (United States)

    2002-09-30

    Smith, 2002]. Finally, our participation in one of the HAARP experimental programs, during which we made much use of the ELF/VLF radio noise data...Porrat, Teague, and Fraser-Smith, 1999]. Our objective was to make the first long-distance detection of ELF signals generated by the HAARP ...ionospheric heater; we did not succeed, but the continuing improve- ments to the HAARP heating facility in Alaska will ultimately lead to the routine

  19. Ionospheric disturbances in D-layer recorded by VLF receiver at Tashkent IHY station

    Science.gov (United States)

    Ahmedov, Bobomurat

    Tashkent International Heliophysical Year (IHY) station is a member of Atmospheric Weather Electromagnetic System for Observation, Modeling and Education (AWESOME) network being operated globally to study the ionosphere and the magnetosphere with the help of electromagnetic waves in Very Low Frequency (VLF) band. Regular monitoring of the D- and F-layers of ionosphere over Central Asia territory is being performed on the permanent basis starting year 2008. Solar flare events are permanently observed and the analysis showed that there is simultaneous correlation between the times of change of amplitude of the waves and the Solar flares. Features of the lightning discharge generated by radio atmospherics are studied and its effectiveness in D-region ionosphere diagnostics is explained. We have studied VLF amplitude anomalies related to the earthquakes (EQs) occurred in the recent years with magnitude more than 5 on the path way from the VLF transmitters to the Tashkent station assuming that propagation of VLF ground-based transmitters signals can be perturbed by EQ preparation can be detectable from the ground-based measurements in the VLF bands. For analyzing narrowband data we have used the Nighttime Fluctuation (NF) method paying attention to the data obtained during the local nighttime (20:00 LT-04:00 LT). The mean nighttime amplitude (or trend) and nighttime fluctuation are found to increase significantly before the EQ occurred on the path way from the transmitters to the receiver. The obtained results have revealed an agreement with VLF amplitude anomalies observed in Tashkent VLF station during the strong EQs occurred on the path way from the transmitters to the receiver. Some results are presented to show the probing potentiality of VLF waves to predict short term EQs with high magnitude.

  20. A new type of daytime high-frequency VLF emissions at auroral latitudes ("bird emissions")

    Science.gov (United States)

    Manninen, J.; Turunen, T.; Kleimenova, N. G.; Gromova, L. I.; Kozlovskii, A. E.

    2017-01-01

    This paper is concerned with a new, previously unknown type of high-frequency (above 4 kHz) VLF emissions that were detected during winter VLF campaigns in Kannuslehto ( L 5.5), Finland. These previously unknown emissions have been discovered as a result of the application of special digital filtering: it clears the VLF records from pulse signals of intensive atmospherics, which prevent other kinds of VLF emissions in the same frequency range from being seen on spectrograms. As it appears, aside from wellknown bursts of auroral hisses and discrete quasiperiodic emissions, a previously unknown type of daytime right-hand polarized VLF waves is also present at frequencies above 4 kHz. These emissions can persist for several hours as series of separate short discrete wideband (from 4 to 10 kHz and higher) signals, each with a duration between one and several minutes. It has been found that such signals can be observed almost daily in winter. These emissions sound like bird's chirping to a human ear; for that reason, they were called "bird emissions." The dynamic spectra of individual signals often resemble flying birds. The signals are observed during daytime, more often in magnetically quiet conditions preceded by geomagnetic disturbances. As a rule, the occurrence of these bird emissions is accompanied by a slight increase in electron density in the lower ionosphere, which is evidence of the precipitation of energetic (>30 keV) electrons. This raises a number of questions as to where and how the VLF bird emissions are generated and how such emissions, at frequencies greatly exceeding half the electron equatorial gyrofrequency at L 5.5, can reach the Earth's surface.

  1. Terrestrial VLF transmitter injection into the magnetosphere

    OpenAIRE

    2012-01-01

    Terrestrial VLF transmitter injection into the magnetosphere M. B. Cohen1 and U. S. Inan1,2 Received 1 June 2012; revised 15 June 2012; accepted 18 June 2012; published 9 August 2012. [1] Very Low Frequency (VLF, 3–30 kHz) radio waves emitted from ground sources (transmitters and lightning) strongly impact the radiation belts, driving electron precipitation via whistler-electron gyroresonance, and contributing to the formation of the slot region. However, calculations of the...

  2. Subionospehric VLF perturbations of red sprites: 3D FDTD modeling and experimental results

    Science.gov (United States)

    Iwamoto, M.; Hobara, Y.; Ohta, K.; Minatohara, T.; Otsuyama, T.; Hayakawa, M.

    2012-04-01

    Majority of red sprites occurs in association with large positive cloud to ground discharges. Although the red sprite consists of highly ionized structure, physical properties of the ionization columns such as electron density and spatial extent have not understood well. In this paper 3D finite-difference time-domain (FDTD) method carried out to compute the subionospheric VLF signal perturbations due to the sprite ionization columns. Spatial scales of columns are determined by the sprite images obtained from our optical observations during winter lightning activities over the sea of Japan. Numerical results indicate that the multiple sprites generate the complicated scattering pattern of the VLF transmitter waves depending on special orientation and extent of sprite ionization columns. Spatial dependence of the scattered amplitude are compared with those from the experimental results of VLF observation network.

  3. 100 Days of ELF/VLF Generation via HF Heating with HAARP (Invited)

    Science.gov (United States)

    Cohen, M.; Golkowski, M.

    2013-12-01

    ELF/VLF radio waves are difficult to generate with conventional antennas. Ionospheric HF heating facilities generate ELF/VLF waves via modulated heating of the lower ionosphere. HF heating of the ionosphere changes the lower ionospheric conductivity, which in the presence of natural currents such as the auroral electrojet, creates an antenna in the sky when heating is modulated at ELF/VLF frequencies. We present a summary of nearly 100 days of ELF/VLF wave generation experiments at the 3.6 MW HAARP facility near Gakona, Alaska, and provide a baseline reference of ELF/VLF generation capabilities with HF heating. Between February 2007 and August 2008, HAARP was operated on close to 100 days for ELF/VLF wave generation experiments, at a variety of ELF/VLF frequencies, seasons and times of day. We present comprehensive statistics of generated ELF/VLF magnetic fields observed at a nearby site, in the 500-3500 Hz band. Transmissions with a specific HF beam configuration (3.25 MHz, vertical beam, amplitude modulation) are isolated so the data comparison is self-consistent, across nearly 5 million individual measurements of either a tone or a piece of a frequency-time ramp. There is a minimum in the average generation close to local midnight. It is found that generation during local nighttime is on average weaker, but more highly variable, with a small number of very strong generation periods. Signal amplitudes from day to day may vary by as much as 20-30 dB. Generation strengthens by ~5 dB during the first ~30 minutes of transmission, which may be a signature of slow electron density changes from sustained HF heating. Theoretical calculations are made to relate the amplitude observed to the power injected into the waveguide and reaching 250 km. The median power generated by HAARP and injected into the waveguide is ~0.05-0.1 W in this base-line configuration (vertical beam, 3.25 MHz, amplitude modulation), but may have generated hundreds of Watts for brief durations

  4. Combined ULF and VLF observations of seismo-electro-magnetic phenomena in Europe

    Science.gov (United States)

    Schwingenschuh, Konrad; Eichelberger, Hans; Wolbang, Daniel; Prattes, Gustav; Besser, Bruno; Boudjada, Mohammed Y.; Stangl, Günter; Magnes, Werner; Berghofer, Gerhard; Aydogar, Özer; Rozhnoi, Alexander; Solovieva, Maria; Vellante, Massimo; Villante, Umberto; Biagi, Pier F.

    2014-05-01

    A combined analysis of magnetic ultra-low-frequency (ULF) and electromagnetic very-low-frequency (VLF) fluctuations before, during and after earthquakes in south and south-east Europe is presented. The magnetic fluctuations are studied in the frame of the South European Geomagnetic Array (SEGMA) network. The fluxgate and searchcoil magnetometers, located in Italy, Bulgaria and Hungary perform measurements of fluctuations in the pico-Tesla and nano-Tesla range from milli-Hertz to 100 Hz. The properties of VLF radio links (10 kHz - 50 kHz) are studied in the frame of the European VLF/LF radio receiver network (INFREP). Single parameter studies of ULF and VLF variations in the vicinity of earthquakes in Europe have been performed in the last decade (Villante et al. 2010, Rozhnoi et al. 2009). We present the first results of a dual parameter study based on single parameter ULF and VLF observations. The proposed method provides the opportunity to decrease the number of false alerts. A dual parameter seismo-electro-magnetic reliability number is developed and compared with single parameter quality numbers. References: Rozhnoi, A., Solovieva, M., Molchanov, O., Schwingenschuh, K., Boudjada, M., Biagi, P. F., Maggipinto, T., Castellana, L., Ermini, A., and Hayakawa, M.: Anomalies in VLF radio signals prior the Abruzzo earthquake (M=6.3) on 6 April 2009, Nat. Hazards Earth Syst. Sci., 9, 1727-1732, doi:10.5194/nhess-9-1727-2009, 2009. Villante, U., De Lauretis, M., De Paulis, C., Francia, P., Piancatelli, A., Pietropaolo, E., Vellante, M., Meloni, A., Palangio, P., Schwingenschuh, K., Prattes, G., Magnes, W., and Nenovski, P.: The 6 April 2009 earthquake at L'Aquila: a preliminary analysis of magnetic field measurements, Nat. Hazards Earth Syst. Sci., 10, 203-214, doi:10.5194/nhess-10-203-2010, 2010.

  5. Early Warning Signals - conceptual limitations and opportunities

    Science.gov (United States)

    Bathiany, Sebastian; Claussen, Martin; Fraedrich, Klaus

    2014-05-01

    Due to potentially large positive feedbacks in the climate system, the existence of tipping points is under debate. At these points, small changes in forcing can lead to abrupt climate change due to the destabilising feedbacks. In order to predict such abrupt changes or to distinguish changes in stability from random state transitions, it has been proposed to exploit statistical precursors of instabilities, also called early warning signals (EWS). However, we argue that the limitations of the underlying concept generally do not allow conclusions on the mechanism of abrupt changes without substantial physical knowledge - the burden of proof lies with the applier of EWS. We demonstrate these limitations with examples from vegetation dynamics and sea ice cover change in models of very different complexity. Apart from the practical problem of short and non-stationary time-series, statistical properties such as variance and autocorrelation usually change for reasons unrelated to the system's stability. In particular, it has to be known, how the natural variability (noise) in a system is caused and how it propagates through the system. A further fundamental limitation is imposed by the large number of spatial degrees of freedom. The benefit of EWS has only been shown in idealised systems of predefined spatial extent. In a more general context like a complex climate system model, the critical subsystem that exhibits a loss in stability (hotspot) and the critical mode of the transition may be unknown. An abrupt change can therefore come as a surprise. However, we suggest that EWS can be applied as a diagnostic tool to find the hotspot of a sudden transition and to distinguish this hotspot from regions experiencing an induced tipping. For this purpose we present a scheme which identifies a hotspot as a certain combination of grid cells which maximise an EWS. The method can provide information on the causality of sudden transitions and may help to improve the knowledge on

  6. FGF signalling: diverse roles during early vertebrate embryogenesis.

    Science.gov (United States)

    Dorey, Karel; Amaya, Enrique

    2010-11-01

    Fibroblast growth factor (FGF) signalling has been implicated during several phases of early embryogenesis, including the patterning of the embryonic axes, the induction and/or maintenance of several cell lineages and the coordination of morphogenetic movements. Here, we summarise our current understanding of the regulation and roles of FGF signalling during early vertebrate development.

  7. Development of ground-based ELF/VLF receiver system in Wuhan and its first results

    Science.gov (United States)

    Chen, Yanping; Yang, Guobin; Ni, Binbin; Zhao, Zhengyu; Gu, Xudong; Zhou, Chen; Wang, Feng

    2016-05-01

    A new digital low-frequency receiver system has been developed at Wuhan University for sensitive reception of low-latitude broadband Extremely Low Frequency (ELF) and Very Low Frequency (VLF) radio waves originating from either natural or artificial sources. These low-frequency radio waves are useful for ionospheric remote sensing, geospace environment monitoring, and submarine communications. This paper presents the principle and architecture of the system framework, including magnetic loop antenna design, low-noise analog front-end and digital receiver with data sampling and transmission. A new structure is adopted in the analog front end to provide high common-mode rejection and to reduce interference. On basis of field programmable gate array (FPGA) device and Universal Serial Bus (USB) architecture, the digital receiver is developed along with time keeping and synchronization module. The validity and feasibility of the self-developed ground-based ELF/VLF receiver system is evaluated by first results of experimental data that show the temporal variation of broadband ELF/VLF wave spectral intensity in Wuhan (30.54 °N, 114.37 °E). In addition to the acquisition of VLF transmitter signals at various frequencies, tweek atmospherics are also clearly captured to occur at multiple modes up to n = 6.

  8. Resonant scattering of energetic electrons in the outer radiation belt by HAARP-induced ELF/VLF waves

    Science.gov (United States)

    Chang, Shanshan; Zhu, Zhengping; Ni, Binbin; Cao, Xing; Luo, Weihua

    2016-10-01

    Several extremely low-frequency (ELF)/very low-frequency (VLF) wave generation experiments have been performed successfully at High-Frequency Active Auroral Research Program (HAARP) heating facility and the artificial ELF/VLF signals can leak into the outer radiation belt and contribute to resonant interactions with energetic electrons. Based on the artificial wave properties revealed by many of in situ observations, we implement test particle simulations to evaluate the effects of energetic electron resonant scattering driven by the HAARP-induced ELF/VLF waves. The results indicate that for both single-frequency/monotonic wave and multi-frequency/broadband waves, the behavior of each electron is stochastic while the averaged diffusion effect exhibits temporal linearity in the wave-particle interaction process. The computed local diffusion coefficients show that, the local pitch-angle scattering due to HARRP-induced single-frequency ELF/VLF whistlers with an amplitude of ∼10 pT can be intense near the loss cone with a rate of ∼10-2 rad2 s-1, suggesting the feasibility of HAARP-induced ELF/VLF waves for removal of outer radiation belt energetic electrons. In contrast, the energy diffusion of energetic electrons is relatively weak, which confirms that pitch-angle scattering by artificial ELF/VLF waves can dominantly lead to the precipitation of energetic electrons. Moreover, diffusion rates of the discrete, broadband waves, with the same amplitude of each discrete frequency as the monotonic waves, can be much larger, which suggests that it is feasible to trigger a reasonable broadband wave instead of the monotonic wave to achieve better performance of controlled precipitation of energetic electrons. Moreover, our test particle scattering simulation show good agreement with the predictions of the quasi-linear theory, confirming that both methods are applied to evaluate the effects of resonant interactions between radiation belt electrons and artificially generated

  9. 100 days of ELF/VLF generation via HF heating with HAARP

    Science.gov (United States)

    Cohen, M. B.; Gołkowski, M.

    2013-10-01

    Extremely low frequency/very low frequency (ELF/VLF) radio waves are difficult to generate with conventional antennas. Ionospheric high frequency (HF) heating facilities generate ELF/VLF waves via modulated heating of the lower ionosphere. HF heating of the ionosphere changes the lower ionospheric conductivity, which in the presence of natural currents such as the auroral electrojet creates an antenna in the sky when heating is modulated at ELF/VLF frequencies. We present a summary of nearly 100 days of ELF/VLF wave generation experiments at the 3.6 MW High Frequency Active Auroral Research Program (HAARP) facility near Gakona, Alaska, at a variety of ELF/VLF frequencies, seasons, and times of day. We present comprehensive statistics of generated ELF/VLF magnetic fields observed at a nearby site, in the 500-3500 Hz band. Transmissions with a specific HF beam configuration (3.25 MHz, vertical beam, amplitude modulation) are isolated so the data comparison is self-consistent, across nearly 5 million individual measurements of either a tone or a piece of a frequency-time ramp. There is a minimum in the average generation close to local midnight. It is found that generation during local nighttime is on average weaker but more highly variable, with a small number of very strong generation periods. Signal amplitudes from day to day may vary by as much as 20-30 dB. Generation strengthens by ˜5 dB during the first ˜30 min of transmission, which may be a signature of slow electron density changes from sustained HF heating. Theoretical calculations are made to relate the amplitude observed to the power injected into the waveguide and reaching 250 km. The median power generated by HAARP and injected into the waveguide is ˜0.05-0.1 W in this baseline configuration (vertical beam, 3.25 MHz, amplitude modulation) but may have generated hundreds of watts for brief durations. Several efficiency improvements have improved the ELF/VLF wave generation efficiency further.

  10. Study of Ionospheric Perturbations in D-Layer Using Awesome VLF Receiver Data at Tashkent Station

    Science.gov (United States)

    Ahmedov, Bobomurat

    2012-07-01

    One VLF receiver and two SuperSID receivers were provided to Uzbekistan IHY cite by Stanford University and are operating in Tashkent, under the International Heliophysical Year (IHY). The results obtained at Tashkent IHY station are applied to earthquake electromagnetic precursors, lightning, and solar flares and to ionospheric disturbances originating from gamma ray flares of Soft Gamma-Ray Repeaters connected with evolution of strongly magnetized neutron stars believed as magnetars. Regular monitoring of the D-layer of ionosphere over Central Asia territory has been performed on the permanent basis. Few Solar flare events are observed during February in 2010-2011 years and the analysis showed that there is simultaneous correlation between the times of change of amplitude of the waves and the Solar flares. Features of the lightning discharge generated by radio atmospherics are studied and its effectiveness in D-region ionosphere diagnostics is explained. Assuming that earthquakes (EQs) can be preceded by the electromagnetic signals in the VLF bands detectable from ground-based measurements we have studied VLF amplitude anomalies related to the earthquakes occurred in 2009-2010 years with magnitude more than 5 on the path way from the VLF transmitters to the Tashkent station. For analysing narrowband data we have used the Nighttime Fluctuation (NF) method paying attention to the data obtained during the local nighttime (18:00 LT-06:00 LT). The amplitude data are analysed only for the reason that perturbations are identified more clearly in the amplitude data than in phase data. The mean nighttime amplitude (or trend) and normalized trend are found to increase significantly before the EQ with the same tendency as the NF and normalized NF. The obtained results have revealed a fine agreement with VLF amplitude anomalies observed in Tashkent VLF station during the strong earthquakes occurred on the path way from the transmitters to the receiver. Some of the initial

  11. Heart Failure Protein May Signal Early Brain Damage

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_162447.html Heart Failure Protein May Signal Early Brain Damage Higher levels ... stress. Blood levels of NT-proBNP rise when heart failure worsens and fall when it gets better. Previous ...

  12. Quantitative proteomic assessment of very early cellular signaling events

    DEFF Research Database (Denmark)

    Dengjel, Joern; Akimov, Vyacheslav; Olsen, Jesper V

    2007-01-01

    Technical limitations have prevented proteomic analyses of events occurring less than 30 s after signal initiation. We developed an automated, continuous quench-flow system allowing quantitative proteomic assessment of very early cellular signaling events (qPACE) with a time resolution of 1 s...

  13. Early black hole signals at the LHC

    Science.gov (United States)

    Koch, Ben; Bleicher, Marcus; Stöcker, Horst

    2007-10-01

    The production of mini black holes due to large extra dimensions is a speculative but possible scenario. We survey estimates for di-jet suppression, and multi-mono-jet emission due to black hole production. We further look for a possible sub-scenario which is the formation of a stable or meta-stable black hole remnant (BHR). We show that the beauty of such objects is, that they are relatively easy to observe, even in the early phase of LHC running.

  14. Coordinated study of non-seismic and weak seismic events (magnitude M less than 5) using VLF radio links

    Science.gov (United States)

    Wolbang, Daniel; Biernat, Helfried K.; Friedrich, Martin; Schwingenschuh, Konrad; Besser, B. P.; Eichelberger, Hans; Prattes, Gustav; Rozhnoi, Alexander; Solovieva, Maria; Biagi, Pier Francesco; Boudjada, Mohammed Y.

    In this study we analyze low seismicity earthquakes (EQs) with magnitudes M earthquake precursor phenomena generated in the lithosphere and then propagating in the atmosphere / ionosphere [1]. The major challenge of this seismo-electromagnetic (SEM) method is to differentiate parameter variations and disentangle seismic from non-seismic sources. In the course of the European radio receiver network (International Network for Frontier Research on Earthquake Precursors, INFREP) radio signals in the VLF/LF frequency range are continuously recorded by dedicated, distributed transmitters. The major VLF receiving station for this study (10-50 kHz, Graz, Austria) operates continuously throughout the year, the selected network-wide temporal resolution is 20 sec, 12 transmitters, located mainly in Europe, are received (amplitude and phase). The facility has a proven high reliability and availability. The VLF links from the transmitters to the receivers are sometimes more, sometimes less influenced by various disturbances. In case the signal is crossing an EQ preparation zone, we are in principle able to detect seismic activity if the signal to noise ratio is high enough [2]. Generally we distinguish between ionospheric or atmospheric disturbances, influences which depend on the EQ properties, and transmitter variations itself. Ionospheric / Atmospheric variations can be generated, e.g. by geomagnetic storms, solar flares or waves in the troposphere. The properties of the sub-ionospheric VLF waveguide are affected by the length of the radio path, the distance to the EQ preparation zone, the parameters of the earthquake (magnitude, depth, type), and daytime / nighttime disturbances. In order to minimize ionospheric influences on the radio path we are considering mainly nighttime periods. Beside the terminator time method, where only the VLF sunrise and sunset period is analyzed, we are using the residual method (2 hours before and after local midnight), where the difference

  15. Lightning Location With Single-Station Observation of VLF Spherics

    Science.gov (United States)

    Nagano, I.; Yagitani, S.; Komonmae, H.; Takezono, N.

    2001-12-01

    Most of the lightning location systems recently available require the simultaneous reception of lightning-generated radio pulses (spherics) at multiple stations. In this work, we develop a lightning location system to determine both the direction and range of a lightning stroke with a single-station observation of VLF spherics. The technique used here is a rather classical one, but we try to improve the ranging accuracy by applying sophisticated signal processing techniques, and our final goal is to develop a portable lightning locator. We observe wave forms of two horizontal magnetic fields and one vertical electric field of VLF spherics, each of which usually consists of a couple of sequential pulses. The first pulse comes directly from a lightning return stroke, and is used for the direction finding of the stroke. On the other hand, the second and later pulses are the multiple reflections of the first pulse inside the Earth-ionosphere waveguide. Since the time-of-arrival (ToA) of each pulse is determined by its propagation path length in the waveguide, by using the observed difference in ToA of two or more pulses, we can inversely estimate not only the reflection height at the ionosphere but also the range of the lightning stroke. By installing the developed system at Kanazawa University, we have been observing lightning-generated spherics since April, 2000. Compared with the lightning location data provided by a local power company, preliminary analysis shows that this system can locate each lightning stroke within several hundred km with a sufficient accuracy.

  16. The impact of PMSE and NLC particles on VLF propagation

    Directory of Open Access Journals (Sweden)

    D. Nunn

    2004-04-01

    Full Text Available PMSE or Polar Mesosphere Summer Echoes are a well-known phenomenon in the summer northern polar regions, in which anomalous VHF/UHF radar echoes are returned from heights ~85km. Noctilucent clouds and electron density biteouts are two phenomena that sometimes occur together with PMSE. Electron density biteouts are electron density depletion layers of up to 90%, which may be several kms thick. Using the NOSC Modefndr code based on Wait's modal theory for subionospheric propagation, we calculate the shifts in received VLF amplitude and phase that occur as a result of electron density biteouts. The code assumes a homogeneous background ionosphere and a homogeneous biteout layer along the Great Circle Path (GCP corridor, for transmitter receiver path lengths in the range of 500–6000km.

    For profiles during the 10h about midnight and under quiet geomagnetic conditions, where the electron density at 85km would normally be less than 500el/cc, it was found that received signal perturbations were significant, of the order of 1–4dB and 5–40° of phase. Perturbation amplitudes increase roughly as the square root of frequency. At short range perturbations are rather erratic, but more consistent at large ranges, readily interpretable in terms of the shifts in excitation factor, attenuation factor and v/c ratios for Wait's modes. Under these conditions such shifts should be detectable by a well constituted experiment involving multiple paths and multiple frequencies in the north polar region in summer. It is anticipated that VLF propagation could be a valuable diagnostic for biteout/PMSE when electron density at 85km is under 500el/cc, under which circumstances PMSE are not directly detectable by VHF/UHF radars.

    Key words. Electromagnetism (wave propagation – Ionosphere (polar ionosphere – Radioscience (ionospheric propagation

  17. Ionosphere-magnetosphere studies using ground based VLF radio propagation technique: an Indian example

    Science.gov (United States)

    Chakravarty, Subhas

    Since IGY period (1957-58), natural and artificially produced Very Low Frequency (VLF) elec-tromagnetic radiations are being recorded at large number of ground stations all over the world and on-board satellites to study various radio wave-thermal/energetic plasma interactive pro-cesses related to earth's ionosphere-plasmasphere-magnetosphere environment. The terrestrial propagation of these VLF radio waves are primarily enabled through the earth ionosphere wave guide (EIWG) mode to long horizontal distances around the globe and ducted along the ge-omagnetic field lines into the conjugate hemisphere through the plasmasphere-magnetosphere regions. The time frequency spectra of the received signals indicate presence of dispersion (wave/group velocities changing with frequency) and various cut-off frequencies based on the width of the EIWG, electron gyro and plasma frequencies etc., providing several types of received signals like whistlers, chorus, tweeks, hiss and hisslers which can be heard on loud-speakers/earphones with distinguishing audio structures. While the VLF technique has been a very effective tool for studying middle and high latitude phenomena, the importance of the similar and anomalous observations over the Indian low latitude stations provide potentially new challenges for their scientific interpretation and modelling. The ducted and non-ducted magnetospheric propagation, pro-longitudinal (PL) mode, low latitude TRIMPI/TLE (Tran-sient Luminous Emissions) or other effects of wave-particle/wave-wave interactions, effects due to ionospheric irregularities and electric fields, full wave solutions to D-region ionisation per-turbations due to solar and stellar energetic X-and γ ray emissions during normal and flaring conditions are a few problems which have been addressed in these low latitude studies over India. Since the conjugate points of Indian stations lie over the Indian oceanic region, the VLF propagation effects would be relatively free from

  18. ELF/VLF Perturbations Above the Haarp Transmitter Recorded by the Demeter Satellite in the Upper Ionosphere

    Science.gov (United States)

    Titova, E. E.; Demekhov, A. G.; Mochalov, A. A.; Gvozdevsky, B. B.; Mogilevsky, M. M.; Parrot, M.

    2015-08-01

    In the studies of the data received from DEMETER (orbit altitude above the Earth is about 700 km), we detected for the first time electromagnetic perturbations, which are due to the ionospheric modification by HAARP, a high-power high-frequency transmitter, simultaneously in the extremely low-frequency (ELF, below 1200 Hz) and very low-frequency (VLF, below 20 kHz) ranges. Of the thirteen analyzed flybys of the satellite above the heated area, the ELF/VLF signals were detected in three cases in the daytime (LT = 11-12 h), when the minimum distance between the geomagnetic projections of the satellite and the heated area center on the Earth's surface did not exceed 31 km. During the nighttime flybys, the ELF/VLF perturbations were not detected. The size of the perturbed region was about 100 km. The amplitude, spectrum, and polarization of the ELF perturbations were analyzed, and their comparison with the characteristics of natural ELF noise above the HAARP transmitter was performed. In particular, it was shown that in the daytime the ELF perturbation amplitude above the heated area can exceed by a factor of 3 to 8 the amplitude of natural ELF noise. The absence of the nighttime records of artificial ELF/VLF perturbations above the heated area can be due to both the lower frequency of the heating signal, at which the heating occurs in the lower ionosphere, and the higher level of natural noise. The spectrum of the VLF signals related to the HAARP transmitter operation had two peaks at frequencies of 8 to 10 kHz and 15 to 18 kHz, which are close to the first and second harmonics of the lower-hybrid resonance in the heated area. The effect of the whistler wave propagation near the lower-hybrid resonance region on the perturbation spectrum recorded in the upper ionosphere for these signals has been demonstrated. In particular, some of the spectrum features can be explained by assuming that the VLF signals propagate in quasiresonance, rather than quasilongitudinal, regime

  19. Circuit Methods for VLF Antenna Couplers. [for use in Loran or Omega receiver systems

    Science.gov (United States)

    Burhans, R. W.

    1977-01-01

    The limitations of different E-field antenna coupler or preamplifier circuits are presented. All circuits were evaluated using actual Loran or Omega signals. Electric field whip or wire antennas are the simplest types which can be used for reception of VLF signals in the 10 to 100 kHz range. JFET or MOSFET transistors provide impedance transformation and some voltage gain in simple circuits where the power for operating the preamplifier uses the same coaxial cable that feeds the signal back to the receiver. The circuit techniques provide useful alternative methods for Loran-Omega receiver system designers.

  20. VLF emissions from ionospheric/magnetospheric plasma

    Indian Academy of Sciences (India)

    R P Patel; R P Singh

    2001-05-01

    VLF emissions such as hiss, chorus, oscillating tones, hiss-triggered chorus and whistler triggered emissions have been observed at low latitude Indian stations. In this paper we present dynamic spectra of these emissions and discuss their various observed features. It is argued that most of the emissions are generated during Doppler shifted cyclotron resonance interaction between the whistler mode wave and counter streaming energetic electrons. Resonance energy of the participating electron and interaction length are evaluated to explain the generation mechanism of some of these emissions observed at Indian stations.

  1. Characterization of early autophagy signaling by quantitative phosphoproteomics

    DEFF Research Database (Denmark)

    Rigbolt, Kristoffer Tg; Zarei, Mostafa; Sprenger, Adrian

    2014-01-01

    . To elucidate the regulation of early signaling events upon autophagy induction, we applied quantitative phosphoproteomics characterizing the temporal phosphorylation dynamics after starvation and rapamycin treatment. We obtained a comprehensive atlas of phosphorylation kinetics within the first 30 min upon...... induction of autophagy with both treatments affecting widely different cellular processes. The identification of dynamic phosphorylation already after 2 min demonstrates that the earliest events in autophagy signaling occur rapidly after induction. The data was subjected to extensive bioinformatics analysis...... of binding partners exhibiting dynamic phosphorylation patterns. The data presented here provide a valuable resource on phosphorylation events underlying early autophagy induction....

  2. Characterization of early autophagy signaling by quantitative phosphoproteomics

    DEFF Research Database (Denmark)

    Rigbolt, Kristoffer Tg; Zarei, Mostafa; Sprenger, Adrian;

    2014-01-01

    Under conditions of nutrient shortage autophagy is the primary cellular mechanism ensuring availability of substrates for continuous biosynthesis. Subjecting cells to starvation or rapamycin efficiently induces autophagy by inhibiting the MTOR signaling pathway triggering increased autophagic flux....... To elucidate the regulation of early signaling events upon autophagy induction, we applied quantitative phosphoproteomics characterizing the temporal phosphorylation dynamics after starvation and rapamycin treatment. We obtained a comprehensive atlas of phosphorylation kinetics within the first 30 min upon...

  3. Fibroblast growth factor signaling during early vertebrate development.

    Science.gov (United States)

    Böttcher, Ralph T; Niehrs, Christof

    2005-02-01

    Fibroblast growth factors (FGFs) have been implicated in diverse cellular processes including apoptosis, cell survival, chemotaxis, cell adhesion, migration, differentiation, and proliferation. This review presents our current understanding on the roles of FGF signaling, the pathways employed, and its regulation. We focus on FGF signaling during early embryonic processes in vertebrates, such as induction and patterning of the three germ layers as well as its function in the control of morphogenetic movements.

  4. The role of auxin signaling in early embryo pattern formation

    NARCIS (Netherlands)

    Smit, Margot E.; Weijers, Dolf

    2015-01-01

    Pattern formation of the early Arabidopsis embryo generates precursors to all major cell types, and is profoundly controlled by the signaling molecule auxin. Here we discuss recent milestones in our understanding of auxin-dependent embryo patterning. Auxin biosynthesis, transport and response mec

  5. Unusually high frequency natural VLF radio emissions observed during daytime in Northern Finland

    Science.gov (United States)

    Manninen, Jyrki; Turunen, Tauno; Kleimenova, Natalia; Rycroft, Michael; Gromova, Liudmila; Sirviö, Iina

    2016-12-01

    Geomagnetic field variations and electromagnetic waves of different frequencies are ever present in the Earth’s environment in which the Earth’s fauna and flora have evolved and live. These waves are a very useful tool for studying and exploring the physics of plasma processes occurring in the magnetosphere and ionosphere. Here we present ground-based observations of natural electromagnetic emissions of magnetospheric origin at very low frequency (VLF, 3-30 kHz), which are neither heard nor seen in their spectrograms because they are hidden by strong impulsive signals (sferics) originating in lightning discharges. After filtering out the sferics, peculiar emissions are revealed in these digital recordings, made in Northern Finland, at unusually high frequencies in the VLF band. These recently revealed emissions, which are observed for several hours almost every day in winter, contain short (˜1-3 min) burst-like structures at frequencies above 4-6 kHz, even up to 15 kHz; fine structure on the 1 s time scale is also prevalent. It seems that these whistler mode emissions are generated deep inside the magnetosphere, but the detailed nature, generation region and propagation behaviour of these newly discovered high latitude VLF emissions remain unknown; however, further research on them may shed new light on wave-particle interactions occurring in the Earth’s radiation belts.

  6. Initial Results from SQUID Sensor: Analysis and Modeling for the ELF/VLF Atmospheric Noise

    Directory of Open Access Journals (Sweden)

    Huan Hao

    2017-02-01

    Full Text Available In this paper, the amplitude probability density (APD of the wideband extremely low frequency (ELF and very low frequency (VLF atmospheric noise is studied. The electromagnetic signals from the atmosphere, referred to herein as atmospheric noise, was recorded by a mobile low-temperature superconducting quantum interference device (SQUID receiver under magnetically unshielded conditions. In order to eliminate the adverse effect brought by the geomagnetic activities and powerline, the measured field data was preprocessed to suppress the baseline wandering and harmonics by symmetric wavelet transform and least square methods firstly. Then statistical analysis was performed for the atmospheric noise on different time and frequency scales. Finally, the wideband ELF/VLF atmospheric noise was analyzed and modeled separately. Experimental results show that, Gaussian model is appropriate to depict preprocessed ELF atmospheric noise by a hole puncher operator. While for VLF atmospheric noise, symmetric α-stable (SαS distribution is more accurate to fit the heavy-tail of the envelope probability density function (pdf.

  7. Statistical study of seismo-ionospheric perturbations around Japan by using VLF/LF transmitters with a focal mechanism

    Science.gov (United States)

    Kawano, Tomoki; Hobara, Yasuhide; Tatsuta, Kenshin

    2016-04-01

    In this paper we perform the statistical analysis to study the response of the lower ionosphere prior to major seismic activities focusing on different earthquake types. The lower ionospheric condition is represented by daily averaged nighttime electric amplitude from various VLF/LF transmitter signals received in Japan by UEC team. Six-year record of ionospheric conditions are used for our data analysis. Over 200 earthquakes occurred around the VLF/LF transmitter - receiver paths during the time period of analysis. They are characterized into three different groups based on the Centroid-Moment-Tensor (CMT) solution such as reverse fault type, normal fault type and stress slip type. The ionospheric anomaly is identified by a large change (2 sigma criteria) in the VLF/LF daily nighttime amplitude. As a result, the highest occurrence rate of ionospheric anomaly is obtained for reverse type fault for both sea and ground earthquakes. The occurrence rate for these earthquakes are statistically significant because they are significantly large in comparison to those calculated from random test. The difference of occurrence rate of the ionospheric perturbations may indicate the coupling efficiency of seismic activity into the overlaying ionosphere originated from the pre-seismic condition of earth's crust. We also perform the trend-based earthquake prediction. Alarm threshold in nighttime VLF amplitude with -3.5 sigma is found to be most effective and significant for the earthquake prediction by using lower ionospheric perturbations.

  8. Involvement of Notch signaling in early chick ovarian follicle development.

    Science.gov (United States)

    Li, Jun; Zhao, Dan; Guo, Changquan; Li, Jian; Mi, Yuling; Zhang, Caiqiao

    2016-01-01

    The formation of primordial follicles is a crucial process in the establishment of follicle pools required for the female's reproductive life span. For laying hens, ample follicles are a prerequisite for high laying performance. Notch signaling plays critical roles in germ cell cysts breakdown and in the formation of primordial follicles. Here, we investigated the role of Notch signaling in the ovarian development of post-hatch chicks. Results showed that around post-hatch day 4 (H4), the germ cell cysts broke apart, oocytes became surrounded by squamous pregranulosa cells, and the primordial follicles were then formed. Subsequently, we detected the expression of Notch signaling-related genes including Notch receptors (Notch1, 2), ligands (Jag1, 2 and Dll1, 4), and target genes (Hes1, Hey1). These genes all showed expression at H4 and some of these genes were up-regulated during primordial follicle formation. To evaluate the Notch signaling requirement for early follicular development, we adopted an in vitro ovary culture system. Suppression of Notch signaling by γ-secretase inhibitor induced a decrease of primordial follicles and an increase of germ cells in cysts. Attenuating Notch signaling also inhibited the phosphatidylinositol 3-kinase/protein kinase B pathways and suppressed cadherin expression. These results suggest that Notch signaling is endowed with an indispensable role in primordial follicle formation in post-hatch chicks.

  9. Phosphorylation site dynamics of early T-cell receptor signaling

    DEFF Research Database (Denmark)

    Chylek, Lily A; Akimov, Vyacheslav; Dengjel, Jörn

    2014-01-01

    a systems-level understanding of how these components cooperate to control signaling dynamics, especially during the crucial first seconds of stimulation. Here, we used quantitative proteomics to characterize reshaping of the T-cell phosphoproteome in response to TCR/CD28 co-stimulation, and found...... that diverse dynamic patterns emerge within seconds. We detected phosphorylation dynamics as early as 5 s and observed widespread regulation of key TCR signaling proteins by 30 s. Development of a computational model pointed to the presence of novel regulatory mechanisms controlling phosphorylation of sites...

  10. The role of auxin signaling in early embryo pattern formation.

    Science.gov (United States)

    Smit, Margot E; Weijers, Dolf

    2015-12-01

    Pattern formation of the early Arabidopsis embryo generates precursors to all major cell types, and is profoundly controlled by the signaling molecule auxin. Here we discuss recent milestones in our understanding of auxin-dependent embryo patterning. Auxin biosynthesis, transport and response mechanisms interact to generate local auxin accumulation in the early embryo. New auxin-dependent reporters help identifying these sites, while atomic structures of transcriptional response mediators help explain the diverse outputs of auxin signaling. Key auxin outputs are control of cell identity and cell division orientation, and progress has been made towards understanding the cellular basis of each. Importantly, a number of studies have combined computational modeling and experiments to analyze the developmental role, genetic circuitry and molecular mechanisms of auxin-dependent cell division control.

  11. The European VLF/LF Radio Network: the current status

    Science.gov (United States)

    Biagi, Pier Francesco; Maggipinto, Tommaso; Schiavulli, Luigi; Ligonzo, Teresa; Colella, Roberto; Ermini, Anita; Martinelli, Giovanni; Palangio, Paolo; Moldovan, Iren; Silva, Hugo; Contadakis, Michael; Frantzis, Xenophon; Katzis, Konstantinos; Buyuksarac, Aydin; D'Amico, Sebastiano

    2014-05-01

    Since 2009 a network of VLF (20-60 kHz) and LF (150-300 kHz) radio receivers has been put into operation in Europe in order to study earthquakes precursors. At the moment the network consists of eleven receivers four of which are located in Italy, two in Greece and one in Portugal, Romania, Malta, Cyprus and Turkey. The data (sampling rate of 1min) are downloaded automatically at the end of each day and they are stored in the server located at the Department of Physics of the University of Bari (Italy), that is the central node of the network. Still, in some case, problems of connection exist. The different trends are open and visible on the web site: http://beta.fisica.uniba.it/infrep/Hom.aspx. The data files can be downloaded by the same web site but they are protected by username and password. Among the different methods of data analysis the Wavelet spectra appear to be the most sensitive ones. The software able to apply this technique on the radio data automatically at the end of each day has been planned and realized. At the moment it operates on four signals collected by one of the Italian receivers; if an anomaly stands up and it is over a fixed threshold a warning advise appears. In the web site, this activity is protected by a specific username and password.

  12. New type of ensemble of quasi-periodic, long-lasting VLF emissions at the auroral zone

    Directory of Open Access Journals (Sweden)

    J. Manninen

    2012-12-01

    Full Text Available A new type of the series of quasi-periodic (QP very low frequency (VLF emissions in frequency range of 1–5 kHz, and not associated with geomagnetic pulsations, has been discovered at auroral latitudes (L = 5.3 during the Finnish VLF campaign (held in December 2011. At least five unusually spectacular events, each with a duration of several hours, have been observed during the night under conditions of quiet geomagnetic activity (Kp = 0–1, although QPs usually occur during the daytime. Contrary to the QP emissions typically occurring during the day, the spectral structure of these QP events represented an extended, complicated sequence of repeated discrete rising VLF signals. Their duration was about 2–3 min each, with the repetition periods ranging from ~1 min to ~10 min. Two such nighttime non-typical events are reported in this paper. The fine structure of the separated QP elements may represent a mixture of the different frequency band signals, which seem to have independent origins. It was found that the periodic signals with lower frequency appear to trigger the strong dispersive upper frequency signals. The temporal dynamics of the spectral structure of the QPs studied were significantly controlled by some disturbances in the solar wind and interplanetary magnetic field (IMF. This finding is very important for future theoretical investigations because the generation mechanism of this new type of QP emissions is not yet understood.

  13. On the numerical modelling of VLF chorus dynamical spectra

    Directory of Open Access Journals (Sweden)

    D. Nunn

    2009-06-01

    Full Text Available This paper presents a study of the use of a one-dimensional Vlasov Hybrid Simulation (VHS computer code to simulate the dynamical spectra (i.e. frequency versus time spectrograms of ELF/VLF chorus signals (from ~a fraction to ~10 kHz. Recently excellent measurements of chorus have been made in the source region close to the geomagnetic equator aboard the four spacecraft Cluster mission. Using Cluster data for wave amplitude, which is up to 300 pT, local gyrofrequency, cold plasma density, and L-shell, observed chorus signals are reproduced with remarkable fidelity and, in particular, sweep rates in the range 1–10 kHz result as observed. Further, we find that the sweep rate is a falling function of increasing cold plasma density, again in accord with observations. Finally, we have satisfactorily simulated the rather rare falling frequency elements of chorus which are sometimes observed aboard Cluster in the generation region. For both rising and falling chorus we have presented detailed structural analyses of the generation regions. The main contributor to the frequency sweep rate is primarily the establishment of wave number/frequency gradients across the generation region by the out of phase component of the resonant particle current. The secondary contributor is the shortening of the wavelength of resonant particle current relative to that of the wave field. In view of the close agreement between observation and simulation, we conclude that nonlinear electron cyclotron resonance is indeed the mechanism underlying the generation of chorus signals just outside the plasmasphere.

  14. Investigations of natural and artificial disturbances in the Earth-ionosphere cavity via VLF radio links for the time span 2009-2015 (sunspot cycle 24)

    Science.gov (United States)

    Eichelberger, Hans; Schwingenschuh, Konrad; Besser, B. P.; Prattes, Gustav; Aydogar; Wolbang, Daniel; Rozhnoi, Alexander; Solovieva, Maria; Biagi, Pier Francesco; Boudjada, Mohammed

    2016-07-01

    We focus on natural disturbances of the sub-ionospheric VLF waveguide in the time span 2009 to 2015 (sunspot cycle 24), i.e. variations in amplitude and phase measurements of the radio paths are considered. In particular we're investigating numerous solar flares (up to X-class), geomagnetic storms and substorms, therefore discuss how to discriminate natural from artificial variations between different transmitters and receivers. Meteorological effects could be important [1] and we estimate the possibility to detect the influence of lithospheric sources in the VLF radio links. As part of the VLF multistation network we're using the single receiver mid-latitude station in Graz, Austria. This facility receives up to 12 transmitter simultaneously (frequency range 10-50 kHz), has 20 sec temporal resolution, and is running continuously since 2009 [2]. We obtain the statistics relating VLF amplitude and phase fluctuations with C/M/X-class solar flares, and characterise night time fluctuations in connection with enhanced particle precipitation in the northern latitude path (Iceland transmitter). The statistics is important to improve the quality of seismo-electromagnetic studies. We conclude that for ionospheric perturbations (D-layer), e.g. solar flares, a reliable real time monitoring service can be established. Atmospheric and lithospheric variations are generally difficult to characterise, it's harder to distinguish between natural and man made signals, therefore - as a future outlook - complementary ground and satellite based measurements can deliver valuable additional information for environmental monitoring. References: [1] A. Rozhnoi et al.: Meteorological effects in the lower ionosphere as based on VLF/LF signal observations, Nat. Hazards Earth Syst. Sci., 14, 2671-2679, 2014. [2] K. Schwingenschuh et al.: The Graz seismo-electromagnetic VLF facility, Nat. Hazards Earth Syst. Sci., 11, 1121-1127, 2011.

  15. Canonical Sonic Hedgehog Signaling in Early Lung Development

    Directory of Open Access Journals (Sweden)

    Hugo Fernandes-Silva

    2017-03-01

    Full Text Available The canonical hedgehog (HH signaling pathway is of major importance during embryonic development. HH is a key regulatory morphogen of numerous cellular processes, namely, cell growth and survival, differentiation, migration, and tissue polarity. Overall, it is able to trigger tissue-specific responses that, ultimately, contribute to the formation of a fully functional organism. Of all three HH proteins, Sonic Hedgehog (SHH plays an essential role during lung development. In fact, abnormal levels of this secreted protein lead to severe foregut defects and lung hypoplasia. Canonical SHH signal transduction relies on the presence of transmembrane receptors, such as Patched1 and Smoothened, accessory proteins, as Hedgehog-interacting protein 1, and intracellular effector proteins, like GLI transcription factors. Altogether, this complex signaling machinery contributes to conveying SHH response. Pulmonary morphogenesis is deeply dependent on SHH and on its molecular interactions with other signaling pathways. In this review, the role of SHH in early stages of lung development, specifically in lung specification, primary bud formation, and branching morphogenesis is thoroughly reviewed.

  16. Deep ocean early warning signals of an Atlantic MOC collapse

    CERN Document Server

    Feng, Qing Yi; Dijkstra, Henk A

    2014-01-01

    The Atlantic Meridional Overturning Circulation (MOC) is a crucial part of the climate system because of its associated northward heat transport. The present-day MOC is sensitive to freshwater anomalies and may collapse to a state with a strongly reduced northward heat transport. A future collapse of the Atlantic MOC has been identified as one of the most dangerous tipping points in the climate system. It is therefore crucial to develop early warning indicators for such a potential collapse based on relatively short time series. So far, attempts to use indicators based on critical slowdown have been marginally successful. Based on complex climate network reconstruction, we here present a promising new indicator for the MOC collapse that efficiently monitors spatial changes in deep ocean circulation. Through our analysis of the performance of this indicator we formulate optimal locations of measurement of the MOC to provide early warning signals of a collapse. Our results imply that an increase in spatial reso...

  17. VLF Perturbations Associated with Solar Eclipses of November 2012 and may 2013 IN the South Pacific Region

    Science.gov (United States)

    Kumar, S.; Kumar, A.

    2015-12-01

    Sub-ionospheric VLF signals from the NWC (19.8 kHz), NPM (21.4 kHz) and NLK (24.8 kHz) MSK VLF transmitters are monitored at Suva, Fiji, with a time resolution of 0.1s using GPS based timing and SoftPAL VLF system. Here one minute averaged amplitude and phase data have been used for analysis. We present perturbations in VLF propagation and D-region changes associated with 13 November 2012 total solar eclipse (SE) and 9-10 May 2013 annular SE using VLF observations at Suva, Fiji. During 13-14 November 2012 total SE, the totality shadow intercepted NWC-Suva path and NWC signal amplitude and phase decreased by about 0.70 dB and 23°, respectively. NPM signal amplitude during 9-10 May 2013 SE decreased by about 2.0 dB. The amplitude perturbation of ~1.8 dB on NLK signal was measured from the unperturbed level associated with 9-10 May 2013 SE. The decrease in the amplitude at the site can be understood in terms of destructive interference of modes converted at the discontinuity created by the eclipse intercepting the different Transmitter-receiver great circle paths (TRGCPs) and changes in the propagation conditions along TRGCPs. The decrease in the amplitude and phase of NWC signal for 13-14 November 2012 SE has been modeled using Long Wave Propagation Capability code to estimate the changes in D-region reflection height (H') and sharpness factor (β) which shows that H' and β were increased by 0.95 km and 0.01 km-1, respectively. The phase changes on NWC signal associated with 9-10 May 2013 SE have been used to estimate the recombination coefficient value, for 75 km height where electron density reduction due to SE was about 40%. The changes in the D-region parameters and the electron density are due to sudden decrease of the photo-ionization creating nighttime like conditions in the D-region ionosphere.

  18. Numerical modelling of VLF radio wave propagation through earth-ionosphere waveguide and its application to sudden ionospheric disturbances

    CERN Document Server

    Pal, Sujay

    2015-01-01

    In this thesis, we theoretically predict the normal characteristics of Very Low Frequency (3~30 kHz) radio wave propagation through Earth-ionosphere waveguide corresponding to normal behavior of the D-region ionosphere. We took the VLF narrow band data from the receivers of Indian Centre for Space Physics (ICSP) to validate our models. Detection of sudden ionospheric disturbances (SIDs) are common to all the measurements. We apply our theoretical models to infer the D-region characteristics and to reproduce the observed VLF signal behavior corresponding to such SIDs. We develop a code based on ray theory to simulate the diurnal behavior of VLF signals over short propagation paths (2000~3000 km). The diurnal variation from this code are comparable to the variation obtained from a more general Long Wave Propagation Capability (LWPC) code which is based on mode theory approach. We simulate the observational results obtained during the Total Solar Eclipse of July 22, 2009 in India. We also report and simulate a h...

  19. Effect of the total solar eclipse of March 20, 2015, on VLF/LF propagation

    Science.gov (United States)

    Solovieva, M. S.; Rozhnoi, A. A.; Fedun, V.; Schwingenschuh, K.

    2016-05-01

    The analyzed amplitude and phase variations in electromagnetic VLF and LF signals at 20-45 kHz, received in Moscow, Graz (Austria), and Sheffield (UK) during the total solar eclipse of March 20, 2015, are considered. The 22 analyzed paths have lengths of 200—6100 km, are differently oriented, and cross 40-100% occultation regions. Fifteen paths crossed the region where the occultation varied from 40 to 90%. Solar eclipse effects were found only on one of these paths in the signal phase (-50°). Four long paths crossed the 90-100% occultation region, and signal amplitude and phase anomalies were detected for all four paths. Negative phase anomalies varied from-75° to-90°, and the amplitude anomalies were both positive and negative and were not larger than 5 dB. It was shown that the effective height of the ionosphere varied from 6.5 to 11 km during the eclipse.

  20. Early-warning signals of topological collapse in interbank networks

    CERN Document Server

    Squartini, Tiziano; Garlaschelli, Diego

    2013-01-01

    The financial crisis marked a paradigm shift, from traditional studies of individual risk to recent research on the "systemic risk" generated by whole networks of institutions. However, the reverse effects of realized defaults on network topology are poorly understood. Here we analyze the Dutch interbank network over the period 1998-2008, ending with the global crisis. We find that many topological properties, after controlling for overall density effects, display an abrupt change in 2008, thus providing a clear but unpredictable signature of the crisis. By contrast, if the intrinsic heterogeneity of banks is controlled for, the same properties undergo a slow and continuous transition, gradually connecting the crisis period to a much earlier stationary phase. This early-warning signal begins in 2005, and is preceded by an even earlier period of "risk autocatalysis" characterized by anomalous debt loops. These remarkable precursors are undetectable if the network is reconstructed from partial bank-specific inf...

  1. Early warning signals of desertification transitions in semiarid ecosystems

    Science.gov (United States)

    Corrado, Raffaele; Cherubini, Anna Maria; Pennetta, Cecilia

    2014-12-01

    The identification of early warning signals for regime shifts in ecosystems is of crucial importance given their impact in terms of economic and social effects. We present here the results of a theoretical study on the desertification transition in semiarid ecosystems under external stress. We performed numerical simulations based on a stochastic cellular automaton model, and we studied the dynamics of the vegetation clusters in terms of percolation theory, assumed as an effective tool for analyzing the geometrical properties of the clusters. Focusing on the role played by the strength of external stresses, measured by the mortality rate m , we followed the progressive degradation of the ecosystem for increasing m , identifying different stages: first, the fragmentation transition occurring at relatively low values of m , then the desertification transition at higher mortality rates, and finally the full desertification transition corresponding to the extinction of the vegetation and the almost complete degradation of the soil, attained at the maximum value of m . For each transition we calculated the spanning probabilities as functions of m and the percolation thresholds according to different spanning criteria. The identification of the different thresholds is proposed as an useful tool for monitoring the increasing degradation of real-world finite-size systems. Moreover, we studied the time fluctuations of the sizes of the biggest clusters of vegetated and nonvegetated cells over the entire range of mortality values. The change of sign in the skewness of the size distributions, occurring at the fragmentation threshold for the biggest vegetation cluster and at the desertification threshold for the nonvegetated cluster, offers new early warning signals for desertification. Other new and robust indicators are given by the maxima of the root-mean-square deviation of the distributions, which are attained respectively inside the fragmentation interval, for the

  2. Early life stress experience may blunt hypothalamic leptin signalling.

    Science.gov (United States)

    Lee, J H; Yoo, S B; Kim, J Y; Lee, J Y; Kim, B T; Park, K; Jahng, J W

    2017-03-01

    The aim of this study was to investigate whether neonatal maternal separation (MS) - chronic stress experience in early life - affects the anorectic efficacy of leptin in the offspring at adolescence. Sprague-Dawley pups were separated from the dam daily for 3 h during postnatal day 1-14 or left undisturbed as non-handled controls (NH). NH and MS male pups received an intraperitoneal leptin (100 μg/kg) or saline on postnatal day (PND) 28, and then food intake and body weight gain were recorded. The hypothalamic levels of leptin-signalling-related genes, phosphorylated signal transducer and activator of transcription-3 (pSTAT3) and protein-tyrosine phosphatase 1B (PTP1B) were examined at 40 min after a single injection of leptin on PND 39 by immunohistochemistry and Western blot analysis. Leptin-induced suppressions in food intake and weight gain was observed in NH pups, but not in MS. Leptin increased pSTAT3 in the hypothalamic arcuate nucleus of NH pups, but not of MS. Interestingly, basal levels of the hypothalamic PTP1B and pSTAT3 were increased in MS pups compared with NH controls. The results suggest that neonatal MS experience may blunt the anorectic efficacy of leptin later in life, possibly in relation with increased expressions of PTP1B and/or pSTAT3 in the hypothalamus.

  3. Early-warning signals for an outbreak of theinfluenza pandemic

    Institute of Scientific and Technical Information of China (English)

    Ren Di; Gao Jie

    2011-01-01

    Over the course of human history,influenza pandemics have been seen as major disasters,so studies on the influenza virus have become an important issue for many experts and scholars.Comprehensive research has been performed over the years on the biological properties,chemical characteristics,external environmental factors and other aspects of the virus,and some results have been achieved.Based on the chaos game representation walk model,this paper uses the time series analysis method to study the DNA sequences of the influenza virus from 1913 to 2010,and works out the early-warning signals indicator value for the outbreak of an influenza pandemic.The variances in the CGR walk sequences for the pandemic years (or + -1 to 2 years) are significantly higher than those for the adjacent years,while those in the non-pandemic years are usually smaller.In this way we can provide an influenza early-warning mechanism so that people can take precautions and be well prepared prior to a pandemic.

  4. An aerostat-supported ELF/VLF transmitter

    Science.gov (United States)

    Field, E. C., Jr.; Kies, L. R.; Bannister, P. R.; Ingram, R. F.; Hopkins, W. D.; Roberts, M. A.

    1989-03-01

    A demonstration of an aerostat-supported extremely low frequency/very low frequency (ELF/VLF) transmitting antenna was performed. At ELF the vertical electric dipole (VED) antenna radiated at least 100,000 times more power than would a horizontal electric dipole having the same moment. That efficiency was achieved with an altitude of 12,500 feet (3810 m). Calculations show that the radiated power will increase as the fourth power of aerostat altitude. The tether antenna exhibited a corona onset voltage of 180 kV and was resistant to the degrading effects of ELF corona. Prolonged in-corona operation is therefore possible. The antenna was continuously tuned, despite changes in height and capacitance caused by the aerostat flight dynamics. The huge 300-H ELF tuning inductor posed no problem. Enhanced VED moments were achieved at ELF by operation at voltages up to 260 kV, 40% above the corona onset voltage. At VLF the antenna emulated a monopole that had a radiation efficiency greater than 90%. The measured bandwidths were large: 1.5 kHz at 23 kHz and 3.5 kHz at 34 kHz. The antenna height exceeded one-quarter wavelength at VLF, so the antenna could be tuned capacitively and required relatively low base voltages. At both VLF and ELF the measured fields agreed closely with predictions.

  5. INSPIRE: A VLF Radio Project for High School Students

    Science.gov (United States)

    Marshall, Jill A.; Pine, Bill; Taylor, William W. L.

    2007-01-01

    Since 1988 the Interactive NASA Space Physics Ionospheric Radio Experiment, or INSPIRE, has given students the opportunity to build research-quality VLF radio receivers and make observations of both natural and stimulated radio waves in the atmosphere. Any high school science class is eligible to join the INSPIRE volunteer observing network and…

  6. Characteristic of Tweek Atmospherics Observed in Mid-latitude using AWESOME VLF Receiver

    Directory of Open Access Journals (Sweden)

    Norbayah Yusop

    2014-03-01

    Full Text Available This study presents the analysis of tweek atmospherics received by AWESOME VLF receiver at station of Gakona (62.71°N, 143.99°W during four months observation from January to April 2011. Tweek which originates from lightning discharge are used to monitor the nighttime D-region ionosphere using the fundamental cut-off frequency to measure the variations of the lower ionosphere’s reflection height, the equivalent electron density at the reflection height and the propagation distance travel by tweeks. In this study, a total of 1316 tweeks are analyzed and from the analysis, it shows that equinox’s season has the highest tweek occurrence compared to winter season in March and April. The maximum harmonic (m of t weeks is found to be up to fourth ( m = 4 and tweeks with mode number one (m = 1 are more dominantly occurred. Our observations indicate that the equivalent electron densities for tweeks varies from 22-27 eL/cm3 in the altitude ranged of 75 to 91 km and demonstrate that these ELF/VLF signals travel considerable distances up to 6700 km from the causative lightning discharges. The ionospheric parameters for three locations (high, middle and low latitude respectively were compared and the results show that they are almost consistent for all the locations.

  7. Spatial early warning signals in a lake manipulation

    Science.gov (United States)

    Butitta, Vince L; Carpenter, Stephen R; Loken, Luke; Pace, Michael L; Stanley, Emily H.

    2017-01-01

    Rapid changes in state have been documented for many of Earth's ecosystems. Despite a growing toolbox of methods for detecting declining resilience or early warning indicators (EWIs) of ecosystem transitions, these methods have rarely been evaluated in whole-ecosystem trials using reference ecosystems. In this study, we experimentally tested EWIs of cyanobacteria blooms based on changes in the spatial structure of a lake. We induced a cyanobacteria bloom by adding nutrients to an experimental lake and mapped fine-resolution spatial patterning of cyanobacteria using a mobile sensor platform. Prior to the bloom, we detected theoretically predicted spatial EWIs based on variance and spatial autocorrelation, as well as a new index based on the extreme values. Changes in EWIs were not discernible in an unenriched reference lake. Despite the fluid environment of a lake where spatial heterogeneity driven by biological processes may be overwhelmed by physical mixing, spatial EWIs detected an approaching bloom suggesting the utility of spatial metrics for signaling ecological thresholds.

  8. An Artificial Particle Precipitation Technique Using HAARP-Generated VLF Waves

    Science.gov (United States)

    2006-11-02

    AFRL-VS-HA-TR-2007-1021 An Artificial Particle Precipitation Technique Using HAARP -Generated VLF Waves O o o r- Q M. J. Kosch T. Pedersen J...Artificial Particle Precipitation Technique Using HAARP Generated VLF Waves. 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 62101F...model. The frequency-time modulated VLF wave patterns have been successfully implemented at the HAARP ionospheric modification facility in Alaska

  9. VLF Tan Delta Measurement for Used XLPE Power Cables

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Woo Sang; Ha, Che Wung; Joo, Kwang Ho [Korea Hydro and Nuclear Power Co., Daejeon (Korea, Republic of)

    2011-05-15

    Medium voltage power cables in nuclear power plants are currently managed through the visual inspection or by monitoring environmental factors such as the temperature and radiation levels. However, these methods are insufficient to monitor aging degradation of power cables. The NRC requires an additional monitoring program to detect the aged degradation, especially for safety-related power cables which are inaccessible or installed underground. EPRI suggested that very low frequency (VLF) tan {delta} test be included in MV power cable diagnostic programs. In addition, the VLF tan {delta} test was recently adopted for domestic submarine distribution cable diagnostics. KEPRI suggested that the impacts of leakage current should be controlled in VLF tan {delta} test for the submarine cables. As a pre-process to develop such a program, tan {delta} tests have been performed for 4.16 kV cables which were removed from the domestic nuclear power plant after approximate 30 years of service to analyze the degradation of long time serviced cables and the effect of leakage current from the both ends of cables

  10. A Novel Approach of Impulsive Signal Extraction for Early Fault Detection of Rolling Element Bearing

    Directory of Open Access Journals (Sweden)

    Hu Aijun

    2017-01-01

    Full Text Available The fault signals of rolling element bearing are often characterized by the presence of periodic impulses, which are modulated high-frequency harmonic components. The features of early fault in rolling bearing are very weak, which are often masked by background noise. The impulsiveness of the vibration signal has affected the identification of characteristic frequency for the early fault detection of the bearing. In this paper, a novel approach based on morphological operators is presented for impulsive signal extraction of early fault in rolling element bearing. The combination Top-Hat (CTH is proposed to extract the impulsive signal and enhance the impulsiveness of the bearing fault signal, and the envelope analysis is applied to reveal the fault-related signatures. The impulsive extraction performance of the proposed CTH is compared with that of finite impulse response filter (FIR by analyzing the simulated bearing fault signals, and the result indicates that the CTH is more effective in extracting impulsive signals. The method is evaluated using real fault signals from defective bearings with early rolling element fault and early fault located on the outer race. The results show that the proposed method is able to enhance the impulsiveness of early bearing fault signals.

  11. Microenvironments and Signaling Pathways Regulating Early Dissemination, Dormancy, and Metastasis

    Science.gov (United States)

    2016-09-01

    the MMTV- Neu -CFP model and we have also performed single cell RNA-seq which will allow us in the next year to identify the early and late gene...signatures in DTCs we proposed in our grant. 15. SUBJECT TERMS dormancy, early dissemination, EMT, macrophages, TMEM 16. SECURITY CLASSIFICATION OF: 17

  12. Retinoic Acid Signaling during Early Spinal Cord Development

    Directory of Open Access Journals (Sweden)

    Ruth Diez del Corral

    2014-06-01

    Full Text Available Retinoic acid signaling is required at several steps during the development of the spinal cord, from the specification of generic properties to the final acquisition of neuronal subtype identities, including its role in trunk neural crest development. These functions are associated with the production of retinoic acid in specific tissues and are highly dependent on context. Here, we review the defects associated with retinoic acid signaling manipulations, mostly in chick and mouse models, trying to separate the different processes where retinoic acid signaling is involved and to highlight common features, such as its ability to promote transitions along the neuronal differentiation cascade.

  13. Biomechanical properties of early keratoconus: Suppressed deformation signal wave.

    Science.gov (United States)

    Hashemi, Hassan; Beiranvand, Asghar; Yekta, Abbasali; Asharlous, Amir; Khabazkhoob, Mehdi

    2017-04-01

    To examine the diagnostic validity of different corneal biomechanical parameters for the detection of early keratoconus METHODS: Sixty-one eyes with a diagnosis of early keratoconus and 61 topographically normal eyes were enrolled in the study. All participants underwent testing with the Ocular Response Analyzer (ORA), and 40 indices from each cornea were included in the analysis. The mean (standard deviation: SD) of keratometry and central corneal thickness in keratoconic corneas was 46.9 (2.5) diopter (D) and 473 (31) μm, respectively. Of the 40 evaluated indices, 32 showed a significant difference between the two groups using t-test (pkeratoconus (pkeratoconus. The best predictors of keratoconus in its early stages are H2(1) and CRF which showed very high sensitivity and specificity for the detection of early keratoconus. Copyright © 2016 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  14. Sugar signalling during germination and early seedling establishment in Arabidopsis

    NARCIS (Netherlands)

    Dekkers, S.J.W.

    2006-01-01

    Sugars have pronounced effects on many plant processes like gene expression, germination and early seedling development. Several screens for sugar insensitive mutants were performed to identify genes involved in sugar response pathways using the model plant Arabidopsis. These include sun, gin and si

  15. Alcohol Expectancy Responses from Teenagers: The Early Forewarning Signals

    OpenAIRE

    B., Sandhya; B.M.S., Carol; M.S., Kotian; B, Ganaraja

    2013-01-01

    Background: The Indian population is overwhelmed by the rapid developmental activities in the new millennium. This has brought in urbanization and several banes of the faster life. Alcoholism is one among the menaces which have to be tackled at an early stage.

  16. An Fgf-Shh signaling hierarchy regulates early specification of the zebrafish skull

    Science.gov (United States)

    McCarthy, Neil; Sidik, Alfire; Bertrand, Julien Y.; Eberhart, Johann K.

    2016-01-01

    The neurocranium generates most of the craniofacial skeleton and consists of prechordal and postchordal regions. Although development of the prechordal is well studied, little is known of the postchordal region. Here we characterize a signaling hierarchy necessary for postchordal neurocranial development involving Fibroblast growth factor (Fgf) signaling for early specification of mesodermally-derived progenitor cells. The expression of hyaluron synthetase 2 (has2) in the cephalic mesoderm requires Fgf signaling and Has2 function, in turn, is required for postchordal neurocranial development. While Hedgehog (Hh)-deficient embryos also lack a postchordal neurocranium, this appears primarily due to a later defect in chondrocyte differentiation. Inhibitor studies demonstrate that postchordal neurocranial development requires early Fgf and later Hh signaling. Collectively, our results provide a mechanistic understanding of early postchordal neurocranial development and demonstrate a hierarchy of signaling between Fgf and Hh in the development of this structure. PMID:27060628

  17. Microenvironments and Signaling Pathways Regulating Early Dissemination, Dormancy, and Metastasis

    Science.gov (United States)

    2016-09-01

    in different target organs. We then processed them using the C1 Fluidigm system and submitted these samples for RNAseq analysis. This effort was...microenvironment. Plans for the coming year: We will receive complete RNAseq data soon and perform bioinformatics analysis to compare the expression...protocol to obtain single-cell RNASeq using C1 Single-Cell and Illumina Systems. This pipeline was applied for single cell analysis from early cancer

  18. Microenvironments and Signaling Pathways Regulating Early Dissemination, Dormancy, and Metastasis

    Science.gov (United States)

    2015-09-01

    metastases (overt and micrometastases) (Fig. 1E- F). Macro-metastases originating from early cancer cell mammospheres displayed a glandular phenotype but...whether a HER2+/P-p38lo profile was linked to the partial or total activation of an epithelium to mesenchyme transition program 19. Treatment of MCF10A...metastasis found in nude mice injected with MMTV-HER2 mammospheres (upper left). Upper right, shows differentiated glandular ductal structures found within

  19. [Signal exchange between plants and Arbuscular Mycorrhizae fungi during the early stage of symbiosis - A review].

    Science.gov (United States)

    Duan, Qianqian; Yang, Xiaohong; Huang, Xianzhi

    2015-07-04

    Much is known about Arbuscular Mycorrhizae (AM), an important component of the ecosystem, whereas little is known about the signal exchange that allows mutual recognition and reprograming for the anticipated physical interaction. This review addresses the latest advances of signal exchange between plants and AM, including signal substances and their function, related genes and regulation function in the early stage of plant-fungal symbiosis.

  20. Earthquake early warning system using real-time signal processing

    Energy Technology Data Exchange (ETDEWEB)

    Leach, R.R. Jr.; Dowla, F.U.

    1996-02-01

    An earthquake warning system has been developed to provide a time series profile from which vital parameters such as the time until strong shaking begins, the intensity of the shaking, and the duration of the shaking, can be derived. Interaction of different types of ground motion and changes in the elastic properties of geological media throughout the propagation path result in a highly nonlinear function. We use neural networks to model these nonlinearities and develop learning techniques for the analysis of temporal precursors occurring in the emerging earthquake seismic signal. The warning system is designed to analyze the first-arrival from the three components of an earthquake signal and instantaneously provide a profile of impending ground motion, in as little as 0.3 sec after first ground motion is felt at the sensors. For each new data sample, at a rate of 25 samples per second, the complete profile of the earthquake is updated. The profile consists of a magnitude-related estimate as well as an estimate of the envelope of the complete earthquake signal. The envelope provides estimates of damage parameters, such as time until peak ground acceleration (PGA) and duration. The neural network based system is trained using seismogram data from more than 400 earthquakes recorded in southern California. The system has been implemented in hardware using silicon accelerometers and a standard microprocessor. The proposed warning units can be used for site-specific applications, distributed networks, or to enhance existing distributed networks. By producing accurate, and informative warnings, the system has the potential to significantly minimize the hazards of catastrophic ground motion. Detailed system design and performance issues, including error measurement in a simple warning scenario are discussed in detail.

  1. Early life stress experience may blunt hypothalamic leptin signalling

    Indian Academy of Sciences (India)

    JH LEE; SB YOO; JY KIM; JY LEE; BT KIM; K PARK; JW JAHNG

    2017-03-01

    The aim of this study was to investigate whether neonatal maternal separation (MS) – chronic stress experience inearly life – affects the anorectic efficacy of leptin in the offspring at adolescence. Sprague–Dawley pups wereseparated from the dam daily for 3 h during postnatal day 1–14 or left undisturbed as non-handled controls (NH).NH and MS male pups received an intraperitoneal leptin (100 μg/kg) or saline on postnatal day (PND) 28, and thenfood intake and body weight gain were recorded. The hypothalamic levels of leptin-signalling-related genes,phosphorylated signal transducer and activator of transcription-3 (pSTAT3) and protein-tyrosine phosphatase 1B(PTP1B) were examined at 40 min after a single injection of leptin on PND 39 by immunohistochemistry and Westernblot analysis. Leptin-induced suppressions in food intake and weight gain was observed in NH pups, but not in MS.Leptin increased pSTAT3 in the hypothalamic arcuate nucleus of NH pups, but not of MS. Interestingly, basal levelsof the hypothalamic PTP1B and pSTAT3 were increased in MS pups compared with NH controls. The results suggestthat neonatal MS experience may blunt the anorectic efficacy of leptin later in life, possibly in relation with increasedexpressions of PTP1B and/or pSTAT3 in the hypothalamus.

  2. The Search for VLF Precursors to Major Earthquakes: A Case Study with the M9.0 Earthquake of 11-Mar-2011 (Invited)

    Science.gov (United States)

    Cohen, M.; Kosovichev, P.; Marshall, R. A.; Droscoll, A.; Scherrer, D. K.

    2013-12-01

    It has been proposed that Very Low Frequency (VLF, 3-30 kHz) radio remote sensing may be used to detect ionospheric changes which may precede major earthquakes by hours or days. We report the results of a search for VLF precursors to the M9.0 Tohoku earthquake of 11-Mar-2011, the fifth most powerful earthquake in recorded history. Broadband and narrowband radio recordings were made at a site in Onagawa, Japan located ~102 km from the epicenter. The receiver operated for about two minutes after the start of the earthquake, after which the receiver lost power. Examination of the VLF data shows no radio emissions preceding or coincident with the onset of the earthquake. However, once the secondary seismic waves reached the receiver, a number of impulses and diffuse noise bands arose which may result from the entire power grid shaking or from radio emissions from compressing or fracturing rocks. Examination of the ELF data (0.2-1 kHz) shows no precursor effect in the hours preceding the seismic activity. We also examine the amplitudes of VLF subionospherically propagating transmitter signals going back months before the earthquake. We apply previously proposed techniques to extract properties of the diurnal amplitude profile that have been thought to correlate with earthquake precursors, but find no anomalous effect despite the remarkable intensity of the earthquake and proximity of the receiver to the epicenter. In general there are anomalous deviations but they cannot be reliably correlated with seismic activity. We also report the results of a global search for a lightning precursor effect on lightning flash rates, using the GLD360 network.

  3. Early redox, Src family kinase, and calcium signaling integrate wound responses and tissue regeneration in zebrafish.

    Science.gov (United States)

    Yoo, Sa Kan; Freisinger, Christina M; LeBert, Danny C; Huttenlocher, Anna

    2012-10-15

    Tissue injury can lead to scar formation or tissue regeneration. How regenerative animals sense initial tissue injury and transform wound signals into regenerative growth is an unresolved question. Previously, we found that the Src family kinase (SFK) Lyn functions as a redox sensor in leukocytes that detects H(2)O(2) at wounds in zebrafish larvae. In this paper, using zebrafish larval tail fins as a model, we find that wounding rapidly activated SFK and calcium signaling in epithelia. The immediate SFK and calcium signaling in epithelia was important for late epimorphic regeneration of amputated fins. Wound-induced activation of SFKs in epithelia was dependent on injury-generated H(2)O(2). A SFK member, Fynb, was responsible for fin regeneration. This work provides a new link between early wound responses and late regeneration and suggests that redox, SFK, and calcium signaling are immediate "wound signals" that integrate early wound responses and late epimorphic regeneration.

  4. Electric and VLF-MT survey of Tegatayama tunnel; Tegatayama tunnel no denki tansa oyobi VLF tansa

    Energy Technology Data Exchange (ETDEWEB)

    Nishitani, T. [Akita University, Akita (Japan). Mining College

    1997-05-27

    To survey the structure at the depth between 20 and 30 m, field tests were conducted by means of vertical electric and VFL-MT (magnetotelluric) survey. Tegatayama tunnel has a total length of 276 m, width of 7.5 m, and height of 4.7 m, and the depth from the surface is about 28 m near the top of mountain. Near the tunnel, the thickness of surface soil is about 60 cm, which consists of clay soil including soft mudstone gravel. It was found that terrace deposit is distributed up to the depth of 8 m, and that mudstone is distributed below the depth of 8 m. Weighted four-electrode method was adopted for the vertical electrical survey. Measurements were conducted at the immediately above the tunnel, 10 m apart from the center of tunnel in the right and left, and 20 m apart from the center in the east. For the VLF-MT method, component of frequency 22.2 kHz was used. As a result of the tests, it was difficult to illustrate the existence of tunnel from the vertical electrical survey only at one point. Feature of the tunnel could be well illustrated by means of the VLF-MT method. 3 refs., 9 figs.

  5. Interpretation of VLF-EM & VLF-R data using tipper and impedance analyses: A case study from Candi Umbul-Telomoyo, Magelang, Indonesia

    Science.gov (United States)

    Prastyani, Erina; Niasari, Sintia Windhi

    2017-07-01

    The goal of all geophysical survey techniques is to image the properties of the Earth's subsurface. Very Low Frequency (VLF) is one of the geophysical survey technique that has been commonly used for ore exploration and mapping faults or fracture zones. Faults or fracture zones are necessary components in providing the fluid pathway in geothermal systems. The Candi Umbul-Telomoyo is one of the geothermal prospect sites in Indonesia, which is located in Magelang, Central Java. Recent studies hypothesized that this site was an outflow area of Telomoyo volcano geothermal complex. We used the VLF-EM and VLF-R techniques to infer faults or fracture zones that might be a path for geothermal fluids in the Candi Umbul-Telomoyo. From the measurements, we got tilt angle, ellipticity, primary and secondary magnetic fieldfor VLF-EM data; and apparent resistivity, phase angle, electric and magnetic field for VLF-R data. To interpret the data, we used tipper and impedance analyses. The result of both analyses show similarities in the directions and positions of anomalous current concentrations. We conclude these anomalous current concentrations as faults. Our interpretation is agreeing with the Geologic Map of the Semarang and Magelang Quadrangles that shows the expected fault beneath the Mt. Telomoyo.

  6. Multiple-Station Observation of Frequency Dependence and Polarization Characteristics of ELF/VLF waves generated via Ionospheric Modification

    Science.gov (United States)

    Maxworth, A. S.; Golkowski, M.; Cohen, M.; Moore, R. C.

    2014-12-01

    Generation of Extremely Low Frequency (ELF) and Very Low Frequency (VLF) signals through ionospheric modification has been practiced for many years. Heating the lower ionosphere with high power HF waves allows for modulation of natural current systems. Our experiments were carried out at the High Frequency Active Auroral Research Program (HAARP) facility in Alaska, USA. In this experiment, the ionosphere was heated with a vertical amplitude modulating signal and the modulation frequency was changed sequentially within an array of 40 frequencies followed by a frequency ramp. The observed magnetic field amplitude and polarization of the generated ELF/VLF signals were analyzed for multiple sites and as a function of modulation frequency. Our three observation sites: Chistochina, Paxson and Paradise are located within 36km (azimuth 47.7°), 50.2km (azimuth -20°) and 99km (azimuth 80.3°) respectively. We show that the peak amplitudes observed as a function of frequency result from vertical resonance in the Earth-ionosphere waveguide and can be used to diagnose the D-region profile. Polarization analysis showed that out of the three sites Paxson shows the highest circularity in the magnetic field polarization, compared to Chistochina and Paradise which show highly linear polarizations. The experimental results were compared with a theoretical simulation model results and it was clear that in both cases, the modulated Hall current dominates the observed signals at Chistochina and Paradise sites and at Paxson there is an equal contribution from Hall and Pedersen currents. The Chistochina site shows the highest magnetic field amplitudes in both experimental and simulation environments. Depending upon the experimental and simulation observations at the three sites, a radiation pattern for the HAARP ionospheric heater can be mapped

  7. Studies on different geophysical and extra-terrestrial events within the Earth-ionosphere cavity in terms of ULF/ELF/VLF radio waves

    Science.gov (United States)

    Sanfui, Minu; Haldar, D. K.; Biswas, Debasish

    2016-10-01

    The space between the two spherical conducting shells, Earth surface and the lower boundary of the ionosphere, behaves as a spherical cavity in which some electromagnetic signals can propagate a long distance and is called Earth-ionosphere waveguide. Through this waveguide ultra low frequency (ULF), extremely low frequency (ELF) and very low frequency (VLF) signals can propagate efficiently with low attenuation. Resonances which occur for ELF waves due to round-the-world propagation interfering with 2n π phase difference are called Schumann resonances. Lightnings are the main sources of energy continuously producing these electromagnetic radiations from the troposphere. Some fixed frequency signals are also transmitted through the waveguide from different stations for navigation purposes. The intensity and phase of these signals at a particular position depend on the waveguide characteristics which are highly influenced by different natural events. Thus the signatures of different geophysical and extra-terrestrial events may be investigated by studying these signals through proper monitoring of the time series data using suitable techniques. In this article, we provide a review on ULF, ELF and VLF signals within the waveguide in terms of different geophysical and extra-terrestrial events like lightning, earthquakes, Leonid meteor shower, solar flares, solar eclipse, geomagnetic storms, and TLEs etc.

  8. Insights into the early evolution of animal calcium signaling machinery: a unicellular point of view.

    Science.gov (United States)

    Cai, Xinjiang; Wang, Xiangbing; Patel, Sandip; Clapham, David E

    2015-03-01

    The basic principles of Ca(2+) regulation emerged early in prokaryotes. Ca(2+) signaling acquired more extensive and varied functions when life evolved into multicellular eukaryotes with intracellular organelles. Animals, fungi and plants display differences in the mechanisms that control cytosolic Ca(2+) concentrations. The aim of this review is to examine recent findings from comparative genomics of Ca(2+) signaling molecules in close unicellular relatives of animals and in common unicellular ancestors of animals and fungi. Also discussed are the evolution and origins of the sperm-specific CatSper channel complex, cation/Ca(2+) exchangers and four-domain voltage-gated Ca(2+) channels. Newly identified evolutionary evidence suggests that the distinct Ca(2+) signaling machineries in animals, plants and fungi likely originated from an ancient Ca(2+) signaling machinery prior to early eukaryotic radiation.

  9. Modeling distinct imaging hemodynamics early after TBI: the relationship between signal amplitude and connectivity.

    Science.gov (United States)

    Medaglia, John D; McAleavey, Andrew A; Rostami, Sohayla; Slocomb, Julia; Hillary, Frank G

    2015-06-01

    Over the past decade, fMRI studies of cognitive change following traumatic brain injury (TBI) have investigated blood oxygen level dependent (BOLD) activity during working memory (WM) performance in individuals in early and chronic phases of recovery. Recently, BOLD fMRI work has largely shifted to focus on WM and resting functional connectivity following TBI. However, fundamental questions in WM remain. Specifically, the effects of injury on the basic relationships between local and interregional functional neuroimaging signals during WM processing early following moderate to severe TBI have not been examined. This study employs a mixed effects model to examine prefrontal cortex and parietal lobe signal change during a WM task, the n-back, and whether there is covariance between regions of high amplitude signal change, (synchrony of elicited activity (SEA) very early following TBI. We also examined whether signal change and SEA differentially predict performance during WM. Overall, percent signal change in the right prefrontal cortex (rPFC) was and important predictor of both reaction time (RT) and SEA in early TBI and matched controls. Right prefrontal cortex (rPFC) percent signal change positively predicted SEA within and between persons regardless of injury status, suggesting that the link between these neurodynamic processes in WM-activated regions remains unaffected even very early after TBI. Additionally, rPFC activity was positively related to RT within and between persons in both groups. Right parietal (rPAR) activity was negatively related to RT within subjects in both groups. Thus, the local signal intensity of the rPFC in TBI appears to be a critical property of network functioning and performance in WM processing and may be a precursor to recruitment observed in chronic samples. The present results suggest that as much research moves toward large scale functional connectivity modeling, it will be essential to develop integrated models of how local and

  10. Characterisation of very low frequency (VLF) fluctuations at the Graz receiver knot in the INFREP system

    Science.gov (United States)

    Eichelberger, H. U.; Prattes, G.; Schwingenschuh, K.; Wolbang, D.; Boudjada, M. Y.; Rozhnoi, A.; Solovieva, M.; Biagi, P. F.; Maggipinto, T.; Stachel, M.; Jernej, I.; Aydogar, Ö.; Besser, B. P.

    2012-04-01

    In the frame of the European VLF/LF radio receiver network (International Network for Frontier Research on Earthquake Precursors - INFREP) we investigate radio paths between several transmitters and receivers, among them the Graz VLF facility. For this knot the data coverage spans more than two years of continuous samples from 11 transmitters with a network wide 20 seconds temporal resolution. The main scientific objective is the characterisation of VLF fluctuations in amplitude and phase related with artificial and natural sources, e.g. disturbances due to seismic phenomena. Examples of VLF disturbances due to seismic activity are given by Rozhnoi et al. (2009) and complementary investigations are carried out by Prattes et al. (2011). For VLF usually the (i) nighttime amplitude variations and (ii) terminator time methods are used. They have been regularly applied in data analysis of seismic events mainly in Asian area. Paths crossing the earthquake preparation zone and control links are used for earthquake events. Various VLF waveguide properties are important, e.g. the length of the individual paths, the lower lithospheric-surface boundary and the upper {day, night}-time ionospheric {D, E}-layer physics. Beside the nominal diurnal and seasonal behaviour we are measuring natural variations, e.g. solar flare effects and manmade noise, i.e. local disturbances related with the urban environment of the receiver location. Measurements indicate that above a threshold of magnitude M 5 the methods are successful applicable. We show for a time span of more than two years how VLF fluctuations and their seasonal variations relate with atmospheric parameters, e.g. temperatures, zonal wind, and heat- and momentum-fluxes and discuss the impact on seismic event detection via VLF methods. Complementary ground- and satellite-based investigations, e.g. in nearby ULF or LF frequency ranges, are useful.

  11. A multiple receiver - multiple transmitter VLF high-order differential analysis evaluation network for near real-time detection and discrimination of seismic-ionospheric precursor phenomena

    Science.gov (United States)

    Skeberis, Christos; Zaharis, Zaharias; Xenos, Thomas; Spatalas, Spyridon; Stratakis, Dimitrios; Maggipinto, Tommaso; Biagi, Pier francesco

    2016-04-01

    This study provides an evaluation of the application of high-order differential analysis on VLF signals on a multiple-receiver multiple-transmitter network. This application provides a method for near-real-time detection of disturbances that can be attributed to seismic-ionospheric precursor phenomena and can discriminate disturbances that could be classified as false positives and thus should be attributed to other geomagnetic influences. VLF data acquired in Thessaloniki, Greece (40.59N, 22,78E) Herakleion, Greece (35.31N, 25.10E), Nicosia, Cyprus (35.17N, 33.35E), Italy (42.42N, 13.08E) and transmitted by the VLF station in Tavolara, Italy (ICV station 40.923N, 9.731E) and the station in Keflavik, Iceland (ICE 64.02N, 22.57W) from January 2015 to January 2016 were used for the purpose of this paper. The receivers have been developed by Elettronika Srl and are part of the International Network for Frontier Research on Earthquake Precursors (INFREP). The process applied for this study has been further developed and is based on differential analysis. The signals undergo transformation using an enhanced version of the Hilbert Huang Transform, and relevant spectra are produced. On the product of this process, differential analysis is applied. Finally, the method produces the correlation coefficient of signals that are on the same path over an earthquake epicenter in order to highlight disturbances, and on the opposite can make comparisons with unrelated transmitted signals of different paths to eliminate disturbances that are not localized to the area of interest. This improvement provides a simple method of noise cancellation to signals that would otherwise be considered as false positives. A further evaluation of the method is provided with the presentation and discussion of sample results. The method seems to be a robust tool of analysis of VLF signals and also an automatic detection tool with built-in noise cancellation of outside disturbances.

  12. One day prediction of nighttime VLF amplitudes using nonlinear autoregression and neural network modeling

    Science.gov (United States)

    Santosa, H.; Hobara, Y.

    2017-01-01

    The electric field amplitude of very low frequency (VLF) transmitter from Hawaii (NPM) has been continuously recorded at Chofu (CHF), Tokyo, Japan. The VLF amplitude variability indicates lower ionospheric perturbation in the D region (60-90 km altitude range) around the NPM-CHF propagation path. We carried out the prediction of daily nighttime mean VLF amplitude by using Nonlinear Autoregressive with Exogenous Input Neural Network (NARX NN). The NARX NN model, which was built based on the daily input variables of various physical parameters such as stratospheric temperature, total column ozone, cosmic rays, Dst, and Kp indices possess good accuracy during the model building. The fitted model was constructed within the training period from 1 January 2011 to 4 February 2013 by using three algorithms, namely, Bayesian Neural Network (BRANN), Levenberg Marquardt Neural Network (LMANN), and Scaled Conjugate Gradient (SCG). The LMANN has the largest Pearson correlation coefficient (r) of 0.94 and smallest root-mean-square error (RMSE) of 1.19 dB. The constructed models by using LMANN were applied to predict the VLF amplitude from 5 February 2013 to 31 December 2013. As a result the one step (1 day) ahead predicted nighttime VLF amplitude has the r of 0.93 and RMSE of 2.25 dB. We conclude that the model built according to the proposed methodology provides good predictions of the electric field amplitude of VLF waves for NPM-CHF (midlatitude) propagation path.

  13. On the effectiveness of the vlf-em method For ground water prospecting in the Basement terrains, Sinai, Egypt

    OpenAIRE

    Shendi, El-Arabi Hendi [العربيى هندي شندي

    1997-01-01

    The VLF-EM method is proved to be an effective, fast and inexpensive tool for ground water prospecting in the basement terrains of Southern Sinai. The resistive shallow alluvial deposits increase the penetration depth of the received VLF waves to as deep as 40 meters which is very reasonable to detect the water bearing alluvium in the studied areas. The measured horizontal and vertical components of the resultant VLF-EM field were used to calculate the apparent resistivities of the conductive...

  14. Canonical Wnt signaling promotes early hematopoietic progenitor formation and erythroid specification during embryonic stem cell differentiation.

    Directory of Open Access Journals (Sweden)

    Anuradha Tarafdar

    Full Text Available The generation of hematopoietic stem cells (HSCs during development is a complex process linked to morphogenic signals. Understanding this process is important for regenerative medicine applications that require in vitro production of HSC. In this study we investigated the effects of canonical Wnt/β-catenin signaling during early embryonic differentiation and hematopoietic specification using an embryonic stem cell system. Our data clearly demonstrates that following early differentiation induction, canonical Wnt signaling induces a strong mesodermal program whilst maintaining a degree of stemness potential. This involved a complex interplay between β-catenin/TCF/LEF/Brachyury/Nanog. β-catenin mediated up-regulation of TCF/LEF resulted in enhanced brachyury levels, which in-turn lead to Nanog up-regulation. During differentiation, active canonical Wnt signaling also up-regulated key transcription factors and cell specific markers essential for hematopoietic specification, in particular genes involved in establishing primitive erythropoiesis. This led to a significant increase in primitive erythroid colony formation. β-catenin signaling also augmented early hematopoietic and multipotent progenitor (MPP formation. Following culture in a MPP specific cytokine cocktail, activation of β-catenin suppressed differentiation of the early hematopoietic progenitor population, with cells displaying a higher replating capacity and a propensity to form megakaryocytic erythroid progenitors. This bias towards erythroid lineage commitment was also observed when hematopoietic progenitors were directed to undergo myeloid colony formation. Overall this study underscores the importance of canonical Wnt/β-catenin signaling in mesodermal specification, primitive erythropoiesis and early hematopietic progenitor formation during hematopoietic induction.

  15. Canonical Wnt signaling promotes early hematopoietic progenitor formation and erythroid specification during embryonic stem cell differentiation.

    Science.gov (United States)

    Tarafdar, Anuradha; Dobbin, Edwina; Corrigan, Pamela; Freeburn, Robin; Wheadon, Helen

    2013-01-01

    The generation of hematopoietic stem cells (HSCs) during development is a complex process linked to morphogenic signals. Understanding this process is important for regenerative medicine applications that require in vitro production of HSC. In this study we investigated the effects of canonical Wnt/β-catenin signaling during early embryonic differentiation and hematopoietic specification using an embryonic stem cell system. Our data clearly demonstrates that following early differentiation induction, canonical Wnt signaling induces a strong mesodermal program whilst maintaining a degree of stemness potential. This involved a complex interplay between β-catenin/TCF/LEF/Brachyury/Nanog. β-catenin mediated up-regulation of TCF/LEF resulted in enhanced brachyury levels, which in-turn lead to Nanog up-regulation. During differentiation, active canonical Wnt signaling also up-regulated key transcription factors and cell specific markers essential for hematopoietic specification, in particular genes involved in establishing primitive erythropoiesis. This led to a significant increase in primitive erythroid colony formation. β-catenin signaling also augmented early hematopoietic and multipotent progenitor (MPP) formation. Following culture in a MPP specific cytokine cocktail, activation of β-catenin suppressed differentiation of the early hematopoietic progenitor population, with cells displaying a higher replating capacity and a propensity to form megakaryocytic erythroid progenitors. This bias towards erythroid lineage commitment was also observed when hematopoietic progenitors were directed to undergo myeloid colony formation. Overall this study underscores the importance of canonical Wnt/β-catenin signaling in mesodermal specification, primitive erythropoiesis and early hematopietic progenitor formation during hematopoietic induction.

  16. Lightning and ionospheric remote sensing using VLF/ELF radio atmospherics

    Science.gov (United States)

    Cummer, Steven Andrew

    Lightning discharges radiate the bulk of their electromagnetic energy in the Very Low Frequency (VLF, 3- 30 kHz) and Extremely Low Frequency (ELF, 3-3000 Hz) frequency ranges. This energy, contained in impulse-like signals called radio atmospherics or sferics, is guided for long distances by multiple reflections from the ground and lower ionosphere. These two facts suggest that observed sferic waveforms radiated from lightning contain a great deal of information about both the state of the ionosphere along the propagation path and the dynamics of the current in the lightning return stroke. The aim of this dissertation is to develop and implement the necessary techniques to use sferic observations to determine the characteristics of the ionosphere and lightning. In this work, a quantitative model of sferic propagation is developed, and with it the spectral characteristics of VLF (> 1.5 kHz) sferics are shown to depend primarily on the propagation-path-averaged ionospheric D region electron density profile. Using this propagation model, a parameterized ionosphere is iteratively varied to find the theoretical sferic spectrum that agrees best with an observed sferic spectrum composed of the average of many individual sferic spectra. In most nighttime cases, the quality of the agreement allows the height of an exponentially-varying electron density profile to be inferred with a precision of 0.2 km. Since the general sferic waveform depends on the source current-moment waveform as well as the ionospherically- controlled propagation, the former quantity can be measured for individual discharges from observed sferics. Of particular interest are those lightning discharges associated with mesospheric optical emissions known as sprites. By using a robust deconvolution technique, source current-moment waveforms are extracted from individual observed ELF (< 1.5 kHz) sferics. The cases studied in detail show that optical emissions are sometimes produced with a smaller vertical

  17. Critical slowing down as an early warning signal for financial crises

    NARCIS (Netherlands)

    Diks, C.; Hommes, C.; Wang, J.

    2015-01-01

    The global impact of the recent financial crisis has once more stressed the urgency of new approaches to designing early warning signals (EWS) for financial crises. In the recent literature on constructing EWS through identifying characteristics of critical slowdown on the basis of time series obser

  18. DEVELOPMENTAL CHANGES IN SEROTONIN SIGNALING: IMPLICATIONS FOR EARLY BRAIN FUNCTION, BEHAVIOR AND ADAPTATION

    Science.gov (United States)

    BRUMMELTE, S.; GLANAGHY, E. MC; BONNIN, A.; OBERLANDER, T. F.

    2017-01-01

    The neurotransmitter serotonin (5-HT) plays a central role in brain development, regulation of mood, stress reactivity and risk of psychiatric disorders, and thus alterations in 5-HT signaling early in life have critical implications for behavior and mental health across the life span. Drawing on preclinical and emerging human evidence this narrative review paper will examine three key aspects when considering the consequences of early life changes in 5-HT: (1) developmental origins of variations of 5-HT signaling; (2) influence of genetic and epigenetic factors; and (3) preclinical and clinical consequences of 5-HT-related changes associated with antidepressant exposure (SSRIs). The developmental consequences of altered prenatal 5-HT signaling varies greatly and outcomes depend on an ongoing interplay between biological (genetic/epigenetic variations) and environmental factors, both pre and postnatally. Emerging evidence suggests that variations in 5-HT signaling may increase sensitivity to risky home environments, but may also amplify a positive response to a nurturing environment. In this sense, factors that change central 5-HT levels may act as ‘plasticity’ rather than ‘risk’ factors associated with developmental vulnerability. Understanding the impact of early changes in 5-HT levels offers critical insights that might explain the variations in early typical brain development that underlies behavioral risk. PMID:26905950

  19. Coping with a life event in bipolar disorder : ambulatory measurement, signalling and early treatment

    NARCIS (Netherlands)

    Knapen, Stefan E; Riemersma-van der Lek, Rixt F; Haarman, Bartholomeus C M; Schoevers, Robert A

    2016-01-01

    Disruption of the biological rhythm in patients with bipolar disorder is a known risk factor for a switch in mood. This case study describes how modern techniques using ambulatory assessment of sleep parameters can help in signalling a mood switch and start early treatment. We studied a 40-year-old

  20. Expression analysis of Shh signaling members in early stages of chick lung development.

    Science.gov (United States)

    Moura, Rute Silva; Silva-Gonçalves, Carla; Vaz-Cunha, Patrícia; Correia-Pinto, Jorge

    2016-10-01

    Lung organogenesis is guided by epithelial-mesenchymal interactions that coordinate cellular events responsible for the formation of the respiratory system. Several signaling pathways have been implicated in this process; among them, sonic hedgehog (Shh) signaling has emerged as a crucial regulator of branching morphogenesis in the mammalian lung. Canonical Shh signaling requires the presence of patched (Ptch) and smoothened (Smo) transmembrane receptors in order to induce the activation of glioblastoma (Gli) zinc finger transcription factors that are the true effectors of the pathway. Signal transduction is finely regulated by Ptch1, Gli, and Hhip (hedgehog-interacting protein). The present work characterizes, for the first time, the expression pattern of shh, ptch1, smo, gli1, and hhip in early stages of the embryonic chick lung. In situ hybridization studies revealed that these genes are expressed in the same cellular compartments as their mammalian counterparts, although their proximo-distal distribution is slightly changed. Moreover, the molecular interactions between fibroblast growth factor (FGF) and Shh signaling pathway were assessed, in vitro, by grafting beads soaked in SU5402 (an FGF receptor inhibitor). In the chick lung, Shh signaling seems to have some features that are species specific since shh is not a downstream target of FGF signaling. Nonetheless and despite the observed differences, these findings suggest a role for Shh signaling in the epithelial-mesenchymal interactions that control chick lung morphogenesis.

  1. A continued role for signaling functions in the early evolution of feathers.

    Science.gov (United States)

    Ruxton, Graeme D; Persons Iv, W Scott; Currie, Philip J

    2017-03-01

    Persons and Currie (2015) argued against either flight, thermoregulation, or signaling as a functional benefit driving the earliest evolution of feathers; rather, they favored simple feathers having an initial tactile sensory function, which changed to a thermoregulatory function as density increased. Here, we explore the relative merits of early simple feathers that may have originated as tactile sensors progressing instead toward a signaling, rather than (or in addition to) a thermoregulatory function. We suggest that signaling could act in concert with a sensory function more naturally than could thermoregulation. As such, the dismissal of a possible signaling function and the presumption that an initial sensory function led directly to a thermoregulatory function (implicit in the title "bristles before down") are premature. © 2017 The Author(s). Evolution © 2017 The Society for the Study of Evolution.

  2. Artificial Neural Network-Based Early-Age Concrete Strength Monitoring Using Dynamic Response Signals.

    Science.gov (United States)

    Kim, Junkyeong; Lee, Chaggil; Park, Seunghee

    2017-06-07

    Concrete is one of the most common materials used to construct a variety of civil infrastructures. However, since concrete might be susceptible to brittle fracture, it is essential to confirm the strength of concrete at the early-age stage of the curing process to prevent unexpected collapse. To address this issue, this study proposes a novel method to estimate the early-age strength of concrete, by integrating an artificial neural network algorithm with a dynamic response measurement of the concrete material. The dynamic response signals of the concrete, including both electromechanical impedances and guided ultrasonic waves, are obtained from an embedded piezoelectric sensor module. The cross-correlation coefficient of the electromechanical impedance signals and the amplitude of the guided ultrasonic wave signals are selected to quantify the variation in dynamic responses according to the strength of the concrete. Furthermore, an artificial neural network algorithm is used to verify a relationship between the variation in dynamic response signals and concrete strength. The results of an experimental study confirm that the proposed approach can be effectively applied to estimate the strength of concrete material from the early-age stage of the curing process.

  3. Enhanced brain signal variability in children with autism spectrum disorder during early childhood.

    Science.gov (United States)

    Takahashi, Tetsuya; Yoshimura, Yuko; Hiraishi, Hirotoshi; Hasegawa, Chiaki; Munesue, Toshio; Higashida, Haruhiro; Minabe, Yoshio; Kikuchi, Mitsuru

    2016-03-01

    Extensive evidence shows that a core neurobiological mechanism of autism spectrum disorder (ASD) involves aberrant neural connectivity. Recent advances in the investigation of brain signal variability have yielded important information about neural network mechanisms. That information has been applied fruitfully to the assessment of aging and mental disorders. Multiscale entropy (MSE) analysis can characterize the complexity inherent in brain signal dynamics over multiple temporal scales in the dynamics of neural networks. For this investigation, we sought to characterize the magnetoencephalography (MEG) signal variability during free watching of videos without sound using MSE in 43 children with ASD and 72 typically developing controls (TD), emphasizing early childhood to older childhood: a critical period of neural network maturation. Results revealed an age-related increase of brain signal variability in a specific timescale in TD children, whereas atypical age-related alteration was observed in the ASD group. Additionally, enhanced brain signal variability was observed in children with ASD, and was confirmed particularly for younger children. In the ASD group, symptom severity was associated region-specifically and timescale-specifically with reduced brain signal variability. These results agree well with a recently reported theory of increased brain signal variability during development and aberrant neural connectivity in ASD, especially during early childhood. Results of this study suggest that MSE analytic method might serve as a useful approach for characterizing neurophysiological mechanisms of typical-developing and its alterations in ASD through the detection of MEG signal variability at multiple timescales. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  4. Enhanced brain signal variability in children with autism spectrum disorder during early childhood

    Science.gov (United States)

    Yoshimura, Yuko; Hiraishi, Hirotoshi; Hasegawa, Chiaki; Munesue, Toshio; Higashida, Haruhiro; Minabe, Yoshio; Kikuchi, Mitsuru

    2016-01-01

    Abstract Extensive evidence shows that a core neurobiological mechanism of autism spectrum disorder (ASD) involves aberrant neural connectivity. Recent advances in the investigation of brain signal variability have yielded important information about neural network mechanisms. That information has been applied fruitfully to the assessment of aging and mental disorders. Multiscale entropy (MSE) analysis can characterize the complexity inherent in brain signal dynamics over multiple temporal scales in the dynamics of neural networks. For this investigation, we sought to characterize the magnetoencephalography (MEG) signal variability during free watching of videos without sound using MSE in 43 children with ASD and 72 typically developing controls (TD), emphasizing early childhood to older childhood: a critical period of neural network maturation. Results revealed an age‐related increase of brain signal variability in a specific timescale in TD children, whereas atypical age‐related alteration was observed in the ASD group. Additionally, enhanced brain signal variability was observed in children with ASD, and was confirmed particularly for younger children. In the ASD group, symptom severity was associated region‐specifically and timescale‐specifically with reduced brain signal variability. These results agree well with a recently reported theory of increased brain signal variability during development and aberrant neural connectivity in ASD, especially during early childhood. Results of this study suggest that MSE analytic method might serve as a useful approach for characterizing neurophysiological mechanisms of typical‐developing and its alterations in ASD through the detection of MEG signal variability at multiple timescales. Hum Brain Mapp 37:1038–1050, 2016. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:26859309

  5. Genomic insights into Wnt signaling in an early diverging metazoan, the ctenophore Mnemiopsis leidyi.

    Science.gov (United States)

    Pang, Kevin; Ryan, Joseph F; Mullikin, James C; Baxevanis, Andreas D; Martindale, Mark Q

    2010-10-04

    Intercellular signaling pathways are a fundamental component of the integrating cellular behavior required for the evolution of multicellularity. The genomes of three of the four early branching animal phyla (Cnidaria, Placozoa and Porifera) have been surveyed for key components, but not the fourth (Ctenophora). Genomic data from ctenophores could be particularly relevant, as ctenophores have been proposed to be one of the earliest branching metazoan phyla. A preliminary assembly of the lobate ctenophore Mnemiopsis leidyi genome generated using next-generation sequencing technologies were searched for components of a developmentally important signaling pathway, the Wnt/β-catenin pathway. Molecular phylogenetic analysis shows four distinct Wnt ligands (MlWnt6, MlWnt9, MlWntA and MlWntX), and most, but not all components of the receptor and intracellular signaling pathway were detected. In situ hybridization of the four Wnt ligands showed that they are expressed in discrete regions associated with the aboral pole, tentacle apparati and apical organ. Ctenophores show a minimal (but not obviously simple) complement of Wnt signaling components. Furthermore, it is difficult to compare the Mnemiopsis Wnt expression patterns with those of other metazoans. mRNA expression of Wnt pathway components appears later in development than expected, and zygotic gene expression does not appear to play a role in early axis specification. Notably absent in the Mnemiopsis genome are most major secreted antagonists, which suggests that complex regulation of this secreted signaling pathway probably evolved later in animal evolution.

  6. Signal and image processing for early detection of coronary artery diseases: A review

    Science.gov (United States)

    Mobssite, Youness; Samir, B. Belhaouari; Mohamad Hani, Ahmed Fadzil B.

    2012-09-01

    Today biomedical signals and image based detection are a basic step to diagnose heart diseases, in particular, coronary artery diseases. The goal of this work is to provide non-invasive early detection of Coronary Artery Diseases relying on analyzing images and ECG signals as a combined approach to extract features, further classify and quantify the severity of DCAD by using B-splines method. In an aim of creating a prototype of screening biomedical imaging for coronary arteries to help cardiologists to decide the kind of treatment needed to reduce or control the risk of heart attack.

  7. Geolocation of RF signals

    CERN Document Server

    Progri, Ilir

    2011-01-01

    ""Geolocation of RF Signals - Principles and Simulations"" offers an overview of the best practices and innovative techniques in the art and science of geolocation over the last twenty years. It covers all research and development aspects including theoretical analysis, RF signals, geolocation techniques, key block diagrams, and practical principle simulation examples in the frequency band from 100 MHz to 18 GHz or even 60 GHz. Starting with RF signals, the book progressively examines various signal bands - such as VLF, LF, MF, HF, VHF, UHF, L, S, C, X, Ku, and, K and the corresponding geoloca

  8. Signaling Proteins and Transcription Factors in Normal and Malignant Early B Cell Development

    Directory of Open Access Journals (Sweden)

    Patricia Pérez-Vera

    2011-01-01

    Full Text Available B cell development starts in bone marrow with the commitment of hematopoietic progenitors to the B cell lineage. In murine models, the IL-7 and preBCR receptors, and the signaling pathways and transcription factors that they regulate, control commitment and maintenance along the B cell pathway. E2A, EBF1, PAX5, and Ikaros are among the most important transcription factors controlling early development and thereby conditioning mice homeostatic B cell lymphopoiesis. Importantly, their gain or loss of function often results in malignant development in humans, supporting conserved roles for these transcription factors. B cell acute lymphoblastic leukemia is the most common cause of pediatric cancer, and it is characterized by unpaired early B cell development resulting from genetic lesions in these critical signaling pathways and transcription factors. Fine mapping of these genetic abnormalities is allowing more specific treatments, more accurately predicting risk profiles for this disease, and improving survival rates.

  9. A critical role for sonic hedgehog signaling in the early expansion of the developing brain.

    Science.gov (United States)

    Britto, Joanne; Tannahill, David; Keynes, Roger

    2002-02-01

    The mechanisms that coordinate the three-dimensional shape of the vertebrate brain during development are largely unknown. We have found that sonic hedgehog (Shh) is crucial in driving the rapid, extensive expansion of the early vesicles of the developing midbrain and forebrain. Transient displacement of the notochord from the midbrain floor plate resulted in abnormal folding and overall collapse of the vesicles, accompanied by reduced cell proliferation and increased cell death in the midbrain. Simultaneously, expression of Shh decreased locally in the notochord and floor plate, whereas overt patterning and differentiation proceeded normally. Normal midbrain expansion was restored by implantation of Shh-secreting cells in a dose-dependent manner; conversely, expansion was retarded following antagonism of the Shh signaling pathway by cyclopamine. Our results indicate that Shh signaling from the ventral midline is essential for regulating brain morphogenesis during early development.

  10. Ezh2 Controls an Early Hematopoietic Program and Growth and Survival Signaling in Early T Cell Precursor Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Etienne Danis

    2016-03-01

    Full Text Available Early T cell precursor acute lymphoblastic leukemia (ETP-ALL is an aggressive subtype of ALL distinguished by stem-cell-associated and myeloid transcriptional programs. Inactivating alterations of Polycomb repressive complex 2 components are frequent in human ETP-ALL, but their functional role is largely undefined. We have studied the involvement of Ezh2 in a murine model of NRASQ61K-driven leukemia that recapitulates phenotypic and transcriptional features of ETP-ALL. Homozygous inactivation of Ezh2 cooperated with oncogenic NRASQ61K to accelerate leukemia onset. Inactivation of Ezh2 accentuated expression of genes highly expressed in human ETP-ALL and in normal murine early thymic progenitors. Moreover, we found that Ezh2 contributes to the silencing of stem-cell- and early-progenitor-cell-associated genes. Loss of Ezh2 also resulted in increased activation of STAT3 by tyrosine 705 phosphorylation. Our data mechanistically link Ezh2 inactivation to stem-cell-associated transcriptional programs and increased growth/survival signaling, features that convey an adverse prognosis in patients.

  11. Parent-offspring conflict theory, signaling of need, and weight gain in early life.

    Science.gov (United States)

    Wells, Jonathan C

    2003-06-01

    Human growth in early life has major implications for fitness. During this period, the mother regulates the growth of her offspring through placental nutrition and lactation. However, parent-offspring conflict theory predicts that offspring are selected to demand more resources than the mother is selected to provide. This general issue has prompted the development of begging theory, which attempts to find the optimal levels of offspring demand and parental provisioning. Several models have been proposed to account for begging behavior, whether by biochemical or behavioral pathways, including: (1) blackmail of parents; (2) scramble competition between multiple offspring; (3) honest signaling of nutritional need; and (4) honest signaling of offspring worth. These models are all supported by data from nonhuman animals, with species varying according to which model is relevant. This paper examines the evidence that human suckling and crying signal nutritional demand, need, and worth to the mother. While suckling provides hormonal stimulation of breast milk production and signals hunger, crying fulfills a different role, with evidence suggesting that it signals both worth and need for resources (nutrition and thermoregulation). The role of signaling in nutritional demand is examined in the context of three common health problems that have traditionally been assumed to have physiological rather than behavioral causes: excess weight gain, failure to thrive, and colic. The value of such an evolutionary approach lies in its potential to enhance behavioral management of these conditions.

  12. Quantitative genetics of plumage color: lifetime effects of early nest environment on a colorful sexual signal

    Science.gov (United States)

    Hubbard, Joanna K; Jenkins, Brittany R; Safran, Rebecca J

    2015-01-01

    Phenotypic differences among individuals are often linked to differential survival and mating success. Quantifying the relative influence of genetic and environmental variation on phenotype allows evolutionary biologists to make predictions about the potential for a given trait to respond to selection and various aspects of environmental variation. In particular, the environment individuals experience during early development can have lasting effects on phenotype later in life. Here, we used a natural full-sib/half-sib design as well as within-individual longitudinal analyses to examine genetic and various environmental influences on plumage color. We find that variation in melanin-based plumage color – a trait known to influence mating success in adult North American barn swallows (Hirundo rustica erythrogaster) – is influenced by both genetics and aspects of the developmental environment, including variation due to the maternal phenotype and the nest environment. Within individuals, nestling color is predictive of adult color. Accordingly, these early environmental influences are relevant to the sexually selected plumage color variation in adults. Early environmental conditions appear to have important lifelong implications for individual reproductive performance through sexual signal development in barn swallows. Our results indicate that feather color variation conveys information about developmental conditions and maternal care alleles to potential mates in North American barn swallows. Melanin-based colors are used for sexual signaling in many organisms, and our study suggests that these signals may be more sensitive to environmental variation than previously thought. PMID:26380676

  13. Quantitative genetics of plumage color: lifetime effects of early nest environment on a colorful sexual signal.

    Science.gov (United States)

    Hubbard, Joanna K; Jenkins, Brittany R; Safran, Rebecca J

    2015-08-01

    Phenotypic differences among individuals are often linked to differential survival and mating success. Quantifying the relative influence of genetic and environmental variation on phenotype allows evolutionary biologists to make predictions about the potential for a given trait to respond to selection and various aspects of environmental variation. In particular, the environment individuals experience during early development can have lasting effects on phenotype later in life. Here, we used a natural full-sib/half-sib design as well as within-individual longitudinal analyses to examine genetic and various environmental influences on plumage color. We find that variation in melanin-based plumage color - a trait known to influence mating success in adult North American barn swallows (Hirundo rustica erythrogaster) - is influenced by both genetics and aspects of the developmental environment, including variation due to the maternal phenotype and the nest environment. Within individuals, nestling color is predictive of adult color. Accordingly, these early environmental influences are relevant to the sexually selected plumage color variation in adults. Early environmental conditions appear to have important lifelong implications for individual reproductive performance through sexual signal development in barn swallows. Our results indicate that feather color variation conveys information about developmental conditions and maternal care alleles to potential mates in North American barn swallows. Melanin-based colors are used for sexual signaling in many organisms, and our study suggests that these signals may be more sensitive to environmental variation than previously thought.

  14. SELF and VLF electromagnetic emissions that preceded the M6.2 Central Italy earthquake occurred on August 24, 2016

    Science.gov (United States)

    Cataldi, Daniele; Cataldi, Gabriele; Straser, Valentino

    2017-04-01

    On August 24, 2016 at 01:36:32 UTC a destructive earthquake hit Central Italy with a magnitude of M6.2. The authors of this study have recorded some electromagnetic signals that have preceded this strong earthquake. These signals were recorded through two electromagnetic monitoring stations realized by Gabriele Cataldi and Daniele Cataldi, located near the town of Albano Laziale (Rome, Italy) and near the city of Lariano (Rome, Italy) and can monitor the radio spectrum 24h7 between 0.001 Hz and 96 kHz (SELF-LF band). The electromagnetic monitoring allowed to identify two interesting types of electromagnetic anomalies: the first electromagnetic anomaly was recorded on August 18, 2016 between 02:47 UTC and 06:21 UTC, in the VLF band prevalently between 18kHz and 26kHz; the second electromagnetic anomaly was registered between 08:00 UTC on August 23, 2016 and 05:00 UTC on August 24, 2016, prevalently between 0.01 and 0.7Hz: the most intense signals were recorded at 08:50 UTC on August 23, 2016 and approximately 1 hour before the strong earthquake. The Earth's electromagnetic background monitoring in the SELF-VLF band (0Hztechnological) have allowed us to understand that there are actually two families of pre-seismic radio emissions: 1) radio emissions identified as Earth's geomagnetic field disturbances related to "near Earth" solar wind proton density increase variations, and for this reason it can be seen from any point on the Earth (this is "no local" type emissions); 2) radio signals are not connected directly to the solar and geomagnetic activity: these radio signals are probably generated by piezoelectricity phenomena occurring near the focal area of the earthquake and are detectable near earthquake epicenter (this is a "local" type emissions). It is therefore clear that the monitoring of solar activity and Earth's geomagnetic activity is an activity of fundamental importance to be able to have a general understanding of pre-seismic radio signals nature. In fact

  15. A Disintegrin and Metalloproteinase10 (ADAM10 Regulates NOTCH Signaling during Early Retinal Development.

    Directory of Open Access Journals (Sweden)

    Joseph A Toonen

    Full Text Available ADAM10 and ADAM17 are two closely related members of the ADAM (a disintegrin and metalloprotease family of membrane-bound sheddases, which proteolytically cleave surface membrane proteins. Both ADAM10 and ADAM17 have been implicated in the proteolytic cleavage of NOTCH receptors and as such regulators of NOTCH signaling. During retinal development, NOTCH signaling facilitates retinal neurogenesis by maintaining progenitor cells in a proliferative state and by mediating retinal cell fates. However, the roles of ADAM10 and ADAM17 in the retina are not well defined. In this study, we set out to clarify the roles of ADAM10 and ADAM17 during early retinal development. The retinal phenotype of conditionally abated Adam17 retinae (Adam17 CKO did not differ from the controls whereas conditionally ablated Adam10 retinae (Adam10 CKO exhibited abnormal morphogenesis characterized by the formation of rosettes and a loss of retinal laminae phenotypically similar to morphological abnormalities identified in mice with retinal NOTCH signaling deficiency. Additionally, Adam10 CKO retinae exhibited abnormal neurogenesis characterized by fewer proliferating progenitor cells and greater differentiation of early photoreceptors and retinal ganglion cells. Moreover, constitutive activation of the NOTCH1-intracellular domain (N1-ICD rescued Adam10 CKO abnormal neurogenesis, as well as abnormal retinal morphology by maintaining retinal cells in the progenitor state. Collectively these findings provide in vivo genetic evidence that ADAM10, and not ADAM17, is indispensable for proper retinal development as a regulator of NOTCH signaling.

  16. A Disintegrin and Metalloproteinase10 (ADAM10) Regulates NOTCH Signaling during Early Retinal Development.

    Science.gov (United States)

    Toonen, Joseph A; Ronchetti, Adam; Sidjanin, D J

    2016-01-01

    ADAM10 and ADAM17 are two closely related members of the ADAM (a disintegrin and metalloprotease) family of membrane-bound sheddases, which proteolytically cleave surface membrane proteins. Both ADAM10 and ADAM17 have been implicated in the proteolytic cleavage of NOTCH receptors and as such regulators of NOTCH signaling. During retinal development, NOTCH signaling facilitates retinal neurogenesis by maintaining progenitor cells in a proliferative state and by mediating retinal cell fates. However, the roles of ADAM10 and ADAM17 in the retina are not well defined. In this study, we set out to clarify the roles of ADAM10 and ADAM17 during early retinal development. The retinal phenotype of conditionally abated Adam17 retinae (Adam17 CKO) did not differ from the controls whereas conditionally ablated Adam10 retinae (Adam10 CKO) exhibited abnormal morphogenesis characterized by the formation of rosettes and a loss of retinal laminae phenotypically similar to morphological abnormalities identified in mice with retinal NOTCH signaling deficiency. Additionally, Adam10 CKO retinae exhibited abnormal neurogenesis characterized by fewer proliferating progenitor cells and greater differentiation of early photoreceptors and retinal ganglion cells. Moreover, constitutive activation of the NOTCH1-intracellular domain (N1-ICD) rescued Adam10 CKO abnormal neurogenesis, as well as abnormal retinal morphology by maintaining retinal cells in the progenitor state. Collectively these findings provide in vivo genetic evidence that ADAM10, and not ADAM17, is indispensable for proper retinal development as a regulator of NOTCH signaling.

  17. Protein Tyrosine Phosphatase PRL2 Mediates Notch and Kit Signals in Early T Cell Progenitors.

    Science.gov (United States)

    Kobayashi, Michihiro; Nabinger, Sarah C; Bai, Yunpeng; Yoshimoto, Momoko; Gao, Rui; Chen, Sisi; Yao, Chonghua; Dong, Yuanshu; Zhang, Lujuan; Rodriguez, Sonia; Yashiro-Ohtani, Yumi; Pear, Warren S; Carlesso, Nadia; Yoder, Mervin C; Kapur, Reuben; Kaplan, Mark H; Daniel Lacorazza, Hugo; Zhang, Zhong-Yin; Liu, Yan

    2017-04-01

    The molecular pathways regulating lymphoid priming, fate, and development of multipotent bone marrow hematopoietic stem and progenitor cells (HSPCs) that continuously feed thymic progenitors remain largely unknown. While Notch signal is indispensable for T cell specification and differentiation, the downstream effectors are not well understood. PRL2, a protein tyrosine phosphatase that regulates hematopoietic stem cell proliferation and self-renewal, is highly expressed in murine thymocyte progenitors. Here we demonstrate that protein tyrosine phosphatase PRL2 and receptor tyrosine kinase c-Kit are critical downstream targets and effectors of the canonical Notch/RBPJ pathway in early T cell progenitors. While PRL2 deficiency resulted in moderate defects of thymopoiesis in the steady state, de novo generation of T cells from Prl2 null hematopoietic stem cells was significantly reduced following transplantation. Prl2 null HSPCs also showed impaired T cell differentiation in vitro. We found that Notch/RBPJ signaling upregulated PRL2 as well as c-Kit expression in T cell progenitors. Further, PRL2 sustains Notch-mediated c-Kit expression and enhances stem cell factor/c-Kit signaling in T cell progenitors, promoting effective DN1-DN2 transition. Thus, we have identified a critical role for PRL2 phosphatase in mediating Notch and c-Kit signals in early T cell progenitors. Stem Cells 2017;35:1053-1064.

  18. The combined study of the middle atmosphere meteorological parameters and lower ionosphere dynamics over Europe by means of remote VLF-LF measurements

    Science.gov (United States)

    Zetzer, J. I.; Lyakhov, A.; Yakymenko, K.

    2012-12-01

    The results of comprehensive analysis of long-term records of VLF-LF European transmitters by means of Mikhnevo geophysical observatory (Institute of Geospheres Dynamics), SID station A118 (France) and a number of AWESOM receivers are presented. In the previous study (A.A.Egoshin et al., Izvestiya, Physics of the Solid Earth, 2012, Vol. 48, No. 3, pp. 275-286) the results obtained under the minimum solar activity were presented that have shown the link between the lower ionosphere parameters and meteorological fields of the middle atmosphere. The current study expands the evidence to the increased solar activity level as well as the number of receivers, thus allowing more dense coverage of the Europe by the radio paths. Middle atmosphere data under study were provided by the EOS Aura Microwave Limb Sounder. These asynoptic data, in turn, were processed by the space-time spectral analysis on various pressure levels for various window lengths. The results are presented for the spatial structure of wave-like perturbations in the VLF-LF signal strength, which result from the lower ionosphere disturbances on various radio paths. Special short-windowed space-time study was evaluated for the periods of anomalous temporal behavior of the VLF-LF signals and the results of the altitude-latitude mode structures of the geopotential height, neutral temperature, water and ozone constituents are presented. It is shown that the spatial properties of the lower ionosphere can vary significantly at relatively small scale. Moreover, the altitude-latitude mode structures do not coincide in space as well as in time, thus, complicating the lower ionosphere response to the meteorological variations of the middle atmosphere. The analysis of all assembled data proves two main points. At first, it is possible to evaluate synoptic long-term monitoring of the middle atmosphere via the lower ionosphere perturbations as seen by VLF-LF receivers. At second, the theoretical models of the lower

  19. MiRNA-mediated regulation of cell signaling and homeostasis in the early mouse embryo.

    Science.gov (United States)

    Pernaute, Barbara; Spruce, Thomas; Rodriguez, Tristan A; Manzanares, Miguel

    2011-02-15

    At the time of implantation the mouse embryo is composed of three tissues the epiblast, trophectoderm and primitive endoderm. As development progresses the epiblast goes on to form the foetus whilst the trophectoderm and primitive endoderm give rise to extra-embryonic structures with important roles in embryo patterning and nutrition. Dramatic changes in gene expression occur during early embryo development and these require regulation at different levels. miRNAs are small non coding RNAs that have emerged over the last decade as important post-transcriptional repressors of gene expression. The roles played by miRNAs during early mammalian development are only starting to be elucidated. In order to gain insight into the function of miRNAs in the different lineages of the early mouse embryo we have analysed in depth the phenotype of embryos and extra-embryonic stem cells mutant for the miRNA maturation protein Dicer. This study revealed that miRNAs are involved in regulating cell signaling and homeostasis in the early embryo. Specifically, we identified a role for miRNAs in regulating the Erk signaling pathway in the extra-embryonic endoderm, cell cycle progression in extra-embryonic tissues and apoptosis in the epiblast.

  20. ELF/VLF wave disturbances detected by the DEMETER satellite over the HAARP transmitter

    Science.gov (United States)

    Titova, Elena; Demekhov, Andrei; Parrot, Michel; Mogilevsky, Mikhail; Mochalov, Alexey; Pashin, Anatoly

    We report observations of electromagnetic the ELF/VLF wave disturbances by the DEMETER satellite (670 km altitude) overflying the HAARP heating facility (62.39(°) N, 145.15(°) W, L = 4.9). The HAARP HF transmitter operated at the maximum available power of 3.6 MW, O-mode polarization, and the beam directed towards the magnetic zenith. ELF/VLF waves caused by the HAARP heating are detected by the DEMETER satellite when the HF radio wave frequency was close to the critical frequency (foF2) of the ionospheric F2 layer but below it. ELF/VLF wave disturbances observed above the HAARP transmitter were detected by electrical antennas in an area with characteristic size 10 (2) km. We analyze amplitude and polarization spectra of the ELF disturbances and compare them with the characteristics of natural ELF hiss above HAARP. The VLF wave disturbances in the topside ionosphere above the HAARP transmitter were detected in the frequency ranges 8-17 kHz and 15-18 kHz which are close to the lower hybrid resonance frequency f _LHR in the heating region and its second harmonic (2f _LHR), respectively. In the case where the HAARP HF power was modulated, the detected VLF waves were also modulated with the same frequency whereas in the ELF frequency range the modulation period of the HAARP power was not observed. Possible mechanisms of generation of the ELF/VLF disturbances produced by the HAARP transmitter in the topside ionosphere are discussed.

  1. Investigation of VLF and HF waves showing seismo-ionospheric anomalies induced by the 29 September 2009 Samoa earthquake (Mw=8.1

    Directory of Open Access Journals (Sweden)

    M. Parrot

    2010-05-01

    Full Text Available In Samoa Islands, a powerful earthquake took place at 17:48:10.99 UTC (06:48:10.99 LT on 29 September 2009 with a magnitude Mw=8.1. Using ICE (Instrument Champ Electrique and IMSC (Instrument Magnetic Search Coil experiments onboard the DEMETER (Detection of Electromagnetic Emissions Transmitted from Earthquake Regions satellite we have surveyed possible variations in electromagnetic signals transmitted by the ground-based VLF transmitter NPM in Hawaii and in HF plasma waves close to the Samoa earthquake during the seismic activity. The indices Dst and Kp were used to distinguish pre-earthquake anomalies from the other anomalies related to the geomagnetic activities. In a previous study we have shown that anomalies in IAP (plasma analyzer and ISL (Langmuir probe experiments onboard the DEMETER and also TEC (Total Electron Content data appear 1 to 5 days before the Samoa earthquake. In this paper we show that the anomalies in the VLF transmitter signal and in the HF range appear with the same time scale. The lack of significant geomagnetic activities indicates that these anomalous behaviors could be regarded as seismo-ionospheric precursors. It is also shown that comparative analysis is more effective in seismo-ionospheric studies.

  2. Extended lateral heating of the nighttime ionosphere by ground-based VLF transmitters

    OpenAIRE

    İnan, Umran Savaş; Graf, K. L.; Spasojevic, M.; Marshall, R. A.; Lehtinen, N. G.; Foust, F. R.

    2013-01-01

    JOURNAL OF GEOPHYSICAL RESEARCH: SPACE PHYSICS, VOL. 118, 7783–7797, doi:10.1002/2013JA019337, 2013 Extended lateral heating of the nighttime ionosphere by ground-based VLF transmitters K. L. Graf,1 M. Spasojevic,1 R. A. Marshall,2 N. G. Lehtinen,1 F. R. Foust,1 and U. S. Inan1,3 Received 16 August 2013; revised 9 October 2013; accepted 11 November 2013; published 3 December 2013. [1] The effects of ground-based very low frequency (VLF) transmitters on the lower ionospher...

  3. Quasi-periodic VLF emissions observed during daytime at a low latitude Indian ground station Jammu

    Indian Academy of Sciences (India)

    K K Singh; J Singh; R P Patel; A K Singh; R P Singh; Rejesh Singh; P A Ganai

    2009-06-01

    This paper reports quasi-periodic pulsing hiss emissions recorded during daytime in the frequency range of 50 Hz –15 kHz at low latitude station Jammu (geomag.lat.=22° 26′N; =1.17). It is noted that pulsing VLF emissions are a rare phenomena at low latitudes.The various spectrograms of pulsing VLF hiss emissions presented in this paper clearly show band limited spectrums regularly pulsing with almost equal period of the order of few seconds in the frequency range of ∼3-8 kHz. Generation and propagation mechanism of these emissions are briefly discussed.

  4. Similar Data Retrieval from Enormous Datasets on ELF/VLF Wave Spectrum Observed by Akebono

    Directory of Open Access Journals (Sweden)

    Y Kasahara

    2010-02-01

    Full Text Available As the total amount of data measured by scientific spacecraft is drastically increasing, it is necessary for researchers to develop new computation methods for efficient analysis of these enormous datasets. In the present study, we propose a new algorithm for similar data retrieval. We first discuss key descriptors that represent characteristics of the VLF/ELF waves observed by the Akebono spacecraft. Second, an algorithm for similar data retrieval is introduced. Finally, we demonstrate that the developed algorithm works well for the retrieval of the VLF spectrum with a small amount of CPU load.

  5. Enhancement of early cardiac differentiation of dedifferentiated fat cells by dimethyloxalylglycine via notch signaling pathway.

    Science.gov (United States)

    Li, Fuhai; Li, Zongzhuang; Jiang, Zhi; Tian, Ye; Wang, Zhi; Yi, Wei; Zhang, Chenyun

    2016-01-01

    Background: Hypoxia has been reported to possess the ability to induce mature lipid-filled adipocytes to differentiate into fibroblast-like multipotent dedifferentiated fat (DFAT) cells and stem cells such as iPSCs (interstitial pluripotent stem cells) and ESCs (embryonic stem cells) and then to differentiate into cardiomyocytes. However, the effect of hypoxia on cardiac differentiation of DFAT cells and its underlying molecular mechanism remains to be investigated. Objective: To investigate the role of hypoxia in early cardiac differentiation of DFAT cells and the underlying molecular mechanism. Methods: DFAT cells were prepared from 4 to 6 week-age mice and cultured under hypoxic conditions by adding Prolyl hydroxylase inhibitor and dimethyloxalylglycine (DMOG) into the culture media. To inhibit or block Notch signaling, γ-secretase inhibitor-II (GSI-II) and Notch1 siRNA (si-Notch1) were used. DFAT cell viability was detected using MTT assay. qRT-PCR, immunofluorescence microscopy and western blotting were used to evaluate the cardiac differentiation of DFAT cells and co-immunoprecipitation was used to study the interaction between HIF-1α and Notch signaling. Results: 0.6-mM DMOG failed to affect the viability of DFAT cells, but stimulated the cells to express early cardiac transcription factors including Islet1, Nkx2.5 and Gata4 in a time-dependent manner and increase the number of cTnT(+) cardiomyocytes (detected at the 28(th) day after stimulation). It was also demonstrated that DMOG was involved in HIF-1α and Notch signaling as well as HIF-1α-NICD complex formation. Conclusion: Hypoxia enhanced early cardiac differentiation of DFAT cells through HIF-1α and Notch signaling pathway.

  6. Thyroid hormone signaling during early neurogenesis and its significance as a vulnerable window for endocrine disruption.

    Science.gov (United States)

    Préau, Laetitia; Fini, Jean Baptiste; Morvan-Dubois, Ghislaine; Demeneix, Barbara

    2015-02-01

    The essential roles of thyroid hormone (TH) in perinatal brain development have been known for decades. More recently, many of the molecular mechanisms underlying the multiple effects of TH on proliferation, differentiation, migration, synaptogenesis and myelination in the developing nervous system have been elucidated. At the same time data from both epidemiological studies and animal models have revealed that the influence of thyroid signaling on development of the nervous system, extends to all periods of life, from early embryogenesis to neurogenesis in the adult brain. This review focuses on recent insights into the actions of TH during early neurogenesis. A key concept is that, in contrast to the previous ideas that only the unliganded receptor was implicated in these early phases, a critical role of the ligand, T3, is increasingly recognized. These findings are considered in the light of increasing knowledge of cell specific control of T3 availability as a function of deiodinase activity and transporter expression. These requirements for TH in the early stages of neurogenesis take on new relevance given the increasing epidemiological data on adverse effects of TH lack in early pregnancy on children's neurodevelopmental outcome. These ideas lead logically into a discussion on how the actions of TH during the first phases of neurogenesis can be potentially disrupted by gestational iodine lack and/or chemical pollution. This article is part of a Special Issue entitled: Nuclear receptors in animal development.

  7. Genomic insights into Wnt signaling in an early diverging metazoan, the ctenophore Mnemiopsis leidyi

    Directory of Open Access Journals (Sweden)

    Pang Kevin

    2010-10-01

    Full Text Available Abstract Background Intercellular signaling pathways are a fundamental component of the integrating cellular behavior required for the evolution of multicellularity. The genomes of three of the four early branching animal phyla (Cnidaria, Placozoa and Porifera have been surveyed for key components, but not the fourth (Ctenophora. Genomic data from ctenophores could be particularly relevant, as ctenophores have been proposed to be one of the earliest branching metazoan phyla. Results A preliminary assembly of the lobate ctenophore Mnemiopsis leidyi genome generated using next-generation sequencing technologies were searched for components of a developmentally important signaling pathway, the Wnt/β-catenin pathway. Molecular phylogenetic analysis shows four distinct Wnt ligands (MlWnt6, MlWnt9, MlWntA and MlWntX, and most, but not all components of the receptor and intracellular signaling pathway were detected. In situ hybridization of the four Wnt ligands showed that they are expressed in discrete regions associated with the aboral pole, tentacle apparati and apical organ. Conclusions Ctenophores show a minimal (but not obviously simple complement of Wnt signaling components. Furthermore, it is difficult to compare the Mnemiopsis Wnt expression patterns with those of other metazoans. mRNA expression of Wnt pathway components appears later in development than expected, and zygotic gene expression does not appear to play a role in early axis specification. Notably absent in the Mnemiopsis genome are most major secreted antagonists, which suggests that complex regulation of this secreted signaling pathway probably evolved later in animal evolution.

  8. Building and the analysis of two radio antennas (SSRT) in vlf zone

    Science.gov (United States)

    Marbouti, Marjan; Khakian Ghomi, Mehdi; Salmanpour Paeen Afrakati, Mohammad Reza; Riahi, Jahad; Ghanbari, Keyvan; Moradi Khanghahi, Abolfazl; Nahavandi, Behzad

    interesting results in this regard. The first result is that the time difference between SRT (time of rise end across ionosphere) and the sunrise as well as the SST (time of set beginning in ionosphere) and the sunset in the geographical location of signal encounter from ionosphere during summer is more as compared to winter season. And the second result is that we could measure a height of ionosphere by means of some calculations; during this period the signal had the maximum absorption. This is called the effective annihilation height and this effective annihilation height was secured for 8 VLF receivers. The results indicated that the effective annihilation height during autumn and winter seasons is higher and more than spring and summer seasons

  9. Response of low latitude D-region ionosphere to the Total Solar Eclipse of 22 July 2009, deduced from ELF/VLF analysis

    Science.gov (United States)

    Singh, A. K.; Singh, R.; Singh, A. K.

    2011-12-01

    Response of the D-region of the ionosphere to the total solar eclipse of 22 July 2009 at low latitude, Varanasi (geomagnetic lat = 140 55'N, longitude = 1540 E, dip. angle = 37.30) was investigated using ELF/VLF radio signal. The solar eclipse started at 05:30:04.4 hrs IST and lasted up to 07:27 hrs IST with totally from 6.25 IST to 6.27 IST.The changes in D-region ionospheric VLF reflection heights and electron density during eclipse have been estimated from tweek analysis. The reflection height increased from ~90 km from the first occurrence of tweek to about 93-94 km at the totality and then decreased to ~89 km at the end of the eclipse. The reflection heights are lower by 2-3 km as compared to the usual nighttime tweek reflection heights. The electron density is found to vary between 25-27 cm-3 at the reflection heights. The significant increase in tweek reflection height of about 15 km during the eclipse as compared to the daytime (morning) reflection heights of ~ 78 km is observed. Observations suggest that about 30-40% obscuration of solar disc can lead to the tweeks occurrence which otherwise occur only in the nighttime. A significant increase of 3dB in the strength of the amplitude of VLF signal is observed around the time of TSE as compared to a control day. These low latitude ionospheric perturbations on the eclipse day are discussed and compared with other normal days. During a solar eclipse, the decrease in solar flux due to moon's shadow causes sudden change in the D-region physical and chemical processes. During the totality due to blocking of Lyman-α 1215Å (major D-region ionizing radiation) by moon's umbral shadow, the electron density decreases drastically towards the nighttime values [Smith, 1972]. During the TSE, there was no production of ionization in the ionosphere and the ions and electrons in the lowest part of it recombined at a rapid rate resulting a depletion in the electron density in the 'D' region of the Ionosphere and hence an

  10. Human amniotic fluid contaminants alter thyroid hormone signalling and early brain development in Xenopus embryos

    Science.gov (United States)

    Fini, Jean-Baptiste; Mughal, Bilal B.; Le Mével, Sébastien; Leemans, Michelle; Lettmann, Mélodie; Spirhanzlova, Petra; Affaticati, Pierre; Jenett, Arnim; Demeneix, Barbara A.

    2017-03-01

    Thyroid hormones are essential for normal brain development in vertebrates. In humans, abnormal maternal thyroid hormone levels during early pregnancy are associated with decreased offspring IQ and modified brain structure. As numerous environmental chemicals disrupt thyroid hormone signalling, we questioned whether exposure to ubiquitous chemicals affects thyroid hormone responses during early neurogenesis. We established a mixture of 15 common chemicals at concentrations reported in human amniotic fluid. An in vivo larval reporter (GFP) assay served to determine integrated thyroid hormone transcriptional responses. Dose-dependent effects of short-term (72 h) exposure to single chemicals and the mixture were found. qPCR on dissected brains showed significant changes in thyroid hormone-related genes including receptors, deiodinases and neural differentiation markers. Further, exposure to mixture also modified neural proliferation as well as neuron and oligodendrocyte size. Finally, exposed tadpoles showed behavioural responses with dose-dependent reductions in mobility. In conclusion, exposure to a mixture of ubiquitous chemicals at concentrations found in human amniotic fluid affect thyroid hormone-dependent transcription, gene expression, brain development and behaviour in early embryogenesis. As thyroid hormone signalling is strongly conserved across vertebrates the results suggest that ubiquitous chemical mixtures could be exerting adverse effects on foetal human brain development.

  11. Human amniotic fluid contaminants alter thyroid hormone signalling and early brain development in Xenopus embryos

    Science.gov (United States)

    Fini, Jean-Baptiste; Mughal, Bilal B.; Le Mével, Sébastien; Leemans, Michelle; Lettmann, Mélodie; Spirhanzlova, Petra; Affaticati, Pierre; Jenett, Arnim; Demeneix, Barbara A.

    2017-01-01

    Thyroid hormones are essential for normal brain development in vertebrates. In humans, abnormal maternal thyroid hormone levels during early pregnancy are associated with decreased offspring IQ and modified brain structure. As numerous environmental chemicals disrupt thyroid hormone signalling, we questioned whether exposure to ubiquitous chemicals affects thyroid hormone responses during early neurogenesis. We established a mixture of 15 common chemicals at concentrations reported in human amniotic fluid. An in vivo larval reporter (GFP) assay served to determine integrated thyroid hormone transcriptional responses. Dose-dependent effects of short-term (72 h) exposure to single chemicals and the mixture were found. qPCR on dissected brains showed significant changes in thyroid hormone-related genes including receptors, deiodinases and neural differentiation markers. Further, exposure to mixture also modified neural proliferation as well as neuron and oligodendrocyte size. Finally, exposed tadpoles showed behavioural responses with dose-dependent reductions in mobility. In conclusion, exposure to a mixture of ubiquitous chemicals at concentrations found in human amniotic fluid affect thyroid hormone-dependent transcription, gene expression, brain development and behaviour in early embryogenesis. As thyroid hormone signalling is strongly conserved across vertebrates the results suggest that ubiquitous chemical mixtures could be exerting adverse effects on foetal human brain development. PMID:28266608

  12. Exos-B/Siple Station VLF wave-particle interaction experiments: 1. General description and wave-particle correlations

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, I.; Hashimoto, K.; Matsumoto, H.; Mukai, T.; Bell, T.F.; Inan, U.S.; Helliwell, R.A.; Katsufrakis, J.P.

    1983-01-01

    In situ measurements of both energetic particles and VLF waves have been carried out in a joint program involving the Japanese satellite EXOS-B and the Siple Station VLF transmitter. A general description of the experiment is given as well as some results concerning wave-particle correlations. Detailed analysis of the observed wave characteristics is given in a companion paper. Correlations of electron flux and pitch angle anisotropy in the energy range from 85 eV to 6.9 keV with waves in a range from 300 Hz to 9 kHz are examined. These electrons sometimes have a pitch angle distributions with a peak flux at 90/sup 0/ pitch angle (so-called pancake distribution). On five passes out of a total of 50 during the summer campaign in 1979, the energy of the electrons that showed a high pitch angle anisotropy shifted upward as the satellite moved into the plasmasphere, crossing the plasmapause in the equatorial region. In two cases out of five, strong Siple signals were observed in the geomagnetic equatorial region just outside the plasmapause, in association with such a pancake pitch angle distribution of electrons. The Siple signals are most likely amplified by the cyclotron instability due to the high pitch angle anisotropy (HPAA), although the flux of resonant electrons was relatively small. For three other cases of HPAA, the satellite location was so far away from the Siple meridian that the signal level, even if amplified, was too weak to be detected by the satellite. Emissions associated with Siple signals were detected on five (two equatorial and three high latitude) passes, which were all confined on 6 days after a large magnetic storm. On the days when the Siple triggered emissions were observed, the pitch angle anisotropy was low, but the electron flux at resonant energies in the equatorial region was four or five times larger than that on other non-triggering days in all energy channels from 85 eV to 6.9 keV.

  13. Jasmonate signaling is activated in the very early stages of iron deficiency responses in rice roots.

    Science.gov (United States)

    Kobayashi, Takanori; Itai, Reiko Nakanishi; Senoura, Takeshi; Oikawa, Takaya; Ishimaru, Yasuhiro; Ueda, Minoru; Nakanishi, Hiromi; Nishizawa, Naoko K

    2016-07-01

    Under low iron availability, plants induce the expression of various genes involved in iron uptake and translocation at the transcriptional level. This iron deficiency response is affected by various plant hormones, but the roles of jasmonates in this response are not well-known. We investigated the involvement of jasmonates in rice iron deficiency responses. High rates of jasmonate-inducible genes were induced during the very early stages of iron deficiency treatment in rice roots. Many jasmonate-inducible genes were also negatively regulated by the ubiquitin ligases OsHRZ1 and OsHRZ2 and positively regulated by the transcription factor IDEF1. Ten out of 35 genes involved in jasmonate biosynthesis and signaling were rapidly induced at 3 h of iron deficiency treatment, and this induction preceded that of known iron deficiency-inducible genes involved in iron uptake and translocation. Twelve genes involved in jasmonate biosynthesis and signaling were also upregulated in HRZ-knockdown roots. Endogenous concentrations of jasmonic acid and jasmonoyl isoleucine tended to be rapidly increased in roots in response to iron deficiency treatment, whereas these concentrations were higher in HRZ-knockdown roots under iron-sufficient conditions. Analysis of the jasmonate-deficient cpm2 mutant revealed that jasmonates repress the expression of many iron deficiency-inducible genes involved in iron uptake and translocation under iron sufficiency, but this repression is partly canceled under an early stage of iron deficiency. These results indicate that jasmonate signaling is activated during the very early stages of iron deficiency, which is partly regulated by IDEF1 and OsHRZs.

  14. α5β1 Integrin Signaling Mediates Oxidized LDL-Induced Inflammation and Early Atherosclerosis

    Science.gov (United States)

    Yurdagul, Arif; Green, Jonette; Albert, Patrick; McInnis, Marshall C.; Mazar, Andrew P.; Orr, A. Wayne

    2014-01-01

    Objective Endothelial cell activation drives early atherosclerotic plaque formation. Both fibronectin deposition and accumulation of oxidized LDL (oxLDL) occur early during atherogenesis and both are implicated in enhanced endothelial cell activation. However, interplay between these responses has not been established. The objective of our study was to determine whether endothelial matrix composition modulates the inflammatory properties of oxLDL. Approach and Results We now show that oxLDL-induced NF-κB activation, proinflammatory gene expression, and monocyte binding is significantly enhanced when endothelial cells are attached to fibronectin compared to basement membrane proteins. This enhanced response does not result from altered oxLDL receptor expression, oxLDL uptake, or reactive oxygen species production, but instead results from oxLDL-induced activation of the fibronectin-binding integrin α5β1. Preventing α5β1 signaling (blocking antibodies, knockout cells) inhibits oxLDL-induced NF-κB activation and VCAM-1 expression. Furthermore, oxLDL-drives α5β1-dependent integrin signaling through the focal adhesion kinase (FAK) pathway and FAK inhibition (PF-573228, siRNA) blunts oxLDL-induced NF-κB activation, VCAM-1 expression, and monocyte adhesion. Lastly, treatment with the α5β1 signaling inhibitor, ATN-161, significantly blunts atherosclerotic plaque development in ApoE deficient mice, characterized by reduced VCAM-1 expression and macrophage accumulation without affecting fibrous cap size. Conclusions Our data suggest that α5β1-mediated crosstalk between fibronectin and oxidized LDL regulates inflammation in early atherogenesis and therapeutics that inhibit α5 integrins may reduce inflammation without adversely affecting plaque structure. PMID:24833794

  15. New early warning system for gravity-driven ruptures based on codetection of acoustic signal

    Science.gov (United States)

    Faillettaz, J.

    2016-12-01

    Gravity-driven rupture phenomena in natural media - e.g. landslide, rockfalls, snow or ice avalanches - represent an important class of natural hazards in mountainous regions. To protect the population against such events, a timely evacuation often constitutes the only effective way to secure the potentially endangered area. However, reliable prediction of imminence of such failure events remains challenging due to the nonlinear and complex nature of geological material failure hampered by inherent heterogeneity, unknown initial mechanical state, and complex load application (rainfall, temperature, etc.). Here, a simple method for real-time early warning that considers both the heterogeneity of natural media and characteristics of acoustic emissions attenuation is proposed. This new method capitalizes on codetection of elastic waves emanating from microcracks by multiple and spatially separated sensors. Event-codetection is considered as surrogate for large event size with more frequent codetected events (i.e., detected concurrently on more than one sensor) marking imminence of catastrophic failure. Simple numerical model based on a Fiber Bundle Model considering signal attenuation and hypothetical arrays of sensors confirms the early warning potential of codetection principles. Results suggest that although statistical properties of attenuated signal amplitude could lead to misleading results, monitoring the emergence of large events announcing impeding failure is possible even with attenuated signals depending on sensor network geometry and detection threshold. Preliminary application of the proposed method to acoustic emissions during failure of snow samples has confirmed the potential use of codetection as indicator for imminent failure at lab scale. The applicability of such simple and cheap early warning system is now investigated at a larger scale (hillslope). First results of such a pilot field experiment are presented and analysed.

  16. The primary cilium coordinates early cardiogenesis and hedgehog signaling in cardiomyocyte differentiation

    DEFF Research Database (Denmark)

    Clement, Christian A; Kristensen, Stine G; Møllgård, Kjeld

    2009-01-01

    Defects in the assembly or function of primary cilia, which are sensory organelles, are tightly coupled to developmental defects and diseases in mammals. Here, we investigated the function of the primary cilium in regulating hedgehog signaling and early cardiogenesis. We report that the pluripotent...... P19.CL6 mouse stem cell line, which can differentiate into beating cardiomyocytes, forms primary cilia that contain essential components of the hedgehog pathway, including Smoothened, Patched-1 and Gli2. Knockdown of the primary cilium by Ift88 and Ift20 siRNA or treatment with cyclopamine......, an inhibitor of Smoothened, blocks hedgehog signaling in P19.CL6 cells, as well as differentiation of the cells into beating cardiomyocytes. E11.5 embryos of the Ift88(tm1Rpw) (Ift88-null) mice, which form no cilia, have ventricular dilation, decreased myocardial trabeculation and abnormal outflow tract...

  17. RssAB signaling coordinates early development of surface multicellularity in Serratia marcescens.

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    Yu-Huan Tsai

    Full Text Available Bacteria can coordinate several multicellular behaviors in response to environmental changes. Among these, swarming and biofilm formation have attracted significant attention for their correlation with bacterial pathogenicity. However, little is known about when and where the signaling occurs to trigger either swarming or biofilm formation. We have previously identified an RssAB two-component system involved in the regulation of swarming motility and biofilm formation in Serratia marcescens. Here we monitored the RssAB signaling status within single cells by tracing the location of the translational fusion protein EGFP-RssB following development of swarming or biofilm formation. RssAB signaling is specifically activated before surface migration in swarming development and during the early stage of biofilm formation. The activation results in the release of RssB from its cognate inner membrane sensor kinase, RssA, to the cytoplasm where the downstream gene promoters are located. Such dynamic localization of RssB requires phosphorylation of this regulator. By revealing the temporal activation of RssAB signaling following development of surface multicellular behavior, our findings contribute to an improved understanding of how bacteria coordinate their lifestyle on a surface.

  18. Proper ciliary assembly is critical for restricting Hedgehog signaling during early eye development in mice.

    Science.gov (United States)

    Burnett, Jacob B; Lupu, Floria I; Eggenschwiler, Jonathan T

    2017-10-01

    Patterning of the vertebrate eye into optic stalk, retinal pigment epithelium (RPE) and neural retina (NR) territories relies on a number of signaling pathways, but how these signals are interpreted by optic progenitors is not well understood. The primary cilium is a microtubule-based organelle that is essential for Hedgehog (Hh) signaling, but it has also been implicated in the regulation of other signaling pathways. Here, we show that the optic primordium is ciliated during early eye development and that ciliogenesis is essential for proper patterning and morphogenesis of the mouse eye. Ift172 mutants fail to generate primary cilia and exhibit patterning defects that resemble those of Gli3 mutants, suggesting that cilia are required to restrict Hh activity during eye formation. Ift122 mutants, which produce cilia with abnormal morphology, generate optic vesicles that fail to invaginate to produce the optic cup. These mutants also lack formation of the lens, RPE and NR. Such phenotypic features are accompanied by strong, ectopic Hh pathway activity, evidenced by altered gene expression patterns. Removal of GLI2 from Ift122 mutants rescued several aspects of optic cup and lens morphogenesis as well as RPE and NR specification. Collectively, our data suggest that proper assembly of primary cilia is critical for restricting the Hedgehog pathway during eye formation in the mouse. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. EARLY RESPONSIVE to DEHYDRATION 15, a new transcription factor that integrates stress signaling pathways.

    Science.gov (United States)

    Alves, Murilo S; Fontes, Elizabeth P B; Fietto, Luciano G

    2011-12-01

    The Early Responsive to Dehydration (ERD) genes are defined as those genes that are rapidly activated during drought stress. The encoded proteins show a great structural and functional diversity, with a particular class of proteins acting as connectors of stress response pathways. Recent studies have shown that ERD15 proteins from different species of plants operate in cross-talk among different response pathways. In this mini-review, we show the recent progress on the functional role of this diverse family of proteins and demonstrate that a soybean ERD15 homolog can act as a connector in stress response pathways that trigger a programmed cell death signal.

  20. Zebrafish foxo3b negatively regulates canonical Wnt signaling to affect early embryogenesis.

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    Xun-wei Xie

    Full Text Available FOXO genes are involved in many aspects of development and vascular homeostasis by regulating cell apoptosis, proliferation, and the control of oxidative stress. In addition, FOXO genes have been showed to inhibit Wnt/β-catenin signaling by competing with T cell factor to bind to β-catenin. However, how important of this inhibition in vivo, particularly in embryogenesis is still unknown. To demonstrate the roles of FOXO genes in embryogenesis will help us to further understand their relevant physiological functions. Zebrafish foxo3b gene, an orthologue of mammalian FOXO3, was expressed maternally and distributed ubiquitously during early embryogenesis and later restricted to brain. After morpholino-mediated knockdown of foxo3b, the zebrafish embryos exhibited defects in axis and neuroectoderm formation, suggesting its critical role in early embryogenesis. The embryo-developmental marker gene staining at different stages, phenotype analysis and rescue assays revealed that foxo3b acted its role through negatively regulating both maternal and zygotic Wnt/β-catenin signaling. Moreover, we found that foxo3b could interact with zebrafish β-catenin1 and β-catenin2 to suppress their transactivation in vitro and in vivo, further confirming its role relevant to the inhibition of Wnt/β-catenin signaling. Taken together, we revealed that foxo3b played a very important role in embryogenesis and negatively regulated maternal and zygotic Wnt/β-catenin signaling by directly interacting with both β-catenin1 and β-catenin2. Our studies provide an in vivo model for illustrating function of FOXO transcription factors in embryogenesis.

  1. Investigation of TEC and VLF space measurements associated to L'Aquila (Italy earthquakes

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    G. Stangl

    2011-04-01

    Full Text Available In this study, we report on Total Electron Content (TEC and Very Low Frequency (VLF space measurements derived from Global Positioning System (GPS and DEMETER satellites, respectively. These measurements are associated with the earthquake (EQ of a magnitude of 6.3, which occurred on 6 April 2009, in L'Aquila (Italy. Anomaly features are derived from the analysis of TEC and VLF observations recorded two weeks before and after the seismic event occurrence. A TEC map with an interpolated regional pixel resolution of 1° × 1° × 15 min in latitude, longitude and time was generated, allowing for the checking of a possible presence of disturbances over the L'Aquila region. This analysis is combined with the study of the time profile associated to the VLF flux density variations recorded by the Instrument Champ Electrique (ICE experiment on-board DEMETER satellite. We discuss, on the one hand, the combination efficiency of the electronic density and the VLF electromagnetic measurements and, on the other hand, the difficulty to distinguish between global effects and regional ones related to the earthquake.

  2. A multiple-mode three-dimensional model of VLF propagation in the earth-ionosphere waveguide in the presence of localized D region disturbances

    Science.gov (United States)

    Poulsen, William L.; Inan, Umran S.; Bell, Timothy F.

    1993-01-01

    Transient localized D region disturbances, such as those associated with lightning discharges, affect the characteristics of VLF waves propagating in the Earth-ionosphere waveguide. In particular, both phase and amplitude changes in the subionospheric signal can be observed at receiving sites as a result of the wave scattering that takes place in the disturbed region. In the present paper we present a multiple-mode three-dimensional model of VLF propagation in the Earth-ionosphere waveguide in the presence of localized D region disturbances. The model takes into account great circle (GC) propagation paths with realistic ground and ionospheric conductivity changes that result in mode conversion along the path. It is assumed that conductivity changes transverse to the GC paths are negligible except in the vicinity of the D region disturbance and that mode coupling is negligible within the disturbed region. This new model is applied to experimental observations and is found to be in general agreement. The diagnostics potential of the model for characterizing energetic particle precipitation events is discussed.

  3. Potentiation of the early visual response to learned danger signals in adults and adolescents.

    Science.gov (United States)

    Levita, Liat; Howsley, Philippa; Jordan, Jeff; Johnston, Pat

    2015-02-01

    The reinforcing effects of aversive outcomes on avoidance behaviour are well established. However, their influence on perceptual processes is less well explored, especially during the transition from adolescence to adulthood. Using electroencephalography, we examined whether learning to actively or passively avoid harm can modulate early visual responses in adolescents and adults. The task included two avoidance conditions, active and passive, where two different warning stimuli predicted the imminent, but avoidable, presentation of an aversive tone. To avoid the aversive outcome, participants had to learn to emit an action (active avoidance) for one of the warning stimuli and omit an action for the other (passive avoidance). Both adults and adolescents performed the task with a high degree of accuracy. For both adolescents and adults, increased N170 event-related potential amplitudes were found for both the active and the passive warning stimuli compared with control conditions. Moreover, the potentiation of the N170 to the warning stimuli was stable and long lasting. Developmental differences were also observed; adolescents showed greater potentiation of the N170 component to danger signals. These findings demonstrate, for the first time, that learned danger signals in an instrumental avoidance task can influence early visual sensory processes in both adults and adolescents.

  4. Baicalein inhibits lipid accumulation by regulating early adipogenesis and m-TOR signaling.

    Science.gov (United States)

    Seo, Min-Jung; Choi, Hyeon-Son; Jeon, Hui-Jeon; Woo, Mi-Seon; Lee, Boo-Yong

    2014-05-01

    Baicalein is a type of flavonoid that originates from Scutellaria baicalensis. In this study, we examined how baicalein inhibits lipid accumulation during adipogenesis in 3T3-L1 cells. Our data show that baicalein inhibited lipid accumulation during adipogenesis in a dose-dependent manner. Baicalein inhibition was limited to the early adipogenic stage. Cell cycle analysis showed that baicalein induced cell cycle arrest in the G0/G1 phase through cyclin downregulation. In addition, baicalein suppressed the mRNA expression of early adipogenic factors leading to downregulation of late adipogenic factors at mRNA and protein levels. Inhibition of adipogenic factors by baicalein was correlated with downregulation of lipid synthetic enzymes. Additionally, baicalein negatively regulated the m-TOR signaling pathway involved in lipid accumulation during adipogenesis, thus inhibiting phosphorylation of m-TOR and p70S6K. In a zebrafish study, baicalein significantly reduced lipid accumulation in Nile Red staining. Consistent with a report using cell lines, mRNA expression of adipogenic factors was decreased in a dose-dependent manner by baicalein. This result reflects a reduction in total triglyceride levels based on a triglyceride assay. Our data suggest that baicalein inhibits lipid accumulation by controlling the cell cycle and m-TOR signaling in 3T3-L1 cells, and its anti-adipogenic effect was found in a zebrafish model.

  5. Increased Nerve Growth Factor Signaling in Sensory Neurons of Early Diabetic Rats Is Corrected by Electroacupuncture

    Directory of Open Access Journals (Sweden)

    Stefania Lucia Nori

    2013-01-01

    Full Text Available Diabetic polyneuropathy (DPN, characterized by early hyperalgesia and increased nerve growth factor (NGF, evolves in late irreversible neuropathic symptoms with reduced NGF support to sensory neurons. Electroacupuncture (EA modulates NGF in the peripheral nervous system, being effective for the treatment of DPN symptoms. We hypothesize that NGF plays an important pathogenic role in DPN development, while EA could be useful in the therapy of DPN by modulating NGF expression/activity. Diabetes was induced in rats by streptozotocin (STZ injection. One week after STZ, EA was started and continued for three weeks. NGF system and hyperalgesia-related mediators were analyzed in the dorsal root ganglia (DRG and in their spinal cord and skin innervation territories. Our results show that four weeks long diabetes increased NGF and NGF receptors and deregulated intracellular signaling mediators of DRG neurons hypersensitization; EA in diabetic rats decreased NGF and NGF receptors, normalized c-Jun N-terminal and p38 kinases activation, decreased transient receptor potential vanilloid-1 ion channel, and possibly activated the nuclear factor kappa-light-chain-enhancer of activated B cells (Nf-κB. In conclusion, NGF signaling deregulation might play an important role in the development of DPN. EA represents a supportive tool to control DPN development by modulating NGF signaling in diabetes-targeted neurons.

  6. Early Warning Signals for Regime Transition in the Stable Boundary Layer: A Model Study

    Science.gov (United States)

    van Hooijdonk, I. G. S.; Moene, A. F.; Scheffer, M.; Clercx, H. J. H.; van de Wiel, B. J. H.

    2017-02-01

    The evening transition is investigated in an idealized model for the nocturnal boundary layer. From earlier studies it is known that the nocturnal boundary layer may manifest itself in two distinct regimes, depending on the ambient synoptic conditions: strong-wind or overcast conditions typically lead to weakly stable, turbulent nights; clear-sky and weak-wind conditions, on the other hand, lead to very stable, weakly turbulent conditions. Previously, the dynamical behaviour near the transition between these regimes was investigated in an idealized setting, relying on Monin-Obukhov (MO) similarity to describe turbulent transport. Here, we investigate a similar set-up, using direct numerical simulation; in contrast to MO-based models, this type of simulation does not need to rely on turbulence closure assumptions. We show that previous predictions are verified, but now independent of turbulence parametrizations. Also, it appears that a regime shift to the very stable state is signaled in advance by specific changes in the dynamics of the turbulent boundary layer. Here, we show how these changes may be used to infer a quantitative estimate of the transition point from the weakly stable boundary layer to the very stable boundary layer. In addition, it is shown that the idealized, nocturnal boundary-layer system shares important similarities with generic non-linear dynamical systems that exhibit critical transitions. Therefore, the presence of other, generic early warning signals is tested as well. Indeed, indications are found that such signals are present in stably stratified turbulent flows.

  7. Intra-plasmaspheric wave power density deduced from long-term DEMETER measurements of terrestrial VLF transmitter wave amplitudes

    Science.gov (United States)

    Lauben, D.; Cohen, M.; Inan, U.

    2012-12-01

    We deduce the 3d intra-plasmaspheric distribution of VLF wave power between conjugate regions of strong VLF wave amplitudes as measured by DEMETER for high-power terrestrial VLF transmitters during its ~6-yr lifetime. We employ a mixed WKB/full-wave technique to solve for the primary and secondary electromagnetic and electrostatic waves which are transmitted and reflected from strong cold-plasma density gradients and posited irregularities, in order to match the respective end-point measured amplitude distributions. Energy arriving in the conjugate region and also escaping to other regions of the magnetosphere is note. The resulting 3d distribution allows improved estimates for the long-term average particle scattering induced by terrestrial VLF transmitters.

  8. Electromagnetic Wave-filled Cavities Observed by the GEODESIC Sounding Rocket: A Direct Encounter with VLF Saucer Source Regions

    Science.gov (United States)

    Kabirzadeh, Rasoul

    The GEODESIC sounding rocket encountered hundreds of localized, VLF-wave-filled density depletions in an auroral return current region at altitudes between 900--1000 km. While these are similar to well-studied lower-hybrid "spikelets", which are electrostatic, many of the GEODESIC events exhibited strong VLF magnetic field enhancements as well. In the present study we show that these magnetic field fluctuations can be interpreted as the result of geomagnetic field-aligned electron currents driven by fluctuating electric fields parallel to the geomagnetic field lines. This observation suggests that the electromagnetic wave-filled cavities are signatures of unstable filaments of return current fluctuating at VLF frequencies. We argue that the cavities' spatial dimensions, their location inside the return current region and their total radiated power are consistent with the properties of VLF saucer source regions inferred from earlier satellite observations taken at higher altitudes.

  9. Van Allen Probes observations of prompt MeV radiation belt electron acceleration in nonlinear interactions with VLF chorus

    Science.gov (United States)

    Foster, J. C.; Erickson, P. J.; Omura, Y.; Baker, D. N.; Kletzing, C. A.; Claudepierre, S. G.

    2017-01-01

    Prompt recovery of MeV (millions of electron Volts) electron populations in the poststorm core of the outer terrestrial radiation belt involves local acceleration of a seed population of energetic electrons in interactions with VLF chorus waves. Electron interactions during the generation of VLF rising tones are strongly nonlinear, such that a fraction of the relativistic electrons at resonant energies are trapped by waves, leading to significant nonadiabatic energy exchange. Through detailed examination of VLF chorus and electron fluxes observed by Van Allen Probes, we investigate the efficiency of nonlinear processes for acceleration of electrons to MeV energies. We find through subpacket analysis of chorus waveforms that electrons with initial energy of hundreds of keV to 3 MeV can be accelerated by 50 keV-200 keV in resonant interactions with a single VLF rising tone on a time scale of 10-100 ms.

  10. Early signaling, referral, and treatment of adolescent chronic pain: a study protocol

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    Voerman Jessica S

    2012-06-01

    Full Text Available Abstract Background Chronic pain is prevalent among young people and negatively influences their quality of life. Furthermore, chronic pain in adolescence may persist into adulthood. Therefore, it is important early on to promote the self-management skills of adolescents with chronic pain by improving signaling, referral, and treatment of these youngsters. In this study protocol we describe the designs of two complementary studies: a signaling study and an intervention study. Methods and design The signaling study evaluates the Pain Barometer, a self-assessed signaling instrument for chronic pain in adolescents. To evaluate the feasibility of the Pain Barometer, the experiences of youth-health care nurses will be evaluated in semi-structured interviews. Also, we will explore the frequencies of referral per health-care provider. The intervention study evaluates Move It Now, a guided self-help intervention via the Internet for teenagers with chronic pain. This intervention uses cognitive behavioural techniques, including relaxation exercises and positive thinking. The objective of the intervention is to improve the ability of adolescents to cope with pain. The efficacy of Move It Now will be examined in a randomized controlled trial, in which 60 adolescents will be randomly assigned to an experimental condition or a waiting list control condition. Discussion If the Pain Barometer is proven to be feasible and Move It Now appears to be efficacious, a health care pathway can be created to provide the best tailored treatment promptly to adolescents with chronic pain. Move It Now can be easily implemented throughout the Netherlands, as the intervention is Internet based. Trial registration Dutch Trial Register NTR1926

  11. The early ELF signals of the gigantic jets captured by the Taiwan ground observation network

    Science.gov (United States)

    Chen, A. B. C.; Huang, P. H.; Su, H. T.; Hsu, R. R.

    2015-12-01

    The in-cloud ignition process of gigantic jets and blue jets receives attentions and discussions in the past years. The polarity and the position of their breakdown were proposed by Krehbiel et al. [2008] but no concrete observational evidence to support it directly. ELF spectrogram is a good tool to explore the electric activities, but traditional spectrograms are generated by a Fourier transform which obtain the frequency information through an integration operation. However the integration greatly limits the lowest frequency revealed by spectrogram and buries the important transient features. In this study, we applied a new but widely-used method, the Hilbert-Huang transform (HHT), to explore the spectrogram. Instead of the integration, HHT obtains the frequency information by differentiating on the phase angle, and become a powerful tool to reveal the fast frequency variation associated with transient luminous events. More than 100 transient luminous events including 25 gigantic jets observed by Taiwan ground optical observation network were analyzed. The results indicate that approximately 70% of gigantic jets can identify a rapid frequency variation in the interval of 300-600 milliseconds before main surge discharge, and this early feature can not find a clear corresponding amplitude variation in its sferic. Since this early signal can not be identified from the traditional Fourier spectrogram, but clear in-cloud lightning was registered correspondingly by the ground optical observation. In contrast to gigantic jets, this feature of early frequency change can be seen only in less than 30% of sprites and elves. These observational evidences are able to provide new constraints on the early discharge process of gigantic jets in clouds.

  12. Reactive oxygen species (ROS) as early signals in root hair cells responding to rhizobial nodulation factors.

    Science.gov (United States)

    Cárdenas, Luis; Quinto, Carmen

    2008-12-01

    Reactive oxygen species (ROS) are involved in supporting polar growth in pollen tubes, fucoid cells and root hair cells. However, there is limited evidence showing ROS changes during the earliest stages of the interaction between legume roots and rhizobia. We recently reported using Phaseolus vulgaris as a model system, the occurrence of a transient increase of ROS, within seconds, at the tip of actively growing root hair cells after treatment with Nod factors (NFs).1 This transient response is NFs-specific, and clearly distinct from the ROS changes induced by a fungal elicitor, with which sustained increases in ROS signal, is observed. Since ROS levels are transiently elevated after NFs perception, we propose that this ROS response is specific of the symbiotic interaction. Furthermore, the observed ROS changes correlate spatially and temporarily with the reported transient increases in calcium levels suggesting key roles for calcium and ROS during the early NF perception.

  13. Early Flood Detection for Rapid Humanitarian Response: Harnessing Near Real-Time Satellite and Twitter Signals

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    Brenden Jongman

    2015-10-01

    Full Text Available Humanitarian organizations have a crucial role in response and relief efforts after floods. The effectiveness of disaster response is contingent on accurate and timely information regarding the location, timing and impacts of the event. Here we show how two near-real-time data sources, satellite observations of water coverage and flood-related social media activity from Twitter, can be used to support rapid disaster response, using case-studies in the Philippines and Pakistan. For these countries we analyze information from disaster response organizations, the Global Flood Detection System (GFDS satellite flood signal, and flood-related Twitter activity analysis. The results demonstrate that these sources of near-real-time information can be used to gain a quicker understanding of the location, the timing, as well as the causes and impacts of floods. In terms of location, we produce daily impact maps based on both satellite information and social media, which can dynamically and rapidly outline the affected area during a disaster. In terms of timing, the results show that GFDS and/or Twitter signals flagging ongoing or upcoming flooding are regularly available one to several days before the event was reported to humanitarian organizations. In terms of event understanding, we show that both GFDS and social media can be used to detect and understand unexpected or controversial flood events, for example due to the sudden opening of hydropower dams or the breaching of flood protection. The performance of the GFDS and Twitter data for early detection and location mapping is mixed, depending on specific hydrological circumstances (GFDS and social media penetration (Twitter. Further research is needed to improve the interpretation of the GFDS signal in different situations, and to improve the pre-processing of social media data for operational use.

  14. Expansion of signaling genes for adaptive immune system evolution in early vertebrates

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    Okada Kinya

    2008-05-01

    Full Text Available Abstract Background The adaptive immune system (AIS of jawed vertebrates is a sophisticated system mediated by numerous genes in specialized cells. Phylogenetic analysis indicates that emergence of the AIS followed the occurrence of two rounds of whole-genome duplication (2R-WGD in early vertebrates, but little direct evidence linking these two events is available. Results We examined the relationship between 2R-WGD and the gain of AIS-related functions by numerous genes. To analyze the evolution of the many genes related to signal transduction in the AIS (defined as AIS genes, we identified groups of genes (defined as AIS subfamilies that included at least one human AIS gene, its paralogs (if any, and its Drosophila ortholog(s. Genomic mapping revealed that numerous pairs of AIS genes and their paralogs were part of paralogons – series of paralogous regions that derive from a common ancestor – throughout the human genome, indicating that the genes were retained as duplicates after 2R-WGD. Outgroup comparison analysis revealed that subfamilies in which human and fly genes shared a nervous system-related function were significantly enriched among AIS subfamilies, as compared with the overall incidence of shared nervous system-related functions among all subfamilies in bilaterians. This finding statistically supports the hypothesis that AIS-related signaling genes were ancestrally involved in the nervous system of urbilaterians. Conclusion The current results suggest that 2R-WGD played a major role in the duplication of many signaling genes, ancestrally used in nervous system development and function, that were later co-opted for new functions during evolution of the AIS.

  15. Lack of Interleukin-1 Signaling Results in Perturbed Early Vein Graft Wall Adaptations

    Science.gov (United States)

    Yu, Peng; Nguyen, Binh T.; Tao, Ming; Jiang, Tianyu; Mauro, Christine R.; Wang, Yuqi; Ozaki, C. Keith

    2012-01-01

    Background Vein grafts fail due to wall mal-adaptations to surgical injury and hemodynamic perturbations. Interleukin-1 signaling has emerged as an important mediator of the vascular response to trauma and hemodynamically induced vascular lesions. We therefore hypothesized that interleukin-1 signaling drives early vein graft wall adaptations. Methods Using interleukin-1 type I receptor knockout (IL-1RI−/−) and wild-type (B6129SF2/J) mice, we investigated morphologic changes 28 days after interposition isograft from donor inferior vena cava to recipient carotid artery, without (n=19) or with (n=13) outflow restriction. The impact of mouse strain on the response to vein arterialization was also evaluated between B6129SF2/J (n=18) and C57BL/6J (n=19) mice. Results No significant differences were observed in the traditional endpoints of intimal thickness and calculated luminal area, yet media+adventitia thickness of the vein graft wall of IL-1RI−/− mice was 44-52% smaller than wild-type mice, at the both proximal (Pinterleukin-1 signaling, the vein graft wall adapts differently compared to the injured artery, showing typical intima hyperplasia though attenuated media+adventitia thickening. B6129SF2/J mice exhibit more media+adventitia response than C57BL/6J mice. The inflammatory networks that underlie the vein response to arterialization hold many roles in the adaptation of the total wall, thus the utility of anti-inflammatory approaches to extend the durability of vein grafts comes into question. PMID:22853857

  16. ELF/VLF/LF Radio Propagation and Systems Aspects (La Propagation des Ondes Radio ELF/VLF/LF et les Aspects Systemes)

    Science.gov (United States)

    1993-05-01

    Umime 11uld sb’ngft R11111M fgM 7-1 INVESTIGATIONS OF EQUATORIAL IONOSPHERE NIGHTTIME MODE CONVERSION AT VLF* Verne Hildebrand IWG Corporation, 1940 Fifth...uniform, Symposium), supposing that has an length equal to Ŗa" and it is MIT, Cambridge oriented on the zz direction (fig.8). USA, Julio 1991 Let us...about 10 to 14 years. My from the floor, would someone like to start off? own experience as a systems engineer is that Verne Hildebrand the systems have

  17. Developing an ancient epithelial appendage: FGF signalling regulates early tail denticle formation in sharks.

    Science.gov (United States)

    Cooper, Rory L; Martin, Kyle J; Rasch, Liam J; Fraser, Gareth J

    2017-01-01

    Vertebrate epithelial appendages constitute a diverse group of organs that includes integumentary structures such as reptilian scales, avian feathers and mammalian hair. Recent studies have provided new evidence for the homology of integumentary organ development throughout amniotes, despite their disparate final morphologies. These structures develop from conserved molecular signalling centres, known as epithelial placodes. It is not yet certain whether this homology extends beyond the integumentary organs of amniotes, as there is a lack of knowledge regarding their development in basal vertebrates. As the ancient sister lineage of bony vertebrates, extant chondrichthyans are well suited to testing the phylogenetic depth of this homology. Elasmobranchs (sharks, skates and rays) possess hard, mineralised epithelial appendages called odontodes, which include teeth and dermal denticles (placoid scales). Odontodes constitute some of the oldest known vertebrate integumentary appendages, predating the origin of gnathostomes. Here, we used an emerging model shark (Scyliorhinus canicula) to test the hypothesis that denticles are homologous to other placode-derived amniote integumentary organs. To examine the conservation of putative gene regulatory network (GRN) member function, we undertook small molecule inhibition of fibroblast growth factor (FGF) signalling during caudal denticle formation. We show that during early caudal denticle morphogenesis, the shark expresses homologues of conserved developmental gene families, known to comprise a core GRN for early placode morphogenesis in amniotes. This includes conserved expression of FGFs, sonic hedgehog (shh) and bone morphogenetic protein 4 (bmp4). Additionally, we reveal that denticle placodes possess columnar epithelial cells with a reduced rate of proliferation, a conserved characteristic of amniote skin appendage development. Small molecule inhibition of FGF signalling revealed placode development is FGF dependent

  18. Regional seismic hazard for Revithoussa, Greece: an earthquake early warning Shield and selection of alert signals

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    Y. Xu

    2003-01-01

    Full Text Available The feasibility of an earthquake early warning Shield in Greece is being explored as a European demonstration project. This will be the first early warning system in Europe. The island of Revithoussa is a liquid natural gas storage facility near Athens from which a pipeline runs to a gas distribution centre in Athens. The Shield is being centred on these facilities. The purpose here is to analyze seismicity and seismic hazard in relation to the Shield centre and the remote sensor sites in the Shield network, eventually to help characterize the hazard levels, seismic signals and ground vibration levels that might be observed or create an alert situation at a station. Thus this paper mainly gives estimation of local seismic hazard in the regional working area of Revithoussa by studying extreme peak ground acceleration (PGA and magnitudes. Within the Shield region, the most important zone to be detected is WNW from the Shield centre and is at a relatively short distance (50 km or less, the Gulf of Corinth (active normal faults region. This is the critical zone for early warning of strong ground shaking. A second key region of seismicity is at an intermediate distance (100 km or more from the centre, the Hellenic seismic zone south or southeast from Peloponnisos. A third region to be detected would be the northeastern region from the centre and is at a relatively long distance (about 150 km, Lemnos Island and neighboring region. Several parameters are estimated to characterize the seismicity and hazard. These include: the 50-year PGA with 90% probability of not being exceeded (pnbe using Theodulidis & Papazachos strong motion attenuation for Greece, PGANTP; the 50-year magnitude and also at the 90% pnbe, M50 and MP50, respectively. There are also estimates of the earthquake that is most likely to be felt at a damaging intensity level, these are the most perceptible earthquakes at intensities VI, VII and VIII with magnitudes MVI, MVII and MVIII

  19. Latest progress on interactions between VLF/ELF waves and energetic electrons in the inner magnetosphere

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Interactions between very/extremely low frequency (VLF/ELF) waves and energetic electrons play a fundamental role in dynamics occurring in the inner magnetosphere. Here, we briefly discuss global properties of VLF/ELF waves, along with the variability of the electron radiation belts associated with wave-particle interactions and radial diffusion. We provide cases of electron loss and acceleration as a result of wave-particle interactions primarily due to such waves, and particularly some preliminary results of 3D evolution of phase space density from our currently developing 3D code. We comment on the existing mechanisms responsible for acceleration and loss, and identify several critical issues that need to be addressed. We review latest progress and suggest open questions for future investigation.

  20. Excitation of VLF quasi-electrostatic oscillations in the ionospheric plasma

    Directory of Open Access Journals (Sweden)

    B. Lundin

    Full Text Available A numerical solution of the dispersion equation for electromagnetic waves in a hot magnetized collisionless plasma has shown that, in a current-free ionospheric plasma, the distortion of the electron distribution function reproducing the downward flow of a thermal electron component and the compensating upward flow of the suprathermal electrons, which are responsible for the resulting heat flux, can destabilize quasi-electrostatic ion sound waves. The numerical analysis, performed with ion densities and electron temperature taken from the data recorded by the Interkosmos-24 (IK-24, Aktivny satellite, is compared with a VLF spectrum registered at the same time on board. This spectrum shows a wide frequency band emission below the local ion plasma frequency. The direction of the electron heat flux inherent to the assumed model of VLF emission generation is discussed

  1. Prediction Capabilities of VLF/LF Emission as the Main Precursor of Earthquake

    CERN Document Server

    Kachakhidze, Manana

    2013-01-01

    Recent satellite and ground-based observations proved that in earthquake preparation period in the seismogenic area we have VLF/LF and ULF electromagnetic emissions. According to the opinion of the authors of the present paper this phenomenon is more universal and reliable than other earthquake indicators. Hypothetically, in case of availability of adequate methodological grounds, in the nearest future, earth VLF/LF electromagnetic emission might be declared as the main precursor of earthquake. In particular, permanent monitoring of frequency spectrum of earth electromagnetic emission generated in the earthquake preparation period might turn out very useful with the view of prediction of large (M 5) inland earthquakes. The present paper offers a scheme of the methodology according to which the reality of the above given hypothesis can be checked up. To prove the prediction capabilities of earth electromagnetic emission we have used avalanche-like unstable model of fault formation and an analogous model of ele...

  2. EGS in sedimentary basins: sensitivity of early-flowback tracer signals to induced-fracture parameters

    Science.gov (United States)

    Karmakar, Shyamal; Ghergut, Julia; Sauter, Martin

    2015-04-01

    -effective aperture, in a water fracture (WF), or - fracture thickness and porosity, for a gel-proppant fracture (GPF). We find that parameter determination from SW early signals can significantly be improved by concomitantly using a number of solute tracers with different transport and retardation behaviour. We considered tracers of different sorptivity to proppant coatings, and to matrix rock surfaces, for GPF, as well as contrasting-diffusivity or -sorptivity tracers, for WF. An advantage of this SW approach is that it requires only small chaser volumes (few times the fracture volume), not relying on advective penetration into the rock matrix. Thus, selected tracer species are to be injected during the very last stage of the fracturing process, when fracture sizes and thus target parameters are supposed to attain more or less stable values. We illustrate the application of these tracer test design principles using hydro- and lithostratigraphy data from the Geothermal Research Platform at Groß Schönebeck [4], targeting a multi-layer reservoir (sedimentary and crystalline formations in 4-5 km depth) in the NE-German Sedimentary Basin. Acknowledgments: This work benefited from long-term support from Baker Hughes (Celle) and from the Lower-Saxonian Science and Culture Ministry (MWK Niedersachsen) within the applied research project gebo (Geothermal Energy and High-Performance Drilling, 2009-2014). The first author gratefully acknowledges continued financial support from the DAAD (German Academic Exchange Service) to pursuing Ph. D. work. References: [1] http://www.sciencedirect.com/science/article/pii/S1876610214017391 [2] http://www.geothermal-energy.org/cpdb/record_detail.php?id=7215 [3] http://www.geothermal-energy.org/cpdb/record_detail.php?id=19034 [4] http://www.gfz-potsdam.de/en/scientific-services/laboratories/gross-schoenebeck/

  3. Electron dispersion events in the morningside auroral zone and their relationship with VLF emissions

    Science.gov (United States)

    Hardy, David A.; Burke, William J.; Villalon, Elena

    1990-05-01

    This paper reports on observations of electron precipitation bursts observed in the morningside auroral zone with the J sensor, an electron detector aboard the Hilat satellite. The characteristics of these precipitation events are documented, and a theoretical explanation that could account for the observed properties is presented. According to this model, the dispersion events result from impulsive interactions of the electrons with intense asymmetric packets of VLF waves via the nonlinear ponderomotive force.

  4. Sequential antagonism of early and late Wnt-signaling by zebrafish colgate promotes dorsal and anterior fates.

    Science.gov (United States)

    Nambiar, Roopa M; Henion, Paul D

    2004-03-01

    The establishment of the vertebrate body plan involves patterning of the ectoderm, mesoderm, and endoderm along the dorsoventral and antero-posterior axes. Interactions among numerous signaling molecules from several multigene families, including Wnts, have been implicated in regulating these processes. Here we provide evidence that the zebrafish colgate(b382) (col) mutation results in increased Wnt signaling that leads to defects in dorsal and anterior development. col mutants display early defects in dorsoventral patterning manifested by a decrease in the expression of dorsal shield-specific markers and ectopic expression of ventrolaterally expressed genes during gastrulation. In addition to these early patterning defects, col mutants display a striking regional posteriorization within the neuroectoderm, resulting in a reduction in anterior fates and an expansion of posterior fates within the forebrain and midbrain-hindbrain regions. We are able to correlate these phenotypes to the overactivation of Wnt signaling in col mutants. The early dorsal and anterior patterning phenotypes of the col mutant embryos are selectively rescued by inactivation of Wnt8 function by morpholino translational interference. In contrast, the regionalized neuroectoderm posterioriorization phenotype is selectively rescued by morpholino-mediated inactivation of Wnt8b. These results suggest that col-mediated antagonism of early and late Wnt-signaling activity during gastrulation is normally required sequentially for both early dorsoventral patterning and the specification and patterning of regional fates within the anterior neuroectoderm.

  5. Resolving Early Signaling Events in T-Cell Activation Leading to IL-2 and FOXP3 Transcription

    Directory of Open Access Journals (Sweden)

    Jeffrey P. Perley

    2014-11-01

    Full Text Available Signal intensity and feedback regulation are known to be major factors in the signaling events stemming from the T-cell receptor (TCR and its various coreceptors, but the exact nature of these relationships remains in question. We present a mathematical model of the complex signaling network involved in T-cell activation with cross-talk between the Erk, calcium, PKC and mTOR signaling pathways. The model parameters are adjusted to fit new and published data on TCR trafficking, Zap70, calcium, Erk and Isignaling. The regulation of the early signaling events by phosphatases, CD45 and SHP1, and the TCR dynamics are critical to determining the behavior of the model. Additional model corroboration is provided through quantitative and qualitative agreement with experimental data collected under different stimulating and knockout conditions. The resulting model is analyzed to investigate how signal intensity and feedback regulation affect TCR- and coreceptor-mediated signal transduction and their downstream transcriptional profiles to predict the outcome for a variety of stimulatory and knockdown experiments. Analysis of the model shows that: (1 SHP1 negative feedback is necessary for preventing hyperactivity in TCR signaling; (2 CD45 is required for TCR signaling, but also partially suppresses it at high expression levels; and (3 elevated FOXP3 and reduced IL-2 signaling, an expression profile often associated with T regulatory cells (Tregs, is observed when the system is subjected to weak TCR and CD28 costimulation or a severe reduction in CD45 activity.

  6. Searching for early-warning signals of impending dieback and death in Mediterranean oaks

    Science.gov (United States)

    Colangelo, Michele; Ripullone, Francesco; Julio Camarero, Jesus; De Micco, Veronica; Gazol, Antonio; Gentilesca, Tiziana; Borghetti, Marco

    2017-04-01

    In recent decades, forest dieback episodes have been recorded worldwide affecting different tree species. In particular, several cases of widespread dieback and increased mortality rates have been described for Mediterranean oak (Quercus spp.) species. These dieback cases are revealing the high vulnerability of Mediterranean oaks, manifested as a loss in tree vigour (leaf shedding, canopy and shoot dieback), growth decline and sometimes tree death, as a consequence of temperatures rising at unprecedented rates and drying trends. However, in the wake of the so-called 'oak decline phenomenon', the attention on these species has generally been limited, perhaps because they are often regarded as well-adapted to the dry conditions typical of Mediterranean areas. Indeed, according to recent studies, the reduced size, the ability to sprout and the anisohydric behavior of Mediterranean oak species (reduced control of water loss and high stomatal conductance rates) would make them better adapted to withstand heat and drought stress then taller and non-sprouting isohydric species (e.g. conifer, with strict control of water loss by closing stomata). Here, we investigated the vulnerability of Mediterranean oaks by comparing neighboring living and recently dead trees in species with low (Q. pubescens), intermediate (Q. cerris, Q. frainetto) and high (Q. robur) sensitivity to water shortage. We analysed changes in tree vigour using tree-ring width and functional wood anatomical traits as proxies to search for early-warning signals of dieback, in connection with the main proposed dieback mechanisms (hydraulic failure and/or carbon starvation). We also modeled the probability of tree death as a function of tree size (diameter, height) by quantifying recent changes in growth and wood anatomy along tree-ring series. Contrary to the general concept that trees tend to experience increasing cavitation risk with increasing height, our studies show that smaller oaks are more prone to die

  7. Elucidating the early signal transduction pathways leading to fetal brain injury in preterm birth.

    Science.gov (United States)

    Elovitz, Michal A; Mrinalini, Conjeevaram; Sammel, Mary D

    2006-01-01

    Adverse neurologic outcome, including cerebral palsy, is a significant contributor to long-term morbidity in preterm neonates. However, the mechanisms leading to brain injury in the setting of a preterm birth are poorly understood. In the last decade, there has been a growing body of evidence correlating infection or inflammation with preterm birth. The presence of intrauterine inflammation significantly increases the risk for adverse neurologic outcome in the neonate. These studies were performed to elucidate the early signal transduction pathways activated in the fetal brain that may result in long-term neurologic injury. Using our mouse model of localized intrauterine inflammation, the activation of TH1/TH2 pathways in the placenta, fetus corpus, fetal liver, and fetal brain was investigated. Additional studies determined whether activation of TH1/TH2 pathways could promote cell death and alter glial development. Real-time PCR studies demonstrated that a robust TH1/TH2 response occurs rapidly in the fetal brain after exposure to intrauterine inflammation. The cytokine response in the fetus and placenta was not significantly correlated with the response in the fetal brain. Along with an immune response, cell death pathways were activated early in the fetal brain in response to intrauterine LPS. Implicating TH1/TH2 and cell death pathways in permanent brain injury are our findings of an increase in GFAP mRNA and protein as well as a loss of pro-oligodendrocytes. With increased understanding of the mechanisms by which inflammation promotes brain injury in the preterm neonate, identification of potential targets to limit adverse neonatal outcomes becomes possible.

  8. Anomalous propagation of Omega VLF waves near the geomagnetic equator

    Science.gov (United States)

    Ohtani, A.; Kikuchi, T.; Nozaki, K.; Kurihara, N.; Kuratani, Y.; Ohse, M.

    1983-09-01

    Omega HAIKU, REUNION, and LIBERIA signals were received and anomalous propagation characteristics were obtained near the geomagnetic equator. Short-period fluctuations were found in the phase of the HAIKU 10.2 kHz signal in November 1979 and in the phase and amplitude of the HAIKU 13.6 kHz signal in November 1981. These cyclic fluctuations are in close correlation with the phase cycle slippings, which occur most frequently when the receiver is located at 6 S geomagnetic latitude. On the basis of anisotropic waveguide mode theory indicating much less attenuation in WE propagation than in EW propagation at the geomagnetic equator, it is concluded that the short-period fluctuations in the phase and amplitude are due to interference between the short-path and the long-path signals.

  9. New Generation of ELF/VLF Wave Injection Experiments for HAARP

    Science.gov (United States)

    Sonwalkar, V. S.; Reddy, A.; Watkins, B. J.

    2016-12-01

    We present a ray tracing study to investigate the feasibility of a new generation of wave injection experiments from HAARP transmitter (L 4.9). Highly successful whistler mode wave injection experiments from SIPLE station, Antarctica, have established the importance of such experiments to study magnetospheric wave-particle interactions, and for cold and hot plasma diagnostics [Helliwell and Katsufrakis, 1974; Carpenter and Miller, 1976; Sonwalkar et al., 1997]. Modulated heating experiments from HAARP have shown that it is possible to launch ELF/VLF waves into the magnetosphere that can be observed on the ground after one-, two-, and multi-hop ducted propagation [Inan et al., 2004]. Recent research has also shown that ionospheric heating experiments using HAARP can lead to the formation of magnetospheric ducts [e.g. Milikh et al., 2010; Fallen et al., 2011]. Collectively, these results indicate that the HAARP (or similar) transmitter can be used first to form ducts on nearby L shells, and then to inject and trap transmitter generated ELF/VLF waves in those ducts. Ray tracing studies using a model magnetosphere shows that ELF/VLF waves in a few kilohertz range can be trapped in ducts with L shells near the HAARP transmitter. For example, 1.5 kHz waves injected from L shell = 4.9 and altitude = 200 km can be trapped in ducts located within 0.3 L of the transmitter L-shell. The duct parameters needed for ray-trapping are typically duct width dL 0.1-0.3 and duct enhancement factor dNe/Ne 10-20% or more. The location of plasmapause with respect to transmitter plays a role in the nature of trapping. The duct locations and parameters required for trapping ELF/VLF waves inside the ducts are consistent with past observations of ducts generated by the HAARP transmitter. Ray tracing calculations provide trapped wave normal angles, time delays, resonant energetic electron energy, estimates of wave intensity inside the duct, on the ground, and on satellites such DEMETER, Van

  10. VLF observation during Leonid Meteor Shower-2002 from Kolkata

    CERN Document Server

    Chakrabarti, S K; Acharyya, K; Mandal, S; Chakrabarti, S; Khan, R; Bose, B; Chakrabarti, Sandip K.

    2002-01-01

    Using a Gyrator-II Loop antenna tuned at 19.0Khz, we monitored the meteor shower during 17-24th November, 2002. We observe the primary peak at 3h58m (UT) on the 19th of November, 2002. We distinctly observed several `beadlike' and `exponentially dropping' signals. The `beadlike' signals were more in abundance on the 18th of November, 2002, one day prior to the actual encounter.

  11. Early estrogen-induced gene 1, a novel RANK signaling component, is essential for osteoclastogenesis

    Institute of Scientific and Technical Information of China (English)

    Han Kyoung Choi; Hye Ri Kang; Eutteum Jung; Tae Eon Kim; Jing Jing Lin; Soo Young Lee

    2013-01-01

    The receptor activator of NF-kB (RANK) and immunoreceptor tyrosine-based activation motif (ITAM)-containing adaptors are essential factors involved in regulating osteoclast formation and bone remodeling.Here,we identify early estrogen-induced gene 1 (EEIG1) as a novel RANK ligand (RANKL)-inducible protein that physically interacts with RANK and further associates with Gab2,PLCγ2 and Tec/Btk kinases upon RANKL stimulation.EEIG1 positively regulates RANKL-induced osteoclast formation,likely due to its ability to facilitate RANKL-stimulated PLCγ2 phosphorylation and NFATc1 induction.In addition,an inhibitory peptide designed to block RANK-EEIG1 interaction inhibited RANKL-induced bone destruction by reducing osteoclast formation.Together,our results identify EEIG1 as a novel RANK signaling component controlling RANK-mediated osteoclast formation,and suggest that targeting EEIG1 might represent a new therapeutic strategy for the treatment of pathological bone resorption.

  12. The early signal substances induced by heat stress in brains of mice

    Institute of Scientific and Technical Information of China (English)

    Chunxu WANG; Hanxing WANG

    2008-01-01

    To study the effects of early signal substances induced by heat stress in brains of Kunming mice, six-month-old mice (n=72) were pretreated with heat stress and subsequent ischemia/reperfusion by clipping of their bilateral cervical common arteries for 7 min. According to different treatments, animals were randomly divided into four groups: (1) normal control group; (2) heat stress pre-treatment followed by ischemia and reperfusion group (HS/IR); (3) ischemia and reperfusion group (IR); (4) heat stress group (HS). Animals in the later three groups were subdivided into 3 subgroups (1 day, 4 days, 14 days), respectively. The changes in the expression of cAMP res-ponse element binding protein (CREB) and calcitonin gene-related peptide (CGRP) were detected by immuno-histochemistry and computer image analysis methods. The results showed that compared with the normal group, the expressions of CREB in the hippocampal CA1 region increased significantly in the HS, HS/IR and IR groups (P<0.05). Compared to the normal group, heat stress could result in CGRP excretion and redistribution in the cerebrum, with the highest level in the 4 d HS/IR group. Following heat stress, CGRP immunoreactivity was observed in varicose fibers and neuronal perikarya within the CA1 region. The results indicate that heat stress can induce CREB expression, which in turn stimulates CGRP secretion.

  13. Maternal Mga is required for Wnt signaling and organizer formation in the early Xenopus embryo

    Institute of Scientific and Technical Information of China (English)

    Fei Gu; Huijuan Shi; Li Gao; Haiyan Zhang; Qinghua Tao

    2012-01-01

    Maternal Wnt11 is both necessary and sufficient for the formation of Spemann organizer in Xenopus embryo.Xnr3 and Siamois have been identified as the direct target genes of maternal Wnt11/β-catenin during organizer induction.The depletion of maternal XTcf3 resulted in the ectopic expression of Xnr3 and Siamois,suggesting the activity of β-catenin/XTcf3 is strictly regulated in the early Xenopus embryos.Here,we show that Xenopus mga (Xmga) is a maternal gene required for dorsal axis formation.Overexpression experiments indicate that mouse Mga potentiates the activity of β-catenin in the induction of organizer-specific genes.Depletion of maternal Xmga results in the dramatic decrease of the expression of organizer genes and ventralization phenotype,indicating that Xmga is required for β-catenin function and organizer formation.Depletion of XTcf3 cannot rescue organizer gene expression and axis formation in Xmga-depleted embryos,suggesting Xmga is downstream of XTcf3 during organizer induction.We conclude that maternal Xmga is critical for the function of β-catenin during organizer formation and dorsal development of Xenopus embryo.To our knowledge,this is a report for the first time to implicate Mga in regulating Wnt signaling.

  14. Redox Signaling Is an Early Event in the Pathogenesis of Renovascular Hypertension

    Directory of Open Access Journals (Sweden)

    Joseph P. Grande

    2013-09-01

    Full Text Available Activation of the renin-angiotensin-aldosterone system plays a critical role in the development of chronic renal damage in patients with renovascular hypertension. Although angiotensin II (Ang II promotes oxidative stress, inflammation, and fibrosis, it is not known how these pathways intersect to produce chronic renal damage. We tested the hypothesis that renal parenchymal cells are subjected to oxidant stress early in the development of RVH and produce signals that promote influx of inflammatory cells, which may then propagate chronic renal injury. We established a reproducible murine model of RVH by placing a tetrafluoroethhylene cuff on the right renal artery. Three days after cuff placement, renal tissue demonstrates no histologic abnormalities despite up regulation of both pro- and anti-oxidant genes. Mild renal atrophy was observed after seven days and was associated with induction of Tnfα and influx of CD3+ T cells and F4/80+ macrophages. By 28 days, kidneys developed severe renal atrophy with interstitial inflammation and fibrosis, despite normalization of plasma renin activity. Based on these considerations, we propose that renal parenchymal cells initiate a progressive cascade of events leading to oxidative stress, interstitial inflammation, renal fibrosis, and atrophy.

  15. Cannabis use in early adolescence: Evidence of amygdala hypersensitivity to signals of threat

    Directory of Open Access Journals (Sweden)

    Philip A. Spechler

    2015-12-01

    Full Text Available Cannabis use in adolescence may be characterized by differences in the neural basis of affective processing. In this study, we used an fMRI affective face processing task to compare a large group (n = 70 of 14-year olds with a history of cannabis use to a group (n = 70 of never-using controls matched on numerous characteristics including IQ, SES, alcohol and cigarette use. The task contained short movies displaying angry and neutral faces. Results indicated that cannabis users had greater reactivity in the bilateral amygdalae to angry faces than neutral faces, an effect that was not observed in their abstinent peers. In contrast, activity levels in the cannabis users in cortical areas including the right temporal-parietal junction and bilateral dorsolateral prefrontal cortex did not discriminate between the two face conditions, but did differ in controls. Results did not change after excluding subjects with any psychiatric symptomology. Given the high density of cannabinoid receptors in the amygdala, our findings suggest cannabis use in early adolescence is associated with hypersensitivity to signals of threat. Hypersensitivity to negative affect in adolescence may place the subject at-risk for mood disorders in adulthood.

  16. EFFECT OF ARSENICALS ON THE EXPRESSION OF CELL CYCLE PROTEINS AND EARLY SIGNALING EVENTS IN PRIMARY HUMAN KERATINOCYTES.

    Science.gov (United States)

    Effect of Arsenicals on the Expression of Cell Cycle Proteins and Early Signaling Events in Primary Human Keratinocytes.Mudipalli, A, Owen R. D. and R. J. Preston, Environmental Carcinogenesis Division, USEPA, RTP, NC 27711.Environmental exposure to arsenic is a m...

  17. Features of discrete VLF emissions observed at Gulmarg, India during the magnetic storm of 6–7 March, 1986

    Indian Academy of Sciences (India)

    R Singh; A K Singh; D Siingh; R P Singh

    2007-12-01

    During the analysis of archived VLF data from Indian low latitude ground stations, some discrete VLF emissions recorded at the low latitude ground station Gulmarg (geomagnetic latitude 24°26′N; geomagnetic longitude 147° 09′E, L = 1.28) during moderate magnetic storm activity ( $K^{−}_{P}$} = 32, index varies from 4 to 6 during the observation period) on 6/7 March, 1986 are presented in this paper. The dynamic spectra of these discrete VLF emissions were observed along with tweeks and its harmonics, which is interesting and complex to explain. In most of the events the harmonic frequency of tweeks correlates with the starting frequency of harmonics of discrete emissions. In order to explain the observed features of discrete VLF emissions, we propose cyclotron resonance interaction between whistler mode wave and energetic electrons of inner radiation belt as possible generation mechanism. An attempt is also made to determine parallel energy, anisotropy and wave growth relevant to the generation process of VLF emissions.

  18. Early Development of UVM based Verification Environment of Image Signal Processing Designs using TLM Reference Model of RTL

    Directory of Open Access Journals (Sweden)

    Abhishek Jain

    2014-01-01

    Full Text Available With semiconductor industry trend of “smaller the better”, from an idea to a final product, more innovation on product portfolio and yet remaining competitive and profitable are few criteria which are culminating into pressure and need for more and more innovation for CAD flow, process management and project execution cycle. Project schedules are very tight and to achieve first silicon success is key for projects. This necessitates quicker verification with better coverage matrix. Quicker Verification requires early development of the verification environment with wider test vectors without waiting for RTL to be available. In this paper, we are presenting a novel approach of early development of reusable multi-language verification flow, by addressing four major activities of verification – 1. Early creation of Executable Specification 2. Early creation of Verification Environment 3. Early development of test vectors and 4. Better and increased Re-use of blocks Although this paper focuses on early development of UVM based Verification Environment of Image Signal Processing designs using TLM Reference Model of RTL, same concept can be extended for non-image signal processing designs.

  19. ELF/VLF/LF Propagation and System Design

    Science.gov (United States)

    1987-06-23

    values [681 to data of Rhoads and Garner 1691 for the path from Haiku to Washington, DC, that occurred in May and June 1965. They found a good fit to...Figs. 106 and 107. Experimental e/amples of the diurnal variation of received signal from Haiku to Washington, DC [691, are shown in Figs. 108 and 109

  20. 电离层人工调制激发的下行ELF/VLF波辐射%The downward ELF/VLF waves radiation excited by ionospheric artificial modulation

    Institute of Scientific and Technical Information of China (English)

    常珊珊; 赵正予; 汪枫

    2011-01-01

    By heating the ionosphere with large ELF/VLF-modulated HF wave, a virtual antenna is produced in the ionosphere, which is an effective means to radiate ELF/VLF waves. This paper uses the modulated-heating models of Wang Feng (2009) to calculate the strength of the LF radiation source produced by HF heating, uses full-wave model to analyze attenuation and reflection of the LF wave transmitting downward, and with HAARP experiment parameter, simulates magnetic field of the LF signals on the sea, which is in PT order, according with the experimental data.%通过大功率ELF/VLF调幅高频波对电离层进行加热,形成电离层虚拟天线,可以作为发射ELF/VLF波的一种有效手段.本文使用汪枫(2009)的调制加热模型,计算高频加热电离层产生的低频辐射源强度,采用全波解算法分析辐射的低频波向下传播过程中的衰减和反射问题,并采用HAARP实验参数,模拟出在海面上接收到的低频信号强度为PT量级,与实验数据一致.模拟结果表明,加热泵波功率、低频调制波频率、以及加热纬度位置是影响ELF/VLF波辐射和传播的三个主要因素.

  1. Signal peptide hydrophobicity is critical for early stages in protein export by Bacillus subtilis

    NARCIS (Netherlands)

    Zanen, G; Meima, R; Tjalsma, H; Jongbloed, JDH; Westers, H; Oudega, B; Luirink, J; van Dijl, JM; Quax, WJ; Houben, E.N.G.

    2005-01-01

    Signal peptides that direct protein export in Bacillus subtilis are overall more hydrophobic than signal peptides in Escherichia coli. To study the importance of signal peptide hydrophobicity for protein export in both organisms, the alpha-amylase AmyQ was provided with leucine-rich (high hydrophobi

  2. 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.

  3. Erythropoietin (EPO): EPO-receptor signaling improves early endochondral ossification and mechanical strength in fracture healing.

    Science.gov (United States)

    Holstein, Joerg H; Menger, Michael D; Scheuer, Claudia; Meier, Christoph; Culemann, Ulf; Wirbel, Rainer J; Garcia, Patric; Pohlemann, Tim

    2007-02-13

    Beyond its role in the regulation of red blood cell proliferation, the glycoprotein erythropoietin (EPO) has been shown to promote cell regeneration and angiogenesis in a variety of different tissues. In addition, EPO has been indicated to share significant functional and structural homologies with the vascular endothelial growth factor (VEGF), a cytokine essential in the process of fracture healing. However, there is complete lack of information on the action of EPO in bone repair and fracture healing. Therefore, we investigated the effect of EPO treatment on bone healing in a murine closed femur fracture model using radiological, histomorphometric, immunohistochemical, biomechanical and protein biochemical analysis. Thirty-six SKH1-hr mice were treated with daily i.p. injections of 5000 U/kg EPO from day 1 before fracture until day 4 after fracture. Controls received equivalent amounts of the vehicle. After 2 weeks of fracture healing, we could demonstrate expression of the EPO-receptor (EPOR) in terminally differentiating chondrocytes within the callus. At this time point EPO-treated animals showed a higher torsional stiffness (biomechanical analysis: 39.6+/-19.4% of the contralateral unfractured femur) and an increased callus density (X-ray analysis (callus density/spongiosa density): 110.5+/-7.1%) when compared to vehicle-treated controls (14.3+/-8.2% and 105.9+/-6.6%; pEPO treatment had vanished at 5 weeks after fracture. We conclude that EPO-EPOR signaling is involved in the process of early endochondral ossification, enhancing the transition of soft callus to hard callus.

  4. Diagnosis of early-stage damage to polymer - glass fibre composites using non-contact measurement of vibration signals

    Energy Technology Data Exchange (ETDEWEB)

    Figlus, Tomasz; Koziol, Mateusz [Silesian University of Technology, Katowice (Poland)

    2016-08-15

    Ensuring reliable operation of the means of transport requires the development of methods for early detection of damage to its components made of composite materials. For diagnostic testing of composite materials during normal operation of the means of transport, the authors propose to use non-contact vibration measurement methods and their subsequent processing and analysis. The paper presents the results of laboratory tests whose aim was to assess the ability to detect early symptoms of damage to composite materials using non-contact vibration measurement methods. The measurements included mechanical curves of the glass composite samples made in a conventional manner and simultaneously their vibrations were measured in a non-contact manner using a laser vibrometer. Continuous wavelet transform was used for processing vibration signals. Calculated time-frequency scale distributions of vibration signals enabled the designation of frequency scale bands in which early, low-energy symptoms of damage to glass composites are observed. The analysis results allow to draw conclusions that the use of non-contact measurements and processing of vibration signals extends the existing range of composites research and enables detection of early, low-energy symptoms of damage to glass fibre reinforced composites.

  5. Doppler-cancelled response to VLF gravitational waves

    Science.gov (United States)

    Caporali, A.

    1981-01-01

    The interaction of long periodic gravitational waves with a three link microwave system known as the Doppler Cancelling System is discussed. This system, which was developed for a gravitational redshift experiment, uses one-way and two-way Doppler informatin to construct the beat signal of two reference oscillators moving with respect to each other. The geometric optics approximation is used to derive the frequency shift produced on a light signal propagating in a gravitational wave space-time. The signature left on the Doppler-cancelled beat by burst and continuous gravitational waves is analyzed. A comparison is made between the response to gravitational waves of the Doppler Cancelling System and that of a Doppler tracking system which employs two-way, round-trip radio waves. A three-fold repetition of the gravitational wave form is found to be a common feature of the response functions of both systems. These two functions otherwise exhibit interesting differences.

  6. Wnt signaling activates Shh signaling in early postnatal intervertebral discs, and re-activates Shh signaling in old discs in the mouse.

    Science.gov (United States)

    Winkler, Tamara; Mahoney, Eric J; Sinner, Debora; Wylie, Christopher C; Dahia, Chitra Lekha

    2014-01-01

    Intervertebral discs (IVDs) are strong fibrocartilaginous joints that connect adjacent vertebrae of the spine. As discs age they become prone to failure, with neurological consequences that are often severe. Surgical repair of discs treats the result of the disease, which affects as many as one in seven people, rather than its cause. An ideal solution would be to repair degenerating discs using the mechanisms of their normal differentiation. However, these mechanisms are poorly understood. Using the mouse as a model, we previously showed that Shh signaling produced by nucleus pulposus cells activates the expression of differentiation markers, and cell proliferation, in the postnatal IVD. In the present study, we show that canonical Wnt signaling is required for the expression of Shh signaling targets in the IVD. We also show that Shh and canonical Wnt signaling pathways are down-regulated in adult IVDs. Furthermore, this down-regulation is reversible, since re-activation of the Wnt or Shh pathways in older discs can re-activate molecular markers of the IVD that are lost with age. These data suggest that biological treatments targeting Wnt and Shh signaling pathways may be feasible as a therapeutic for degenerative disc disease.

  7. Increase in FLAIR Signal of the Fluid Within the Resection Cavity as Early Recurrence Marker: Also Valid for Brain Metastases?

    Science.gov (United States)

    Bette, Stefanie; Gempt, Jens; Wiestler, Benedikt; Huber, Thomas; Specht, Hanno; Meyer, Bernhard; Zimmer, Claus; Kirschke, Jan S; Boeckh-Behrens, Tobias

    2017-01-01

    Purpose Increase in FLAIR signal of the fluid within the resection cavity is described as a highly specific and early sign for tumor recurrence in gliomas. The aim of this study was to assess the prognostic value of FLAIR signal increase in partially or completely resected brain metastases. Materials and Methods 209 cases of surgery for brain metastases were assessed. 41 cases with at least two follow-up MRIs were retrospectively included in this study. Quantitative and qualitative assessment of the FLAIR signal intensity of the fluid within the resection cavity was performed in the MRI examination at recurrent disease/last contact and in the previous MRI examination. Results 3 of 6 cases with local tumor recurrence showed a FLAIR signal increase (sensitivity 50.0 %, specificity 100.0 %). In one case, this sign was observed even about 3 months before tumor recurrence. The specificity of FLAIR signal increase for overall tumor recurrence (local and distant) was also 100.0 %, but with a lower sensitivity of 13.0 %. Quantitative analysis showed significant differences for signal intensity of the resection cavity as well as for the change of signal intensity of the resection cavity in cases with or without local tumor recurrence. Conclusion An increase in FLAIR signal of the fluid within the resection cavity might be a highly specific and early sign of local tumor recurrence/tumor progression also for brain metastases. Key points: · An increase in FLAIR signal intensity of the fluid within the resection cavity is also observed in previously resected brain metastases.. · The pathophysiology of this sign might be due to a cell-proliferative process.. Citation Format · Bette S, Gempt J, Wiestler B et al. Increase of the FLAIR Signal of the Fluid within the Resection Cavity as Early Recurrence Marker: Also Valid for Brain Metastases?. Fortschr Röntgenstr 2017; 189: 63 - 70. © Georg Thieme Verlag KG Stuttgart · New York.

  8. Application of gamma ray spectrometric measurements and VLF-EM data for tracing vein type uranium mineralization

    Directory of Open Access Journals (Sweden)

    Ibrahim Gaafar

    2015-12-01

    Full Text Available This study is an attempt to use the gamma ray spectrometric measurements and VLF-EM data to identify the subsurface structure and map uranium mineralization along El Sela shear zone, South Eastern Desert of Egypt. Many injections more or less mineralized with uranium and associated with alteration processes were recorded in El Sela shear zone. As results from previous works, the emplacement of these injections is structurally controlled and well defined by large shear zones striking in an ENE–WSW direction and crosscut by NW–SE to NNW–SSE fault sets. VLF method has been applied to map the structure and the presence of radioactive minerals that have been delineated by the detection of high uranium mineralization. The electromagnetic survey was carried out to detect the presence of shallow and deep conductive zones that cross the granites along ENE–WSW fracturing directions and to map its spatial distribution. The survey comprised seventy N–S spectrometry and VLF-EM profiles with 20 m separation. The resulted data were displayed as composite maps for K, eU and eTh as well as VLF-Fraser map. Twelve profiles with 100 m separation were selected for detailed description. The VLF-EM data were interpreted qualitatively as well as quantitatively using the Fraser and the Karous–Hjelt filters. Fraser filtered data and relative current density pseudo-sections indicate the presence of shallow and deep conductive zones that cross the granites along ENE–WSW shearing directions. High uranium concentrations found just above the higher apparent current-density zones that coincide with El-Sela shear zone indicate a positive relation between conductivity and uranium minerals occurrence. This enables to infer that the anomalies detected by VLF-EM data are due to the highly conductive shear zone enriched with uranium mineralization extending for more than 80 m.

  9. Early spatiotemporal-specific changes in intermediate signals are predictive of cytotoxic sensitivity to TNFα and co-treatments

    Science.gov (United States)

    Loo, Lit-Hsin; Bougen-Zhukov, Nicola Michelle; Tan, Wei-Ling Cecilia

    2017-03-01

    Signaling pathways can generate different cellular responses to the same cytotoxic agents. Current quantitative models for predicting these differential responses are usually based on large numbers of intracellular gene products or signals at different levels of signaling cascades. Here, we report a study to predict cellular sensitivity to tumor necrosis factor alpha (TNFα) using high-throughput cellular imaging and machine-learning methods. We measured and compared 1170 protein phosphorylation events in a panel of human lung cancer cell lines based on different signals, subcellular regions, and time points within one hour of TNFα treatment. We found that two spatiotemporal-specific changes in an intermediate signaling protein, p90 ribosomal S6 kinase (RSK), are sufficient to predict the TNFα sensitivity of these cell lines. Our models could also predict the combined effects of TNFα and other kinase inhibitors, many of which are not known to target RSK directly. Therefore, early spatiotemporal-specific changes in intermediate signals are sufficient to represent the complex cellular responses to these perturbations. Our study provides a general framework for the development of rapid, signaling-based cytotoxicity screens that may be used to predict cellular sensitivity to a cytotoxic agent, or identify co-treatments that may sensitize or desensitize cells to the agent.

  10. Detecting leachate plumes and groundwater pollution at Ruseifa municipal landfill utilizing VLF-EM method

    Science.gov (United States)

    Al-Tarazi, E.; Abu Rajab, J.; Al-Naqa, A.; El-Waheidi, M.

    2008-09-01

    A Very Low Frequency-Electromagnetic (VLF-EM) survey was carried out in two sites of domestic waste of old and recent landfills. The landfill structures lie on a major highly fractured limestone aquifer of shallow groundwater less than 30 m, which is considered as the main source of fresh water in Amman-Zarqa region. A total of 18 VLF-EM profiles were conducted with length ranges between 250 and 1500 m. Hydrochemical and biochemical analysis of water samples, taken from wells in the region, has also been conducted. The integrated results of previous DC resistivity method of the same study area and the outcomes of the 2-D tipper inversion of VLF-EM data proved the efficiency of this method in locating shallow and deep leachate plume with resistivity less than 20 Ω m, and enabling the mapping of anomalous bodies and their extensions down to 40 m depth. The sign of groundwater contamination was noticed in many surrounding wells resulting in the high number of fecal coliform bacteria and total coliform bacteria and the increase in inorganic parameters such as chloride (Cl). The pollution of groundwater wells in the landfill area is attributed to the leachate bodies which flow through the upper part of Wadi Es Sir (A7) or Amman-Wadi Es Sir Aquifer (B2/A7). Furthermore, several structural features were detected and the direction of local groundwater movement has been determined. The structural features have been found to have critical effects on the flowing of leachate plume towards north-northeast and west-southwest of the potable aquifer in the area.

  11. Numerical simulation of whistler-triggered VLF emissions observed in Antartica

    Energy Technology Data Exchange (ETDEWEB)

    Nunn, D. [Southhampton Univ., Southhampton (United Kingdom); Smith, A.J. [British Antarctic Survey, Cambridge (United Kingdom)

    1996-03-01

    The authors have extracted from VLF databases from British Antarctica Survey data taken at Halley and Faraday stations, examples of whistler-triggered emissions (WTE). The WTE are relatively narrow band emissions triggered by natural background whistlers undergoing nonlinear wave particle interactions generally in the equatorial regions. They occur with either rising or falling frequency relative to the triggering waves. Using a Vlasov type code the authors are able to simulate the types of emissions which are observed. 24 refs., 8 figs., 3 tabs.

  12. LINFOMA RELACIONADO AO VÍRUS DA LEUCEMIA FELINA (VLF) – RELATO DE CASO

    OpenAIRE

    Eleutério, Daniela Aparecida Sampaio; Faculdade Dr. Francisco Maeda - FAFRAM

    2014-01-01

    O presente trabalho tem como objetivo relatar um caso de linfoma relacionado ao vírus da leucemia felina (VLF) ocorrido na cidade de Uberlândia-MG. Um felino, macho, de três anos de idade, foi encaminhado ao Hospital Veterinário da Universidade Federal de Uberlândia, apresentando-se apático, dispneico, com alterações oculares, mucosas hipocoradas e linfonodos reativos. O hemograma do animal indicou anemia normocítica. No exame radiográfico observou deslocamento da traquéia dorsalmente e não f...

  13. Full-wave model of D-region upward VLF coupling to whistlers in the plasmasphere

    Science.gov (United States)

    Jacobson, A. R.; Shao, X.; Lay, E. H.

    2012-12-01

    Atmospheric-lightning-to-plasmasphere VLF coupling via whistlers is key to understanding the problem of radiation-belt losses and the slot region. In the lowermost ionosphere, the "D-region" (roughly 60 - 100 km altitude), the coupling occurs between the VLF incident from the "vacuum" below, to the electron whistler capable of transiting upward through the E- and F-regions above. We have modified our successful and data-validated D-region VLF downward-reflection model to predict upward-coupled whistler waveforms recorded on topside satellites. The model has been run in production mode for predicting downward-reflected waveforms recorded at ground stations, but the model's internal calculation also fully describes the "penetrating" solution that merges into the oblique electron whistler. We have begun to test the model against VLF, three-dimensional electric-field recordings from the Vector Electric Field Instrument (VEFI) [Pfaff et al., 2010] on the C/NOFS satellite. VEFI's broadband recording and large on-board memory serendipitously provide an excellent platform for studying lightning whistlers in the plasmasphere. We have already demonstrated [Jacobson et al., 2011] that VEFI is superbly suited for testing transionospheric propagation, in conjunction with the World Wide Lightning Location Network (WWLLN; see www.wwlln.net) to provide groundtruth location/time of the lightning strokes. This poster will describe latest results. Jacobson, A. R., R. H. Holzworth, R. F. Pfaff, and M. P. McCarthy (2011), Study of oblique whistlers in the low-latitude ionosphere, jointly with the C/NOFS satellite and the World-Wide Lightning Location Network, Annales Geophysicae, 29, 851-863. Pfaff, R., D. Rowland, H. Freudenreich, K. Bromund, K. Le, M. Acuna, J. Klenzing, C. Liebrecht, S. Martin, W. J. Burke, N. C. Maynard, D. E. Hunton, P. A. Roddy, J. O. Ballenthin, and G. R. Wilson (2010), Observations of DC electric fields in the low-latitude ionosphere and their variations with

  14. Microprocessor implementation of an FFT for ionospheric VLF observations

    Science.gov (United States)

    Elvidge, J.; Kintner, P.; Holzworth, R.

    1984-01-01

    A fast Fourier transform algorithm is implemented on a CMOS microprocessor for application to very low-frequency electric fields (less than 10 kHz) sensed on high-altitude scientific balloons. Two FFT's are calculated simultaneously by associating them with conjugate symmetric and conjugate antisymmetric results. One goal of the system was to detect spectral signatures associated with fast time variations present in natural signals such as whistlers and chorus. Although a full evaluation of the system was not possible for operational reasons, a measure of the system's success has been defined and evaluated.

  15. The Carboxy Terminal Region of the Human Cytomegalovirus Immediate Early 1 (IE1 Protein Disrupts Type II Inteferon Signaling

    Directory of Open Access Journals (Sweden)

    Bindu Raghavan

    2014-04-01

    Full Text Available Interferons (IFNs activate the first lines of defense against viruses, and promote innate and adaptive immune responses to viruses. We report that the immediate early 1 (IE1 protein of human cytomegalovirus (HCMV disrupts signaling by IFNγ. The carboxyl-terminal region of IE1 is required for this function. We found no defect in the initial events in IFNγ signaling or in nuclear accumulation of signal transducer and activator of transcription 1 (STAT1 in IE1-expressing cells. Moreover, we did not observe an association between disruption of IFNγ signaling and nuclear domain 10 (ND10 disruption. However, there is reduced binding of STAT1 homodimers to target gamma activated sequence (GAS elements in the presence of IE1. Co-immunoprecipitation studies failed to support a direct interaction between IE1 and STAT1, although these studies revealed that the C-terminal region of IE1 was required for interaction with STAT2. Together, these results indicate that IE1 disrupts IFNγ signaling by interfering with signaling events in the nucleus through a novel mechanism.

  16. TNF-alpha and Notch signaling regulates the expression of HOXB4 and GATA3 during early T lymphopoiesis.

    Science.gov (United States)

    Dos Santos Schiavinato, Josiane Lilian; Oliveira, Lucila Habib Bourguignon; Araujo, Amélia Goes; Orellana, Maristela Delgado; de Palma, Patrícia Viana Bonini; Covas, Dimas Tadeu; Zago, Marco Antonio; Panepucci, Rodrigo Alexandre

    2016-10-01

    During the early thymus colonization, Notch signaling activation on hematopoietic progenitor cells (HPCs) drives proliferation and T cell commitment. Although these processes are driven by transcription factors such as HOXB4 and GATA3, there is no evidence that Notch directly regulates their transcription. To evaluate the role of NOTCH and TNF signaling in this process, human CD34(+) HPCs were cocultured with OP9-DL1 cells, in the presence or absence of TNF. The use of a Notch signaling inhibitor and a protein synthesis inhibitor allowed us to distinguish primary effects, mediated by direct signaling downstream Notch and TNF, from secondary effects, mediated by de novo synthesized proteins. A low and physiologically relevant concentration of TNF promoted T lymphopoiesis in OP9-DL1 cocultures. TNF positively modulated the expression of both transcripts in a Notch-dependent manner; however, GATA3 induction was mediated by a direct mechanism, while HOXB4 induction was indirect. Induction of both transcripts was repressed by a GSK3β inhibitor, indicating that activation of canonical Wnt signaling inhibits rather than induces their expression. Our study provides novel evidences of the mechanisms integrating Notch and TNF-alpha signaling in the transcriptional induction of GATA3 and HOXB4. This mechanism has direct implications in the control of self-renewal, proliferation, commitment, and T cell differentiation.

  17. Early signals for emerging food safety risks: From past cases to future identification

    NARCIS (Netherlands)

    Brug, F,J, van de; Luijckx, N.B.L.; Cnossen, H.J.; Houben, G.F.

    2014-01-01

    During the last decades multiple unexpected and wide spread food safety incidents have occurred. The aim of this study is to learn from the past by studying the early emergence of historic food safety risks and apply these lessons for future early identification of emerging food safety risks. Inform

  18. Early signals for emerging food safety risks: From past cases to future identification

    NARCIS (Netherlands)

    Brug, F,J, van de; Luijckx, N.B.L.; Cnossen, H.J.; Houben, G.F.

    2014-01-01

    During the last decades multiple unexpected and wide spread food safety incidents have occurred. The aim of this study is to learn from the past by studying the early emergence of historic food safety risks and apply these lessons for future early identification of emerging food safety risks.

  19. FLAIR signal increase of the fluid within the resection cavity after glioma surgery: generally valid as early recurrence marker?

    Science.gov (United States)

    Bette, Stefanie; Gempt, Jens; Huber, Thomas; Delbridge, Claire; Meyer, Bernhard; Zimmer, Claus; Kirschke, Jan S; Boeckh-Behrens, Tobias

    2017-08-01

    OBJECTIVE Recent studies have indicated that a signal intensity increase of the fluid within the resection cavity on FLAIR images may predict tumor recurrence after glioma surgery. The aim of this study was to assess the increase in FLAIR signal intensity in a large patient cohort and in subgroups to assess its prognostic value for early tumor recurrence in glioma patients. METHODS A total of 212 patients (213 cases) who had undergone surgery for an intracranial glioma (WHO Grade IV [n = 103], WHO Grade III [n = 57], and WHO Grade II [n = 53]) were included in this retrospective study. FLAIR signal within the resection cavity at the time of tumor recurrence/last contact and on the previous MRI study was assessed qualitatively and quantitatively. Appearance of FLAIR signal increase was studied over time using Kaplan-Meier estimates in subgroups. RESULTS Patients with WHO Grade II glioma and connection of the resection cavity to CSF who did not undergo radiotherapy did not regularly develop this sign and were excluded from further analysis. For the remaining 87 cases, FLAIR signal intensity increase was observed in 27 cases. Recurrent disease was found in 26 of these 27 cases, resulting in a specificity of 80.0%, a sensitivity of 31.7%, and positive and negative predictive values of 96.3% and 6.7%, respectively. In 4 cases this sign had been observed prior (range 2.8-8.5 months) to tumor recurrence defined by standard criteria. Quantitative analysis underlined the results of qualitative analysis, but it did not add a diagnostic value. CONCLUSIONS Signal intensity increase of the fluid within the resection cavity on FLAIR images is a rare but highly specific and early sign for tumor recurrence/tumor progression in completely and incompletely resected high-grade glioma without connection of the resection cavity to CSF and with radiotherapy.

  20. Regulation of early signaling and gene expression in the α-particle and bystander response of IMR-90 human fibroblasts

    Directory of Open Access Journals (Sweden)

    Hei Tom K

    2010-07-01

    Full Text Available Abstract Background The existence of a radiation bystander effect, in which non-irradiated cells respond to signals from irradiated cells, is well established. To understand early signaling and gene regulation in bystander cells, we used a bio-informatics approach, measuring global gene expression at 30 minutes and signaling pathways between 30 minutes and 4 hours after exposure to α-particles in IMR-90 fibroblasts. Methods We used whole human genome microarrays and real time quantitative PCR to measure and validate gene expression. Microarray analysis was done using BRB-Array Tools; pathway and ontology analyses were done using Ingenuity Pathway Analysis and PANTHER, respectively. We studied signaling in irradiated and bystander cells using immunoblotting and semi-quantitative image analysis. Results Gene ontology suggested signal transduction and transcriptional regulation responding 30 minutes after treatment affected cell structure, motility and adhesion, and interleukin synthesis. We measured time-dependent expression of genes controlled by the NF-κB pathway; matrix metalloproteinases 1 and 3; chemokine ligands 2, 3 and 5 and interleukins 1β, 6 and 33. There was an increased response of this set of genes 30 minutes after treatment and another wave of induction at 4 hours. We investigated AKT-GSK3β signaling and found both AKT and GSK3β are hyper-phosphorylated 30 minutes after irradiation and this effect is maintained through 4 hours. In bystander cells, a similar response was seen with a delay of 30 minutes. We proposed a network model where the observed decrease in phosphorylation of β-catenin protein after GSK3β dependent inactivation can trigger target gene expression at later times after radiation exposure Conclusions These results are the first to show that the radiation induced bystander signal induces a widespread gene expression response at 30 minutes after treatment and these changes are accompanied by modification of

  1. Characteristics of VLF/LF Sferics from Elve-producing Lightning Discharges

    Science.gov (United States)

    Blaes, P.; Zoghzoghy, F. G.; Marshall, R. A.

    2013-12-01

    Lightning return strokes radiate an electromagnetic pulse (EMP) which interacts with the D-region ionosphere; the largest EMPs produce new ionization, heating, and optical emissions known as elves. Elves are at least six times more common than sprites and other transient luminous events. Though the probability that a lightning return stroke will produce an elve is correlated with the return stroke peak current, many large peak current strokes do not produce visible elves. Apart from the lightning peak current, elve production may depend on the return stroke speed, lightning altitude, and ionospheric conditions. In this work we investigate the detailed structure of lightning that gives rise to elves by analyzing the characteristics of VLF/LF lightning sferics in conjunction with optical elve observations. Lightning sferics were observed using an array of six VLF/LF receivers (1 MHz sample-rate) in Oklahoma, and elves were observed using two high-speed photometers pointed over the Oklahoma region: one located at Langmuir Laboratory, NM and the other at McDonald Observatory, TX. Hundreds of elves with coincident LF sferics were observed during the summer months of 2013. We present data comparing the characteristics of elve-producing and non-elve producing lightning as measured by LF sferics. In addition, we compare these sferic and elve observations with FDTD simulations to determine key properties of elve-producing lightning.

  2. Solar flare induced D-region ionospheric perturbations evaluated from VLF measurements

    Science.gov (United States)

    Singh, Ashutosh K.; Singh, A. K.; Singh, Rajesh; Singh, R. P.

    2014-03-01

    The results of very low frequency (VLF) wave amplitude measurements carried out at the low latitude station Varanasi (geom. lat. 14∘55'N, long. 154∘E), India during solar flares are presented for the first time. The VLF waves (19.8 kHz) transmitted from the NWC-transmitter, Australia propagated in the Earth-ionosphere waveguide to long distances and were recorded at Varanasi. Data are analyzed and the reflection height H' and the sharpness factor β are evaluated. It is found that the reflection height decreases whereas sharpness factor increases with the increase of solar flare power. The H' is found to be higher and β smaller at low latitudes than the corresponding values at mid and high latitudes. The sunspot numbers were low during the considered period 2011-2012, being the rising phase of solar cycle 24 and as a result cosmic rays may impact the D-region ionosphere. The increased ionization from the flare lowers the effective reflecting height, H', of the D-region roughly in proportion to the logarithm of the X-ray flare intensity from a typical mid-day unperturbed value of about 71-72 km down to about 65 km for an X class flare. The sharpness ( β) of the lower edge of the D-region is also significantly increased by the flare but reaches a clear saturation value of about 0.48 km-1 for flares of magnitude greater than about X1 class.

  3. Some unusual discrete VLF emissions observed at a low-latitude ground station at Agra

    Directory of Open Access Journals (Sweden)

    B. Singh

    Full Text Available A detailed analysis of the VLF emissions data obtained during occasional whistler campaigns at the low-latitude ground station Agra (geomagnetic latitude 17°1' N, L = 1.15 has yielded some unusual discrete VLF emissions of the rising type. These include (1 emissions occurring at time intervals increasing in ge ommetrical progression, (2 emissions occuring simulta neously in different frequency ranges and (3 emissions observed during daytime. In the present study, the observed characteristics of these emissions are described and interpreted. It is shown that the increasing time delay between different components of the emissions match closely with the propagation time delays between different hops of a whistler of dispersion 19 s1/2, the unusual occurrence of the emissions in two different frequency ranges approximately at the same time may possibly be linked with their generation at two different locations, and the occurrence of emissions during daytime may be due to propagation under the influence of equatorial anomaly.

  4. In connection with identification of VLF emissions before L'Aquila earthquake

    CERN Document Server

    Kachakhidze, M; Kachakhidze, N

    2012-01-01

    The present paper deals with an attempt to check up the theoretical model of self-generated seismo-electromagnetic oscillations of LAI system on the basis of retrospective data. Application of the offered simple model enables one to explain qualitatively the mechanism of VLF electromagnetic emission initiated in the process of an earthquake preparation. It is worth to pay attention to the fact that frequency changes from MHz to kHz in electromagnetic emission spectrum comes to a good agreement with avalanche-like unstable model of fault formation. L'Aquila earthquake taken as an example to isolate reliably the Earth VLF emission from the magnetospheric electromagnetic emission of the same frequency range, MHD criterion is offered together with geomagnetic activity indexes. On the basis of the considered three earthquakes, according to the opinion of authors the model of self-generated seismo-electromagnetic oscillations of the LAI system will enable us to approach the problem of resolution of earthquake predi...

  5. Study of Ionospheric Perturbations in D-Layer Using VLF Receiver at Tashkent IHY Station

    Science.gov (United States)

    Ahmedov, Bobomurat

    2016-07-01

    Tashkent International Heliophysical Year (IHY) station is a member of Atmospheric Weather Electromagnetic System for Observation, Modeling and Education (AWESOME) network being operated globally to study the ionosphere and the magnetosphere with the help of electromagnetic waves in Very Low Frequency (VLF) band. Regular monitoring of the D- and F-layers of ionosphere over Central Asia territory is being performed on the permanent basis starting year 2008 when one VLF receiver and two SuperSID receivers were provided to Uzbekistan IHY cite by Stanford University. The results obtained at Tashkent IHY station are applied to earthquake electromagnetic precursors, lightning, and Solar flares and to ionospheric disturbances originating from gamma ray flares of Soft Gamma-Ray Repeaters connected with evolution of strongly magnetized neutron stars believed as magnetars. Regular monitoring of the D-layer of ionosphere over Central Asia territory has been performed on the permanent basis. Several Solar events are observed and the analysis has shown that there is simultaneous correlation between the times of change of amplitude of the waves and the Solar flares. Features of the lightning discharge generated by radio atmospherics are studied and its effectiveness in D-region ionosphere diagnostics is examined.

  6. In connection with identification of VLF emissions before L'Aquila earthquake

    Directory of Open Access Journals (Sweden)

    M. K. Kachakhidze

    2012-04-01

    Full Text Available The present paper deals with an attempt to check the theoretical model of self-generated seismo-electromagnetic oscillations of LAI system on the basis of retrospective data.

    Application of the offered simple model enables one to explain qualitatively the mechanism of VLF electromagnetic emission initiated in the process of an earthquake preparation. Besides, the model enables us to associate telluric character geoelectric and geomagnetic perturbations incited by rock polarization and self-generated electromagnetic oscillations of lithosphere-atmosphere system.

    L'Aquila earthquake taken as an example to isolate reliably the Earth VLF emission from the magnetospheric electromagnetic emission of the same frequency range, MHD criterion is offered together with geomagnetic activity indexes.

    On the basis of the considered three earthquakes, according to the opinion of authors the model of self-generated seismo-electromagnetic oscillations of the LAI system will enable us to approach the problem of resolution of earthquake prediction with certain accuracy.

  7. Orbiting transmitter and antenna for spaceborne communications at ELF/VLF to submerged submarines

    Science.gov (United States)

    Bannister, P. R.; Harrison, J. K.; Rupp, C. C.; King, R. W. P.; Cosmo, M. L.; Lorenzini, E. C.; Dyer, C. J.; Grossi, M. D.

    1993-01-01

    An orbital emplacement for the transmitter and the antenna of a communications link at ELF (30 to 300 Hz) and VLF (3 kHz to 30 kHz) to submerged submarines has been considered since the very inception of the space age. However, only recently has space technology reached a sufficient level of maturity for system designers to undertake serious studies of this link configuration. The optimistic outlook stems from recent space technology developments, such as the design and construction by NASA of long orbiting tethers, and the testing, onboard Shuttle Orbiter ATLANTIS, of the first spaceborne 20 km metal wire. This is known as the Tethered Satellite System-1 (TSS-1), a space mission that might be possibly followed by other flights, with tether lengths that could reach 100 km. Once deployed at a height of, say, 300 km, from a Shuttle Orbiter, or from another suitable platform, a long, thin tether aligns itself along the local vertical by virtue of the gradient of the Earth gravity field. If made of metal, the tether can function as a VED (Vertical Electric Dipole) transmitting antenna at ELF and VLF.

  8. Involvement of ethylene biosynthesis and signalling in fruit set and early fruit development in zucchini squash (Cucurbita pepo L.).

    Science.gov (United States)

    Martínez, Cecilia; Manzano, Susana; Megías, Zoraida; Garrido, Dolores; Picó, Belén; Jamilena, Manuel

    2013-09-22

    We have identified a kind of parthenocarpy in zucchini squash which is associated with an incomplete andromonoecy, i.e. a partial conversion of female into bisexual flowers. Given that andromonoecy in this and other cucurbit species is caused by a reduction of ethylene production in the female flower, the associated parthenocarpic development of the fruit suggested the involvement of ethylene in fruit set and early fruit development. We have compared the production of ethylene as well as the expression of 13 ethylene biosynthesis and signalling genes in pollinated and unpollinated ovaries/fruits of two cultivars, one of which is parthenocarpic (Cavili), while the other is non-parthenocarpic (Tosca). In the latter, unpollinated ovaries show an induction of ethylene biosynthesis and ethylene signal transduction pathway genes three days after anthesis, which is concomitant with the initiation of fruit abortion and senescence. Fruit set and early fruit development in pollinated flowers of both cultivars and unpollinated flowers of Cavili is coupled with low ethylene biosynthesis and signalling, which would also explain the partial andromonoecy in the parthenocarpic genotype. The reduction of ethylene production in the ovary cosegregates with parthenocarpy and partial andromonoecy in the selfing progeny of Cavili. Moreover, the induction of ethylene in anthesis (by ethephon treatments) reduced the percentage of bisexual parthenocarpic flowers in Cavili, while the inhibition of ethylene biosynthesis or response (by AVG and STS treatments) induces not only andromonoecy but also the parthenocarpic development of the fruit in both cultivars. Results demonstrate that a reduction of ethylene production or signalling in the zucchini flower is able to induce fruit set and early fruit development, and therefore that ethylene is actively involved in fruit set and early fruit development. Auxin and TIBA treatments, inducing fruit set and early fruit development in this species

  9. ELF/VLF signatures of sprite-producing lightning discharges observed during the 2005 EuroSprite campaign

    DEFF Research Database (Denmark)

    Greenberg, E.; Price, C.; Yair, Y.

    2009-01-01

    During the summer of 2005, transient luminous events were optically imaged from the French Pyrénées as part of the EuroSprite campaign. Simultaneously, extremely low frequency (ELF: 3–3000 Hz) and broadband very low frequency (VLF: 3–30 kHz) data were recorded continuously at two separate receive...

  10. Early activation of FGF and nodal pathways mediates cardiac specification independently of Wnt/beta-catenin signaling.

    Directory of Open Access Journals (Sweden)

    Lee J Samuel

    Full Text Available BACKGROUND: Cardiac induction, the first step in heart development in vertebrate embryos, is thought to be initiated by anterior endoderm during gastrulation, but what the signals are and how they act is unknown. Several signaling pathways, including FGF, Nodal, BMP and Wnt have been implicated in cardiac specification, in both gain- and loss-of-function experiments. However, as these pathways regulate germ layer formation and patterning, their specific roles in cardiac induction have been difficult to define. METHODOLOGY/PRINCIPAL FINDINGS: To investigate the mechanisms of cardiac induction directly we devised an assay based on conjugates of anterior endoderm from early gastrula stage Xenopus embryos as the inducing tissue and pluripotent ectodermal explants as the responding tissue. We show that the anterior endoderm produces a specific signal, as skeletal muscle is not induced. Cardiac inducing signal needs up to two hours of interaction with the responding tissue to produce an effect. While we found that the BMP pathway was not necessary, our results demonstrate that the FGF and Nodal pathways are essential for cardiogenesis. They were required only during the first hour of cardiogenesis, while sustained activation of ERK was required for at least four hours. Our results also show that transient early activation of the Wnt/beta-catenin pathway has no effect on cardiogenesis, while later activation of the pathway antagonizes cardiac differentiation. CONCLUSIONS/SIGNIFICANCE: We have described an assay for investigating the mechanisms of cardiac induction by anterior endoderm. The assay was used to provide evidence for a direct, early and transient requirement of FGF and Nodal pathways. In addition, we demonstrate that Wnt/beta-catenin pathway plays no direct role in vertebrate cardiac specification, but needs to be suppressed just prior to differentiation.

  11. Prospects for early localization of gravitational-wave signals from compact binary coalescences with advanced detectors

    OpenAIRE

    Manzotti, Alessandro; Dietz, Alexander

    2012-01-01

    A leading candidate source of detectable gravitational waves is the inspiral and merger of pairs of stellar-mass compact objects. The advanced LIGO and advanced Virgo detectors will allow scientists to detect inspiral signals from more massive systems and at earlier times in the detector band, than with first generation detectors. The signal from a coalescence of two neutron stars is expected to stay in the sensitive band of advanced detectors for several minutes, thus allowing detection befo...

  12. Early redox, Src family kinase, and calcium signaling integrate wound responses and tissue regeneration in zebrafish

    OpenAIRE

    Yoo, Sa Kan; Freisinger, Christina M.; LeBert, Danny C.; Huttenlocher, Anna

    2012-01-01

    Tissue injury can lead to scar formation or tissue regeneration. How regenerative animals sense initial tissue injury and transform wound signals into regenerative growth is an unresolved question. Previously, we found that the Src family kinase (SFK) Lyn functions as a redox sensor in leukocytes that detects H2O2 at wounds in zebrafish larvae. In this paper, using zebrafish larval tail fins as a model, we find that wounding rapidly activated SFK and calcium signaling in epithelia. The immedi...

  13. Daily genetic profiling indicates JAK/STAT signaling promotes early hepatic stellate cell transdifferentiation

    Institute of Scientific and Technical Information of China (English)

    Ashley; M; Lakner; Cathy; C; Moore; Alyssa; A; Gulledge; Laura; W; Schrum

    2010-01-01

    AIM: To identify signaling pathways and genes that initiate and commit hepatic stellate cells (HSCs) to transdifferentiation. METHODS: Primary HSCs were isolated from male Sprague-Dawley rats and cultured on plastic for 0-10 d. Gene expression was assessed daily (quiescent to day 10 culture-activation) by real time polymerase chain reaction and data clustered using AMADA software. The significance of JAK/STAT signaling to HSC transdifferentiation was determined by treating cells with a JAK2 inhibitor. RESUL...

  14. Early Intervention of Didang Decoction on MLCK Signaling Pathways in Vascular Endothelial Cells of Type 2 Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Shoujiao Ye

    2016-01-01

    Full Text Available In the study, type 2 diabetic rat model was established using streptozotocin (STZ combined with a high-fat diet, and the rats were divided into control and diabetic groups. Diabetic groups were further divided into nonintervening, simvastatin, Didang Decoction (DDD early-phase intervening, DDD mid-phase intervening, and DDD late-phase intervening groups. The expression level of MLCK was detected using Western Blot analysis, and the levels of cyclic adenosine monophosphate (cAMP, protein kinase C (PKC, and protein kinase A (PKA were examined using Real Time PCR. Under the electron microscope, the cells in the early-DDD-intervention group and the simvastatin group were significantly more continuous and compact than those in the diabetic group. Compared with the control group, the expression of cAMP-1 and PKA was decreased in all diabetic groups, whereas the expression of MLCK and PKC was increased in early- and mid-phase DDD-intervening groups (P<0.05; compared with the late-phase DDD-intervening group, the expression of cAMP-1 and PKA was higher, but the level of MLCK and PKC was lower in early-phase DDD-intervening group (P<0.05. In conclusion, the early use of DDD improves the permeability of vascular endothelial cells by regulating the MLCK signaling pathway.

  15. 大气噪声对甚低频通信系统干扰仿真分析%Simulation and Analysis of Almospheric Noise Interference on VLF/LF Communication

    Institute of Scientific and Technical Information of China (English)

    施意; 张爽; 张昕

    2013-01-01

    甚低频通信又称为长波通信,具有传播距离远,水下传播,传播信号稳定、衰减小等特点,大气噪声会对甚低频通信系统产生严重影响,结合大气噪声经典模型和CCIR 322报告中多年的测量结果,对大气噪声干扰下的甚低频通信系统进行仿真,得出在不同强度的大气噪声干扰下,甚低频通信系统的误码率,验证了大气噪声中的主要为脉冲噪声对甚低频通信系统产生严重影响。%The very low frequency/low frequency communication systems althrough greatly influenced by atmospheric noise generally has the features of long propagation distance, stable propagation signal, low attenuation and underwater propagation. In combination of classical model of atmospheric noise and observational data from CCIR Report 322, the simulation on VLF/LF communication with atmospheric noise is done, and this simulation indicates that the impulse noise in the atmospheric noise has a serious impact on VLF communication system.

  16. Determining the relative impact of electrical conductivity and dielectric permittivity on the GPR early-time signal

    Science.gov (United States)

    Algeo, J.; Slater, L. D.; Binley, A. M.; Van Dam, R. L.; Watts, C. W.

    2016-12-01

    We employ early-time amplitude analysis, a recently developed ground-penetrating radar (GPR) methodology, in conjunction with electrical resistivity tomography (ERT) to determine the relative impact of dielectric permittivity and electrical conductivity on the GPR early-time signal (ETS). Early-time amplitude analysis uses changes in the amplitude of the overlapping GPR air- and ground-waves to resolve the electromagnetic properties of the subsurface. It has been employed to assess the water content of geologic materials at laboratory and field scales. As the amplitude of the ETS is dependent on both conductivity and permittivity, both of which can be affected by changes in soil water content, it is important to understand the relative magnitude of the impacts of these two parameters on GPR amplitude. Previous work in this field has related the early-time signal to conductivity and permittivity changes in a field setting, however these variations in electromagnetic properties were caused by changes in both lithology and water content. We carried out an irrigation experiment at the Butt Close and Honey Pot field sites in Woburn, Bedfordshire, UK, managed by Rothamstead Research, to explore how changes in conductivity and permittivity, caused by changes in water content, impact the ETS. Our GPR data provide early-time information and a measurement of permittivity from reflections off of a plow pan layer located at a constant depth in the subsurface. Data from the ERT survey provide a measurement of electrical conductivity. We modified the conductivity and permittivity of the subsurface by irrigating with groundwater. We carry out a multiple regression analysis to determine the relative impacts of changing conductivity and permittivity at the Butt Close and Honey Pot sites, and what effect these changes might have on estimates of soil water content. The results of our investigation help in the development of GPR ETS techniques for mapping and monitoring water content

  17. Early

    Directory of Open Access Journals (Sweden)

    Kamel Abd Elaziz Mohamed

    2014-04-01

    Conclusion: Early PDT is recommended for patients who require prolonged tracheal intubation in the ICU as outcomes like the duration of mechanical ventilation length of ICU stay and hospital stay were significantly shorter in early tracheostomy.

  18. Unmanned airborne vehicle (UAV): Flight testing and evaluation of two-channel E-field very low frequency (VLF) instrument

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-12-01

    Using VLF frequencies, transmitted by the Navy`s network, for airborne remote sensing of the earth`s electrical, magnetic characteristics was first considered by the United States Geological Survey (USGS) around the mid 1970s. The first VLF system was designed and developed by the USGS for installation and operation on a single engine, fixed wing aircraft used by the Branch of Geophysics for geophysical surveying. The system consisted of five channels. Two E-field channels with sensors consisting of a fixed vertical loaded dipole antenna with pre-amp mounted on top of the fuselage and a gyro stabilized horizontal loaded dipole antenna with pre-amp mounted on a tail boom. The three channel magnetic sensor consisted of three orthogonal coils mounted on the same gyro stabilized platform as the horizontal E-field antenna. The main features of the VLF receiver were: narrow band-width frequency selection using crystal filters, phase shifters for zeroing out system phase variances, phase-lock loops for generating real and quadrature gates, and synchronous detectors for generating real and quadrature outputs. In the mid 1990s the Branch of Geophysics designed and developed a two-channel E-field ground portable VLF system. The system was built using state-of-the-art circuit components and new concepts in circuit architecture. Small size, light weight, low power, durability, and reliability were key considerations in the design of the instrument. The primary purpose of the instrument was for collecting VLF data during ground surveys over small grid areas. Later the system was modified for installation on a Unmanned Airborne Vehicle (UAV). A series of three field trips were made to Easton, Maryland for testing and evaluating the system performance.

  19. Characteristics of VLF wave propagation in the Earth's magnetosphere in the presence of an artificial density duct

    Science.gov (United States)

    Pasmanik, Dmitry; Demekhov, Andrei

    We study the propagation of VLF waves in the Earth's ionosphere and magnetosphere in the presence of large-scale artificial plasma inhomogeneities which can be created by HF heating facilities like HAARP and ``Sura''. A region with enhanced cold plasma density can be formed due to the action of HF heating. This region is extended along geomagnetic field (up to altitudes of several thousand km) and has rather small size across magnetic field (about 1 degree). The geometric-optical approximation is used to study wave propagation. The plasma density and ion composition are calculated with the use of SAMI2 model, which was modified to take the effect of HF heating into account. We calculate ray trajectories of waves with different initial frequency and wave-normal angles and originating at altitudes of about 100 km in the region near the heating area. The source of such waves could be the lightning discharges, modulated HF heating of the ionosphere, or VLF transmitters. Variation of the wave amplitude along the ray trajectories due to refraction is considered and spatial distribution of wave intensity in the magnetosphere is analyzed. We show that the presence of such a density disturbances can lead to significant changes of wave propagation trajectories, in particular, to efficient guiding of VLF waves in this region. This can result in a drastic increase of the VLF-wave intensity in the density duct. The dependence of wave propagation properties on parameters of heating facility operation regime is considered. We study the variation of the spatial distribution of VLF wave intensity related to the slow evolution of the artificial inhomogeneity during the heating.

  20. Sonic hedgehog signaling regulates mode of cell division of early cerebral cortex progenitors and increases astrogliogenesis

    Directory of Open Access Journals (Sweden)

    Geissy LL Araújo

    2014-03-01

    Full Text Available The morphogen Sonic Hedgehog (SHH plays a critical role in the development of different tissues. In the central nervous system, SHH is well known to contribute to the patterning of the spinal cord and separation of the brain hemispheres. In addition, it has recently been shown that SHH signaling also contributes to the patterning of the telencephalon and establishment of adult neurogenic niches. In this work, we investigated whether SHH signaling influences the behavior of neural progenitors isolated from the dorsal telencephalon, which generate excitatory neurons and macroglial cells in vitro. We observed that SHH increases proliferation of cortical progenitors and generation of astrocytes, whereas blocking SHH signaling with cyclopamine has opposite effects. In both cases, generation of neurons did not seem to be affected. However, cell survival was broadly affected by blockade of SHH signaling. SHH effects were related to three different cell phenomena: mode of cell division, cell cycle length and cell growth. Together, our data in vitro demonstrate that SHH signaling controls cell behaviors that are important for proliferation of cerebral cortex progenitors, as well as differentiation and survival of neurons and astroglial cells.

  1. Early signaling network in rice PRR-mediated and R-mediated immunity.

    Science.gov (United States)

    Kawano, Yoji; Shimamoto, Ko

    2013-08-01

    Recent studies on plant immunity and pathogen infection have revealed sophisticated forms of plant-pathogen interaction. Considerable progress has been made recently in our understanding of the molecular mechanism underlying chitin signaling in rice. The identification and characterization of two direct substrates, OsRacGEF1 and OsRLCK185, as components in the chitin receptor complex of OsCERK1 have revealed how pattern recognition receptors transduce pathogen signals to downstream molecules in rice. In this review, we highlight these and other recent studies that have contributed to our current understanding of the signaling network in rice immunity, especially with regard to pattern recognition receptors, disease resistance (R) proteins, and their downstream targets.

  2. Toll-like receptor 4/nuclear factor-kappa B signaling detected in brain after early subarachnoid hemorrhage

    Institute of Scientific and Technical Information of China (English)

    MA Chun-xiao; YIN Wei-ning; CAI Bo-wen; WU Jian; WANG Jun-yi; HE Min; SUN Hong; DING Jun-li; YOU Chao

    2009-01-01

    Background Inflammation and immunity play a vital role in the pathogenesis of early brain injury after subarachnoid hemorrhage (SAH). Nuclear factor-kappa B (NF-KB) regulates many genes essential for inflammation and immunity and is activated by toll-like receptor (TLR). This study aimed to detect the expression of the toll-like receptor 4/nuclear factor-kappa B (TLR4/NF-KB) signaling in the rat brain after early SAH. Methods The rats were decapitated and their brains were removed at 0, 2, 4, 6, 12, 24 and 48 hours after a single injection of blood into the prechiasmatic cistern, mRNA expression of TLR4 was measured by Taqman real-time RT-PCR, and protein expression by immunohistochemistry and Western blotting. NF-KB activity and concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-lbeta (IL-β) and intedeukin-6 (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA).Results TaqMan real-time RT-PCR and Western blotting identified a biphasic change in TLR4 expression in both mRNA and protein: an initial peak (2-6 hours) and a sustained elevation (12-48 hours). Immunohistochemical staining showed the inducible expression of TLR4-1ike immunoreactions predominantly in glial cells and vascular endothelium. A similar biphasic change in the activation of NF-KB subunit p65 as well as the production of NF-KB-regulated proinflammatory cytokines (TNF-α, IL-1β and IL-6) were detected by ELISA. Conclusions These data suggest that experimental SAH induces significant up-regulation of TLR4 expression and the NF-KB signaling in early brain injury. Activation of the TLR4/NF-KB signaling may regulate the inflammatory responses after SAH.

  3. α5β1 integrin signaling mediates oxidized low-density lipoprotein-induced inflammation and early atherosclerosis.

    Science.gov (United States)

    Yurdagul, Arif; Green, Jonette; Albert, Patrick; McInnis, Marshall C; Mazar, Andrew P; Orr, A Wayne

    2014-07-01

    Endothelial cell activation drives early atherosclerotic plaque formation. Both fibronectin deposition and accumulation of oxidized low-density lipoprotein (oxLDL) occur early during atherogenesis, and both are implicated in enhanced endothelial cell activation. However, interplay between these responses has not been established. The objective of our study was to determine whether endothelial matrix composition modulates the inflammatory properties of oxLDL. We now show that oxLDL-induced nuclear factor-κB activation, proinflammatory gene expression, and monocyte binding are significantly enhanced when endothelial cells are attached to fibronectin compared with basement membrane proteins. This enhanced response does not result from altered oxLDL receptor expression, oxLDL uptake, or reactive oxygen species production, but results from oxLDL-induced activation of the fibronectin-binding integrin α5β1. Preventing α5β1 signaling (blocking antibodies, knockout cells) inhibits oxLDL-induced nuclear factor-κB activation and vascular cell adhesion molecule-1 expression. Furthermore, oxLDL drives α5β1-dependent integrin signaling through the focal adhesion kinase pathway, and focal adhesion kinase inhibition (PF-573228, small interfering RNA) blunts oxLDL-induced nuclear factor-κB activation, vascular cell adhesion molecule-1 expression, and monocyte adhesion. Last, treatment with the α5β1 signaling inhibitor, ATN-161, significantly blunts atherosclerotic plaque development in apolipoprotein E-deficient mice, characterized by reduced vascular cell adhesion molecule-1 expression and macrophage accumulation without affecting fibrous cap size. Our data suggest that α5β1-mediated cross-talk between fibronectin and oxLDL regulates inflammation in early atherogenesis and that therapeutics that inhibit α5 integrins may reduce inflammation without adversely affecting plaque structure. © 2014 American Heart Association, Inc.

  4. Nod factor signaling genes and their function in the early stages of Rhizobium infection

    NARCIS (Netherlands)

    Geurts, R.; Fedorova, E.; Bisseling, T.

    2005-01-01

    A lipochitosaccharide-based signal molecule that is secreted by Rhizobium, named Nod factor (NF), induces root nodule formation in legumes. This molecule is also essential for the establishment of bacterial infection. Genetic analyses in the legume species Lotus japonicus and Medicago truncatula hav

  5. Calcium signaling during the early meroblastic cleavages of zebrafish and medaka embryos

    Institute of Scientific and Technical Information of China (English)

    Andrew L.MILLER

    2010-01-01

    @@ The regulation of cytokinesis in"gianf' embryonic cells(i.e.,> 500 μm in diameter)presents exacting challenges that include long-range signaling with respect to time and space; the transport and assembly,followed by disassembly,of an extensive contractile apparatus; and the remodeling and addition of new surface membrane to the resulting daughter cells.

  6. Early Warning Signals of Financial Crises with Multi-Scale Quantile Regressions of Log-Periodic Power Law Singularities.

    Science.gov (United States)

    Zhang, Qun; Zhang, Qunzhi; Sornette, Didier

    2016-01-01

    We augment the existing literature using the Log-Periodic Power Law Singular (LPPLS) structures in the log-price dynamics to diagnose financial bubbles by providing three main innovations. First, we introduce the quantile regression to the LPPLS detection problem. This allows us to disentangle (at least partially) the genuine LPPLS signal and the a priori unknown complicated residuals. Second, we propose to combine the many quantile regressions with a multi-scale analysis, which aggregates and consolidates the obtained ensembles of scenarios. Third, we define and implement the so-called DS LPPLS Confidence™ and Trust™ indicators that enrich considerably the diagnostic of bubbles. Using a detailed study of the "S&P 500 1987" bubble and presenting analyses of 16 historical bubbles, we show that the quantile regression of LPPLS signals contributes useful early warning signals. The comparison between the constructed signals and the price development in these 16 historical bubbles demonstrates their significant predictive ability around the real critical time when the burst/rally occurs.

  7. Interrogating a cell signalling network sensitively monitors cell fate transition during early differentiation of mouse embryonic stem cells

    Institute of Scientific and Technical Information of China (English)

    LIU; Yi-Hsin; HO; Chih-ming

    2010-01-01

    The different cell types in an animal are often considered to be specified by combinations of transcription factors,and defined by marker gene expression.This paradigm is challenged,however,in stem cell research and application.Using a mouse embryonic stem cell(mESC) culture system,here we show that the expression level of many key stem cell marker genes/transcription factors such as Oct4,Sox2 and Nanog failed to monitor cell status transition during mESC differentiation.On the other hand,the response patterns of cell signalling network to external stimuli,as monitored by the dynamics of protein phosphorylation,changed dramatically.Our results also suggest that an irreversible alternation in the cell signalling network precedes the adjustment of transcription factor levels.This is consistent with the notion that signal transduction events regulate cell fate specification.We propose that interrogating a cell signalling network can assess the cell property more precisely,and provide a sensitive measurement for the early events in cell fate transition.We wish to bring attention to the potential problem of cell identification using a few marker genes,and suggest a novel methodology to address this issue.

  8. Targeting exosomes from preadipocytes inhibits preadipocyte to cancer stem cell signaling in early-stage breast cancer.

    Science.gov (United States)

    Gernapudi, Ramkishore; Yao, Yuan; Zhang, Yongshu; Wolfson, Benjamin; Roy, Sanchita; Duru, Nadire; Eades, Gabriel; Yang, Peixin; Zhou, Qun

    2015-04-01

    The tumor microenvironment plays a critical role in regulating breast tumor progression. Signaling between preadipocytes and breast cancer cells has been found to promote breast tumor formation and metastasis. Exosomes secreted from preadipocytes are important components of the cancer stem cell niche. Mouse preadipocytes (3T3L1) are treated with the natural antitumor compound shikonin (SK) and exosomes derived from mouse preadipocytes are co-cultured with MCF10DCIS cells. We examine how preadipocyte-derived exosomes can regulate early-stage breast cancer via regulating stem cell renewal, cell migration, and tumor formation. We identify a critical miR-140/SOX2/SOX9 axis that regulates differentiation, stemness, and migration in the tumor microenvironment. Next, we find that the natural antitumor compound SK can inhibit preadipocyte signaling inhibiting nearby ductal carcinoma in situ (DCIS) cells. Through co-culture experiments, we find that SK-treated preadipocytes secrete exosomes with high levels of miR-140, which can impact nearby DCIS cells through targeting SOX9 signaling. Finally, we find that preadipocyte-derived exosomes promote tumorigenesis in vivo, providing strong support for the importance of exosomal signaling in the tumor microenvironment. Our data also show that targeting the tumor microenvironment may assist in blocking tumor progression.

  9. ON STRONG SIGNALS OF MONTHLY PRECIPITATION ANOMALIES IN EARLY RAINING SEASON OF GUANGDONG AND CONCEPTUAL MODELS OF PREDICTION

    Institute of Scientific and Technical Information of China (English)

    林爱兰

    2002-01-01

    Reanalysis data from NCEP/NCAR are used to systematically study preceding signals of monthly precipitation anomalies in the early raining season of Guangdong province, from the viewpoints of 500-hPa geopotential height field, outgoing longwave radiation (OLR) field, sea surface temperature (SST) and fourteen indexes of general circulation depicting atmosphere activity at high, middle and low latitutes. Being multiple tools of information, a number of conceptual models are formulated that are useful for prediction of the magnitude of monthly precipitation (drought, flood and normal conditionss).

  10. Release of targeted p53 from the mitochondrion as an early signal during mitochondrial dysfunction

    Science.gov (United States)

    Increased accumulation of p53 tumor suppressor protein is an early response to low-level stressors. To investigate the fate of mitochondrial-sequestered p53, mouse embryonic fibroblast cells (MEFs) on a p53-deficient genetic background were transfected with p53-EGFP fusion protei...

  11. T-dependent B-cell activation is signalled by an early increase in potassium influx

    DEFF Research Database (Denmark)

    Owens, T; Kaplan, J G

    1982-01-01

    (previously demonstrated when B and T lymphocytes were separately stimulated) also occurs when B cells are stimulated through cooperation with mitogen-activated T cells, and is also detectable early in culture. T-dependent activation of B cells is therefore detectable considerably earlier than by conventional...

  12. T-dependent B-cell activation is signalled by an early increase in potassium influx

    DEFF Research Database (Denmark)

    Owens, T; Kaplan, J G

    1982-01-01

    (previously demonstrated when B and T lymphocytes were separately stimulated) also occurs when B cells are stimulated through cooperation with mitogen-activated T cells, and is also detectable early in culture. T-dependent activation of B cells is therefore detectable considerably earlier than by conventional...

  13. MITOGENIC SIGNALS CONTROL TRANSLATION OF THE EARLY GROWTH-RESPONSE GENE-1 IN MYOGENIC CELLS

    NARCIS (Netherlands)

    MAASS, A; GROHE, C; OBERDORF, S; SUKHATME, VP; VETTER, H; NEYSES, L

    1994-01-01

    Muscle is a major site of expression of the early growth reponse gene-1 (Egr-1). To investigate its role in muscle proliferation and/or differentiation we studied the effect of a variety of growth factors on cultured mouse muscle So18 cells. Three groups of responses could be distinguished: 1. AII,

  14. Early warning signals of regime shifts from cross-scale connectivity of land-cover patterns

    Science.gov (United States)

    Giovanni Zurlini; Kenneth Bruce Jones; Kurt Hans Riitters; Bai-Lian Li; Irene Petrosillo

    2014-01-01

    Increasing external pressures from human activities and climate change can lead to desertification, affecting the livelihood of more than 25% of the world’s population. Thus, determining proximity to transition to desertification is particularly central for arid regions before they may convert into deserts, and recent research has focused on devising early warning...

  15. Violation of the strong Huygen's principle and timelike signals from the early universe.

    Science.gov (United States)

    Blasco, Ana; Garay, Luis J; Martín-Benito, Mercedes; Martín-Martínez, Eduardo

    2015-04-10

    We analyze the implications of the violations of the strong Huygen's principle in the transmission of information from the early Universe to the current era via massless fields. We show that much more information reaches us through timelike channels (not mediated by real photons) than is carried by rays of light, which are usually regarded as the only carriers of information.

  16. Early signaling, referral, and treatment of adolescent chronic pain: A study protocol

    NARCIS (Netherlands)

    J.S. Voerman (Jane); S.C. Remerie (Sylvia); L.E. de Graaf (Esther); P.M. van de Looij-Jansen (Petra); T. Westendorp (Tessa); I. van Elderen (Ina); F. de Waart (Frouwkje); J. Passchier (Jan); A. Dommisse-Van Berkel (Anke); C. de Klerk (Cora)

    2012-01-01

    textabstractBackground: Chronic pain is prevalent among young people and negatively influences their quality of life. Furthermore, chronic pain in adolescence may persist into adulthood. Therefore, it is important early on to promote the self-management skills of adolescents with chronic pain by imp

  17. Next speakers plan their turn early and speak after turn-final "go-signals"

    NARCIS (Netherlands)

    Barthel, M.; Meyer, A.S.; Levinson, S.C.

    2017-01-01

    In conversation, turn-taking is usually fluid, with next speakers taking their turn right after the end of the previous turn. One reason for this fluency is early content planning of the next turn, if possible while the current turn is still coming in, as found by Barthel et al. (2016) using the

  18. Endogenous repair by the activation of cell survival signalling cascades during the early stages of rat Parkinsonism.

    Directory of Open Access Journals (Sweden)

    Nga-Ping Lui

    Full Text Available Here we report a previously unknown self repair mechanism during extremely early stages of rat Parkinsonism. Two important cell survival signaling cascades, Phosphatidylinositol-3 kinases (PI3K/Akt pathway and extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK pathway, could be responsible for this potential endogenous rescue system. In the 6-hydroxydopamine-lesioned rat, the phosphorylated p44/42 MAPK and its downstream target, the phosphorylated Bad at Ser 112, were up-regulated at post-lesion day 3 and lasted for a couple of weeks. Although the change in the phosphorylated Akt kinase was negligible throughout the studied period, its downstream target, the phosphorylated Bad at 136, was increased from post-lesion day 3 to post-lesion day 14. In the mean time, nestin-positive reactive astrocytes with low levels of brain-derived neurotrophic factor (BDNF and glial cell line-derived neurotrophic factor (GDNF appeared at post-lesion day 3 in 6-hydroxydopamine-lesioned rat. BDNF was expressed in both striatum and substantia nigra whereas GDNF was displayed in striatum only. At post-lesion day 14, nestin, BDNF and GDNF expressions were diminished. These neurotrophic factors were believed to initiate the above anti-apoptotic signal transduction cascades as we could see that their expression patterns were similar. The data strongly suggest that there is an endogenous repair effort by evoking the cell survival signaling and possibly via the releases of BDNF and GDNF from nestin-immunoreactive reactive astrocytes. ERK/MAPK pathway was proposed to be the key endogenous neuroprotective mechanisms, particularly in early stages of rat Parkinsonism. However, the self repair effort is only functional within an extremely short time window immediately after onset.

  19. Early pre- and postsynaptic calcium signaling abnormalities mask underlying synaptic depression in presymptomatic Alzheimer’s disease mice

    Science.gov (United States)

    Chakroborty, Shreaya; Kim, Joyce; Schneider, Corinne; Jacobson, Christopher; Molgó, Jordi; Stutzmann, Grace E.

    2012-01-01

    Alzheimer’s disease (AD)-linked presenilin mutations result in pronounced endoplasmic reticulum (ER) calcium disruptions that occur prior to detectable histopathology and cognitive deficits. More subtly, these early AD-linked calcium alterations also reset neurophysiological homeostasis, such that calcium-dependent pre- and postsynaptic signaling appear functionally normal yet are actually operating under aberrant calcium signaling systems. In these 3xTg-AD mouse brains, upregulated RyR activity is associated with a shift towards synaptic depression, likely through a reduction in presynaptic vesicle stores and increased postsynaptic outward currents through SK2 channels. The deviant RyR-calcium involvement in the 3xTg-AD mice also compensates for an intrinsic predisposition for hippocampal LTD and reduced LTP. In this study we detail the impact of disrupted ryanodine receptor (RyR)-mediated calcium stores on synaptic transmission properties, long term depression (LTD) and calcium-activated membrane channels of hippocampal CA1 pyramidal neurons in presymptomatic 3xTg-AD mice. Using electrophysiological recordings in young 3xTg-AD and NonTg hippocampal slices, we show that increased RyR-evoked calcium release in 3xTg-AD mice ‘normalizes’ an altered synaptic transmission system operating under a shifted homeostatic state that is not present in NonTg mice. In the process, we uncover compensatory signaling mechanisms recruited early in the disease process which counterbalance the disrupted RyR-calcium dynamics, namely increases in presynaptic spontaneous vesicle release, altered probability of vesicle release, and upregulated postsynaptic SK channel activity. As AD is increasingly recognized as a ‘synaptic disease’, calcium-mediated signaling alterations may serve as a proximal trigger for the synaptic degradation driving the cognitive loss in AD. PMID:22699914

  20. Signalling pathways implicated in early mammary gland morphogenesis and breast cancer.

    Directory of Open Access Journals (Sweden)

    Beatrice Howard

    2006-08-01

    Full Text Available Specification of mammary epithelial cell fate occurs during embryogenesis as cells aggregate to form the mammary anlage. Within the embryonic mammary bud, a population of epithelial cells exists that will subsequently proliferate to form a ductal tree filling the stromal compartment, and which can produce milk upon terminal differentiation after birth. Subsequently, these structures can be remodelled and returned to a basal state after weaning before regenerating in future pregnancies. The plasticity of the mammary epithelial cell, and its responsiveness to hormone receptors, facilitates this amazing biological feat, but aberrant signalling may also result in unintended consequences in the form of frequent malignancies. Reflecting this intimate connection, a considerable number of signalling pathways have been implicated in both mammary gland morphogenesis and carcinogenesis.

  1. Lipid modulation of early G protein-coupled receptor signalling events.

    Science.gov (United States)

    Dijkman, Patricia M; Watts, Anthony

    2015-11-01

    Upon binding of extracellular ligands, G protein coupled-receptors (GPCRs) initiate signalling cascades by activating heterotrimeric G proteins through direct interactions with the α subunit. While the lipid dependence of ligand binding has previously been studied for one class A GPCR, the neurotensin receptor 1 (NTS1), the role the lipid environment plays in the interaction of activated GPCRs with G proteins is less well understood. It is therefore of interest to understand the balance of lipid interactions required to support both ligand binding and G protein activation, not least since some receptors have multiple locations, and may experience different membrane environments when signalling in the plasma membrane or during endocytosis. Here, using the sensitive biophysical technique of microscale thermophoresis in conjunction with nanodisc lipid bilayer reconstitution, we show that in more native lipid environments rich in phosphatidyl ethanolamine (PE), the Gαi1 subunit has a ~4-fold higher affinity for NTS1 than in the absence of native lipids. The G protein-receptor affinity was further shown to be dependent on the ligand-binding state of the receptor, with potential indication of biased signalling for the known antagonist SR142948A. Gαi1 also showed preferential interaction with empty nanodiscs of native lipid mixtures rich in PE by around 2- to 4-fold over phosphatidyl choline (PC)/phosphatidyl glycerol (PG) lipid mixtures. The lipid environment may therefore play a role in creating favourable micro-environments for efficient GPCR signalling. Our approach combining nanodiscs with microscale thermophoresis will be useful in future studies to elucidate further the complexity of the GPCR interactome.

  2. Salt stress sensing and early signalling events in plant roots: Current knowledge and hypothesis.

    Science.gov (United States)

    Shabala, Sergey; Wu, Honghong; Bose, Jayakumar

    2015-12-01

    Soil salinity is a major environmental constraint to crop production. While the molecular identity and functional expression of Na(+) transport systems mediating Na(+) exclusion from the cytosol has been studied in detail, far less is known about the mechanisms by which plants sense high Na(+) levels in the soil and the rapid signalling events that optimise plant performance under saline conditions. This review aims to fill this gap. We first discuss the nature of putative salt stress sensors, candidates which include Na(+) transport systems, mechanosensory proteins, proteins with regulatory Na(+) binding sites, sensing mediated by cyclic nucleotide-gated channels, purine receptors, annexin and voltage gating. We suggest that several transport proteins may be clustered together to form a microdomain in a lipid raft, allowing rapid changes in the activity of an individual protein to be translated into stress-induced Ca(2+) and H2O2 signatures. The pathways of stress signalling to downstream targets are discussed, and the kinetics and specificity of salt stress signalling between glycophytes and halophytes is compared. We argue that these sensing mechanisms operate in parallel, providing plants with a robust system for decoding information about the specific nature and severity of the imposed salt stress.

  3. CdiGMP signaling at early stages of biofilm formation in Pseudomonas Aeruginosa

    Science.gov (United States)

    Zhao, Kun; Gibiansky, Maxsim; Xian, Wujing; Utada, Andrew; Wong, Gerard

    2014-03-01

    Biofilm communities on surfaces constitute an important physiological state of bacteria. CdiGMP is a secondary messenger that has recently emerged as a master regulator of biofilm behavior. It has been shown that cdiGMP can affect bacterial adhesion, motility and exopolysaccharides production, which are important in regulating biofilm formation. However, at a single cell level, the details of how cdiGMP regulate bacterial behavior are largely unknown. Here we examine the dynamics of intracellular cdiGMP levels at early stages of biofilm in Pseudomonas Aeruginosa, by using cell tracking techniques. We show that cells with different cdiGMP levels play different roles in the microcolony development at early stages of biofilm. The correlation between Psl and cdiGMP levels is also investigated.

  4. Next Speakers Plan Their Turn Early and Speak after Turn-Final "Go-Signals".

    Science.gov (United States)

    Barthel, Mathias; Meyer, Antje S; Levinson, Stephen C

    2017-01-01

    In conversation, turn-taking is usually fluid, with next speakers taking their turn right after the end of the previous turn. Most, but not all, previous studies show that next speakers start to plan their turn early, if possible already during the incoming turn. The present study makes use of the list-completion paradigm (Barthel et al., 2016), analyzing speech onset latencies and eye-movements of participants in a task-oriented dialogue with a confederate. The measures are used to disentangle the contributions to the timing of turn-taking of early planning of content on the one hand and initiation of articulation as a reaction to the upcoming turn-end on the other hand. Participants named objects visible on their computer screen in response to utterances that did, or did not, contain lexical and prosodic cues to the end of the incoming turn. In the presence of an early lexical cue, participants showed earlier gaze shifts toward the target objects and responded faster than in its absence, whereas the presence of a late intonational cue only led to faster response times and did not affect the timing of participants' eye movements. The results show that with a combination of eye-movement and turn-transition time measures it is possible to tease apart the effects of early planning and response initiation on turn timing. They are consistent with models of turn-taking that assume that next speakers (a) start planning their response as soon as the incoming turn's message can be understood and (b) monitor the incoming turn for cues to turn-completion so as to initiate their response when turn-transition becomes relevant.

  5. Endothelin-1 signalling controls early embryonic heart rate in vitro and in vivo.

    Science.gov (United States)

    Karppinen, S; Rapila, R; Mäkikallio, K; Hänninen, S L; Rysä, J; Vuolteenaho, O; Tavi, P

    2014-02-01

    Spontaneous activity of embryonic cardiomyocytes originates from sarcoplasmic reticulum (SR) Ca(2+) release during early cardiogenesis. However, the regulation of heart rate during embryonic development is still not clear. The aim of this study was to determine how endothelin-1 (ET-1) affects the heart rate of embryonic mice, as well as the pathway through which it exerts its effects. The effects of ET-1 and ET-1 receptor inhibition on cardiac contraction were studied using confocal Ca(2+) imaging of isolated mouse embryonic ventricular cardiomyocytes and ultrasonographic examination of embryonic cardiac contractions in utero. In addition, the amount of ET-1 peptide and ET receptor a (ETa) and b (ETb) mRNA levels were measured during different stages of development of the cardiac muscle. High ET-1 concentration and expression of both ETa and ETb receptors was observed in early cardiac tissue. ET-1 was found to increase the frequency of spontaneous Ca(2+) oscillations in E10.5 embryonic cardiomyocytes in vitro. Non-specific inhibition of ET receptors with tezosentan caused arrhythmia and bradycardia in isolated embryonic cardiomyocytes and in whole embryonic hearts both in vitro (E10.5) and in utero (E12.5). ET-1-mediated stimulation of early heart rate was found to occur via ETb receptors and subsequent inositol trisphosphate receptor activation and increased SR Ca(2+) leak. Endothelin-1 is required to maintain a sufficient heart rate, as well as to prevent arrhythmia during early development of the mouse heart. This is achieved through ETb receptor, which stimulates Ca(2+) leak through IP3 receptors. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  6. Reinstatement of associative memories in early visual cortex is signaled by the hippocampus.

    Science.gov (United States)

    Bosch, Sander E; Jehee, Janneke F M; Fernández, Guillén; Doeller, Christian F

    2014-05-28

    The cortical reinstatement hypothesis of memory retrieval posits that content-specific cortical activity at encoding is reinstated at retrieval. Evidence for cortical reinstatement was found in higher-order sensory regions, reflecting reactivation of complex object-based information. However, it remains unclear whether the same detailed sensory, feature-based information perceived during encoding is subsequently reinstated in early sensory cortex and what the role of the hippocampus is in this process. In this study, we used a combination of visual psychophysics, functional neuroimaging, multivoxel pattern analysis, and a well controlled cued recall paradigm to address this issue. We found that the visual information human participants were retrieving could be predicted by the activation patterns in early visual cortex. Importantly, this reinstatement resembled the neural pattern elicited when participants viewed the visual stimuli passively, indicating shared representations between stimulus-driven activity and memory. Furthermore, hippocampal activity covaried with the strength of stimulus-specific cortical reinstatement on a trial-by-trial level during cued recall. These findings provide evidence for reinstatement of unique associative memories in early visual cortex and suggest that the hippocampus modulates the mnemonic strength of this reinstatement.

  7. Electron dispersion events in the morningside auroral zone and their relationship with VLF emissions

    Energy Technology Data Exchange (ETDEWEB)

    Hardy, D.A.; Burke, W.J. (Hanscom Air Force Base, MA (United States)); Villalon, E. (Northeastern Univ., Boston, MA (United States))

    1990-05-01

    Energy/time dispersion events have been observed in the precipitating electron data in the energy range from 630 eV to 20 keV recorded by the J sensor on the low-altitude, polar-orbiting HILAT satellite. The dispersions are such that the higher-energy electrons are observed earlier in time than the lower-energy electrons The time interval for single dispersion event is from 1 to 2 s. Within an auroral pass in which such energy/time dispersion events are observed, there are typically several such events, and they can be spaced within the pass in either a periodic or aperiodic manner. The events are typically observed within and toward the equatorward edge of the region of diffuse auroral electron precipitation. During a given pass the events can be observed over a wide range of L shells. The occurrence of these events maximizes in the interval 0600-1,200 hours MLT. The energy/time dispersion is generally consistent with the electrons originating from a common source. The events are seen at L shells from 3.7 to greater than 15. The source distance for the electrons is inferred to be generally beyond the equator for events at L shells less than approximately 8 and before the equator for events at higher L shells. Because of the low energies at which the dispersions are observed, it is unlikely that their occurrence can be explained by resonant interaction with VLF waves. Based on circumstantial evidence from other reported observations common to the morning sector, and alternative theoretical explanation is presented. According to this model the dispersion events result from impulsive interactions of the electrons with intense, asymmetric packets of VLF waves via the nonlinear, ponderomotive force.

  8. Cone structure and focusing of VLF and LF electromagnetic waves at high altitudes in the ionosphere

    Science.gov (United States)

    Alpert, Ya. L.; Green, J. L.

    1994-01-01

    The frequency and angle dependencies of the electric field radiated by an electric dipole E = E(sub 0) cos omega(t) are studied through numerical calculations of absolute value of E in the VLF and LF frequency bands where F is less than or equal 0.02 to 0.05 f(sub b) in a model ionosphere over an altitude region of 800-6000 km where the wave frequency and electron gyrofrequency varies between F approximately 4-500 kHz and f(sub b) is approximately equal (1.1 to 0.2) MHz respectively. It is found that the amplitudes of the electric field have large maxima in four regions: close to the direction of the Earth magnetic field line B(sub 0) (it is called the axis field E(sub 0), in the Storey E(sub St), reversed Storey E(sub RevSt), and resonance E(sub Res) cones. The maximal values of E(sub 0), E(sub Res), and E(sub RevSt) are the most pronounced close to the lower hybrid frequency, F approximately F(sub L). The flux of the electric field is concentrated in very narrow regions, with the apex angles of the cones Delta-B is approximately (0.1-1) deg. The enhancement and focusing of the electric field increases with altitude starting at Z greater than 800 km. At Z greater than or equal to 1000 up to 6000 km, the relative value of absolute value of E, in comparison with its value at Z = 800 km is about (10(exp 2) to 10(exp 4)) times larger. Thus the flux of VLF and LF electromagnetic waves generated at high altitudes in the Earth's ionosphere are trapped into very narrow conical beams similar to laser beams.

  9. Cone structure and focusing of VLF and LF electromagnetic waves at high altitudes in the ionosphere

    Science.gov (United States)

    Alpert, Ya. L.; Green, J. L.

    1994-01-01

    The frequency and angle dependencies of the electric field radiated by an electric dipole E = E(sub 0) cos omega(t) are studied through numerical calculations of absolute value of E in the VLF and LF frequency bands where F is less than or equal 0.02 to 0.05 f(sub b) in a model ionosphere over an altitude region of 800-6000 km where the wave frequency and electron gyrofrequency varies between F approximately 4-500 kHz and f(sub b) is approximately equal (1.1 to 0.2) MHz respectively. It is found that the amplitudes of the electric field have large maxima in four regions: close to the direction of the Earth magnetic field line B(sub 0) (it is called the axis field E(sub 0), in the Storey E(sub St), reversed Storey E(sub RevSt), and resonance E(sub Res) cones. The maximal values of E(sub 0), E(sub Res), and E(sub RevSt) are the most pronounced close to the lower hybrid frequency, F approximately F(sub L). The flux of the electric field is concentrated in very narrow regions, with the apex angles of the cones Delta-B is approximately (0.1-1) deg. The enhancement and focusing of the electric field increases with altitude starting at Z greater than 800 km. At Z greater than or equal to 1000 up to 6000 km, the relative value of absolute value of E, in comparison with its value at Z = 800 km is about (10(exp 2) to 10(exp 4)) times larger. Thus the flux of VLF and LF electromagnetic waves generated at high altitudes in the Earth's ionosphere are trapped into very narrow conical beams similar to laser beams.

  10. Physics based model of D-region variability related to VLF propagation effects

    Science.gov (United States)

    Chakravarty, S. C.

    2012-07-01

    D-region (~60-85 km) electron density profiles measured using large number of sounding rocket experiments carried out from two Indian low latitude stations show large variations with solar zenith angle, season and solar activity. Similarly the ground based multi frequency radio wave absorption technique has provided continuous data on the morphology of the hourly electron density variations. However suitable models of the D-region electron density profile variations both during quiet and disturbed solar conditions over the Indian region are lacking. The renewed interest in the study of the VLF/LF propagation anomalies taking place through perturbations in the D-region electron densities due to various geophysical phenomena requires the availability of a baseline D-region model over low latitudes. The purpose of this paper is to critically review the physical processes of D-region production and loss of free electrons, dynamical coupling due to variety of vertically propagating atmospheric waves, sudden changes brought about by the solar energetic events like CMEs and different categories of X-ray flares. Low latitude region is not likely to be affected by the PMSE or PCA type of events but the changes due to lightning induced mesospheric red sprites and LEPs need to be considered. Based on this analysis, a preliminary low latitude D-region electron density profile model development is proposed. Sample results would illustrate key requirements from such a model in terms of its effectiveness to simulate the low latitude observations of VLF/LF amplitude and phase variations using waveguide propagation models like LWPC.

  11. Memory signals from the thalamus: early thalamocortical phase synchronization entrains gamma oscillations during long-term memory retrieval.

    Science.gov (United States)

    Staudigl, Tobias; Zaehle, Tino; Voges, Jürgen; Hanslmayr, Simon; Esslinger, Christine; Hinrichs, Hermann; Schmitt, Friedhelm C; Heinze, Hans-Jochen; Richardson-Klavehn, Alan

    2012-12-01

    The thalamus is believed to be a key node in human memory networks, however, very little is known about its real-time functional role. Here we examined the dynamics of thalamocortical communication during long-term episodic memory retrieval in two experiments. In experiment 1, intrathalamic and surface EEG was recorded in an epileptic patient implanted with depth electrodes for brain stimulation therapy. In a recognition memory test, early (300-500 ms) stimulus-linked oscillatory synchrony between mediodorsal thalamic and frontal surface electrodes at beta frequency (20 Hz) was enhanced for correctly remembered old compared to correctly rejected new items. Directionality measures (Granger causality) indicated that the thalamus was the sender, and the neocortex the receiver, of this beta signal, which also modulated the power of neocortical gamma (55-80 Hz) oscillations (cross-frequency coupling). Experiment 2 validated the cross-frequency coupling effects in a healthy participant sample. Confirming the findings from experiment 1, significantly increased cross-frequency coupling was found over frontal scalp electrodes during successful recognition. Extending anatomical knowledge on thalamic connectivity with frontal neocortex, these results suggest that the thalamus sends an early memory signal to frontal regions, triggering further memory search processes.

  12. C/NOFS-VEFI results on magnetic-latitude control over coupling of lightning-generated VLF into zero-hop whistlers

    Science.gov (United States)

    Jacobson, A. R.; Holzworth, R.; Pfaff, R. F., Jr.; Heelis, R. A.

    2016-12-01

    The C/NOFS satellite had a low-inclination (13 deg) orbit and provided multi-year observations (2008 - 2015) of the innermost plasmasphere within 26 deg of the magnetic equator. We report on VEFI (Vector Electric Field Instrument) recordings of zero-hop whistler-wave electric fields in this low-latitude region. We describe evidence regarding the VLF coupling variabilities, in particular versus magnetic latitude. We rely critically on data provided by the CINDI (C/NOFS Ion and Neutral Drift Investigation) measurements of the ion-composition, and by WWLLN (World-Wide Lightning-Location Network) groundtruthing of lightning-VLF source location, energy, and time. This low-latitude region has been predicted to permit only reduced VLF coupling, due essentially to a Snell's Law total reflection from the underside of the ionosphere. Nonetheless various studies of VLF coupling at discrete frequencies (from naval VLF transmitters) indicate that there is some intermittent, anomalous coupling not predicted by a simple Snell's Law. We address this problem using broadband illumination by lightning-generated VLF.

  13. Notch signalling in the paraxial mesoderm is most sensitive to reduced Pofut1 levels during early mouse development

    Directory of Open Access Journals (Sweden)

    Serth Jürgen

    2009-01-01

    Full Text Available Abstract Background The evolutionarily conserved Notch signalling pathway regulates multiple developmental processes in a wide variety of organisms. One critical posttranslational modification of Notch for its function in vivo is the addition of O-linked fucose residues by protein O-fucosyltransferase 1 (POFUT1. In addition, POFUT1 acts as a chaperone and is required for Notch trafficking. Mouse embryos lacking POFUT1 function die with a phenotype indicative of global inactivation of Notch signalling. O-linked fucose residues on Notch can serve as substrates for further sugar modification by Fringe (FNG proteins. Notch modification by Fringe differently affects the ability of ligands to activate Notch receptors in a context-dependent manner indicating a complex modulation of Notch activity by differential glycosylation. Whether the context-dependent effects of Notch receptor glycosylation by FNG reflect different requirements of distinct developmental processes for O-fucosylation by POFUT1 is unclear. Results We have identified and characterized a spontaneous mutation in the mouse Pofut1 gene, referred to as "compact axial skeleton" (cax. Cax carries an insertion of an intracisternal A particle retrotransposon into the fourth intron of the Pofut1 gene and represents a hypomorphic Pofut1 allele that reduces transcription and leads to reduced Notch signalling. Cax mutant embryos have somites of variable size, showed partly abnormal Lfng expression and, consistently defective anterior-posterior somite patterning and axial skeleton development but had virtually no defects in several other Notch-regulated early developmental processes outside the paraxial mesoderm that we analyzed. Conclusion Notch-dependent processes apparently differ with respect to their requirement for levels of POFUT1. Normal Lfng expression and anterior-posterior somite patterning is highly sensitive to reduced POFUT1 levels in early mammalian embryos, whereas other early Notch

  14. Regulation of Early Steps of GPVI Signal Transduction by Phosphatases: A Systems Biology Approach.

    Directory of Open Access Journals (Sweden)

    Joanne L Dunster

    2015-11-01

    Full Text Available We present a data-driven mathematical model of a key initiating step in platelet activation, a central process in the prevention of bleeding following Injury. In vascular disease, this process is activated inappropriately and causes thrombosis, heart attacks and stroke. The collagen receptor GPVI is the primary trigger for platelet activation at sites of injury. Understanding the complex molecular mechanisms initiated by this receptor is important for development of more effective antithrombotic medicines. In this work we developed a series of nonlinear ordinary differential equation models that are direct representations of biological hypotheses surrounding the initial steps in GPVI-stimulated signal transduction. At each stage model simulations were compared to our own quantitative, high-temporal experimental data that guides further experimental design, data collection and model refinement. Much is known about the linear forward reactions within platelet signalling pathways but knowledge of the roles of putative reverse reactions are poorly understood. An initial model, that includes a simple constitutively active phosphatase, was unable to explain experimental data. Model revisions, incorporating a complex pathway of interactions (and specifically the phosphatase TULA-2, provided a good description of the experimental data both based on observations of phosphorylation in samples from one donor and in those of a wider population. Our model was used to investigate the levels of proteins involved in regulating the pathway and the effect of low GPVI levels that have been associated with disease. Results indicate a clear separation in healthy and GPVI deficient states in respect of the signalling cascade dynamics associated with Syk tyrosine phosphorylation and activation. Our approach reveals the central importance of this negative feedback pathway that results in the temporal regulation of a specific class of protein tyrosine phosphatases in

  15. Transcriptional regulatory network triggered by oxidative signals configures the early response mechanisms of japonica rice to chilling stress

    KAUST Repository

    Yun, Kil-Young

    2010-01-25

    Background: The transcriptional regulatory network involved in low temperature response leading to acclimation has been established in Arabidopsis. In japonica rice, which can only withstand transient exposure to milder cold stress (10C), an oxidative-mediated network has been proposed to play a key role in configuring early responses and short-term defenses. The components, hierarchical organization and physiological consequences of this network were further dissected by a systems-level approach.Results: Regulatory clusters responding directly to oxidative signals were prominent during the initial 6 to 12 hours at 10C. Early events mirrored a typical oxidative response based on striking similarities of the transcriptome to disease, elicitor and wounding induced processes. Targets of oxidative-mediated mechanisms are likely regulated by several classes of bZIP factors acting on as1/ocs/TGA-like element enriched clusters, ERF factors acting on GCC-box/JAre-like element enriched clusters and R2R3-MYB factors acting on MYB2-like element enriched clusters.Temporal induction of several H2O2-induced bZIP, ERF and MYB genes coincided with the transient H2O2spikes within the initial 6 to 12 hours. Oxidative-independent responses involve DREB/CBF, RAP2 and RAV1 factors acting on DRE/CRT/rav1-like enriched clusters and bZIP factors acting on ABRE-like enriched clusters. Oxidative-mediated clusters were activated earlier than ABA-mediated clusters.Conclusion: Genome-wide, physiological and whole-plant level analyses established a holistic view of chilling stress response mechanism of japonica rice. Early response regulatory network triggered by oxidative signals is critical for prolonged survival under sub-optimal temperature. Integration of stress and developmental responses leads to modulated growth and vigor maintenance contributing to a delay of plastic injuries. 2010 Yun et al; licensee BioMed Central Ltd.

  16. Chronic exposure to bisphenol a impairs progesterone receptor-mediated signaling in the uterus during early pregnancy

    Science.gov (United States)

    Li, Quanxi; Davila, Juanmahel; Bagchi, Milan K.; Bagchi, Indrani C.

    2016-01-01

    Environmental and occupational exposure to endocrine disrupting chemicals (EDCs) is a major threat to female reproductive health. Bisphenol A (BPA), an environmental toxicant that is commonly found in polycarbonate plastics and epoxy resins, has received much attention due to its estrogenic activity and high risk of chronic exposure in human. Whereas BPA has been linked to infertility and recurrent miscarriage in women, the impact of its exposure on uterine function during early pregnancy remains unclear. In a recent publication in Endocrinology, we demonstrated that prolonged exposure to an environmental relevant dose of BPA disrupts progesterone receptor-regulated uterine functions, thus affecting uterine receptivity for embryo implantation and decidua morphogenesis, two critical events for establishment and maintenance of early pregnancy. In particular we reported a marked impairment of progesterone receptor (PGR) expression and its downstream effector HAND2 in the uterine stromal cells in response to chronic BPA exposure. In an earlier study we have shown that HAND2 controls embryo implantation by repressing fibroblast growth factor (FGF) expression and the MAP kinase signaling pathway, thus inhibiting epithelial proliferation. Interestingly we observed that downregulation of PGR and HAND2 expression in uterine stroma upon BPA exposure was associated with an enhanced activation of FGFR and MAPK signaling, aberrant proliferation, and lack of uterine receptivity in the epithelium. In addition, the proliferation and differentiation of endometrial stromal cells to decidual cells, an event critical for the maintenance of early pregnancy, was severely compromised in response to BPA. This research highlight will provide an overview of our findings and discuss the potential mechanisms by which chronic BPA impairs PGR-HAND2 pathway and adversely affects implantation and the establishment of pregnancy.

  17. Induction of Matrix Metalloproteinase Expression by Synovial Wnt Signaling and Association With Disease Progression in Early Symptomatic Osteoarthritis.

    Science.gov (United States)

    van den Bosch, Martijn H; Blom, Arjen B; van de Loo, Fons A; Koenders, Marije I; Lafeber, Floris P; van den Berg, Wim B; van der Kraan, Peter M; van Lent, Peter L

    2017-07-05

    Increased Wnt signaling in chondrocytes is associated with development of osteoarthritis (OA). However, OA is considered a disease of the entire joint, where the synovium has been attributed an important role in disease pathogenesis and progression. This study was undertaken to determine whether Wnt signaling in synovial tissue could contribute to pathologic development of OA through the production of matrix metalloproteinases (MMPs), and to assess the relationship of synovial expression of Frizzled (FZD) receptors and the Wnt inhibitor FRZB to MMP expression and disease progression in patients with early OA in the Dutch Cohort Hip and Cohort Knee (CHECK) study cohort. In mouse knee joints, human WNT8A and mouse Wnt16 were overexpressed using adenoviral vectors, and expression of messenger RNA (mRNA) for MMPs in the synovium was determined by reverse transcription-polymerase chain reaction or Luminex assay. In human synovial tissue from a subgroup of patients with early OA with knee pain enrolled in the CHECK cohort, levels of Wnt family members were assessed for linkage to MMP expression and disease progression. In addition, MMP production in human synovium from patients with end-stage OA was determined after stimulation of Wnt signaling with WNT3A or inhibition with FRZB or DKK1 in the synovium. Overexpression of WNT8A and Wnt16 in mouse knee joints induced MMP expression in vivo. Expression of MMPs relevant to human OA in the synovium from CHECK study participants significantly correlated with expression of FZD1, FZD10, and FRZB mRNA. Moreover, increased FZD1 mRNA expression and decreased FRZB mRNA expression were observed in CHECK study patients who experienced disease progression compared to those who were nonprogressors. Stimulation of human OA synovium with WNT3A induced the production of various MMPs, whereas inhibition of Wnt signaling with FRZB or DKK1 reduced the production of MMPs. Wnt signaling in the synovium may potently induce progression of OA via

  18. Decreased SAP expression in T cells from patients with SLE contributes to early signaling abnormalities and reduced IL-2 production

    Science.gov (United States)

    Karampetsou, Maria P.; Comte, Denis; Kis-Toth, Katalin; Terhorst, Cox; Kyttaris, Vasileios C.; Tsokos, George C.

    2016-01-01

    T cells from patients with systemic lupus erythematosus (SLE) display a number of functions including increased early signaling events following engagement of the T cell receptor (TCR). Signaling lymphocytic activation molecule family (SLAMF) cell surface receptors and the X-chromosome-defined signaling lymphocytic activation molecule-associated protein (SAP) adaptor are important in the development of several immunocyte lineages and modulating immune response. Here we present evidence that SAP protein levels are decreased in T cells and in their main subsets isolated from 32 women and 3 men with SLE independently of disease activity. In SLE T cells the SAP protein is also subject to increased degradation by a caspase-3. Forced expression of SAP in SLE T cells simultaneously heightened IL-2 production, calcium (Ca2+) responses and tyrosine phosphorylation of a number of proteins. Exposure of normal T cells to SLE serum IgG, known to contain anti-CD3/TCR antibodies, resulted in SAP downregulation. We conclude that SLE T cells display reduced levels of the adaptor protein SAP probably as a result of continuous T cell activation and degradation by caspase-3. Restoration of SAP levels in SLE T cells corrects the overexcitable lupus T cell phenotype. PMID:27183584

  19. Ligand Perception, Activation, and Early Signaling of Plant Steroid Receptor Brassinosteroid Insensitive 1

    Institute of Scientific and Technical Information of China (English)

    Jianjun Jiang; Chi Zhang; Xuelu Wang

    2013-01-01

    Leucine-rich repeat receptor-like kinases (LRR-RLKs) belong to a large group of cell surface proteins involved in many aspects of plant development and environmental responses in both monocots and dicots. Brassinosteroid insensitive 1 (BRI1), a member of the LRR X subfamily, was first identified through several forward genetic screenings for mutants insensitive to brassinosteroids (BRs), which are a class of plant-specific steroid hormones. Since its identification, BRI1 and its homologs had been proved as receptors perceiving BRs and initiating BR signaling. The co-receptor BRI1-associated kinase 1 and its homologs, and other BRI1 interacting proteins such as its inhibitor BRI1 kinase inhibitor 1 (BKI1) were identified by genetic and biochemical approaches. The detailed mechanisms of BR perception by BRI1 and the activation of BRI1 receptor complex have also been elucidated. Moreover, several mechanisms for termination of the activated BRI1 signaling were also discovered. In this review, we will focus on the recent advances on the mechanism of BRI1 phosphorylation and activation, the regulation of its receptor complex, the structure basis of BRI1 ectodomain and BR recognition, its direct substrates, and the termination of the activated BRI1 receptor complex.

  20. Astaxanthin Alleviates Early Brain Injury Following Subarachnoid Hemorrhage in Rats: Possible Involvement of Akt/Bad Signaling

    Directory of Open Access Journals (Sweden)

    Xiang-Sheng Zhang

    2014-07-01

    Full Text Available Apoptosis has been proven to play a crucial role in early brain injury pathogenesis and to represent a target for the treatment of subarachnoid hemorrhage (SAH. Previously, we demonstrated that astaxanthin (ATX administration markedly reduced neuronal apoptosis in the early period after SAH. However, the underlying molecular mechanisms remain obscure. In the present study, we tried to investigate whether ATX administration is associated with the phosphatidylinositol 3-kinase-Akt (PI3K/Akt pathway, which can play an important role in the signaling of apoptosis. Our results showed that post-SAH treatment with ATX could cause a significant increase of phosphorylated Akt and Bad levels, along with a significant decrease of cleaved caspase-3 levels in the cortex after SAH. In addition to the reduced neuronal apoptosis, treatment with ATX could also significantly reduce secondary brain injury characterized by neurological dysfunction, cerebral edema and blood-brain barrier disruption. In contrast, the PI3K/Akt inhibitor, LY294002, could partially reverse the neuroprotection of ATX in the early period after SAH by downregulating ATX-induced activation of Akt/Bad and upregulating cleaved caspase-3 levels. These results provided the evidence that ATX could attenuate apoptosis in a rat SAH model, potentially, in part, through modulating the Akt/Bad pathway.

  1. Regulation of Arabidopsis Early Anther Development by Putative Cell-Cell Signaling Molecules and Transcriptional Regulators

    Institute of Scientific and Technical Information of China (English)

    Yu-Jin Sun; Carey LH Hord; Chang-Bin Chen; Hong Ma

    2007-01-01

    Anther development in flowering plants involves the formation of several cell types, including the tapetal and pollen mother cells. The use of genetic and molecular tools has led to the identification and characterization of genes that are critical for normal cell division and differentiation in Arabidopsis early anther development. We review here several recent studies on these genes, including the demonstration that the putative receptor protein kinases BAM1 and BAM2 together play essential roles in the control of early cell division and differentiation. In addition, we discuss the hypothesis that BAM1/2 may form a positive-negative feedback regulatory loop with a previously identified key regulator, SPOROCYTELESS (also called NOZZLE),to control the balance between sporogenous and somatic cell types in the anther. Furthermore, we summarize the isolation and functional analysis of the DYSFUNCTIONAL TAPETUM1 (DYT1) gene in promoting proper tapetal cell differentiation. Our finding that DYT1 encodes a putative transcription factor of the bHLH family, as well as relevant expression analyses, strongly supports a model that DYT1 serves as a critical link between upstream factors and downstream target genes that are critical for normal tapetum development and function. These studies, together with other recently published works, indicate that cell-cell communication and transcriptional control are key processes essential for cell fate specification in anther development.

  2. FGFs and BMP4 induce both Msx1-independent and Msx1-dependent signaling pathways in early tooth development.

    Science.gov (United States)

    Bei, M; Maas, R

    1998-11-01

    During early tooth development, multiple signaling molecules are expressed in the dental lamina epithelium and induce the dental mesenchyme. One signal, BMP4, has been shown to induce morphologic changes in dental mesenchyme and mesenchymal gene expression via Msx1, but BMP4 cannot substitute for all the inductive functions of the dental epithelium. To investigate the role of FGFs during early tooth development, we examined the expression of epithelial and mesenchymal Fgfs in wild-type and Msx1 mutant tooth germs and tested the ability of FGFs to induce Fgf3 and Bmp4 expression in wild-type and Msx1 mutant dental mesenchymal explants. Fgf8 expression is preserved in Msx1 mutant epithelium while that of Fgf3 is not detected in Msx1 mutant dental mesenchyme. Moreover, dental epithelium as well as beads soaked in FGF1, FGF2 or FGF8 induce Fgf3 expression in dental mesenchyme in an Msx1-dependent manner. These results indicate that, like BMP4, FGF8 constitutes an epithelial inductive signal capable of inducing the expression of downstream signaling molecules in dental mesenchyme via Msx1. However, the BMP4 and FGF8 signaling pathways are distinct. BMP4 cannot induce Fgf3 nor can FGFs induce Bmp4 expression in dental mesenchyme, even though both signaling molecules can induce Msx1 and Msx1 is necessary for Fgf3 and Bmp4 expression in dental mesenchyme. In addition, we have investigated the effects of FGFs and BMP4 on the distal-less homeobox genes Dlx1 and Dlx2 and we have clarified the relationship between Msx and Dlx gene function in the developing tooth. Dlx1,Dlx2 double mutants exhibit a lamina stage arrest in maxillary molar tooth development (Thomas B. L., Tucker A. S., Qiu M. , Ferguson C. A., Hardcastle Z., Rubenstein J. L. R. and Sharpe P. T. (1997) Development 124, 4811-4818). Although the maintenance of molar mesenchymal Dlx2 expression at the bud stage is Msx1-dependent, both the maintenance of Dlx1 expression and the initial activation of mesenchymal Dlx1

  3. Correlation of VLF-EM Data with Radiometric Measurements: Implications for Uranium Exploration around Beldih, South Purulia Shear Zone, India

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    Saurabh Mittal

    2014-01-01

    Full Text Available This study is an attempt to correlate VLF-EM data with the radiometric measurements to decipher the subsurface structure and to locate uranium mineralization in the shear zone. The study area is around Beldih mine which is an open cast apatite mine located on the South Purulia Shear Zone. VLF method has been applied to map the structure and the presence of radioactive minerals has been delineated by the detection of high α and γ counts with respect to the background radiations. High radiation counts and high surface γ activity are found just above the higher apparent current-density zones in all the profiles studied, at various locations, indicating uranium and/or thorium mineralization as well as good correlation between these techniques.

  4. Effects of solar and geomagnetic activities on the sub-ionospheric very low frequency transmitter signals received by the DEMETER micro-satellite

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    Günter Stangl

    2012-04-01

    Full Text Available

    In the framework of seismic precursor electromagnetic investigations, we analyzed the very low frequency (VLF amplitude signals recorded by the Instrument Champ Electrique (ICE experiment on board the DEMETER micro-satellite. The sun-synchronous orbits of the micro-satellite allowed us to cover an invariant latitude of between –65° and +65° in a time interval of about 40 min. We considered four transmitter signals emitted by stations in Europe (France, FTU, 18.3 kHz; Germany, DFY, 16.58 kHz, Asia (Japan, JP, 17.8 kHz and Australia (Australia, NWC, 19.8 kHz. We studied the variations of these VLF signals, taking into consideration: the signal-to-noise ratio, sunspots, and the geomagnetic activity. We show that the degree of correlation in periods of high geomagnetic and solar activities is, on average, about 40%. Such effects can be fully neglected in the period of weak activity. We also find that the solar activity can have a more important effect on the VLF transmitter signal than the geomagnetic activity. Our data are combined with models where the coupling between the lithosphere, atmosphere and ionosphere is essential to explain how ionospheric disturbances scatter the VLF transmitter signal.


  5. On the occurrence of ground observations of ELF/VLF magnetospheric amplification induced by the HAARP facility

    OpenAIRE

    İnan, Umran Savaş; Golkowski, M.; Cohen, M. B.; Carpenter, D. L.

    2011-01-01

    The ionospheric heating facility of the High Frequency Active Auroral Research Program (HAARP) has been used extensively in the last 3 years for injection of ELF/VLF waves into the magnetosphere via modulated heating of the overhead auroral electrojet currents. Of particular interest are waves that are observed to be nonlinearly amplified after interaction with hot plasma electrons in the Earth's radiation belts. Past results have shown HAARP to be an effective platform for controlled studies...

  6. Replicating the Ice-Volume Signal of the Early Pleistocene with a Complex Earth System Model

    Science.gov (United States)

    Tabor, C. R.; Poulsen, C. J.; Pollard, D.

    2013-12-01

    Milankovitch theory proposes high-latitude summer insolation intensity paces the ice ages by controlling perennial snow cover amounts (Milankovitch, 1941). According to theory, the ~21 kyr cycle of precession should dominate the ice-volume records since it has the greatest influence on high-latitude summer insolation. Modeling experiments frequently support Milankovitch theory by attributing the majority of Northern Hemisphere high-latitude summer snowmelt to changes in the cycle of precession (e.g. Jackson and Broccoli, 2003). However, ice-volume proxy records, especially those of the Early Pleistocene (2.6-0.8 Ma), display variability with a period of ~41 kyr (Raymo and Lisiecki, 2005), indicative of insolation forcing from obliquity, which has a much smaller influence on summer insolation intensity than precession. Several hypotheses attempt to explain the discrepancies between Milkankovitch theory and the proxy records by invoking phenomena such as insolation gradients (Raymo and Nisancioglu, 2003), hemispheric offset (Raymo et al., 2006; Lee and Poulsen, 2009), and integrated summer energy (Huybers, 2006); however, all of these hypotheses contain caveats (Ruddiman, 2006) and have yet to be supported by modeling studies that use a complex GCM. To explore potential solutions to this '41 kyr problem,' we use an Earth system model composed of the GENESIS GCM and Land Surface model, the BIOME4 vegetation model, and the Pennsylvania State ice-sheet model. Using an asynchronous coupling technique, we run four idealized transient combinations of obliquity and precession, representing the orbital extremes of the Pleistocene (Berger and Loutre, 1991). Each experiment is run through several complete orbital cycles with a dynamic ice domain spanning North America and Greenland, and fixed preindustrial greenhouse-gas concentrations. For all orbital configurations, model results produce greater ice-volume spectral power at the frequency of obliquity despite significantly

  7. Classification of Parameters Extracted from Cardiotocographic Signals for Early Detection of Metabolic Acidemia in Newborns

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    ROTARIU, C.

    2015-08-01

    Full Text Available Fetal acidosis is reflected by the values of umbilical cord pH and base deficit (BDecf: normal recordings (pH over 7.2 and BDecf under 8 mmol/l and abnormal recordings (pH under 7.2 and BDecf over 8 mmol/l. The purpose of this paper is to present the implementation of an automated system for detecting fetal acidosis in cardiotocographic recordings. The method uses spectral analysis of medium (0.07-0.13 Hz and high (0.13-1 Hz frequency spectrum. We implement the algorithm for segments of the recordings without signal loss for better classification. We determined the normalized medium and high frequency components and mid to high frequency ratio. The recordings in the database are divided into a control group (100 normal recordings and a test group (431 normal or abnormal recordings. A t-test with the p value under 0.05 between the two groups is used to classify the test group. The classification is improved by including the presence of late and prolonged decelerations in the classification process, obtaining the final results, which are comparable to the best ones in current literature.

  8. Early Growth Response Genes Signaling Supports Strong Paracrine Capability of Mesenchymal Stem Cells

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    Kenichi Tamama

    2012-01-01

    Full Text Available MSCs provide a promising method for cell therapy through their wound healing and tissue regenerative properties. Originally, MSCs' role in wound healing was thought to be tied to their multipotency, but it is now accepted that MSCs mediate the healing process through their strong paracrine capability. EGF was shown to facilitate in vitro expansion of MSCs without altering multipotency. Our previous data suggest that the molecular machinery underlying MSCs' strong paracrine capability lies downstream of EGFR signaling, and we focus on transcription factors EGR1 and EGR2. Evidence suggests that EGR1 regulates angiogenic and fibrogenic factor production in MSCs, and an EGFR-EGR1-EGFR ligands autocrine loop is one of the underlying mechanisms supporting their strong paracrine machinery through EGR1. EGR2 appears to regulate the expression of immunomodulatory molecules. Chronic nonhealing wounds are ischemic, inflammatory, and often fibrotic, and the hypoxic micro-environment of these wounds may compromise MSCs' wound healing properties in vivo by upregulating the EGR1's fibrogenic effects and downregulating the EGR2's immuno-modulatory effects. Thus, these transcription factors can be potential targets in the optimization of cell-based therapies. Further study in vitro is required to understand MSCs' paracrine machinery and to optimize it as a tool for effective cell-based therapies.

  9. HTLV-1 Tax upregulates early growth response protein 1 through nuclear factor-κB signaling.

    Science.gov (United States)

    Huang, Qingsong; Niu, Zhiguo; Han, Jingxian; Liu, Xihong; Lv, Zhuangwei; Li, Huanhuan; Yuan, Lixiang; Li, Xiangping; Sun, Shuming; Wang, Hui; Huang, Xinxiang

    2017-08-01

    Human T cell leukemia virus type 1 (HTLV-1) is a complex retrovirus that causes adult T cell leukemia (ATL) in susceptible individuals. The HTLV-1-encoded oncoprotein Tax induces persistent activation of the nuclear factor-κB (NF-κB) pathway. Early growth response protein 1 (EGR1) is overexpressed in HTLV-1-infected T cell lines and ATL cells. Here, we showed that both Tax expression and HTLV-1 infection promoted EGR1 overexpression. Loss of the NF-κB binding site in the EGR1 promotor or inhibition of NF-κB activation reduced Tax-induced EGR1 upregulation. Tax mutants unable to activate NF-κB induced only slight EGR1 upregulation as compared with wild-type Tax, confirming NF-κB pathway involvement in EGR1 regulation. Tax also directly interacted with the EGR1 protein and increased endogenous EGR1 stability. Elevated EGR1 in turn promoted p65 nuclear translocation and increased NF-κB activation. These results demonstrate a positive feedback loop between EGR1 expression and NF-κB activation in HTLV-1-infected and Tax-expressing cells. Both NF-κB activation and Tax-induced EGR1 stability upregulated EGR1, which in turn enhanced constitutive NF-κB activation and facilitated ATL progression in HTLV-1-infected cells. These findings suggest EGR1 may be an effective anti-ATL therapeutic target.

  10. Information dissipation as an early-warning signal for the Lehman Brothers collapse in financial time series

    Science.gov (United States)

    Quax, Rick; Kandhai, Drona; Sloot, Peter M. A.

    2013-05-01

    In financial markets, participants locally optimize their profit which can result in a globally unstable state leading to a catastrophic change. The largest crash in the past decades is the bankruptcy of Lehman Brothers which was followed by a trust-based crisis between banks due to high-risk trading in complex products. We introduce information dissipation length (IDL) as a leading indicator of global instability of dynamical systems based on the transmission of Shannon information, and apply it to the time series of USD and EUR interest rate swaps (IRS). We find in both markets that the IDL steadily increases toward the bankruptcy, then peaks at the time of bankruptcy, and decreases afterwards. Previously introduced indicators such as `critical slowing down' do not provide a clear leading indicator. Our results suggest that the IDL may be used as an early-warning signal for critical transitions even in the absence of a predictive model.

  11. Role of Corticotropin Releasing Factor 1 Signaling in Cocaine Seeking during Early Extinction in Female and Male Rats.

    Directory of Open Access Journals (Sweden)

    Angie M Cason

    Full Text Available Locus coeruleus norepinephrine (LC-NE and corticotropin releasing factor (CRF neurons are involved in stress responses, including stress's ability to drive drug relapse. Previous animal studies indicate that female rats exhibit greater drug seeking than male rats during initial drug abstinence. Moreover, females are more sensitive to the effect of stress to drive drug seeking than males. Finally, LC-NE neurons are more sensitive to CRF in females compared to males. We hypothesized that increased drug seeking in females on extinction day one (ED1 is due to increased response to the stress of early withdrawal and is dependent upon the increased response of LC in females to CRF. We predicted that LC-NE neurons would exhibit Fos activation on ED1, and that blocking CRF1 signaling would decrease drug seeking on ED1 measured by responding on an active lever previously associated with cocaine self- administration. After chronic cocaine self-administration, female and male rats underwent a test for initial extinction responding by measuring lever pressing in the absence of cocaine. Prior to this Extinction Day 1 (ED1 session, rats were injected with vehicle or the selective CRF1 antagonist (CP to measure effects of CRF antagonism on drug seeking during early abstinence. ED1 increased corticosterone in female rats, in proportion to lever responding in male and female, indicating that ED1 was stressful. Pretreatment with CP decreased cocaine seeking on ED1 more effectively in female compared to male rats. This increase in responding was associated with an increase in activation of LC NE neurons. Together, these findings indicate that stress, and signaling at CRF receptors in LC, may be involved in the increased drug seeking during initial abstinence.

  12. Increase in estrogen signaling in the early brain of orange-spotted grouper Epinephelus coioides: a mini-review.

    Science.gov (United States)

    Nagarajan, Ganesan; Aruna, Adimoolam; Chang, Ching-Fong

    2013-02-01

    Despite neurosteroidogenic enzymes are playing important roles in the regulation of brain development and function, the potential link between brain and gonad by the action of steroid hormones during gonadal sex differentiation is still not clear in teleosts. In this mini-review, we summarized our understanding on the early brain development related to the synthesis of neurosteroids and receptor signaling during gonadal sex differentiation in protogynous orange-spotted grouper, Epinephelus coioides (functional females for the first 6 years of life and start to sex change around the age of 7 years) and protandrous black porgy (functional males for the first 2 years of life but begin to change sex during the third year). We found a similar profile in the increased expression of brain aromatase gene (aromatatse B or cyp19a1b), aromatase activity, estradiol (E(2)), and estrogen signaling in the brain of both grouper and black porgy fish during gonadal sex differentiation. In contrast to mammals, teleost fish Cyp19a1b expressed in a unique cell type, a radial glial cell, which is acted as progenitors in the brain of developing and adult fish. In agreement with these pioneer studies, we demonstrated that the grouper cyp19a1b/Cyp19a1b was expressed in radial glial cells. Further, in vivo data in the grouper brain showed that exogenous E(2) upregulated Cyp19a1b immunoreactivity (ir) in radial glial cells. These data suggest the possible roles of Cyp19a1b and E(2) in early brain development which is presumably related to gonadal sex differentiation.

  13. Phylogenetics of early branching eudicots: Comparing phylogenetic signal across plastid introns, spacers, and genes

    Institute of Scientific and Technical Information of China (English)

    Anna-Magdalena BARNISKE; Thomas BORSCH; Kai M(U)LLER; Michael KRUG; Andreas WORBERG; Christoph NEINHUIS; Dietmar QUANDT

    2012-01-01

    Recent phylogenetic analyses revealed a grade with Ranunculales,Sabiales,Proteales,Trochodendrales,and Buxales as first branching eudicots,with the respective positions of Proteales and Sabiales still lacking statistical confidence.As previous analyses of conserved plastid genes remain inconclusive,we aimed to use and evaluate a representative set of plastid introns (group Ⅰ:trnL; group Ⅱ:petD,rpll6,trnK) and intergenic spacers (trnL-F,petB-petD,atpB-rbcL,rps3-rpll6) in comparison to the rapidly evolving matK and slowly evolving atpB and rbcL genes.Overall patterns of microstructural mutations converged across genomic regions,underscoring the existence of a general mutational pattern throughout the plastid genome.Phylogenetic signal differed strongly between functionally and structurally different genomic regions and was highest in matK,followed by spacers,then group Ⅱ and group Ⅰ introns.The more conserved atpB and rbcL coding regions showed distinctly lower phylogenetic information content.Parsimony,maximum likelihood,and Bayesian phylogenetic analyses based on the combined dataset of non-coding and rapidly evolving regions (>14 000 aligned characters) converged to a backbone topology ofeudicots with Ranunculales branching first,a Proteales-Sabiales clade second,followed by Trochodendrales and Buxales.Gunnerales generally appeared as sister to all remaining core eudicots with maximum support.Our results show that a small number of intron and spacer sequences allow similar insights into phylogenetic relationships of eudicots compared to datasets of many combined genes.The non-coding proportion of the plastid genome thus can be considered an important information source for plastid phylogenomics.

  14. Paleoenvironmental signals and paleoclimatic condition of the Early Maastrichtian oil shales from Central Eastern Desert, Egypt

    Science.gov (United States)

    Fathy, Douaa; Wagreich, Michael; Zaki, Rafat; Mohamed, Ramadan S. A.

    2016-04-01

    Early Maastrichtian oil shales are hosted in the Duwi Formation of the Central Eastern Desert, Egypt. The examined member represents up to 20% of the total Duwi Formation. This interval is mainly composed of siliciclastic facies, phosphorites facies and carbonate facies. Oil shales microfacies is mainly composed of smectite, kaolinite, calcite, fluorapatite, quartz and pyrite. They are enriched in a number of major elements and trace metals in particular Ca, P, V, Ni, Cr, Sr, Zn, Mo, Nb, U and Y compared to the post-Archaean Australian shale (PAAS). Chondrite-normalized REEs patterns of oil shales for the studied area display light rare earth elements enrichment relatively to heavy rare earth elements with negative Ce/Ce* and Eu/Eu* anomalies. The most remarkable indicators for redox conditions are enrichments of V, Mo, Ni, Cr, U content and depletion of Mn content. Besides, V/V+Ni, V/Ni, U/Th, Ni/Co, authigentic uranium ratios with presence of framboidal shape of pyrite and its size are reflecting the deposition of these shales under marine anoxic to euxinic environmental conditions. Additionally, the ratio of Strontium (Sr) to Barium (Ba) Sr/Ba reflected highly saline water during deposition. Elemental ratios critical to paleoclimate and paleoweathering (Rb /Sr, Al2O3/TiO2), CIA values, binary diagram between (Al2O3+K2O+Na2O) and SiO2 and types of clay minerals dominated reflect warm to humid climate conditions prevailing during the accumulation of these organic-rich petroleum source rocks.

  15. miRNA targeted signaling pathway in the early stage of denervated fast and slow muscle atrophy

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    Gang Li

    2016-01-01

    Full Text Available Denervation often results in skeletal muscle atrophy. Different mechanisms seem to be involved in the determination between denervated slow and fast skeletal muscle atrophy. At the epigenetic level, miRNAs are thought to be highly involved in the pathophysiological progress of denervated muscles. We used miRNA microarrays to determine miRNA expression profiles from a typical slow muscle (soleus muscle and a typical fast muscle (tibialis anterior muscle at an early denervation stage in a rat model. Results showed that miR-206, miR-195, miR-23a, and miR-30e might be key factors in the transformation process from slow to fast muscle in denervated slow muscles. Additionally, certain miRNA molecules (miR-214, miR-221, miR-222, miR-152, miR-320, and Let-7e could be key regulatory factors in the denervated atrophy process involved in fast muscle. Analysis of signaling pathway networks revealed the miRNA molecules that were responsible for regulating certain signaling pathways, which were the final targets (e.g., p38 MAPK pathway; Pax3/Pax7 regulates Utrophin and follistatin by HDAC4; IGF1/PI3K/Akt/mTOR pathway regulates atrogin-1 and MuRF1 expression via FoxO phosphorylation. Our results provide a better understanding of the mechanisms of denervated skeletal muscle pathophysiology.

  16. FOXO3a governs early and late apoptotic endothelial programs during elevated glucose through mitochondrial and caspase signaling.

    Science.gov (United States)

    Hou, Jinling; Chong, Zhao Zhong; Shang, Yan Chen; Maiese, Kenneth

    2010-06-10

    Mechanisms that preserve endothelial cell (EC) integrity remain elusive, but are critical for new strategies directed against endocrine disorders such as diabetes mellitus (DM). Here we demonstrate in primary cerebral ECs with a clinically relevant model of elevated d-glucose that Akt1 and the post-translational modification and subcellular trafficking of the forkhead transcription factor FoxO3a are critical for early apoptotic membrane signaling and subsequent degradation of nuclear DNA. FoxO3a also directly governs apoptotic mitochondrial signal transduction pathways, since gene knockdown of FoxO3a prevents mitochondrial membrane depolarization as well as the release of cytochrome c. Control of this apoptotic cascade extends to the rapid and progressive activation of caspases. The presence of FoxO3a is necessary for cleaved (active) caspase 1 and 3 expression, since loss of FoxO3a abrogates the induction of caspase activity. Our work identifies Akt1, FoxO3a and closely aligned pathways as key therapeutic targets during impaired glucose tolerance and DM.

  17. Augmented D1 dopamine receptor signaling and immediate-early gene induction in adult striatum following prenatal cocaine

    Science.gov (United States)

    Tropea, Thomas F.; Guerriero, Réjean M.; Willuhn, Ingo; Unterwald, Ellen M.; Ehrlich, Michelle E.; Steiner, Heinz; Kosofsky, Barry E.

    2009-01-01

    Background Prenatal exposure to cocaine can impede normal brain development triggering a range of neuroanatomical and behavioral anomalies that are evident throughout life. Mouse models have been especially helpful in delineating neuro-teratogenic consequences following prenatal exposure tococaine. The present study employed a mouse model to investigate alterations in D1 dopamine receptor signaling and downstream immediate-early gene induction in the striatum of mice exposed to cocaine in utero. Methods Basal, forskolin- and D1 receptor agonist-induced cAMP levels were measured ex vivo in the adult male striatum in mice exposed to cocaine in utero. Further studies assessed cocaine-induced zif 268 and homer 1 expression in the striatum of juvenile (P15), adolescent (P36), and adult (P60) male mice. Results The D1 dopamine receptor agonist SKF82958 induced significantly higher levels of cAMP in adult male mice treated with cocaine in utero compared to saline controls. No effects of the prenatal treatment were found for cAMP formation induced by forskolin. Following an acute cocaine challenge (15 mg/kg, i.p.), these mice showed greater induction of zif 268 and homer 1, an effect that was most robust in the medial part of the mid-level striatum and became more pronounced with increasing age. Conclusions Together these findings indicate abnormally enhanced D1 receptor signal transduction in adult mice following prenatal cocaine exposure. Such changes in dopamine receptor signaling may underlie aspects of long-lasting neuro-teratogenic effects evident in some humans following in utero exposure to cocaine, and identify the striatum as one target potentially vulnerable to gestational cocaine exposure. PMID:18275938

  18. Midazolam sedation increases fluctuation and synchrony of the resting brain BOLD signal.

    Science.gov (United States)

    Kiviniemi, Vesa J; Haanpää, Hannu; Kantola, Juha-Heikki; Jauhiainen, Jukka; Vainionpää, Vilho; Alahuhta, Seppo; Tervonen, Osmo

    2005-05-01

    The blood oxygen level-dependent (BOLD) magnetic resonance signal of functional brain cortices is dominated by very low frequency (VLF) fluctuations in anesthetized child patients. The temporal synchrony of the BOLD signal is also higher in anesthetized children compared with awake adults. The origin of the synchronous fluctuations can be related to maturation, pathological status or the anesthesia used in the imaging. Two of the three confounding variables (maturation and pathology) were controlled in this study. The effect of midazolam (4+/-0.8 mg) sedation on the BOLD signal was assessed in 12 healthy adults (aged 24+/-1.5 years) at 1.5 T. The VLF fluctuation power and temporal synchrony of the BOLD signal increased significantly after the sedation in the auditory and visual cortices. The fast Fourier transformation power spectral baseline fit parameters of the BOLD signal were also found to change significantly after sedation. It is concluded that the VLF fluctuation and temporal synchrony of the BOLD signal become increased after sedation in functional brain regions.

  19. Early apoptotic vascular signaling is determined by Sirt1 through nuclear shuttling, forkhead trafficking, bad, and mitochondrial caspase activation.

    Science.gov (United States)

    Hou, Jinling; Chong, Zhao Zhong; Shang, Yan Chen; Maiese, Kenneth

    2010-05-01

    Complications of diabetes mellitus (DM) weigh heavily upon the endothelium that ultimately affect multiple organ systems. These concerns call for innovative treatment strategies that employ molecular pathways responsible for cell survival and longevity. Here we show in a clinically relevant model of DM with elevated D-glucose that endothelial cell (EC) SIRT1 is vital for the prevention of early membrane apoptotic phosphatidylserine externalization and subsequent DNA degradation supported by studies with modulation of SIRT1 activity and gene knockdown of SIRT1. Furthermore, during elevated D-glucose exposure, we show that SIRT1 is sequestered in the cytoplasm of ECs, but specific activation of SIRT1 shuttles the protein to the nucleus to allow for cytoprotection. The ability of SIRT1 to avert apoptosis employs the activation of protein kinase B (Akt1), the post-translational phosphorylation of the forkhead member FoxO3a, the blocked trafficking of FoxO3a to the nucleus, and the inhibition of FoxO3a to initiate a "pro-apoptotic" program as shown by complimentary gene knockdown studies of FoxO3a. Vascular apoptotic oversight by SIRT1 extends to the direct modulation of mitochondrial membrane permeability, cytochrome c release, Bad activation, and caspase 1 and 3 activation, since inhibition of SIRT1 activity and gene knockdown of SIRT1 significantly accentuate cascade progression while SIRT1 activation abrogates these apoptotic elements. Our work identifies vascular SIRT1 and its control over early apoptotic membrane signaling, Akt1 activation, post-translational modification and trafficking of FoxO3a, mitochondrial permeability, Bad activation, and rapid caspase induction as new avenues for the treatment of vascular complications during DM.

  20. Early Apoptotic Vascular Signaling is Determined by Sirt1 Through Nuclear Shuttling, Forkhead Trafficking, Bad, and Mitochondrial Caspase Activation

    Science.gov (United States)

    Hou, Jinling; Chong, Zhao Zhong; Shang, Yan Chen; Maiese, Kenneth

    2010-01-01

    Complications of diabetes mellitus (DM) weigh heavily upon the endothelium that ultimately affect multiple organ systems. These concerns call for innovative treatment strategies that employ molecular pathways responsible for cell survival and longevity. Here we show in a clinically relevant model of DM with elevated D-glucose that endothelial cell (EC) SIRT1 is vital for the prevention of early membrane apoptotic phosphatidylserine externalization and subsequent DNA degradation supported by studies with modulation of SIRT1 activity and gene knockdown of SIRT1. Furthermore, during elevated D-glucose exposure, we show that SIRT1 is sequestered in the cytoplasm of ECs, but specific activation of SIRT1 shuttles the protein to the nucleus to allow for cytoprotection. The ability of SIRT1 to avert apoptosis employs the activation of protein kinase B (Akt1), the post-translational phosphorylation of the forkhead member FoxO3a, the blocked trafficking of FoxO3a to the nucleus, and the inhibition of FoxO3a to initiate a “pro-apoptotic” program as shown by complimentary gene knockdown studies of FoxO3a. Vascular apoptotic oversight by SIRT1 extends to the direct modulation of mitochondrial membrane permeability, cytochrome c release, Bad activation, and caspase 1 and 3 activation, since inhibition of SIRT1 activity and gene knockdown of SIRT1 significantly accentuate cascade progression while SIRT1 activation abrogates these apoptotic elements. Our work identifies vascular SIRT1 and its control over early apoptotic membrane signaling, Akt1 activation, post-translational modification and trafficking of FoxO3a, mitochondrial permeability, Bad activation, and rapid caspase induction as new avenues for the treatment of vascular complications during DM. PMID:20370652

  1. Early-Stage Pilot Study on Using Fractional-Order Calculus-Based Filtering for the Purpose of Analysis of Electroencephalography Signals

    Directory of Open Access Journals (Sweden)

    Kawala-Janik Aleksandra

    2016-12-01

    Full Text Available Analysis of Electroencephalography (EEG signals has recently awoken the increased interest of numerous researchers all around the world with regard to rapid development of Brain-Computer Interaction-related research areas and because EEG signals are implemented in most of the non-invasive BCI systems, as they provide necessary information regarding activity of the brain. In this paper, a very early stage pilot study on implementation of filtering based on fractional-order calculus (Bi-Fractional Filters – BFF for the purpose of EEG signal classification is presented in brief.

  2. Remediation of radiation belt electrons caused by ground based man-made VLF wave%地基人工 VLF电波对辐射带电子的调制

    Institute of Scientific and Technical Information of China (English)

    王平; 徐岩冰; 于晓霞; 赵小芸; 吴峰; 王焕玉; 马宇蒨; 李新乔; 卢红; 孟祥承; 张吉龙; 王辉; 石峰

    2011-01-01

    辐射带电子的加速与沉降机理是空间物理研究的重要课题.法国DEMETER电磁卫星观测到了美国NPM发射站VLF信号及与之相关的高能电子沉降事例.本研究工作将根据基于回旋共振相互作用的准线性扩散理论,通过对局域投掷角扩散系数的计算,来说明受VLF影响的高能电子的投掷角分布与电子的能量及所处位置的关系.理论计算较好地解释了DEMETER卫星在NPM实验期间所观测到的电子沉降事例.在此基础上进一步讨论了通过人工方式对辐射带高能电子施加影响的效率问题.%The physics mechanisms of radiation belt electrons loss and acceleration are important issues in space physics research. Recently, France Microsatellite DEMETER has discovered the correlation between man- made VLF signals and radiation belt electrons precipitation in the NPM ( the U. S. VLF transmitter located at Lualualei ) experiment. Our research focuses on the explanation of the relation among affected pitch angle distribution, kinetic energy and position of electrons. This is achieved by calculating the local diffusion coeffcient based on the theory of qusi-linear diffusion with resonant interaction. Our result has a good explanation of radiation belt electron precipitation discovered by DEMETER during NPM experiment. Furthermore, we have discussed the effciency of radiation belt remediation in an artificial way.

  3. Comparative gene expression analysis of Dtg, a novel target gene of Dpp signaling pathway in the early Drosophila melanogaster embryo.

    Science.gov (United States)

    Hodar, Christian; Zuñiga, Alejandro; Pulgar, Rodrigo; Travisany, Dante; Chacon, Carlos; Pino, Michael; Maass, Alejandro; Cambiazo, Verónica

    2014-02-10

    In the early Drosophila melanogaster embryo, Dpp, a secreted molecule that belongs to the TGF-β superfamily of growth factors, activates a set of downstream genes to subdivide the dorsal region into amnioserosa and dorsal epidermis. Here, we examined the expression pattern and transcriptional regulation of Dtg, a new target gene of Dpp signaling pathway that is required for proper amnioserosa differentiation. We showed that the expression of Dtg was controlled by Dpp and characterized a 524-bp enhancer that mediated expression in the dorsal midline, as well as, in the differentiated amnioserosa in transgenic reporter embryos. This enhancer contained a highly conserved region of 48-bp in which bioinformatic predictions and in vitro assays identified three Mad binding motifs. Mutational analysis revealed that these three motifs were necessary for proper expression of a reporter gene in transgenic embryos, suggesting that short and highly conserved genomic sequences may be indicative of functional regulatory regions in D. melanogaster genes. Dtg orthologs were not detected in basal lineages of Dipterans, which unlike D. melanogaster develop two extra-embryonic membranes, amnion and serosa, nevertheless Dtg orthologs were identified in the transcriptome of Musca domestica, in which dorsal ectoderm patterning leads to the formation of a single extra-embryonic membrane. These results suggest that Dtg was recruited as a new component of the network that controls dorsal ectoderm patterning in the lineage leading to higher Cyclorrhaphan flies, such as D. melanogaster and M. domestica. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Connectivity Reveals Sources of Predictive Coding Signals in Early Visual Cortex During Processing of Visual Optic Flow.

    Science.gov (United States)

    Schindler, Andreas; Bartels, Andreas

    2016-05-24

    Superimposed on the visual feed-forward pathway, feedback connections convey higher level information to cortical areas lower in the hierarchy. A prominent framework for these connections is the theory of predictive coding where high-level areas send stimulus interpretations to lower level areas that compare them with sensory input. Along these lines, a growing body of neuroimaging studies shows that predictable stimuli lead to reduced blood oxygen level-dependent (BOLD) responses compared with matched nonpredictable counterparts, especially in early visual cortex (EVC) including areas V1-V3. The sources of these modulatory feedback signals are largely unknown. Here, we re-examined the robust finding of relative BOLD suppression in EVC evident during processing of coherent compared with random motion. Using functional connectivity analysis, we show an optic flow-dependent increase of functional connectivity between BOLD suppressed EVC and a network of visual motion areas including MST, V3A, V6, the cingulate sulcus visual area (CSv), and precuneus (Pc). Connectivity decreased between EVC and 2 areas known to encode heading direction: entorhinal cortex (EC) and retrosplenial cortex (RSC). Our results provide first evidence that BOLD suppression in EVC for predictable stimuli is indeed mediated by specific high-level areas, in accord with the theory of predictive coding.

  5. Melatonin attenuated early brain injury induced by subarachnoid hemorrhage via regulating NLRP3 inflammasome and apoptosis signaling.

    Science.gov (United States)

    Dong, Yushu; Fan, Chongxi; Hu, Wei; Jiang, Shuai; Ma, Zhiqiang; Yan, Xiaolong; Deng, Chao; Di, Shouyin; Xin, Zhenlong; Wu, Guiling; Yang, Yang; Reiter, Russel J; Liang, Guobiao

    2016-04-01

    Subarachnoid hemorrhage (SAH) is a devastating condition with high morbidity and mortality rates due to the lack of effective therapy. Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation associated with the upregulation of apoptotic signaling pathway has been implicated in various inflammatory diseases including hemorrhagic insults. Melatonin is reported to possess substantial anti-inflammatory properties, which is beneficial for early brain injury (EBI) after SAH. However, the molecular mechanisms have not been clearly identified. This study was designed to investigate the protective effects of melatonin against EBI induced by SAH and to elucidate the potential mechanisms. The adult mice were subjected to SAH. Melatonin or vehicle was injected intraperitoneally 2 hr after SAH. Melatonin was neuroprotective, as shown by increased survival rate, as well as elevated neurological score, greater survival of neurons, preserved brain glutathione levels, and reduced brain edema, malondialdehyde concentrations, apoptotic ratio, and blood-brain barrier (BBB) disruption. Melatonin also attenuated the expressions of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cleaved caspase-1, interleukin-1β (IL-1β), and interleukin-6 (IL-6); these changes were also associated with an increase in the anti-apoptotic factor (Bcl2) and reduction in the pro-apoptotic factor (Bim). In summary, our results demonstrate that melatonin treatment attenuates the EBI following SAH by inhibiting NLRP3 inflammasome-associated apoptosis.

  6. Can we Detect Ecosystem Critical Transitions and Early Warning Signals of Catastrophic Shifts from Palaeo-Ecological Records?

    Science.gov (United States)

    Perga, M. E.; Taranu, Z. E.; Gregory-Eaves, I.; Frossard, V.; Thomas, Z.; Legendre, P.; Anderson, N. J.; Leavitt, P.; Gell, P.

    2015-12-01

    The observation that managed ecosystems often fail to respond smoothly to changing external pressures has shed some light on their complex non-linear dynamics. The concept of critical transitions (i.e., ecosystem regime shifts), thresholds and alternative stable states has since spread to the ecological and environmental management literature. Most recently, however, reviews have raised some skepticism about whether these catastrophic transitions are the exceptions rather than the rule. Overall, a better understanding of the occurrence and processes of such critical transitions requires more empirical testing and evidence on the mechanistic links between pressures and consequent ecological change. Many of the changes observed, or modeled, by ecologists extend beyond the monitoring record. Palaeo-ecological records thus represent a unique opportunity to extend our temporal perspective to the relevancy of critical transitions. Yet, paleo-ecological records have their own biases and shortcomings, such as sediment focusing, irregular temporal integration and often studied in a semi-quantitative way. As such, palaeo-ecological time series are not strictly analogous to instrumental datasets. In this work, we aimed to test, using both modeled and actual records, how different properties that are common in palaeo-ecological records affect our ability to detect past non-linear dynamics, such as early-warning signals of catastrophic shifts.

  7. Rutin-Mediated Priming of Plant Resistance to Three Bacterial Pathogens Initiating the Early SA Signal Pathway.

    Directory of Open Access Journals (Sweden)

    Wei Yang

    Full Text Available Flavonoids are ubiquitous in the plant kingdom and have many diverse functions, including UV protection, auxin transport inhibition, allelopathy, flower coloring and insect resistance. Here we show that rutin, a proud member of the flavonoid family, could be functional as an activator to improve plant disease resistances. Three plant species pretreated with 2 mM rutin were found to enhance resistance to Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, and Pseudomonas syringae pv. tomato strain DC3000 in rice, tobacco and Arabidopsis thaliana respectively. While they were normally propagated on the cultural medium supplemented with 2 mM rutin for those pathogenic bacteria. The enhanced resistance was associated with primed expression of several pathogenesis-related genes. We also demonstrated that the rutin-mediated priming resistance was attenuated in npr1, eds1, eds5, pad4-1, ndr1 mutants, and NahG transgenic Arabidopsis plant, while not in either snc1-11, ein2-5 or jar1 mutants. We concluded that the rutin-priming defense signal was modulated by the salicylic acid (SA-dependent pathway from an early stage upstream of NDR1 and EDS1.

  8. Rutin-Mediated Priming of Plant Resistance to Three Bacterial Pathogens Initiating the Early SA Signal Pathway.

    Science.gov (United States)

    Yang, Wei; Xu, Xiaonan; Li, Yang; Wang, Yingzi; Li, Ming; Wang, Yong; Ding, Xinhua; Chu, Zhaohui

    2016-01-01

    Flavonoids are ubiquitous in the plant kingdom and have many diverse functions, including UV protection, auxin transport inhibition, allelopathy, flower coloring and insect resistance. Here we show that rutin, a proud member of the flavonoid family, could be functional as an activator to improve plant disease resistances. Three plant species pretreated with 2 mM rutin were found to enhance resistance to Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, and Pseudomonas syringae pv. tomato strain DC3000 in rice, tobacco and Arabidopsis thaliana respectively. While they were normally propagated on the cultural medium supplemented with 2 mM rutin for those pathogenic bacteria. The enhanced resistance was associated with primed expression of several pathogenesis-related genes. We also demonstrated that the rutin-mediated priming resistance was attenuated in npr1, eds1, eds5, pad4-1, ndr1 mutants, and NahG transgenic Arabidopsis plant, while not in either snc1-11, ein2-5 or jar1 mutants. We concluded that the rutin-priming defense signal was modulated by the salicylic acid (SA)-dependent pathway from an early stage upstream of NDR1 and EDS1.

  9. Enhanced aldosterone signaling in the early nephropathy of rats with metabolic syndrome: possible contribution of fat-derived factors.

    Science.gov (United States)

    Nagase, Miki; Yoshida, Shigetaka; Shibata, Shigeru; Nagase, Takashi; Gotoda, Takanari; Ando, Katsuyuki; Fujita, Toshiro

    2006-12-01

    Metabolic syndrome is an important risk factor for proteinuria and chronic kidney disease independent of diabetes and hypertension; however, the underlying mechanisms have not been elucidated. Aldosterone is implicated in target organ injury of obesity-related disorders. This study investigated the role of aldosterone in the early nephropathy of 17-wk-old SHR/NDmcr-cp, a rat model of metabolic syndrome. Proteinuria was prominent in SHR/NDmcr-cp compared with nonobese SHR, which was accompanied by podocyte injury as evidenced by foot process effacement, induction of desmin and attenuation of nephrin. Serum aldosterone level, renal and glomerular expressions of aldosterone effector kinase Sgk1, and oxidative stress markers all were elevated in SHR/NDmcr-cp. Mineralocorticoid receptors were expressed in glomerular podocytes. Eplerenone, a selective aldosterone blocker, effectively improved podocyte damage, proteinuria, Sgk1, and oxidant stress. An antioxidant tempol also alleviated podocyte impairment and proteinuria, along with inhibition of Sgk1. As for the mechanisms of aldosterone excess, visceral adipocytes that were isolated from SHR/NDmcr-cp secreted substances that stimulate aldosterone production in adrenocortical cells. The aldosterone-releasing activity of adipocytes was not inhibited by candesartan. Adipocytes from nonobese SHR did not show such activity. In conclusion, SHR/NDmcr-cp exhibit enhanced aldosterone signaling, podocyte injury, and proteinuria, which are ameliorated by eplerenone or tempol. The data also suggest that adipocyte-derived factors other than angiotensin II might contribute to the aldosterone excess of this model.

  10. The response of early neural genes to FGF signaling or inhibition of BMP indicate the absence of a conserved neural induction module

    Directory of Open Access Journals (Sweden)

    Rogers Crystal D

    2011-12-01

    Full Text Available Abstract Background The molecular mechanism that initiates the formation of the vertebrate central nervous system has long been debated. Studies in Xenopus and mouse demonstrate that inhibition of BMP signaling is sufficient to induce neural tissue in explants or ES cells respectively, whereas studies in chick argue that instructive FGF signaling is also required for the expression of neural genes. Although additional signals may be involved in neural induction and patterning, here we focus on the roles of BMP inhibition and FGF8a. Results To address the question of necessity and sufficiency of BMP inhibition and FGF signaling, we compared the temporal expression of the five earliest genes expressed in the neuroectoderm and determined their requirements for induction at the onset of neural plate formation in Xenopus. Our results demonstrate that the onset and peak of expression of the genes vary and that they have different regulatory requirements and are therefore unlikely to share a conserved neural induction regulatory module. Even though all require inhibition of BMP for expression, some also require FGF signaling; expression of the early-onset pan-neural genes sox2 and foxd5α requires FGF signaling while other early genes, sox3, geminin and zicr1 are induced by BMP inhibition alone. Conclusions We demonstrate that BMP inhibition and FGF signaling induce neural genes independently of each other. Together our data indicate that although the spatiotemporal expression patterns of early neural genes are similar, the mechanisms involved in their expression are distinct and there are different signaling requirements for the expression of each gene.

  11. FGF signaling via MAPK is required early and improves Activin A-induced definitive endoderm formation from human embryonic stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Sui, Lina, E-mail: linasui@vub.ac.be [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium); Mfopou, Josue K. [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium); Geens, Mieke; Sermon, Karen [Department of Embryology and Genetics, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium); Bouwens, Luc [Cell Differentiation Unit, Diabetes Research Center, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels (Belgium)

    2012-09-28

    Highlights: Black-Right-Pointing-Pointer Deep study the FGF signaling role during DE specification in the context of hESCs. Black-Right-Pointing-Pointer DE differentiation from hESCs has an early dependence on FGF signaling. Black-Right-Pointing-Pointer A serum-free DE protocol is developed based on the findings. Black-Right-Pointing-Pointer The DE cells showed potential to differentiate into pancreatic progenitor cells. -- Abstract: Considering their unlimited proliferation and pluripotency properties, human embryonic stem cells (hESCs) constitute a promising resource applicable for cell replacement therapy. To facilitate this clinical translation, it is critical to study and understand the early stage of hESCs differentiation wherein germ layers are defined. In this study, we examined the role of FGF signaling in Activin A-induced definitive endoderm (DE) differentiation in the absence of supplemented animal serum. We found that activated FGF/MAPK signaling is required at the early time point of Activin A-induced DE formation. In addition, FGF activation increased the number of DE cells compared to Activin A alone. These DE cells could further differentiate into PDX1 and NKX6.1 positive pancreatic progenitors in vitro. We conclude that Activin A combined with FGF/MAPK signaling efficiently induce DE cells in the absence of serum. These findings improve our understanding of human endoderm formation, and constitute a step forward in the generation of clinical grade hESCs progenies for cell therapy.

  12. Applications of the VLF-EM method for rapid Sumatran fault identification in Leuser national park, Aceh

    Science.gov (United States)

    Irwandi, Marwan, Muksin, Fashbir

    2017-07-01

    Aceh is an area which is located at volcanically active region and at the meeting point of the Eurasian and the Indo-Australian plates. Many mountain formations and folds are formed as a result of the meeting of these plates. One of the mountains in Aceh is The Gunung Leuser, the highest mountain in the province with altitude of 3,404 m. The active geodynamic conditions could lead to the formation of potentially active faults which produce earthquakes. Due to safety reason, there are few researches done to identify active faults in the LE (Leuser Ecosystem). Therefore, we propose a preliminary study to identify morphological patterns of the fault system from the topography data of SRTM (Shuttle Radar Topography Mission). Having obtained the approximate location of fault, then a Very Low Frequency method is applied to determine the detail characteristic of the fault. This method can determine the subsurface structure to a depth of 50 m without digging or drilling. In this study, we measure three profiles with length of each profile of 12-16 km. Along profile 1, the VLF data fluctuated due to relatively high iron deposition along the line. For profile 2, the results are very consistent with the adjacent to the fault Blangkejeren which is the main part of the Sumatran Fault. Profile 3 Lokop - Kutacane fault also shows the correction of the topography. In general, VLF method is relatively influenced by noise as the consequences of the passive electromagnetic measurement. Thus, it is important to develop an analysis method of VLF data that includes the topographical correction so that better lateral anomaly map can be created.

  13. Resistivity soundings and VLF profiles for siting groundwater wells in a fractured basement aquifer in the Arabian Shield, Saudi Arabia

    Science.gov (United States)

    Ammar, A. I.; Kruse, S. E.

    2016-04-01

    Seasonal shortages of groundwater are common in parts of the Arabian Shield, where complex basement hydrogeology can make siting of water wells difficult. To identify optimal production well locations, six 200-400 m-long Very Low Frequency (VLF) electromagnetic traverses and ten Vertical Electrical Soundings (VESes) were run at the western edge of the Arabian Shield near At-Taif town, Saudi Arabia. Here wadi sediments overlie fractured Precambrian basement, which in turn overlies unfractured basement. The fractured basement forms the water supply aquifer. Both VLF and VES data indicate significant lateral heterogeneity in the electrical conductivity of both wadi and basement deposits over lengths scales as small as ∼100 m. VES results correlate closely with data from two wells in the study area. The change in resistivity at the wadi-to-fractured basement contact is relatively subtle, but the transition from low resistivity fractured basement to high resistivity unfractured basement is well resolved. Inferred wadi thicknesses range from 0 to 14 m; the electrically conductive fractured basement extends from wadi down to 12-32 m depth. VES data indicate the fractured basement aquifer thickens progressively to the south in this area. A production well, sited on the basis of the VES analysis, successfully yielded 70m3/day. The relationship between VLF and VES data is complex, suggesting that the terrain is heterogeneous on the scale of the different effective sampling volumes of the two methods, and/or that fracture azimuth is locally heterogeneous. Overall resistivities in this study are similar to those observed at other locations in Saudi Arabia, suggesting these methods may be widely applicable for siting of groundwater wells in the complex basement of the Arabian Shield.

  14. Characterization and applications of VLF/LF source locations from lightning using the Huntsville Alabama Marx Meter Array

    Science.gov (United States)

    Bitzer, Phillip M.; Christian, Hugh J.; Stewart, Mike; Burchfield, Jeff; Podgorny, Scott; Corredor, David; Hall, John; Kuznetsov, Evgeny; Franklin, Veronica

    2013-04-01

    Arrays that detect and locate the four-dimensional spacetime positions of radiation sources from lightning have largely utilized sensors sensitive to the very high frequency (VHF) regime with ˜ 15 km baselines or very low frequency/low frequency (VLF/LF) regime with ˜ 100 km baselines. This paper details initial results from the newly developed Huntsville Alabama Marx Meter Array (HAMMA), consisting of Marx meters (electric field change meters) sensitive to a frequency band ˜ 1 Hz to 400 kHz. The arrival time of HAMMA waveforms due to radiation sources from lightning are used to determine the spacetime position of these sources. The locations are compared with two well-documented and operational arrays, the National Lightning Detection Network (NLDN) and the North Alabama Lightning Mapping Array (NALMA). The standard deviation of the difference between HAMMA and NLDN locations of return strokes is 305 and 266 m in x and y, respectively, while the standard deviation of the difference between HAMMA and NALMA sources is 237, 226, and 688 m in x, y and z, respectively. We further show that NLDN intracloud locations differ in horizontal distance from the corresponding HAMMA locations by a median value of 479 m. In addition, we use HAMMA source locations to map several lightning flashes in the VLF/LF and show HAMMA sources largely map out the same electrical extent as VHF sources and provide unique insights to the properties of the discharges occurring. Finally, we show that VLF/LF sources can determine the leader polarity in several example flashes but not necessarily whether a flash comes to ground. Copyright 2013 American Geophysical Union. All rights reserved.

  15. Interruption of env gene expression depending on the length of the SV40 early region used for the polyA signal.

    Science.gov (United States)

    Yamakawa, Kei; Takase-Yoden, Sayaka; Watanabe, Rihito

    2005-12-01

    In order to invent a screening system to check in vivo gene function and the efficiency of gene transfer mediated by a retroviral vector system, we established a novel packaging cell, PacNIH/A8, based on the neuropathogenic retrovirus A8-V. To construct the expression vector, pA8(Psi-), which expresses the genes gag, pol and env derived from A8-V, the SV40 early region was used for the polyadenylation signal (polyA signal). When a 0.85 kbp fragment in the SV40 early region was employed for the expression vector (pA8(Psi-)beta), env expression was abolished. This abolition was rescued by shortening the SV40 early region to 0.14 kbp (pA8(Psi-)delta). The NHI3T3 cells transfected with pA8(Psi-)delta showed expressions of both env and gag genes.

  16. VLF/ELF wave activity in the vicinity of the polar cusp: Cluster observations

    Directory of Open Access Journals (Sweden)

    N. Lin

    2006-08-01

    Full Text Available Observations by the Cluster spacecraft of VLF/ELF wave activity show distinct signatures for different regions in the vicinity of high altitude polar cusps, which are identified by using magnetic field and plasma data along spacecraft trajectories. These waves include: (1 Broad band magnetic noise observed in the polar cusp at frequencies from several Hz to ~100 Hz, below the local electron cyclotron frequency, fce. Similar magnetic noise is also observed in the high latitude magnetosheath and the magnetopause boundary layer. (2 Strong broad band electrostatic emissions observed in the cusp, in the magnetosheath, and in the high latitude magnetopause boundary layer, at frequencies extending from several Hz to tens of kHz, with maximum intensities below ~100 Hz. (3 Narrow-band electromagnetic whistler waves at frequencies ~0.2–0.6 fce, frequently observed in the closed boundary layer (CBL adjacent to the polar cusp. These waves are for the first time observed in this region to be accompanied by counter-streaming electron beams of ~100 eV, which suggests that the waves are excited by these electrons through wave-particle interaction. (4 Narrow-band electrostatic waves observed slightly above the local fce in the CBL. (5 Lion roars, observed in the high latitude magnetosheath, often in magnetic troughs of mirror mode oscillations. The above wave signatures can serve as indicators of the regions in the vicinity of the magnetospheric cusp.

  17. Measurement of Noise Figure for a VLF LNA%甚低频低噪声放大器噪声系数测量*

    Institute of Scientific and Technical Information of China (English)

    陈传克; 蒋宇中; 张曙霞

    2015-01-01

    A VLF low‐noise amplifier in a multi combination way can achieve lower noise figure .It has great signifi‐cance for deep water radio receiver .This kind of amplifier's noise voltage is about 3nv/sqrt(Hz) ,can't be measured directly due to the value is far less than the commonly used spectrum analyzer's sensitivity .Allowing for its particularity ,a redesign of the noise coefficient measurement is in demand .In this paper ,the factors affecting the noise coefficient measurement of LNA are discussed in detail ,such as impedance matching ,RF signal generator's background interference etc .Eventually a new means of measuring the noise coefficient ,with thorough scheme and implementation steps is proposed .%使用晶体管多管组合构成甚低频低噪声放大器可以获得较低的噪声系数,在深水无线电接收中有重要应用。这种放大器噪声电压约为3nv/sqrt(Hz),其指标已经远小于常用的频谱分析仪灵敏度指标,难以实现直接测量。正是由于其特殊性,甚低频低噪声放大器噪声系数的测量方案必须重新设计。论文详细讨论了影响低噪声放大器噪声系数测量的各种因素,包括阻抗匹配、射频信号发生器的背景干扰等因素,提出了完整的测量方案及实施步骤。

  18. SPATIALLY EXTENDED 21 cm SIGNAL FROM STRONGLY CLUSTERED UV AND X-RAY SOURCES IN THE EARLY UNIVERSE

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Kyungjin [Department of Earth Sciences, Chosun University, Gwangju, 501-759 (Korea, Republic of); Xu, Hao; Norman, Michael L. [Center for Astrophysics and Space Sciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093 (United States); Alvarez, Marcelo A. [Canadian Institute for Theoretical Astrophysics, 60 St. George St., Toronto, ON M5S 3H8 (Canada); Wise, John H., E-mail: kjahn@chosun.ac.kr [Center for Relativistic Astrophysics, School of Physics, Georgia Institute of Technology, 837 State Street, Atlanta, GA 30332 (United States)

    2015-03-20

    We present our prediction for the local 21 cm differential brightness temperature (δT{sub b}) from a set of strongly clustered sources of Population III (Pop III) and II (Pop II) objects in the early universe, by a numerical simulation of their formation and radiative feedback. These objects are located inside a highly biased environment, which is a rare, high-density peak (“Rarepeak”) extending to ∼7 comoving Mpc. We study the impact of ultraviolet and X-ray photons on the intergalactic medium (IGM) and the resulting δT{sub b}, when Pop III stars are assumed to emit X-ray photons by forming X-ray binaries very efficiently. We parameterize the rest-frame spectral energy distribution of X-ray photons, which regulates X-ray photon-trapping, IGM-heating, secondary Lyα pumping and the resulting morphology of δT{sub b}. A combination of emission (δT{sub b} > 0) and absorption (δT{sub b} < 0) regions appears in varying amplitudes and angular scales. The boost of the signal by the high-density environment (δ ∼ 0.64) and on a relatively large scale combines to make Rarepeak a discernible, spatially extended (θ ∼ 10′) object for 21 cm observation at 13 ≲ z ≲ 17, which is found to be detectable as a single object by SKA with integration time of ∼1000 hr. Power spectrum analysis by some of the SKA precursors (Low Frequency Array, Murchison Widefield Array, Precision Array for Probing the Epoch of Reionization) of such rare peaks is found to be difficult due to the rarity of these peaks, and the contribution only by these rare peaks to the total power spectrum remains subdominant compared to that by all astrophysical sources.

  19. FGF-2 signal promotes proliferation of cerebellar progenitor cells and their oligodendrocytic differentiation at early postnatal stage

    Energy Technology Data Exchange (ETDEWEB)

    Naruse, Masae; Shibasaki, Koji; Ishizaki, Yasuki, E-mail: yasukiishizaki@gunma-u.ac.jp

    2015-08-07

    The origins and developmental regulation of cerebellar oligodendrocytes are largely unknown, although some hypotheses of embryonic origins have been suggested. Neural stem cells exist in the white matter of postnatal cerebellum, but it is unclear whether these neural stem cells generate oligodendrocytes at postnatal stages. We previously showed that cerebellar progenitor cells, including neural stem cells, widely express CD44 at around postnatal day 3. In the present study, we showed that CD44-positive cells prepared from the postnatal day 3 cerebellum gave rise to neurospheres, while CD44-negative cells prepared from the same cerebellum did not. These neurospheres differentiated mainly into oligodendrocytes and astrocytes, suggesting that CD44-positive neural stem/progenitor cells might generate oligodendrocytes in postnatal cerebellum. We cultured CD44-positive cells from the postnatal day 3 cerebellum in the presence of signaling molecules known as mitogens or inductive differentiation factors for oligodendrocyte progenitor cells. Of these, only FGF-2 promoted survival and proliferation of CD44-positive cells, and these cells differentiated into O4+ oligodendrocytes. Furthermore, we examined the effect of FGF-2 on cerebellar oligodendrocyte development ex vivo. FGF-2 enhanced proliferation of oligodendrocyte progenitor cells and increased the number of O4+ and CC1+ oligodendrocytes in slice cultures. These results suggest that CD44-positive cells might be a source of cerebellar oligodendrocytes and that FGF-2 plays important roles in their development at an early postnatal stage. - Highlights: • CD44 is expressed in cerebellar neural stem/progenitor cells at postnatal day 3 (P3). • FGF-2 promoted proliferation of CD44-positive progenitor cells from P3 cerebellum. • FGF-2 promoted oligodendrocytic differentiation of CD44-positive progenitor cells. • FGF-2 increased the number of oligodendrocytes in P3 cerebellar slice culture.

  20. Ionospheric perturbations in possible association with the 2010 Haiti earthquake, as based on medium-distance subionospheric VLF propagation data

    Directory of Open Access Journals (Sweden)

    M. Hayakawa

    2011-02-01

    Full Text Available Ionospheric perturbations in possible association with the 2010 Haiti earthquake occurred on 12 January 2010 (with a magnitude of 7.0 and depth of 10 km are investigated on the basis of subionospheric propagation data from the NAA transmitter on the east coast of the USA to a VLF receiving station in Peru. The local nighttime VLF amplitude data are extensively investigated during the period from the beginning of October 2009 to the end of March 2010, in which the trend (nighttime average amplitude, dispersion and nighttime fluctuation are analysed. It is found that a clear precursory ionosphere perturbation is detected just around New Years day of 2010, about 12 days before the main shock, which is characterised by the simultaneous decrease in the trend and the increases in dispersion and nighttime fluctuation. An additional finding might be the presence of the effect of the Earth's tide one and two months before the main shock, which can only be seen for a huge EQ.

  1. Genetic variants of the Wnt signaling pathway as predictors of recurrence and survival in early-stage non-small cell lung cancer patients.

    Science.gov (United States)

    Coscio, Angela; Chang, David W; Roth, Jack A; Ye, Yuanqing; Gu, Jian; Yang, Ping; Wu, Xifeng

    2014-06-01

    Early-stage non-small cell lung cancer (NSCLC) is potentially curative. Nevertheless, many patients will show disease recurrence after curative treatment. The Wnt signaling pathway is a developmental and stem cell pathway that plays an important role in tumorigenesis and may affect cancer progression. We hypothesize that genetic variants of the Wnt pathway may influence clinical outcome in early-stage NSCLC patients. We genotyped 441 functional and tagging single nucleotide polymorphisms (SNPs) from 54 genes of the Wnt pathway in 535 early-stage NSCLC patients treated with curative intent therapy including surgery and chemotherapy. For validation, 4 top SNPs were genotyped in 301 early-stage NSCLC patients from the Mayo Clinic. Cox proportional hazard model and combined SNP analyses were performed to identify significant SNPs correlated with recurrence-free and overall survival. Results from discovery group showed a total of 40 SNPs in 20 genes correlated with disease recurrence (P recurrence-free and overall survival. Joint SNP analyses identified predictive markers for recurrence stratified by treatment. Our findings suggest inherited genetic variation in the Wnt signaling pathway may contribute to variable clinical outcomes for patients with early-stage NSCLC. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  2. The effect of increased T2 signal intensity in the spinal cord on the injury severity and early neurological recovery in patients with central cord syndrome.

    Science.gov (United States)

    Schroeder, Gregory D; Hjelm, Nik; Vaccaro, Alexander R; Weinstein, Michael S; Kepler, Christopher K

    2016-05-01

    OBJECTIVE The aim of this paper was to compare the severity of the initial neurological injury as well as the early changes in the American Spinal Injury Association (ASIA) motor score (AMS) between central cord syndrome (CCS) patients with and without an increased T2 signal intensity in their spinal cord. METHODS Patients with CCS were identified and stratified based on the presence of increased T2 signal intensity in their spinal cord. The severity of the initial neurological injury and the progression of the neurological injury over the 1st week were measured according to the patient's AMS. The effect of age, sex, congenital stenosis, surgery within 24 hours, and surgery in the initial hospitalization on the change in AMS was determined using an analysis of variance. RESULTS Patients with increased signal intensity had a more severe initial neurological injury (AMS 57.6 vs 75.3, respectively, p = 0.01). However, the change in AMS over the 1st week was less severe in patients with an increase in T2 signal intensity (-0.85 vs -4.3, p = 0.07). Analysis of variance did not find that age, sex, Injury Severity Score, congenital stenosis, surgery within 24 hours, or surgery during the initial hospitalization affected the change in AMS. CONCLUSIONS The neurological injury is different between patients with and without an increased T2 signal intensity. Patients with an increased T2 signal intensity are likely to have a more severe initial neurological deficit but will have relatively minimal early neurological deterioration. Comparatively, patients without an increase in the T2 signal intensity will likely have a less severe initial injury but can expect to have a slight decline in neurological function in the 1st week.

  3. Subcellular distribution and early signalling events of P2X7 receptors from mouse cerebellar granule neurons.

    Science.gov (United States)

    Sánchez-Nogueiro, Jesús; Marín-García, Patricia; Bustillo, Diego; Olivos-Oré, Luis Alcides; Miras-Portugal, María Teresa; Artalejo, Antonio R

    2014-12-05

    The subcellular distribution and early signalling events of P2X7 receptors were studied in mouse cerebellar granule neurons. Whole-cell patch-clamp recordings evidenced inwardly directed non-desensitizing currents following adenosine 5'-triphosphate (ATP; 600 µM) or 2'-3'-o-(4-benzoylbenzoyl)-adenosine 5'-triphosphate (BzATP; 100 µM) administration to cells bathed in a medium with no-added divalent cations (Ca(2+) and Mg(2+)). Nucleotide-activated currents were inhibited by superfusion of 2.5 mM Ca(2+), 1.2 mM Mg(2+) or 100 nM Brilliant Blue G (BBG), hence indicating the expression of ionotropic P2X7 receptors. Fura-2 calcium imaging showed [Ca(2+)]i elevations in response to ATP or BzATP at the somas and at a small number of axodendritic regions of granule neurons. Differential sensitivity of these [Ca(2+)]i increases to three different P2X7 receptor antagonists (100 nM BBG, 10 μM 4-[(2S)-2-[(5-isoquinolinylsulfonyl)methylamino]-3-oxo-3-(4-phenyl-1-piperazinyl)propyl] phenyl isoquinolinesulfonic acid ester, KN-62, and 1 μM 3-(5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl)methyl pyridine hydrochloride hydrate, A-438079) revealed that P2X7 receptors are co-expressed with different P2Y receptors along the plasmalemma of granule neurons. Finally, experiments with the fluorescent dye YO-PRO-1 indicated that prolonged stimulation of P2X7 receptors does not lead to the opening of a membrane pore permeable to large cations. Altogether, our results emphasise the expression of functional P2X7 receptors at both the axodendritic and somatic levels in mouse cerebellar granule neurons, and favour the notion that P2X7 receptors might function in a subcellular localisation-specific manner: presynaptically, by controlling glutamate release, and on the cell somas, by supporting granule neuron survival against glutamate excytotoxicity.

  4. HBV cccDNA in patients′ sera as an indicator for HBV reactivation and an early signal of liver damage

    Institute of Scientific and Technical Information of China (English)

    Ying Chen; Johnny Sze; Ming-Liang He

    2004-01-01

    AIM: To evaluate the covalently closed circle DNA (cccDNA)level of hepatitis B virus (HBV) in patients′ liver and sera.METHODS: HBV DNA was isolated from patients′liver biopsies and sera. A sensitive real-time PCR method, which is capable of differentiation of HBV viral genomic DNA and cccDNA, was used to quantify the total HBV cccDNA. The total HBV viral DNA was quantitated by real-time PCR using a HBV diagnostic kit (PG Biotech, LTD, Shenzhen, China)described previously.RESULTS: For the first time, we measured the level of HBV DNA and cccDNA isolated from ten HBV patients′liver biopsies and sera. In the liver biopsies, cccDNA was detected from all the biopsy samples. The copy number of cccDNA ranged from from 0.03 to 173.1 per cell, the copy number of total HBV DNA ranged from 0.08 to 3 717 per cell. The ratio of total HBV DNA to cccDNA ranged from 1 to 3 406. In the sera,cccDNA was only detected from six samples whereas HBV viral DNA was detected from all ten samples. The ratio of cccDNA to total HBV DNA ranged from 0 to 1.77%. To further investigate the reason why cccDNA could only be detected in some patients′sera, we performed longitudinal studies. The cccDNA was detected from the patients′sera with HBV reactivation but not from the patients′sera without HBV reactivation. The level of cccDNA in the sera was correlated with ALT and viral load in the HBV reactivation patients.CONCLUSION: HBV cccDNA is actively transcribed and replicated in some patients′hepatocytes, which is reflected by a high ratio of HBV total DNA vs cccDNA. Detection of cccDNA in the liver biopsy will provide an end-point for the anti-HBV therapy. The occurrence of cccDNA in the sera is an early signal of liver damage, which may be another important clinical parameter.

  5. The Early Activation of CD8+ T Cells Is Dependent on Type I IFN Signaling following Intramuscular Vaccination of Adenovirus Vector

    Directory of Open Access Journals (Sweden)

    Masahisa Hemmi

    2014-01-01

    Full Text Available Few of the vaccines in current use can induce antigen- (Ag- specific immunity in both mucosal and systemic compartments. Hence, the development of vaccines that realize both mucosal and systemic protection against various pathogens is a high priority in global health. Recently, it has been reported that intramuscular (i.m. vaccination of an adenovirus vector (Adv can induce Ag-specific cytotoxic T lymphocytes (CTLs in both systemic and gut mucosal compartments. We previously revealed that type I IFN signaling is required for the induction of gut mucosal CTLs, not systemic CTLs. However, the molecular mechanism via type I IFN signaling is largely unknown. Here, we report that type I IFN signaling following i.m. Adv vaccination is required for the expression of type I IFN in the inguinal lymph nodes (iLNs, which are the draining lymph nodes of the administration site. We also showed that the type I IFN signaling is indispensable for the early activation of CTLs in iLNs. These data suggested that type I IFN signaling has an important role in the translation of systemic innate immune response into mucosal adaptive immunity by amplifying the innate immune signaling and activating CTLs in the iLN.

  6. Effect of Angiotensin II and Small GTPase Ras Signaling Pathway Inhibition on Early Renal Changes in a Murine Model of Obstructive Nephropathy

    Directory of Open Access Journals (Sweden)

    Ana B. Rodríguez-Peña

    2014-01-01

    Full Text Available Tubulointerstitial fibrosis is a major feature of chronic kidney disease. Unilateral ureteral obstruction (UUO in rodents leads to the development of renal tubulointerstitial fibrosis consistent with histopathological changes observed in advanced chronic kidney disease in humans. The purpose of this study was to assess the effect of inhibiting angiotensin II receptors or Ras activation on early renal fibrotic changes induced by UUO. Animals either received angiotensin II or underwent UUO. UUO animals received either losartan, atorvastatin, and farnesyl transferase inhibitor (FTI L-744,832, or chaetomellic acid A (ChA. Levels of activated Ras, phospho-ERK1/2, phospho-Akt, fibronectin, and α-smooth muscle actin were subsequently quantified in renal tissue by ELISA, Western blot, and/or immunohistochemistry. Our results demonstrate that administration of angiotensin II induces activation of the small GTPase Ras/Erk/Akt signaling system, suggesting an involvement of angiotensin II in the early obstruction-induced activation of renal Ras. Furthermore, upstream inhibition of Ras signalling by blocking either angiotensin AT1 type receptor or by inhibiting Ras prenylation (atorvastatin, FTI o ChA reduced the activation of the Ras/Erk/Akt signaling system and decreased the early fibrotic response in the obstructed kidney. This study points out that pharmacological inhibition of Ras activation may hold promise as a future strategy in the prevention of renal fibrosis.

  7. Extra and intracellular calcium signaling pathway(s) differentially regulate histamine-induced myometrial contractions during early and mid-pregnancy stages in buffaloes (Bubalus bubalis).

    Science.gov (United States)

    Sharma, Abhishek; Nakade, Udayraj P; Choudhury, Soumen; Yadav, Rajkumar Singh; Garg, Satish Kumar

    2017-04-01

    This study examines the differential role of calcium signaling pathway(s) in histamine-induced uterotonic action during early and mid-pregnancy stages in buffaloes. Compared to mid pregnancy, tonic contraction, amplitude and mean-integral tension were significantly increased by histamine to produce myometrial contraction during early pregnancy with small effects on phasic contraction and frequency. Although uterotonic action of histamine during both stages of pregnancy is sensitive to nifedipine (a L-type Ca(2+) channels blocker) and NNC55-0396 (T-type Ca(2+) channels blocker), the role of extracellular calcium seems to be more significant during mid-pregnancy as in this stage histamine produced only 9.38±0.96% contraction in Ca(2+) free-RLS compared to 21.60±1.45% in uteri of early pregnancy stage. Intracellular calcium plays major role in histamine-induced myometrial contraction during early pregnancy as compared to mid pregnancy, as in the presence of cyclopiazonic acid (CPA) Ca(2+)-free RLS, histamine produced significantly higher contraction in myometrial strips of early-pregancy in comparison to mid-pregnancy (10.59±1.58% and 3.13±0.46%, respectively). In the presence of U-73122, the DRC of histamine was significantly shifted towards right with decrease in maximal effect (Emax) only in early pregnancy suggesting the predominant role of phospholipase-C (PL-C) in this stage of pregnancy.

  8. TE/TM (Transverse Magnetic/Transverse Electric) Height Profile Measurements of Transpolar VLF (Very Low Frequency) Signals,

    Science.gov (United States)

    1987-10-01

    GQD U.K. 096 3740 [NA]’ 19.6 GBZ Criggion, U.K. 096 3740 10, 20.25 IDO Rome, Italy 086 5260 [NA] 21.4 NSS Annapolis, Md. 190 4180 266 23.4 NPM Haiku ...night no yes yes 23.4 Haiku , Hawaii night no yes yes 24.8 Jim Creek, Wash. night no yes yes 26.1 TACAMO night no no yes 50 TE 40 TM -- 30- M 20- 10

  9. The physical principles of the combined ELF/VLF method for single-station global location of lightning

    Science.gov (United States)

    Mushtak, V.; Price, C.; Williams, E.

    Single -station electromagnetic methods for global lightning location are based on specific features of ELF wave propagation. First, ELF waves propagate with an extremely low attenuation not exceeding 1.5 dB/Mm up to 100 Hz. For this reason, the propagation has a resonant character (the Schumann resonance phenomena) imparting a unique pattern to the spectrum of a lightning waveform depending on the parent lightning's location relative to the given observer. The wave impedance technique realized by Kemp and Jones (1971) and widely adopted afterwards eliminates any need for the frequency dependence of the spectral density of the source's current moment for the location purpose. At the same time, an adequate single-mode propagation model can be applied for recovering this dependence and providing additional information about the source. As the only shortcoming of ELF location procedure, considerable error in estimates of the arrival directions of lightning waveforms was revealed by means of the satellite (OTD) identification of parent lightning events. These azimuthal deviations result in global location accuracies of 1-2 Mm (Boccippio et al, 1998) hardly acceptable in many geophysical problems. Price et al. (2002) found similar azimuthal errors in the ELF technique by means of the ground-truth (NLDN) identification of sprite-producing thunderstorms in Colorado when observing atmospherics in the Negev Desert, Israel. The location accuracy had been essentially improved - to better than 0.2 Mm on this 11 Mm path - by combining ELF distance estimates with VLF direction finding. Theoretical considerations show that this improvement is to be explained by a distinction between the ELF and VLF refraction effects at the day-night boundary of the Earth- ionosphere waveguide. While the difference between the day-time and night-time values of the phase velocity in the ELF range reaches 15%, it does not exceed 1% in the VLF range, with a corresponding diminishment of azimuthal

  10. Shh信号通路在牙早期发育中的研究进展%Advances about Shh signaling pathway during early tooth development

    Institute of Scientific and Technical Information of China (English)

    赵武奎; 林恒; 黄心怡; 李汉梁; 林程琳; 王冰梅

    2012-01-01

    Sonic hedgehog (Shh)信号通路在牙早期发育中起关键作用,Shh通过与其特定的受体Ptc/Smo蛋白复合物相互作用来激活整个信号通路.Shh在牙早期发育过程中的表达具有时间和空间特异性,通过自分泌和旁分泌作用于上皮组织以及周围的间充质,促进细胞增殖、分化,调控牙的形态发生.Shh基因缺失将导致小鼠在帽状期牙形态的严重畸形,牙体变小,牙索缺失.对Shh信号通路在牙早期发育的作用及其与Wnt信号通路、BMP家族、FGF家族和MSX家族之间的相互关系进行综述.%Sonic hedgehog (Shh) signaling pathway plays a critical role during the early tooth development. Shh activates the whole signaling pathway via interacting with its specific receptor, Ptc/Smo protein complex. During the early tooth development process, Shh expresses in a temporal and spatial specific manner, affects the epithelial and mesenchymal dental tissues through autocrine and paracrine, promotes cell proliferation and differentiation, and then regulates the tooth morphogenesis. Shh gene deletion will result in severely abnormal tooth morphology, reduce tooth size and dental cord absence during the cap stage in mouse. This present review mainly discussed the role of Shh signaling pathway in early tooth development and its interrelationship with Wnt signaling, and BMP, FGF and MSX families.

  11. Early interference with p44/42 mitogen-activated protein kinase signaling in hypothalamic paraventricular nucleus attenuates angiotensin II-induced hypertension.

    Science.gov (United States)

    Yu, Yang; Xue, Bao-Jian; Zhang, Zhi-Hua; Wei, Shun-Guang; Beltz, Terry G; Guo, Fang; Johnson, Alan Kim; Felder, Robert B

    2013-04-01

    Blood-borne angiotensin II (ANG II) can upregulate p44/42 mitogen-activated protein kinase (MAPK) signaling and ANG II type-1 receptors in the hypothalamic paraventricular nucleus (PVN), a critical cardiovascular and autonomic center. We tested the hypothesis that brain p44/42 MAPK signaling contributes to the development of ANG II-induced hypertension. The ANG II infusion (120 ng/kg per min, subcutaneously) induced increases in phosphorylated p44/42 MAPK and ANG II type-1 receptors in the PVN after 1 week, before the onset of hypertension, that were sustained as hypertension developed during a 2- or 3-week infusion protocol. Bilateral PVN microinjections of small interfering RNAs for p44/42 MAPK, at the onset of the ANG II infusion or 1 week later, prevented the early increase in p44/42 MAPK activity. The early treatment normalized ANG II type-1 receptor expression in the PVN and attenuated the hypertensive response to the 2-week infusion of ANG II. The later small interfering RNA microinjections had a transient effect on ANG II type-1 receptor expression in PVN and no effect on the hypertensive response to the 3-week infusion of ANG II. The early treatment also normalized the pressure response to ganglionic blockade. The ANG II infusion induced increases in mRNA for proinflammatory cytokines that were not affected by either small interfering RNA treatment. These results suggest that the full expression of ANG II-induced hypertension depends on p44/42 MAPK-mediated effects. A potential role for p44/42 MAPK in modulating the ANG II-induced central inflammatory response might also be considered. MAPK signaling in PVN may be a novel target for early intervention in the progression of ANG II-dependent hypertension.

  12. Paradoxical Neurobehavioral Rescue by Memories of Early-Life Abuse: The Safety Signal Value of Odors Learned during Abusive Attachment

    OpenAIRE

    Raineki, Charlis; Sarro, Emma; Rincón-Cortés, Millie; Perry, Rosemarie; Boggs, Joy; Holman, Colin J; Wilson, Donald A.; Sullivan, Regina M.

    2014-01-01

    Caregiver-associated cues, including those learned in abusive attachment, provide a sense of safety and security to the child. Here, we explore how cues associated with abusive attachment, such as maternal odor, can modify the enduring neurobehavioral effects of early-life abuse. Two early-life abuse models were used: a naturalistic paradigm, where rat pups were reared by an abusive mother; and a more controlled paradigm, where pups underwent peppermint odor-shock conditioning that produces a...

  13. Implementation of Wavelet-Based Neural Network for the detection of Very Low Frequency (VLF) Whistlers Transients

    Science.gov (United States)

    Sondhiya, Deepak Kumar; Gwal, Ashok Kumar; Verma, Shivali; Kasde, Satish Kumar

    Abstract: In this paper, a wavelet-based neural network system for the detection and identification of four types of VLF whistler’s transients (i.e. dispersive, diffuse, spiky and multipath) is implemented and tested. The discrete wavelet transform (DWT) technique is integrated with the feed forward neural network (FFNN) model to construct the identifier. First, the multi-resolution analysis (MRA) technique of DWT and the Parseval’s theorem are employed to extract the characteristics features of the transients at different resolution levels. Second, the FFNN identifies these extracted features to identify the transients according to the features extracted. The proposed methodology can reduce a great quantity of the features of transients without losing its original property; less memory space and computing time are required. Various transient events are tested; the results show that the identifier can detect whistler transients efficiently. Keywords: Discrete wavelets transform, Multi-resolution analysis, Parseval’s theorem and Feed forward neural network

  14. Evolution of magnetotelluric, total magnetic field, and VLF field parameters in Central Italy. Relations to local seismic activity

    Energy Technology Data Exchange (ETDEWEB)

    Meloni, A.; Di Mauro, D.; Mele, G.; Palangio, P. [Istituto Nazionale di Geofisica e Vulcanologia, Rome (Italy); Ernst, T.; Teisseyre, R. [Institute of Geophysics, Warszawa (Poland)

    2001-04-01

    Magnetotelluric data were collected at Collemeluccio (41.72{sup 0}N, 14.37{sup 0}E) in Central Italy from summer 1991 to spring 1998. Analyzed by means of tensor decomposition on the geoelectric potential and robust estimation on the geomagnetic field, this set of data allowed the investigation of the electromagnetic induction, is presented here in its time evolution and compared to local and regional seismic activity. Tecto magnetic field observations from absolute magnetic field level in Central Italy were also made on data simultaneously recorded at four magnetometer stations, using L'Aquila Geomagnetic Observatory as a reference for differentiation. Recent results gathered from a system of two VLF search coil wide-band antennas, installed in the L'Aquila Observatory, are also discussed in relation to local seismic activity.

  15. Survey of ELF-VLF plasma waves in outer radiation belt observed by Cluster STAFF-SA experiment

    Directory of Open Access Journals (Sweden)

    D. Pokhotelov

    2008-10-01

    Full Text Available Various types of plasma waves have profound effects on acceleration and scattering of radiation belt particles. For the purposes of radiation belt modeling it is necessary to know statistical distributions of plasma wave parameters. This paper analyzes four years of plasma wave observations in the Earth's outer radiation belt obtained by the STAFF-SA experiment on board Cluster spacecraft. Statistical distributions of spectral density of different plasma waves observed in ELF-VLF range (chorus, plasmaspheric hiss, magnetosonic waves are presented as a function of magnetospheric coordinates and geomagnetic activity indices. Comparison with other spacecraft studies supports some earlier conclusions about the distribution of chorus and hiss waves and helps to remove the long-term controversy regarding the distribution of equatorial magnetosonic waves. This study represents a step towards the development of multi-spacecraft database of plasma wave activity in radiation belts.

  16. Hydrogeologic Prospection With Vlf (very Low Frequency) In A Low Potential Hard Rock Aquifer Near Beja (south Portugal)

    Science.gov (United States)

    Duque, J.

    The use of geophysics prospection in hydrogeology is widely used as a way to find groundwater under difficult hydrogeologic potential rocks. The porphyric rocks lay- ered in the northern part of Beja city, are the most unproductive regional aquifer. Usu- ally this aquifer has an upper layer of 5 to 15 meters deep of weathered rock and a second layer build by fractures rock till 30 metres deep. Above this deep the probabil- ity to find groundwater is extremely low. For instance it is a very superficial aquifer that usually accomplish the topographic surface. The water use is essential for human purposes and here are used mainly for human and cattle supply. In order verify the goodness of a geophysic method and at the same time to supply a large farm called Herdade da Apariça, it was performed the geophysical method of Very Low Frequency (VLF-EM) with ABEM (WADI) equipment, in three areas previously defined by inter- pretation of aerial photography, as zones that have relative hydrogeological potential. It was performed a total of 5 profiles with 1970 m. The geophysic prospecting and hydrogeologic research allowed to drill 5 boreholes, being 4 extraction wells and 1 piezometric well. The productivity of the abstraction wells are between 2,000 L/h and 10,000 L/h, which is a very good yield when compared with the other yield values get from wells inside this aquifer. VLF proved in this conditions to be an essential tool to increment the tax success of drilling wells.

  17. Paradoxical neurobehavioral rescue by memories of early-life abuse: the safety signal value of odors learned during abusive attachment.

    Science.gov (United States)

    Raineki, Charlis; Sarro, Emma; Rincón-Cortés, Millie; Perry, Rosemarie; Boggs, Joy; Holman, Colin J; Wilson, Donald A; Sullivan, Regina M

    2015-03-01

    Caregiver-associated cues, including those learned in abusive attachment, provide a sense of safety and security to the child. Here, we explore how cues associated with abusive attachment, such as maternal odor, can modify the enduring neurobehavioral effects of early-life abuse. Two early-life abuse models were used: a naturalistic paradigm, where rat pups were reared by an abusive mother; and a more controlled paradigm, where pups underwent peppermint odor-shock conditioning that produces an artificial maternal odor through engagement of the attachment circuit. Animals were tested for maternal odor preference in infancy, forced swim test (FST), social behavior, and sexual motivation in adulthood-in the presence or absence of maternal odors (natural or peppermint). Amygdala odor-evoked local field potentials (LFPs) via wireless electrodes were also examined in response to the maternal odors in adulthood. Both early-life abuse models induced preference for the maternal odors in infancy. In adulthood, these early-life abuse models produced FST deficits and decreased social behavior, but did not change sexual motivation. Presentation of the maternal odors rescued FST and social behavior deficits induced by early-life abuse and enhanced sexual motivation in all animals. In addition, amygdala LFPs from both abuse animal models showed unique activation within the gamma frequency (70-90 Hz) bands in response to the specific maternal odor present during early-life abuse. These results suggest that attachment-related cues learned during infancy have a profound ability to rescue neurobehavioral dysregulation caused by early-life abuse. Paradoxically, abuse-associated cues seem to acquire powerful and enduring antidepressive properties and alter amygdala modulation.

  18. Arabidopsis WRKY6 Transcription Factor Acts as a Positive Regulator of Abscisic Acid Signaling during Seed Germination and Early Seedling Development.

    Science.gov (United States)

    Huang, Yun; Feng, Cui-Zhu; Ye, Qing; Wu, Wei-Hua; Chen, Yi-Fang

    2016-02-01

    The phytohormone abscisic acid (ABA) plays important roles during seed germination and early seedling development. Here, we characterized the function of the Arabidopsis WRKY6 transcription factor in ABA signaling. The transcript of WRKY6 was repressed during seed germination and early seedling development, and induced by exogenous ABA. The wrky6-1 and wrky6-2 mutants were ABA insensitive, whereas WRKY6-overexpressing lines showed ABA-hypersensitive phenotypes during seed germination and early seedling development. The expression of RAV1 was suppressed in the WRKY6-overexpressing lines and elevated in the wrky6 mutants, and the expression of ABI3, ABI4, and ABI5, which was directly down-regulated by RAV1, was enhanced in the WRKY6-overexpressing lines and repressed in the wrky6 mutants. Electrophoretic mobility shift and chromatin immunoprecipitation assays showed that WRKY6 could bind to the RAV1 promoter in vitro and in vivo. Overexpression of RAV1 in WRKY6-overexpressing lines abolished their ABA-hypersensitive phenotypes, and the rav1 wrky6-2 double mutant showed an ABA-hypersensitive phenotype, similar to rav1 mutant. Together, the results demonstrated that the Arabidopsis WRKY6 transcription factor played important roles in ABA signaling by directly down-regulating RAV1 expression.

  19. VLF Remote -Sensing of the Lower Ionosphere with AWESOME Receivers: Solar Flares, Lightning-induced Electron Precipitation, Sudden Ionospheric Disturbances, Sprites, Gravity Waves and Gamma-ray Flares

    Science.gov (United States)

    Inan, U. S.; Cohen, M.; Scherrer, P.; Scherrer, D.

    2006-11-01

    Stanford University Very Low Frequency (VLF) radio receivers have been used extensively for remote sensing of the ionosphere and the magnetosphere. Among the phenomena that can be uniquely measured via VLF receivers are radio atmospherics, whistlers, electron precipitation, solar flares, sudden ionospheric disturbances, gravity waves, sprites, and cosmic gamma-ray flares. With the use of simple square air-core magnetic loop antennas of a couple of meters in size, the sensitivity of these instruments allows the measurement of magnetic fields as low as several tens of femtoTesla per root Hz, in the frequency range of ~300 Hz to 50 kHz. This sensitivity well exceeds that required to detect any event above the ambient atmospheric noise floor, determined by the totality of lightning activity on this planet. In recent years, as cost of production, timing accuracy (due to low cost GPS cards), and data handling flexibility of the systems has improved, it has become possible to distribute many of these instruments in the form of arrays, to perform interferometric and holographic imaging of the lower ionosphere. These goals can be achieved using the newest version of the Stanford VLF receiver, known as AWESOME: Atmospheric Weather Educational System for Observation and Modeling of Electromagnetics. In the context of the IHY/UNBSS program for 2007, the AWESOME receivers can be used extensively as part of the United Nations initiative to place scientific instruments in developing countries. Drawing on the Stanford experiences from setting up arrays of VLF receivers, including an interferometer in Alaska, the Holographic Array for Ionospheric and Lightning research (HAIL) consisting of instruments at 13 different high schools in mid-western United States, a broader set of ELF/VLF receivers in Alaska, and various receivers abroad, including in France, Japan, Greece, Turkey, and India, a global network of ELF/VLF receivers offer possibilities for a wide range of scientific topics

  20. Formation of proximal and anterior limb skeleton requires early function of Irx3 and Irx5 and is negatively regulated by Shh signaling.

    Science.gov (United States)

    Li, Danyi; Sakuma, Rui; Vakili, Niki A; Mo, Rong; Puviindran, Vijitha; Deimling, Steven; Zhang, Xiaoyun; Hopyan, Sevan; Hui, Chi-chung

    2014-04-28

    Limb skeletal pattern relies heavily on graded Sonic hedgehog (Shh) signaling. As a morphogen and growth cue, Shh regulates identities of posterior limb elements, including the ulna/fibula and digits 2 through 5. In contrast, proximal and anterior structures, including the humerus/femur, radius/tibia, and digit 1, are regarded as Shh independent, and mechanisms governing their specification are unclear. Here, we show that patterning of the proximal and anterior limb skeleton involves two phases. Irx3 and Irx5 (Irx3/5) are essential in the initiating limb bud to specify progenitors of the femur, tibia, and digit 1. However, these skeletal elements can be restored in Irx3/5 null mice when Shh signaling is diminished, indicating that Shh negatively regulates their formation after initiation. Our data provide genetic evidence supporting the concept of early specification and progressive determination of anterior limb pattern.

  1. [Effect of supplementing Qi-nourishing Yin-dispersing blood stasis-dredging collateral herbs on p38 MAPK signaling pathway in kidney of early diabetic rats].

    Science.gov (United States)

    Zhao, Wenhong; Chen, Zhiqiang; Zhang, Jianghua; Sun, Yufeng; Wang, Yuehua; Wang, Huiqing

    2010-03-01

    To study the effect of supplementing Qi-nourishing Yin and dispersing blood stasis-dredging collateral herbs on p38 mitogen activated protein kinase (p38 MAPK) signaling pathway in the kidney of early diabetic rats. Dividing SD rats randomly into 6 groups: Simple nephrectomy group, model group, irbesatan group, traditional Chinese medicine (TCM) low dose group, TCM middle dose group and TCM high dose group. Each group of rats was fed with the corresponding dose of medicine. After 6 weeks, detecting 24 h urine protein (UPro) level, renal function, p38 MAPK mRNA and p-p38 MAPK protein level. UPro levels of irbesatan group, TCM low group and TCM middle dose group decreased significantly (P herbs could treat DN rats effectively by inhibiting the expression of p38 MAPK signaling pathway.

  2. The Role of Paracrine and Autocrine Signaling in the Early Phase of Adipogenic Differentiation of Adipose-derived Stem Cells

    DEFF Research Database (Denmark)

    Hemmingsen, Mette; Vedel, Søren; Skafte-Pedersen, Peder;

    2013-01-01

    Using different cell densities and microfluidic perfusion cell cultures to suppress the effects of cell-released factors, we have demonstrated the significant role played by auto- or paracrine signaling in adipocyte differentiation. The cell-released factor(s) were shown to act in the recruitment...

  3. Excessive Leucine-mTORC1-Signalling of Cow Milk-Based Infant Formula: The Missing Link to Understand Early Childhood Obesity

    Directory of Open Access Journals (Sweden)

    Bodo C. Melnik

    2012-01-01

    Full Text Available Increased protein supply by feeding cow-milk-based infant formula in comparison to lower protein content of human milk is a well-recognized major risk factor of childhood obesity. However, there is yet no conclusive biochemical concept explaining the mechanisms of formula-induced childhood obesity. It is the intention of this article to provide the biochemical link between leucine-mediated signalling of mammalian milk proteins and adipogenesis as well as early adipogenic programming. Leucine has been identified as the predominant signal transducer of mammalian milk, which stimulates the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1. Leucine thus functions as a maternal-neonatal relay for mTORC1-dependent neonatal β-cell proliferation and insulin secretion. The mTORC1 target S6K1 plays a pivotal role in stimulation of mesenchymal stem cells to differentiate into adipocytes and to induce insulin resistance. It is of most critical concern that infant formulas provide higher amounts of leucine in comparison to human milk. Exaggerated leucine-mediated mTORC1-S6K1 signalling induced by infant formulas may thus explain increased adipogenesis and generation of lifelong elevated adipocyte numbers. Attenuation of mTORC1 signalling of infant formula by leucine restriction to physiologic lower levels of human milk offers a great chance for the prevention of childhood obesity and obesity-related metabolic diseases.

  4. A novel transcription factor, ERD15 (Early Responsive to Dehydration 15), connects endoplasmic reticulum stress with an osmotic stress-induced cell death signal.

    Science.gov (United States)

    Alves, Murilo S; Reis, Pedro A B; Dadalto, Silvana P; Faria, Jerusa A Q A; Fontes, Elizabeth P B; Fietto, Luciano G

    2011-06-03

    As in all other eukaryotic organisms, endoplasmic reticulum (ER) stress triggers the evolutionarily conserved unfolded protein response in soybean, but it also communicates with other adaptive signaling responses, such as osmotic stress-induced and ER stress-induced programmed cell death. These two signaling pathways converge at the level of gene transcription to activate an integrated cascade that is mediated by N-rich proteins (NRPs). Here, we describe a novel transcription factor, GmERD15 (Glycine max Early Responsive to Dehydration 15), which is induced by ER stress and osmotic stress to activate the expression of NRP genes. GmERD15 was isolated because of its capacity to stably associate with the NRP-B promoter in yeast. It specifically binds to a 187-bp fragment of the NRP-B promoter in vitro and activates the transcription of a reporter gene in yeast. Furthermore, GmERD15 was found in both the cytoplasm and the nucleus, and a ChIP assay revealed that it binds to the NRP-B promoter in vivo. Expression of GmERD15 in soybean protoplasts activated the NRP-B promoter and induced expression of the NRP-B gene. Collectively, these results support the interpretation that GmERD15 functions as an upstream component of stress-induced NRP-B-mediated signaling to connect stress in the ER to an osmotic stress-induced cell death signal.

  5. The immune receptor NOD1 and kinase RIP2 interact with bacterial peptidoglycan on early endosomes to promote autophagy and inflammatory signaling.

    Science.gov (United States)

    Irving, Aaron T; Mimuro, Hitomi; Kufer, Thomas A; Lo, Camden; Wheeler, Richard; Turner, Lorinda J; Thomas, Belinda J; Malosse, Christian; Gantier, Michael P; Casillas, Linda N; Votta, Bartholomew J; Bertin, John; Boneca, Ivo G; Sasakawa, Chihiro; Philpott, Dana J; Ferrero, Richard L; Kaparakis-Liaskos, Maria

    2014-05-14

    The intracellular innate immune receptor NOD1 detects Gram-negative bacterial peptidoglycan (PG) to induce autophagy and inflammatory responses in host cells. To date, the intracellular compartment in which PG is detected by NOD1 and whether NOD1 directly interacts with PG are two questions that remain to be resolved. To address this, we used outer membrane vesicles (OMVs) from pathogenic bacteria as a physiological mechanism to deliver PG into the host cell cytosol. We report that OMVs induced autophagosome formation and inflammatory IL-8 responses in epithelial cells in a NOD1- and RIP2-dependent manner. PG contained within OMVs colocalized with both NOD1 and RIP2 in EEA1-positive early endosomes. Further, we provide evidence for direct interactions between NOD1 and PG. Collectively, these findings demonstrate that NOD1 detects PG within early endosomes, thereby promoting RIP2-dependent autophagy and inflammatory signaling in response to bacterial infection.

  6. Early postnatal amylin treatment enhances hypothalamic leptin signaling and neural development in the selectively bred diet-induced obese rat.

    Science.gov (United States)

    Johnson, Miranda D; Bouret, Sebastien G; Dunn-Meynell, Ambrose A; Boyle, Christina N; Lutz, Thomas A; Levin, Barry E

    2016-12-01

    Selectively bred diet-induced obese (DIO) rats become obese on a high-fat diet and are leptin resistant before becoming obese. Compared with diet-resistant (DR) neonates, DIO neonates have impaired leptin-dependent arcuate (ARC) neuropeptide Y/agouti-related peptide (NPY/AgRP) and α-melanocyte-stimulating hormone (α-MSH; from proopiomelanocortin (POMC) neurons) axon outgrowth to the paraventricular nucleus (PVN). Using phosphorylation of STAT3 (pSTAT3) as a surrogate, we show that reduced DIO ARC leptin signaling develops by postnatal day 7 (P7) and is reduced within POMC but not NPY/AgRP neurons. Since amylin increases leptin signaling in adult rats, we treated DIO neonates with amylin during postnatal hypothalamic development and assessed leptin signaling, leptin-dependent ARC-PVN pathway development, and metabolic changes. DIO neonates treated with amylin from P0-6 and from P0-16 increased ARC leptin signaling and both AgRP and α-MSH ARC-PVN pathway development, but increased only POMC neuron number. Despite ARC-PVN pathway correction, P0-16 amylin-induced reductions in body weight did not persist beyond treatment cessation. Since amylin enhances adult DIO ARC signaling via an IL-6-dependent mechanism, we assessed ARC-PVN pathway competency in IL-6 knockout mice and found that the AgRP, but not the α-MSH, ARC-PVN pathway was reduced. These results suggest that both leptin and amylin are important neurotrophic factors for the postnatal development of the ARC-PVN pathway. Amylin might act as a direct neurotrophic factor in DIO rats to enhance both the number of POMC neurons and their α-MSH ARC-PVN pathway development. This suggests important and selective roles for amylin during ARC hypothalamic development.

  7. Workshop "Emerging risks and early warning systems" : deelproject 1.2 : miniconferentie over roegtijdig signalering en waarschuwingssystemen

    NARCIS (Netherlands)

    Koenderink, N.J.J.P.; Kreft, F.

    2007-01-01

    This report is the result of the workshop “Emerging risks and early warning system” held in Wageningen, the Netherlands on October the 19th 2006. The workshop is part of the project “Emerging risks in Dutch food chains”. The purpose of this project is to develop a procedure to identify potential ris

  8. Workshop "Emerging risks and early warning systems" : deelproject 1.2 : miniconferentie over roegtijdig signalering en waarschuwingssystemen

    NARCIS (Netherlands)

    Koenderink, N.J.J.P.; Kreft, F.

    2007-01-01

    This report is the result of the workshop “Emerging risks and early warning system” held in Wageningen, the Netherlands on October the 19th 2006. The workshop is part of the project “Emerging risks in Dutch food chains”. The purpose of this project is to develop a procedure to identify potential

  9. Maternal warmth buffers the effects of low early-life socioeconomic status on pro-inflammatory signaling in adulthood.

    Science.gov (United States)

    Chen, E; Miller, G E; Kobor, M S; Cole, S W

    2011-07-01

    The notion that family support may buffer individuals under adversity from poor outcomes has been theorized to have important implications for mental and physical health, but little is known about the biological mechanisms that explain these links. We hypothesized that adults who grew up in low socioeconomic status (SES) households but who experienced high levels of maternal warmth would be protected from the pro-inflammatory states typically associated with low SES. A total of 53 healthy adults (aged 25-40 years) low in SES early in life were assessed on markers of immune activation and systemic inflammation. Genome-wide transcriptional profiling also was conducted. Low early-life SES individuals who had mothers, who expressed high warmth toward them, exhibited less Toll-like receptor-stimulated production of interleukin 6, and reduced bioinformatic indications of pro-inflammatory transcription factor activity (NF-κB) and immune activating transcription factor activity (AP-1) compared to those who were low in SES early in life but experienced low maternal warmth. To the extent that such effects are causal, they suggest the possibility that the detrimental immunologic effects of low early-life SES environments may be partly diminished through supportive family climates.

  10. Further study on the role of atmospheric gravity waves on the seismo-ionospheric perturbations as detected by subionospheric VLF/LF propagation

    Directory of Open Access Journals (Sweden)

    F. Muto

    2009-07-01

    Full Text Available As the target earthquake we have taken a huge earthquake (EQ named Miyagi-oki earthquake on 16 August 2005 (with magnitude of 7.2 and we have analyzed the 4 month period including the date of this EQ. In addition to our previous analysis on the nighttime average amplitude (trend and nighttime fluctuation, we have proposed the use of fluctuation power spectra in the frequency rage of atmospheric gravity waves (period=10 min to 100 min as a third parameter of subionospheric VLF/LF propagation characteristics. Then it is found that this third parameter would be of additional importance in confirming the presence of seismo-ionospheric perturbations. Finally, we have discovered an important role of lunar tidal effect in the VLF/LF data, which appears one and two months before this large EQ.

  11. The role of the sonic hedgehog signaling pathway in early brain injury after experimental subarachnoid hemorrhage in rats.

    Science.gov (United States)

    Li, Tao; Zhang, Jie; Liu, Rong-Yao; Lian, Zhi-Gang; Chen, Xiao-Lin; Ma, Li; Sun, Hao-Min; Zhao, Yuan-Li

    2013-09-27

    Previous studies have demonstrated that the sonic hedgehog (Shh) pathway plays a neuro-protective role. However, whether the Shh pathway is induced by subarachnoid hemorrhage (SAH) has not been investigated. We sought to investigate Shh activation in the cortex in the early stage of SAH, and assessed the effect of cyclopamine (a specific inhibitor of the Shh pathway) on Shh pathway regulation and evaluated the impact of cyclopamine on SAH. We found that the Shh pathway was up-regulated in the cortex after SAH, and that blocking the Shh pathway increased cell apoptosis. Early brain damages, including brain edema, blood-brain barrier impairment, and cortical apoptosis were significantly aggravated following with cyclopamine treatment compared with vehicle treatment. Our results suggest that the Shh pathway should be activated in the brain after SAH, and plays a beneficial role in SAH development, possibly by inhibiting cerebral oxidative stress through induction of antioxidant and detoxifying enzymes.

  12. Horizontal Ionospheric Electron Density Gradients Observed by FORMOSAT-3/COSMIC TIP: Spatial Distributions and Effects on VLF Wave Propagation at Mid-Latitudes

    Directory of Open Access Journals (Sweden)

    Damien H. Chua

    2009-01-01

    Full Text Available We investigate the spatial variability of electron densities in the nightside ionosphere and its effects on very-low frequency (VLF wave propagation using a suite of instruments from the FORMOSAT-3/Constellation Observing System for Meteorology Ionosphere and Climate (COSMIC spacecraft.We use observations from the Tiny Ionospheric Photometer (TIP instruments to infer the horizontal electron density gradients along each satellite track. We demonstrate that the OI 1356 _ radiance measured by the TIP instruments tracks the horizontal electron density structure well with high spatial resolution and unprecedented sensitivity. Accurate measurements of the horizontal electron density gradients are important for improving retrieved electron density profiles from GPS occultation and other tomographic remote sensing techniques. The processes underlying the variability in the large-scale, nightside electron density gradients are the main drivers of ionospheric weather. TIP observations reveal significant variability in both the small and large scale structure of the nightside ionosphere. The relative intensities, relative widths, and latitudinal separation of the northern and southern ionization crests of the Appleton anomalies show a high degree of longitudinal variation.We demonstrate how the TIP observations can be used to measure the horizontal gradient of the refractive index of whistler-mode VLF waves propagating in a cold, collisionless plasma. These measurements are critical for understanding how gradients in electron density associated with ionospheric structure such as depletions and the Appleton anomalies affect VLF wave propagation through the equatorial and mid-latitude ionosphere.

  13. Transient RUNX1 Expression during Early Mesendodermal Differentiation of hESCs Promotes Epithelial to Mesenchymal Transition through TGFB2 Signaling

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    Jennifer J. VanOudenhove

    2016-11-01

    Full Text Available The transition of human embryonic stem cells (hESCs from pluripotency to lineage commitment is not fully understood, and a role for phenotypic transcription factors in the initial stages of hESC differentiation remains to be explored. From a screen of candidate factors, we found that RUNX1 is selectively and transiently upregulated early in hESC differentiation to mesendodermal lineages. Transcriptome profiling and functional analyses upon RUNX1 depletion established a role for RUNX1 in promoting cell motility. In parallel, we discovered a loss of repression for several epithelial genes, indicating that loss of RUNX1 impaired an epithelial to mesenchymal transition during differentiation. Cell biological and biochemical approaches revealed that RUNX1 depletion specifically compromised TGFB2 signaling. Both the decrease in motility and deregulated epithelial marker expression upon RUNX1 depletion were rescued by reintroduction of TGFB2, but not TGFB1. These findings identify roles for RUNX1-TGFB2 signaling in early events of mesendodermal lineage commitment.

  14. An early role for WNT signaling in specifying neural patterns of Cdx and Hox gene expression and motor neuron subtype identity.

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    Ulrika Nordström

    2006-07-01

    Full Text Available The link between extrinsic signaling, progenitor cell specification and neuronal subtype identity is central to the developmental organization of the vertebrate central nervous system. In the hindbrain and spinal cord, distinctions in the rostrocaudal identity of progenitor cells are associated with the generation of different motor neuron subtypes. Two fundamental classes of motor neurons, those with dorsal (dMN and ventral (vMN exit points, are generated over largely non-overlapping rostrocaudal domains of the caudal neural tube. Cdx and Hox genes are important determinants of the rostrocaudal identity of neural progenitor cells, but the link between early patterning signals, neural Cdx and Hox gene expression, and the generation of dMN and vMN subtypes, is unclear. Using an in vitro assay of neural differentiation, we provide evidence that an early Wnt-based program is required to interact with a later retinoic acid- and fibroblast growth factor-mediated mechanism to generate a pattern of Cdx and Hox profiles characteristic of hindbrain and spinal cord progenitor cells that prefigure the generation of vMNs and dMNs.

  15. Early life exposure to 2.45GHz WiFi-like signals: effects on development and maturation of the immune system.

    Science.gov (United States)

    Sambucci, Manolo; Laudisi, Federica; Nasta, Francesca; Pinto, Rosanna; Lodato, Rossella; Lopresto, Vanni; Altavista, Pierluigi; Marino, Carmela; Pioli, Claudio

    2011-12-01

    The development of the immune system begins during embryogenesis, continues throughout fetal life, and completes its maturation during infancy. Exposure to immune-toxic compounds at levels producing limited/transient effects in adults, results in long-lasting or permanent immune deficits when it occurs during perinatal life. Potentially harmful radiofrequency (RF) exposure has been investigated mainly in adult animals or with cells from adult subjects, with most of the studies showing no effects. Is the developing immune system more susceptible to the effects of RF exposure? To address this question, newborn mice were exposed to WiFi signals at constant specific absorption rates (SAR) of 0.08 or 4 W/kg, 2h/day, 5 days/week, for 5 consecutive weeks, starting the day after birth. The experiments were performed with a blind procedure using sham-exposed groups as controls. No differences in body weight and development among the groups were found in mice of both sexes. For the immunological analyses, results on female and male newborn mice exposed during early post-natal life did not show any effects on all the investigated parameters with one exception: a reduced IFN-γ production in spleen cells from microwaves (MW)-exposed (SAR 4 W/kg) male (not in female) mice compared with sham-exposed mice. Altogether our findings do not support the hypothesis that early post-natal life exposure to WiFi signals induces detrimental effects on the developing immune system.

  16. Characterization of asgC a Gene Required for Cell-Cell Signaling Early Development of Myxococcus Xanthus

    Science.gov (United States)

    2007-11-02

    induction and curing of bacteriophage P1 lysogens. Virology 48: 679-689. Sambrook, J., Fritsch, E.F., and Maniatis , T. (1989) Molecular Cloning : A...Genetics of gliding motility in Myxococcus xanthus: molecular cloning of the mgl locus. Mol Gen Genet 207: 256-266. Stock, J.B., Ninfa, A.J., and...Plamann. 1995. A missense mutation in rpoD results in an A-signaling defect in Myxococcus xanthus. Molecular Microbiology 18:943-952. Appendix B

  17. Disruption of Early Tumor Necrosis Factor Alpha Signaling Prevents Classical Activation of Dendritic Cells in Lung-Associated Lymph Nodes and Development of Protective Immunity against Cryptococcal Infection

    Directory of Open Access Journals (Sweden)

    Jintao Xu

    2016-07-01

    Full Text Available Anti-tumor necrosis factor alpha (anti-TNF-α therapies have been increasingly used to treat inflammatory diseases and are associated with increased risk of invasive fungal infections, including Cryptococcus neoformans infection. Using a mouse model of cryptococcal infection, we investigated the mechanism by which disruption of early TNF-α signaling results in the development of nonprotective immunity against C. neoformans. We found that transient depletion of TNF-α inhibited pulmonary fungal clearance and enhanced extrapulmonary dissemination of C. neoformans during the adaptive phase of the immune response. Higher fungal burdens in TNF-α-depleted mice were accompanied by markedly impaired Th1 and Th17 responses in the infected lungs. Furthermore, early TNF-α depletion also resulted in disrupted transcriptional initiation of the Th17 polarization program and subsequent upregulation of Th1 genes in CD4+ T cells in the lung-associated lymph nodes (LALN of C. neoformans-infected mice. These defects in LALN T cell responses were preceded by a dramatic shift from a classical toward an alternative activation of dendritic cells (DC in the LALN of TNF-α-depleted mice. Taken together, our results indicate that early TNF-α signaling is required for optimal DC activation, and the initial Th17 response followed by Th1 transcriptional prepolarization of T cells in the LALN, which further drives the development of protective immunity against cryptococcal infection in the lungs. Thus, administration of anti-TNF-α may introduce a particularly greater risk for newly acquired fungal infections that require generation of protective Th1/Th17 responses for their containment and clearance.

  18. Blocking TGF-β Signaling Pathway Preserves Mitochondrial Proteostasis and Reduces Early Activation of PDGFRβ+ Pericytes in Aristolochic Acid Induced Acute Kidney Injury in Wistar Male Rats.

    Directory of Open Access Journals (Sweden)

    Agnieszka A Pozdzik

    Full Text Available The platelet-derived growth factor receptor β (PDGFRβ+ perivascular cell activation becomes increasingly recognized as a main source of scar-associated kidney myofibroblasts and recently emerged as a new cellular therapeutic target.In this regard, we first confirmed the presence of PDGFRβ+ perivascular cells in a human case of end-stage aristolochic acid nephropathy (AAN and thereafter we focused on the early fibrosis events of transforming growth factor β (TGFβ inhibition in a rat model of AAN.Neutralizing anti-TGFβ antibody (1D11 and its control isotype (13C4 were administered (5 mg/kg, i.p. at Days -1, 0, 2 and 4; AA (15 mg/kg, sc was injected daily.At Day 5, 1D11 significantly suppressed p-Smad2/3 signaling pathway improving renal function impairment, reduced the score of acute tubular necrosis, peritubular capillaritis, interstitial inflammation and neoangiogenesis. 1D11 markedly decreased interstitial edema, disruption of tubular basement membrane loss of brush border, cytoplasmic edema and organelle ultrastructure alterations (mitochondrial disruption and endoplasmic reticulum edema in proximal tubular epithelial cells. Moreover, 1D11 significantly inhibited p-PERK activation and attenuated dysregulation of unfolded protein response (UPR pathways, endoplasmic reticulum and mitochondrial proteostasis in vivo and in vitro.The early inhibition of p-Smad2/3 signaling pathway improved acute renal function impairment, partially prevented epithelial-endothelial axis activation by maintaining PTEC proteostasis and reduced early PDGFRβ+ pericytes-derived myofibroblasts accumulation.

  19. Disruption of hypothalamic leptin signaling in mice leads to early-onset obesity, but physiological adaptations in mature animals stabilize adiposity levels.

    Science.gov (United States)

    Ring, Laurence E; Zeltser, Lori M

    2010-08-01

    Distinct populations of leptin-sensing neurons in the hypothalamus, midbrain, and brainstem contribute to the regulation of energy homeostasis. To assess the requirement for leptin signaling in the hypothalamus, we crossed mice with a floxed leptin receptor allele (Leprfl) to mice transgenic for Nkx2.1-Cre, which drives Cre expression in the hypothalamus and not in more caudal brain regions, generating LeprNkx2.1KO mice. From weaning, LeprNkx2.1KO mice exhibited phenotypes similar to those observed in mice with global loss of leptin signaling (Leprdb/db mice), including increased weight gain and adiposity, hyperphagia, cold intolerance, and insulin resistance. However, after 8 weeks of age, LeprNkx2.1KO mice maintained stable adiposity levels, whereas the body fat percentage of Leprdb/db animals continued to escalate. The divergence in the adiposity phenotypes of Leprdb/db and LeprNkx2.1KO mice with age was concomitant with increased rates of linear growth and energy expenditure in LeprNkx2.1KO mice. These data suggest that remaining leptin signals in LeprNkx2.1KO mice mediate physiological adaptations that prevent the escalation of the adiposity phenotype in adult mice. The persistence of severe adiposity in LeprNkx2.1KO mice, however, suggests that compensatory actions of circuits regulating growth and energy expenditure are not sufficient to reverse obesity established at an early age.

  20. Decreased SAP Expression in T Cells from Patients with Systemic Lupus Erythematosus Contributes to Early Signaling Abnormalities and Reduced IL-2 Production.

    Science.gov (United States)

    Karampetsou, Maria P; Comte, Denis; Kis-Toth, Katalin; Terhorst, Cox; Kyttaris, Vasileios C; Tsokos, George C

    2016-06-15

    T cells from patients with systemic lupus erythematosus (SLE) display a number of abnormalities, including increased early signaling events following engagement of the TCR. Signaling lymphocytic activation molecule family cell surface receptors and the X-chromosome-defined signaling lymphocytic activation molecule-associated protein (SAP) adaptor are important in the development of several immunocyte lineages and modulating the immune response. We present evidence that SAP protein levels are decreased in T cells and in their main subsets isolated from 32 women and three men with SLE, independent of disease activity. In SLE T cells, SAP protein is also subject to increased degradation by caspase-3. Forced expression of SAP in SLE T cells normalized IL-2 production, calcium (Ca(2+)) responses, and tyrosine phosphorylation of a number of proteins. Exposure of normal T cells to SLE serum IgG, known to contain anti-CD3/TCR Abs, resulted in SAP downregulation. We conclude that SLE T cells display reduced levels of the adaptor protein SAP, probably as a result of continuous T cell activation and degradation by caspase-3. Restoration of SAP levels in SLE T cells corrects the overexcitable lupus T cell phenotype. Copyright © 2016 by The American Association of Immunologists, Inc.

  1. Jarid2 Coordinates Nanog Expression and PCP/Wnt Signaling Required for Efficient ESC Differentiation and Early Embryo Development

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    David Landeira

    2015-07-01

    Full Text Available Jarid2 is part of the Polycomb Repressor complex 2 (PRC2 responsible for genome-wide H3K27me3 deposition. Unlike other PRC2-deficient embryonic stem cells (ESCs, however, Jarid2-deficient ESCs show a severe differentiation block, altered colony morphology, and distinctive patterns of deregulated gene expression. Here, we show that Jarid2−/− ESCs express constitutively high levels of Nanog but reduced PCP signaling components Wnt9a, Prickle1, and Fzd2 and lowered β-catenin activity. Depletion of Wnt9a/Prickle1/Fzd2 from wild-type ESCs or overexpression of Nanog largely phenocopies these cellular defects. Co-culture of Jarid2−/− with wild-type ESCs restores variable Nanog expression and β-catenin activity and can partially rescue the differentiation block of mutant cells. In addition, we show that ESCs lacking Jarid2 or Wnt9a/Prickle1/Fzd2 or overexpressing Nanog induce multiple ICM formation when injected into normal E3.5 blastocysts. These data describe a previously unrecognized role for Jarid2 in regulating a core pluripotency and Wnt/PCP signaling circuit that is important for ESC differentiation and for pre-implantation development.

  2. Association of CD147 and Calcium Exporter PMCA4 Uncouples IL-2 Expression from Early TCR Signaling.

    Science.gov (United States)

    Supper, Verena; Schiller, Herbert B; Paster, Wolfgang; Forster, Florian; Boulègue, Cyril; Mitulovic, Goran; Leksa, Vladimir; Ohradanova-Repic, Anna; Machacek, Christian; Schatzlmaier, Philipp; Zlabinger, Gerhard J; Stockinger, Hannes

    2016-02-01

    The Ig superfamily member CD147 is upregulated following T cell activation and was shown to serve as a negative regulator of T cell proliferation. Thus, Abs targeting CD147 are being tested as new treatment strategies for cancer and autoimmune diseases. How CD147 mediates immunosuppression and whether association with other coreceptor complexes is needed have remained unknown. In the current study, we show that silencing of CD147 in human T cells increases IL-2 production without affecting the TCR proximal signaling components. We mapped the immunosuppressive moieties of CD147 to its transmembrane domain and Ig-like domain II. Using affinity purification combined with mass spectrometry, we determined the domain specificity of CD147 interaction partners and identified the calcium exporter plasma membrane calcium ATPase isoform 4 (PMCA4) as the interaction partner of the immunosuppressive moieties of CD147. CD147 does not control the proper membrane localization of PMCA4, but PMCA4 is essential for the CD147-dependent inhibition of IL-2 expression via a calcium-independent mechanism. In summary, our data show that CD147 interacts via its immunomodulatory domains with PMCA4 to bypass TCR proximal signaling and inhibit IL-2 expression.

  3. Exploiting LF/MF signals of opportunity for lower ionospheric remote sensing

    Science.gov (United States)

    Higginson-Rollins, Marc A.; Cohen, Morris B.

    2017-08-01

    We introduce a method to diagnose and track the D region ionosphere (60-100 km). This region is important for long-distance terrestrial communication and is impacted by a variety of geophysical phenomena, but it is traditionally very difficult to detect. Modern remote sensing methods used to study the D region are predominately near the very low frequency (VLF, 3-30 kHz) band, with some work also done in the high-frequency and very high frequency bands (HF/VHF, 3-300 MHz). However, the frequency band between VLF and HF has been largely ignored as a diagnostic tool for the ionosphere. In this paper, we evaluate the use of 300 kHz radio reflections as a diagnostic tool for characterizing the D region of the ionosphere. We present radio receiver data, analyze diurnal trends in the signal from these transmitters, and identify ionospheric disturbances impacting LF/MF propagation. We find that 300 kHz remote sensing may allow a unique method for D region diagnostics compared to both the VLF and HF/VHF frequency bands, due to a more direct ionospheric reflection coefficient calculation method with high temporal resolution without the use of forward modeling.

  4. TNF-TNFR2/p75 signaling inhibits early and increases delayed nontargeted effects in bone marrow-derived endothelial progenitor cells.

    Science.gov (United States)

    Sasi, Sharath P; Song, Jin; Park, Daniel; Enderling, Heiko; McDonald, J Tyson; Gee, Hannah; Garrity, Brittany; Shtifman, Alexander; Yan, Xinhua; Walsh, Kenneth; Natarajan, Mohan; Kishore, Raj; Goukassian, David A

    2014-05-16

    TNF-α, a pro-inflammatory cytokine, is highly expressed after being irradiated (IR) and is implicated in mediating radiobiological bystander responses (RBRs). Little is known about specific TNF receptors in regulating TNF-induced RBR in bone marrow-derived endothelial progenitor cells (BM-EPCs). Full body γ-IR WT BM-EPCs showed a biphasic response: slow decay of p-H2AX foci during the initial 24 h and increase between 24 h and 7 days post-IR, indicating a significant RBR in BM-EPCs in vivo. Individual TNF receptor (TNFR) signaling in RBR was evaluated in BM-EPCs from WT, TNFR1/p55KO, and TNFR2/p75KO mice, in vitro. Compared with WT, early RBR (1-5 h) were inhibited in p55KO and p75KO EPCs, whereas delayed RBR (3-5 days) were amplified in p55KO EPCs, suggesting a possible role for TNFR2/p75 signaling in delayed RBR. Neutralizing TNF in γ-IR conditioned media (CM) of WT and p55KO BM-EPCs largely abolished RBR in both cell types. ELISA protein profiling of WT and p55KO EPC γ-IR-CM over 5 days showed significant increases in several pro-inflammatory cytokines, including TNF-α, IL-1α (Interleukin-1 alpha), RANTES (regulated on activation, normal T cell expressed and secreted), and MCP-1. In vitro treatments with murine recombinant (rm) TNF-α and rmIL-1α, but not rmMCP-1 or rmRANTES, increased the formation of p-H2AX foci in nonirradiated p55KO EPCs. We conclude that TNF-TNFR2 signaling may induce RBR in naïve BM-EPCs and that blocking TNF-TNFR2 signaling may prevent delayed RBR in BM-EPCs, conceivably, in bone marrow milieu in general.

  5. VLF Remote Sensing of the Lower Ionosphere: Solar Flares, Electron Precipitation, Sudden Ionospheric Disturbances, Sprites, Gravity Waves and Gamma-ray Flares

    Science.gov (United States)

    Tan, J. H.; Cohen, M.; Inan, U. S.; Scherrer, P. H.; Scherrer, D.

    2005-12-01

    Stanford University Very Low Frequency (VLF) and Extremely Low Frequency (ELF) radio receivers have been used extensively for remote sensing of the ionosphere and the magnetosphere. Among the phenomena that can be uniquely measured via ELF/VLF receivers are radio atmospherics, whistlers, electron precipitation, solar flares, sudden ionospheric disturbances, gravity waves, sprites, and cosmic gamma-ray flares. With the use of simple square air-core magnetic loop antennas of a couple of meters in size, the sensitivity of these instruments allows the measurement of magnetic fields as low as several tens of femtoTesla per root-Hz, in the frequency range of ~30 Hz to 50 kHz. This sensitivity well exceeds that required to detect any event above the ambient atmospheric noise floor, determined by the totality of lightning activity on the planet. In recent years, as cost of production, timing accuracy (due to low cost GPS clocks), and data handling flexibility of the systems has improved, it has become possible to distribute many of these instruments in the form of arrays, to perform interferometric and holographic imaging of the lower ionosphere. In the context of the IHY in 2007, the ELF/VLF receiver can used extensively as part of the United Nations initiative to place scientific instruments in developing countries. Stanford University's past experiences setting up arrays of ELF/VLF receivers include an interferometer in Alaska, the Holographic Array for Ionospheric and Lightning research (HAIL) consisting of instruments at 13 different high schools in mid-western United States, a broader set of ELF/VLF receivers in Alaska, and various receivers abroad, including in France, Japan, Greece, Turkey, Ireland, and India. A global network of ELF/VLF receivers offer possibilities for a wide range of scientific topics, as well as serving as a means for educational outreach. These goals will be achieved using the newest version of the Stanford VLF receiver, known as AWESOME

  6. Neurotrophin/Trk receptor signaling mediates C/EBPα, -β and NeuroD recruitment to immediate-early gene promoters in neuronal cells and requires C/EBPs to induce immediate-early gene transcription

    Directory of Open Access Journals (Sweden)

    von Bohlen und Halbach Oliver

    2007-01-01

    Full Text Available Abstract Background Extracellular signaling through receptors for neurotrophins mediates diverse neuronal functions, including survival, migration and differentiation in the central nervous system, but the transcriptional targets and regulators that mediate these diverse neurotrophin functions are not well understood. Results We have identified the immediate-early (IE genes Fos, Egr1 and Egr2 as transcriptional targets of brain derived neurotrophic factor (BDNF/TrkB signaling in primary cortical neurons, and show that the Fos serum response element area responds to BDNF/TrkB in a manner dependent on a combined C/EBP-Ebox element. The Egr1 and Egr2 promoters contain homologous regulatory elements. We found that C/EBPα/β and NeuroD formed complexes in vitro and in vivo, and were recruited to all three homologous promoter regions. C/EBPα and NeuroD co-operatively activated the Fos promoter in transfection assays. Genetic depletion of Trk receptors led to impaired recruitment of C/EBPs and NeuroD in vivo, and elimination of Cebpa and Cebpb alleles reduced BDNF induction of Fos, Egr1 and Egr2 in primary neurons. Finally, defective differentiation of cortical dendrites, as measured by MAP2 staining, was observed in both compound Cebp and Ntrk knockout mice. Conclusion We here identify three IE genes as targets for BDNF/TrkB signaling, show that C/EBPα and -β are recruited along with NeuroD to target promoters, and that C/EBPs are essential mediators of Trk signaling in cortical neurons. We show also that C/EBPs and Trks are required for cortical dendrite differentiation, consistent with Trks regulating dendritic differentiation via a C/EBP-dependent mechanism. Finally, this study indicates that BDNF induction of IE genes important for neuronal function depends on transcription factors (C/EBP, NeuroD up-regulated during neuronal development, thereby coupling the functional competence of the neuronal cells to their differentiation.

  7. TGF-β/Smad2/3 signaling directly regulates several miRNAs in mouse ES cells and early embryos.

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    Nicholas Redshaw

    Full Text Available The Transforming Growth Factor-β (TGF-β signaling pathway is one of the major pathways essential for normal embryonic development and tissue homeostasis, with anti-tumor but also pro-metastatic properties in cancer. This pathway directly regulates several target genes that mediate its downstream functions, however very few microRNAs (miRNAs have been identified as targets. miRNAs are modulators of gene expression with essential roles in development and a clear association with diseases including cancer. Little is known about the transcriptional regulation of the primary transcripts (pri-miRNA, pri-miR from which several mature miRNAs are often derived. Here we present the identification of miRNAs regulated by TGF-β signaling in mouse embryonic stem (ES cells and early embryos. We used an inducible ES cell system to maintain high levels of the TGF-β activated/phosphorylated Smad2/3 effectors, which are the transcription factors of the pathway, and a specific inhibitor that blocks their activation. By performing short RNA deep-sequencing after 12 hours Smad2/3 activation and after 16 hours inhibition, we generated a database of responsive miRNAs. Promoter/enhancer analysis of a subset of these miRNAs revealed that the transcription of pri-miR-181c/d and the pri-miR-341∼3072 cluster were found to depend on activated Smad2/3. Several of these miRNAs are expressed in early mouse embryos, when the pathway is known to play an essential role. Treatment of embryos with TGF-β inhibitor caused a reduction of their levels confirming that they are targets of this pathway in vivo. Furthermore, we showed that pri-miR-341∼3072 transcription also depends on FoxH1, a known Smad2/3 transcription partner during early development. Together, our data show that miRNAs are regulated directly by the TGF-β/Smad2/3 pathway in ES cells and early embryos. As somatic abnormalities in functions known to be regulated by the TGF-β/Smad2/3 pathway underlie tumor

  8. The role of NgR-Rhoa-Rock signal pathway in retinal ganglion cell apoptosis of early diabetic rats

    Directory of Open Access Journals (Sweden)

    Yun-Jie Fu

    2014-09-01

    Full Text Available AIM: To study the function and mechanism of the NgR-Rhoa-Rock signal pathways which exists in the retinal ganglion cells apoptosis in diabetes mellitus(DMrats. METHODS: Some healthy SD rats were operated by means of single intraperitoneal injection of 1% streptozotocin based on the standard of 50mg/kg wight, after that the blood sugar value was greater than 16.7mmol/L as DM model, then randomly divided into 3 groups, each group was 10 rats. In addition to take 10 healthy SD rats as control group. Four groups of rats were bilaterally eyeball intravitreal injection in turn with NgR-siRNA virus 10μL(siRNA group, NgR-siRNA virus diluted 10μL(DM group, NgR-siRNA virus-negative-control solution 10μL(siRNA blank group, NgR-siRNA virus diluted 10μL(normal control group, and fed normally. During that time, some life indexes like blood glucose, body mass, etc. were measured and recorded. After 12wk, the expression of NgR and Rhoa, HE staining, and TUNNEL staining were detected by Western blot analysis. RESULTS: Western blot analysis: compared with normal control group, the expression of NgR and Rhoa in DM group and siRNA blank group increased significantly(PP>0.05; compared with DM group and siRNA blank group, the expression of those proteins significantly lowered in siRNA group. HE staining: compared with normal control group, some extent ganglion cells arranged disorder, irregular shape, spacing not consistent were all found in three groups of model rats; compared with DM group and siRNA blank group, there was some improvement in siRNA group of ganglion cells about the order and shape size. TUNEL staining: compared with normal control group, there were retinal ganglion cells apoptosis in all of three groups of model rats. Compared with DM group and siRNA blank group, the number of retinal ganglion cells apoptotic cells was less, and the shape of cells had improved significantly in siRNA group. CONCLUSION: In the DM phase, the expression of NgR and

  9. Remodelling of Membrane Rafts Expression in Lung Cells as an Early Sign of Mechanotransduction-Signalling in Pulmonary Edema

    Directory of Open Access Journals (Sweden)

    Paola Palestini

    2011-01-01

    Full Text Available Membrane rafts (MRs are clusters of lipids, organized in a “quasicrystalline” liquid-order phase, organized on the cell surface and whose pattern of molecules and physicochemical properties are distinct from those of the surrounding plasma membrane. MRs may be considered an efficient and fairly rapid cell-activated mechanism to express or mask surface receptors aimed at triggering specific response pathways. This paper reports observations concerning the role of MRs in the control of lung extravascular water that ought to be kept at minimum to assure gas diffusion, supporting the hypothesis that MRs expression is a potential mechanism of sensing minor changes in the volume of extravascular water. We present the evidence that MRs expression specifically relates to signal-transduction processes evoked by mechanical stimuli arising in the interstitial lung compartment when a small increase in extravascular volume occurs. We further hypothesize that a differential expression of MRs might also reflect the damage to precise components of the extracellular matrix caused by the perturbation in water balance and thus can trigger a molecule-oriented specific matrix remodelling.

  10. Disruption of planar cell polarity signaling results in congenital heart defects and cardiomyopathy attributable to early cardiomyocyte disorganization.

    Science.gov (United States)

    Phillips, Helen M; Rhee, Hong Jun; Murdoch, Jennifer N; Hildreth, Victoria; Peat, Jonathan D; Anderson, Robert H; Copp, Andrew J; Chaudhry, Bill; Henderson, Deborah J

    2007-07-20

    The Drosophila scribble gene regulates apical-basal polarity and is implicated in control of cellular architecture and cell growth control. Mutations in mammalian Scrib (circletail; Crc mutant) also result in abnormalities suggestive of roles in planar cell polarity regulation. We show that Crc mutants develop heart malformations and cardiomyopathy attributable to abnormalities in cardiomyocyte organization within the early heart tube. N-Cadherin is lost from the cardiomyocyte cell membrane and cell-cell adhesion is disrupted. This results in abnormalities in heart looping and formation of both the trabeculae and compact myocardium, which ultimately results in cardiac misalignment defects and ventricular noncompaction. Thus, these late abnormalities arise from defects occurring at the earliest stages of heart development. Mislocalization of Vangl2 in Crc/Crc cardiomyocytes suggests Scrib is acting in the planar cell polarity pathway in this tissue. Moreover, double heterozygosity for mutations in both Scrib and Vangl2 can cause cardiac defects similar to those found in homozygous mutants for each gene but without other major defects. We propose that heterozygosity for mutations in different genes in the planar cell polarity pathway may be an important mechanism for congenital heart defects and cardiomyopathy in humans.

  11. Spatially Extended 21 cm Signal from Strongly Clustered Uv and X-Ray Sources in the Early Universe

    Science.gov (United States)

    Ahn, Kyungjin; Xu, Hao; Norman, Michael L.; Alvarez, Marcelo A.; Wise, John H.

    2015-03-01

    We present our prediction for the local 21 cm differential brightness temperature (δTb) from a set of strongly clustered sources of Population III (Pop III) and II (Pop II) objects in the early universe, by a numerical simulation of their formation and radiative feedback. These objects are located inside a highly biased environment, which is a rare, high-density peak (“Rarepeak”) extending to ∼7 comoving Mpc. We study the impact of ultraviolet and X-ray photons on the intergalactic medium (IGM) and the resulting δTb, when Pop III stars are assumed to emit X-ray photons by forming X-ray binaries very efficiently. We parameterize the rest-frame spectral energy distribution of X-ray photons, which regulates X-ray photon-trapping, IGM-heating, secondary Lyα pumping and the resulting morphology of δTb. A combination of emission (δTb > 0) and absorption (δTb Frequency Array, Murchison Widefield Array, Precision Array for Probing the Epoch of Reionization) of such rare peaks is found to be difficult due to the rarity of these peaks, and the contribution only by these rare peaks to the total power spectrum remains subdominant compared to that by all astrophysical sources.

  12. Early-Warning Signals for the onsets of Greenland Interstadials and the Younger Dryas-Preboreal transition

    CERN Document Server

    Rypdal, M

    2015-01-01

    The high-frequency band of the $\\delta^{18}\\mbox{O}$ variations in the North Greenland Ice Core Project displays fluctuation levels that increase as one approaches the onset of an interstadial (warm) period. For some of the events it is possible to establish statistical significance using Monte-Carlo simulations with a non-parametric null model with random phases and the same spectral density as the $\\delta^{18}\\mbox{O}$ record during the stadial periods. Similar results are found for the locally estimated Hurst exponent for the high-frequency fluctuations, and it is therefore natural to interpret these findings as so-called "critical slowing down" signatures, i.e. early-warning signs of tipping points. The observed "slowing down" is found to be similar (and perhaps even stronger) in the Younger Dryas, suggesting that there are some similarities between mechanisms of the Younger Dryas-Preboreal transition and the onsets of the Greenland interstadials. It is also verified that the temperature fluctuations duri...

  13. Early cytoskeletal rearrangement during dendritic cell maturation enhances synapse formation and Ca(2+) signaling in CD8(+) T cells.

    Science.gov (United States)

    Averbeck, Marco; Braun, Thorsten; Pfeifer, Gunther; Sleeman, Jonathan; Dudda, Jan; Martin, Stefan F; Kremer, Bernhard; Aktories, Klaus; Simon, Jan C; Termeer, Christian

    2004-10-01

    The interplay between dendritic cells (DC) and T cells is a dynamic process critically depending on DC maturation. Ca(2+) influx is one of the initial events occurring during DC/T cell contacts. To determine how DC maturation influences DC/T cell contacts, time-lapse video microscopy was established using TCR-transgenic CD8(+) T cells from P14 mice. DC maturation shifted DC/T cell contacts from short-lived interactions with transient Ca(2+) influx in T cells to long-lasting interactions and sustained Ca(2+) influx of 30 min and more. Follow-up of DC/T cell interactions after 2 h using confocal microscopy revealed that long-lasting Ca(2+) responses in T cells were preferentially associated with the formation of an immunological synapse involving CD54 and H2-K(b) at the DC/T cell interface. Such synapse formation preceded MHC or B7 up-regulation, since DC developed into potent Ca(2+) stimulators 7 h after initiation of maturation. Instead, the enhanced capacity of 7 h-matured DC to induce sustained Ca(2+) responses in CD8(+) T cells is critically dependent on the polarization and rearrangement of the cytoskeleton, as shown by Clostridium difficile toxin B inhibitor experiments. These data indicate that already very early after receiving a maturation stimulus, DC display enhanced cytoskeletal activity resulting in the rapid formation of immunological synapses and effective CD8(+) T cell stimulation.

  14. The environmental signal of an early Holocene pollen record from the Shiyang River basin lake sediments, NW China

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Pollen analyses of 85 samples from the Sanjiaocheng section well along the margin of a palaeolake at the end of the Shiyang River, NW China, show that Picea and Sabina dominate the pollen assemblage. Together they reach as high as 40%-60%, with the percentage of Picea varying inversely with that of Sabina. Similar results were obtained from another section in the Shiyang River drainage.Using modern ecological habitat relationship analogues, pollen transport characteristics, and the overall pollen assemblage, we propose that both Picea and Sabina pollen were transported by the river from the mountains at the upper reaches of the Shiyang River, and that the assemblage is more indicative of changes in upland vegetation than of local conditions near the section. This interpretation is supported by pollen data derived from surface samples, water samples,and riverbed samples. Using a moisture indicator (the Picea to Sabina ratio) and calculated pollen concentrations, we identify a series of palaeoenvironmental changes during the early Holocene (10 6.3 14C kaBP).

  15. microRNA-208a in an early stage myocardial infarction rat model and the effect on cAMP-PKA signaling pathway.

    Science.gov (United States)

    Feng, Gao; Yan, Zhang; Li, Chuanchuan; Hou, Yuemei

    2016-08-01

    The expression level of microRNA-208a (miR-208a) in a rat model with myocardial infarction and the effect of cAMP-PKA signaling pathway in early stage of myocardial infarction in rats were investigated. The early myocardial infarction model was established in 12 male Sprague-Dawley rats by ligation of the anterior descending coronary artery, and 12 rats were selected as the control group (sham operation group). Reverse-transcription quantitative PCR was conducted to detect the expression levels of miR-208a in the myocardium of and the expression levels of miR‑208a in the serum of rats in the two groups. Western blot analysis was used to evaluate the expression levels of cAMP-PKA protein in the rat tissues in the two groups. After stimulating high levels of miR‑208a expression in human myocardial cells (HCM), western blot analysis was used to detect the cAMP-PKA protein levels. The expression levels of miR‑208a in myocardial tissues in rats with myocardial infarction were significantly higher than those in the control group, and the difference was statistically significant (PcAMP-PKA protein in myocardial tissue in rats with chronic myocardial infarction was also significantly higher. Transfection of human myocardial cells with miR‑208a analogue significantly increased the cAMP-PKA protein levels in human myocardial cells. In conclusion, the over-expression of miR-208a in myocardial infarction tissue and the high levels of this miRNA in the serum, may be involved in the process of myocardial infarction by influencing the cAMP-PKA signaling pathway in myocardial cells.

  16. Early warning signal for dengue outbreaks and identification of high risk areas for dengue fever in Colombia using climate and non-climate datasets.

    Science.gov (United States)

    Lee, Jung-Seok; Carabali, Mabel; Lim, Jacqueline K; Herrera, Victor M; Park, Il-Yeon; Villar, Luis; Farlow, Andrew

    2017-07-10

    Dengue has been prevalent in Colombia with high risk of outbreaks in various locations. While the prediction of dengue epidemics will bring significant benefits to the society, accurate forecasts have been a challenge. Given competing health demands in Colombia, it is critical to consider the effective use of the limited healthcare resources by identifying high risk areas for dengue fever. The Climate Risk Factor (CRF) index was constructed based upon temperature, precipitation, and humidity. Considering the conditions necessary for vector survival and transmission behavior, elevation and population density were taken into account. An Early Warning Signal (EWS) model was developed by estimating the elasticity of the climate risk factor function to detect dengue epidemics. The climate risk factor index was further estimated at the smaller geographical unit (5 km by 5 km resolution) to identify populations at high risk. From January 2007 to December 2015, the Early Warning Signal model successfully detected 75% of the total number of outbreaks 1 ~ 5 months ahead of time, 12.5% in the same month, and missed 12.5% of all outbreaks. The climate risk factors showed that populations at high risk are concentrated in the Western part of Colombia where more suitable climate conditions for vector mosquitoes and the high population level were observed compared to the East. This study concludes that it is possible to detect dengue outbreaks ahead of time and identify populations at high risk for various disease prevention activities based upon observed climate and non-climate information. The study outcomes can be used to minimize potential societal losses by prioritizing limited healthcare services and resources, as well as by conducting vector control activities prior to experiencing epidemics.

  17. Modulation of Bmp4 signalling in the epithelial-mesenchymal interactions that take place in early thymus and parathyroid development in avian embryos.

    Science.gov (United States)

    Neves, Hélia; Dupin, Elisabeth; Parreira, Leonor; Le Douarin, Nicole M

    2012-01-15

    Epithelial-mesenchymal interactions are crucial for the development of the endoderm of the pharyngeal pouches into the epithelia of thymus and parathyroid glands. Here we investigated the dynamics of epithelial-mesenchymal interactions that take place at the earliest stages of thymic and parathyroid organogenesis using the quail-chick model together with a co-culture system capable of reproducing these early events in vitro. The presumptive territories of thymus and parathyroid epithelia were identified in three-dimensionally preserved pharyngeal endoderm of embryonic day 4.5 chick embryos on the basis of the expression of Foxn1 and Gcm2, respectively: the thymic rudiment is located in the dorsal domain of the third and fourth pouches, while the parathyroid rudiment occupies a more medial/anterior pouch domain. Using in vitro quail-chick tissue associations combined with in ovo transplantations, we show that the somatopleural but not the limb bud mesenchyme, can mimic the role of neural crest-derived pharyngeal mesenchyme to sustain development of these glands up to terminal differentiation. Furthermore, mesenchymal-derived Bmp4 appears to be essential to promote early stages of endoderm development during a short window of time, irrespective of the mesenchymal source. In vivo studies using the quail-chick system and implantation of growth factor soaked-beads further showed that expression of Bmp4 by the mesenchyme is necessary during a 24 h-period of time. After this period however, Bmp4 is no longer required and another signalling factor produced by the mesenchyme, Fgf10, influences later differentiation of the pouch endoderm. These results show that morphological development and cell differentiation of thymus and parathyroid epithelia require a succession of signals emanating from the associated mesenchyme, among which Bmp4 plays a pivotal role for triggering thymic epithelium specification.

  18. The NO-cGMP-PKG signal transduction pathway is involved in the analgesic effect of early hyperbaric oxygen treatment of neuropathic pain.

    Science.gov (United States)

    Ding, Yuanyuan; Yao, Peng; Hong, Tao; Han, Zhenkai; Zhao, Baisong; Chen, Weimin

    2017-12-01

    Hyperbaric oxygen (HBO) has the potential to relieve neuropathic pain. The purpose of this study was to determine whether the NO-cGMP-PKG signaling pathway is involved in the analgesic effects of early hyperbaric oxygen treatment of neuropathic pain in rats. Rats were randomly grouped for establishment of chronic constriction injury (CCI) models. Intrathecal catheters were inserted and 2.5ATA HBO therapy was administered from day 1 post-surgery for 60 minutes daily, continuously for 5 days; menstruum NS, DMSO, NO synthase(NOS) nonspecific inhibitor (L-NAME), soluble guanylyl cyclase(sGC) inhibitor (ODQ) and protein kinase G(PKG) inhibitor (KT5823) were administered intrathecally 30 minutes prior to HBO therapy. Pain-related behaviors in rats were observed at specific time points. Western blot and real-time RT-PCR were used to observe the expressions of PKG1 mRNA and protein in the spinal dorsal horn. Compared with the CCI group, HBO could significantly relieve mechanical and thermal hyperalgesia in rats. After intrathecal administration of L-NAME, ODQ and KT5823, effects of HBO on relieving hyperalgesia in rats were reversed (P < 0.05 vs. HBO), and expression of PKG1 mRNA and protein decreased in the spinal dorsal horn of the animals (P < 0.05 vs. HBO). Early HBO therapy could significantly improve symptoms of hyperalgesia of neuropathic pain in rats, possibly via activation of the NO-cGMP-PKG signaling transduction pathway.

  19. Continental European Eemian and early Würmian climate evolution: comparing signals using different quantitative reconstruction approaches based on pollen

    Science.gov (United States)

    Klotz, Stefan; Guiot, Joel; Mosbrugger, Volker

    2003-05-01

    Analyses of Eemian climate dynamics based on different reconstruction methods were conducted for several pollen sequences in the northern alpine foreland. The modern analogue and mutual climate sphere techniques used, which are briefly presented, complement one another with respect to comparable results. The reconstructions reveal the occurrence of at least two similar thermal periods, representing temperate oceanic conditions warmer and with a higher humidity than today. Intense changes of climate processes become obvious with a shift of winter temperatures of about 15 °C from the late Rissian to the first thermal optimum of the Eemian. The transition shows a pattern of summer temperatures and precipitation increasing more rapidly than winter temperatures. With the first optimum during the Pinus-Quercetum mixtum-Corylus phase (PQC) at an early stage of the Eemian and a second optimum period at a later stage, which is characterised by widespread Carpinus, climate gradients across the study area were less intense than today. Average winter temperatures vary between -1.9 and 0.4 °C (present-day -3.6 to 1.4 °C), summer temperatures between 17.8 and 19.6 °C (present-day 14 to 18.9 °C). The timberline expanded about 350 m when compared to the present-day limit represented by Pinus mugo. Whereas the maximum of temperature parameters is related to the first optimum, precipitation above 1100 mm is higher during the second warm period concomitant to somewhat reduced temperatures. Intermediate, smaller climate oscillations and a cooling becomes obvious, which admittedly represent moderate deterioration but not extreme chills. During the boreal semicontinental Eemian Pinus-Picea-Abies phase, another less distinct fluctuation occurs, initiating the oscillating shift from temperate to cold conditions.

  20. Energy status and HIF signalling in chorionic villi show no evidence of hypoxic stress during human early placental development.

    Science.gov (United States)

    Cindrova-Davies, T; van Patot, M Tissot; Gardner, L; Jauniaux, E; Burton, G J; Charnock-Jones, D S

    2015-03-01

    Early human placental and embryonic development occurs in a physiologically low oxygen environment supported by histiotrophic secretions from endometrial glands. In this study, we compare the placental metabolomic profile in the first, second and third trimesters to determine whether the energy demands are adequately met in the first trimester. We investigated whether hypoxia-inducible factors, HIF-1α and/or HIF-2α, might regulate transcription during the first trimester. First and second trimester tissue was collected using a chorionic villus sampling-like (CVS) technique. Part of each villus sample was frozen immediately and the remainder cultured under 2 or 21% O2 ± 1 mM H2O2, and ±the p38 MAPK pathway inhibitor, PD169316. Levels of HIF-1α were assessed by western blotting and VEGFA, PlGF and GLUT3 transcripts were quantified by RT-PCR. Term samples were collected from normal elective Caesarean deliveries. There were no significant differences in concentrations of ADP, NAD(+), lactate, and glucose, and in the ATP/ADP ratio, across gestational age. Neither HIF-1α nor HIF-2α could be detected in time-zero CVS samples. However, culture under any condition (2 or 21% O2 ± 1 mM H2O2) increased HIF-1α and HIF-2α. HIF-1α and HIF-2α were additionally detected in specimens retrieved after curettage. HIF-1α stabilization was accompanied by significant increases in VEGFA and GLUT3 and a decrease in PlGF mRNAs. These effects were suppressed by PD169316. In conclusion, our data suggest that first trimester placental tissues are not energetically compromised, and that HIF-1α is unlikely to play an appreciable role in regulating transcriptional activity under steady-state conditions in vivo. However, the pathway may be activated by stress conditions.

  1. A role for the immediate early gene product c-fos in imprinting T cells with short-term memory for signal summation.

    Directory of Open Access Journals (Sweden)

    Carolyn E Clark

    Full Text Available T cells often make sequential contacts with multiple DCs in the lymph nodes and are likely to be equipped with mechanisms that allow them to sum up the successive signals received. We found that a period of stimulation as short as two hours could imprint on a T cell a "biochemical memory" of that activation signal that persisted for several hours. This was evidenced by more rapid induction of activation markers and earlier commitment to proliferation upon subsequent stimulation, even when that secondary stimulation occurred hours later. Upregulation of the immediate early gene product c-fos, a component of the AP-1 transcription factor, was maximal by 1-2 hours of stimulation, and protein levels remained elevated for several hours after stimulus withdrawal. Moreover, phosphorylated forms of c-fos that are stable and transcriptionally active persisted for a least a day. Upon brief antigenic stimulation in vivo, we also observed a rapid upregulation of c-fos that could be boosted by subsequent stimulation. Accumulation of phosphorylated c-fos may therefore serve as a biochemical fingerprint of previous suboptimal stimulation, leaving the T cell poised to rapidly resume its activation program upon its next encounter with an antigen-bearing DC.

  2. Notch signaling differentially regulates the cell fate of early endocrine precursor cells and their maturing descendants in the mouse pancreas and intestine.

    Science.gov (United States)

    Li, Hui Joyce; Kapoor, Archana; Giel-Moloney, Maryann; Rindi, Guido; Leiter, Andrew B

    2012-11-15

    Notch signaling inhibits differentiation of endocrine cells in the pancreas and intestine. In a number of cases, the observed inhibition occurred with Notch activation in multipotential cells, prior to the initiation of endocrine differentiation. It has not been established how direct activation of Notch in endocrine precursor cells affects their subsequent cell fate. Using conditional activation of Notch in cells expressing Neurogenin3 or NeuroD1, we examined the effects of Notch in both organs, on cell fate of early endocrine precursors and maturing endocrine-restricted cells, respectively. Notch did not preclude the differentiation of a limited number of endocrine cells in either organ when activated in Ngn3(+) precursor cells. In addition, in the pancreas most Ngn3(+) cells adopted a duct but not acinar cell fate; whereas in intestinal Ngn3(+) cells, Notch favored enterocyte and goblet cell fates, while selecting against endocrine and Paneth cell differentiation. A small fraction of NeuroD1(+) cells in the pancreas retain plasticity to respond to Notch, giving rise to intraislet ductules as well as cells with no detectable pancreatic lineage markers that appear to have limited ultrastructural features of both endocrine and duct cells. These results suggest that Notch directly regulates cell fate decisions in multipotential early endocrine precursor cells. Some maturing endocrine-restricted NeuroD1(+) cells in the pancreas switch to the duct lineage in response to Notch, indicating previously unappreciated plasticity at such a late stage of endocrine differentiation.

  3. Theobromine inhibits differentiation of 3T3-L1 cells during the early stage of adipogenesis via AMPK and MAPK signaling pathways.

    Science.gov (United States)

    Jang, Yeon Jeong; Koo, Hyun Jung; Sohn, Eun-Hwa; Kang, Se Chan; Rhee, Dong-Kwon; Pyo, Suhkneung

    2015-07-01

    Obesity is characterized by hypertrophy and/or by the differentiation or adipogenesis of pre-existing adipocytes. In this study, we investigated the inhibitory effects of theobromine, a type of alkaloid in cocoa, on adipocyte differentiation of 3T3-L1 preadipocytes and its mechanisms of action. Theobromine inhibited the accumulation of lipid droplets, the expression of PPARγ and C/EBPα, and the mRNA expression of aP2 and leptin. The inhibition of adipogenic differentiation by theobromine occurred primarily in the early stages of differentiation. In addition, theobromine arrested the cell cycle at the G0/G1 phase and regulated the expressions of CDK2, p27, and p21. Theobromine treatment increased AMPK phosphorylation and knockdown of AMPKα1/α2 prevented the ability of theobromine to inhibit PPARγ expression in the differentiating 3T3-L1 cells. Theobromine reduced the phosphorylation of ERK and JNK. Moreover, the secretion and the mRNA level of TNF-α and IL-6 were inhibited by theobromine treatment. These data suggest that theobromine inhibits adipocyte differentiation during the early stages of adipogenesis by regulating the expression of PPARγ and C/EBPα through the AMPK and ERK/JNK signaling pathways in 3T3-L1 preadipocytes.

  4. Glycolytic-to-oxidative fiber-type switch and mTOR signaling activation are early-onset features of SBMA muscle modified by high-fat diet.

    Science.gov (United States)

    Rocchi, Anna; Milioto, Carmelo; Parodi, Sara; Armirotti, Andrea; Borgia, Doriana; Pellegrini, Matteo; Urciuolo, Anna; Molon, Sibilla; Morbidoni, Valeria; Marabita, Manuela; Romanello, Vanina; Gatto, Pamela; Blaauw, Bert; Bonaldo, Paolo; Sambataro, Fabio; Robins, Diane M; Lieberman, Andrew P; Sorarù, Gianni; Vergani, Lodovica; Sandri, Marco; Pennuto, Maria

    2016-07-01

    Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by the expansion of a polyglutamine tract in the androgen receptor (AR). The mechanism by which expansion of polyglutamine in AR causes muscle atrophy is unknown. Here, we investigated pathological pathways underlying muscle atrophy in SBMA knock-in mice and patients. We show that glycolytic muscles were more severely affected than oxidative muscles in SBMA knock-in mice. Muscle atrophy was associated with early-onset, progressive glycolytic-to-oxidative fiber-type switch. Whole genome microarray and untargeted lipidomic analyses revealed enhanced lipid metabolism and impaired glycolysis selectively in muscle. These metabolic changes occurred before denervation and were associated with a concurrent enhancement of mechanistic target of rapamycin (mTOR) signaling, which induced peroxisome proliferator-activated receptor γ coactivator 1 alpha (PGC1α) expression. At later stages of disease, we detected mitochondrial membrane depolarization, enhanced transcription factor EB (TFEB) expression and autophagy, and mTOR-induced protein synthesis. Several of these abnormalities were detected in the muscle of SBMA patients. Feeding knock-in mice a high-fat diet (HFD) restored mTOR activation, decreased the expression of PGC1α, TFEB, and genes involved in oxidative metabolism, reduced mitochondrial abnormalities, ameliorated muscle pathology, and extended survival. These findings show early-onset and intrinsic metabolic alterations in SBMA muscle and link lipid/glucose metabolism to pathogenesis. Moreover, our results highlight an HFD regime as a promising approach to support SBMA patients.

  5. Apoptosis is signalled early by low doses of ionising radiation in a radiation-induced bystander effect

    Energy Technology Data Exchange (ETDEWEB)

    Furlong, Hayley, E-mail: hayley.furlong@dit.ie [DIT Centre for Radiation and Environmental Science, Focas Research Institute, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland); School of Biological Sciences, College of Sciences and Health, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland); Mothersill, Carmel [Medical Physics and Applied Radiation Sciences, Nuclear Research Building, 1280 Hamilton, Ontario L8S 4K1 (Canada); Lyng, Fiona M. [DIT Centre for Radiation and Environmental Science, Focas Research Institute, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland); Howe, Orla [DIT Centre for Radiation and Environmental Science, Focas Research Institute, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland); School of Biological Sciences, College of Sciences and Health, Dublin Institute of Technology, Kevin St, Dublin 8 (Ireland)

    2013-01-15

    Highlights: ► Molecular mechanisms involved in the production of a radiation induced bystander effect are not well known. ► We investigate gene expression changes in apoptotic genes in both direct and bystander responses. ► We demonstrate initiation of the apoptotic cascade in a bystander response. ► Lower doses reveal a specific but differential response related to apoptosis compared to higher doses. - Abstract: It is known that ionising radiation (IR) induces a complex signalling apoptotic cascade post-exposure to low doses ultimately to remove damaged cells from a population, specifically via the intrinsic pathway. Therefore, it was hypothesised that bystander reporter cells may initiate a similar apoptotic response if exposed to low doses of IR (0.05 Gy and 0.5 Gy) and compared to directly irradiated cells. Key apoptotic genes were selected according to their role in the apoptotic cascade; tumour suppressor gene TP53, pro-apoptotic Bax and anti-apoptotic Bcl2, pro-apoptotic JNK and anti-apoptotic ERK, initiator caspase 2 and 9 and effector caspase 3, 6 and 7. The data generated consolidated the role of apoptosis following direct IR exposure for all doses and time points as pro-apoptotic genes such as Bax and JNK as well as initiator caspase 7 and effector caspase 3 and 9 were up-regulated. However, the gene expression profile for the bystander response was quite different and more complex in comparison to the direct response. The 0.05 Gy dose point had a more significant apoptosis gene expression profile compared to the 0.5 Gy dose point and genes were not always expressed within 1 h but were sometimes expressed 24 h later. The bystander data clearly demonstrates initiation of the apoptotic cascade by the up-regulation of TP53, Bax, Bcl-2, initiator caspase 2 and effector caspase 6. The effector caspases 3 and 7 of the bystander samples demonstrated down-regulation in their gene expression levels at 0.05 Gy and 0.5 Gy at both time points therefore not

  6. Deconvolving the lightning sferic VLF source waveform from its temporally-superposed ionospheric reflections

    Science.gov (United States)

    Jacobson, A. R.; Holzworth, R. H.; Shao, X.

    2010-12-01

    Powerful sferic signals can be used for ionospheric sounding. We have recently applied sferics from Narrow Bipolar Events (NBEs) to studying the ionospheric D-regions’ electron-density profile. The NBE sferic’s narrow temporal support allows the ionospheric reflection signal to be easily separated from the source sferic waveform, at least for ranges up to several-hundred km. Both NBEs and cloud-to-ground (CG) sferics are sufficiently powerful for practical use in ionospheric sounding of this sort. Unfortunately, the incidence of NBEs is small compared to CGs (perhaps on the order of 1:100). The Duke University group has benefited from use of CG sferics in D-region monitoring. The Duke approach does not require separation of the “source” waveform from the ionospheric reflections. By contrast, our approach relies on separating these two signal components. CG sferics observed at ranges up to several-hundred km present their own challenge. The CG source waveform is quite long compared to NBEs. Thus much of the CG source waveform is confounded by partial temporal overlap of signals reflected from the ionospheric D-region. This is especially true at night, when D-region attenuation is minimal, causing the strongest reflection amplitudes. How then can we separate the source waveform from the confounding ionospheric reflections? We will present a formal solution to this problem, based on using simultaneous sferic recordings at two or more sensor stations. The approach will be illustrated with CG recordings from multiple stations of the Los Alamos Sferic Array. Potentially the method will allow copious CG recordings to be exploited for D-region sounding as well as for gaining better “ground truth” on the CG source function.

  7. Signaling aggression.

    Science.gov (United States)

    van Staaden, Moira J; Searcy, William A; Hanlon, Roger T

    2011-01-01

    From psychological and sociological standpoints, aggression is regarded as intentional behavior aimed at inflicting pain and manifested by hostility and attacking behaviors. In contrast, biologists define aggression as behavior associated with attack or escalation toward attack, omitting any stipulation about intentions and goals. Certain animal signals are strongly associated with escalation toward attack and have the same function as physical attack in intimidating opponents and winning contests, and ethologists therefore consider them an integral part of aggressive behavior. Aggressive signals have been molded by evolution to make them ever more effective in mediating interactions between the contestants. Early theoretical analyses of aggressive signaling suggested that signals could never be honest about fighting ability or aggressive intentions because weak individuals would exaggerate such signals whenever they were effective in influencing the behavior of opponents. More recent game theory models, however, demonstrate that given the right costs and constraints, aggressive signals are both reliable about strength and intentions and effective in influencing contest outcomes. Here, we review the role of signaling in lieu of physical violence, considering threat displays from an ethological perspective as an adaptive outcome of evolutionary selection pressures. Fighting prowess is conveyed by performance signals whose production is constrained by physical ability and thus limited to just some individuals, whereas aggressive intent is encoded in strategic signals that all signalers are able to produce. We illustrate recent advances in the study of aggressive signaling with case studies of charismatic taxa that employ a range of sensory modalities, viz. visual and chemical signaling in cephalopod behavior, and indicators of aggressive intent in the territorial calls of songbirds.

  8. VLF/LF EM emissions as main precursor of earthquakes and their searching possibilities for Georgian s/a region

    Science.gov (United States)

    Kachakhidze, Manana; Kachakhidze, Nino

    2016-04-01

    Authors of abstract have created work which offers model of earth electromagnetic emissions generation detected in the process of earthquake preparation on the basis of electrodynamics. The model gives qualitative explanation of a mechanism of generation of electromagnetic waves emitted in the earthquake preparation period. Besides, scheme of the methodology of earthquake forecasting is created based on avalanche-like unstable model of fault formation and an analogous model of electromagnetic contour, synthesis of which, is rather harmonious. According to the authors of the work electromagnetic emissions in radiodiapason is more universal and reliable than other anomalous variations of various geophysical phenomena in earthquake preparation period; Besides, VLF/LF electromagnetic emissions might be declared as the main precursor of earthquake because it might turn out very useful with the view of prediction of large (M ≥5) inland earthquakes and to govern processes going on in lithosphere-atmosphere - ionosphere coupling (LAIC) system. Since the other geophysical phenomena, which may accompany earthquake preparation process and expose themselves several months, weeks or days prior to earthquakes are less informative with the view of earthquake forecasting, it is admissible to consider them as earthquake indicators. Physical mechanisms of mentioned phenomena are explained on the basis of the model of generation of electromagnetic emissions detected before earthquake, where a process of earthquake preparation and its realization are considered taking into account distributed and conservative systems properties. Up to these days electromagnetic emissions detection network did not exist in Georgia. European colleagues helped us (Prof. Dr. PF Biagi, Prof. Dr. Aydın BÜYÜKSARAÇ) and made possible the installation of a receiver. We are going to develop network and put our share in searching of earthquakes problem. Participation in conference is supported by financial

  9. Regional early and progressive loss of brain pericytes but not vascular smooth muscle cells in adult mice with disrupted platelet-derived growth factor receptor-β signaling

    Science.gov (United States)

    Nikolakopoulou, Angeliki Maria; Zhao, Zhen; Montagne, Axel

    2017-01-01

    Pericytes regulate key neurovascular functions of the brain. Studies in pericyte-deficient transgenic mice with aberrant signaling between endothelial-derived platelet-derived growth factor BB (PDGF-BB) and platelet-derived growth factor receptor β (PDGFRβ) in pericytes have contributed to better understanding of the role of pericytes in the brain. Here, we studied PdgfrβF7/F7 mice, which carry seven point mutations that disrupt PDGFRβ signaling causing loss of pericytes and vascular smooth muscle cells (VSMCs) in the developing brain. We asked whether these mice have a stable or progressive vascular phenotype after birth, and whether both pericyte and VSMCs populations are affected in the adult brain. We found an early and progressive region-dependent loss of brain pericytes, microvascular reductions and blood-brain barrier (BBB) breakdown, which were more pronounced in the cortex, hippocampus and striatum than in the thalamus, whereas VSMCs population remained unaffected at the time when pericyte loss was already established. For example, compared to age-matched controls, PdgfrβF7/F7 mice between 4–6 and 36–48 weeks of age developed a region-dependent loss in pericyte coverage (22–46, 24–44 and 4–31%) and cell numbers (36–49, 34–64 and 11–36%), reduction in capillary length (20–39, 13–46 and 1–30%), and an increase in extravascular fibrinogen-derived deposits (3.4–5.2, 2.8–4.1 and 0–3.6-fold) demonstrating BBB breakdown in the cortex, hippocampus and thalamus, respectively. Capillary reductions and BBB breakdown correlated with loss of pericyte coverage. Our data suggest that PdgfrβF7/F7 mice develop an aggressive and rapid vascular phenotype without appreciable early involvement of VSMCs, therefore providing a valuable model to study regional effects of pericyte loss on brain vascular and neuronal functions. This model could be a useful tool for future studies directed at understanding the role of pericytes in the pathogenesis

  10. Huntington disease iPSCs show early molecular changes in intracellular signaling, the expression of oxidative stress proteins and the p53 pathway.

    Science.gov (United States)

    Szlachcic, Wojciech J; Switonski, Pawel M; Krzyzosiak, Wlodzimierz J; Figlerowicz, Marek; Figiel, Maciej

    2015-09-01

    Huntington disease (HD) is a brain disorder characterized by the late onset of motor and cognitive symptoms, even though the neurons in the brain begin to suffer dysfunction and degeneration long before symptoms appear. There is currently no cure. Several molecular and developmental effects of HD have been identified using neural stem cells (NSCs) and differentiated cells, such as neurons and astrocytes. Still, little is known regarding the molecular pathogenesis of HD in pluripotent cells, such as embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Therefore, we examined putative signaling pathways and processes involved in HD pathogenesis in pluripotent cells. We tested naïve mouse HD YAC128 iPSCs and two types of human HD iPSC that were generated from HD and juvenile-HD patients. Surprisingly, we found that a number of changes affecting cellular processes in HD were also present in undifferentiated pluripotent HD iPSCs, including the dysregulation of the MAPK and Wnt signaling pathways and the dysregulation of the expression of genes related to oxidative stress, such as Sod1. Interestingly, a common protein interactor of the huntingtin protein and the proteins in the above pathways is p53, and the expression of p53 was dysregulated in HD YAC128 iPSCs and human HD iPSCs. In summary, our findings demonstrate that multiple molecular pathways that are characteristically dysregulated in HD are already altered in undifferentiated pluripotent cells and that the pathogenesis of HD might begin during the early stages of life.

  11. A novel missense mutation in the signal peptide of the human POMC gene: a possible additional link between early-onset type 2 diabetes and obesity.

    Science.gov (United States)

    Mencarelli, Monica; Zulian, Alessandra; Cancello, Raffaella; Alberti, Luisella; Gilardini, Luisa; Di Blasio, Anna Maria; Invitti, Cecilia

    2012-12-01

    Rare mutations in several genes have a critical role in the control of homeostatic mechanisms such as food-intake, energy balance and glucose metabolism. In this study, we performed a mutational screening in a 58-year-old woman presenting early-onset type 2 diabetes and central obesity. The entire coding regions of MC4R, MC3R, HNF1A, GCK and POMC (pro-opiomelanocortin) genes were analyzed by direct sequencing. A new missense mutation was identified within the POMC gene signal peptide sequence, resulting in a heterozygous substitution of an arginine for a glycine at codon 15 (p.A15G) that was excluded in 300 healthy normal weight controls. The mutation segregated in the family and was associated with overweight, type 2 diabetes, hypertension and coronary heart disease in the carriers. Functional studies demonstrated that POMC protein was not detectable in β-TC3 cells transfected with A15G-POMC vector as well as in their culture media, despite POMC mRNA levels were comparable for amount and stability to those of wild-type-transfected cells. In silico RNA folding prediction indicated that the mutation gives rise to a different RNA secondary structure, suggesting that it might affect translation and protein synthesis. To the best of our knowledge, this is the first report addressing the functional consequences of a mutation in the signal peptide of POMC. These findings further support the hypothesis that POMC-derived peptides might have a role in the control of peripheral glucose metabolism and suggest that disruption of central POMC secretion might represent an additional link between type 2 diabetes and obesity.

  12. A key role for early growth response-1 and nuclear factor-kappaB in mediating and maintaining GRO/CXCR2 proliferative signaling in esophageal cancer.

    Science.gov (United States)

    Wang, Bo; Khachigian, Levon M; Esau, Luke; Birrer, Michael J; Zhao, Xiaohang; Parker, M Iqbal; Hendricks, Denver T

    2009-05-01

    Although early growth response-1 (EGR-1) has been shown as a key transcription factor in controlling cell growth, proliferation, differentiation, and angiogenesis, its role in the development of esophageal cancer is poorly understood despite the high frequency of this disease in many parts of the world. Here, immunohistochemistry showed that EGR-1 is overexpressed in 80% of esophageal tumor tissues examined. Furthermore, EGR-1 is constitutively expressed in all esophageal cancer cell lines analyzed. Esophageal squamous carcinoma WHCO1 cells stably transfected with EGR-1 short hairpin RNA displayed a 55% reduction in EGR-1 protein levels, 50% reduction in cell proliferation, a 50% reduction in cyclin-dependent kinase 4 levels, and a 2-fold induction in p27(Kip1) levels associated with a G(2)-M cell cycle arrest. EGR-1 knockdown also caused a marked induction in IkappaBalpha expression, an effect also observed in GRObeta RNA interference-expressing WHCO1 cells, because EGR-1 lies downstream of GRO/CXCR2 signaling. Furthermore, p65 mRNA levels were also reduced in cells treated with either short hairpin RNA EGR-1 or small interfering RNA EGR-1. Immunohistochemical analysis indicated that p65 is elevated in 78% (n = 61) of esophageal tumor sections analyzed. Moreover, nuclear factor-kappaB inhibition with either sodium salicylate or p65 RNA interference led to a significant reduction in GROalpha and GRObeta expression. These results indicate that EGR-1 and nuclear factor-kappaB mediate GRO/CXCR2 proliferative signaling in esophageal cancer and may represent potential target molecules for therapeutic intervention.

  13. VGF (TLQP-62)-induced neurogenesis targets early phase neural progenitor cells in the adult hippocampus and requires glutamate and BDNF signaling.

    Science.gov (United States)

    Thakker-Varia, Smita; Behnke, Joseph; Doobin, David; Dalal, Vidhi; Thakkar, Keya; Khadim, Farah; Wilson, Elizabeth; Palmieri, Alicia; Antila, Hanna; Rantamaki, Tomi; Alder, Janet

    2014-05-01

    The neuropeptide VGF (non-acronymic), which has antidepressant-like effects, enhances adult hippocampal neurogenesis as well as synaptic activity and plasticity in the hippocampus, however the interaction between these processes and the mechanism underlying this regulation remain unclear. In this study, we demonstrate that VGF-derived peptide TLQP-62 specifically enhances the generation of early progenitor cells in nestin-GFP mice. Specifically, TLQP-62 significantly increases the number of Type 2a neural progenitor cells (NPCs) while reducing the number of more differentiated Type 3 cells. The effect of TLQP-62 on proliferation rather than differentiation was confirmed using NPCs in vitro; TLQP-62 but not scrambled peptide PEHN-62 increases proliferation in a cell line as well as in primary progenitors from adult hippocampus. Moreover, TLQP-62 but not scrambled peptide increases Cyclin D mRNA expression. The proliferation of NPCs induced by TLQP-62 requires synaptic activity, in particular through NMDA and metabotropic glutamate receptors. The activation of glutamate receptors by TLQP-62 activation induces phosphorylation of CaMKII through NMDA receptors and protein kinase D through metabotropic glutamate receptor 5 (mGluR5). Furthermore, pharmacological antagonists to CaMKII and PKD inhibit TLQP-62-induced proliferation of NPCs indicating that these signaling molecules downstream of glutamate receptors are essential for the actions of TLQP-62 on neurogenesis. We also show that TLQP-62 gradually activates Brain-Derived Neurotrophic Factor (BDNF)-receptor TrkB in vitro and that Trk signaling is required for TLQP-62-induced proliferation of NPCs. Understanding the precise molecular mechanism of how TLQP-62 influences neurogenesis may reveal mechanisms by which VGF-derived peptides act as antidepressant-like agents.

  14. EPO improves the proliferation and inhibits apoptosis of trophoblast and decidual stromal cells through activating STAT-5 and inactivating p38 signal in human early pregnancy.

    Science.gov (United States)

    Ji, Yu Qing; Zhang, Yu Quan; Li, Ming Qing; Du, Mei Rong; Wei, Wei Wei; Li, Da Jin

    2011-01-01

    The erythropoietin (EPO) belongs to the family of angiogenic factors, which is regulated by Hypoxia-inducible factor- 1α (HIF-1α). As known, EPO are expressed in human villi and decidua, but the function is not clear. In this study, we investigated the expression and roles of HIF-1α, EPO and its receptor (EPOR) in the biological functions of trophoblast and decidual stromal cell (DSC) in human early pregnancy. The expression of EPO, EPOR and HIF-1α was evaluated in the villi and deciduas by RT-PCR and immunohistochemistry. Thereafter, we silenced HIF-1α expression in HTR-8/SVneo cell line and decidual stromal cells (DSCs). The effects of EPO on the proliferation and apoptosis of trophoblasts and DSCs, and activation of signal molecules were investigated by BrdU proliferation assay, flow cytometry and western blot, respectively. We have observed that the HIF-1α silence results in the lower expression of EPO in trophoblasts and DSCs. The anti-EPO neutralizing antibody can inactivate the phosphorylation of STAT5 and activate p38 of these cells in a dosage-dependent manner. Furthermore, the expressions of EPO, EPOR and HIF-1α in the villi and decidua from the unexplained miscarriage were significantly lower than that of the normal early pregnancy. This study suggests that HIF-1α may regulate the expression of EPO, which plays a favorable regulatory role in the proliferation and survival of human first-trimester trophoblast cells and DSCs via inactivating p38 and activating STAT5 in an autocrine manner, while the inadequate EPO expression at maternal-fetal interface may lead to pregnancy wastage in humans.

  15. Clathrin assembly protein CALM plays a critical role in KIT signaling by regulating its cellular transport from early to late endosomes in hematopoietic cells.

    Directory of Open Access Journals (Sweden)

    Shinya Rai

    Full Text Available CALM is implicated in the formation of clathrin-coated vesicles, which mediate endocytosis and intracellular trafficking of growth factor receptors and nutrients. We previously found that CALM-deficient mice suffer from severe anemia due to the impaired clathrin-mediated endocytosis of transferrin receptor in immature erythroblast. However, CALM has been supposed to regulate the growth and survival of hematopoietic stem/progenitor cells. So, in this study, we focused on the function of CALM in these cells. We here show that the number of Linage-Sca-1+KIT+ (LSK cells decreased in the fetal liver of CALM-/- mice. Also, colony forming activity was impaired in CALM-/- LSK cells. In addition, SCF, FLT3, and TPO-dependent growth was severely impaired in CALM-/- LSK cells, while they can normally proliferate in response to IL-3 and IL-6. We also examined the intracellular trafficking of KIT using CALM-/- murine embryonic fibroblasts (MEFs engineered to express KIT. At first, we confirmed that endocytosis of SCF-bound KIT was not impaired in CALM-/- MEFs by the internalization assay. However, SCF-induced KIT trafficking from early to late endosome was severely impaired in CALM-/- MEFs. As a result, although intracellular KIT disappeared 30 min after SCF stimulation in wild-type (WT MEFs, it was retained in CALM-/- MEFs. Furthermore, SCF-induced phosphorylation of cytosolic KIT was enhanced and prolonged in CALM-/- MEFs compared with that in WT MEFs, leading to the excessive activation of Akt. Similar hyperactivation of Akt was observed in CALM-/- KIT+ cells. These results indicate that CALM is essential for the intracellular trafficking of KIT and its normal functions. Also, our data demonstrate that KIT located in the early endosome can activate downstream molecules as a signaling endosome. Because KIT activation is involved in the pathogenesis of some malignancies, the manipulation of CALM function would be an attractive therapeutic strategy.

  16. Observation of Magnetic Signals from Earthquake Faulting Using High-resolution HTS-SQUID Magnetometer: Feasibility of Super-early Warning of Earthquakes

    Science.gov (United States)

    Katori, Y.; Okubo, K.; Hato, T.; Tsukamoto, A.; Tanabe, K.; Onishi, N.; Furukawa, H.; Isogami, S.; Takeuchi, N.

    2015-12-01

    Electromagnetic changes associated with earthquakes have been investigated previously. Our research group has also employed the magnetometers for seismomagnetic observations since March 2004. Our observation site happened to be situated at an epicentral distance of 26 km from the 2008 Iwate-Miyagi Nairiku earthquake ofM7.2, NE Japan. In this earthquake, we have reported successful observation of "co-faulting" Earth's magnetic field changes (Okubo et al., 2011 EPSL). Magnetic fields began to change almost simultaneously with the onset of the earthquake rupture and grew before the first P wave arrival. Such magnetic signals are most probably generated by the changing stress field due to earthquake rupturing, i.e. the piezomagnetic effect. On the other hand, this observation result suggested that the geomagnetic variation signal accompanying fault movement, whose sources are the piezomagnetic effects, is very small. The observed change of geomagnetic field might be approximately less than several hundred pico-tesla. Therefore, to obtain more observation data of "co-faulting" magnetic field change, development of a higher-sensitive magnetometer system is very important. Then, our research group tried to develop the HTS-SQUID (high-temperature-superconductor based superconducting-quantum-interference-device) magnetometer systems for high-resolution observation of Earth's magnetic field. Since March 2012 we have introduced long-term precise geomagnetic observations using the HTS-SQUID magnetometer system Unit No.1 (mark I) at Iwaki observation site (IWK) in Fukushima, Japan. Additionally, since October 2014, we have also introduced the new HTS- SQUID magnetometer system Unit No.2 (mark II). The sampling interval of the magnetometers is 0.02 sec (50Hz). The system clock has been synchronized by use of GPS signals. A high-resolution accelerometer is also installed at observation point. In this study, we show the observation results of geomagnetic field changes associated

  17. Melatonin Attenuates Early Brain Injury via the Melatonin Receptor/Sirt1/NF-κB Signaling Pathway Following Subarachnoid Hemorrhage in Mice.

    Science.gov (United States)

    Zhao, Lei; Liu, Haixiao; Yue, Liang; Zhang, Jingbo; Li, Xia; Wang, Bodong; Lin, Yan; Qu, Yan

    2017-04-01

    Melatonin (Mel) has been reported to alleviate early brain injury (EBI) following subarachnoid hemorrhage (SAH). The activation of silent information regulator 1 (Sirt1), a histone deacetylase, has been suggested to be beneficial in SAH. However, the precise role of Sirt1 in Mel-mediated protection against EBI following SAH has not been elucidated. The present study aims to evaluate the role of melatonin receptor/Sirt1/nuclear factor-kappa B (NF-κB) in this process. The endovascular perforation SAH model was used in male C57BL/6J mice, and melatonin was administrated intraperitoneally (150 mg/kg). The mortality, SAH grade, neurological score, brain water content, and neuronal apoptosis were evaluated. The expression of Sirt1, acetylated-NF-κB (Ac-NF-κB), Bcl-2, and Bax were detected by western blot. To study the underlying mechanisms, melatonin receptor (MR) antagonist luzindole and Sirt1 small interfering RNA (siRNA) were administrated to different groups. The results suggest that Mel improved the neurological deficits and reduced the brain water content and neuronal apoptosis. In addition, Mel enhanced the expression of Sirt1 and Bcl-2 and decreased the expression of Ac-NF-κB and Bax. However, the protective effects of Mel were abolished by luzindole or Sirt1 siRNA. In conclusion, our results demonstrate that Mel attenuates EBI following SAH via the MR/Sirt1/NF-κB signaling pathway.

  18. Estimating the regional climate signal in a late Pleistocene and early Holocene lake-sediment δ18O record from Vermont, USA.

    Science.gov (United States)

    Mandl, Maximilian Benedict; Shuman, Bryan Nolan; Marsicek, Jeremiah; Grigg, Laurie

    2016-07-01

    We present a new oxygen isotope (δ18O) record from carbonate-rich lake sediments from central Vermont. The record from Twin Ponds spans from 13.5 cal ka BP (1950 AD) to present, but contains a 6 ka long hiatus starting shortly after 7.5 cal ka BP. We compare the record for ca. 13.5-7.5 cal ka BP with published δ18O data from the region after using a Bayesian approach to produce many possible chronologies for each site. Principal component analysis then identified chronologically-robust, multi-site oxygen isotope signals, including negative values during the Younger Dryas, but no significant deviations from the early Holocene mean of the regional records. However, differences among sites indicate significant trends that likely relate to interacting changes in the regional gradients of seasonal temperatures and precipitation as well as moisture sources, moisture pathways, and aridity that were controlled by large-scale climatic controls such as insolation, the progressive decline of the Laurentide Ice Sheet, and changes in oceanic circulation. Centennial shifts punctuate these trends at ca. 9.3 and 8.2 cal ka BP, and reveal that the local character of these short-lived features requires a detailed understanding of lake hydrology and regional isotopic gradients to yield reliable information for regional climate reconstructions.

  19. Investigating the source of contaminated plumes downstream of the Alborz Sharghi coal washing plant using EM34 conductivity data, VLF-EM and DC-resistivity geophysical methods

    Science.gov (United States)

    Shiraz, Farzin Amirkhani; Ardejani, Faramarz Doulati; Moradzadeh, Ali; Arab-Amiri, Ali Reza

    2013-01-01

    Coal washing factories may create serious environmental problems due to pyrite oxidation and acid mine drainage generation from coal waste piles on nearby land. Infiltration of pyrite oxidation products through the porous materials of the coal waste pile by rainwater cause changes in the conductivity of underground materials and groundwater downstream of the pile. Electromagnetic and electrical methods are effective for investigation and monitoring of the contaminated plumes caused by coal waste piles and tailings impoundments. In order to investigate the environmental impact from a coal waste pile at the Alborz Sharghi coal washing plant, an EM34 ground conductivity meter was used on seven parallel lines in an E-W direction, downstream of the waste pile. Two-dimensional resistivity models obtained by the inversion of EM34 conductivity data identified conductive leachate plumes. In addition, quasi-3D inversion of EM34 data has confirmed the decreasing resistivity at depth due to the contaminated plumes. Comparison between EM34, VLF and DC-resistivity datasets, which were acquired for similar survey lines, agree well in identifying changes in the resistivity trend. The EM34 and DC-resistivity sections have greater similarity and better smoothness rather than those of the VLF model. Two-dimensional inversion models of these methods have shown some contaminated plumes with low resistivity.

  20. Source locations for impulsive electric signals seen in the night ionosphere of Venus

    Science.gov (United States)

    Russell, C. T.; Von Dornum, M.; Scarf, F. L.

    1989-01-01

    A mapping of the rate of occurrence of impulsive VLF noise bursts in Venus' dark low altitude ionosphere, which increases rapidly with decreasing altitude, as a function of latitude and longitude indicates enhanced occurrence rates over Atla. In a 30-sec observing period, there are impulsive signals 70 percent of the time at 160 km in the region of maximum occurrence; the occurrence rates, moreover, increase with decreasing latitude, so that the equatorial rate is of the order of 1.6 times that at 30 deg latitude. These phenomena are in keeping with lightning-generated wave sources.

  1. Measurement of electromagnetic waves in ELF and VLF bands to monitor lightning activity in the Maritime Continent

    Science.gov (United States)

    Yamashita, Kozo; Takahashi, Yukihiro; Ohya, Hiroyo; Tsuchiya, Fuminori; Sato, Mitsuteru; Matsumoto, Jun

    2013-04-01

    Data of lightning discharge has been focused on as an effective way for monitoring and nowcasting of thunderstorm activity which causes extreme weather. Spatial distribution of lightning discharge has been used as a proxy of the presence or absence of deep convection. Latest observation shows that there is extremely huge lightning whose scale is more than hundreds times bigger than that of averaged event. This result indicates that lightning observation should be carried out to estimate not only existence but also scale for quantitative evaluation of atmospheric convection. In this study, lightning observation network in the Maritime Continent is introduced. This network is consisted of the sensors which make possible to measure electromagnetic wave radiated from lightning discharges. Observation frequency is 0.1 - 40 kHz for the measurement of magnetic field and 1 - 40 kHz for that of electric field. Sampling frequency is 100 kHz. Waveform of electromagnetic wave is recorded by personal computer. We have already constructed observation stations at Tainan in Taiwan (23.1N, 121.1E), Saraburi in Thailand (14.5N, 101.0E), and Pontianak in Indonesia (0.0N, 109.4E). Furthermore, we plan to install the monitoring system at Los Banos in Philippines (14.18, 121.25E) and Hanoi in Viet Nam. Data obtained by multipoint observation is synchronized by GPS receiver installed at each station. By using data obtained by this network, location and scale of lightning discharge can be estimated. Location of lightning is determined based on time of arrival method. Accuracy of geolocation could be less than 10km. Furthermore, charge moment is evaluated as a scale of each lightning discharge. It is calculated from electromagnetic waveform in ELF range (3-30 kHz). At the presentation, we will show the initial result about geolocation for source of electromagnetic wave and derivation of charge moment value based on the measurement of ELF and VLF sferics.

  2. Human Cytomegalovirus Immediate-Early 1 Protein Rewires Upstream STAT3 to Downstream STAT1 Signaling Switching an IL6-Type to an IFNγ-Like Response.

    Directory of Open Access Journals (Sweden)

    Thomas Harwardt

    2016-07-01

    Full Text Available The human cytomegalovirus (hCMV major immediate-early 1 protein (IE1 is best known for activating transcription to facilitate viral replication. Here we present transcriptome data indicating that IE1 is as significant a repressor as it is an activator of host gene expression. Human cells induced to express IE1 exhibit global repression of IL6- and oncostatin M-responsive STAT3 target genes. This repression is followed by STAT1 phosphorylation and activation of STAT1 target genes normally induced by IFNγ. The observed repression and subsequent activation are both mediated through the same region (amino acids 410 to 445 in the C-terminal domain of IE1, and this region serves as a binding site for STAT3. Depletion of STAT3 phenocopies the STAT1-dependent IFNγ-like response to IE1. In contrast, depletion of the IL6 receptor (IL6ST or the STAT kinase JAK1 prevents this response. Accordingly, treatment with IL6 leads to prolonged STAT1 instead of STAT3 activation in wild-type IE1 expressing cells, but not in cells expressing a mutant protein (IE1dl410-420 deficient for STAT3 binding. A very similar STAT1-directed response to IL6 is also present in cells infected with a wild-type or revertant hCMV, but not an IE1dl410-420 mutant virus, and this response results in restricted viral replication. We conclude that IE1 is sufficient and necessary to rewire upstream IL6-type to downstream IFNγ-like signaling, two pathways linked to opposing actions, resulting in repressed STAT3- and activated STAT1-responsive genes. These findings relate transcriptional repressor and activator functions of IE1 and suggest unexpected outcomes relevant to viral pathogenesis in response to cytokines or growth factors that signal through the IL6ST-JAK1-STAT3 axis in hCMV-infected cells. Our results also reveal that IE1, a protein considered to be a key activator of the hCMV productive cycle, has an unanticipated role in tempering viral replication.

  3. Ethyl Pyruvate Attenuates Early Brain Injury Following Subarachnoid Hemorrhage in the Endovascular Perforation Rabbit Model Possibly Via Anti-inflammation and Inhibition of JNK Signaling Pathway.

    Science.gov (United States)

    Lv, Tao; Miao, Yi-Feng; Jin, Yi-Chao; Yang, Shao-Feng; Wu, Hui; Dai, Jiong; Zhang, Xiao-Hua

    2017-02-25

    Early brain injury (EBI) following subarachnoid hemorrhage (SAH) is the main cause to poor outcomes of SAH patients, and early inflammation plays an important role in the acute pathophysiological events. It has been demonstrated that ethyl pyruvate (EP) has anti-inflammatory and neuroprotective effects in various critical diseases, however, the role of EP on EBI following SAH remains to be elucidated. Our study aimed to evaluate the effects of EP on EBI following SAH in the endovascular perforation rabbit model. All rabbits were randomly divided into three groups: sham, SAH + Vehicle (equal volume) and SAH + EP (30 mg/kg/day). MRI was performed to estimate the reliability of the EBI at 24 and 72 h after SAH. Neurological scores were recorded to evaluate the neurological deficit, ELISA kit was used to measure the level of tumor necrosis factor-α (TNF-α), and western blot was used to detect the expression of TNF-α, tJNK, pJNK, bax and bcl-2 at 24 and 72 h after SAH. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and Fluoro-jade B (FJB) staining were used to detect neuronal apoptosis and neurodegeneration respectively, meanwhile hematoxylin and eosin (H&E) staining was used to assess the degree of vasospasm. Our results demonstrated that EP alleviated brain tissue injury (characterized by diffusion weighted imaging and T2 sequence in MRI scan), and significantly improved neurological scores at 72 h after SAH. EP decreased the level of TNF-α and downregulated pJNK/tJNK and bax/bcl-2 in cerebral cortex and hippocampus effectively both at 24 and 72 h after SAH. Furthermore, EP reduced TUNEL and FJB positive cells significantly. In conclusion, the present study supported that EP afforded neuroprotective effects possibly via reducing TNF-α expression and inhibition of the JNK signaling pathway. Therefore, EP may be a potent therapeutic agent to attenuate EBI following SAH.

  4. Tamoxifen as an effective neuroprotectant against early brain injury and learning deficits induced by subarachnoid hemorrhage: possible involvement of inflammatory signaling.

    Science.gov (United States)

    Sun, Xuebo; Ji, Chengyuan; Hu, Tong; Wang, Zhong; Chen, Gang

    2013-12-28

    Tamoxifen, a selective estrogen receptor modulator, has successfully been used to treat several animal models of brain injury, but the underlying mechanisms remain unclear. This study was undertaken to evaluate the effect of tamoxifen on the toll-like receptor 4 (TLR4)- and nuclear factor-κB (NF-κB)-related inflammatory signaling pathway and secondary brain injury in rats after subarachnoid hemorrhage (SAH). Adult male Sprague-Dawley rats were divided into four groups: (1) control group (n = 28); (2) SAH group (n = 28); (3) SAH + vehicle group (n = 28); and (4) SAH + tamoxifen group (n = 28). All SAH animals were subjected to injection of autologous blood into the prechiasmatic cistern once on day 0. In SAH + tamoxifen group, tamoxifen was administered intraperitoneally at a dose of 5 mg/kg at 2 h, 12 h, and 36 h after SAH. In the first set of experiments, brain samples were extracted and evaluated at 48 h after SAH. In the second set of experiments, the Morris water maze was used to investigate cognitive and memory changes. We found that treatment with tamoxifen markedly inhibited the protein expressions of TLR4, NF-κB and the downstream inflammatory agents, such as interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and intercellular adhesion molecule-1 (ICAM-1). Administration of tamoxifen following SAH significantly ameliorated the early brain injury (EBI), such as brain edema, blood-brain barrier (BBB) impairment, and clinical behavior scale. Learning deficits induced by SAH were markedly alleviated after tamoxifen treatment. Post-SAH tamoxifen administration may attenuate TLR4/NF-kappaB-mediated inflammatory response in the rat brain and result in abatement of the development of EBI and cognitive dysfunction after SAH.

  5. Early Change in FDG-PET Signal and Plasma Cell-Free DNA Level Predicts Erlotinib Response in EGFR Wild-Type NSCLC Patients

    DEFF Research Database (Denmark)

    Winther-Larsen, Anne; Fledelius, Joan; Demuth, Christina

    2016-01-01

    indicated %∆cfDNA to be the strongest predictor of OS. CONCLUSION: Early increase in TLG on F-18-FDG-PET/CT correlates with radiological progression, and shorter PFS and OS. Early increase in cfDNA predicts shorter PFS and OS. Both assessments are promising tools for early detection of nonresponders...

  6. Detection of ionospheric perturbations associated with Japanese earthquakes on the basis of reception of LF transmitter signals on the satellite DEMETER

    Directory of Open Access Journals (Sweden)

    F. Muto

    2008-02-01

    Full Text Available There have been recently reported a lot of electromagnetic phenomena associated with earthquakes (EQs. Among these, the ground-based reception of subionospheric waves from VLF/LF transmitters, is recognized as a promising tool to investigate the ionospheric perturbations associated with EQs. This paper deals with the corresponding whistler-mode signals in the upper ionosphere from those VLF/LF transmitters, which is the counterpart of subionospheric signals. The whistler-mode VLF/LF transmitter signals are detected on board the French satellite, DEMETER launched on 29 June 2004. We have chosen several large Japanese EQs including the Miyagi-oki EQ (16 August 2005; M=7.2, depth=36 km, and the target transmitter is a Japanese LF transmitter (JJY whose transmitter frequency is 40 kHz. Due to large longitudinal separation of each satellite orbit (2500 km, we have to adopt a statistical analysis over a rather long period (such as 3 weeks or one month to have reliable data set. By analyzing the spatial distribution of JJY signal intensity (in the form of signal to noise ratio SNR during a period of 4 months including the Miyagi-oki EQ, we have found significant changes in the intensity; generally the SNR is significantly depleted before the EQ, which is considered to be a precursory ionospheric signature of the EQ. This abnormal effect is reasonably explained in terms of either (1 enhanced absorption of whistler-mode LF signals in the lower ionosphere due to the lowering of the lower ionosphere, or (2 nonlinear wave-wave scattering. Finally, this analysis suggests an important role of satellite observation in the study of lithosphere-atmosphere-ionosphere coupling.

  7. Early Signaling in Primary T Cells Activated by Antigen Presenting Cells Is Associated with a Deep and Transient Lamellal Actin Network.

    Directory of Open Access Journals (Sweden)

    Kole T Roybal

    Full Text Available Cellular signaling transduction critically depends on molecular interactions that are in turn governed by dynamic subcellular distributions of the signaling system components. Comprehensive insight into signal transduction requires an understanding of such distributions and cellular structures driving them. To investigate the activation of primary murine T cells by antigen presenting cells (APC we have imaged more than 60 signaling intermediates during T cell stimulation with microscopy across resolution limits. A substantial number of signaling intermediates associated with a transient, wide, and actin-associated lamellum extending from an interdigitated T cell:APC interface several micrometers into the T cell, as characterized in detail here. By mapping the more than 60 signaling intermediates onto the spatiotemporal features of cell biological structures, the lamellum and other ones previously described, we also define distinct spatial and temporal characteristics of T cell signal initiation, amplification, and core signaling in the activation of primary T cells by APCs. These characteristics differ substantially from ones seen when T cells are activated using common reductionist approaches.

  8. Recent developments in the use of acoustic sensors and signal processing tools to target early infestations of red palm weevil (Coleopter: Curculionidae) in agricultural environments

    Science.gov (United States)

    Much of the damage caused by red palm weevil larvae to date palms, ornamental palms, and palm offshoots could be mitigated by early detection and treatment of infestations. Acoustic technology has potential to enable early detection, but the short, high-frequency sound impulses produced by red palm ...

  9. Recent developments in the use of acoustic sensors and signal processing tools to target early infestations of Red Palm Weevil in agricultural environments

    Science.gov (United States)

    Much of the damage caused by red palm weevil larvae to date palms, ornamental palms, and palm offshoots could be mitigated by early detection and treatment of infestations. Acoustic technology has potential to enable early detection, but the short, high-frequency sound impulses produced by red palm ...

  10. Neural network approach to the prediction of seismic events based on low-frequency signal monitoring of the Kuril-Kamchatka and Japanese regions

    Directory of Open Access Journals (Sweden)

    Irina Popova

    2013-08-01

    Full Text Available Very-low-frequency/ low-frequency (VLF/LF sub-ionospheric radiowave monitoring has been widely used in recent years to analyze earthquake preparatory processes. The connection between earthquakes with M ≥5.5 and nighttime disturbances of signal amplitude and phase has been established. Thus, it is possible to use nighttime anomalies of VLF/LF signals as earthquake precursors. Here, we propose a method for estimation of the VLF/LF signal sensitivity to seismic processes using a neural network approach. We apply the error back-propagation technique based on a three-level perceptron to predict a seismic event. The back-propagation technique involves two main stages to solve the problem; namely, network training, and recognition (the prediction itself. To train a neural network, we first create a so-called ‘training set’. The ‘teacher’ specifies the correspondence between the chosen input and the output data. In the present case, a representative database includes both the LF data received over three years of monitoring at the station in Petropavlovsk-Kamchatsky (2005-2007, and the seismicity parameters of the Kuril-Kamchatka and Japanese regions. At the first stage, the neural network established the relationship between the characteristic features of the LF signal (the mean and dispersion of a phase and an amplitude at nighttime for a few days before a seismic event and the corresponding level of correlation with a seismic event, or the absence of a seismic event. For the second stage, the trained neural network was applied to predict seismic events from the LF data using twelve time intervals in 2004, 2005, 2006 and 2007. The results of the prediction are discussed.

  11. Loss of Intralipid®- but not sevoflurane-mediated cardioprotection in early type-2 diabetic hearts of fructose-fed rats: importance of ROS signaling.

    Directory of Open Access Journals (Sweden)

    Phing-How Lou

    Full Text Available Insulin resistance and early type-2 diabetes are highly prevalent. However, it is unknown whether Intralipid® and sevoflurane protect the early diabetic heart against ischemia-reperfusion injury.Early type-2 diabetic hearts from Sprague-Dawley rats fed for 6 weeks with fructose were exposed to 15 min of ischemia and 30 min of reperfusion. Intralipid® (1% was administered at the onset of reperfusion. Peri-ischemic sevoflurane (2 vol.-% served as alternative protection strategy. Recovery of left ventricular function was recorded and the activation of Akt and ERK 1/2 was monitored. Mitochondrial function was assessed by high-resolution respirometry and mitochondrial ROS production was measured by Amplex Red and aconitase activity assays. Acylcarnitine tissue content was measured and concentration-response curves of complex IV inhibition by palmitoylcarnitine were obtained.Intralipid® did not exert protection in early diabetic hearts, while sevoflurane improved functional recovery. Sevoflurane protection was abolished by concomitant administration of the ROS scavenger N-2-mercaptopropionyl glycine. Sevoflurane, but not Intralipid® produced protective ROS during reperfusion, which activated Akt. Intralipid® failed to inhibit respiratory complex IV, while sevoflurane inhibited complex I. Early diabetic hearts exhibited reduced carnitine-palmitoyl-transferase-1 activity, but palmitoylcarnitine could not rescue protection and enhance postischemic functional recovery. Cardiac mitochondria from early diabetic rats exhibited an increased content of subunit IV-2 of respiratory complex IV and of uncoupling protein-3.Early type-2 diabetic hearts lose complex IV-mediated protection by Intralipid® potentially due to a switch in complex IV subunit expression and increased mitochondrial uncoupling, but are amenable to complex I-mediated sevoflurane protection.

  12. Inhibition of signaling between human CXCR4 and zebrafish ligands by the small molecule IT1t impairs the formation of triple-negative breast cancer early metastases in a zebrafish xenograft model

    Directory of Open Access Journals (Sweden)

    Claudia Tulotta

    2016-02-01

    Full Text Available Triple-negative breast cancer (TNBC is a highly aggressive and recurrent type of breast carcinoma that is associated with poor patient prognosis. Because of the limited efficacy of current treatments, new therapeutic strategies need to be developed. The CXCR4-CXCL12 chemokine signaling axis guides cell migration in physiological and pathological processes, including breast cancer metastasis. Although targeted therapies to inhibit the CXCR4-CXCL12 axis are under clinical experimentation, still no effective therapeutic approaches have been established to block CXCR4 in TNBC. To unravel the role of the CXCR4-CXCL12 axis in the formation of TNBC early metastases, we used the zebrafish xenograft model. Importantly, we demonstrate that cross-communication between the zebrafish and human ligands and receptors takes place and human tumor cells expressing CXCR4 initiate early metastatic events by sensing zebrafish cognate ligands at the metastatic site. Taking advantage of the conserved intercommunication between human tumor cells and the zebrafish host, we blocked TNBC early metastatic events by chemical and genetic inhibition of CXCR4 signaling. We used IT1t, a potent CXCR4 antagonist, and show for the first time its promising anti-tumor effects. In conclusion, we confirm the validity of the zebrafish as a xenotransplantation model and propose a pharmacological approach to target CXCR4 in TNBC.

  13. Early Change in FDG-PET Signal and Plasma Cell-Free DNA Level Predicts Erlotinib Response in EGFR Wild-Type NSCLC Patients

    Directory of Open Access Journals (Sweden)

    Anne Winther-Larsen

    2016-12-01

    Full Text Available INTRODUCTION: Epidermal growth factor receptor (EGFR tyrosine kinase inhibitors (TKIs are a treatment option in the second- or third-line palliative setting in EGFR wild-type (wt non–small cell lung cancer (NSCLC patients. However, response rates are low, and only approximately 25% will achieve disease control. Early prediction of treatment resistance could accelerate discontinuation of ineffective treatment and reduce unnecessary toxicity. In this study, we evaluated early changes on 18F-fluoro-D-glucose (F-18-FDG positron emission tomography/computed tomography (PET/CT and in total plasma cell-free DNA (cfDNA as markers of erlotinib response in EGFR-wt patients. METHODS: F-18-FDG-PET/CT scans and blood samples were obtained prior to erlotinib initiation and were repeated after 1 week (PET/CT and 1 to 4 weeks (blood sample of treatment. Level of cfDNA was measured by droplet digital polymerase chain reaction. Percentage change (%∆ in SULpeak and total lesion glycolysis (TLG on FDG-PET/CT and in plasma cfDNA was correlated to radiological response, progression-free survival (PFS, and overall survival (OS. RESULTS: Fifty patients were prospectively enrolled. A significant correlation was found between CT response and %∆TLG (P = .003. All patients with early metabolic progression showed radiological progression. Increased %∆TLG and %∆cfDNA were significantly correlated with shorter PFS (P = .002 and P = .004, respectively and OS (P = .009 and P = .009, respectively. Multivariate analysis indicated %∆cfDNA to be the strongest predictor of OS. CONCLUSION: Early increase in TLG on F-18-FDG-PET/CT correlates with radiological progression, and shorter PFS and OS. Early increase in cfDNA predicts shorter PFS and OS. Both assessments are promising tools for early detection of nonresponders and reduced OS in TKI-treated EGFR-wt NSCLC patients.

  14. 甚低频拖曳天线的稳态动力学研究%Research on the Steady Dynamic of VLF Trailing Antenna on an Aircraft

    Institute of Scientific and Technical Information of China (English)

    郑小洪; 侯志强; 韩维; 李冀鑫

    2012-01-01

    甚低频(Very low frequency,VLF)拖曳天线力学特征和控制是飞机对潜通信系统进一步深入论证需要解决的关键问题之一,而对其稳态动力学研究是进行甚低频拖曳天线力学特征和控制研究的基础.通过对载机盘旋时甚低频天线运动状态及其受力进行分析,应用牛顿定律建立机载甚低频拖曳天线稳态动力学模型.运用打靶法对其稳态动力学模型进行求解,分析载机速度、倾斜角和天线末端锥袋质量对天线末端锥袋量纲一半径和天线垂直度的影响.仿真结果表明在阻力系数较小时,在一定的倾斜角和载机飞行速度范围内其垂直度和天线末端量纲一半径存在多值情况,会导致拖曳天线系统的不稳定;在一定的阻力系数下,减小飞机速度,增加载机的倾斜角,能够提高甚低频拖曳天线的垂直度;单一增加天线末端锥袋质量来提高垂直度是不可行的.%The dynamic character and control of very low frequency(VLF) trailing antenna on a aircraft is one of most important problems which needs to research. The steady dynamic is the base of the dynamic character and control of the VLF trailing antenna. The mathematics model based Newton law of the trailing antenna is founded, and solved via a shooting technique. The influences of the angle of bank and the velocity of aircraft to the non-dismensionalization end radius and verticality are researched. The result shows that under the low drag, for certain ranges of the angle of bank and the velocity, the equilibrium solution is multi volume; under certain ranges of air drag, it is possible to descend the velocity of the aircraft and increase the bank angle to improve the verticality of the antenna. But it's impossible to increase the mass of the drogue only to improve the verticality of the antenna.

  15. A20 zinc finger protein inhibits TNF-induced apoptosis and stress response early in the signaling cascades and independently of binding to TRAF2 or 14-3-3 proteins.

    Science.gov (United States)

    Lademann, U; Kallunki, T; Jäättelä, M

    2001-03-01

    A20 zinc finger protein is a negative regulator of tumor necrosis factor (TNF)-induced signaling pathways leading to apoptosis, stress response and inflammation. A20 has been shown to bind to TNF-receptor-associated factor 2 (TRAF2) and 14-3-3 chaperone proteins. Our data indicate that the zinc finger domain of A20 is sufficient and that neither TRAF2 nor 14-3-3 binding is necessary for the inhibitory effects of A20. Mutations in the 14-3-3 binding site of A20 did, however, result in a partial cleavage of A20 protein suggesting that 14-3-3 chaperone proteins may stabilize A20. Furthermore, we show that A20 acts early in TNF-induced signaling cascades blocking both TNF-induced rapid activation of c-Jun N-terminal kinase and processing of the receptor-associated caspase-8. Taken together our data indicate that the zinc finger domain of A20 contains all necessary functional domains required for the inhibition of TNF signaling and that A20 may function at the level of the receptor signaling complex.

  16. Tgfβ2 and 3 are coexpressed with their extracellular regulator Ltbp1 in the early limb bud and modulate mesodermal outgrowth and BMP signaling in chicken embryos

    Directory of Open Access Journals (Sweden)

    Garcia-Porrero Juan A

    2010-06-01

    Full Text Available Abstract Background Transforming growth factor β proteins (Tgfβs are secreted cytokines with well-defined functions in the differentiation of the musculoskeletal system of the developing limb. Here we have studied in chicken embryos, whether these cytokines are implicated in the development of the embryonic limb bud at stages preceding tissue differentiation. Results Immunohistochemical detection of phosphorylated Smad2 and Smad3 indicates that signaling by this pathway is active in the undifferentiated mesoderm and AER. Gene expression analysis shows that transcripts of tgfβ2 and tgfβ3 but not tgfβ1 are abundant in the growing undifferentiated limb mesoderm. Transcripts of tgfβ2 are also found in the AER, which is the signaling center responsible for limb outgrowth. Furthermore, we show that Latent Tgfβ Binding protein 1 (LTBP1, which is a key extracellular modulator of Tgfβ ligand bioavailability, is coexpressed with Tgfβs in the early limb bud. Administration of exogenous Tgfβs to limb buds growing in explant cultures provides evidence of these cytokines playing a role in the regulation of mesodermal limb proliferation. In addition, analysis of gene regulation in these experiments revealed that Tgfβ signaling has no effect on the expression of master genes of musculoskeletal tissue differentiation but negatively regulates the expression of the BMP-antagonist Gremlin. Conclusion We propose the occurrence of an interplay between Tgfβ and BMP signaling functionally associated with the regulation of early limb outgrowth by modulating limb mesenchymal cell proliferation.

  17. A role for Nrf2 in redox signalling of the invasive extravillous trophoblast in severe early onset IUGR associated with preeclampsia.

    Directory of Open Access Journals (Sweden)

    Nisreen Kweider

    Full Text Available BACKGROUND: Preeclampsia (PE is characterized by increased lipid oxidation and diminished antioxidant capacity, while intrauterine growth restriction (IUGR is characterized by impaired invasion of the extravillous trophoblast. Vascular endothelial growth factor (VEGF has been reported to be altered in preeclampsia. A relationship between VEGF and nuclear factor erythroid 2-related factor-2 (Nrf2 has been shown in vitro, where VEGF prevents oxidative damage via activation of the Nrf2 pathway. In this study the expression of Nrf2, VEGF and 4-hydroxynonenal (4-HNE, was determined in interstitial and endovascular/intramural extravillous trophoblast (EVT in normal pregnancies and those complicated by severe early onset IUGR associated with preeclampsia IUGR/PE. MATERIALS AND METHODS: Full-thickness uterine tissues derived from caesarean hysterectomies performed in 5 healthy normotensive women delivering term infants and 6 women with severe early onset IUGR with preeclampsia (29-34 weeks gestation were analyzed. Interstitial and endovascular extravillous trophoblast were quantified after immunohistochemical staining of paraffin sections using antibodies against Nrf2, 4-HNE, VEGF, and cytokeratin 7. RESULTS: Uterine tissues from women suffering from severe early onset IUGR/PE were characterized by reduced invasion of extravillous trophoblast into the endometrial and myometrial segments of spiral arteries in the placental bed. Extravillous trophoblast showed an increased cytoplasmic expression of Nrf2 and 4-HNE in IUGR/PE cases. The increased expression of Nrf2 in cases of IUGR/PE was associated with decreased expression of VEGF in these cells compared to controls. CONCLUSION: Our data suggests that besides villous cytotrophoblast, also the extravillous trophoblast is a source of Nrf2-dependent genes. VEGF deficiency may cause higher oxidative stress in extravillous trophoblast in cases with IUGR/PE. The resulting reduced basal defence against oxidative

  18. Human LH and hCG stimulate differently the early signalling pathways but result in equal testosterone synthesis in mouse Leydig cells in vitro.

    Science.gov (United States)

    Riccetti, Laura; De Pascali, Francesco; Gilioli, Lisa; Potì, Francesco; Giva, Lavinia Beatrice; Marino, Marco; Tagliavini, Simonetta; Trenti, Tommaso; Fanelli, Flaminia; Mezzullo, Marco; Pagotto, Uberto; Simoni, Manuela; Casarini, Livio

    2017-01-05

    Human luteinizing hormone (LH) and chorionic gonadotropin (hCG) are glycoprotein hormones regulating development and reproductive functions by acting on the same receptor (LHCGR). We compared the LH and hCG activity in gonadal cells from male mouse in vitro, i.e. primary Leydig cells, which is a common tool used for gonadotropin bioassay. Murine Leydig cells are naturally expressing the murine LH receptor (mLhr), which binds human LH/hCG. Cultured Leydig cells were treated by increasing doses of recombinant LH and hCG, and cell signaling, gene expression and steroid synthesis were evaluated. We found that hCG is about 10-fold more potent than LH in cAMP recruitment, and slightly but significantly more potent on cAMP-dependent Erk1/2 phosphorylation. However, no significant differences occur between LH and hCG treatments, measured as activation of downstream signals, such as Creb phosphorylation, Stard1 gene expression and testosterone synthesis. These data demonstrate that the responses to human LH/hCG are only quantitatively and not qualitatively different in murine cells, at least in terms of cAMP and Erk1/2 activation, and equal in activating downstream steroidogenic events. This is at odds with what we previously described in human primary granulosa cells, where LHCGR mediates a different pattern of signaling cascades, depending on the natural ligand. This finding is relevant for gonadotropin quantification used in the official pharmacopoeia, which are based on murine, in vivo bioassay and rely on the evaluation of long-term, testosterone-dependent effects mediated by rodent receptor.

  19. Single-trial EEG-informed fMRI reveals spatial dependency of BOLD signal on early and late IC-ERP amplitudes during face recognition.

    Science.gov (United States)

    Wirsich, Jonathan; Bénar, Christian; Ranjeva, Jean-Philippe; Descoins, Médéric; Soulier, Elisabeth; Le Troter, Arnaud; Confort-Gouny, Sylviane; Liégeois-Chauvel, Catherine; Guye, Maxime

    2014-10-15

    Simultaneous EEG-fMRI has opened up new avenues for improving the spatio-temporal resolution of functional brain studies. However, this method usually suffers from poor EEG quality, especially for evoked potentials (ERPs), due to specific artifacts. As such, the use of EEG-informed fMRI analysis in the context of cognitive studies has particularly focused on optimizing narrow ERP time windows of interest, which ignores the rich diverse temporal information of the EEG signal. Here, we propose to use simultaneous EEG-fMRI to investigate the neural cascade occurring during face recognition in 14 healthy volunteers by using the successive ERP peaks recorded during the cognitive part of this process. N170, N400 and P600 peaks, commonly associated with face recognition, were successfully and reproducibly identified for each trial and each subject by using a group independent component analysis (ICA). For the first time we use this group ICA to extract several independent components (IC) corresponding to the sequence of activation and used single-trial peaks as modulation parameters in a general linear model (GLM) of fMRI data. We obtained an occipital-temporal-frontal stream of BOLD signal modulation, in accordance with the three successive IC-ERPs providing an unprecedented spatio-temporal characterization of the whole cognitive process as defined by BOLD signal modulation. By using this approach, the pattern of EEG-informed BOLD modulation provided improved characterization of the network involved than the fMRI-only analysis or the source reconstruction of the three ERPs; the latter techniques showing only two regions in common localized in the occipital lobe.

  20. Early intraplatelet signaling enhances the release of human platelet PAR-1 and -4 amino-terminal peptides in response to thrombin.

    Science.gov (United States)

    Ofosu, Frederick A; Dewar, Lori; Song, Yingqi; Cedrone, Aisha C; Hortelano, Gonzalo; Craven, Sharon J

    2009-02-24

    Activation of washed human platelets initiated with alpha-thrombin, SFLLRN, or AYPGKF invariably results in the generation of PAR-1-(1-41) and PAR-4-(1-47). PAR-1-(1-41) and PAR-4-(1-47) are amino-terminal peptides generated when PAR-1 and -4 are cleaved in their first extracellular domains after R(41) and R(47), respectively, to expose the tethered ligand domains of PAR-1 and -4. Since soybean trypsin inhibitor decreases generation of PAR-1-(1-41) and PAR-4-(1-47) and other platelet aggregation-related responses to these three agonists, but does not inactivate alpha-thrombin, a platelet trypsin-like proteinase apparently activates PAR-1 and -4 to propagate PAR-dependent platelet responses. This study identified the signaling pathways implicated in the generation of the platelet proteinase that in turn produces PAR-1-(1-41) and PAR-4-(1-47), to thereby drive the subsequent PAR-dependent platelet aggregation-related responses to alpha-thrombin, SFLLRN, or AYPGKF. Only inhibitors of signaling enzymes that prevented ATP release (forskolin, PGE(1), or BIMI-1) prevented or delayed the generation of PAR-1-(1-41) and PAR-4-(1-47) in response to all three agonists. SBTI prevented platelet aggregation initiated by alpha-thrombin, SFLLRN, or AYPGKF but did so less effectively when it was added 10 s after each agonist. Thus, the platelet-derived proteinase acts within 10 s of each agonist addition to generate PAR-1-(1-41) and PAR-4-(1-47). Furthermore, alpha-thrombin may not effectively catalyze PAR-1-(1-41) and PAR-4-(1-47) generation. We propose that unidentified ATP-dependent phosphorylation reactions catalyzed by PKC help to generate the platelet-derived proteinase that propagates human platelet PAR-1 and -4 activation by the three agonists.

  1. Modeling mechanical signals on the surface of µCT and CAD based rapid prototype scaffold models to predict (early stage) tissue development.

    Science.gov (United States)

    Hendrikson, W J; van Blitterswijk, C A; Verdonschot, N; Moroni, L; Rouwkema, J

    2014-09-01

    In the field of tissue engineering, mechano-regulation theories have been applied to help predict tissue development in tissue engineering scaffolds in the past. For this, finite element models (FEMs) were used to predict the distribution of strains within a scaffold. However, the strains reported in these studies are volumetric strains of the material or strains developed in the extracellular matrix occupying the pore space. The initial phase of cell attachment and growth on the biomaterial surface has thus far been neglected. In this study, we present a model that determines the magnitude of biomechanical signals on the biomaterial surface, enabling us to predict cell differentiation stimulus values at this initial stage. Results showed that magnitudes of the 2D strain--termed surface strain--were lower when compared to the 3D volumetric strain or the conventional octahedral shear strain as used in current mechano-regulation theories. Results of both µCT and CAD derived FEMs from the same scaffold were compared. Strain and fluid shear stress distributions, and subsequently the cell differentiation stimulus, were highly dependent on the pore shape. CAD models were not able to capture the distributions seen in the µCT FEM. The calculated mechanical stimuli could be combined with current mechanobiological models resulting in a tool to predict cell differentiation in the initial phase of tissue engineering. Although experimental data is still necessary to properly link mechanical signals to cell behavior in this specific setting, this model is an important step towards optimizing scaffold architecture and/or stimulation regimes. © 2014 Wiley Periodicals, Inc.

  2. Penetration Characteristics of VLF Wave From Atmosphere Into the Lower Ionosphere%VLF波从大气层到低电离层的传输特性分析

    Institute of Scientific and Technical Information of China (English)

    赵庶凡; 申旭辉; 潘威炎; 张学民

    2011-01-01

    Many papers have indicated that earthquake happens associated with a width frequency band of VLF (Very Low Frequency), ULF (Ultra Low Frequency), ELF (Extremely Low Frequency)electromagnetic radiation, which have been recorded by satellites in the ionosphere and low magnetosphere.In this paper, the reflection and transmission coefficient of the homogeneous half-space ionosphere has been calculated using propagation matrix method.Simultaneously the Booker quartic equation is solved to get the refractive index in the ionosphere.The analysis of the factors which influence the reflection and transmission coefficient of the ionosphere and the propagation characteristics in the ionosphere of VLF wave have been performed, such as wave frequency, incident angle, geomagnetic inclination, electron density and collision frequency in the ionosphere to provide fundamental basis for further studies on numerical calculation of propagation of ULF/VLF waves in the stratified ionosphere and support the study of seismo-ionosphere coupling mechanism.The results show that it is easier for the TE (Traverse Electric) wave radiated by vertical electric dipole to penetrate into the ionosphere, but the TM (Traverse Magnetic) wave radiated by horizontal electric dipole is reflected again and again in the ground-ionosphere waveguide.It is easier to observe the VLF wave anomaly when the electron density is lower or at the high-latitude region.The O wave experiences severer attenuation than X wave, so X wave is a penetration mode whereas O wave is a non penetration mode in the ionosphere.The attenuation of the two characteristic wave decrease as the decrease of the angle between the geomagnetic field and wave vector, that is to say the attenuation is the smallest when longitudinal propagation.When the geomagnetic field is considered, the ULF/VLF wave related with earthquake can penetrate into the ionosphere which is confirmed by the satellite observation.But the further physical mechanism will

  3. Signal Words

    Science.gov (United States)

    SIGNAL WORDS TOPIC FACT SHEET NPIC fact sheets are designed to answer questions that are commonly asked by the ... making decisions about pesticide use. What are Signal Words? Signal words are found on pesticide product labels, ...

  4. Probing geomagnetic storm-driven magnetosphere-ionosphere dynamics in D-region via propagation characteristics of very low frequency radio signals

    Science.gov (United States)

    Nwankwo, Victor U. J.; Chakrabarti, Sandip K.; Ogunmodimu, Olugbenga

    2016-07-01

    The amplitude and phase of VLF/LF radio signals are sensitive to changes in electrical conductivity of the lower ionosphere which imprints its signature on the Earth-ionosphere waveguide. This characteristic makes it useful in studying sudden ionospheric disturbances, especially those related to prompt X-ray flux output from solar flares and gamma ray bursts (GRBs). However, strong geomagnetic disturbance and storm conditions are known to produce large and global ionospheric disturbances, which can significantly affect VLF radio propagation in the D region of the ionosphere. In this paper, using the data of three propagation paths at mid-latitudes (40-54°), we analyse the trend in variation of aspects of VLF diurnal signal under varying solar and geomagnetic space environmental conditions in order to identify possible geomagnetic footprints on the D region characteristics. We found that the trend of variations generally reflected the prevailing space weather conditions in various time scales. In particular, the 'dipping' of mid-day signal amplitude peak (MDP) occurs after significant geomagnetic perturbed or storm conditions in the time scale of 1-2 days. The mean signal amplitude before sunrise (MBSR) and mean signal amplitude after sunset (MASS) also exhibit storm-induced dipping, but they appear to be influenced by event's exact occurrence time and the highly variable conditions of dusk-to-dawn ionosphere. We also observed few cases of the signals rise (e.g., MDP, MBSR or MASS) following a significant geomagnetic event. This effect may be related to storms associated phenomena or effects arising from sources other than solar origin. The magnitude of induced dipping (or rise) significantly depends on the intensity and duration of event(s), as well as the propagation path of the signal. The post-storm day signal (following a main event, with lesser or significantly reduced geomagnetic activity) exhibited a tendency of recovery to pre-storm day level. In the

  5. Cholesterol-lowering drug, in combination with chromium chloride, induces early apoptotic signals in intracellular L. donovani amastigotes, leading to death

    Indian Academy of Sciences (India)

    AMIT KUMAR VERMA; BHAKTI LAHA; MONIKA PANDEY; UTTARIYA PAL; MONIDIPA GHOSH

    2017-09-01

    Leishmania establishes a successful parasitism by evading both oxidative and non-oxidative killing pathways, and its drugresistance against the currently available therapeutics demands for a safe and cheap drug. Since the parasite synthesizesergosterol instead of cholesterol, using the same biochemical pathway and enzymes, an inhibitor of HMG-CoA-Reductase,Lovastatin, has been tried for its anti-Leishmanial effect. Lovastatin, being an inhibitor of HMG-CoA-Reductase, inhibitsinfection by cholesterol depletion, while chromium chloride complexes, at their higher concentrations, are reported toexhibit cytotoxicity. In intracellular amastigotes, cytotoxicity has been checked by assessing various manifestation of celldeath, viz. DNA fragmentation, AnnexinV-FITC binding and JC-1 fluorescence ratio. Release of hydrogen peroxide (HPO)and nitric oxide (NO) has been assessed in live cell. Lovastatin and CrCl3.6H2O in combination has appeared to beineffective on promastigotes but has induced cytotoxic effect on the intracellular amastigotes through up-regulation ofcellular signalling mechanisms. CrCl3.6H2O stimulates generation of NO, leading to reduction of the number of intracellularamastigote, while Lovastatin shows HPO-mediated killing of the same, keeping the host cell unaffected. This noveltherapeutic approach, involving two known safe compounds in suboptimal doses, may resolve human visceralLeishmaniasis.

  6. Tau-driven 26S proteasome impairment and cognitive dysfunction can be prevented early in disease by activating cAMP-PKA signaling.

    Science.gov (United States)

    Myeku, Natura; Clelland, Catherine L; Emrani, Sheina; Kukushkin, Nikolay V; Yu, Wai Haung; Goldberg, Alfred L; Duff, Karen E

    2016-01-01

    The ubiquitin proteasome system (UPS) degrades misfolded proteins including those implicated in neurodegenerative diseases. We investigated the effects of tau accumulation on proteasome function in a mouse model of tauopathy and in a cross to a UPS reporter mouse (line Ub-G76V-GFP). Accumulation of insoluble tau was associated with a decrease in the peptidase activity of brain 26S proteasomes, higher levels of ubiquitinated proteins and undegraded Ub-G76V-GFP. 26S proteasomes from mice with tauopathy were physically associated with tau and were less active in hydrolyzing ubiquitinated proteins, small peptides and ATP. 26S proteasomes from normal mice incubated with recombinant oligomers or fibrils also showed lower hydrolyzing capacity in the same assays, implicating tau as a proteotoxin. Administration of an agent that activates cAMP-protein kinase A (PKA) signaling led to attenuation of proteasome dysfunction, probably through proteasome subunit phosphorylation. In vivo, this led to lower levels of aggregated tau and improvements in cognitive performance.

  7. The LVD signals during the early-mid stages of the L'Aquila seismic sequence and the radon signature of some aftershocks of moderate magnitude.

    Science.gov (United States)

    Cigolini, C; Laiolo, M; Coppola, D

    2015-01-01

    The L'Aquila seismic swarm culminated with the mainshock of April 6, 2009 (ML = 5.9). Here, we report and analyze the Large Volume Detector (LVD, used in neutrinos research) low energy traces (∼0.8 MeV), collected during the early-mid stages of the seismic sequence, together with the data of a radon monitoring experiment. The peaks of LVD traces do not correlate with the evolution and magnitude of earthquakes, including major aftershocks. Conversely, our radon measurements obtained by utilizing three automatic stations deployed along the regional NW-SE faulting system, seem to be, in one case, more efficient. In fact, the timeseries collected on the NW-SE Paganica fracture recorded marked variations and peaks that occurred during and prior moderate aftershocks (with ML > 3). The Paganica monitoring station (PGN) seems to better responds to active seismicity due to the fact that the radon detector was placed directly within the bedrock of an active fault. It is suggested that future networks for radon monitoring of active seismicity should preferentially implement this setting.

  8. Low frequency signal spectrum analysis for strong earthquakes

    Directory of Open Access Journals (Sweden)

    Masashi Hayakawa

    2012-04-01

    Full Text Available

    We examined changes in the spectral composition of the low frequency (LF subionospheric signals from the NRK transmitter (37.5 kHz in Iceland that were received in Bari (Italy relative to the earthquake that occurred in L’Aquila on April 6, 2009. In our previous studies, we have reported the occurrence of preseismic night-time anomalies using observations from three receivers located in Bari, Graz (Austria and Moscow (Russia. The strongest anomalies in the signals were observed in the NRK-Bari propagation path during the period 5-6 days before the L’Aquila earthquake, as well as during the series of aftershocks. During this period, similar very low frequency (VLF/LF amplitude anomalies were also observed along several other propagation paths that crossed the L’Aquila seismogenic zone. Spectral analysis of the LF signals filtered in the frequency range 0.28 mHz to 15 mHz shows differences in the spectra for seismo-disturbed days when compared to those for either quiet or geomagnetically disturbed days. These spectral anomalies, which are only observed in the propagation path between NRK and Bari, contain signals with periods of about 10 min to 20 min. These periodic signals are absent both in the spectra of the undisturbed signals for the control paths, and in the spectra of the signals received during geomagnetic storms. The same changes in the spectral composition were observed in the analysis of LF (40 kHz signals from the JJY transmitter in Japan that were received in Petropavlovsk-Kamchatsky (Russia during the occurrence of three strong earthquakes with M ≥7.0. The results of this study support the theoretical prediction that the possible mechanism for energy penetration from the origin of an earthquake through the atmosphere and into the ionosphere is based on the excitation and upward propagation of internal gravity waves.

     

  9. Quantitation of signal transduction.

    Science.gov (United States)

    Krauss, S; Brand, M D

    2000-12-01

    Conventional qualitative approaches to signal transduction provide powerful ways to explore the architecture and function of signaling pathways. However, at the level of the complete system, they do not fully depict the interactions between signaling and metabolic pathways and fail to give a manageable overview of the complexity that is often a feature of cellular signal transduction. Here, we introduce a quantitative experimental approach to signal transduction that helps to overcome these difficulties. We present a quantitative analysis of signal transduction during early mitogen stimulation of lymphocytes, with steady-state respiration rate as a convenient marker of metabolic stimulation. First, by inhibiting various key signaling pathways, we measure their relative importance in regulating respiration. About 80% of the input signal is conveyed via identifiable routes: 50% through pathways sensitive to inhibitors of protein kinase C and MAP kinase and 30% through pathways sensitive to an inhibitor of calcineurin. Second, we quantify how each of these pathways differentially stimulates functional units of reactions that produce and consume a key intermediate in respiration: the mitochondrial membrane potential. Both the PKC and calcineurin routes stimulate consumption more strongly than production, whereas the unidentified signaling routes stimulate production more than consumption, leading to no change in membrane potential despite increased respiration rate. The approach allows a quantitative description of the relative importance of signal transduction pathways and the routes by which they activate a specific cellular process. It should be widely applicable.

  10. Contributions of dynamic environmental signals during life-cycle transitions to early life-history traits in lodgepole pine (Pinus contorta Dougl.)

    Science.gov (United States)

    Liu, Yang; Wang, Tongli; El-Kassaby, Yousry A.

    2016-05-01

    Environmental signals are important triggers in the life-cycle transitions and play a crucial role in the life-history evolution. Yet very little is known about the leading ecological factors contributing to the variations of life-history traits in perennial plants. This paper explores both the causes and consequences for the evolution of life-history traits (i.e., seed dormancy and size) in lodgepole pine (Pinus contorta Dougl.) across British Columbia (B.C.), Canada. We selected 83 logepole pine populations covering 22 ecosystem zones of B.C. and through their geographic coordinate, 197 climatic variables were generated accordingly for the reference (1961-1990) and future (2041-2070) periods. We found that dynamic climatic variables rather than constant geographic variables are the true environmental driving forces in seed dormancy and size variations and thus provide reliable predictors in response to global climate change. Evapotranspiration and precipitation in the plant-to-seed chronology are the most critical climate variables for seed dormancy and size variations, respectively. Hence, we predicted that levels of seed dormancy in lodgepole pine would increase across large tracts of B.C. in 2050s. Winter-chilling is able to increase the magnitude of life-history plasticity and lower the bet-hedge strategy in the seed-to-plant transition; however, winter-chilling is likely to be insufficient in the north of 49° N in 2050s, which may delay germination while unfavorable conditions during dry summers may result in adverse consequences in the survival of seedlings owing to extended germination span. These findings provide useful information to studies related to assessments of seed transfer and tree adaptation.

  11. Fisetin alleviates early brain injury following experimental subarachnoid hemorrhage in rats possibly by suppressing TLR 4/NF-κB signaling pathway.

    Science.gov (United States)

    Zhou, Chen-hui; Wang, Chun-xi; Xie, Guang-bin; Wu, Ling-yun; Wei, Yong-xiang; Wang, Qiang; Zhang, Hua-sheng; Hang, Chun-hua; Zhou, Meng-liang; Shi, Ji-xin

    2015-12-10

    Early brain injury (EBI) determines the unfavorable outcomes after subarachnoid hemorrhage (SAH). Fisetin, a natural flavonoid, has anti-inflammatory and neuroprotection properties in several brain injury models, but the role of fisetin on EBI following SAH remains unknown. Our study aimed to explore the effects of fisetin on EBI after SAH in rats. Adult male Sprague-Dawley rats were randomly divided into the sham and SAH groups, fisetin (25mg/kg or 50mg/kg) or equal volume of vehicle was given at 30min after SAH. Neurological scores and brain edema were assayed. The protein expression of toll-like receptor 4 (TLR 4), p65, ZO-1 and bcl-2 was examined by Western blot. TLR 4 and p65 were also assessed by immunohistochemistry (IHC). Enzyme-linked immunosorbent assay (ELISA) was performed to detect the production of pro-inflammatory cytokines. Terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) was perform to assess neural cell apoptosis. High-dose (50mg/kg) fisetin significantly improved neurological function and reduced brain edema at both 24h and 72h after SAH. Remarkable reductions of TLR 4 expression and nuclear factor κB (NF-κB) translocation to nucleus were detected after fisetin treatment. In addition, fisetin significantly reduced the productions of pro-inflammatory cytokines, decreased neural cell apoptosis and increased the protein expression of ZO-1 and bcl-2. Our data provides the evidence for the first time that fisetin plays a protective role in EBI following SAH possibly by suppressing TLR 4/NF-κB mediated inflammatory pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. In situ expression of heat-shock proteins and 3-nitrotyrosine in brains of young rats exposed to a WiFi signal in utero and in early life.

    Science.gov (United States)

    Aït-Aïssa, Saliha; de Gannes, Florence Poulletier; Taxile, Murielle; Billaudel, Bernard; Hurtier, Annabelle; Haro, Emmanuelle; Ruffié, Gilles; Athané, Axel; Veyret, Bernard; Lagroye, Isabelle

    2013-06-01

    The bioeffects of exposure to Wireless High-Fidelity (WiFi) signals on the developing nervous systems of young rodents was investigated by assessing the in vivo and in situ expression levels of three stress markers: 3-Nitrotyrosine (3-NT), an oxidative stress marker and two heat-shock proteins (Hsp25 and Hsp70). These biomarkers were measured in the brains of young rats exposed to a 2450 MHz WiFi signal by immunohistochemistry. Pregnant rats were first exposed or sham exposed to WiFi from day 6 to day 21 of gestation. In addition three newborns per litter were further exposed up to 5 weeks old. Daily 2-h exposures were performed blind in a reverberation chamber and whole-body specific absorption rate levels were 0, 0.08, 0.4 and 4 W/kg. 3-NT and stress protein expression was assayed in different areas of the hippocampus and cortex. No significant difference was observed among exposed and sham-exposed groups. These results suggest that repeated exposure to WiFi during gestation and early life has no deleterious effects on the brains of young rats.

  13. Meta-analysis of estrogen response in MCF-7 distinguishes early target genes involved in signaling and cell proliferation from later target genes involved in cell cycle and DNA repair

    Directory of Open Access Journals (Sweden)

    Jagannathan Vidhya

    2011-08-01

    Full Text Available Abstract Background Many studies have been published outlining the global effects of 17β-estradiol (E2 on gene expression in human epithelial breast cancer derived MCF-7 cells. These studies show large variation in results, reporting between ~100 and ~1500 genes regulated by E2, with poor overlap. Results We performed a meta-analysis of these expression studies, using the Rank product method to obtain a more accurate and stable list of the differentially expressed genes, and of pathways regulated by E2. We analyzed 9 time-series data sets, concentrating on response at 3-4 hrs (early and at 24 hrs (late. We found >1000 statistically significant probe sets after correction for multiple testing at 3-4 hrs, and >2000 significant probe sets at 24 hrs. Differentially expressed genes were examined by pathway analysis. This revealed 15 early response pathways, mostly related to cell signaling and proliferation, and 20 late response pathways, mostly related to breast cancer, cell division, DNA repair and recombination. Conclusions Our results confirm that meta-analysis identified more differentially expressed genes than the individual studies, and that these genes act together in networks. These results provide new insight into E2 regulated mechanisms, especially in the context of breast cancer.

  14. Transcriptome Analysis Reveals New Insights into the Modulation of Endometrial Stromal Cell Receptive Phenotype by Embryo-Derived Signals Interleukin-1 and Human Chorionic Gonadotropin: Possible Involvement in Early Embryo Implantation

    Science.gov (United States)

    Bourdiec, Amélie; Calvo, Ezequiel; Rao, C. V.; Akoum, Ali

    2013-01-01

    The presence of the conceptus in uterine cavity necessitates an elaborate network of interactions between the implanting embryo and a receptive endometrial tissue. We believe that embryo-derived signals play an important role in the remodeling and the extension of endometrial receptivity period. Our previous studies provided original evidence that human Chorionic Gonadotropin (hCG) modulates and potentiates endometrial epithelial as well as stromal cell responsiveness to interleukin 1 (IL1), one of the earliest embryonic signals, which may represent a novel pathway by which the embryo favors its own implantation and growth within the maternal endometrial host. The present study was designed to gain a broader understanding of hCG impact on the modulation of endometrial cell receptivity, and in particular, cell responsiveness to IL1 and the acquisition of growth-promoting phenotype capable of receiving, sustaining, and promoting early and crucial steps of embryonic development. Our results showed significant changes in the expression of genes involved in cell proliferation, immune modulation, tissue remodeling, apoptotic and angiogenic processes. This points to a relevant impact of these embryonic signals on the receptivity of the maternal endometrium, its adaptation to the implanting embryo and the creation of an environment that is favorable for the implantation and the growth of this latter within a new and likely hostile host tissue. Interestingly our data further identified a complex interaction between IL1 and hCG, which, despite a synergistic action on several significant endometrial target genes, may encompass a tight control of endogenous IL1 and extends to other IL1 family members. PMID:23717664

  15. Activation of stress-related signalling pathway in human cells upon SiO2 nanoparticles exposure as an early indicator of cytotoxicity

    LENUS (Irish Health Repository)

    Mohamed, Bashir M

    2011-07-29

    analysis of more subtle signalling pathways associated with accumulation mechanisms, which is essential for establishing the bio-safety of existing and new nanomaterials.

  16. Design of monitoring and early warning system for roller coaster based on acceleration signal%基于加速度信号的过山车监测预警系统设计

    Institute of Scientific and Technical Information of China (English)

    李根; 朱玉田; 谢波

    2012-01-01

    Based on the requirements of special equipment safety and the current status of recreation facilities test system,a safety monitoring and early warning system for roller coaster is designed. The signal acquisition device of the system is set on the roller coaster. Digital signal processor( DSP) is used as the main control chip for its high calculation speed. Low-power consumption chips with 3. 3 V are used on the acquisition for their energy conservation and environment protection. High-frequency vibration acceleration and low-frequency motion acceleration signals are acquired in real time, and datas are transmitted to upper machine by WiFi. By using LabVlEW,the software of upper machine is developed. Wavelet analysis is applied to process the data. BP neural network is applied for fault diagnosis. Meanwhile, FFT analysis is used to process the acquired signal and standard signal and draw frequency spectrogram to check on the result of the fault diagnosis. If any fault is diagnosed, the system will sound the alarm and send out the early warning information to the relevant staff by GPRS. The experimental result shows that the system is quick, accurate and reliable.%鉴于国家对特种设备安全的要求和大型游乐设施测试系统的现状,设计了一种过山车监测预警系统.系统的信号采集装置安装在过山车上,采用数字信号处理器(DSP)作为主控芯片,运算速度快,可实现数据的实时采集,硬件电路多采用3.3V的低功耗芯片,节能环保.系统采集高频振动加速度和低频运动加速度信号,通过WiFi将数据传输给上位机,上位机软件使用LabVIEW开发,运用小波分析处理数据,并采用BP神经网络算法诊断故障,同时,对采集的信号和标准信号进行快速傅立叶变换(FFT)分析并作频谱图,可直观的检验诊断结果.如果诊断出故障,系统可发出警报并通过通用分组无线业务(GPRS)通知相关工作人员.实验结果表明:系统的运算速度快,诊断结果可靠.

  17. Whistler-triggered VLF noise bursts observed on the DE-1 satellite and simultaneously at Antarctic ground stations

    Science.gov (United States)

    Smith, A. J.; Carpenter, D. L.; Inan, U. S.

    1985-01-01

    Simultaneous observations of whistler-triggered very low-frequency noise bursts on the ground at Anarctic stations, Halley and Siple, and on the high-altitude satellite DE-1 are reported. Results of a case study from June 25, 1982 in which the satellite data were recorded near 25 deg south magnetic latitude and the L = 4.7 magnetic shell, are presented. Analysis indicates that the chorus bursts that are triggered in whistler ducts travel downwards in the ducts to low altitudes in the ionosphere, and that propagation to DE-1 is by upward reflection into a nonducted mode. A means of estimating the propagation characteristics of the wave bursts is provided by comparisons of nonducted signals from the Siple transmitter and discrete periodic emissions. The ducted-nonducted mode conversion process is a mechanism for the large-scale spreading into the magnetosphere of coherent whistler-mode wave energy which is generated, amplified, or triggered in small localized ducts. The DE-1 data show that a strong interaction exists between whistler-triggered noise bursts and prevailing hiss levels.

  18. ATP signals

    DEFF Research Database (Denmark)

    Novak, Ivana

    2016-01-01

    The Department of Biology at the University of Copenhagen explains the function of ATP signalling in the pancreas......The Department of Biology at the University of Copenhagen explains the function of ATP signalling in the pancreas...

  19. Signal transduction by growth factor receptors: signaling in an instant

    DEFF Research Database (Denmark)

    Dengjel, Joern; Akimov, Vyacheslav; Blagoev, Blagoy;

    2007-01-01

    -out by mass spectrometry-based proteomics has allowed exciting views on the very early events in signal transduction. Activation profiles of regulated phosphorylation sites on epidermal growth factor receptor and downstream signal transducers showed different kinetics within the first ten seconds...

  20. Gender differences in the association between stop-signal reaction times, body mass indices and/or spontaneous food intake in pre-school children: an early model of compromised inhibitory control and obesity.

    Science.gov (United States)

    Levitan, R D; Rivera, J; Silveira, P P; Steiner, M; Gaudreau, H; Hamilton, J; Kennedy, J L; Davis, C; Dube, L; Fellows, L; Wazana, A; Matthews, S; Meaney, M J

    2015-04-01

    Poor inhibitory control is associated with overeating and/or obesity in school-age children, adolescents and adults. The current study examined whether an objective and reliable marker of response inhibition, the stop-signal reaction time (SSRT), is associated with body mass index (BMI) z-scores and/or food intake during a snack test in pre-school children. The current sample consisted of 193 pre-school children taking part in a longitudinal study of early brain development (Maternal Adversity, Vulnerability and Neurodevelopment (the MAVAN project)). Linear mixed-effect models were used to examine whether the SSRT measured at age 48 months associated with BMI z-scores and/or dietary intake during a laboratory-based snack test. After controlling for significant covariates including maternal BMI, there was a significant gender by SSRT interaction effect in predicting 48-month BMI z-scores. Post-hoc analysis revealed an association between longer SSRTs (poor response inhibition) and higher BMIs in girls but not boys. Across both girls and boys, longer SSRTs were associated with greater intake of carbohydrates and sugars during the snack test. The association between SSRT scores and BMI z-scores in girls was not statistically mediated by carbohydrate or sugar intake. At 48 months of age, slower response inhibition on the Stop-Signal Task associates with higher BMI z-scores in girls, and with higher intake of carbohydrates and sugars during a snack test across both genders. Ongoing follow-up of these children will help clarify the implications of these associations for longer term macronutrient intake, eating-related pathology and/or pathological weight gain over time.

  1. The application of breast DCE-MRI combined with time signal curve in diagnosing early breast cancer%磁共振动态增强乳腺扫描及时间信号曲线结合在早期乳腺癌诊断中的应用价值

    Institute of Scientific and Technical Information of China (English)

    Yakun He; Guohui Xu; Jing Ren; Min Wang; Jin Liu

    2013-01-01

    Objective:The aim of this study was to investigate the application value of breast dynamic contrast-enhanced magnetic resonance imaging combined with time signal curve in diagnosis of early breast cancer. Methods:Conducted dynamic contrast-enhanced MRI and drew the time signal curves of breast lesions in 60 patients with breast disease (malignant 46, benign 14). Results:Morphological features of malignant tumors mostly showed blurred or thin spiculate outlines, irregular shape or lobular signs, signal heterogeneity or peripheral enhancement in dynamic contrast-enhanced MRI. Time signal curve showed type III or II. Morphologic features of benign tumors mostly showed clear edge, regular shape and homogeneous signal, or diffuse spot enhancement. Time signal curve showed type I or II. Conclusion:breast dynamic contrast enhanced scan in MRI can provide morphology and functional diagnosis information of the breast tissues. Dynamic contrast-enhanced MRI combined with time signal curve can further improve the accuracy of diagnosis of early breast cancer.

  2. Analysis of the asymmetrically expressed Ablim1 locus reveals existence of a lateral plate Nodal-independent left sided signal and an early, left-right independent role for nodal flow

    Directory of Open Access Journals (Sweden)

    Hilton Helen

    2010-05-01

    Full Text Available Abstract Background Vertebrates show clear asymmetry in left-right (L-R patterning of their organs and associated vasculature. During mammalian development a cilia driven leftwards flow of liquid leads to the left-sided expression of Nodal, which in turn activates asymmetric expression of the transcription factor Pitx2. While Pitx2 asymmetry drives many aspects of asymmetric morphogenesis, it is clear from published data that additional asymmetrically expressed loci must exist. Results A L-R expression screen identified the cytoskeletally-associated gene, actin binding lim protein 1 (Ablim1, as asymmetrically expressed in both the node and left lateral plate mesoderm (LPM. LPM expression closely mirrors that of Nodal. Significantly, Ablim1 LPM asymmetry was detected in the absence of detectable Nodal. In the node, Ablim1 was initially expressed symmetrically across the entire structure, resolving to give a peri-nodal ring at the headfold stage in a flow and Pkd2-dependent manner. The peri-nodal ring of Ablim1 expression became asymmetric by the mid-headfold stage, showing stronger right than left-sided expression. Node asymmetry became more apparent as development proceeded; expression retreated in an anticlockwise direction, disappearing first from the left anterior node. Indeed, at early somite stages Ablim1 shows a unique asymmetric expression pattern, in the left lateral plate and to the right side of the node. Conclusion Left LPM Ablim1 is expressed in the absence of detectable LPM Nodal, clearly revealing existence of a Pitx2 and Nodal-independent left-sided signal in mammals. At the node, a previously unrecognised action of early nodal flow and Pkd2 activity, within the pit of the node, influences gene expression in a symmetric manner. Subsequent Ablim1 expression in the peri-nodal ring reveals a very early indication of L-R asymmetry. Ablim1 expression analysis at the node acts as an indicator of nodal flow. Together these results make

  3. Early-warning signals for critical transitions

    NARCIS (Netherlands)

    Scheffer, M.; Bascompte, J.; Brock, W.A.; Brovkin, V.; Carpenter, S.R.; Dakos, V.; Held, H.; Nes, van E.H.; Rietkerk, M.; Sugihara, G.

    2009-01-01

    Complex dynamical systems, ranging from ecosystems to financial markets and the climate, can have tipping points at which a sudden shift to a contrasting dynamical regime may occur. Although predicting such critical points before they are reached is extremely difficult, work in different scientific

  4. Ducted whistler-mode signals received at two widely spaced locations

    Directory of Open Access Journals (Sweden)

    M. A. Clilverd

    Full Text Available Whistler-mode signals from a single VLF transmitter that have propagated in the same duct, have been observed simultaneously at Faraday, Antarctica (65°S, 64°W and Dunedin, New Zealand (46°S, 171°E. The signals received have group-delay times that differ in the order of 10 ms, which can be explained by the differences in southern-hemisphere sub-ionospheric propagation time from duct exit region to receiver for the two sites. This difference has been used to determine the location of the duct exit region, with confirmation provided by arrival-bearing information from both sites. The whistler-mode signals typically occur one or two days after geomagnetic activity, with Kpgeq5. The sub-ionospheric-propagation model, LWPC, is used to estimate the whistler-mode power radiated from the duct exit region. These results are then combined with estimated loss values for ionospheric and ducted transmission to investigate the role of wave-particle amplification or absorption. On at least half of the events studied, plasmaspheric amplification of the signals appears to be needed to explain the observed whistler-mode signal strengths.

  5. Alteration of mTOR signaling occurs early in the progression of Alzheimer disease (AD): analysis of brain from subjects with pre-clinical AD, amnestic mild cognitive impairment and late-stage AD.

    Science.gov (United States)

    Tramutola, Antonella; Triplett, Judy C; Di Domenico, Fabio; Niedowicz, Dana M; Murphy, Michael P; Coccia, Raffaella; Perluigi, Marzia; Butterfield, D Allan

    2015-06-01

    The clinical symptoms of Alzheimer disease (AD) include a gradual memory loss and subsequent dementia, and neuropathological deposition of senile plaques and neurofibrillary tangles. At the molecular level, AD subjects present overt amyloid β (Aβ) production and tau hyperphosphorylation. Aβ species have been proposed to overactivate the phosphoinositide3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) axis, which plays a central role in proteostasis. The current study investigated the status of the PI3K/Akt/mTOR pathway in post-mortem tissue from the inferior parietal lobule (IPL) at three different stages of AD: late AD, amnestic mild cognitive impairment (MCI) and pre-clinical AD (PCAD). Our findings suggest that the alteration of mTOR signaling and autophagy occurs at early stages of AD. We found a significant increase in Aβ (1-42) levels, associated with reduction in autophagy (Beclin-1 and LC-3) observed in PCAD, MCI, and AD subjects. Related to the autophagy impairment, we found a hyperactivation of PI3K/Akt/mTOR pathway in IPL of MCI and AD subjects, but not in PCAD, along with a significant decrease in phosphatase and tensin homolog. An increase in two mTOR downstream targets, p70S6K and 4EBP1, occurred in AD and MCI subjects. Both AD and MCI subjects showed increased, insulin receptor substrate 1, a candidate biomarker of brain insulin resistance, and GSK-3β, a kinase targeting tau phosphorylation. Nevertheless, tau phosphorylation was increased in the clinical groups. The results hint at a link between Aβ and the PI3K/Akt/mTOR axis and provide further insights into the relationship between AD pathology and insulin resistance. In addition, we speculate that the alteration of mTOR signaling in the IPL of AD and MCI subjects, but not in PCAD, is due to the lack of substantial increase in oxidative stress. The figure represents the three different stages of Alzheimer Disease: Preclinical Alzheimer Disease (PCAD), Mild cognitive impairment (MCI

  6. VLF Force 1 V10

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    TG:你们旗下已有Fisker—Karma改造而成的Destino V8,Force 1用意何在?HF:显而易见,Force1是我们阵中的跑车型号,设计大胆激进。我们尝试在赛车和豪华汽车之间探讨一些新事物。

  7. Inhibitory effects of omega-3 fatty acids on early brain injury after subarachnoid hemorrhage in rats: Possible involvement of G protein-coupled receptor 120/β-arrestin2/TGF-β activated kinase-1 binding protein-1 signaling pathway.

    Science.gov (United States)

    Yin, Jia; Li, Haiying; Meng, Chengjie; Chen, Dongdong; Chen, Zhouqing; Wang, Yibin; Wang, Zhong; Chen, Gang

    2016-06-01

    Omega-3 fatty acids have been reported to improve neuron functions during aging and in patients affected by mild cognitive impairment, and mediate potent anti-inflammatory via G protein-coupled receptor 120 (GPR120) signal pathway. Neuron dysfunction and inflammatory response also contributed to the progression of subarachnoid hemorrhage (SAH)-induced early brain injury (EBI). This study was to examine the effects of omega-3 fatty acids on SAH-induced EBI. Two weeks before SAH, 30% Omega-3 fatty acids was administered by oral gavage at 1g/kg body weight once every 24h. Specific siRNA for GPR120 was exploited. Terminal deoxynucleotidyl transferase dUTP nick end labeling, fluoro-Jade B staining, and neurobehavioral scores and brain water content test showed that omega-3 fatty acids effectively suppressed SAH-induced brain cell apoptosis and neuronal degradation, behavioral impairment, and brain edema. Western blot, immunoprecipitation, and electrophoretic mobility shift assays results showed that omega-3 fatty acids effectively suppressed SAH-induced elevation of inflammatory factors, including cyclooxygenase-2, monocyte chemoattractant protein-1, and inducible nitric oxide synthase. In addition, omega-3 fatty acids could inhibit phosphorylation of transforming growth factor β activated kinase-1 (TAK1), MEK4, c-Jun N-terminal kinase, and IkappaB kinase as well as activation of nuclear factor kappa B through regulating GPR120/β-arrestin2/TAK1 binding protein-1 pathway. Furthermore, siRNA-induced GPR120 silencing blocked the protective effects of omega-3 fatty acids. Here, we show that stimulation of GPR120 with omega-3 fatty acids pretreatment causes anti-apoptosis and anti-inflammatory effects via β-arrestin2/TAK1 binding protein-1/TAK1 pathway in the brains of SAH rats. Fish omega-3 fatty acids as part of a daily diet may reduce EBI in an experimental rat model of SAH.

  8. Skeletal muscle hypertrophy adaptations predominate in the early stages of resistance exercise training, matching deuterium oxide-derived measures of muscle protein synthesis and mechanistic target of rapamycin complex 1 signaling.

    Science.gov (United States)

    Brook, Matthew S; Wilkinson, Daniel J; Mitchell, William K; Lund, Jonathan N; Szewczyk, Nathaniel J; Greenhaff, Paul L; Smith, Ken; Atherton, Philip J

    2015-11-01

    Resistance exercise training (RET) is widely used to increase muscle mass in athletes and also aged/cachectic populations. However, the time course and metabolic and molecular control of hypertrophy remain poorly defined. Using newly developed deuterium oxide (D2O)-tracer techniques, we investigated the relationship between long-term muscle protein synthesis (MPS) and hypertrophic responses to RET. A total of 10 men (23 ± 1 yr) undertook 6 wk of unilateral (1-legged) RET [6 × 8 repetitions, 75% 1 repetition maximum (1-RM) 3/wk], rendering 1 leg untrained (UT) and the contralateral, trained (T). After baseline bilateral vastus lateralis (VL) muscle biopsies, subjects consumed 150 ml D2O (70 atom percentage; thereafter 50 ml/wk) with regular body water monitoring in saliva via high-temperature conversion elemental analyzer:isotope ratio mass spectrometer. Further bilateral VL muscle biopsies were taken at 3 and 6 wk to temporally quantify MPS via gas chromatography:pyrolysis:isotope ratio mass spectrometer. Expectedly, only the T leg exhibited marked increases in function [i.e., 1-RM/maximal voluntary contraction (60°)] and VL thickness (peaking at 3 wk). Critically, whereas MPS remained unchanged in the UT leg (e.g., ∼1.35 ± 0.08%/d), the T leg exhibited increased MPS at 0-3 wk (1.6 ± 0.01%/d), but not at 3-6 wk (1.29 ± 0.11%/d); this was reflected by dampened acute mechanistic target of rapamycin complex 1 signaling responses to RET, beyond 3 wk. Therefore, hypertrophic remodeling is most active during the early stages of RET, reflecting longer-term MPS. Moreover, D2O heralds promise for coupling MPS and muscle mass and providing insight into the control of hypertrophy and efficacy of anabolic interventions.

  9. Bayesian signaling

    OpenAIRE

    Hedlund, Jonas

    2014-01-01

    This paper introduces private sender information into a sender-receiver game of Bayesian persuasion with monotonic sender preferences. I derive properties of increasing differences related to the precision of signals and use these to fully characterize the set of equilibria robust to the intuitive criterion. In particular, all such equilibria are either separating, i.e., the sender's choice of signal reveals his private information to the receiver, or fully disclosing, i.e., the outcome of th...

  10. Aberrant Signaling through the HER2-ERK1/2 Pathway is Predictive of Reduced Disease-Free and Overall Survival in Early Stage Non-Small Cell Lung Cancer (NSCLC) Patients.

    Science.gov (United States)

    Scrima, Marianna; Zito Marino, Federica; Oliveira, Duarte Mendes; Marinaro, Cinzia; La Mantia, Elvira; Rocco, Gaetano; De Marco, Carmela; Malanga, Donatella; De Rosa, Nicla; Rizzuto, Antonia; Botti, Gerardo; Franco, Renato; Zoppoli, Pietro; Viglietto, Giuseppe

    2017-01-01

    Background: Purpose of this study was to evaluate the contribution of the Extracellular-regulated protein kinase (ERK)-1/2 pathway to oncogenic signaling elicited by the tyrosine kinase receptor HER2 in Non-Small Cell Lung Cancer (NSCLC) and to assess the prognostic value of these oncoproteins in NSCLC patients. Methods: Immunohistochemistry was performed to determine expression and activation of HER2 and ERK1/2 (detected by phosphorylation of Y1248 and T202/Y204, respectively) using Tissue Micro Arrays (TMA) containing matched normal and neoplastic tissues from 132 NSCLC patients. Survival analysis was carried out using the Kaplan-Meier method. Univariate and multivariate analysis were used to evaluate the prognostic value of pERK1/2, pHER2 and a combination thereof with clinical-pathological parameters such as age, lymph node status (N), size (T), stage (TNM) and grade. Results: We found that HER2 was overexpressed in 33/120 (27%) and activated in 41/114 (36%) cases; ERK1/2 was activated in 44/102 (43%) cases. A direct association was found between pERK1/2 and pHER2 (23/41; p=0.038). In addition, patients positive for pERK1/2 and for both pHER2 and pERK1/2 showed significantly worse overall survival (OS) and disease-free survival (DFS) compared with negative patients. Univariate and multivariate analysis of patients' survival revealed that positivity for pHER2-pERK1/2 and for pERK1/2 alone were independent prognostic factors of poor survival in NSCLC patients. In particular, this association was significantly important for DFS in stage I+II patients. Conclusion: This study provides evidence that activated ERK1/2 and/or the combined activation of HER2 and ERK1/2 are good indicators of poor prognosis in NSCLC patients, not only in unselected patients but also in early stage disease.

  11. Extracellular-signal regulated kinase (Erk1/2), mitogen-activated protein kinase-activated protein kinase 2 (MK2) and tristetraprolin (TTP) comprehensively regulate injury-induced immediate early gene (IEG) response in in vitro liver organ culture.

    Science.gov (United States)

    Tran, Doan Duy Hai; Koch, Alexandra; Saran, Shashank; Armbrecht, Marcel; Ewald, Florian; Koch, Martina; Wahlicht, Tom; Wirth, Dagmar; Braun, Armin; Nashan, Björn; Gaestel, Matthias; Tamura, Teruko

    2016-05-01</