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Sample records for signal discrimination module

  1. Learning and Visualizing Modulation Discriminative Radio Signal Features

    Science.gov (United States)

    2016-09-01

    method may be successfully applied to pre-trained models with neg- ligible impact on classification performance on an automated modulation...to as a Stacked What -Where Autoencoder (SWWAE). In an SWWAE, the encoder is composed of convolutions and max-pooling operations, and the de- coder is...work automated modulation classification (AMC) models tend to over-predict GMSK and OFDM at low SNR at the expense of other categories. Intuitively

  2. Limiter discriminator detection of M-ary FSK signals

    Science.gov (United States)

    Fonseka, John P.

    1990-10-01

    The performance of limiter discriminator detection of M-ary FSK signals is analyzed at arbitrary modulation indices. It is shown that the error rate performance of limiter discriminator detection can be significantly improved by increasing the modulation index above 1/M. The optimum modulation index that minimizes the overall error probability is determined for the cases M = 2, 4 and 8. The analysis is carried out for wideband and bandlimited channels with Gaussian and second-order Butterworth filters. It is shown that the optimum modulation index depends on the signal/noise ratio (SNR), in a wideband channel, and on both SNR and time-bandwidth product in a bandlimited channel. Finally, it is shown that the optimum sampling instance in presence of a nonzero phase IF filter can be approximately determined by using only the worst case symbol pattern.

  3. Study of signal discrimination for timing measurements

    CERN Document Server

    Krepelkova, Marta

    2017-01-01

    The timing detectors of the CMS-TOTEM Precision Proton Spectrometer (CT-PPS) are currently read out using discrete components, separated into three boards; the first board hosts the sensors and the amplifiers, the second one hosts the discriminators and the third is dedicated to the Time to Digital Converter (TDC) and to the interface with the data acquisition system (DAQ). This work proposes a new front-end electronics for the timing detector, with sensors, amplifiers and discriminators integrated on the same board. We simulated an updated version of the amplifier together with a discriminator designed using commercial components. We decided to use an LVDS buffer as a discriminator, because of its cost, availability, speed and lo w power consumption. As a proof of concept, we used the LVDS input of an FPGA to discriminate signals produced by a detector prototype, using a radioactive source.

  4. Intracellular signal modulation by nanomaterials.

    Science.gov (United States)

    Hussain, Salik; Garantziotis, Stavros; Rodrigues-Lima, Fernando; Dupret, Jean-Marie; Baeza-Squiban, Armelle; Boland, Sonja

    2014-01-01

    A thorough understanding of the interactions of nanomaterials with biological systems and the resulting activation of signal transduction pathways is essential for the development of safe and consumer friendly nanotechnology. Here we present an overview of signaling pathways induced by nanomaterial exposures and describe the possible correlation of their physicochemical characteristics with biological outcomes. In addition to the hierarchical oxidative stress model and a review of the intrinsic and cell-mediated mechanisms of reactive oxygen species (ROS) generating capacities of nanomaterials, we also discuss other oxidative stress dependent and independent cellular signaling pathways. Induction of the inflammasome, calcium signaling, and endoplasmic reticulum stress are reviewed. Furthermore, the uptake mechanisms can be of crucial importance for the cytotoxicity of nanomaterials and membrane-dependent signaling pathways have also been shown to be responsible for cellular effects of nanomaterials. Epigenetic regulation by nanomaterials, effects of nanoparticle-protein interactions on cell signaling pathways, and the induction of various cell death modalities by nanomaterials are described. We describe the common trigger mechanisms shared by various nanomaterials to induce cell death pathways and describe the interplay of different modalities in orchestrating the final outcome after nanomaterial exposures. A better understanding of signal modulations induced by nanomaterials is not only essential for the synthesis and design of safer nanomaterials but will also help to discover potential nanomedical applications of these materials. Several biomedical applications based on the different signaling pathways induced by nanomaterials are already proposed and will certainly gain a great deal of attraction in the near future.

  5. Automatic modulation recognition of communication signals

    CERN Document Server

    Azzouz, Elsayed Elsayed

    1996-01-01

    Automatic modulation recognition is a rapidly evolving area of signal analysis. In recent years, interest from the academic and military research institutes has focused around the research and development of modulation recognition algorithms. Any communication intelligence (COMINT) system comprises three main blocks: receiver front-end, modulation recogniser and output stage. Considerable work has been done in the area of receiver front-ends. The work at the output stage is concerned with information extraction, recording and exploitation and begins with signal demodulation, that requires accurate knowledge about the signal modulation type. There are, however, two main reasons for knowing the current modulation type of a signal; to preserve the signal information content and to decide upon the suitable counter action, such as jamming. Automatic Modulation Recognition of Communications Signals describes in depth this modulation recognition process. Drawing on several years of research, the authors provide a cr...

  6. Dopamine modulates memory consolidation of discrimination learning in the auditory cortex.

    Science.gov (United States)

    Schicknick, Horst; Reichenbach, Nicole; Smalla, Karl-Heinz; Scheich, Henning; Gundelfinger, Eckart D; Tischmeyer, Wolfgang

    2012-03-01

    In Mongolian gerbils, the auditory cortex is critical for discriminating rising vs. falling frequency-modulated tones. Based on our previous studies, we hypothesized that dopaminergic inputs to the auditory cortex during and shortly after acquisition of the discrimination strategy control long-term memory formation. To test this hypothesis, we studied frequency-modulated tone discrimination learning of gerbils in a shuttle box GO/NO-GO procedure following differential treatments. (i) Pre-exposure of gerbils to the frequency-modulated tones at 1 day before the first discrimination training session severely impaired the accuracy of the discrimination acquired in that session during the initial trials of a second training session, performed 1 day later. (ii) Local injection of the D1/D5 dopamine receptor antagonist SCH-23390 into the auditory cortex after task acquisition caused a discrimination deficit of similar extent and time course as with pre-exposure. This effect was dependent on the dose and time point of injection. (iii) Injection of the D1/D5 dopamine receptor agonist SKF-38393 into the auditory cortex after retraining caused a further discrimination improvement at the beginning of subsequent sessions. All three treatments, which supposedly interfered with dopamine signalling during conditioning and/or retraining, had a substantial impact on the dynamics of the discrimination performance particularly at the beginning of subsequent training sessions. These findings suggest that auditory-cortical dopamine activity after acquisition of a discrimination of complex sounds and after retrieval of weak frequency-modulated tone discrimination memory further improves memory consolidation, i.e. the correct association of two sounds with their respective GO/NO-GO meaning, in support of future memory recall. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  7. Joint probability discrimination between stationary tissue and blood velocity signals

    DEFF Research Database (Denmark)

    Schlaikjer, Malene; Jensen, Jørgen Arendt

    2001-01-01

    before and after echo-canceling, and (b) the amplitude variations between samples in consecutive RF-signals before and after echo-canceling. The statistical discriminator was obtained by computing the probability density functions (PDFs) for each feature through histogram analysis of data....... This study presents a new statistical discriminator. Investigation of the RF-signals reveals that features can be derived that distinguish the segments of the signal, which do an do not carry information on the blood flow. In this study 4 features, have been determined: (a) the energy content in the segments....... The discrimination is performed by determining the joint probability of the features for the segment under investigation and choosing the segment type that is most likely. The method was tested on simulated data resembling RF-signals from the carotid artery....

  8. Optimal Fisher Discriminant Ratio for an Arbitrary Spatial Light Modulator

    Science.gov (United States)

    Juday, Richard D.

    1999-01-01

    Optimizing the Fisher ratio is well established in statistical pattern recognition as a means of discriminating between classes. I show how to optimize that ratio for optical correlation intensity by choice of filter on an arbitrary spatial light modulator (SLM). I include the case of additive noise of known power spectral density.

  9. Audibility of modulation noise in stationary signals

    NARCIS (Netherlands)

    Neelen, J.J.M.

    1970-01-01

    Recordings of an acoustic signal on magnetic tape often show noise, which may be divided into two main classes: additive noise and multiplicative noise. A characteristic of the latter is that it is weak with weak signals and strong with strong signals. This modulation noise has been subjected to a

  10. Pulse shape discrimination based on fast signals from silicon photomultipliers

    Science.gov (United States)

    Yu, Junhao; Wei, Zhiyong; Fang, Meihua; Zhang, Zixia; Cheng, Can; Wang, Yi; Su, Huiwen; Ran, Youquan; Zhu, Qingwei; Zhang, He; Duan, Kai; Chen, Ming; Liu, Meng

    2018-06-01

    Recent developments in organic plastic scintillators capable of pulse shape discrimination (PSD) enable a breakthrough in discrimination between neutrons and gammas. Plastic scintillator detectors coupled with silicon photomultipliers (SiPMs) offer many advantages, such as lower power consumption, smaller volume, and especially insensitivity to magnetic fields, compared with conventional photomultiplier tubes (PMTs). A SensL SiPM has two outputs: a standard output and a fast output. It is known that the charge injected into the fast output electrode is typically approximately 2% of the total charge generated during the avalanche, whereas the charge injected into the standard output electrode is nearly 98% of the total. Fast signals from SiPMs exhibit better performance in terms of timing and time-correlated measurements compared with standard signals. The pulse duration of a standard signal is on the order of hundreds of nanoseconds, whereas the pulse duration of the main monopole waveform of a fast signal is a few tens of nanoseconds. Fast signals are traditionally thought to be suitable for photon counting at very high speeds but unsuitable for PSD due to the partial charge collection. Meanwhile, the standard outputs of SiPMs coupled with discriminating scintillators have yielded nice PSD performances, but there have been no reports on PSD using fast signals. Our analysis shows that fast signals can also provide discrimination if the rate of charge injection into the fast output electrode is fixed for each event, even though only a portion of the charge is collected. In this work, we achieved successful PSD using fast signals; meanwhile, using a coincidence timing window of less 3 nanoseconds between the readouts from both ends of the detector reduced the influence of the high SiPM dark current. We experimentally achieved good timing performance and PSD capability simultaneously.

  11. Decoding a combined amplitude modulated and frequency modulated signal

    DEFF Research Database (Denmark)

    2015-01-01

    The present disclosure relates to a method for decoding a combined AM/FM encoded signal, comprising the steps of: combining said encoded optical signal with light from a local oscillator configured with a local oscillator frequency; converting the combined local oscillator and encoded optical...... signal into one or more electrical signals by means of at least one opto-electrical converter having a predefined frequency bandwidth, thereby providing an amplified and encoded electrical signal having one or more encoded signal current(s), where one type of states have a higher oscillation frequency...... than other type of states; rectifying the encoded signal current(s), thereby obtaining an encoded power spectrum, wherein said power spectrum has different states, such as "0"-states and "1"-states, with different power levels such that they can be discriminated, said local oscillator frequency...

  12. Multisensory interaction in vibrotactile detection and discrimination of amplitude modulation

    DEFF Research Database (Denmark)

    Teodorescu, Kinneret; Bouchigny, Sylvain; Hoffmann, Pablo F.

    2011-01-01

    Perception of vibration during drilling demands integration of haptic and auditory information with force information. In this study we explored the ability to detect and discriminate changes in vibrotactile stimuli amplitude based either on purely haptic feedback or together with congruent...... skill of maxilla-facial surgery strongly relies on enhanced touch perception, as measured in reaction times and discrimination ability in bi-modal vibro-auditory conditions. These observations suggest that acquisition of mandibular surgery skill has brought to an enhanced representation of vibro......-tactile modulations in relevant stimuli ranges. Altogether, our results provide basis to assume that during acquisition of mandibular drilling skill, trainees may benefit from training of relevant basic aspects of touch perception - sensitivity to vibration and accompanying modulations of sound....

  13. KNN BASED CLASSIFICATION OF DIGITAL MODULATED SIGNALS

    Directory of Open Access Journals (Sweden)

    Sajjad Ahmed Ghauri

    2016-11-01

    Full Text Available Demodulation process without the knowledge of modulation scheme requires Automatic Modulation Classification (AMC. When receiver has limited information about received signal then AMC become essential process. AMC finds important place in the field many civil and military fields such as modern electronic warfare, interfering source recognition, frequency management, link adaptation etc. In this paper we explore the use of K-nearest neighbor (KNN for modulation classification with different distance measurement methods. Five modulation schemes are used for classification purpose which is Binary Phase Shift Keying (BPSK, Quadrature Phase Shift Keying (QPSK, Quadrature Amplitude Modulation (QAM, 16-QAM and 64-QAM. Higher order cummulants (HOC are used as an input feature set to the classifier. Simulation results shows that proposed classification method provides better results for the considered modulation formats.

  14. Modulator-free quadrature amplitude modulation signal synthesis

    Science.gov (United States)

    Liu, Zhixin; Kakande, Joseph; Kelly, Brian; O'Carroll, John; Phelan, Richard; Richardson, David J.; Slavík, Radan

    2014-12-01

    The ability to generate high-speed on-off-keyed telecommunication signals by directly modulating a semiconductor laser’s drive current was one of the most exciting prospective applications of the nascent field of laser technology throughout the 1960s. Three decades of progress led to the commercialization of 2.5 Gbit s-1-per-channel submarine fibre optic systems that drove the growth of the internet as a global phenomenon. However, the detrimental frequency chirp associated with direct modulation forced industry to use external electro-optic modulators to deliver the next generation of on-off-keyed 10 Gbit s-1 systems and is absolutely prohibitive for today’s (>)100 Gbit s-1 coherent systems, which use complex modulation formats (for example, quadrature amplitude modulation). Here we use optical injection locking of directly modulated semiconductor lasers to generate complex modulation format signals showing distinct advantages over current and other currently researched solutions.

  15. Phase ramping and modulation of reflectometer signals

    International Nuclear Information System (INIS)

    Conway, G.D.; Bartlett, D.V.; Stoff, P.E.

    1999-01-01

    The phase and amplitude signals of JET heterodyne reflectometers show varying levels of high frequency turbulence superimposed on a slow changing mean. The phase signal also shows multi-radian (> 1 fringe) variations with two quite different time scales (2-10 ms and sub-ms). In both cases the mean reflected power, together with turbulent phase and amplitude fluctuation levels, are modulated synchronously with the are modulated synchronously with the phase fringes. The slow fringes appear to result radial movement of the cutoff layer with the amplitude modulation possibly due to multiple reflection between plasma and wall. The fast fringes occur in intermittent bursts and appear to be phase runaway resulting from antenna misalignment. Using a 2-D physical optics simulation code it is possible to replicate the fast bursts of phase runaway from steady-state turbulence and misaligned antennas. This offers a possible alternative explanation for some of the observations of bursting turbulence seen in reflectometer signals. (authors)

  16. Amplification and discrimination of signals from proportional multiwire chambers

    International Nuclear Information System (INIS)

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

    1976-03-01

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

  17. Modulation of radial blood flow during Braille character discrimination task.

    Science.gov (United States)

    Murata, Jun; Matsukawa, K; Komine, H; Tsuchimochi, H

    2012-03-01

    Human hands are excellent in performing sensory and motor function. We have hypothesized that blood flow of the hand is dynamically regulated by sympathetic outflow during concentrated finger perception. To identify this hypothesis, we measured radial blood flow (RBF), radial vascular conductance (RVC), heart rate (HR), and arterial blood pressure (AP) during Braille reading performed under the blind condition in nine healthy subjects. The subjects were instructed to read a flat plate with raised letters (Braille reading) for 30 s by the forefinger, and to touch a blank plate as control for the Braille discrimination procedure. HR and AP slightly increased during Braille reading but remained unchanged during the touching of the blank plate. RBF and RVC were reduced during the Braille character discrimination task (decreased by -46% and -49%, respectively). Furthermore, the changes in RBF and RVC were much greater during the Braille character discrimination task than during the touching of the blank plate (decreased by -20% and -20%, respectively). These results have suggested that the distribution of blood flow to the hand is modulated via sympathetic nerve activity during concentrated finger perception.

  18. Phase ramping and modulation of reflectometer signals

    International Nuclear Information System (INIS)

    Conway, G.; Bartlett, D.; Stott, P.

    1999-06-01

    The phase and amplitude signals of JET heterodyne reflectometers show varying levels of high frequency turbulence superimposed on a slow changing mean. The phase signal also shows multi-radian (>1 fringe) variations with two quite different time scales (2-10ms and sub-ms). In both cases the mean reflected power, together with turbulent phase and amplitude fluctuation levels, are modulated synchronously with the phase fringes. The slow fringes appear to result from radial movement of the cutoff layer with the amplitude modulation possibly due to multiple reflection between plasma and wall. The fast fringes occur in intermittent bursts and appear to be phase runaway resulting from antenna misalignment. Using a 2D physical optics simulation code it is possible to replicate the fast bursts of phase runaway from steady-state turbulence and misaligned antennas. This offers a possible alternative explanation for some of the observations of bursting turbulence seen in reflectometer signals. (author)

  19. Bias and discriminability during emotional signal detection in melancholic depression.

    Science.gov (United States)

    Hyett, Matthew; Parker, Gordon; Breakspear, Michael

    2014-04-27

    Cognitive disturbances in depression are pernicious and so contribute strongly to the burden of the disorder. Cognitive function has been traditionally studied by challenging subjects with modality-specific psychometric tasks and analysing performance using standard analysis of variance. Whilst informative, such an approach may miss deeper perceptual and inferential mechanisms that potentially unify apparently divergent emotional and cognitive deficits. Here, we sought to elucidate basic psychophysical processes underlying the detection of emotionally salient signals across individuals with melancholic and non-melancholic depression. Sixty participants completed an Affective Go/No-Go (AGN) task across negative, positive and neutral target stimuli blocks. We employed hierarchical Bayesian signal detection theory (SDT) to model psychometric performance across three equal groups of those with melancholic depression, those with a non-melancholic depression and healthy controls. This approach estimated likely response profiles (bias) and perceptual sensitivity (discriminability). Differences in the means of these measures speak to differences in the emotional signal detection between individuals across the groups, while differences in the variance reflect the heterogeneity of the groups themselves. Melancholic participants showed significantly decreased sensitivity to positive emotional stimuli compared to those in the non-melancholic group, and also had a significantly lower discriminability than healthy controls during the detection of neutral signals. The melancholic group also showed significantly higher variability in bias to both positive and negative emotionally salient material. Disturbances of emotional signal detection in melancholic depression appear dependent on emotional context, being biased during the detection of positive stimuli, consistent with a noisier representation of neutral stimuli. The greater heterogeneity of the bias across the melancholic

  20. Selective Sensing of Gas Mixture via a Temperature Modulation Approach: New Strategy for Potentiometric Gas Sensor Obtaining Satisfactory Discriminating Features.

    Science.gov (United States)

    Li, Fu-An; Jin, Han; Wang, Jinxia; Zou, Jie; Jian, Jiawen

    2017-03-12

    A new strategy to discriminate four types of hazardous gases is proposed in this research. Through modulating the operating temperature and the processing response signal with a pattern recognition algorithm, a gas sensor consisting of a single sensing electrode, i.e., ZnO/In₂O₃ composite, is designed to differentiate NO₂, NH₃, C₃H₆, CO within the level of 50-400 ppm. Results indicate that with adding 15 wt.% ZnO to In₂O₃, the sensor fabricated at 900 °C shows optimal sensing characteristics in detecting all the studied gases. Moreover, with the aid of the principle component analysis (PCA) algorithm, the sensor operating in the temperature modulation mode demonstrates acceptable discrimination features. The satisfactory discrimination features disclose the future that it is possible to differentiate gas mixture efficiently through operating a single electrode sensor at temperature modulation mode.

  1. Plant MAPK cascades: Just rapid signaling modules?

    KAUST Repository

    Boudsocq, Marie

    2015-08-27

    © 2015 Taylor & Francis Group, LLC. Abscisic acid (ABA) is a major phytohormone mediating important stress-related processes. We recently unveiled an ABA-activated MAPK signaling module constituted of MAP3K17/18-MKK3-MPK1/2/7/14. Unlike classical rapid MAPK activation, we showed that the activation of the new MAPK module is delayed and relies on the MAP3K protein synthesis. In this addendum, we discuss the role of this original and unexpected activation mechanism of MAPK cascades which suggests that MAPKs can regulate both early and longterm plant stress responses.

  2. Visual discrimination transfer and modulation by biogenic amines in honeybees.

    Science.gov (United States)

    Vieira, Amanda Rodrigues; Salles, Nayara; Borges, Marco; Mota, Theo

    2018-05-10

    For more than a century, visual learning and memory have been studied in the honeybee Apis mellifera using operant appetitive conditioning. Although honeybees show impressive visual learning capacities in this well-established protocol, operant training of free-flying animals cannot be combined with invasive protocols for studying the neurobiological basis of visual learning. In view of this, different attempts have been made to develop new classical conditioning protocols for studying visual learning in harnessed honeybees, though learning performance remains considerably poorer than that for free-flying animals. Here, we investigated the ability of honeybees to use visual information acquired during classical conditioning in a new operant context. We performed differential visual conditioning of the proboscis extension reflex (PER) followed by visual orientation tests in a Y-maze. Classical conditioning and Y-maze retention tests were performed using the same pair of perceptually isoluminant chromatic stimuli, to avoid the influence of phototaxis during free-flying orientation. Visual discrimination transfer was clearly observed, with pre-trained honeybees significantly orienting their flights towards the former positive conditioned stimulus (CS+), thus showing that visual memories acquired by honeybees are resistant to context changes between conditioning and the retention test. We combined this visual discrimination approach with selective pharmacological injections to evaluate the effect of dopamine and octopamine in appetitive visual learning. Both octopaminergic and dopaminergic antagonists impaired visual discrimination performance, suggesting that both these biogenic amines modulate appetitive visual learning in honeybees. Our study brings new insight into cognitive and neurobiological mechanisms underlying visual learning in honeybees. © 2018. Published by The Company of Biologists Ltd.

  3. Visible light communications modulation and signal processing

    CERN Document Server

    Wang, Zhaocheng; Huang, Wei; Xu, Zhengyuan

    2018-01-01

    This informative new book on state-of-the-art visible light communication (VLC) provides, for the first time, a systematical and advanced treatment of modulation and signal processing for VLC. Visible Light Communications: Modulation and Signal Processing offers a practical guide to designing VLC, linking academic research with commercial applications. In recent years, VLC has attracted attention from academia and industry since it has many advantages over the traditional radio frequency, including wide unregulated bandwidth, high security, and low cost. It is a promising complementary technique in 5G and beyond wireless communications, especially in indoor applications. However, lighting constraints have not been fully considered in the open literature when considering VLC system design, and its importance has been underestimated. That’s why this book—written by a team of experts with both academic research experience and industrial development experience in the field—is so welcome. To help readers u...

  4. Multi-channel logical circuit module used for high-speed, low amplitude signals processing and QDC gate signals generation

    International Nuclear Information System (INIS)

    Su Hong; Li Xiaogang; Zhu Haidong; Ma Xiaoli; Yin Weiwei; Li Zhuyu; Jin Genming; Wu Heyu

    2001-01-01

    A new kind of logical circuit will be introduced in brief. There are 16 independent channels in the module. The module receives low amplitude signals(≥40 mV), and processes them to amplify, shape, delay, sum and etc. After the processing each channel produces 2 pairs of ECL logical signal to feed the gate of QDC as the gate signal of QDC. The module consists of high-speed preamplifier unit, high-speed discriminate unit, delaying and shaping unit, summing unit and trigger display unit. The module is developed for 64 CH. 12 BIT Multi-event QDC. The impedance of QDC is 110 Ω. Each gate signal of QDC requires a pair of differential ECL level, Min. Gate width 30 ns and Max. Gate width 1 μs. It has showed that the outputs of logical circuit module satisfy the QDC requirements in experiment. The module can be used on data acquisition system to acquire thousands of data at high-speed ,high-density and multi-parameter, in heavy particle nuclear physics experiment. It also can be used to discriminate multi-coincidence events

  5. Nuclear Instrumentation Module (NIM) standard logic processor as a portal signal analyzer

    International Nuclear Information System (INIS)

    Minges, G.P.

    1978-01-01

    A general purpose electronic logic processor has been designed into a 2 wide NIM (Nuclear Instrumentation Module) bin module. The unit utilizes a microprocessor to achieve necessary versatility. The processor's first use is as a new generation signal analyzer for use in radiometric personnel and vehicle portal monitors. Significant improvements have been obtained in sensitivity and stability over existing analog discriminators. The new analyzer is presently being used to update personnel and vehicle portal monitoring systems

  6. MITF Modulates Therapeutic Resistance through EGFR Signaling.

    Science.gov (United States)

    Ji, Zhenyu; Erin Chen, Yiyin; Kumar, Raj; Taylor, Michael; Jenny Njauw, Ching-Ni; Miao, Benchun; Frederick, Dennie T; Wargo, Jennifer A; Flaherty, Keith T; Jönsson, Göran; Tsao, Hensin

    2015-07-01

    Response to targeted therapies varies significantly despite shared oncogenic mutations. Nowhere is this more apparent than in BRAF (V600E)-mutated melanomas where initial drug response can be striking and yet relapse is commonplace. Resistance to BRAF inhibitors have been attributed to the activation of various receptor tyrosine kinases (RTKs), although the underlying mechanisms have been largely uncharacterized. Here, we found that EGFR-induced vemurafenib resistance is ligand dependent. We employed whole-genome expression analysis and discovered that vemurafenib resistance correlated with the loss of microphthalmia-associated transcription factor (MITF), along with its melanocyte lineage program, and with the activation of EGFR signaling. An inverse relationship between MITF, vemurafenib resistance, and EGFR was then observed in patient samples of recurrent melanoma and was conserved across melanoma cell lines and patients' tumor specimens. Functional studies revealed that MITF depletion activated EGFR signaling and consequently recapitulated the resistance phenotype. In contrast, forced expression of MITF in melanoma and colon cancer cells inhibited EGFR and conferred sensitivity to BRAF/MEK inhibitors. These findings indicate that an "autocrine drug resistance loop" is suppressed by melanocyte lineage signal(s), such as MITF. This resistance loop modulates drug response and could explain the unique sensitivity of melanomas to BRAF inhibition.

  7. Phonological experience modulates voice discrimination: Evidence from functional brain networks analysis.

    Science.gov (United States)

    Hu, Xueping; Wang, Xiangpeng; Gu, Yan; Luo, Pei; Yin, Shouhang; Wang, Lijun; Fu, Chao; Qiao, Lei; Du, Yi; Chen, Antao

    2017-10-01

    Numerous behavioral studies have found a modulation effect of phonological experience on voice discrimination. However, the neural substrates underpinning this phenomenon are poorly understood. Here we manipulated language familiarity to test the hypothesis that phonological experience affects voice discrimination via mediating the engagement of multiple perceptual and cognitive resources. The results showed that during voice discrimination, the activation of several prefrontal regions was modulated by language familiarity. More importantly, the same effect was observed concerning the functional connectivity from the fronto-parietal network to the voice-identity network (VIN), and from the default mode network to the VIN. Our findings indicate that phonological experience could bias the recruitment of cognitive control and information retrieval/comparison processes during voice discrimination. Therefore, the study unravels the neural substrates subserving the modulation effect of phonological experience on voice discrimination, and provides new insights into studying voice discrimination from the perspective of network interactions. Copyright © 2017. Published by Elsevier Inc.

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

    Indian Academy of Sciences (India)

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

  9. Discrimination in the Forest Industry: A Teaching Module.

    Science.gov (United States)

    Eylon, Dafna; Langton, Nancy

    1998-01-01

    A case study of a female chief executive officer denied membership in an industry-related social club helps students understand discrimination and the interaction of personal and organizational goals. The exercise creates awareness of ways to respond to discrimination and of gender and power issues in the workplace. (SK)

  10. Modulating wavelength discrimination in goldfish with ethambutol and stimulus intensity

    NARCIS (Netherlands)

    Sjoerdsma, T.; Kamermans, M.; Spekreijse, H.

    1996-01-01

    Wavelength discrimination in goldfish was measured behaviourally. Both acute application of ethambutol injected into the eye and chronic application by feeding the animals daily 25 mg ethambutol for 1 month had the same effect on wavelength discrimination in the range of 560-640 nm. This means that:

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

    Indian Academy of Sciences (India)

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

  12. Computational expressions for signals in frequency-modulation spectroscopy.

    Science.gov (United States)

    Di Rosa, Michael D; Reiten, M T

    2015-06-01

    General expressions for the signals in frequency-modulation spectroscopy (FMS) appear in the literature but are often reduced to simple analytical equations following the assumption of a weak modulation index. This is little help to the experimentalist who wants to predict signals for modulation depths of the order of unity or greater, where strong FMS signals reside. Here, we develop general formulas for FMS signals in the case of an absorber with a Voigt line shape and then link these expressions to an example and existing numerical code for the line shape. The resulting computational recipe is easy to implement and exercised here to show where the larger FMS signals are found over the coordinates of modulation index and modulation frequency. One can also estimate from provided curves the in-phase FMS signal over a wide range of modulation parameters at either the Lorentzian-broadening or Doppler-broadening limit, or anywhere in between by interpolation.

  13. Infants Discriminate Voicing and Place of Articulation with Reduced Spectral and Temporal Modulation Cues

    Science.gov (United States)

    Cabrera, Laurianne; Lorenzi, Christian; Bertoncini, Josiane

    2015-01-01

    Purpose: This study assessed the role of spectro-temporal modulation cues in the discrimination of 2 phonetic contrasts (voicing and place) for young infants. Method: A visual-habituation procedure was used to assess the ability of French-learning 6-month-old infants with normal hearing to discriminate voiced versus unvoiced (/aba/-/apa/) and…

  14. Role of the middle ear muscle apparatus in mechanisms of speech signal discrimination

    Science.gov (United States)

    Moroz, B. S.; Bazarov, V. G.; Sachenko, S. V.

    1980-01-01

    A method of impedance reflexometry was used to examine 101 students with hearing impairment in order to clarify the interrelation between speech discrimination and the state of the middle ear muscles. Ability to discriminate speech signals depends to some extent on the functional state of intraaural muscles. Speech discrimination was greatly impaired in the absence of stapedial muscle acoustic reflex, in the presence of low thresholds of stimulation and in very small values of reflex amplitude increase. Discrimination was not impeded in positive AR, high values of relative thresholds and normal increase of reflex amplitude in response to speech signals with augmenting intensity.

  15. Gearbox Vibration Signal Amplitude and Frequency Modulation

    Directory of Open Access Journals (Sweden)

    Fakher Chaari

    2012-01-01

    Full Text Available Gearboxes usually run under fluctuating load conditions during service, however most of papers available in the literature describe models of gearboxes under stationary load conditions. Main task of published papers is fault modeling for their detection. Considering real situation from industry, the assumption of stationarity of load conditions cannot be longer kept. Vibration signals issued from monitoring in maintenance operations differ from mentioned models (due to load non-stationarity and may be difficult to analyze which lead to erroneous diagnosis of the system. The objective of this paper is to study the influence of time varying load conditions on a gearbox dynamic behavior. To investigate this, a simple spur gear system without defects is modeled. It is subjected to a time varying load. The speed-torque characteristic of the driving motor is considered. The load variation induces speed variation, which causes a variation in the gearmesh stiffness period. Computer simulation shows deep amplitude modulations with sidebands that don't differ from those obtained when there is a defective tooth. In order to put in evidence the time varying load effects, Short Time Fourier Transform and then Smoothed Wigner-Ville distribution are used. Results show that the last one is well suited for the studied case.

  16. Integrated InP frequency discriminator for Phase-modulated microwave photonic links.

    Science.gov (United States)

    Fandiño, J S; Doménech, J D; Muñoz, P; Capmany, J

    2013-02-11

    We report the design, fabrication and characterization of an integrated frequency discriminator on InP technology for microwave photonic phase modulated links. The optical chip is, to the best of our knowledge, the first reported in an active platform and the first to include the optical detectors. The discriminator, designed as a linear filter in intensity, features preliminary SFDR values the range between 67 and 79 dB.Hz(2/3) for signal frequencies in the range of 5-9 GHz limited, in principle, by the high value of the optical losses arising from the use of several free space coupling devices in our experimental setup. As discussed, these losses can be readily reduced by the use of integrated spot-size converters improving the SFDR by 17.3 dB (84-96 dB.Hz(2/3)). Further increase up to a range of (104-116 dB.Hz(2/3)) is possible by reducing the system noise eliminating the EDFA employed in the setup and using a commercially available laser source providing higher output power and lower relative intensity noise. Other paths for improvement requiring a filter redesign to be linear in the optical field are also discussed.

  17. Discrimination of acoustic communication signals by grasshoppers (Chorthippus biguttulus): temporal resolution, temporal integration, and the impact of intrinsic noise.

    Science.gov (United States)

    Ronacher, Bernhard; Wohlgemuth, Sandra; Vogel, Astrid; Krahe, Rüdiger

    2008-08-01

    A characteristic feature of hearing systems is their ability to resolve both fast and subtle amplitude modulations of acoustic signals. This applies also to grasshoppers, which for mate identification rely mainly on the characteristic temporal patterns of their communication signals. Usually the signals arriving at a receiver are contaminated by various kinds of noise. In addition to extrinsic noise, intrinsic noise caused by stochastic processes within the nervous system contributes to making signal recognition a difficult task. The authors asked to what degree intrinsic noise affects temporal resolution and, particularly, the discrimination of similar acoustic signals. This study aims at exploring the neuronal basis for sexual selection, which depends on exploiting subtle differences between basically similar signals. Applying a metric, by which the similarities of spike trains can be assessed, the authors investigated how well the communication signals of different individuals of the same species could be discriminated and correctly classified based on the responses of auditory neurons. This spike train metric yields clues to the optimal temporal resolution with which spike trains should be evaluated. (c) 2008 APA, all rights reserved

  18. Spatial Long-Range Modulation of Contrast Discrimination

    Science.gov (United States)

    2000-07-01

    details. power p and then divided by the divisive 91 inhibitory input (I) plus an additive constant. That is, R EPR = -- (1) I+a where c is an...contrast and contrast discrimination. Vision Research, 38, 1935 -1945. 18. Solomon, J. A., Watson, A. B. & Morgan, M. J. (1999). Transducer model produces

  19. Simulation of neutrons and gamma pulse signal and research on the pulse shape discrimination technology

    International Nuclear Information System (INIS)

    Zuo Guangxia; He Bin; Xu Peng; Qiu Xiaolin; Ma Wenyan; Li Sufen

    2012-01-01

    In neutrons detection, it is important to discriminate the neutron signals from the gamma-ray background. In this article, simulation of neutrons and gamma pulse signals is developed based on the LabVIEW platform. Two digital algorithms of the charge comparison method and the pulse duration time method are realized using 10000 simulation signals. Experimental results show that neutron and gamma pulse signals can be discriminated by the two methods, and the pulse duration time method is better than the charge comparison method. (authors)

  20. Research on n-γ discrimination method based on spectrum gradient analysis of signals

    International Nuclear Information System (INIS)

    Luo Xiaoliang; Liu Guofu; Yang Jun; Wang Yueke

    2013-01-01

    Having discovered that there are distinct differences between the spectrum gradient of the output neutron and γ-ray signal from liquid scintillator detectors, this paper presented a n-γ discrimination method called spectrum gradient analysis (SGA) based on frequency-domain features of the pulse signals. The basic principle and feasibility of SGA method were discussed and the validity of n-γ discrimination results of SGA was verified by the associated particle neutron flight experiment. The discrimination performance of SGA was evaluated under different conditions of sampling rates ranging from 5 G/s to 250 M/s. The results show that SGA method exhibits insensitivity to noise, strong anti-interference ability, stable discrimination performance and lower amount of calculation in contrast with time-domain n-γ discrimination methods. (authors)

  1. Signal modulation as a mechanism for handicap disposal

    Science.gov (United States)

    Gavassa, Sat; Silva, Ana C.; Gonzalez, Emmanuel; Stoddard, Philip K.

    2012-01-01

    Signal honesty may be compromised when heightened competition provides incentive for signal exaggeration. Some degree of honesty might be maintained by intrinsic handicap costs on signalling or through imposition of extrinsic costs, such as social punishment of low quality cheaters. Thus, theory predicts a delicate balance between signal enhancement and signal reliability that varies with degree of social competition, handicap cost, and social cost. We investigated whether male sexual signals of the electric fish Brachyhypopomus gauderio would become less reliable predictors of body length when competition provides incentives for males to boost electric signal amplitude. As expected, social competition under natural field conditions and in controlled lab experiments drove males to enhance their signals. However, signal enhancement improved the reliability of the information conveyed by the signal, as revealed in the tightening of the relationship between signal amplitude and body length. Signal augmentation in male B. gauderio was independent of body length, and thus appeared not to be curtailed through punishment of low quality (small) individuals. Rather, all individuals boosted their signals under high competition, but those whose signals were farthest from the predicted value under low competition boosted signal amplitude the most. By elimination, intrinsic handicap cost of signal production, rather than extrinsic social cost, appears to be the basis for the unexpected reinforcement of electric signal honesty under social competition. Signal modulation may provide its greatest advantage to the signaller as a mechanism for handicap disposal under low competition rather than as a mechanism for exaggeration of quality under high competition. PMID:22665940

  2. Frequency modulator. Transmission of meteorological signals in LVC

    International Nuclear Information System (INIS)

    Rivero G, P.T.; Ramirez S, R.; Gonzalez M, J.L.; Rojas N, P.; Celis del Angel, L.

    2007-01-01

    The development of the frequency modulator and demodulator circuit for transmission of meteorological signals by means of fiber optics of the meteorology station to the nuclear reactor unit 1 in the Laguna Verde Central in Veracruz is described. (Author)

  3. All-optical microwave signal processing based on optical phase modulation

    Science.gov (United States)

    Zeng, Fei

    This thesis presents a theoretical and experimental study of optical phase modulation and its applications in all-optical microwave signal processing, which include all-optical microwave filtering, all-optical microwave mixing, optical code-division multiple-access (CDMA) coding, and ultrawideband (UWB) signal generation. All-optical microwave signal processing can be considered as the use of opto-electronic devices and systems to process microwave signals in the optical domain, which provides several significant advantages such as low loss, low dispersion, light weight, high time bandwidth products, and immunity to electromagnetic interference. In conventional approaches, the intensity of an optical carrier is modulated by a microwave signal based on direct modulation or external modulation. The intensity-modulated optical signal is then fed to a photonic circuit or system to achieve specific signal processing functionalities. The microwave signal being processed is usually obtained based on direct detection, i.e., an opto-electronic conversion by use of a photodiode. In this thesis, the research efforts are focused on the optical phase modulation and its applications in all-optical microwave signal processing. To avoid using coherent detection which is complicated and costly, simple and effective phase modulation to intensity modulation (PM-IM) conversion schemes are pursued. Based on a theoretical study of optical phase modulation, two approaches to achieving PM-IM conversions are proposed. In the first approach, the use of chromatic dispersion induced by a dispersive device to alter the phase relationships among the sidebands and the optical carrier of a phase-modulated optical signal to realize PM-IM conversion is investigated. In the second approach, instead of using a dispersive device, the PM-IM conversion is realized based on optical frequency discrimination implemented using an optical filter. We show that the proposed PM-IM conversion schemes can be

  4. Signal Constellations for Multilevel Coded Modulation with Sparse Graph Codes

    NARCIS (Netherlands)

    Cronie, H.S.

    2005-01-01

    A method to combine error-correction coding and spectral efficient modulation for transmission over channels with Gaussian noise is presented. The method of modulation leads to a signal constellation in which the constellation symbols have a nonuniform distribution. This gives a so-called shape gain

  5. Spectral Correlation of Multicarrier Modulated Signals and Its Application for Signal Detection

    Directory of Open Access Journals (Sweden)

    Zhang Haijian

    2010-01-01

    Full Text Available Spectral correlation theory for cyclostationary time-series signals has been studied for decades. Explicit formulas of spectral correlation function for various types of analog-modulated and digital-modulated signals are already derived. In this paper, we investigate and exploit the cyclostationarity characteristics for two kinds of multicarrier modulated (MCM signals: conventional OFDM and filter bank based multicarrier (FBMC signals. The spectral correlation characterization of MCM signal can be described by a special linear periodic time-variant (LPTV system. Using this LPTV description, we have derived the explicit theoretical formulas of nonconjugate and conjugate cyclic autocorrelation function (CAF and spectral correlation function (SCF for OFDM and FBMC signals. According to theoretical spectral analysis, Cyclostationary Signatures (CS are artificially embedded into MCM signal and a low-complexity signature detector is, therefore, presented for detecting MCM signal. Theoretical analysis and simulation results demonstrate the efficiency and robustness of this CS detector compared to traditionary energy detector.

  6. Chemical Modulation of WNT Signaling in Cancer.

    Science.gov (United States)

    Zhang, Li-Shu; Lum, Lawrence

    2018-01-01

    Genetically based observations stemming from defects in development and in regeneration form the foundation of our understanding regarding how the secreted WNT proteins control coordinated cell fate decision-making in adult tissues. At the same time, our anticipation of potential benefits and unwanted toxicities associated with candidate anticancer agents targeting WNT signal transduction are also reliant upon this blueprint of WNT-associated physiology. Despite the long established role of WNT signaling in cancer, the emergence of WNT signaling as a suppressor of immunological attack in melanoma reveals an unanticipated anticancer potential in targeting WNT signaling. Here we review the literature associated with WNT signaling in cancer and discuss potential challenges that may be associated with the chemical attack of this important cellular process in achieving therapeutic goals. Although a number of small molecules targeting WNT signaling are introduced here, we center our discussion on antagonists of the WNT acyltransferase porcupine (PORCN) given the recent entry of two candidate molecules in clinical testing. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. On chip frequency discriminator for microwave photonics signal processing

    NARCIS (Netherlands)

    Marpaung, D.A.I.; Roeloffzen, C.G.H.

    2012-01-01

    Microwave photonics (MWP) techniques for the generation, distribution and pro- cessing of radio frequency (RF) signals have enjoyed a surge of interest in the last few years. The workhorse behind these MWP functionalities is a high performance MWP link. Such a link needs to fulfill several criteria

  8. Plant MAPK cascades: Just rapid signaling modules?

    KAUST Repository

    Boudsocq, Marie; Danquah, Agyemang; Zé licourt, Axel de; Hirt, Heribert; Colcombet, Jean

    2015-01-01

    rapid MAPK activation, we showed that the activation of the new MAPK module is delayed and relies on the MAP3K protein synthesis. In this addendum, we discuss the role of this original and unexpected activation mechanism of MAPK cascades which suggests

  9. Wavelet transform and real-time learning method for myoelectric signal in motion discrimination

    International Nuclear Information System (INIS)

    Liu Haihua; Chen Xinhao; Chen Yaguang

    2005-01-01

    This paper discusses the applicability of the Wavelet transform for analyzing an EMG signal and discriminating motion classes. In many previous works, researchers have dealt with steady EMG and have proposed suitable analyzing methods for the EMG, for example FFT and STFT. Therefore, it is difficult for the previous approaches to discriminate motions from the EMG in the different phases of muscle activity, i.e., pre-activity, in activity, postactivity phases, as well as the period of motion transition from one to another. In this paper, we introduce the Wavelet transform using the Coiflet mother wavelet into our real-time EMG prosthetic hand controller for discriminating motions from steady and unsteady EMG. A preliminary experiment to discriminate three hand motions from four channel EMG in the initial pre-activity and in activity phase is carried out to show the effectiveness of the approach. However, future research efforts are necessary to discriminate more motions much precisely

  10. Distortions caused by the signal processing in analog AM modulators

    International Nuclear Information System (INIS)

    Njau, E.C.

    1988-08-01

    Complete analytical expressions for distortions caused by signal processing in analog AM modulators are developed. The salient features in these expressions are shown to be consistent with displays of actual spectra of AM signals. Finally suggestions are given on how the distortions may be practically minimized. (author). 6 refs, 3 figs

  11. Study on non-linear bistable dynamics model based EEG signal discrimination analysis method.

    Science.gov (United States)

    Ying, Xiaoguo; Lin, Han; Hui, Guohua

    2015-01-01

    Electroencephalogram (EEG) is the recording of electrical activity along the scalp. EEG measures voltage fluctuations generating from ionic current flows within the neurons of the brain. EEG signal is looked as one of the most important factors that will be focused in the next 20 years. In this paper, EEG signal discrimination based on non-linear bistable dynamical model was proposed. EEG signals were processed by non-linear bistable dynamical model, and features of EEG signals were characterized by coherence index. Experimental results showed that the proposed method could properly extract the features of different EEG signals.

  12. A common signal detection model accounts for both perception and discrimination of the watercolor effect.

    Science.gov (United States)

    Devinck, Frédéric; Knoblauch, Kenneth

    2012-03-21

    Establishing the relation between perception and discrimination is a fundamental objective in psychophysics, with the goal of characterizing the neural mechanisms mediating perception. Here, we show that a procedure for estimating a perceptual scale based on a signal detection model also predicts discrimination performance. We use a recently developed procedure, Maximum Likelihood Difference Scaling (MLDS), to measure the perceptual strength of a long-range, color, filling-in phenomenon, the Watercolor Effect (WCE), as a function of the luminance ratio between the two components of its generating contour. MLDS is based on an equal-variance, gaussian, signal detection model and yields a perceptual scale with interval properties. The strength of the fill-in percept increased 10-15 times the estimate of the internal noise level for a 3-fold increase in the luminance ratio. Each observer's estimated scale predicted discrimination performance in a subsequent paired-comparison task. A common signal detection model accounts for both the appearance and discrimination data. Since signal detection theory provides a common metric for relating discrimination performance and neural response, the results have implications for comparing perceptual and neural response functions.

  13. Automated identification of RNA 3D modules with discriminative power in RNA structural alignments

    DEFF Research Database (Denmark)

    Theis, Corinna; Höner zu Siederdissen, Christian; Hofacker, Ivo L.

    2013-01-01

    Recent progress in predicting RNA structure is moving towards filling the 'gap' in 2D RNA structure prediction where, for example, predicted internal loops often form non-canonical base pairs. This is increasingly recognized with the steady increase of known RNA 3D modules. There is a general...... comparative evidence. Subsequently, the modules, initially represented by a graph, are turned into models for the RMDetect program, which allows to test their discriminative power using real and randomized Rfam alignments. An initial extraction of 22495 3D modules in all PDB files results in 977 internal loop...

  14. Concentrated pitch discrimination modulates auditory brainstem responses during contralateral noise exposure.

    Science.gov (United States)

    Ikeda, Kazunari; Sekiguchi, Takahiro; Hayashi, Akiko

    2010-03-31

    This study examined a notion that auditory discrimination is a requisite for attention-related modulation of the auditory brainstem response (ABR) during contralateral noise exposure. Given that the right ear was exposed continuously with white noise at an intensity of 60-80 dB sound pressure level, tone pips at 80 dB sound pressure level were delivered to the left ear through either single-stimulus or oddball procedures. Participants conducted reading (ignoring task) and counting target tones (attentive task) during stimulation. The oddball but not the single-stimulus procedures elicited task-related modulations in both early (ABR) and late (processing negativity) event-related potentials simultaneously. The elicitation of the attention-related ABR modulation during contralateral noise exposure is thus considered to require auditory discrimination and have the corticofugal nature evidently.

  15. MTR2: a discriminator and dead-time module used in counting systems

    International Nuclear Information System (INIS)

    Bouchard, J.

    2000-01-01

    In the field of radioactivity measurement, there is a constant need for highly specialized electronic modules such as ADCs, amplifiers, discriminators, dead-time modules, etc. But sometimes it is almost impossible to find on the market the modules having the performances corresponding to our needs. The purpose of the module presented here, called MTR2 (Module de Temps-mort Reconductible), is to process, in terms of pulse height discrimination and dead-time corrections, the pulses delivered by the detectors used in counting systems. This dead-time, of the extendible type, is triggered by both the positive and negative parts of the incoming pulse and the dead-time corrections are made according to the live-time method. This module, which has been developed and tested at LPRI, can be used alone in simple counting channels or in more complex systems such as coincidence systems. The philosophy governing the choice and the implementation of this type of dead-time as well as the system used for the dead-time corrections is presented. The electronic scheme and the performances are also presented. This module is available in the NIM standard

  16. Isolating spectral cues in amplitude and quasi-frequency modulation discrimination by reducing stimulus duration.

    Science.gov (United States)

    Borucki, Ewa; Berg, Bruce G

    2017-05-01

    This study investigated the psychophysical effects of distortion products in a listening task traditionally used to estimate the bandwidth of phase sensitivity. For a 2000 Hz carrier, estimates of modulation depth necessary to discriminate amplitude modulated (AM) tones and quasi-frequency modulated (QFM) were measured in a two interval forced choice task as a function modulation frequency. Temporal modulation transfer functions were often non-monotonic at modulation frequencies above 300 Hz. This was likely to be due to a spectral cue arising from the interaction of auditory distortion products and the lower sideband of the stimulus complex. When the stimulus duration was decreased from 200 ms to 20 ms, thresholds for low-frequency modulators rose to near-chance levels, whereas thresholds in the region of non-monotonicities were less affected. The decrease in stimulus duration appears to hinder the listener's ability to use temporal cues in order to discriminate between AM and QFM, whereas spectral information derived from distortion product cues appears more resilient. Copyright © 2017. Published by Elsevier B.V.

  17. Device for the track useful signal discrimination during the image scanning form bubble chambers

    International Nuclear Information System (INIS)

    Osipov, E.A.; Uvarov, V.A.

    1976-01-01

    A device for the image processing from the bubble chambers, developed to increase the reliability of the track useful signal discrimination at the image scanning from the background component is described. The device consists of a low-pass filter, repetition and memory circuit and subtraction circuit. Besides a delay line and extra channel consisting of a differentiating circuit in series with the selective shaping circuit are introduced into the device. The output signal of the selective shaping is the controlling signal of the repetition and memory circuit, at the output of which a signal corresponding the background component is formed. The functional diagram of the device operation is presented

  18. Agmatine modulates melanogenesis via MITF signaling pathway.

    Science.gov (United States)

    Kwon, Eun-Jeong; Kim, Moon-Moo

    2017-01-01

    Agmatine contained in soybean is also found in Manaca, an anti-aging plant, inhabited in Amazon and induces vasodilation by the promotion of NO synthesis in blood vessel. However, the research of agmatine on melanin synthesis related to hair greying is lacking. The aim of this study was to investigate the melanogenic effect of agmatine via regulation of MITF signaling pathway in B16F1 cells. It was determined whether agmatine regulates melanin synthesis at cellular level in addition to the effect of agmatine on mushroom tyrosinase in vitro in the presence of different concentrations of agmatine. Furthermore, the effect of agmatine on the protein expressions of tyrosinase, TRP-1, TRP-2, BMP-4, BMP-6, C-KIT, p-p38, MITF and C-FOS were examined by western blot analysis. In addition, immunofluorescence staining was carried out to visualize the location of MITF expression in cell. Agmatine at 256μM or more increased melanin synthesis as well as tyrosinase activity. Moreover, whereas agmatine increased the expression levels of TRP-1, BMP-6, p-p38 and MITF, it reduced the expression level of BMP-4. It was also found that agmatine enhanced the expression level of MITF in nucleus. These results suggest that agmatine could induce melanin synthesis though the regulation of MITF transcription factor via BMP-6/p38 signaling pathway. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Input from the Medial Geniculate Nucleus Modulates Amygdala Encoding of Fear Memory Discrimination

    Science.gov (United States)

    Ferrara, Nicole C.; Cullen, Patrick K.; Pullins, Shane P.; Rotondo, Elena K.; Helmstetter, Fred J.

    2017-01-01

    Generalization of fear can involve abnormal responding to cues that signal safety and is common in people diagnosed with post-traumatic stress disorder. Differential auditory fear conditioning can be used as a tool to measure changes in fear discrimination and generalization. Most prior work in this area has focused on elevated amygdala activity…

  20. Real-time detection and discrimination of visual perception using electrocorticographic signals

    Science.gov (United States)

    Kapeller, C.; Ogawa, H.; Schalk, G.; Kunii, N.; Coon, W. G.; Scharinger, J.; Guger, C.; Kamada, K.

    2018-06-01

    Objective. Several neuroimaging studies have demonstrated that the ventral temporal cortex contains specialized regions that process visual stimuli. This study investigated the spatial and temporal dynamics of electrocorticographic (ECoG) responses to different types and colors of visual stimulation that were presented to four human participants, and demonstrated a real-time decoder that detects and discriminates responses to untrained natural images. Approach. ECoG signals from the participants were recorded while they were shown colored and greyscale versions of seven types of visual stimuli (images of faces, objects, bodies, line drawings, digits, and kanji and hiragana characters), resulting in 14 classes for discrimination (experiment I). Additionally, a real-time system asynchronously classified ECoG responses to faces, kanji and black screens presented via a monitor (experiment II), or to natural scenes (i.e. the face of an experimenter, natural images of faces and kanji, and a mirror) (experiment III). Outcome measures in all experiments included the discrimination performance across types based on broadband γ activity. Main results. Experiment I demonstrated an offline classification accuracy of 72.9% when discriminating among the seven types (without color separation). Further discrimination of grey versus colored images reached an accuracy of 67.1%. Discriminating all colors and types (14 classes) yielded an accuracy of 52.1%. In experiment II and III, the real-time decoder correctly detected 73.7% responses to face, kanji and black computer stimuli and 74.8% responses to presented natural scenes. Significance. Seven different types and their color information (either grey or color) could be detected and discriminated using broadband γ activity. Discrimination performance maximized for combined spatial-temporal information. The discrimination of stimulus color information provided the first ECoG-based evidence for color-related population

  1. Probiotic Modulation of Innate Cell Pathogen Sensing and Signaling Events

    Directory of Open Access Journals (Sweden)

    Amy Llewellyn

    2017-10-01

    Full Text Available There is a growing body of evidence documenting probiotic bacteria to have a beneficial effect to the host through their ability to modulate the mucosal immune system. Many probiotic bacteria can be considered to act as either immune activators or immune suppressors, which have appreciable influence on homeostasis, inflammatory- and suppressive-immunopathology. What is becoming apparent is the ability of these probiotics to modulate innate immune responses via direct or indirect effects on the signaling pathways that drive these activatory or suppressive/tolerogenic mechanisms. This review will focus on the immunomodulatory role of probiotics on signaling pathways in innate immune cells: from positive to negative regulation associated with innate immune cells driving gut mucosal functionality. Research investigations have shown probiotics to modulate innate functionality in many ways including, receptor antagonism, receptor expression, binding to and expression of adaptor proteins, expression of negative regulatory signal molecules, induction of micro-RNAs, endotoxin tolerisation and finally, the secretion of immunomodulatory proteins, lipids and metabolites. The detailed understanding of the immunomodulatory signaling effects of probiotic strains will facilitate strain-specific selective manipulation of innate cell signal mechanisms in the modulation of mucosal adjuvanticity, immune deviation and tolerisation in both healthy subjects and patients with inflammatory and suppressive pathology.

  2. Probiotic Modulation of Innate Cell Pathogen Sensing and Signaling Events

    Science.gov (United States)

    Llewellyn, Amy; Foey, Andrew

    2017-01-01

    There is a growing body of evidence documenting probiotic bacteria to have a beneficial effect to the host through their ability to modulate the mucosal immune system. Many probiotic bacteria can be considered to act as either immune activators or immune suppressors, which have appreciable influence on homeostasis, inflammatory- and suppressive-immunopathology. What is becoming apparent is the ability of these probiotics to modulate innate immune responses via direct or indirect effects on the signaling pathways that drive these activatory or suppressive/tolerogenic mechanisms. This review will focus on the immunomodulatory role of probiotics on signaling pathways in innate immune cells: from positive to negative regulation associated with innate immune cells driving gut mucosal functionality. Research investigations have shown probiotics to modulate innate functionality in many ways including, receptor antagonism, receptor expression, binding to and expression of adaptor proteins, expression of negative regulatory signal molecules, induction of micro-RNAs, endotoxin tolerisation and finally, the secretion of immunomodulatory proteins, lipids and metabolites. The detailed understanding of the immunomodulatory signaling effects of probiotic strains will facilitate strain-specific selective manipulation of innate cell signal mechanisms in the modulation of mucosal adjuvanticity, immune deviation and tolerisation in both healthy subjects and patients with inflammatory and suppressive pathology. PMID:29065562

  3. Vitamin D Signaling Modulators in Cancer Therapy.

    Science.gov (United States)

    Luo, Wei; Johnson, Candace S; Trump, Donald L

    2016-01-01

    The antiproliferative and pro-apoptotic effects of 1α,25-dihydroxycholecalciferol (1,25(OH)2D3, 1,25D3, calcitriol) have been demonstrated in various tumor model systems in vitro and in vivo. However, limited antitumor effects of 1,25D3 have been observed in clinical trials. This may be attributed to a variety of factors including overexpression of the primary 1,25D3 degrading enzyme, CYP24A1, in tumors, which would lead to rapid local inactivation of 1,25D3. An alternative strategy for improving the antitumor activity of 1,25D3 involves the combination with a selective CYP24A1 inhibitor. The validity of this approach is supported by numerous preclinical investigations, which demonstrate that CYP24A1 inhibitors suppress 1,25D3 catabolism in tumor cells and increase the effects of 1,25D3 on gene expression and cell growth. Studies are now required to determine whether selective CYP24A1 inhibitors+1,25D3 can be used safely and effectively in patients. CYP24A1 inhibitors plus 1,25D3 can cause dose-limiting toxicity of vitamin D (hypercalcemia) in some patients. Dexamethasone significantly reduces 1,25D3-mediated hypercalcemia and enhances the antitumor activity of 1,25D3, increases VDR-ligand binding, and increases VDR protein expression. Efforts to dissect the mechanisms responsible for CYP24A1 overexpression and combinational effect of 1,25D3/dexamethasone in tumors are underway. Understanding the cross talk between vitamin D receptor (VDR) and glucocorticoid receptor (GR) signaling axes is of crucial importance to the design of new therapies that include 1,25D3 and dexamethasone. Insights gained from these studies are expected to yield novel strategies to improve the efficacy of 1,25D3 treatment. © 2016 Elsevier Inc. All rights reserved.

  4. Load-induced modulation of signal transduction networks.

    Science.gov (United States)

    Jiang, Peng; Ventura, Alejandra C; Sontag, Eduardo D; Merajver, Sofia D; Ninfa, Alexander J; Del Vecchio, Domitilla

    2011-10-11

    Biological signal transduction networks are commonly viewed as circuits that pass along information--in the process amplifying signals, enhancing sensitivity, or performing other signal-processing tasks--to transcriptional and other components. Here, we report on a "reverse-causality" phenomenon, which we call load-induced modulation. Through a combination of analytical and experimental tools, we discovered that signaling was modulated, in a surprising way, by downstream targets that receive the signal and, in doing so, apply what in physics is called a load. Specifically, we found that non-intuitive changes in response dynamics occurred for a covalent modification cycle when load was present. Loading altered the response time of a system, depending on whether the activity of one of the enzymes was maximal and the other was operating at its minimal rate or whether both enzymes were operating at submaximal rates. These two conditions, which we call "limit regime" and "intermediate regime," were associated with increased or decreased response times, respectively. The bandwidth, the range of frequency in which the system can process information, decreased in the presence of load, suggesting that downstream targets participate in establishing a balance between noise-filtering capabilities and a circuit's ability to process high-frequency stimulation. Nodes in a signaling network are not independent relay devices, but rather are modulated by their downstream targets.

  5. Analysis of pulse-shape discrimination techniques for BC501A using GHz digital signal processing

    International Nuclear Information System (INIS)

    Rooney, B.D.; Dinwiddie, D.R.; Nelson, M.A.; Rawool-Sullivan, Mohini W.

    2001-01-01

    A comparison study of pulse-shape analysis techniques was conducted for a BC501A scintillator using digital signal processing (DSP). In this study, output signals from a preamplifier were input directly into a 1 GHz analog-to-digital converter. The digitized data obtained with this method was post-processed for both pulse-height and pulse-shape information. Several different analysis techniques were evaluated for neutron and gamma-ray pulse-shape discrimination. It was surprising that one of the simplest and fastest techniques resulted in some of the best pulse-shape discrimination results. This technique, referred to here as the Integral Ratio technique, was able to effectively process several thousand detector pulses per second. This paper presents the results and findings of this study for various pulse-shape analysis techniques with digitized detector signals.

  6. Psilocybin modulates functional connectivity of the amygdala during emotional face discrimination.

    Science.gov (United States)

    Grimm, O; Kraehenmann, R; Preller, K H; Seifritz, E; Vollenweider, F X

    2018-04-24

    Recent studies suggest that the antidepressant effects of the psychedelic 5-HT2A receptor agonist psilocybin are mediated through its modulatory properties on prefrontal and limbic brain regions including the amygdala. To further investigate the effects of psilocybin on emotion processing networks, we studied for the first-time psilocybin's acute effects on amygdala seed-to-voxel connectivity in an event-related face discrimination task in 18 healthy volunteers who received psilocybin and placebo in a double-blind balanced cross-over design. The amygdala has been implicated as a salience detector especially involved in the immediate response to emotional face content. We used beta-series amygdala seed-to-voxel connectivity during an emotional face discrimination task to elucidate the connectivity pattern of the amygdala over the entire brain. When we compared psilocybin to placebo, an increase in reaction time for all three categories of affective stimuli was found. Psilocybin decreased the connectivity between amygdala and the striatum during angry face discrimination. During happy face discrimination, the connectivity between the amygdala and the frontal pole was decreased. No effect was seen during discrimination of fearful faces. Thus, we show psilocybin's effect as a modulator of major connectivity hubs of the amygdala. Psilocybin decreases the connectivity between important nodes linked to emotion processing like the frontal pole or the striatum. Future studies are needed to clarify whether connectivity changes predict therapeutic effects in psychiatric patients. Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.

  7. Coco is a dual activity modulator of TGFβ signaling

    Science.gov (United States)

    Deglincerti, Alessia; Haremaki, Tomomi; Warmflash, Aryeh; Sorre, Benoit; Brivanlou, Ali H.

    2015-01-01

    The TGFβ signaling pathway is a crucial regulator of developmental processes and disease. The activity of TGFβ ligands is modulated by various families of soluble inhibitors that interfere with the interactions between ligands and receptors. In an unbiased, genome-wide RNAi screen to identify genes involved in ligand-dependent signaling, we unexpectedly identified the BMP/Activin/Nodal inhibitor Coco as an enhancer of TGFβ1 signaling. Coco synergizes with TGFβ1 in both cell culture and Xenopus explants. Molecularly, Coco binds to TGFβ1 and enhances TGFβ1 binding to its receptor Alk5. Thus, Coco acts as both an inhibitor and an enhancer of signaling depending on the ligand it binds. This finding raises the need for a global reconsideration of the molecular mechanisms regulating TGFβ signaling. PMID:26116664

  8. Spatiotemporal Relationships among Audiovisual Stimuli Modulate Auditory Facilitation of Visual Target Discrimination.

    Science.gov (United States)

    Li, Qi; Yang, Huamin; Sun, Fang; Wu, Jinglong

    2015-03-01

    Sensory information is multimodal; through audiovisual interaction, task-irrelevant auditory stimuli tend to speed response times and increase visual perception accuracy. However, mechanisms underlying these performance enhancements have remained unclear. We hypothesize that task-irrelevant auditory stimuli might provide reliable temporal and spatial cues for visual target discrimination and behavioral response enhancement. Using signal detection theory, the present study investigated the effects of spatiotemporal relationships on auditory facilitation of visual target discrimination. Three experiments were conducted where an auditory stimulus maintained reliable temporal and/or spatial relationships with visual target stimuli. Results showed that perception sensitivity (d') to visual target stimuli was enhanced only when a task-irrelevant auditory stimulus maintained reliable spatiotemporal relationships with a visual target stimulus. When only reliable spatial or temporal information was contained, perception sensitivity was not enhanced. These results suggest that reliable spatiotemporal relationships between visual and auditory signals are required for audiovisual integration during a visual discrimination task, most likely due to a spread of attention. These results also indicate that auditory facilitation of visual target discrimination follows from late-stage cognitive processes rather than early stage sensory processes. © 2015 SAGE Publications.

  9. Note: Demodulation of spectral signal modulated by optical chopper with unstable modulation frequency.

    Science.gov (United States)

    Zhang, Shengzhao; Li, Gang; Wang, Jiexi; Wang, Donggen; Han, Ying; Cao, Hui; Lin, Ling; Diao, Chunhong

    2017-10-01

    When an optical chopper is used to modulate the light source, the rotating speed of the wheel may vary with time and subsequently cause jitter of the modulation frequency. The amplitude calculated from the modulated signal would be distorted when the frequency fluctuations occur. To precisely calculate the amplitude of the modulated light flux, we proposed a method to estimate the range of the frequency fluctuation in the measurement of the spectrum and then extract the amplitude based on the sum of power of the signal in the selected frequency range. Experiments were designed to test the feasibility of the proposed method and the results showed lower root means square error than the conventional way.

  10. From bird to sparrow: Learning-induced modulations in fine-grained semantic discrimination.

    Science.gov (United States)

    De Meo, Rosanna; Bourquin, Nathalie M-P; Knebel, Jean-François; Murray, Micah M; Clarke, Stephanie

    2015-09-01

    Recognition of environmental sounds is believed to proceed through discrimination steps from broad to more narrow categories. Very little is known about the neural processes that underlie fine-grained discrimination within narrow categories or about their plasticity in relation to newly acquired expertise. We investigated how the cortical representation of birdsongs is modulated by brief training to recognize individual species. During a 60-minute session, participants learned to recognize a set of birdsongs; they improved significantly their performance for trained (T) but not control species (C), which were counterbalanced across participants. Auditory evoked potentials (AEPs) were recorded during pre- and post-training sessions. Pre vs. post changes in AEPs were significantly different between T and C i) at 206-232ms post stimulus onset within a cluster on the anterior part of the left superior temporal gyrus; ii) at 246-291ms in the left middle frontal gyrus; and iii) 512-545ms in the left middle temporal gyrus as well as bilaterally in the cingulate cortex. All effects were driven by weaker activity for T than C species. Thus, expertise in discriminating T species modulated early stages of semantic processing, during and immediately after the time window that sustains the discrimination between human vs. animal vocalizations. Moreover, the training-induced plasticity is reflected by the sharpening of a left lateralized semantic network, including the anterior part of the temporal convexity and the frontal cortex. Training to identify birdsongs influenced, however, also the processing of C species, but at a much later stage. Correct discrimination of untrained sounds seems to require an additional step which results from lower-level features analysis such as apperception. We therefore suggest that the access to objects within an auditory semantic category is different and depends on subject's level of expertise. More specifically, correct intra

  11. Discrimination of Rock Fracture and Blast Events Based on Signal Complexity and Machine Learning

    Directory of Open Access Journals (Sweden)

    Zilong Zhou

    2018-01-01

    Full Text Available The automatic discrimination of rock fracture and blast events is complex and challenging due to the similar waveform characteristics. To solve this problem, a new method based on the signal complexity analysis and machine learning has been proposed in this paper. First, the permutation entropy values of signals at different scale factors are calculated to reflect complexity of signals and constructed into a feature vector set. Secondly, based on the feature vector set, back-propagation neural network (BPNN as a means of machine learning is applied to establish a discriminator for rock fracture and blast events. Then to evaluate the classification performances of the new method, the classifying accuracies of support vector machine (SVM, naive Bayes classifier, and the new method are compared, and the receiver operating characteristic (ROC curves are also analyzed. The results show the new method obtains the best classification performances. In addition, the influence of different scale factor q and number of training samples n on discrimination results is discussed. It is found that the classifying accuracy of the new method reaches the highest value when q = 8–15 or 8–20 and n=140.

  12. Detecting modulated signals in modulated noise: (II) neural thresholds in the songbird forebrain.

    Science.gov (United States)

    Bee, Mark A; Buschermöhle, Michael; Klump, Georg M

    2007-10-01

    Sounds in the real world fluctuate in amplitude. The vertebrate auditory system exploits patterns of amplitude fluctuations to improve signal detection in noise. One experimental paradigm demonstrating these general effects has been used in psychophysical studies of 'comodulation detection difference' (CDD). The CDD effect refers to the fact that thresholds for detecting a modulated, narrowband noise signal are lower when the envelopes of flanking bands of modulated noise are comodulated with each other, but fluctuate independently of the signal compared with conditions in which the envelopes of the signal and flanking bands are all comodulated. Here, we report results from a study of the neural correlates of CDD in European starlings (Sturnus vulgaris). We manipulated: (i) the envelope correlations between a narrowband noise signal and a masker comprised of six flanking bands of noise; (ii) the signal onset delay relative to masker onset; (iii) signal duration; and (iv) masker spectrum level. Masked detection thresholds were determined from neural responses using signal detection theory. Across conditions, the magnitude of neural CDD ranged between 2 and 8 dB, which is similar to that reported in a companion psychophysical study of starlings [U. Langemann & G.M. Klump (2007) Eur. J. Neurosci., 26, 1969-1978]. We found little evidence to suggest that neural CDD resulted from the across-channel processing of auditory grouping cues related to common envelope fluctuations and synchronous onsets between the signal and flanking bands. We discuss a within-channel model of peripheral processing that explains many of our results.

  13. Pump-To-Signal Intensity Modulation Transfer Characteristics in FOPAs: Modulation Frequency and Saturation Effect

    DEFF Research Database (Denmark)

    Lali-Dastjerdi, Zohreh; Cristofori, Valentina; Lund-Hansen, Toke

    2012-01-01

    This paper reports a comprehensive study of pump- to-signal intensity modulation transfer (IMT) in single-pump fiber optic parametric amplifiers (FOPAs). In particular, the IMT is studied for the first time for high-frequency fluctuations of the pump as well as in the saturated gain regime. The IMT...... cut-off frequency in typical single-pump FOPAs is around 100–200 GHz. The possibilities to shift this frequency based on dispersion and nonlinearities involved in the parametric gain are discussed. The severe IMT to the signal at low modulation frequencies can be suppressed by more than 50...

  14. A method for discrimination of noise and EMG signal regions recorded during rhythmic behaviors.

    Science.gov (United States)

    Ying, Rex; Wall, Christine E

    2016-12-08

    Analyses of muscular activity during rhythmic behaviors provide critical data for biomechanical studies. Electrical potentials measured from muscles using electromyography (EMG) require discrimination of noise regions as the first step in analysis. An experienced analyst can accurately identify the onset and offset of EMG but this process takes hours to analyze a short (10-15s) record of rhythmic EMG bursts. Existing computational techniques reduce this time but have limitations. These include a universal threshold for delimiting noise regions (i.e., a single signal value for identifying the EMG signal onset and offset), pre-processing using wide time intervals that dampen sensitivity for EMG signal characteristics, poor performance when a low frequency component (e.g., DC offset) is present, and high computational complexity leading to lack of time efficiency. We present a new statistical method and MATLAB script (EMG-Extractor) that includes an adaptive algorithm to discriminate noise regions from EMG that avoids these limitations and allows for multi-channel datasets to be processed. We evaluate the EMG-Extractor with EMG data on mammalian jaw-adductor muscles during mastication, a rhythmic behavior typified by low amplitude onsets/offsets and complex signal pattern. The EMG-Extractor consistently and accurately distinguishes noise from EMG in a manner similar to that of an experienced analyst. It outputs the raw EMG signal region in a form ready for further analysis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Assessing ECG signal quality indices to discriminate ECGs with artefacts from pathologically different arrhythmic ECGs.

    Science.gov (United States)

    Daluwatte, C; Johannesen, L; Galeotti, L; Vicente, J; Strauss, D G; Scully, C G

    2016-08-01

    False and non-actionable alarms in critical care can be reduced by developing algorithms which assess the trueness of an arrhythmia alarm from a bedside monitor. Computational approaches that automatically identify artefacts in ECG signals are an important branch of physiological signal processing which tries to address this issue. Signal quality indices (SQIs) derived considering differences between artefacts which occur in ECG signals and normal QRS morphology have the potential to discriminate pathologically different arrhythmic ECG segments as artefacts. Using ECG signals from the PhysioNet/Computing in Cardiology Challenge 2015 training set, we studied previously reported ECG SQIs in the scientific literature to differentiate ECG segments with artefacts from arrhythmic ECG segments. We found that the ability of SQIs to discriminate between ECG artefacts and arrhythmic ECG varies based on arrhythmia type since the pathology of each arrhythmic ECG waveform is different. Therefore, to reduce the risk of SQIs classifying arrhythmic events as noise it is important to validate and test SQIs with databases that include arrhythmias. Arrhythmia specific SQIs may also minimize the risk of misclassifying arrhythmic events as noise.

  16. Modulation of EEG Theta Band Signal Complexity by Music Therapy

    Science.gov (United States)

    Bhattacharya, Joydeep; Lee, Eun-Jeong

    The primary goal of this study was to investigate the impact of monochord (MC) sounds, a type of archaic sounds used in music therapy, on the neural complexity of EEG signals obtained from patients undergoing chemotherapy. The secondary goal was to compare the EEG signal complexity values for monochords with those for progressive muscle relaxation (PMR), an alternative therapy for relaxation. Forty cancer patients were randomly allocated to one of the two relaxation groups, MC and PMR, over a period of six months; continuous EEG signals were recorded during the first and last sessions. EEG signals were analyzed by applying signal mode complexity, a measure of complexity of neuronal oscillations. Across sessions, both groups showed a modulation of complexity of beta-2 band (20-29Hz) at midfrontal regions, but only MC group showed a modulation of complexity of theta band (3.5-7.5Hz) at posterior regions. Therefore, the neuronal complexity patterns showed different changes in EEG frequency band specific complexity resulting in two different types of interventions. Moreover, the different neural responses to listening to monochords and PMR were observed after regular relaxation interventions over a short time span.

  17. Postnatal Ablation of Synaptic Retinoic Acid Signaling Impairs Cortical Information Processing and Sensory Discrimination in Mice.

    Science.gov (United States)

    Park, Esther; Tjia, Michelle; Zuo, Yi; Chen, Lu

    2018-06-06

    Retinoic acid (RA) and its receptors (RARs) are well established essential transcriptional regulators during embryonic development. Recent findings in cultured neurons identified an independent and critical post-transcriptional role of RA and RARα in the homeostatic regulation of excitatory and inhibitory synaptic transmission in mature neurons. However, the functional relevance of synaptic RA signaling in vivo has not been established. Here, using somatosensory cortex as a model system and the RARα conditional knock-out mouse as a tool, we applied multiple genetic manipulations to delete RARα postnatally in specific populations of cortical neurons, and asked whether synaptic RA signaling observed in cultured neurons is involved in cortical information processing in vivo Indeed, conditional ablation of RARα in mice via a CaMKIIα-Cre or a layer 5-Cre driver line or via somatosensory cortex-specific viral expression of Cre-recombinase impaired whisker-dependent texture discrimination, suggesting a critical requirement of RARα expression in L5 pyramidal neurons of somatosensory cortex for normal tactile sensory processing. Transcranial two-photon imaging revealed a significant increase in dendritic spine elimination on apical dendrites of somatosensory cortical layer 5 pyramidal neurons in these mice. Interestingly, the enhancement of spine elimination is whisker experience-dependent as whisker trimming rescued the spine elimination phenotype. Additionally, experiencing an enriched environment improved texture discrimination in RARα-deficient mice and reduced excessive spine pruning. Thus, RA signaling is essential for normal experience-dependent cortical circuit remodeling and sensory processing. SIGNIFICANCE STATEMENT The importance of synaptic RA signaling has been demonstrated in in vitro studies. However, whether RA signaling mediated by RARα contributes to neural circuit functions in vivo remains largely unknown. In this study, using a RARα conditional

  18. Low Rate Transmission of Video Signals Using Adaptive Delta Modulation.

    Science.gov (United States)

    1983-08-15

    903-80-C-0476 / . PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT. PROJECT, TASK AREA & WORK UNIT NUMBERS Research Foundation of CUNY on...transmitted phase, for the demodulation of the signal. AM is presently being used to transmit multilevel * symbols by vestigial or single sideband...34: Vestigial Sideband -- Duobinary 3600 4-Phase + AM 4800" 4-Phase + AM * Vestigial Sideband 8-PSK 7200 Phase and Amplitude Modulation 9600 Phase anl

  19. Amplitude Modulated Sinusoidal Signal Decomposition for Audio Coding

    DEFF Research Database (Denmark)

    Christensen, M. G.; Jacobson, A.; Andersen, S. V.

    2006-01-01

    In this paper, we present a decomposition for sinusoidal coding of audio, based on an amplitude modulation of sinusoids via a linear combination of arbitrary basis vectors. The proposed method, which incorporates a perceptual distortion measure, is based on a relaxation of a nonlinear least......-squares minimization. Rate-distortion curves and listening tests show that, compared to a constant-amplitude sinusoidal coder, the proposed decomposition offers perceptually significant improvements in critical transient signals....

  20. Curcumin mediates anticancer effects by modulating multiple cell signaling pathways.

    Science.gov (United States)

    Kunnumakkara, Ajaikumar B; Bordoloi, Devivasha; Harsha, Choudhary; Banik, Kishore; Gupta, Subash C; Aggarwal, Bharat B

    2017-08-01

    Curcumin, a component of a spice native to India, was first isolated in 1815 by Vogel and Pelletier from the rhizomes of Curcuma longa (turmeric) and, subsequently, the chemical structure of curcumin as diferuloylmethane was reported by Milobedzka et al. [(1910) 43., 2163-2170]. Since then, this polyphenol has been shown to exhibit antioxidant, anti-inflammatory, anticancer, antiviral, antibacterial, and antifungal activities. The current review primarily focuses on the anticancer potential of curcumin through the modulation of multiple cell signaling pathways. Curcumin modulates diverse transcription factors, inflammatory cytokines, enzymes, kinases, growth factors, receptors, and various other proteins with an affinity ranging from the pM to the mM range. Furthermore, curcumin effectively regulates tumor cell growth via modulation of numerous cell signaling pathways and potentiates the effect of chemotherapeutic agents and radiation against cancer. Curcumin can interact with most of the targets that are modulated by FDA-approved drugs for cancer therapy. The focus of this review is to discuss the molecular basis for the anticancer activities of curcumin based on preclinical and clinical findings. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  1. A Versatile Multichannel Digital Signal Processing Module for Microcalorimeter Arrays

    Science.gov (United States)

    Tan, H.; Collins, J. W.; Walby, M.; Hennig, W.; Warburton, W. K.; Grudberg, P.

    2012-06-01

    Different techniques have been developed for reading out microcalorimeter sensor arrays: individual outputs for small arrays, and time-division or frequency-division or code-division multiplexing for large arrays. Typically, raw waveform data are first read out from the arrays using one of these techniques and then stored on computer hard drives for offline optimum filtering, leading not only to requirements for large storage space but also limitations on achievable count rate. Thus, a read-out module that is capable of processing microcalorimeter signals in real time will be highly desirable. We have developed multichannel digital signal processing electronics that are capable of on-board, real time processing of microcalorimeter sensor signals from multiplexed or individual pixel arrays. It is a 3U PXI module consisting of a standardized core processor board and a set of daughter boards. Each daughter board is designed to interface a specific type of microcalorimeter array to the core processor. The combination of the standardized core plus this set of easily designed and modified daughter boards results in a versatile data acquisition module that not only can easily expand to future detector systems, but is also low cost. In this paper, we first present the core processor/daughter board architecture, and then report the performance of an 8-channel daughter board, which digitizes individual pixel outputs at 1 MSPS with 16-bit precision. We will also introduce a time-division multiplexing type daughter board, which takes in time-division multiplexing signals through fiber-optic cables and then processes the digital signals to generate energy spectra in real time.

  2. Optical spectral reshaping for directly modulated 4-pulse amplitude modulation signals

    DEFF Research Database (Denmark)

    Ozolins, Oskars; Da Ros, Francesco; Cristofori, Valentina

    2017-01-01

    The tremendous traffic growth in intra/inter-datacenters requires low-cost high-speed integrated solutions [1]. To enable a significantly reduced footprint directly modulated lasers (DMLs) have been proposed instead of large external modulators. However, it is challenging to use DMLs due to their......The tremendous traffic growth in intra/inter-datacenters requires low-cost high-speed integrated solutions [1]. To enable a significantly reduced footprint directly modulated lasers (DMLs) have been proposed instead of large external modulators. However, it is challenging to use DMLs due...... (PAM) [3] signals. However, moving to 4-PAM,many of the impressive demonstrations reported so far rely heavily on off-line digital signal processing (DSP), which increases latency, power consumption and cost. In this talk, we report on (i) a detailed numerical analysis on the complex transfer function...... of the optical filter for optical spectral reshaping in case of pulse amplitude modulation and(ii) an experimental demonstration of real-time dispersion-uncompensated transmission of 10-GBd and 14-GBd 4-PAM signals up to 10- and 26-km SSMF. This is achieved by combining a commercial 10-Gb/s DML with optical...

  3. Orphan nuclear receptor TLX regulates astrogenesis by modulating BMP signaling

    Directory of Open Access Journals (Sweden)

    Song eQin

    2014-04-01

    Full Text Available Neural stem cells (NSCs are self-renewing multipotent progenitors that generate both neurons and glia. The precise control of NSC behavior is fundamental to the architecture and function of the central nervous system. We previously demonstrated that the orphan nuclear receptor TLX is required for postnatal NSC activation and neurogenesis in the neurogenic niche. Here, we show that TLX modulates BMP-SMAD signaling to control the timing of postnatal astrogenesis. Genes involved in the BMP signaling pathway, such as Bmp4, Hes1, and Id3, are upregulated in postnatal brains lacking Tlx. Chromatin immunoprecipitation and electrophoretic mobility shift assays reveal that TLX can directly bind the enhancer region of Bmp4. In accordance with elevated BMP signaling, the downstream effectors SMAD1/5/8 are activated by phosphorylation in Tlx mutant mice. Consequently, Tlx mutant brains exhibit an early appearance and increased number of astrocytes with marker expression of glial fibrillary acidic protein (GFAP and S100B. Taken together, these results suggest that TLX tightly controls postnatal astrogenesis through the modulation of BMP-SMAD signaling pathway activity.

  4. Orphan nuclear receptor TLX regulates astrogenesis by modulating BMP signaling.

    Science.gov (United States)

    Qin, Song; Niu, Wenze; Iqbal, Nida; Smith, Derek K; Zhang, Chun-Li

    2014-01-01

    Neural stem cells (NSCs) are self-renewing multipotent progenitors that generate both neurons and glia. The precise control of NSC behavior is fundamental to the architecture and function of the central nervous system. We previously demonstrated that the orphan nuclear receptor TLX is required for postnatal NSC activation and neurogenesis in the neurogenic niche. Here, we show that TLX modulates bone morphogenetic protein (BMP)-SMAD signaling to control the timing of postnatal astrogenesis. Genes involved in the BMP signaling pathway, such as Bmp4, Hes1, and Id3, are upregulated in postnatal brains lacking Tlx. Chromatin immunoprecipitation and electrophoretic mobility shift assays reveal that TLX can directly bind the enhancer region of Bmp4. In accordance with elevated BMP signaling, the downstream effectors SMAD1/5/8 are activated by phosphorylation in Tlx mutant mice. Consequently, Tlx mutant brains exhibit an early appearance and increased number of astrocytes with marker expression of glial fibrillary acidic protein (GFAP) and S100B. Taken together, these results suggest that TLX tightly controls postnatal astrogenesis through the modulation of BMP-SMAD signaling pathway activity.

  5. An improved discriminative filter bank selection approach for motor imagery EEG signal classification using mutual information.

    Science.gov (United States)

    Kumar, Shiu; Sharma, Alok; Tsunoda, Tatsuhiko

    2017-12-28

    Common spatial pattern (CSP) has been an effective technique for feature extraction in electroencephalography (EEG) based brain computer interfaces (BCIs). However, motor imagery EEG signal feature extraction using CSP generally depends on the selection of the frequency bands to a great extent. In this study, we propose a mutual information based frequency band selection approach. The idea of the proposed method is to utilize the information from all the available channels for effectively selecting the most discriminative filter banks. CSP features are extracted from multiple overlapping sub-bands. An additional sub-band has been introduced that cover the wide frequency band (7-30 Hz) and two different types of features are extracted using CSP and common spatio-spectral pattern techniques, respectively. Mutual information is then computed from the extracted features of each of these bands and the top filter banks are selected for further processing. Linear discriminant analysis is applied to the features extracted from each of the filter banks. The scores are fused together, and classification is done using support vector machine. The proposed method is evaluated using BCI Competition III dataset IVa, BCI Competition IV dataset I and BCI Competition IV dataset IIb, and it outperformed all other competing methods achieving the lowest misclassification rate and the highest kappa coefficient on all three datasets. Introducing a wide sub-band and using mutual information for selecting the most discriminative sub-bands, the proposed method shows improvement in motor imagery EEG signal classification.

  6. Wide-band analog frequency modulation of optic signals using indirect techniques

    Science.gov (United States)

    Fitzmartin, D. J.; Balboni, E. J.; Gels, R. G.

    1991-01-01

    The wideband frequency modulation (FM) of an optical carrier by a radio frequency (RF) or microwave signal can be accomplished independent of laser type when indirect modulation is employed. Indirect modulators exploit the integral relation of phase to frequency so that phase modulators can be used to impress frequency modulation on an optical carrier. The use of integrated optics phase modulators, which are highly linear, enables the generation of optical wideband FM signals with very low intermodulation distortion. This modulator can be used as part of an optical wideband FM link for RF and microwave signals. Experimental results from the test of an indirect frequency modulator for an optical carrier are discussed.

  7. Stimulation of the Locus Ceruleus Modulates Signal-to-Noise Ratio in the Olfactory Bulb.

    Science.gov (United States)

    Manella, Laura C; Petersen, Nicholas; Linster, Christiane

    2017-11-29

    Norepinephrine (NE) has been shown to influence sensory, and specifically olfactory processing at the behavioral and physiological levels, potentially by regulating signal-to-noise ratio (S/N). The present study is the first to look at NE modulation of olfactory bulb (OB) in regards to S/N in vivo We show, in male rats, that locus ceruleus stimulation and pharmacological infusions of NE into the OB modulate both spontaneous and odor-evoked neural responses. NE in the OB generated a non-monotonic dose-response relationship, suppressing mitral cell activity at high and low, but not intermediate, NE levels. We propose that NE enhances odor responses not through direct potentiation of the afferent signal per se, but rather by reducing the intrinsic noise of the system. This has important implications for the ways in which an animal interacts with its olfactory environment, particularly as the animal shifts from a relaxed to an alert behavioral state. SIGNIFICANCE STATEMENT Sensory perception can be modulated by behavioral states such as hunger, fear, stress, or a change in environmental context. Behavioral state often affects neural processing via the release of circulating neurochemicals such as hormones or neuromodulators. We here show that the neuromodulator norepinephrine modulates olfactory bulb spontaneous activity and odor responses so as to generate an increased signal-to-noise ratio at the output of the olfactory bulb. Our results help interpret and improve existing ideas for neural network mechanisms underlying behaviorally observed improvements in near-threshold odor detection and discrimination. Copyright © 2017 the authors 0270-6474/17/3711605-11$15.00/0.

  8. Fast digitization and discrimination of prompt neutron and photon signals using a novel silicon carbide detector

    International Nuclear Information System (INIS)

    Brandon W. Blackburn; James T. Johnson; Scott M. Watson; David L. Chichester; James L. Jones; Frank H. Ruddy; John G. Seidel; Robert W. Flammang

    2007-01-01

    Current requirements of some Homeland Security active interrogation projects for the detection of Special Nuclear Material (SNM) necessitate the development of faster inspection and acquisition capabilities. In order to do so, fast detectors which can operate during and shortly after intense interrogation radiation flashes are being developed. Novel silicon carbide (SiC) semiconductor Schottky diodes have been utilized as robust neutron and photon detectors in both pulsed photon and pulsed neutron fields and are being integrated into active inspection environments to allow exploitation of both prompt and delayed emissions. These detectors have demonstrated the capability of detecting both photon and neutron events during intense photon flashes typical of an active inspection environment. Beyond the inherent insensitivity of SiC to gamma radiation, fast digitization and processing has demonstrated that pulse shape discrimination (PSD) in combination with amplitude discrimination can further suppress unwanted gamma signals and extract fast neutron signatures. Usable neutron signals have been extracted from mixed radiation fields where the background has exceeded the signals of interest by >1000:1

  9. NSP-CAS Protein Complexes: Emerging Signaling Modules in Cancer.

    Science.gov (United States)

    Wallez, Yann; Mace, Peter D; Pasquale, Elena B; Riedl, Stefan J

    2012-05-01

    The CAS (CRK-associated substrate) family of adaptor proteins comprises 4 members, which share a conserved modular domain structure that enables multiple protein-protein interactions, leading to the assembly of intracellular signaling platforms. Besides their physiological role in signal transduction downstream of a variety of cell surface receptors, CAS proteins are also critical for oncogenic transformation and cancer cell malignancy through associations with a variety of regulatory proteins and downstream effectors. Among the regulatory partners, the 3 recently identified adaptor proteins constituting the NSP (novel SH2-containing protein) family avidly bind to the conserved carboxy-terminal focal adhesion-targeting (FAT) domain of CAS proteins. NSP proteins use an anomalous nucleotide exchange factor domain that lacks catalytic activity to form NSP-CAS signaling modules. Additionally, the NSP SH2 domain can link NSP-CAS signaling assemblies to tyrosine-phosphorylated cell surface receptors. NSP proteins can potentiate CAS function by affecting key CAS attributes such as expression levels, phosphorylation state, and subcellular localization, leading to effects on cell adhesion, migration, and invasion as well as cell growth. The consequences of these activities are well exemplified by the role that members of both families play in promoting breast cancer cell invasiveness and resistance to antiestrogens. In this review, we discuss the intriguing interplay between the NSP and CAS families, with a particular focus on cancer signaling networks.

  10. Hierarchical feedback modules and reaction hubs in cell signaling networks.

    Science.gov (United States)

    Xu, Jianfeng; Lan, Yueheng

    2015-01-01

    Despite much effort, identification of modular structures and study of their organizing and functional roles remain a formidable challenge in molecular systems biology, which, however, is essential in reaching a systematic understanding of large-scale cell regulation networks and hence gaining capacity of exerting effective interference to cell activity. Combining graph theoretic methods with available dynamics information, we successfully retrieved multiple feedback modules of three important signaling networks. These feedbacks are structurally arranged in a hierarchical way and dynamically produce layered temporal profiles of output signals. We found that global and local feedbacks act in very different ways and on distinct features of the information flow conveyed by signal transduction but work highly coordinately to implement specific biological functions. The redundancy embodied with multiple signal-relaying channels and feedback controls bestow great robustness and the reaction hubs seated at junctions of different paths announce their paramount importance through exquisite parameter management. The current investigation reveals intriguing general features of the organization of cell signaling networks and their relevance to biological function, which may find interesting applications in analysis, design and control of bio-networks.

  11. Hierarchical feedback modules and reaction hubs in cell signaling networks.

    Directory of Open Access Journals (Sweden)

    Jianfeng Xu

    Full Text Available Despite much effort, identification of modular structures and study of their organizing and functional roles remain a formidable challenge in molecular systems biology, which, however, is essential in reaching a systematic understanding of large-scale cell regulation networks and hence gaining capacity of exerting effective interference to cell activity. Combining graph theoretic methods with available dynamics information, we successfully retrieved multiple feedback modules of three important signaling networks. These feedbacks are structurally arranged in a hierarchical way and dynamically produce layered temporal profiles of output signals. We found that global and local feedbacks act in very different ways and on distinct features of the information flow conveyed by signal transduction but work highly coordinately to implement specific biological functions. The redundancy embodied with multiple signal-relaying channels and feedback controls bestow great robustness and the reaction hubs seated at junctions of different paths announce their paramount importance through exquisite parameter management. The current investigation reveals intriguing general features of the organization of cell signaling networks and their relevance to biological function, which may find interesting applications in analysis, design and control of bio-networks.

  12. Hierarchical Feedback Modules and Reaction Hubs in Cell Signaling Networks

    Science.gov (United States)

    Xu, Jianfeng; Lan, Yueheng

    2015-01-01

    Despite much effort, identification of modular structures and study of their organizing and functional roles remain a formidable challenge in molecular systems biology, which, however, is essential in reaching a systematic understanding of large-scale cell regulation networks and hence gaining capacity of exerting effective interference to cell activity. Combining graph theoretic methods with available dynamics information, we successfully retrieved multiple feedback modules of three important signaling networks. These feedbacks are structurally arranged in a hierarchical way and dynamically produce layered temporal profiles of output signals. We found that global and local feedbacks act in very different ways and on distinct features of the information flow conveyed by signal transduction but work highly coordinately to implement specific biological functions. The redundancy embodied with multiple signal-relaying channels and feedback controls bestow great robustness and the reaction hubs seated at junctions of different paths announce their paramount importance through exquisite parameter management. The current investigation reveals intriguing general features of the organization of cell signaling networks and their relevance to biological function, which may find interesting applications in analysis, design and control of bio-networks. PMID:25951347

  13. Genetic variation in glia-neuron signalling modulates ageing rate.

    Science.gov (United States)

    Yin, Jiang-An; Gao, Ge; Liu, Xi-Juan; Hao, Zi-Qian; Li, Kai; Kang, Xin-Lei; Li, Hong; Shan, Yuan-Hong; Hu, Wen-Li; Li, Hai-Peng; Cai, Shi-Qing

    2017-11-08

    The rate of behavioural decline in the ageing population is remarkably variable among individuals. Despite the considerable interest in studying natural variation in ageing rate to identify factors that control healthy ageing, no such factor has yet been found. Here we report a genetic basis for variation in ageing rates in Caenorhabditis elegans. We find that C. elegans isolates show diverse lifespan and age-related declines in virility, pharyngeal pumping, and locomotion. DNA polymorphisms in a novel peptide-coding gene, named regulatory-gene-for-behavioural-ageing-1 (rgba-1), and the neuropeptide receptor gene npr-28 influence the rate of age-related decline of worm mating behaviour; these two genes might have been subjected to recent selective sweeps. Glia-derived RGBA-1 activates NPR-28 signalling, which acts in serotonergic and dopaminergic neurons to accelerate behavioural deterioration. This signalling involves the SIR-2.1-dependent activation of the mitochondrial unfolded protein response, a pathway that modulates ageing. Thus, natural variation in neuropeptide-mediated glia-neuron signalling modulates the rate of ageing in C. elegans.

  14. Discrimination of Parkinsonian Tremor From Essential Tremor by Voting Between Different EMG Signal Processing Techniques

    Directory of Open Access Journals (Sweden)

    A Hossen

    2014-06-01

    Full Text Available Parkinson's disease (PD and essential tremor (ET are the two most common disorders that cause involuntary muscle shaking movements, or what is called "tremor”. PD is a neurodegenerative disease caused by the loss of dopamine receptors which control and adjust the movement of the body. On the other hand, ET is a neurological movement disorder which also causes tremors and shaking, but it is not related to dopamine receptor loss; it is simply a tremor. The differential diagnosis between these two disorders is sometimes difficult to make clinically because of the similarities of their symptoms; additionally, the available tests are complex and expensive. Thus, the objective of this paper is to discriminate between these two disorders with simpler, cheaper and easier ways by using electromyography (EMG signal processing techniques. EMG and accelerometer records of 39 patients with PD and 41 with ET were acquired from the Hospital of Kiel University in Germany and divided into a trial group and a test group. Three main techniques were applied: the wavelet-based soft-decision technique, statistical signal characterization (SSC of the spectrum of the signal, and SSC of the amplitude variation of the Hilbert transform. The first technique resulted in a discrimination efficiency of 80% on the trial set and 85% on the test set. The second technique resulted in an efficiency of 90% on the trial set and 82.5% on the test set. The third technique resulted in an 87.5% efficiency on the trial set and 65.5% efficiency on the test set. Lastly, a final vote was done to finalize the discrimination using these three techniques, and as a result of the vote, accuracies of 92.5%, 85.0% and 88.75% were obtained on the trial data, test data and total data, respectively.

  15. Optical modulation techniques for analog signal processing and CMOS compatible electro-optic modulation

    Science.gov (United States)

    Gill, Douglas M.; Rasras, Mahmoud; Tu, Kun-Yii; Chen, Young-Kai; White, Alice E.; Patel, Sanjay S.; Carothers, Daniel; Pomerene, Andrew; Kamocsai, Robert; Beattie, James; Kopa, Anthony; Apsel, Alyssa; Beals, Mark; Mitchel, Jurgen; Liu, Jifeng; Kimerling, Lionel C.

    2008-02-01

    Integrating electronic and photonic functions onto a single silicon-based chip using techniques compatible with mass-production CMOS electronics will enable new design paradigms for existing system architectures and open new opportunities for electro-optic applications with the potential to dramatically change the management, cost, footprint, weight, and power consumption of today's communication systems. While broadband analog system applications represent a smaller volume market than that for digital data transmission, there are significant deployments of analog electro-optic systems for commercial and military applications. Broadband linear modulation is a critical building block in optical analog signal processing and also could have significant applications in digital communication systems. Recently, broadband electro-optic modulators on a silicon platform have been demonstrated based on the plasma dispersion effect. The use of the plasma dispersion effect within a CMOS compatible waveguide creates new challenges and opportunities for analog signal processing since the index and propagation loss change within the waveguide during modulation. We will review the current status of silicon-based electrooptic modulators and also linearization techniques for optical modulation.

  16. Using Dynamic Fourier Analysis to Discriminate Between Seismic Signals from Natural Earthquakes and Mining Explosions

    Directory of Open Access Journals (Sweden)

    Maria C. Mariani

    2017-08-01

    Full Text Available A sequence of intraplate earthquakes occurred in Arizona at the same location where miningexplosions were carried out in previous years. The explosions and some of the earthquakes generatedvery similar seismic signals. In this study Dynamic Fourier Analysis is used for discriminating signalsoriginating from natural earthquakes and mining explosions. Frequency analysis of seismogramsrecorded at regional distances shows that compared with the mining explosions the earthquake signalshave larger amplitudes in the frequency interval ~ 6 to 8 Hz and significantly smaller amplitudes inthe frequency interval ~ 2 to 4 Hz. This type of analysis permits identifying characteristics in theseismograms frequency yielding to detect potentially risky seismic events.

  17. Modulation of Hippocampal Neural Plasticity by Glucose-Related Signaling

    Directory of Open Access Journals (Sweden)

    Marco Mainardi

    2015-01-01

    Full Text Available Hormones and peptides involved in glucose homeostasis are emerging as important modulators of neural plasticity. In this regard, increasing evidence shows that molecules such as insulin, insulin-like growth factor-I, glucagon-like peptide-1, and ghrelin impact on the function of the hippocampus, which is a key area for learning and memory. Indeed, all these factors affect fundamental hippocampal properties including synaptic plasticity (i.e., synapse potentiation and depression, structural plasticity (i.e., dynamics of dendritic spines, and adult neurogenesis, thus leading to modifications in cognitive performance. Here, we review the main mechanisms underlying the effects of glucose metabolism on hippocampal physiology. In particular, we discuss the role of these signals in the modulation of cognitive functions and their potential implications in dysmetabolism-related cognitive decline.

  18. Isolation of key retinoid signalling and metabolic modules in invertebrates

    Directory of Open Access Journals (Sweden)

    Ana André

    2014-05-01

    Full Text Available Retinoids are a class of molecules related to vitamin A (Retinol that are required for regulation of critical chordate ndocrine-mediated process, such as embryonic development, reproduction, and vision. To maintain such physiological process, chordates have a complex mechanism to regulate the spatial and temporal distribution of retinoids that includes metabolic and signalling modules. Initially, retinoid modules were seen as a chordate novelty. However, emerging biochemical and genomic evidences have challenged this view, clearly pointing to a more basal ancestry than previously thought. However, for the majority of non-chordate invertebrate lineages a clearly characterization of the main enzymatic/molecular players is still missing. Despite limited, the available evidence supports the presence of biologically active retinoid pathways in invertebrates. In order to enhance our insights on retinoid biology, evolution, and its putative disruption by environmental chemicals, the isolation and functional characterization of key retinoid metabolic players in marine invertebrates has been carried out.

  19. Prefrontal cortical GABA transmission modulates discrimination and latent inhibition of conditioned fear: relevance for schizophrenia.

    Science.gov (United States)

    Piantadosi, Patrick T; Floresco, Stan B

    2014-09-01

    Inhibitory gamma-aminobutyric acid (GABA) transmission within the prefrontal cortex (PFC) regulates numerous functions, and perturbations in GABAergic transmission within this region have been proposed to contribute to some of the cognitive and behavioral abnormalities associated with disorders such as schizophrenia. These abnormalities include deficits in emotional regulation and aberrant attributions of affective salience. Yet, how PFC GABA regulates these types of emotional processes are unclear. To address this issue, we investigated the contribution of PFC GABA transmission to different aspects of Pavlovian emotional learning in rats using translational discriminative fear conditioning and latent inhibition (LI) assays. Reducing prelimbic PFC GABAA transmission via infusions of the antagonist bicuculline before the acquisition or expression of fear conditioning eliminated the ability to discriminate between an aversive conditioned stimulus (CS+) paired with footshock vs a neutral CS-, resembling similar deficits observed in schizophrenic patients. In a separate experiment, blockade of PFC GABAA receptors before CS preexposure (PE) and conditioning did not affect subsequent expression of LI, but did enhance fear in rats that were not preexposed to the CS. In contrast, PFC GABA-blockade before a fear expression test disrupted the recall of learned irrelevance and abolished LI. These data suggest that normal PFC GABA transmission is critical for regulating and mitigating multiple aspects of aversive learning, including discrimination between fear vs safety signals and recall of information about the irrelevance of stimuli. Furthermore, they suggest that similar deficits in emotional regulation observed in schizophrenia may be driven in part by deficient PFC GABA activity.

  20. Eight-Channel Digital Signal Processor and Universal Trigger Module

    Science.gov (United States)

    Skulski, Wojtek; Wolfs, Frank

    2003-04-01

    A 10-bit, 8-channel, 40 megasamples per second digital signal processor and waveform digitizer DDC-8 (nicknamed Universal Trigger Module) is presented. The digitizer features 8 analog inputs, 1 analog output for a reconstructed analog waveform, 16 NIM logic inputs, 8 NIM logic outputs, and a pool of 16 TTL logic lines which can be individually configured as either inputs or outputs. The first application of this device is to enhance the present trigger electronics for PHOBOS at RHIC. The status of the development and the first results are presented. Possible applications of the new device are discussed. Supported by the NSF grant PHY-0072204.

  1. Neutron/gamma discrimination employing the power spectrum analysis of the signal from the liquid scintillator BC501A

    International Nuclear Information System (INIS)

    Luo, X.L.; Wang, Y.K; Yang, J.; Liu, G.; Lin, C.B.; Hu, Q.Q.; Peng, J.X.

    2013-01-01

    A digital method for the discrimination of neutron and γ-ray events based on analyzing the power spectra of the signals from a BC501A liquid scintillator detector was presented and investigated in this paper. In order to evaluate the feasibility of this novel pulse shape discrimination method, a 5GSample/s 8-bit oscilloscope was used to acquire waveforms for n/γ discrimination. Furthermore, the performance of this novel n/γ discrimination method was compared with that of a widely used method called the reference-pulses method which averaged a large number of neutron and γ-ray pulses to obtain the reference-pulse as the criterion for n/γ discrimination. The results showed that the proposed method performed well over the reference-pulses method, which was verified by the considerable decrease in the error rate of n/γ discrimination and the improvement of the Figure of Merit

  2. Frequency modulation excursion and rate discrimination in normal-hearing and hearing-impaired listeners

    DEFF Research Database (Denmark)

    Schindwolf, Isabel; Vatti, Marianna; Santurette, Sébastien

    Most natural sounds contain frequency fluctuations over time such as changes in their fundamental frequency, non-periodic speech formant transitions, or periodic fluctuations like musical vibrato. These are sometimes characterized as frequency modulation (FM) with a given excursion (FMe) and rate......, this study investigated the effects of age and SNHL on FMe and FMr difference limens (DLs) for reference values typical of frequency fluctuations observed in speech and music signals....

  3. Combination of Empirical Mode Decomposition Components of HRV Signals for Discriminating Emotional States

    Directory of Open Access Journals (Sweden)

    Ateke Goshvarpour

    2016-06-01

    Full Text Available Introduction Automatic human emotion recognition is one of the most interesting topics in the field of affective computing. However, development of a reliable approach with a reasonable recognition rate is a challenging task. The main objective of the present study was to propose a robust method for discrimination of emotional responses thorough examination of heart rate variability (HRV. In the present study, considering the non-stationary and non-linear characteristics of HRV, empirical mode decomposition technique was utilized as a feature extraction approach. Materials and Methods In order to induce the emotional states, images indicating four emotional states, i.e., happiness, peacefulness, sadness, and fearfulness were presented. Simultaneously, HRV was recorded in 47 college students. The signals were decomposed into some intrinsic mode functions (IMFs. For each IMF and different IMF combinations, 17 standard and non-linear parameters were extracted. Wilcoxon test was conducted to assess the difference between IMF parameters in different emotional states. Afterwards, a probabilistic neural network was used to classify the features into emotional classes. Results Based on the findings, maximum classification rates were achieved when all IMFs were fed into the classifier. Under such circumstances, the proposed algorithm could discriminate the affective states with sensitivity, specificity, and correct classification rate of 99.01%, 100%, and 99.09%, respectively. In contrast, the lowest discrimination rates were attained by IMF1 frequency and its combinations. Conclusion The high performance of the present approach indicated that the proposed method is applicable for automatic emotion recognition.

  4. Input from the medial geniculate nucleus modulates amygdala encoding of fear memory discrimination.

    Science.gov (United States)

    Ferrara, Nicole C; Cullen, Patrick K; Pullins, Shane P; Rotondo, Elena K; Helmstetter, Fred J

    2017-09-01

    Generalization of fear can involve abnormal responding to cues that signal safety and is common in people diagnosed with post-traumatic stress disorder. Differential auditory fear conditioning can be used as a tool to measure changes in fear discrimination and generalization. Most prior work in this area has focused on elevated amygdala activity as a critical component underlying generalization. The amygdala receives input from auditory cortex as well as the medial geniculate nucleus (MgN) of the thalamus, and these synapses undergo plastic changes in response to fear conditioning and are major contributors to the formation of memory related to both safe and threatening cues. The requirement for MgN protein synthesis during auditory discrimination and generalization, as well as the role of MgN plasticity in amygdala encoding of discrimination or generalization, have not been directly tested. GluR1 and GluR2 containing AMPA receptors are found at synapses throughout the amygdala and their expression is persistently up-regulated after learning. Some of these receptors are postsynaptic to terminals from MgN neurons. We found that protein synthesis-dependent plasticity in MgN is necessary for elevated freezing to both aversive and safe auditory cues, and that this is accompanied by changes in the expressions of AMPA receptor and synaptic scaffolding proteins (e.g., SHANK) at amygdala synapses. This work contributes to understanding the neural mechanisms underlying increased fear to safety signals after stress. © 2017 Ferrara et al.; Published by Cold Spring Harbor Laboratory Press.

  5. Signal peptide discrimination and cleavage site identification using SVM and NN.

    Science.gov (United States)

    Kazemian, H B; Yusuf, S A; White, K

    2014-02-01

    About 15% of all proteins in a genome contain a signal peptide (SP) sequence, at the N-terminus, that targets the protein to intracellular secretory pathways. Once the protein is targeted correctly in the cell, the SP is cleaved, releasing the mature protein. Accurate prediction of the presence of these short amino-acid SP chains is crucial for modelling the topology of membrane proteins, since SP sequences can be confused with transmembrane domains due to similar composition of hydrophobic amino acids. This paper presents a cascaded Support Vector Machine (SVM)-Neural Network (NN) classification methodology for SP discrimination and cleavage site identification. The proposed method utilises a dual phase classification approach using SVM as a primary classifier to discriminate SP sequences from Non-SP. The methodology further employs NNs to predict the most suitable cleavage site candidates. In phase one, a SVM classification utilises hydrophobic propensities as a primary feature vector extraction using symmetric sliding window amino-acid sequence analysis for discrimination of SP and Non-SP. In phase two, a NN classification uses asymmetric sliding window sequence analysis for prediction of cleavage site identification. The proposed SVM-NN method was tested using Uni-Prot non-redundant datasets of eukaryotic and prokaryotic proteins with SP and Non-SP N-termini. Computer simulation results demonstrate an overall accuracy of 0.90 for SP and Non-SP discrimination based on Matthews Correlation Coefficient (MCC) tests using SVM. For SP cleavage site prediction, the overall accuracy is 91.5% based on cross-validation tests using the novel SVM-NN model. © 2013 Published by Elsevier Ltd.

  6. Gear wear monitoring by modulation signal bispectrum based on motor current signal analysis

    Science.gov (United States)

    Zhang, Ruiliang; Gu, Fengshou; Mansaf, Haram; Wang, Tie; Ball, Andrew D.

    2017-09-01

    Gears are important mechanical components for power transmissions. Tooth wear is one of the most common failure modes, which can present throughout a gear's lifetime. It is significant to accurately monitor gear wear progression in order to take timely predictive maintenances. Motor current signature analysis (MCSA) is an effective and non-intrusive approach which is able to monitor faults from both electrical and mechanical systems. However, little research has been reported in monitoring the gear wear and estimating its severity based on MCSA. This paper presents a novel gear wear monitoring method through a modulation signal bispectrum based motor current signal analysis (MSB-MCSA). For a steady gear transmission, it is inevitable to exist load and speed oscillations due to various errors including wears. These oscillations can induce small modulations in the current signals of the driving motor. MSB is particularly effective in characterising such small modulation signals. Based on these understandings, the monitoring process was implemented based on the current signals from a run-to-failure test of an industrial two stages helical gearbox under a moderate accelerated fatigue process. At the initial operation of the test, MSB analysis results showed that the peak values at the bifrequencies of gear rotations and the power supply can be effective monitoring features for identifying faulty gears and wear severity as they exhibit agreeable changes with gear loads. A monotonically increasing trend established by these features allows a clear indication of the gear wear progression. The dismantle inspection at 477 h of operation, made when one of the monitored features is about 123% higher than its baseline, has found that there are severe scuffing wear marks on a number of tooth surfaces on the driving gear, showing that the gear endures a gradual wear process during its long test operation. Therefore, it is affirmed that the MSB-MSCA approach proposed is reliable

  7. Arrays of surface-normal electroabsorption modulators for the generation and signal processing of microwave photonics signals

    NARCIS (Netherlands)

    Noharet, Bertrand; Wang, Qin; Platt, Duncan; Junique, Stéphane; Marpaung, D.A.I.; Roeloffzen, C.G.H.

    2011-01-01

    The development of an array of 16 surface-normal electroabsorption modulators operating at 1550nm is presented. The modulator array is dedicated to the generation and processing of microwave photonics signals, targeting a modulation bandwidth in excess of 5GHz. The hybrid integration of the

  8. DMPD: Modulation of Toll-interleukin 1 receptor mediated signaling. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15662540 Modulation of Toll-interleukin 1 receptor mediated signaling. Li X, Qin J.... J Mol Med. 2005 Apr;83(4):258-66. Epub 2005 Jan 21. (.png) (.svg) (.html) (.csml) Show Modulation of Toll-i...nterleukin 1 receptor mediated signaling. PubmedID 15662540 Title Modulation of Toll-interleukin 1 receptor

  9. The Hedgehog Signal Induced Modulation of Bone Morphogenetic Protein Signaling: An Essential Signaling Relay for Urinary Tract Morphogenesis

    Science.gov (United States)

    Nakagata, Naomi; Miyagawa, Shinichi; Suzuki, Kentaro; Kitazawa, Sohei; Yamada, Gen

    2012-01-01

    Background Congenital diseases of the urinary tract are frequently observed in infants. Such diseases present a number of developmental anomalies such as hydroureter and hydronephrosis. Although some genetically-modified mouse models of growth factor signaling genes reproduce urinary phenotypes, the pathogenic mechanisms remain obscure. Previous studies suggest that a portion of the cells in the external genitalia and bladder are derived from peri-cloacal mesenchymal cells that receive Hedgehog (Hh) signaling in the early developmental stages. We hypothesized that defects in such progenitor cells, which give rise to urinary tract tissues, may be a cause of such diseases. Methodology/Principal Findings To elucidate the pathogenic mechanisms of upper urinary tract malformations, we analyzed a series of Sonic hedgehog (Shh) deficient mice. Shh−/− displayed hydroureter and hydronephrosis phenotypes and reduced expression of several developmental markers. In addition, we suggested that Shh modulation at an early embryonic stage is responsible for such phenotypes by analyzing the Shh conditional mutants. Tissue contribution assays of Hh-responsive cells revealed that peri-cloacal mesenchymal cells, which received Hh signal secreted from cloacal epithelium, could contribute to the ureteral mesenchyme. Gain- and loss-of-functional mutants for Hh signaling revealed a correlation between Hh signaling and Bone morphogenetic protein (Bmp) signaling. Finally, a conditional ablation of Bmp receptor type IA (BmprIA) gene was examined in Hh-responsive cell lineages. This system thus made it possible to analyze the primary functions of the growth factor signaling relay. The defective Hh-to-Bmp signaling relay resulted in severe urinary tract phenotypes with a decrease in the number of Hh-responsive cells. Conclusions/Significance This study identified the essential embryonic stages for the pathogenesis of urinary tract phenotypes. These results suggested that Hh

  10. Bioelectric signal classification using a recurrent probabilistic neural network with time-series discriminant component analysis.

    Science.gov (United States)

    Hayashi, Hideaki; Shima, Keisuke; Shibanoki, Taro; Kurita, Yuichi; Tsuji, Toshio

    2013-01-01

    This paper outlines a probabilistic neural network developed on the basis of time-series discriminant component analysis (TSDCA) that can be used to classify high-dimensional time-series patterns. TSDCA involves the compression of high-dimensional time series into a lower-dimensional space using a set of orthogonal transformations and the calculation of posterior probabilities based on a continuous-density hidden Markov model that incorporates a Gaussian mixture model expressed in the reduced-dimensional space. The analysis can be incorporated into a neural network so that parameters can be obtained appropriately as network coefficients according to backpropagation-through-time-based training algorithm. The network is considered to enable high-accuracy classification of high-dimensional time-series patterns and to reduce the computation time taken for network training. In the experiments conducted during the study, the validity of the proposed network was demonstrated for EEG signals.

  11. Neutron-Gamma Pulse Shape Discrimination With Ne-213 Liquid Scintillator By Using Digital Signal Processing Combined With Similarity Method

    International Nuclear Information System (INIS)

    Mardiyanto

    2008-01-01

    Neutron-Gamma Pulse Shape Discrimination with a NE-213 Liquid Scintillator by Using Digital Signal Processing Combined with Similarity Method. Measurement of mixed neutron-gamma radiation is difficult because a nuclear detector is usually sensitive to both radiations. A new attempt of neutron-gamma pulse shape discrimination for a NE-213 liquid scintillator is presented by using digital signal processing combined with an off-line similarity method. The output pulse shapes are digitized with a high speed digital oscilloscope. The n-γ discrimination is done by calculating the index of each pulse shape, which is determined by the similarity method, and then fusing it with its corresponding pulse height. Preliminary results demonstrate good separation of neutron and gamma-ray signals from a NE-213 scintillator with a simple digital system. The results were better than those with a conventional rise time method. Figure of Merit is used to determine the quality of discrimination. The figure of merit of the discrimination using digital signal processing combined with off-line similarity method are 1.9; 1.7; 1.1; 1.1; and 0.8; on the other hand by using conventional method the rise time are 0.9; 0.9; 0.9; 0.7; and 0.4 for the equivalent electron energy of 800; 278; 139; 69; and 30 keV. (author)

  12. Pump-to-Signal Intensity Modulation Transfer in Saturated- Gain Fiber Optical Parametric Amplifiers

    DEFF Research Database (Denmark)

    Lali-Dastjerdi, Zohreh; Lund-Hansen, Toke; Rottwitt, Karsten

    2011-01-01

    The pump-to-signal intensity modulation transfer in saturated degenerate FOPAs is numerically investigated over the whole gain bandwidth. The intensity modulation transfer decreases and the OSNR improves when the amplifier operates in the saturation regime....

  13. Signal modulation in cold-dark-matter detection

    International Nuclear Information System (INIS)

    Freese, K.; Frieman, J.; Gould, A.

    1988-01-01

    If weakly interacting massive particles (WIMP's) are the dark matter in the galactic halo, they may be detected in low-background ionization detectors now operating or with low-temperature devices under development. In detecting WIMP's of low mass or WIMP's with spin-dependent nuclear interactions (e.g., photinos), a principal technical difficulty appears to be achieving very low thresholds (approx. < keV) in large (∼ kg) detectors with low background noise. We present an analytic treatment of WIMP detection and show that the seasonal modulation of the signal can be used to detect WIMP's even at low-signal-to-background levels and thus without the necessity of going to very-low-energy thresholds. As a result, the prospects for detecting a variety of cold-dark-matter candidates may be closer at hand than previously thought. We discuss in detail the detector characteristics required for a number of WIMP candidates, and carefully work out expected event rates for several present and proposed detectors

  14. Actin cytoskeleton modulates calcium signaling during maturation of starfish oocytes.

    Science.gov (United States)

    Kyozuka, Keiichiro; Chun, Jong T; Puppo, Agostina; Gragnaniello, Gianni; Garante, Ezio; Santella, Luigia

    2008-08-15

    Before successful fertilization can occur, oocytes must undergo meiotic maturation. In starfish, this can be achieved in vitro by applying 1-methyladenine (1-MA). The immediate response to 1-MA is the fast Ca2+ release in the cell cortex. Here, we show that this Ca2+ wave always initiates in the vegetal hemisphere and propagates through the cortex, which is the space immediately under the plasma membrane. We have observed that alteration of the cortical actin cytoskeleton by latrunculin-A and jasplakinolide can potently affect the Ca2+ waves triggered by 1-MA. This indicates that the cortical actin cytoskeleton modulates Ca2+ release during meiotic maturation. The Ca2+ wave was inhibited by the classical antagonists of the InsP(3)-linked Ca2+ signaling pathway, U73122 and heparin. To our surprise, however, these two inhibitors induced remarkable actin hyper-polymerization in the cell cortex, suggesting that their inhibitory effect on Ca2+ release may be attributed to the perturbation of the cortical actin cytoskeleton. In post-meiotic eggs, U73122 and jasplakinolide blocked the elevation of the vitelline layer by uncaged InsP(3), despite the massive release of Ca2+, implying that exocytosis of the cortical granules requires not only a Ca2+ rise, but also regulation of the cortical actin cytoskeleton. Our results suggest that the cortical actin cytoskeleton of starfish oocytes plays critical roles both in generating Ca2+ signals and in regulating cortical granule exocytosis.

  15. Data acquisition electronics for gamma ray emission tomography using width-modulated leading-edge discriminators

    Energy Technology Data Exchange (ETDEWEB)

    Lage, E; Tapias, G; Villena, J; Desco, M; Vaquero, J J, E-mail: desco@mce.hggm.e [Unidad de Medicina y CirugIa Experimental, Hospital General Universitario Gregorio Maranon, Madrid (Spain)

    2010-08-07

    We present a new high-performance and low-cost approach for implementing radiation detection acquisition systems. The basic elements used are charge-integrating ADCs and a set of components encapsulated in an HDL (hardware definition language) library which makes it possible to implement several acquisition tasks such as time pickoff and coincidence detection using a new and simple trigger technique that we name WMLET (width-modulated leading-edge timing). As proof of concept, a 32-channel hybrid PET/SPECT acquisition system based on these elements was developed and tested. This demonstrator consists of a master module responsible for the generation and distribution of trigger signals, 2 x 16-channel ADC cards (12-bit resolution) for data digitization and a 32-bit digital I/O PCI card for handling data transmission to a personal computer. System characteristics such as linearity, maximum transmission rates or timing resolution in coincidence mode were evaluated with test and real detector signals. Imaging capabilities of the prototype were also evaluated using different detector configurations. The performance tests showed that this implementation is able to handle data rates in excess of 600k events s{sup -1} when acquiring simultaneously 32 channels (96-byte events). ADC channel linearity is >98.5% in energy quantification. Time resolution in PET mode for the tested configurations ranges from 3.64 ns FWHM to 7.88 ns FWHM when signals from LYSO-based detectors are used. The measured energy resolution matched the expected values for the detectors evaluated and single elements of crystal matrices can be neatly separated in the acquired flood histograms.

  16. Data acquisition electronics for gamma ray emission tomography using width-modulated leading-edge discriminators

    Science.gov (United States)

    Lage, E.; Tapias, G.; Villena, J.; Desco, M.; Vaquero, J. J.

    2010-08-01

    We present a new high-performance and low-cost approach for implementing radiation detection acquisition systems. The basic elements used are charge-integrating ADCs and a set of components encapsulated in an HDL (hardware definition language) library which makes it possible to implement several acquisition tasks such as time pickoff and coincidence detection using a new and simple trigger technique that we name WMLET (width-modulated leading-edge timing). As proof of concept, a 32-channel hybrid PET/SPECT acquisition system based on these elements was developed and tested. This demonstrator consists of a master module responsible for the generation and distribution of trigger signals, 2 × 16-channel ADC cards (12-bit resolution) for data digitization and a 32-bit digital I/O PCI card for handling data transmission to a personal computer. System characteristics such as linearity, maximum transmission rates or timing resolution in coincidence mode were evaluated with test and real detector signals. Imaging capabilities of the prototype were also evaluated using different detector configurations. The performance tests showed that this implementation is able to handle data rates in excess of 600k events s-1 when acquiring simultaneously 32 channels (96-byte events). ADC channel linearity is >98.5% in energy quantification. Time resolution in PET mode for the tested configurations ranges from 3.64 ns FWHM to 7.88 ns FWHM when signals from LYSO-based detectors are used. The measured energy resolution matched the expected values for the detectors evaluated and single elements of crystal matrices can be neatly separated in the acquired flood histograms.

  17. Stochastic resonance in a single-mode laser driven by frequency modulated signal and coloured noises

    Institute of Scientific and Technical Information of China (English)

    Jin Guo-Xiang; Zhang Liang-Ying; Cao Li

    2009-01-01

    By adding frequency modulated signals to the intensity equation of gain-noise model of the single-mode laser driven by two coloured noises which are correlated, this paper uses the linear approximation method to calculate the power spectrum and signal-to-noise ratio (SNR) of the laser intensity. The results show that the SNR appears typical stochastic resonance with the variation of intensity of the pump noise and quantum noise. As the amplitude of a modulated signal has effects on the SNR, it shows suppression, monotone increasing, stochastic resonance, and multiple stochastic resonance with the variation of the frequency of a carrier signal and modulated signal.

  18. A PCA aided cross-covariance scheme for discriminative feature extraction from EEG signals.

    Science.gov (United States)

    Zarei, Roozbeh; He, Jing; Siuly, Siuly; Zhang, Yanchun

    2017-07-01

    Feature extraction of EEG signals plays a significant role in Brain-computer interface (BCI) as it can significantly affect the performance and the computational time of the system. The main aim of the current work is to introduce an innovative algorithm for acquiring reliable discriminating features from EEG signals to improve classification performances and to reduce the time complexity. This study develops a robust feature extraction method combining the principal component analysis (PCA) and the cross-covariance technique (CCOV) for the extraction of discriminatory information from the mental states based on EEG signals in BCI applications. We apply the correlation based variable selection method with the best first search on the extracted features to identify the best feature set for characterizing the distribution of mental state signals. To verify the robustness of the proposed feature extraction method, three machine learning techniques: multilayer perceptron neural networks (MLP), least square support vector machine (LS-SVM), and logistic regression (LR) are employed on the obtained features. The proposed methods are evaluated on two publicly available datasets. Furthermore, we evaluate the performance of the proposed methods by comparing it with some recently reported algorithms. The experimental results show that all three classifiers achieve high performance (above 99% overall classification accuracy) for the proposed feature set. Among these classifiers, the MLP and LS-SVM methods yield the best performance for the obtained feature. The average sensitivity, specificity and classification accuracy for these two classifiers are same, which are 99.32%, 100%, and 99.66%, respectively for the BCI competition dataset IVa and 100%, 100%, and 100%, for the BCI competition dataset IVb. The results also indicate the proposed methods outperform the most recently reported methods by at least 0.25% average accuracy improvement in dataset IVa. The execution time

  19. Modulation of neurotrophic signaling pathways by polyphenols

    Directory of Open Access Journals (Sweden)

    Moosavi F

    2015-12-01

    response element-binding protein (CREB phosphorylation. Finally, the antioxidant activity of polyphenols reflected in the activation of Nrf2 pathway and the consequent upregulation of detoxification enzymes such as heme oxygenase-1 as well as the contribution of these effects to the neurotrophic activity have also been discussed. In conclusion, a better understanding of the neurotrophic effects of polyphenols and the concomitant modulations of signaling pathways is useful for designing more effective agents for management of neurodegenerative diseases. Keywords: flavonoids, hydroxycinnamic acids, neuroprotective, neurodegeneration, Trk

  20. Searching for the annual modulation of dark matter signal with the GENIUS-TF experiment

    International Nuclear Information System (INIS)

    Tomei, C.; Dietz, A.; Krivosheina, I.; Klapdor-Kleingrothaus, H.V.

    2003-01-01

    The annual modulation of the recoil spectrum observed in an underground detector is well known as the main signature of a possible WIMP signal. The GENIUS-TF experiment, under construction in the Gran Sasso National Laboratory, can search for the annual modulation of the Dark Matter signal using 40 kg of naked-Ge detectors in liquid nitrogen. Starting from a set of data simulated under the hypothesis of modulation and using different methods, we show the potential of GENIUS-TF for extracting the modulated signal and the expected WIMP mass and WIMP cross-section

  1. Multisensory interaction in vibrotactile detection and discrimination of amplitude modulation: insights from expert MFS surgeons and naive participants

    Directory of Open Access Journals (Sweden)

    Korman Maria

    2011-12-01

    Full Text Available Perception of vibration during drilling demands integration of haptic and auditory information with force information. In this study we explored the ability to detect and discriminate changes in vibrotactile stimuli amplitude based either on purely haptic feedback or together with congruent synthesized auditory cues in groups of naive subjects and expert surgeons. Our results point toward the complex influence of multimodal experience during vibration perception. First, in naive subjects, we showed that detection and discrimination of amplitude change in complex vibro-tactile stimulus is selectively sensitive to combination of modality and previous experience. In the domain of discrimination, our results suggest that bi-modal performance is always better than uni-modal performance regardless of order of experience. Second, experiments with expert surgeons revealed that expertise in complex skill of maxilla-facial surgery strongly relies on enhanced touch perception, as measured in reaction times and discrimination ability in bi-modal vibro-auditory conditions. These observations suggest that acquisition of mandibular surgery skill has brought to an enhanced representation of vibro-tactile modulations in relevant stimuli ranges. Altogether, our results provide basis to assume that during acquisition of mandibular drilling skill, trainees may benefit from training of relevant basic aspects of touch perception - sensitivity to vibration and accompanying modulations of sound.

  2. System and method of modulating electrical signals using photoconductive wide bandgap semiconductors as variable resistors

    Science.gov (United States)

    Harris, John Richardson; Caporaso, George J; Sampayan, Stephen E

    2013-10-22

    A system and method for producing modulated electrical signals. The system uses a variable resistor having a photoconductive wide bandgap semiconductor material construction whose conduction response to changes in amplitude of incident radiation is substantially linear throughout a non-saturation region to enable operation in non-avalanche mode. The system also includes a modulated radiation source, such as a modulated laser, for producing amplitude-modulated radiation with which to direct upon the variable resistor and modulate its conduction response. A voltage source and an output port, are both operably connected to the variable resistor so that an electrical signal may be produced at the output port by way of the variable resistor, either generated by activation of the variable resistor or propagating through the variable resistor. In this manner, the electrical signal is modulated by the variable resistor so as to have a waveform substantially similar to the amplitude-modulated radiation.

  3. Demonstration of the frequency modulation of optical signals with a high frequency deviation parameter

    International Nuclear Information System (INIS)

    Shamray, A V; Kozlov, A S; Il'ichev, I V; Petrov, M P

    2008-01-01

    A new type of an integrated optical modulator for the frequency coding of optical signals is developed and fabricated. The modulator operation is based on the original technology of the electric control of a Bragg grating. The frequency modulation of an optical signal with the frequency deviation of 25 GHz is demonstrated experimentally. The modular was used to transfer the ASCII code through an optical fibre. (optical communication)

  4. Contextual modulation of primary visual cortex by auditory signals.

    Science.gov (United States)

    Petro, L S; Paton, A T; Muckli, L

    2017-02-19

    Early visual cortex receives non-feedforward input from lateral and top-down connections (Muckli & Petro 2013 Curr. Opin. Neurobiol. 23, 195-201. (doi:10.1016/j.conb.2013.01.020)), including long-range projections from auditory areas. Early visual cortex can code for high-level auditory information, with neural patterns representing natural sound stimulation (Vetter et al. 2014 Curr. Biol. 24, 1256-1262. (doi:10.1016/j.cub.2014.04.020)). We discuss a number of questions arising from these findings. What is the adaptive function of bimodal representations in visual cortex? What type of information projects from auditory to visual cortex? What are the anatomical constraints of auditory information in V1, for example, periphery versus fovea, superficial versus deep cortical layers? Is there a putative neural mechanism we can infer from human neuroimaging data and recent theoretical accounts of cortex? We also present data showing we can read out high-level auditory information from the activation patterns of early visual cortex even when visual cortex receives simple visual stimulation, suggesting independent channels for visual and auditory signals in V1. We speculate which cellular mechanisms allow V1 to be contextually modulated by auditory input to facilitate perception, cognition and behaviour. Beyond cortical feedback that facilitates perception, we argue that there is also feedback serving counterfactual processing during imagery, dreaming and mind wandering, which is not relevant for immediate perception but for behaviour and cognition over a longer time frame.This article is part of the themed issue 'Auditory and visual scene analysis'. © 2017 The Authors.

  5. Drug states as modulators of conditioned immobility in a latent discrimination procedure.

    NARCIS (Netherlands)

    Maes, J.H.R.; Rijn, C.M. van; Vossen, J.M.H.

    1996-01-01

    Midazolam, amphetamine, and flesinoxan were used in four rat experiments to examine the usefulness of a latent Pavlovian discrimination procedure to assess the discriminative-stimulus, or occasion-setting, properties of drugs. Experiment 1 first assessed the unconditioned effect of each of the drugs

  6. An information-theoretical approach to image resolution applied to neutron imaging detectors based upon individual discriminator signals

    International Nuclear Information System (INIS)

    Clergeau, Jean-Francois; Ferraton, Matthieu; Guerard, Bruno; Khaplanov, Anton; Piscitelli, Francesco; Platz, Martin; Rigal, Jean-Marie; Van Esch, Patrick; Daulle, Thibault

    2013-06-01

    1D or 2D neutron imaging detectors with individual wire or strip readout using discriminators have the advantage of being able to treat several neutron impacts partially overlapping in time, hence reducing global dead time. A single neutron impact usually gives rise to several discriminator signals. In this paper, we introduce an information-theoretical definition of image resolution. Two point-like spots of neutron impacts with a given distance between them act as a source of information (each neutron hit belongs to one spot or the other), and the detector plus signal treatment is regarded as an imperfect communication channel that transmits this information. The maximal mutual information obtained from this channel as a function of the distance between the spots allows to define a calibration-independent measure of resolution. We then apply this measure to quantify the power of resolution of different algorithms treating these individual discriminator signals which can be implemented in firmware. The method is then applied to different detectors existing at the ILL. Center-of-gravity methods usually improve the resolution over best-wire algorithms which are the standard way of treating these signals. (authors)

  7. An information-theoretical approach to image resolution applied to neutron imaging detectors based upon individual discriminator signals

    Energy Technology Data Exchange (ETDEWEB)

    Clergeau, Jean-Francois; Ferraton, Matthieu; Guerard, Bruno; Khaplanov, Anton; Piscitelli, Francesco; Platz, Martin; Rigal, Jean-Marie; Van Esch, Patrick [Institut Laue Langevin, Neutron Detector Service, Grenoble (France); Daulle, Thibault [PHELMA Grenoble - INP Grenoble (France)

    2013-06-15

    1D or 2D neutron imaging detectors with individual wire or strip readout using discriminators have the advantage of being able to treat several neutron impacts partially overlapping in time, hence reducing global dead time. A single neutron impact usually gives rise to several discriminator signals. In this paper, we introduce an information-theoretical definition of image resolution. Two point-like spots of neutron impacts with a given distance between them act as a source of information (each neutron hit belongs to one spot or the other), and the detector plus signal treatment is regarded as an imperfect communication channel that transmits this information. The maximal mutual information obtained from this channel as a function of the distance between the spots allows to define a calibration-independent measure of resolution. We then apply this measure to quantify the power of resolution of different algorithms treating these individual discriminator signals which can be implemented in firmware. The method is then applied to different detectors existing at the ILL. Center-of-gravity methods usually improve the resolution over best-wire algorithms which are the standard way of treating these signals. (authors)

  8. Differences in the reliance on cuticular hydrocarbons as sexual signaling and species discrimination cues in parasitoid wasps.

    Science.gov (United States)

    Buellesbach, Jan; Vetter, Sebastian G; Schmitt, Thomas

    2018-01-01

    Cuticular hydrocarbons (CHC) have been documented to play crucial roles as species- and sex-specific cues in the chemical communication systems of a wide variety of insects. However, whether they are sufficient by themselves as the sole cue triggering sexual behavior as well as preference of con- over heterospecific mating partners is rarely assessed. We conducted behavioral assays in three representative species of parasitoid wasps (Hymenoptera: Pteromalidae) to determine their reliance on CHC as species-specific sexual signaling cues. We found a surprising degree of either unspecific or insufficient sexual signaling when CHC are singled out as recognition cues. Most strikingly, the cosmopolitan species Nasonia vitripennis , expected to experience enhanced selection pressure to discriminate against other co-occurring parasitoids, did not discriminate against CHC of a partially sympatric species from another genus, Trichomalopsis sarcophagae . Focusing on the latter species, in turn, it became apparent that CHC are even insufficient as the sole cue triggering conspecific sexual behavior, hinting at the requirement of additional, synergistic sexual cues particularly important in this species. Finally, in the phylogenetically and chemically most divergent species Muscidifurax uniraptor, we intriguingly found both CHC-based sexual signaling as well as species discrimination behavior intact although this species is naturally parthenogenetic with sexual reproduction only occurring under laboratory conditions. Our findings implicate a discrepancy in the reliance on and specificity of CHC as sexual cues in our tested parasitioid wasps. CHC profiles were not sufficient for unambiguous discrimination and preference behavior, as demonstrated by clear cross-attraction between some of our tested wasp genera. Moreover, we could show that only in T. sarcophagae , additional behavioral cues need to be present for triggering natural mating behavior, hinting at an interesting

  9. Re-modulated technology of WDM-PON employing different DQPSK downstream signals

    Science.gov (United States)

    Gao, Chao; Xin, Xiang-jun; Yu, Chong-xiu

    2012-11-01

    This paper proposes a kind of modulation architecture for wavelength-division-multiplexing passive optical network (WDMPON) employing optical differential quadrature phase shift keying (DQPSK) downstream signals and two different modulation formats of re-modulated upstream signals. At the optical line terminal (OLT), 10 Gbit/s signal is modulated with DQPSK. At the optical network unit (ONU), part of the downstream signal is re-modulated with on-off keying (OOK) or inverse-return-to-zero (IRZ). Simulation results show the impact on the system employing NRZ, RZ and carrier-suppressed return-to-zero (CSRZ). The analyses also reflect that the architecture can restrain chromatic dispersion and channel crosstalk, which makes it the best architecture of access network in the future.

  10. Analysis of interference of QPSK and QDPSK modulation signals by mathematical

    Science.gov (United States)

    Li, Dairuo; Xu, Kai

    2017-03-01

    In today's society, with the rapid development and extensive application of the information technology of the network central station and the integrated information system technology, information plays an important role in the military communication, mastering the information right to the competition Important role, how to protect one's own security, smooth access to and transmission of information, and to maximize the elimination of interference has become an important issue at home and abroad. QPSK modulation and its improved QPSK modulation as the mainstream signal modulation, the most widely used. In this paper, the principle of QPSK and QDPSK modulation and demodulation are introduced in this paper. Then, how to interfere with QPSK modulation signal is analyzed, and the interference of QPSK modulation signal is simulated by Matlab scripting program, which can be used in the next step. And to study the next step of anti-jamming measures provided the basis and preparatory work.

  11. Presynaptic signal transduction pathways that modulate synaptic transmission

    NARCIS (Netherlands)

    de Jong, A.P.H.; Verhage, M.

    2009-01-01

    Presynaptic modulation is a crucial factor in the adaptive capacity of the nervous system. The coupling between incoming action potentials and neurotransmitter secretion is modulated by firstly, recent activity of the presynaptic axon that leads to the accumulation of residual calcium in the

  12. Use of the discriminant Fourier-derived cepstrum with feature-level post-processing for surface electromyographic signal classification

    International Nuclear Information System (INIS)

    Chen, Xinpu; Zhu, Xiangyang; Zhang, Dingguo

    2009-01-01

    Myoelectrical pattern classification is a crucial part in multi-functional prosthesis control. This paper investigates a discriminant Fourier-derived cepstrum (DFC) and feature-level post-processing (FLPP) to discriminate hand and wrist motions using the surface electromyographic signal. The Fourier-derived cepstrum takes advantage of the Fourier magnitude or sub-band power energy of signals directly and provides flexible use of spectral information changing with different motions. Appropriate cepstral coefficients are selected by a proposed separability criterion to construct DFC features. For the post-processing, FLPP which combines features from several analysis windows is used to improve the feature performance further. In this work, two classifiers (a linear discriminant classifier and quadratic discriminant classifier) without hyper-parameter optimization are employed to simplify the training procedure and avoid the possible bias of feature evaluation. Experimental results of the 11-motion problem show that the proposed DFC feature outperforms traditional features such as time-domain statistics and autoregressive-derived cepstrum in terms of the classification accuracy, and it is a promising method for the multi-functionality and high-accuracy control of myoelectric prostheses

  13. The atmospheric signal of terrestrial carbon isotopic discrimination and its implication for partitioning carbon fluxes

    International Nuclear Information System (INIS)

    Miller, John B.; Tans, Pieter P.; Conway, Thomas J.; White, James W.C.; Vaughn, Bruce W.

    2003-01-01

    The 13 C/ 12 C ratio in atmospheric carbon dioxide has been measured in samples taken in the NOAA/CMDL network since 1991. By examining the relationship between weekly anomalies in 13 C and CO 2 at continental sites in the network, we infer temporal and spatial values for the isotopic signature of terrestrial CO 2 fluxes. We can convert these isotopic signatures to values of discrimination if we assume the atmospheric starting point for photosynthesis. The average discrimination in the Northern Hemisphere between 30 and 50 deg N is calculated to be 16.6 ± 0.2 per mil. In contrast to some earlier modeling studies, we find no strong latitudinal gradient in discrimination. However, we do observe that discrimination in Eurasia is larger than in North America, which is consistent with two modeling studies. We also observe a possible trend in the North American average of discrimination toward less discrimination. There is no apparent trend in the Eurasian average or at any individual sites. However, there is interannual variability on the order of 2 per mil at several sites and regions. Finally, we calculate the northern temperate terrestrial CO 2 flux replacing our previous discrimination values of about 18 per mil with the average value of 16.6 calculated in this study. We find this enhances the terrestrial sink by about 0.4 GtC/yr

  14. n-Order and maximum fuzzy similarity entropy for discrimination of signals of different complexity: Application to fetal heart rate signals.

    Science.gov (United States)

    Zaylaa, Amira; Oudjemia, Souad; Charara, Jamal; Girault, Jean-Marc

    2015-09-01

    This paper presents two new concepts for discrimination of signals of different complexity. The first focused initially on solving the problem of setting entropy descriptors by varying the pattern size instead of the tolerance. This led to the search for the optimal pattern size that maximized the similarity entropy. The second paradigm was based on the n-order similarity entropy that encompasses the 1-order similarity entropy. To improve the statistical stability, n-order fuzzy similarity entropy was proposed. Fractional Brownian motion was simulated to validate the different methods proposed, and fetal heart rate signals were used to discriminate normal from abnormal fetuses. In all cases, it was found that it was possible to discriminate time series of different complexity such as fractional Brownian motion and fetal heart rate signals. The best levels of performance in terms of sensitivity (90%) and specificity (90%) were obtained with the n-order fuzzy similarity entropy. However, it was shown that the optimal pattern size and the maximum similarity measurement were related to intrinsic features of the time series. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Neutron-gamma discrimination employing pattern recognition of the signal from liquid scintillator

    International Nuclear Information System (INIS)

    Kamada, Kohji; Enokido, Uhji; Ogawa, Seiji

    1999-01-01

    A pattern recognition method was applied to the neutron-gamma discrimination of the pulses from the liquid scintillator, NE-213. The circuit for the discrimination is composed of A/D converter, fast SCA, memory control circuit, two digital delay lines and two buffer memories. All components are packed on a small circuit board and are installed into a personal computer. Experiments using a weak 252 Cf n-γ source were undertaken to test the feasibility of the circuit. The circuit is of very easy adjustment and, at the same time, of very economical price when compared with usual discrimination circuits, such as the TAC system

  16. Neutron-gamma discrimination employing pattern recognition of the signal from liquid scintillator

    CERN Document Server

    Kamada, K; Ogawa, S

    1999-01-01

    A pattern recognition method was applied to the neutron-gamma discrimination of the pulses from the liquid scintillator, NE-213. The circuit for the discrimination is composed of A/D converter, fast SCA, memory control circuit, two digital delay lines and two buffer memories. All components are packed on a small circuit board and are installed into a personal computer. Experiments using a weak sup 2 sup 5 sup 2 Cf n-gamma source were undertaken to test the feasibility of the circuit. The circuit is of very easy adjustment and, at the same time, of very economical price when compared with usual discrimination circuits, such as the TAC system.

  17. A Study on Signal Group Processing of AUTOSAR COM Module

    International Nuclear Information System (INIS)

    Lee, Jeong-Hwan; Hwang, Hyun Yong; Han, Tae Man; Ahn, Yong Hak

    2013-01-01

    In vehicle, there are many ECU(Electronic Control Unit)s, and ECUs are connected to networks such as CAN, LIN, FlexRay, and so on. AUTOSAR COM(Communication) which is a software platform of AUTOSAR(AUTomotive Open System ARchitecture) in the international industry standards of automotive electronic software processes signals and signal groups for data communications between ECUs. Real-time and reliability are very important for data communications in the vehicle. Therefore, in this paper, we analyze functions of signals and signal groups used in COM, and represent that functions of signal group are more efficient than signals in real-time data synchronization and network resource usage between the sender and receiver.

  18. A Study on Signal Group Processing of AUTOSAR COM Module

    Science.gov (United States)

    Lee, Jeong-Hwan; Hwang, Hyun Yong; Han, Tae Man; Ahn, Yong Hak

    2013-06-01

    In vehicle, there are many ECU(Electronic Control Unit)s, and ECUs are connected to networks such as CAN, LIN, FlexRay, and so on. AUTOSAR COM(Communication) which is a software platform of AUTOSAR(AUTomotive Open System ARchitecture) in the international industry standards of automotive electronic software processes signals and signal groups for data communications between ECUs. Real-time and reliability are very important for data communications in the vehicle. Therefore, in this paper, we analyze functions of signals and signal groups used in COM, and represent that functions of signal group are more efficient than signals in real-time data synchronization and network resource usage between the sender and receiver.

  19. Autonomous Non-Linear Classification of LPI Radar Signal Modulations

    National Research Council Canada - National Science Library

    Gulum, Taylan O

    2007-01-01

    ...) radar modulations is investigated. A software engineering architecture that allows a full investigation of various preprocessing algorithms and classification techniques is applied to a database of important LPI radar waveform...

  20. Gap junction modulation by extracellular signaling molecules: the thymus model

    Directory of Open Access Journals (Sweden)

    Alves L.A.

    2000-01-01

    Full Text Available Gap junctions are intercellular channels which connect adjacent cells and allow direct exchange of molecules of low molecular weight between them. Such a communication has been described as fundamental in many systems due to its importance in coordination, proliferation and differentiation. Recently, it has been shown that gap junctional intercellular communication (GJIC can be modulated by several extracellular soluble factors such as classical hormones, neurotransmitters, interleukins, growth factors and some paracrine substances. Herein, we discuss some aspects of the general modulation of GJIC by extracellular messenger molecules and more particularly the regulation of such communication in the thymus gland. Additionally, we discuss recent data concerning the study of different neuropeptides and hormones in the modulation of GJIC in thymic epithelial cells. We also suggest that the thymus may be viewed as a model to study the modulation of gap junction communication by different extracellular messengers involved in non-classical circuits, since this organ is under bidirectional neuroimmunoendocrine control.

  1. Signal discrimination of ULF electromagnetic data with using singular spectrum analysis – an attempt to detect train noise

    Directory of Open Access Journals (Sweden)

    S. Saito

    2011-07-01

    Full Text Available Electromagnetic phenomena associated with crustal activities have been reported in a wide frequency range (DC-HF. In particular, ULF electromagnetic phenomena are the most promising among them because of the deeper skin depth. However, ULF geoelctromagnetic data are a superposition of signals of different origins. They originated from interactions between the geomagnetic field and the solar wind, leak current by a DC-driven train (train noise, precipitation, and so on. In general, the intensity of electromagnetic signals associated with crustal activity is smaller than the above variations. Therefore, in order to detect a smaller signal, signal discrimination such as noise reduction or identification of noises is very important. In this paper, the singular spectrum analysis (SSA has been performed to detect the DC-driven train noise in geoelectric potential difference data. The aim of this paper is to develop an effective algorithm for the DC-driven train noise detection.

  2. 10 CFR 431.224 - Uniform test method for the measurement of energy consumption for traffic signal modules and...

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 3 2010-01-01 2010-01-01 false Uniform test method for the measurement of energy consumption for traffic signal modules and pedestrian modules. 431.224 Section 431.224 Energy DEPARTMENT OF... measurement of energy consumption for traffic signal modules and pedestrian modules. (a) Scope. This section...

  3. Operation, analysis, and design of signalized intersections : a module for the introductory course in transportation engineering.

    Science.gov (United States)

    2014-02-01

    This report presents materials that can be used as the basis for a module on signalized intersections in the introductory : course in transportation engineering. The materials were developed based on studies of the work of students who took : this in...

  4. Direct UV written Michelson interferometer for RZ signal generation using phase-to-intensity modulation conversion

    DEFF Research Database (Denmark)

    Peucheret, Christophe; Geng, Yan; Zsigri, Beata

    2005-01-01

    An integrated Michelson delay interferometer structure making use of waveguide gratings as reflective elements is proposed and fabricated by direct ultraviolet writing. Successful return-to-zero alternate-mark-inversion signal generation using phase-to-intensity modulation conversion...

  5. Coding of amplitude-modulated signals in the cochlear nucleus of a grass frog

    Science.gov (United States)

    Bibikov, N. G.

    2002-07-01

    To study the mechanisms that govern the coding of temporal features of complex sound signals, responses of single neurons located in the dorsal nucleus of the medulla oblongata (the cochlear nucleus) of a curarized grass frog ( Rana temporaria) to pure tone bursts and amplitude modulated tone bursts with a modulation frequency of 20 Hz and modulation depths of 10 and 80% were recorded. The carrier frequency was equal to the characteristic frequency of a neuron, the average signal level was 20 30 dB above the threshold, and the signal duration was equal to ten full modulation periods. Of the 133 neurons studied, 129 neurons responded to 80% modulated tone bursts by discharges that were phase-locked with the envelope waveform. At this modulation depth, the best phase locking was observed for neurons with the phasic type of response to tone bursts. For tonic neurons with low characteristic frequencies, along with the reproduction of the modulation, phase locking with the carrier frequency of the signal was observed. At 10% amplitude modulation, phasic neurons usually responded to only the onset of a tone burst. Almost all tonic units showed a tendency to reproduce the envelope, although the efficiency of the reproduction was low, and for half of these neurons, it was below the reliability limit. Some neurons exhibited a more efficient reproduction of the weak modulation. For almost half of the neurons, a reliable improvement was observed in the phase locking of the response during the tone burst presentation (from the first to the tenth modulation period). The cooperative histogram of a set of neurons responding to 10% modulated tone bursts within narrow ranges of frequencies and intensities retains the information on the dynamics of the envelope variation. The data are compared with the results obtained from the study of the responses to similar signals in the acoustic midbrain center of the same object and also with the psychophysical effect of a differential

  6. All-optical wavelength conversion and signal regeneration using an electroabsorption modulator

    DEFF Research Database (Denmark)

    Højfeldt, Sune; Bischoff, Svend; Mørk, Jesper

    2000-01-01

    All-optical wavelength conversion and signal regeneration based on cross-absorption modulation in an InGaAsP quantum well electroabsorption modulator (EAM) is studied at different bit rates. We present theoretical results showing wavelength conversion efficiency in agreement with existing...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  8. Signal recognition and parameter estimation of BPSK-LFM combined modulation

    Science.gov (United States)

    Long, Chao; Zhang, Lin; Liu, Yu

    2015-07-01

    Intra-pulse analysis plays an important role in electronic warfare. Intra-pulse feature abstraction focuses on primary parameters such as instantaneous frequency, modulation, and symbol rate. In this paper, automatic modulation recognition and feature extraction for combined BPSK-LFM modulation signals based on decision theoretic approach is studied. The simulation results show good recognition effect and high estimation precision, and the system is easy to be realized.

  9. Detection and processing of phase modulated optical signals at 40 Gbit/s and beyond

    DEFF Research Database (Denmark)

    Geng, Yan

    the amplitude regeneration capability based on FWM in a highly nonlinear fiber (HNLF). The first reported experimental demonstration of amplitude equalization of 40 Gbit/s RZ-DPSK signals using a 500 m long HNLF is presented. Using four possible phase levels to carry the information, DQPSK allows generation......This thesis addresses demodulation in direct detection systems and signal processing of high speed phase modulated signals in future all-optical wavelength division multiplexing (WDM) communication systems where differential phase shift keying (DPSK) or differential quadrature phase shift keying...... (DQPSK) are used to transport information. All-optical network functionalities -such as optical labeling, wavelength conversion and signal regeneration- are experimentally investigated. Direct detection of phase modulated signals requires phase-to-intensity modulation conversion in a demodulator...

  10. Cognitive flexibility modulates maturation and music-training-related changes in neural sound discrimination.

    Science.gov (United States)

    Saarikivi, Katri; Putkinen, Vesa; Tervaniemi, Mari; Huotilainen, Minna

    2016-07-01

    Previous research has demonstrated that musicians show superior neural sound discrimination when compared to non-musicians, and that these changes emerge with accumulation of training. Our aim was to investigate whether individual differences in executive functions predict training-related changes in neural sound discrimination. We measured event-related potentials induced by sound changes coupled with tests for executive functions in musically trained and non-trained children aged 9-11 years and 13-15 years. High performance in a set-shifting task, indexing cognitive flexibility, was linked to enhanced maturation of neural sound discrimination in both musically trained and non-trained children. Specifically, well-performing musically trained children already showed large mismatch negativity (MMN) responses at a young age as well as at an older age, indicating accurate sound discrimination. In contrast, the musically trained low-performing children still showed an increase in MMN amplitude with age, suggesting that they were behind their high-performing peers in the development of sound discrimination. In the non-trained group, in turn, only the high-performing children showed evidence of an age-related increase in MMN amplitude, and the low-performing children showed a small MMN with no age-related change. These latter results suggest an advantage in MMN development also for high-performing non-trained individuals. For the P3a amplitude, there was an age-related increase only in the children who performed well in the set-shifting task, irrespective of music training, indicating enhanced attention-related processes in these children. Thus, the current study provides the first evidence that, in children, cognitive flexibility may influence age-related and training-related plasticity of neural sound discrimination. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  11. Large-signal modulation characteristics of a GaN-based micro-LED for Gbps visible-light communication

    Science.gov (United States)

    Tian, Pengfei; Wu, Zhengyuan; Liu, Xiaoyan; Fang, Zhilai; Zhang, Shuailong; Zhou, Xiaolin; Liu, Kefu; Liu, Ming-Gang; Chen, Shu-Jhih; Lee, Chia-Yu; Cong, Chunxiao; Hu, Laigui; Qiu, Zhi-Jun; Zheng, Lirong; Liu, Ran

    2018-04-01

    The large-signal modulation characteristics of a GaN-based micro-LED have been studied for Gbps visible-light communication. With an increasing signal modulation depth the modulation bandwidth decreases, which matches up with the increase in the sum of the signal rise time and fall time. By simulating the band diagram and the carrier recombination rate of the micro-LED under large-signal modulation, carrier recombination and the carrier sweep-out effect are analyzed and found to be the dominant mechanisms behind the variation of modulation bandwidth. These results give further insight into improving the modulation bandwidth for high-speed visible-light communication.

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

    Science.gov (United States)

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

    2011-03-01

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

  13. Near optimal discrimination of binary coherent signals via atom–light interaction

    Science.gov (United States)

    Han, Rui; Bergou, János A.; Leuchs, Gerd

    2018-04-01

    We study the discrimination of weak coherent states of light with significant overlaps by nondestructive measurements on the light states through measuring atomic states that are entangled to the coherent states via dipole coupling. In this way, the problem of measuring and discriminating coherent light states is shifted to finding the appropriate atom–light interaction and atomic measurements. We show that this scheme allows us to attain a probability of error extremely close to the Helstrom bound, the ultimate quantum limit for discriminating binary quantum states, through the simple Jaynes–Cummings interaction between the field and ancilla with optimized light–atom coupling and projective measurements on the atomic states. Moreover, since the measurement is nondestructive on the light state, information that is not detected by one measurement can be extracted from the post-measurement light states through subsequent measurements.

  14. Modulation of β-catenin signaling by glucagon receptor activation.

    Directory of Open Access Journals (Sweden)

    Jiyuan Ke

    Full Text Available The glucagon receptor (GCGR is a member of the class B G protein-coupled receptor family. Activation of GCGR by glucagon leads to increased glucose production by the liver. Thus, glucagon is a key component of glucose homeostasis by counteracting the effect of insulin. In this report, we found that in addition to activation of the classic cAMP/protein kinase A (PKA pathway, activation of GCGR also induced β-catenin stabilization and activated β-catenin-mediated transcription. Activation of β-catenin signaling was PKA-dependent, consistent with previous reports on the parathyroid hormone receptor type 1 (PTH1R and glucagon-like peptide 1 (GLP-1R receptors. Since low-density-lipoprotein receptor-related protein 5 (Lrp5 is an essential co-receptor required for Wnt protein mediated β-catenin signaling, we examined the role of Lrp5 in glucagon-induced β-catenin signaling. Cotransfection with Lrp5 enhanced the glucagon-induced β-catenin stabilization and TCF promoter-mediated transcription. Inhibiting Lrp5/6 function using Dickkopf-1(DKK1 or by expression of the Lrp5 extracellular domain blocked glucagon-induced β-catenin signaling. Furthermore, we showed that Lrp5 physically interacted with GCGR by immunoprecipitation and bioluminescence resonance energy transfer assays. Together, these results reveal an unexpected crosstalk between glucagon and β-catenin signaling, and may help to explain the metabolic phenotypes of Lrp5/6 mutations.

  15. Spectral-Temporal Modulated Ripple Discrimination by Children With Cochlear Implants.

    Science.gov (United States)

    Landsberger, David M; Padilla, Monica; Martinez, Amy S; Eisenberg, Laurie S

    A postlingually implanted adult typically develops hearing with an intact auditory system, followed by periods of deafness (or near deafness) and adaptation to the implant. For an early implanted child whose brain is highly plastic, the auditory system matures with consistent input from a cochlear implant. It is likely that the auditory system of early implanted cochlear implant users is fundamentally different than postlingually implanted adults. The purpose of this study is to compare the basic psychophysical capabilities and limitations of these two populations on a spectral resolution task to determine potential effects of early deprivation and plasticity. Performance on a spectral resolution task (Spectral-temporally Modulated Ripple Test [SMRT]) was measured for 20 bilaterally implanted, prelingually deafened children (between 5 and 13 years of age) and 20 hearing children within the same age range. Additionally, 15 bilaterally implanted, postlingually deafened adults, and 10 hearing adults were tested on the same task. Cochlear implant users (adults and children) were tested bilaterally, and with each ear alone. Hearing listeners (adults and children) were tested with the unprocessed SMRT and with a vocoded version that simulates an 8-channel cochlear implant. For children with normal hearing, a positive correlation was found between age and SMRT score for both the unprocessed and vocoded versions. Older hearing children performed similarly to hearing adults in both the unprocessed and vocoded test conditions. However, for children with cochlear implants, no significant relationship was found between SMRT score and chronological age, age at implantation, or years of implant experience. Performance by children with cochlear implants was poorer than performance by cochlear implanted adults. It was also found that children implanted sequentially tended to have better scores with the first implant compared with the second implant. This difference was not

  16. Direct modulation and detection link using polybinary signaling

    DEFF Research Database (Denmark)

    Suhr, L.F.; Vegas Olmos, Juan José; Peucheret, Christophe

    2014-01-01

    This paper presents experimental results on a spectral efficient optical fiber link by using a novel seven-level polybinary signaling at 14.32 Gbps achieving a potential 7.95 b/s/Hz with very little complexity and processing footprint.......This paper presents experimental results on a spectral efficient optical fiber link by using a novel seven-level polybinary signaling at 14.32 Gbps achieving a potential 7.95 b/s/Hz with very little complexity and processing footprint....

  17. A Processing Technique for OFDM-Modulated Wideband Radar Signals

    NARCIS (Netherlands)

    Tigrek, R.F.

    2010-01-01

    The orthogonal frequency division multiplexing (OFDM) is a multicarrier spread-spectrum technique which finds wide-spread use in communications. The OFDM pulse compression method that utilizes an OFDM communication signal for radar tasks has been developed and reported in this dissertation. Using

  18. Jasmonic acid signaling modulates ozone-induced hypersensitive cell death.

    Science.gov (United States)

    Rao, M V; Lee, H; Creelman, R A; Mullet, J E; Davis, K R

    2000-09-01

    Recent studies suggest that cross-talk between salicylic acid (SA)-, jasmonic acid (JA)-, and ethylene-dependent signaling pathways regulates plant responses to both abiotic and biotic stress factors. Earlier studies demonstrated that ozone (O(3)) exposure activates a hypersensitive response (HR)-like cell death pathway in the Arabidopsis ecotype Cvi-0. We now have confirmed the role of SA and JA signaling in influencing O(3)-induced cell death. Expression of salicylate hydroxylase (NahG) in Cvi-0 reduced O(3)-induced cell death. Methyl jasmonate (Me-JA) pretreatment of Cvi-0 decreased O(3)-induced H(2)O(2) content and SA concentrations and completely abolished O(3)-induced cell death. Cvi-0 synthesized as much JA as did Col-0 in response to O(3) exposure but exhibited much less sensitivity to exogenous Me-JA. Analyses of the responses to O(3) of the JA-signaling mutants jar1 and fad3/7/8 also demonstrated an antagonistic relationship between JA- and SA-signaling pathways in controlling the magnitude of O(3)-induced HR-like cell death.

  19. Automatic Modulation Classification of LFM and Polyphase-coded Radar Signals

    Directory of Open Access Journals (Sweden)

    S. B. S. Hanbali

    2017-12-01

    Full Text Available There are several techniques for detecting and classifying low probability of intercept radar signals such as Wigner distribution, Choi-Williams distribution and time-frequency rate distribution, but these distributions require high SNR. To overcome this problem, we propose a new technique for detecting and classifying linear frequency modulation signal and polyphase coded signals using optimum fractional Fourier transform at low SNR. The theoretical analysis and simulation experiments demonstrate the validity and efficiency of the proposed method.

  20. Lrp4: a novel modulator of extracellular signaling in craniofacial organogenesis

    OpenAIRE

    Ohazama, Atsushi; Porntaveetus, Thantrira; Ota, Masato S.; Herz, Joachim; Sharpe, Paul T.

    2010-01-01

    The low-density lipoprotein (LDL) receptor family is a large evolutionarily conserved group of transmembrane proteins. It has been shown that LDL receptor family members can also function as direct signal transducers or modulators for a broad range of cellular signalling pathways. We have identified a novel mode of signalling pathway integration/coordination that occurs outside cells during development that involves an LDL family member. Physical interaction between an extracellular protein (...

  1. Use of modulated excitation signals in ultrasound. Part I: Basic concepts and expected benefits

    DEFF Research Database (Denmark)

    Misaridis, Thanassis; Jensen, Jørgen Arendt

    2005-01-01

    This paper, the first from a series of three papers on the application of coded excitation signals in medical ultrasound, discusses the basic principles and ultrasound-related problems of pulse compression. The concepts of signal modulation and matched filtering are given, and a simple model...... of attenuation relates the matched filter response with the ambiguity function, known from radar. Based on this analysis and the properties of the ambiguity function, the selection of coded waveforms suitable for ultrasound imaging is discussed. It is shown that linear frequency modulation (FM) signals have...... that in the case of linear FM signals, a SNR improvement of 12 to 18 dB can be expected for large imaging depths in attenuating media, without any depth-dependent filter compensation. In contrast, nonlinear FM modulation and binary codes are shown to give a SNR improvement of only 4 to 9 dB when processed...

  2. Differential discriminator

    International Nuclear Information System (INIS)

    Dukhanov, V.I.; Mazurov, I.B.

    1981-01-01

    A principal flowsheet of a differential discriminator intended for operation in a spectrometric circuit with statistical time distribution of pulses is described. The differential discriminator includes four integrated discriminators and a channel of piled-up signal rejection. The presence of the rejection channel enables the discriminator to operate effectively at loads of 14x10 3 pulse/s. The temperature instability of the discrimination thresholds equals 250 μV/ 0 C. The discrimination level changes within 0.1-5 V, the level shift constitutes 0.5% for the filling ratio of 1:10. The rejection coefficient is not less than 90%. Alpha spectrum of the 228 Th source is presented to evaluate the discriminator operation with the rejector. The rejector provides 50 ns time resolution

  3. Modulators of Stomatal Lineage Signal Transduction Alter Membrane Contact Sites and Reveal Specialization among ERECTA Kinases.

    Science.gov (United States)

    Ho, Chin-Min Kimmy; Paciorek, Tomasz; Abrash, Emily; Bergmann, Dominique C

    2016-08-22

    Signal transduction from a cell's surface to its interior requires dedicated signaling elements and a cellular environment conducive to signal propagation. Plant development, defense, and homeostasis rely on plasma membrane receptor-like kinases to perceive endogenous and environmental signals, but little is known about their immediate downstream targets and signaling modifiers. Using genetics, biochemistry, and live-cell imaging, we show that the VAP-RELATED SUPPRESSOR OF TMM (VST) family is required for ERECTA-mediated signaling in growth and cell-fate determination and reveal a role for ERECTA-LIKE2 in modulating signaling by its sister kinases. We show that VSTs are peripheral plasma membrane proteins that can form complexes with integral ER-membrane proteins, thereby potentially influencing the organization of the membrane milieu to promote efficient and differential signaling from the ERECTA-family members to their downstream intracellular targets. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Diurnal modulation signal from dissipative hidden sector dark matter

    Directory of Open Access Journals (Sweden)

    R. Foot

    2015-09-01

    Full Text Available We consider a simple generic dissipative dark matter model: a hidden sector featuring two dark matter particles charged under an unbroken U(1′ interaction. Previous work has shown that such a model has the potential to explain dark matter phenomena on both large and small scales. In this framework, the dark matter halo in spiral galaxies features nontrivial dynamics, with the halo energy loss due to dissipative interactions balanced by a heat source. Ordinary supernovae can potentially supply this heat provided kinetic mixing interaction exists with strength ϵ∼10−9. This type of kinetically mixed dark matter can be probed in direct detection experiments. Importantly, this self-interacting dark matter can be captured within the Earth and shield a dark matter detector from the halo wind, giving rise to a diurnal modulation effect. We estimate the size of this effect for detectors located in the Southern hemisphere, and find that the modulation is large (≳10% for a wide range of parameters.

  5. Method for Signal Processing of Electric Field Modulation Sensor in a Conductive Environment

    Directory of Open Access Journals (Sweden)

    O. I. Miseyk

    2015-01-01

    Full Text Available In investigating the large waters and deep oceans the most promising are modulation sensors for measuring electric field in a conducting environment in a very low frequency range in devices of autonomous or non-autonomous vertical sounding. When using sensors of this type it is necessary to solve the problem of enhancement and measurement of the modulated signal from the baseband noise.The work analyses hydrodynamic and electromagnetic noise at the input of transducer with "rotating" sensitive axis. By virtue of matching the measuring electrodes with the signal processing circuit a conclusion has been drawn that the proposed basic model of a transducer with "rotating” sensitive axis is the most efficient in terms of enhancement and measurement of modulated signal from the baseband noise. It has been shown that it is undesirable for transducers to have the rotation of electrodes resulting, in this case, in arising noise to be synchronously changed with transducer rotation frequency (modulation frequency. This will complicate the further signal-noise enhancement later in their processing.The paper justifies the choice of demodulation output signal, called synchronous demodulation using a low-pass filter with a cutoff frequency much lower than the carrier frequency to provide an output signal in the range of very low frequency and dc electric fields.The paper offers an original circuit to process the signals taken from the modulation sensor with "rotating" measurement base. This circuit has advantages over the earlier known circuits for measuring electric fields in a conducting (marine environment in the ultralow frequency range of these fields in terms of sensitivity and measuring accuracy of modulation sensors.

  6. Hypoxia signaling pathways: modulators of oxygen-related organelles

    Science.gov (United States)

    Schönenberger, Miriam J.; Kovacs, Werner J.

    2015-01-01

    Oxygen (O2) is an essential substrate in cellular metabolism, bioenergetics, and signaling and as such linked to the survival and normal function of all metazoans. Low O2 tension (hypoxia) is a fundamental feature of physiological processes as well as pathophysiological conditions such as cancer and ischemic diseases. Central to the molecular mechanisms underlying O2 homeostasis are the hypoxia-inducible factors-1 and -2 alpha (HIF-1α and EPAS1/HIF-2α) that function as master regulators of the adaptive response to hypoxia. HIF-induced genes promote characteristic tumor behaviors, including angiogenesis and metabolic reprogramming. The aim of this review is to critically explore current knowledge of how HIF-α signaling regulates the abundance and function of major O2-consuming organelles. Abundant evidence suggests key roles for HIF-1α in the regulation of mitochondrial homeostasis. An essential adaptation to sustained hypoxia is repression of mitochondrial respiration and induction of glycolysis. HIF-1α activates several genes that trigger mitophagy and represses regulators of mitochondrial biogenesis. Several lines of evidence point to a strong relationship between hypoxia, the accumulation of misfolded proteins in the endoplasmic reticulum, and activation of the unfolded protein response. Surprisingly, although peroxisomes depend highly on molecular O2 for their function, there has been no evidence linking HIF signaling to peroxisomes. We discuss our recent findings that establish HIF-2α as a negative regulator of peroxisome abundance and suggest a mechanism by which cells attune peroxisomal function with O2 availability. HIF-2α activation augments peroxisome turnover by pexophagy and thereby changes lipid composition reminiscent of peroxisomal disorders. We discuss potential mechanisms by which HIF-2α might trigger pexophagy and place special emphasis on the potential pathological implications of HIF-2α-mediated pexophagy for human health. PMID:26258123

  7. Neuroendocrine signaling modulates specific neural networks relevant to migraine.

    Science.gov (United States)

    Martins-Oliveira, Margarida; Akerman, Simon; Holland, Philip R; Hoffmann, Jan R; Tavares, Isaura; Goadsby, Peter J

    2017-05-01

    Migraine is a disabling brain disorder involving abnormal trigeminovascular activation and sensitization. Fasting or skipping meals is considered a migraine trigger and altered fasting glucose and insulin levels have been observed in migraineurs. Therefore peptides involved in appetite and glucose regulation including insulin, glucagon and leptin could potentially influence migraine neurobiology. We aimed to determine the effect of insulin (10U·kg -1 ), glucagon (100μg·200μl -1 ) and leptin (0.3, 1 and 3mg·kg -1 ) signaling on trigeminovascular nociceptive processing at the level of the trigeminocervical-complex and hypothalamus. Male rats were anesthetized and prepared for craniovascular stimulation. In vivo electrophysiology was used to determine changes in trigeminocervical neuronal responses to dural electrical stimulation, and phosphorylated extracellular signal-regulated kinases 1 and 2 (pERK1/2) immunohistochemistry to determine trigeminocervical and hypothalamic neural activity; both in response to intravenous administration of insulin, glucagon, leptin or vehicle control in combination with blood glucose analysis. Blood glucose levels were significantly decreased by insulin (pneuronal firing in the trigeminocervical-complex was significantly inhibited by insulin (pmetabolic homeostasis may occur through disturbed glucose regulation and a transient hypothalamic dysfunction. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  8. Optical signal processing techniques and applications of optical phase modulation in high-speed communication systems

    Science.gov (United States)

    Deng, Ning

    In recent years, optical phase modulation has attracted much research attention in the field of fiber optic communications. Compared with the traditional optical intensity-modulated signal, one of the main merits of the optical phase-modulated signal is the better transmission performance. For optical phase modulation, in spite of the comprehensive study of its transmission performance, only a little research has been carried out in terms of its functions, applications and signal processing for future optical networks. These issues are systematically investigated in this thesis. The research findings suggest that optical phase modulation and its signal processing can greatly facilitate flexible network functions and high bandwidth which can be enjoyed by end users. In the thesis, the most important physical-layer technology, signal processing and multiplexing, are investigated with optical phase-modulated signals. Novel and advantageous signal processing and multiplexing approaches are proposed and studied. Experimental investigations are also reported and discussed in the thesis. Optical time-division multiplexing and demultiplexing. With the ever-increasing demand on communication bandwidth, optical time division multiplexing (OTDM) is an effective approach to upgrade the capacity of each wavelength channel in current optical systems. OTDM multiplexing can be simply realized, however, the demultiplexing requires relatively complicated signal processing and stringent timing control, and thus hinders its practicability. To tackle this problem, in this thesis a new OTDM scheme with hybrid DPSK and OOK signals is proposed. Experimental investigation shows this scheme can greatly enhance the demultiplexing timing misalignment and improve the demultiplexing performance, and thus make OTDM more practical and cost effective. All-optical signal processing. In current and future optical communication systems and networks, the data rate per wavelength has been approaching

  9. Identifying colon cancer risk modules with better classification performance based on human signaling network.

    Science.gov (United States)

    Qu, Xiaoli; Xie, Ruiqiang; Chen, Lina; Feng, Chenchen; Zhou, Yanyan; Li, Wan; Huang, Hao; Jia, Xu; Lv, Junjie; He, Yuehan; Du, Youwen; Li, Weiguo; Shi, Yuchen; He, Weiming

    2014-10-01

    Identifying differences between normal and tumor samples from a modular perspective may help to improve our understanding of the mechanisms responsible for colon cancer. Many cancer studies have shown that signaling transduction and biological pathways are disturbed in disease states, and expression profiles can distinguish variations in diseases. In this study, we integrated a weighted human signaling network and gene expression profiles to select risk modules associated with tumor conditions. Risk modules as classification features by our method had a better classification performance than other methods, and one risk module for colon cancer had a good classification performance for distinguishing between normal/tumor samples and between tumor stages. All genes in the module were annotated to the biological process of positive regulation of cell proliferation, and were highly associated with colon cancer. These results suggested that these genes might be the potential risk genes for colon cancer. Copyright © 2013. Published by Elsevier Inc.

  10. Optical-wireless-optical full link for polarization multiplexing quadrature amplitude/phase modulation signal transmission.

    Science.gov (United States)

    Li, Xinying; Yu, Jianjun; Chi, Nan; Zhang, Junwen

    2013-11-15

    We propose and experimentally demonstrate an optical wireless integration system at the Q-band, in which up to 40 Gb/s polarization multiplexing multilevel quadrature amplitude/phase modulation (PM-QAM) signal can be first transmitted over 20 km single-mode fiber-28 (SMF-28), then delivered over a 2 m 2 × 2 multiple-input multiple-output wireless link, and finally transmitted over another 20 km SMF-28. The PM-QAM modulated wireless millimeter-wave (mm-wave) signal at 40 GHz is generated based on the remote heterodyning technique, and demodulated by the radio-frequency transparent photonic technique based on homodyne coherent detection and baseband digital signal processing. The classic constant modulus algorithm equalization is used at the receiver to realize polarization demultiplexing of the PM-QAM signal. For the first time, to the best of our knowledge, we realize the conversion of the PM-QAM modulated wireless mm-wave signal to the optical signal as well as 20 km fiber transmission of the converted optical signal.

  11. Modulation, resolution and signal processing in radar, sonar and related systems

    CERN Document Server

    Benjamin, R; Costrell, L

    1966-01-01

    Electronics and Instrumentation, Volume 35: Modulation, Resolution and Signal Processing in Radar, Sonar and Related Systems presents the practical limitations and potentialities of advanced modulation systems. This book discusses the concepts and techniques in the radar context, but they are equally essential to sonar and to a wide range of signaling and data-processing applications, including seismology, radio astronomy, and band-spread communications.Organized into 15 chapters, this volume begins with an overview of the principal developments sought in pulse radar. This text then provides a

  12. Targeting CB2-GPR55 Receptor Heteromers Modulates Cancer Cell Signaling*

    Science.gov (United States)

    Moreno, Estefanía; Andradas, Clara; Medrano, Mireia; Caffarel, María M.; Pérez-Gómez, Eduardo; Blasco-Benito, Sandra; Gómez-Cañas, María; Pazos, M. Ruth; Irving, Andrew J.; Lluís, Carme; Canela, Enric I.; Fernández-Ruiz, Javier; Guzmán, Manuel; McCormick, Peter J.; Sánchez, Cristina

    2014-01-01

    The G protein-coupled receptors CB2 (CB2R) and GPR55 are overexpressed in cancer cells and human tumors. Because a modulation of GPR55 activity by cannabinoids has been suggested, we analyzed whether this receptor participates in cannabinoid effects on cancer cells. Here we show that CB2R and GPR55 form heteromers in cancer cells, that these structures possess unique signaling properties, and that modulation of these heteromers can modify the antitumoral activity of cannabinoids in vivo. These findings unveil the existence of previously unknown signaling platforms that help explain the complex behavior of cannabinoids and may constitute new targets for therapeutic intervention in oncology. PMID:24942731

  13. Extracting a shape function for a signal with intra-wave frequency modulation.

    Science.gov (United States)

    Hou, Thomas Y; Shi, Zuoqiang

    2016-04-13

    In this paper, we develop an effective and robust adaptive time-frequency analysis method for signals with intra-wave frequency modulation. To handle this kind of signals effectively, we generalize our data-driven time-frequency analysis by using a shape function to describe the intra-wave frequency modulation. The idea of using a shape function in time-frequency analysis was first proposed by Wu (Wu 2013 Appl. Comput. Harmon. Anal. 35, 181-199. (doi:10.1016/j.acha.2012.08.008)). A shape function could be any smooth 2π-periodic function. Based on this model, we propose to solve an optimization problem to extract the shape function. By exploring the fact that the shape function is a periodic function with respect to its phase function, we can identify certain low-rank structure of the signal. This low-rank structure enables us to extract the shape function from the signal. Once the shape function is obtained, the instantaneous frequency with intra-wave modulation can be recovered from the shape function. We demonstrate the robustness and efficiency of our method by applying it to several synthetic and real signals. One important observation is that this approach is very stable to noise perturbation. By using the shape function approach, we can capture the intra-wave frequency modulation very well even for noise-polluted signals. In comparison, existing methods such as empirical mode decomposition/ensemble empirical mode decomposition seem to have difficulty in capturing the intra-wave modulation when the signal is polluted by noise. © 2016 The Author(s).

  14. Modulation Classification of Satellite Communication Signals Using Cumulants and Neural Networks

    Science.gov (United States)

    Smith, Aaron; Evans, Michael; Downey, Joseph

    2017-01-01

    National Aeronautics and Space Administration (NASA)'s future communication architecture is evaluating cognitive technologies and increased system intelligence. These technologies are expected to reduce the operational complexity of the network, increase science data return, and reduce interference to self and others. In order to increase situational awareness, signal classification algorithms could be applied to identify users and distinguish sources of interference. A significant amount of previous work has been done in the area of automatic signal classification for military and commercial applications. As a preliminary step, we seek to develop a system with the ability to discern signals typically encountered in satellite communication. Proposed is an automatic modulation classifier which utilizes higher order statistics (cumulants) and an estimate of the signal-to-noise ratio. These features are extracted from baseband symbols and then processed by a neural network for classification. The modulation types considered are phase-shift keying (PSK), amplitude and phase-shift keying (APSK),and quadrature amplitude modulation (QAM). Physical layer properties specific to the Digital Video Broadcasting - Satellite- Second Generation (DVB-S2) standard, such as pilots and variable ring ratios, are also considered. This paper will provide simulation results of a candidate modulation classifier, and performance will be evaluated over a range of signal-to-noise ratios, frequency offsets, and nonlinear amplifier distortions.

  15. Light and gravity signals synergize in modulating plant development

    Science.gov (United States)

    Vandenbrink, Joshua P.; Kiss, John Z.; Herranz, Raul; Medina, F. Javier

    2014-01-01

    Tropisms are growth-mediated plant movements that help plants to respond to changes in environmental stimuli. The availability of water and light, as well as the presence of a constant gravity vector, are all environmental stimuli that plants sense and respond to via directed growth movements (tropisms). The plant response to gravity (gravitropism) and the response to unidirectional light (phototropism) have long been shown to be interconnected growth phenomena. Here, we discuss the similarities in these two processes, as well as the known molecular mechanisms behind the tropistic responses. We also highlight research done in a microgravity environment in order to decouple two tropisms through experiments carried out in the absence of a significant unilateral gravity vector. In addition, alteration of gravity, especially the microgravity environment, and light irradiation produce important effects on meristematic cells, the undifferentiated, highly proliferating, totipotent cells which sustain plant development. Microgravity produces the disruption of meristematic competence, i.e., the decoupling of cell proliferation and cell growth, affecting the regulation of the cell cycle and ribosome biogenesis. Light irradiation, especially red light, mediated by phytochromes, has an activating effect on these processes. Phytohormones, particularly auxin, also are key mediators in these alterations. Upcoming experiments on the International Space Station will clarify some of the mechanisms and molecular players of the plant responses to these environmental signals involved in tropisms and the cell cycle. PMID:25389428

  16. Modulation of signal transduction by tea catechins and related phytochemicals

    International Nuclear Information System (INIS)

    Shimizu, Masahito; Weinstein, I. Bernard

    2005-01-01

    Epidemiologic studies in human populations and experimental studies in rodents provide evidence that green tea and its constituents can inhibit both the development and growth of tumors at a variety of tissue sites. In addition, EGCG, a major biologically active component of green tea, inhibits growth and induces apoptosis in a variety of cancer cell lines. The purpose of this paper is to review evidence that these effects are mediated, at least in part, through inhibition of the activity of specific receptor tyrosine kinases (RTKs) and related downstream pathways of signal transduction. We also review evidence indicating that the antitumor effects of the related polyphenolic phytochemicals resveratrol, genistein, curcumin, and capsaicin are exerted via similar mechanisms. Some of these agents (EGCG, genistein, and curcumin) appear to directly target specific RTKs, and all of these compounds cause inhibition of the activity of the transcription factors AP-1 and NF-κB, thus inhibiting cell proliferation and enhancing apoptosis. Critical areas of future investigation include: (1) identification of the direct molecular target(s) of EGCG and related polyphenolic compounds in cells; (2) the in vivo metabolism and bioavailability of these compounds; (3) the ancillary effects of these compounds on tumor-stromal interactions; (4) the development of synergistic combinations with other antitumor agents to enhance efficacy in cancer prevention and therapy, and also minimize potential toxicities

  17. Light and gravity signals synergize in modulating plant development

    Directory of Open Access Journals (Sweden)

    Joshua P. Vandenbrink

    2014-10-01

    Full Text Available Tropisms are growth-mediated plant movements that help plants to respond to changes in environmental stimuli. The availability of water and light, as well as the presence of a constant gravity vector, are all environmental stimuli that plants sense and respond to via directed growth movements (tropisms. The plant response to gravity (gravitropism and the response to unidirectional light (phototropism have long been shown to be interconnected growth phenomena. Here, we discuss the similarities in these two processes, as well as the known molecular mechanisms behind the tropistic responses. We also highlight experiments done in a microgravity environment in order to decouple two tropisms through experiments carried out in the absence of a significant unilateral gravity vector. In addition, alteration of gravity, especially the microgravity environment, and light irradiation produce important effects on meristematic cells, the undifferentiated, highly proliferating, totipotent cells which sustain plant development. Microgravity produces the disruption of meristematic competence, i.e. the decoupling of cell proliferation and cell growth, affecting the regulation of cell cycle and ribosome biogenesis. Light irradiation, especially red light, mediated by phytochromes, has an activating effect on these processes. Phytohormones, particularly auxin, are key mediators in these alterations. Upcoming experiments on the International Space Station will clarify some of the unknown mechanisms and molecular players of the plant responses to these environmental signals involved in tropisms and the cell cycle.

  18. The behaviour of basic autocatalytic signalling modules in isolation and embedded in networks

    Energy Technology Data Exchange (ETDEWEB)

    Krishnan, J. [Department of Chemical Engineering, Centre for Process Systems Engineering, Institute for Systems and Synthetic Biology, Imperial College London, London SW7 2AZ (United Kingdom); Mois, Kristina; Suwanmajo, Thapanar [Department of Chemical Engineering, Centre for Process Systems Engineering, Imperial College London, London SW7 2AZ (United Kingdom)

    2014-11-07

    In this paper, we examine the behaviour of basic autocatalytic feedback modules involving a species catalyzing its own production, either directly or indirectly. We first perform a systematic study of the autocatalytic feedback module in isolation, examining the effect of different factors, showing how this module is capable of exhibiting monostable threshold and bistable switch-like behaviour. We then study the behaviour of this module embedded in different kinds of basic networks including (essentially) irreversible cycles, open and closed reversible chains, and networks with additional feedback. We study the behaviour of the networks deterministically and also stochastically, using simulations, analytical work, and bifurcation analysis. We find that (i) there are significant differences between the behaviour of this module in isolation and in a network: thresholds may be altered or destroyed and bistability may be destroyed or even induced, even when the ambient network is simple. The global characteristics and topology of this network and the position of the module in the ambient network can play important and unexpected roles. (ii) There can be important differences between the deterministic and stochastic dynamics of the module embedded in networks, which may be accentuated by the ambient network. This provides new insights into the functioning of such enzymatic modules individually and as part of networks, with relevance to other enzymatic signalling modules as well.

  19. Microbiota promote secretory cell determination in the intestinal epithelium by modulating host Notch signaling.

    Science.gov (United States)

    Troll, Joshua V; Hamilton, M Kristina; Abel, Melissa L; Ganz, Julia; Bates, Jennifer M; Stephens, W Zac; Melancon, Ellie; van der Vaart, Michiel; Meijer, Annemarie H; Distel, Martin; Eisen, Judith S; Guillemin, Karen

    2018-02-23

    Resident microbes promote many aspects of host development, although the mechanisms by which microbiota influence host tissues remain unclear. We showed previously that the microbiota is required for allocation of appropriate numbers of secretory cells in the zebrafish intestinal epithelium. Because Notch signaling is crucial for secretory fate determination, we conducted epistasis experiments to establish whether the microbiota modulates host Notch signaling. We also investigated whether innate immune signaling transduces microbiota cues via the Myd88 adaptor protein. We provide the first evidence that microbiota-induced, Myd88-dependent signaling inhibits host Notch signaling in the intestinal epithelium, thereby promoting secretory cell fate determination. These results connect microbiota activity via innate immune signaling to the Notch pathway, which also plays crucial roles in intestinal homeostasis throughout life and when impaired can result in chronic inflammation and cancer. © 2018. Published by The Company of Biologists Ltd.

  20. Oxytocin signaling in the medial amygdala is required for sex discrimination of social cues

    OpenAIRE

    Yao, Shenqin; Bergan, Joseph; Lanjuin, Anne; Dulac, Catherine

    2017-01-01

    The neural control of social behaviors in rodents requires the encoding of pheromonal cues by the vomeronasal system. Here we show that the typical preference of male mice for females is eliminated in mutants lacking oxytocin, a neuropeptide modulating social behaviors in many species. Ablation of the oxytocin receptor in aromatase-expressing neurons of the medial amygdala (MeA) fully recapitulates the elimination of female preference in males. Further, single-unit recording in the MeA uncove...

  1. Oxytocin Signaling in the Medial Amygdala is required for Sex Discrimination of Social Cues

    OpenAIRE

    Bergan, Joseph; Yao, Shenqin; Lanjuin, Anne; Dulac, Catherine

    2017-01-01

    The neural control of social behaviors in rodents requires the encoding of pheromonal cues by the vomeronasal system. Here we show that the typical preference of male mice for females is eliminated in mutants lacking oxytocin, a neuropeptide modulating social behaviors in many species. Ablation of the oxytocin receptor in aromatase expressing neurons of the medial amygdala (MeA) fully recapitulates the elimination of female preference in males. Further, single unit recording in the MeA uncove...

  2. Cell Size and Growth Rate Are Modulated by TORC2-Dependent Signals.

    Science.gov (United States)

    Lucena, Rafael; Alcaide-Gavilán, Maria; Schubert, Katherine; He, Maybo; Domnauer, Matthew G; Marquer, Catherine; Klose, Christian; Surma, Michal A; Kellogg, Douglas R

    2018-01-22

    The size of all cells, from bacteria to vertebrates, is proportional to the growth rate set by nutrient availability, but the underlying mechanisms are unknown. Here, we show that nutrients modulate cell size and growth rate via the TORC2 signaling network in budding yeast. An important function of the TORC2 network is to modulate synthesis of ceramide lipids, which play roles in signaling. TORC2-dependent control of ceramide signaling strongly influences both cell size and growth rate. Thus, cells that cannot make ceramides fail to modulate their growth rate or size in response to changes in nutrients. PP2A associated with the Rts1 regulatory subunit (PP2A Rts1 ) is embedded in a feedback loop that controls TORC2 signaling and helps set the level of TORC2 signaling to match nutrient availability. Together, the data suggest a model in which growth rate and cell size are mechanistically linked by ceramide-dependent signals arising from the TORC2 network. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. A Preliminary Assessment of Soviet Development of Optimum Signal Discrimination Techniques: Optimum Space-Time Processing

    Science.gov (United States)

    1982-10-01

    thermal noise and radioastronomy is probably the application Shirman had in mind for that work. Kuriksha considers a wide class of two-dimensional...this point has been discussed In terms of EM wave propagation, signal detection, and parameter estimation in such fields as radar and radioastronomy

  4. Response-Retrieval in Identity Negative Priming is Modulated by Temporal Discriminability

    Directory of Open Access Journals (Sweden)

    Matthias eMittner

    2014-06-01

    Full Text Available Reaction times to previously ignored information are often delayed, a phenomenon referred to as negative priming (NP. Rothermund, Wentura & De Houwer (2005 proposed that negative priming is caused by the retrieval of incidental stimulus-response associations when consecutive displays share visual features but require different responses. In two experiments we examined whether the features (color, shape that reappear in consecutive displays, or their level of processing (early-perceptual, late-semantic moderate the likelihood that stimulus-response associations are retrieved. Using a perceptual matching task (experiment 1, negative priming occurred independently of whether responses were repeated or switched. Only when implementing a semantic-matching task (experiment 2, negative priming was determined by response-repetition as predicted by response-retrieval theory. The results can be explained in terms of a task-dependent temporal discrimination process (Milliken et al., 1998: Response-relevant features are encoded more strongly and/or are more likely to be retrieved than irrelevant features.

  5. All-optical wavelength conversion and signal regeneration using an electroabsorption modulator

    DEFF Research Database (Denmark)

    Højfeldt, Sune; Bischoff, Svend; Mørk, Jesper

    1999-01-01

    All-optical wavelength conversion in an InGaAsP quantum well electroabsorption modulator is studied at different bit-rates. We present theoretical results showing wavelength conversion efficiency in agreement with existing experimental results, and signal regeneration capability is demonstrated....

  6. A Signal Processing Module for the Analysis of Heart Sounds and Heart Murmurs

    International Nuclear Information System (INIS)

    Javed, Faizan; Venkatachalam, P A; H, Ahmad Fadzil M

    2006-01-01

    In this paper a Signal Processing Module (SPM) for the computer-aided analysis of heart sounds has been developed. The module reveals important information of cardiovascular disorders and can assist general physician to come up with more accurate and reliable diagnosis at early stages. It can overcome the deficiency of expert doctors in rural as well as urban clinics and hospitals. The module has five main blocks: Data Acquisition and Pre-processing, Segmentation, Feature Extraction, Murmur Detection and Murmur Classification. The heart sounds are first acquired using an electronic stethoscope which has the capability of transferring these signals to the near by workstation using wireless media. Then the signals are segmented into individual cycles as well as individual components using the spectral analysis of heart without using any reference signal like ECG. Then the features are extracted from the individual components using Spectrogram and are used as an input to a MLP (Multiple Layer Perceptron) Neural Network that is trained to detect the presence of heart murmurs. Once the murmur is detected they are classified into seven classes depending on their timing within the cardiac cycle using Smoothed Pseudo Wigner-Ville distribution. The module has been tested with real heart sounds from 40 patients and has proved to be quite efficient and robust while dealing with a large variety of pathological conditions

  7. A Signal Processing Module for the Analysis of Heart Sounds and Heart Murmurs

    Energy Technology Data Exchange (ETDEWEB)

    Javed, Faizan; Venkatachalam, P A; H, Ahmad Fadzil M [Signal and Imaging Processing and Tele-Medicine Technology Research Group, Department of Electrical and Electronics Engineering, Universiti Teknologi PETRONAS, 31750 Tronoh, Perak (Malaysia)

    2006-04-01

    In this paper a Signal Processing Module (SPM) for the computer-aided analysis of heart sounds has been developed. The module reveals important information of cardiovascular disorders and can assist general physician to come up with more accurate and reliable diagnosis at early stages. It can overcome the deficiency of expert doctors in rural as well as urban clinics and hospitals. The module has five main blocks: Data Acquisition and Pre-processing, Segmentation, Feature Extraction, Murmur Detection and Murmur Classification. The heart sounds are first acquired using an electronic stethoscope which has the capability of transferring these signals to the near by workstation using wireless media. Then the signals are segmented into individual cycles as well as individual components using the spectral analysis of heart without using any reference signal like ECG. Then the features are extracted from the individual components using Spectrogram and are used as an input to a MLP (Multiple Layer Perceptron) Neural Network that is trained to detect the presence of heart murmurs. Once the murmur is detected they are classified into seven classes depending on their timing within the cardiac cycle using Smoothed Pseudo Wigner-Ville distribution. The module has been tested with real heart sounds from 40 patients and has proved to be quite efficient and robust while dealing with a large variety of pathological conditions.

  8. Optical mixing of microwave signals in a nonlinear semiconductor laser amplifier modulator.

    Science.gov (United States)

    Capmany, José; Sales, Salvador; Pastor, Daniel; Ortega, Beatriz

    2002-02-11

    In this paper we propose and evaluate the optical mixing of RF signals by means of exploiting the nonlinearity of a SLA modulator. The results show the potential for devices with low conversion losses (and even gain) and polarization insensitivity and reduced insertion losses.

  9. A High Density Low Cost Digital Signal Processing Module for Large Scale Radiation Detectors

    International Nuclear Information System (INIS)

    Tan, Hui; Hennig, Wolfgang; Walby, Mark D.; Breus, Dimitry; Harris, Jackson T.; Grudberg, Peter M.; Warburton, William K.

    2013-06-01

    A 32-channel digital spectrometer PIXIE-32 is being developed for nuclear physics or other radiation detection applications requiring digital signal processing with large number of channels at relatively low cost. A single PIXIE-32 provides spectrometry and waveform acquisition for 32 input signals per module whereas multiple modules can be combined into larger systems. It is based on the PCI Express standard which allows data transfer rates to the host computer of up to 800 MB/s. Each of the 32 channels in a PIXIE-32 module accepts signals directly from a detector preamplifier or photomultiplier. Digitally controlled offsets can be individually adjusted for each channel. Signals are digitized in 12-bit, 50 MHz multi-channel ADCs. Triggering, pile-up inspection and filtering of the data stream are performed in real time, and pulse heights and other event data are calculated on an event-by event basis. The hardware architecture, internal and external triggering features, and the spectrometry and waveform acquisition capability of the PIXIE- 32 as well as its capability to distribute clock and triggers among multiple modules, are presented. (authors)

  10. XUV pulse effect on signal modulations of harmonic spectra from H2+ and T2+

    Science.gov (United States)

    Feng, Liqiang; Liu, Hang; Kapteyn, Henry J.; Feng, April Y.

    2018-05-01

    The effects of signal modulations on the molecular high-order harmonic generations in H2^{+ } and T2+ have been theoretically investigated. It is found that with the introduction of the XUV pulse, due to the absorption of the extra XUV photons in the recombination process, multiplateaus on the harmonic spectra, separated by the XUV photon energy can be found. Moreover, this multiplateau structure is insensitive to the wavelength of the XUV pulse. In shorter pulse duration, the intensities of the multiplateaus from H2+ are higher than those from T2+; while in longer pulse duration, the opposite results can be found. Finally, by changing the delay time of the XUV pulse, the signal modulations (including the amplitude and the frequency modulations) of the multiplateaus can be controlled.

  11. Low modulation index RF signal detection for a passive UHF RFID transponder

    International Nuclear Information System (INIS)

    Liu Zhongqi; Zhang Chun; Li Yongming; Wang Zhihua

    2009-01-01

    In a typical RFID system the reader transmits modulated RF power to provide both data and energy for the passive transponder. Low modulation index RF energy is preferable for an adequate tag power supply and increase in communication range but gives rise to difficulties for near-field conventional demodulation. Therefore, a novel ASK demodulator for minimum 20% modulation index RF signal detection over a range of 23 dB is presented. Thanks to the proposed innovative divisional linear conversion from the power into voltage signal, the detection sensitivity is ensured over a wide power range with low power consumption of 8.6 μW. The chip is implemented in UMC 0.18 μm mix-mode CMOS technology, and the chip area is 0.06 mm 2 .

  12. Low modulation index RF signal detection for a passive UHF RFID transponder

    Energy Technology Data Exchange (ETDEWEB)

    Liu Zhongqi [Department of Electronic Engineering, Tsinghua University, Beijing 100084 (China); Zhang Chun; Li Yongming; Wang Zhihua, E-mail: liu-zq04@mails.tsinghua.edu.c [Institute of Microelectronics, Tsinghua University, Beijing 100084 (China)

    2009-09-15

    In a typical RFID system the reader transmits modulated RF power to provide both data and energy for the passive transponder. Low modulation index RF energy is preferable for an adequate tag power supply and increase in communication range but gives rise to difficulties for near-field conventional demodulation. Therefore, a novel ASK demodulator for minimum 20% modulation index RF signal detection over a range of 23 dB is presented. Thanks to the proposed innovative divisional linear conversion from the power into voltage signal, the detection sensitivity is ensured over a wide power range with low power consumption of 8.6 {mu}W. The chip is implemented in UMC 0.18 {mu}m mix-mode CMOS technology, and the chip area is 0.06 mm{sup 2}.

  13. Pressure modulation algorithm to separate cerebral hemodynamic signals from extracerebral artifacts.

    Science.gov (United States)

    Baker, Wesley B; Parthasarathy, Ashwin B; Ko, Tiffany S; Busch, David R; Abramson, Kenneth; Tzeng, Shih-Yu; Mesquita, Rickson C; Durduran, Turgut; Greenberg, Joel H; Kung, David K; Yodh, Arjun G

    2015-07-01

    We introduce and validate a pressure measurement paradigm that reduces extracerebral contamination from superficial tissues in optical monitoring of cerebral blood flow with diffuse correlation spectroscopy (DCS). The scheme determines subject-specific contributions of extracerebral and cerebral tissues to the DCS signal by utilizing probe pressure modulation to induce variations in extracerebral blood flow. For analysis, the head is modeled as a two-layer medium and is probed with long and short source-detector separations. Then a combination of pressure modulation and a modified Beer-Lambert law for flow enables experimenters to linearly relate differential DCS signals to cerebral and extracerebral blood flow variation without a priori anatomical information. We demonstrate the algorithm's ability to isolate cerebral blood flow during a finger-tapping task and during graded scalp ischemia in healthy adults. Finally, we adapt the pressure modulation algorithm to ameliorate extracerebral contamination in monitoring of cerebral blood oxygenation and blood volume by near-infrared spectroscopy.

  14. Application of Nonnegative Tensor Factorization for neutron-gamma discrimination of Monte Carlo simulated fission chamber’s output signals

    Directory of Open Access Journals (Sweden)

    Mounia Laassiri

    Full Text Available For efficient exploitation of research reactors, it is important to discern neutron flux distribution inside the reactor with the best possible precision. For this reason, fission and ionization chambers are used to measure the neutron field. In these arrays, the sequences of the neutron interaction points in the fission chamber can correctly be identified in order to obtain true neutron energies emitted by nuclei of interest. However, together with the neutrons, gamma-rays are also emitted from nuclei and thereby affect neutron spectra. The originality of this study consists in the application of tensor based blind source separation methods to extract independent components from signals recorded at the fission chamber preamplifier’s output. The objective is to achieve software neutron-gamma discrimination using Nonnegative Tensor Factorization tools. For reasons of nuclear safety, we first simulate the neutron flux inside the TRIGA Mark II Reactor using Monte Carlo methods under Geant4 platform linked to Garfield++. Geant4 simulations allow the fission chamber construction whereas linking the model to Garfield++ permits to simulate drift parameters from the ionization of the filling gas, which is not possible otherwise. Keywords: Fission chamber (FC, Geant4, Garfield++, Neutron-gamma discrimination, Nonnegative Tensor Factorization (NTF

  15. Discrimination of Cylinders with Different Wall Thicknesses using Neural Networks and Simulated Dolphin Sonar Signals

    DEFF Research Database (Denmark)

    Andersen, Lars Nonboe; Au, Whitlow; Larsen, Jan

    1999-01-01

    This paper describes a method integrating neural networks into a system for recognizing underwater objects. The system is based on a combination of simulated dolphin sonar signals, simulated auditory filters and artificial neural networks. The system is tested on a cylinder wall thickness...... difference experiment and demonstrates high accuracy for small wall thickness differences. Results from the experiment are compared with results obtained by a false killer whale (pseudorca crassidens)....

  16. Inhibitory neurons modulate spontaneous signaling in cultured cortical neurons: density-dependent regulation of excitatory neuronal signaling

    International Nuclear Information System (INIS)

    Serra, Michael; Guaraldi, Mary; Shea, Thomas B

    2010-01-01

    Cortical neuronal activity depends on a balance between excitatory and inhibitory influences. Culturing of neurons on multi-electrode arrays (MEAs) has provided insight into the development and maintenance of neuronal networks. Herein, we seeded MEAs with murine embryonic cortical/hippocampal neurons at different densities ( 1000 cells mm −2 ) and monitored resultant spontaneous signaling. Sparsely seeded cultures displayed a large number of bipolar, rapid, high-amplitude individual signals with no apparent temporal regularity. By contrast, densely seeded cultures instead displayed clusters of signals at regular intervals. These patterns were observed even within thinner and thicker areas of the same culture. GABAergic neurons (25% of total neurons in our cultures) mediated the differential signal patterns observed above, since addition of the inhibitory antagonist bicuculline to dense cultures and hippocampal slice cultures induced the signal pattern characteristic of sparse cultures. Sparsely seeded cultures likely lacked sufficient inhibitory neurons to modulate excitatory activity. Differential seeding of MEAs can provide a unique model for analyses of pertubation in the interaction between excitatory and inhibitory function during aging and neuropathological conditions where dysregulation of GABAergic neurons is a significant component

  17. Temporal integration: intentional sound discrimination does not modulate stimulus-driven processes in auditory event synthesis.

    Science.gov (United States)

    Sussman, Elyse; Winkler, István; Kreuzer, Judith; Saher, Marieke; Näätänen, Risto; Ritter, Walter

    2002-12-01

    Our previous study showed that the auditory context could influence whether two successive acoustic changes occurring within the temporal integration window (approximately 200ms) were pre-attentively encoded as a single auditory event or as two discrete events (Cogn Brain Res 12 (2001) 431). The aim of the current study was to assess whether top-down processes could influence the stimulus-driven processes in determining what constitutes an auditory event. Electroencepholagram (EEG) was recorded from 11 scalp electrodes to frequently occurring standard and infrequently occurring deviant sounds. Within the stimulus blocks, deviants either occurred only in pairs (successive feature changes) or both singly and in pairs. Event-related potential indices of change and target detection, the mismatch negativity (MMN) and the N2b component, respectively, were compared with the simultaneously measured performance in discriminating the deviants. Even though subjects could voluntarily distinguish the two successive auditory feature changes from each other, which was also indicated by the elicitation of the N2b target-detection response, top-down processes did not modify the event organization reflected by the MMN response. Top-down processes can extract elemental auditory information from a single integrated acoustic event, but the extraction occurs at a later processing stage than the one whose outcome is indexed by MMN. Initial processes of auditory event-formation are fully governed by the context within which the sounds occur. Perception of the deviants as two separate sound events (the top-down effects) did not change the initial neural representation of the same deviants as one event (indexed by the MMN), without a corresponding change in the stimulus-driven sound organization.

  18. Perceived discrimination, psychological distress, and current smoking status: results from the Behavioral Risk Factor Surveillance System Reactions to Race module, 2004-2008.

    Science.gov (United States)

    Purnell, Jason Q; Peppone, Luke J; Alcaraz, Kassandra; McQueen, Amy; Guido, Joseph J; Carroll, Jennifer K; Shacham, Enbal; Morrow, Gary R

    2012-05-01

    We examined the association between perceived discrimination and smoking status and whether psychological distress mediated this relationship in a large, multiethnic sample. We used 2004 through 2008 data from the Behavioral Risk Factor Surveillance System Reactions to Race module to conduct multivariate logistic regression analyses and tests of mediation examining associations between perceived discrimination in health care and workplace settings, psychological distress, and current smoking status. Regardless of race/ethnicity, perceived discrimination was associated with increased odds of current smoking. Psychological distress was also a significant mediator of the discrimination-smoking association. Our results indicate that individuals who report discriminatory treatment in multiple domains may be more likely to smoke, in part, because of the psychological distress associated with such treatment.

  19. Evoked responses of the superior olive to amplitude-modulated signals.

    Science.gov (United States)

    Andreeva, N G; Lang, T T

    1977-01-01

    Evoked potentials of some auditory centers of Rhinolophidae bats to amplitude-modulated signals were studied. A synchronization response was found in the cochlear nuclei (with respect to the fast component of the response) and in the superior olivary complex (with respect to both fast and slow components of the response) within the range of frequency modulation from 50 to 2000 Hz. In the inferior colliculus a synchronized response was recorded at modulation frequencies below 150 Hz, but in the medial geniculate bodies no such response was found. Evoked responses of the superior olivary complex were investigated in detail. The lowest frequencies of synchronization were recorded within the carrier frequency range of 15-30 and 80-86 kHz. The amplitude of the synchronized response is a function of the frequency and coefficient of modulation and also of the angle of stimulus presentation.

  20. Modulation of taste sensitivity by GLP-1 signaling in taste buds.

    Science.gov (United States)

    Martin, Bronwen; Dotson, Cedrick D; Shin, Yu-Kyong; Ji, Sunggoan; Drucker, Daniel J; Maudsley, Stuart; Munger, Steven D

    2009-07-01

    Modulation of sensory function can help animals adjust to a changing external and internal environment. Even so, mechanisms for modulating taste sensitivity are poorly understood. Using immunohistochemical, biochemical, and behavioral approaches, we found that the peptide hormone glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R) are expressed in mammalian taste buds. Furthermore, we found that GLP-1 signaling plays an important role in the modulation of taste sensitivity: GLP-1R knockout mice exhibit a dramatic reduction in sweet taste sensitivity as well as an enhanced sensitivity to umami-tasting stimuli. Together, these findings suggest a novel paracrine mechanism for the hormonal modulation of taste function in mammals.

  1. The Role of MAPK Modules and ABA during Abiotic Stress Signaling

    KAUST Repository

    Zélicourt, Axel de

    2016-05-01

    To respond to abiotic stresses, plants have developed specific mechanisms that allow them to rapidly perceive and respond to environmental changes. The phytohormone abscisic acid (ABA) was shown to be a pivotal regulator of abiotic stress responses in plants, triggering major changes in plant physiology. The ABA core signaling pathway largely relies on the activation of SnRK2 kinases to mediate several rapid responses, including gene regulation, stomatal closure, and plant growth modulation. Mitogen-activated protein kinases (MAPKs) have also been implicated in ABA signaling, but an entire ABA-activated MAPK module was uncovered only recently. In this review, we discuss the evidence for a role of MAPK modules in the context of different plant ABA signaling pathways. Abiotic stresses impact average yield in agriculture by more than 50% globally.Since ABA is a key regulator of abiotic stress responses, an understanding of its functioning at the molecular level is essential for plant breeding. Although the ABA core signaling pathway has been unraveled, several downstream events are still unclear.MAPKs are involved in most plant developmental stages and in response to stresses. Several members of the MAPK family were shown to be directly or indirectly activated by the ABA core signaling pathway.Recent evidence shows that the complete MAP3K17/18-MKK3-MPK1/2/7/14 module is under the control of ABA, whose members are under the transcriptional and post-translational control of the ABA core signaling pathway. © 2016 Elsevier Ltd.

  2. Developmental Mechanisms Underlying Improved Contrast Thresholds for Discriminations of Orientation Signals Embedded in Noise

    Directory of Open Access Journals (Sweden)

    Seong Taek eJeon

    2014-09-01

    Full Text Available We combined an external noise paradigm with an efficient procedure for obtaining contrast thresholds (Lesmes et al., 2006 in order to model developmental changes during childhood. Specifically, we measured the contrast thresholds of 5-, 7-, 9-year-olds and adults (n = 20/age in a two alternative forced-choice orientation discrimination task over a wide range of external noise levels and at three levels of accuracy. Overall, as age increased, contrast thresholds decreased over the entire range of external noise levels tested. The decrease was greatest between 5 and 7 years of age. The reduction in threshold after age 5 was greater in the high than the low external noise region, a pattern implying greater tolerance to the irrelevant background noise as children became older. To model the mechanisms underlying these developmental changes in terms of internal noise components, we adapted the original perceptual template model (Lu and Dosher, 1998 and normalized the magnitude of performance changes against the performance of 5-year-olds. The resulting model provided an excellent fit (r2 = 0.985 to the contrast thresholds at multiple levels of accuracy (60, 75, and 90% across a wide range of external noise levels. The improvements in contrast thresholds with age were best modelled by a combination of reductions in internal additive noise, reductions in internal multiplicative noise, and improvements in excluding external noise by template retuning. In line with the data, the improvement was greatest between 5 and 7 years of age, accompanied by a 39% reduction in additive noise, 71% reduction in multiplicative noise, and 45% improvement in external noise exclusion. The modelled improvements likely reflect developmental changes at the cortical level, rather than changes in front-end structural properties (Kiorpes et al., 2003.

  3. Stimulus familiarity modulates functional connectivity of the perirhinal cortex and anterior hippocampus during visual discrimination of faces and objects

    Science.gov (United States)

    McLelland, Victoria C.; Chan, David; Ferber, Susanne; Barense, Morgan D.

    2014-01-01

    Recent research suggests that the medial temporal lobe (MTL) is involved in perception as well as in declarative memory. Amnesic patients with focal MTL lesions and semantic dementia patients showed perceptual deficits when discriminating faces and objects. Interestingly, these two patient groups showed different profiles of impairment for familiar and unfamiliar stimuli. For MTL amnesics, the use of familiar relative to unfamiliar stimuli improved discrimination performance. By contrast, patients with semantic dementia—a neurodegenerative condition associated with anterolateral temporal lobe damage—showed no such facilitation from familiar stimuli. Given that the two patient groups had highly overlapping patterns of damage to the perirhinal cortex, hippocampus, and temporal pole, the neuroanatomical substrates underlying their performance discrepancy were unclear. Here, we addressed this question with a multivariate reanalysis of the data presented by Barense et al. (2011), using functional connectivity to examine how stimulus familiarity affected the broader networks with which the perirhinal cortex, hippocampus, and temporal poles interact. In this study, healthy participants were scanned while they performed an odd-one-out perceptual task involving familiar and novel faces or objects. Seed-based analyses revealed that functional connectivity of the right perirhinal cortex and right anterior hippocampus was modulated by the degree of stimulus familiarity. For familiar relative to unfamiliar faces and objects, both right perirhinal cortex and right anterior hippocampus showed enhanced functional correlations with anterior/lateral temporal cortex, temporal pole, and medial/lateral parietal cortex. These findings suggest that in order to benefit from stimulus familiarity, it is necessary to engage not only the perirhinal cortex and hippocampus, but also a network of regions known to represent semantic information. PMID:24624075

  4. Fringe proteins modulate Notch-ligand cis and trans interactions to specify signaling states.

    Science.gov (United States)

    LeBon, Lauren; Lee, Tom V; Sprinzak, David; Jafar-Nejad, Hamed; Elowitz, Michael B

    2014-09-25

    The Notch signaling pathway consists of multiple types of receptors and ligands, whose interactions can be tuned by Fringe glycosyltransferases. A major challenge is to determine how these components control the specificity and directionality of Notch signaling in developmental contexts. Here, we analyzed same-cell (cis) Notch-ligand interactions for Notch1, Dll1, and Jag1, and their dependence on Fringe protein expression in mammalian cells. We found that Dll1 and Jag1 can cis-inhibit Notch1, and Fringe proteins modulate these interactions in a way that parallels their effects on trans interactions. Fringe similarly modulated Notch-ligand cis interactions during Drosophila development. Based on these and previously identified interactions, we show how the design of the Notch signaling pathway leads to a restricted repertoire of signaling states that promote heterotypic signaling between distinct cell types, providing insight into the design principles of the Notch signaling system, and the specific developmental process of Drosophila dorsal-ventral boundary formation.

  5. A conserved PHD finger protein and endogenous RNAi modulate insulin signaling in Caenorhabditis elegans.

    Science.gov (United States)

    Mansisidor, Andres R; Cecere, Germano; Hoersch, Sebastian; Jensen, Morten B; Kawli, Trupti; Kennedy, Lisa M; Chavez, Violeta; Tan, Man-Wah; Lieb, Jason D; Grishok, Alla

    2011-09-01

    Insulin signaling has a profound effect on longevity and the oxidative stress resistance of animals. Inhibition of insulin signaling results in the activation of DAF-16/FOXO and SKN-1/Nrf transcription factors and increased animal fitness. By studying the biological functions of the endogenous RNA interference factor RDE-4 and conserved PHD zinc finger protein ZFP-1 (AF10), which regulate overlapping sets of genes in Caenorhabditis elegans, we identified an important role for these factors in the negative modulation of transcription of the insulin/PI3 signaling-dependent kinase PDK-1. Consistently, increased expression of pdk-1 in zfp-1 and rde-4 mutants contributed to their reduced lifespan and sensitivity to oxidative stress and pathogens due to the reduction in the expression of DAF-16 and SKN-1 targets. We found that the function of ZFP-1 in modulating pdk-1 transcription was important for the extended lifespan of the age-1(hx546) reduction-of-function PI3 kinase mutant, since the lifespan of the age-1; zfp-1 double mutant strain was significantly shorter compared to age-1(hx546). We further demonstrate that overexpression of ZFP-1 caused an increased resistance to oxidative stress in a DAF-16-dependent manner. Our findings suggest that epigenetic regulation of key upstream signaling components in signal transduction pathways through chromatin and RNAi may have a large impact on the outcome of signaling and expression of numerous downstream genes.

  6. Jumping the energetics queue: Modulation of pulsar signals by extraterrestrial civilizations

    Science.gov (United States)

    Chennamangalam, Jayanth; Siemion, Andrew P. V.; Lorimer, D. R.; Werthimer, Dan

    2015-01-01

    It has been speculated that technological civilizations evolve along an energy consumption scale first formulated by Kardashev, ranging from human-like civilizations that consume energy at a rate of ∼1019 erg s-1 to hypothetical highly advanced civilizations that can consume ∼1044 erg s-1. Since the transmission power of a beacon a civilization can build depends on the energy it possesses, to make it bright enough to be seen across the Galaxy would require high technological advancement. In this paper, we discuss the possibility of a civilization using naturally-occurring radio transmitters - specifically, radio pulsars - to overcome the Kardashev limit of their developmental stage and transmit super-Kardashev power. This is achieved by the use of a modulator situated around a pulsar, that modulates the pulsar signal, encoding information onto its natural emission. We discuss a simple modulation model using pulse nulling and considerations for detecting such a signal. We find that a pulsar with a nulling modulator will exhibit an excess of thermal emission peaking in the ultraviolet during its null phases, revealing the existence of a modulator.

  7. VizieR Online Data Catalog: Refracted light signals to discriminate exoplanets (Misra+, 2014)

    Science.gov (United States)

    Misra, A. K.; Meadows, V. S.

    2017-05-01

    We used a suite of planetary atmospheres to calculate the refracted light signal. We have selected a combination of solar system analogs as well possible super-Earth and mini-Neptune atmospheres to cover a wide range of potential planetary atmospheres. We assumed the H2-dominated atmospheres have a solar H/He ratio (90% H, 10% He) for simplicity, but the small change in the refractive index for different H/He ratios should have a negligible effect on our results. For the super-Earth and mini-Neptune planets, we ran our models on four test cases to span the most likely bulk atmospheric compositions: 100% N2, solar composition, 100% H2O, and 100% CO2. (1 data file).

  8. Cellular Interrogation: Exploiting Cell-to-Cell Variability to Discriminate Regulatory Mechanisms in Oscillatory Signalling.

    Science.gov (United States)

    Estrada, Javier; Andrew, Natalie; Gibson, Daniel; Chang, Frederick; Gnad, Florian; Gunawardena, Jeremy

    2016-07-01

    The molecular complexity within a cell may be seen as an evolutionary response to the external complexity of the cell's environment. This suggests that the external environment may be harnessed to interrogate the cell's internal molecular architecture. Cells, however, are not only nonlinear and non-stationary, but also exhibit heterogeneous responses within a clonal, isogenic population. In effect, each cell undertakes its own experiment. Here, we develop a method of cellular interrogation using programmable microfluidic devices which exploits the additional information present in cell-to-cell variation, without requiring model parameters to be fitted to data. We focussed on Ca2+ signalling in response to hormone stimulation, which exhibits oscillatory spiking in many cell types and chose eight models of Ca2+ signalling networks which exhibit similar behaviour in simulation. We developed a nonlinear frequency analysis for non-stationary responses, which could classify models into groups under parameter variation, but found that this question alone was unable to distinguish critical feedback loops. We further developed a nonlinear amplitude analysis and found that the combination of both questions ruled out six of the models as inconsistent with the experimentally-observed dynamics and heterogeneity. The two models that survived the double interrogation were mathematically different but schematically identical and yielded the same unexpected predictions that we confirmed experimentally. Further analysis showed that subtle mathematical details can markedly influence non-stationary responses under parameter variation, emphasising the difficulty of finding a "correct" model. By developing questions for the pathway being studied, and designing more versatile microfluidics, cellular interrogation holds promise as a systematic strategy that can complement direct intervention by genetics or pharmacology.

  9. Analysis of Filter-Bank-Based Methods for Fast Serial Acquisition of BOC-Modulated Signals

    Directory of Open Access Journals (Sweden)

    Elena Simona Lohan

    2007-09-01

    Full Text Available Binary-offset-carrier (BOC signals, selected for Galileo and modernized GPS systems, pose significant challenges for the code acquisition, due to the ambiguities (deep fades which are present in the envelope of the correlation function (CF. This is different from the BPSK-modulated CDMA signals, where the main correlation lobe spans over 2-chip interval, without any ambiguities or deep fades. To deal with the ambiguities due to BOC modulation, one solution is to use lower steps of scanning the code phases (i.e., lower than the traditional step of 0.5 chips used for BPSK-modulated CDMA signals. Lowering the time-bin steps entails an increase in the number of timing hypotheses, and, thus, in the acquisition times. An alternative solution is to transform the ambiguous CF into an “unambiguous” CF, via adequate filtering of the signal. A generalized class of frequency-based unambiguous acquisition methods is proposed here, namely the filter-bank-based (FBB approaches. The detailed theoretical analysis of FBB methods is given for serial-search single-dwell acquisition in single path static channels and a comparison is made with other ambiguous and unambiguous BOC acquisition methods existing in the literature.

  10. Modulation of learning and memory by cytokines: signaling mechanisms and long term consequences.

    Science.gov (United States)

    Donzis, Elissa J; Tronson, Natalie C

    2014-11-01

    This review describes the role of cytokines and their downstream signaling cascades on the modulation of learning and memory. Immune proteins are required for many key neural processes and dysregulation of these functions by systemic inflammation can result in impairments of memory that persist long after the resolution of inflammation. Recent research has demonstrated that manipulations of individual cytokines can modulate learning, memory, and synaptic plasticity. The many conflicting findings, however, have prevented a clear understanding of the precise role of cytokines in memory. Given the complexity of inflammatory signaling, understanding its modulatory role requires a shift in focus from single cytokines to a network of cytokine interactions and elucidation of the cytokine-dependent intracellular signaling cascades. Finally, we propose that whereas signal transduction and transcription may mediate short-term modulation of memory, long-lasting cellular and molecular mechanisms such as epigenetic modifications and altered neurogenesis may be required for the long lasting impact of inflammation on memory and cognition. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Functional Redundancy Between Canonical Endocannabinoid Signaling Systems in the Modulation of Anxiety.

    Science.gov (United States)

    Bedse, Gaurav; Hartley, Nolan D; Neale, Emily; Gaulden, Andrew D; Patrick, Toni A; Kingsley, Philip J; Uddin, Md Jashim; Plath, Niels; Marnett, Lawrence J; Patel, Sachin

    2017-10-01

    Increasing the available repertoire of effective treatments for mood and anxiety disorders represents a critical unmet need. Pharmacological augmentation of endogenous cannabinoid (eCB) signaling has been suggested to represent a novel approach to the treatment of anxiety disorders; however, the functional interactions between two canonical eCB pathways mediated via anandamide (N-arachidonylethanolamine [AEA]) and 2-arachidonoylglycerol (2-AG) in the regulation of anxiety are not well understood. We utilized pharmacological augmentation and depletion combined with behavioral and electrophysiological approaches to probe the role of 2-AG signaling in the modulation of stress-induced anxiety and the functional redundancy between AEA and 2-AG signaling in the modulation of anxiety-like behaviors in mice. Selective 2-AG augmentation reduced anxiety in the light/dark box assay and prevented stress-induced increases in anxiety associated with limbic AEA deficiency. In contrast, acute 2-AG depletion increased anxiety-like behaviors, which was normalized by selective pharmacological augmentation of AEA signaling and via direct cannabinoid receptor 1 stimulation with Δ 9 -tetrahydrocannabinol. Electrophysiological studies revealed 2-AG modulation of amygdala glutamatergic transmission as a key synaptic correlate of the anxiolytic effects of 2-AG augmentation. Although AEA and 2-AG likely subserve distinct physiological roles, a pharmacological and functional redundancy between these canonical eCB signaling pathways exists in the modulation of anxiety-like behaviors. These data support development of eCB-based treatment approaches for mood and anxiety disorders and suggest a potentially wider therapeutic overlap between AEA and 2-AG augmentation approaches than was previously appreciated. Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Quasi-periodic synchronisation of self-modulation oscillations in a ring chip laser by an external periodic signal

    International Nuclear Information System (INIS)

    Aulova, T V; Kravtsov, Nikolai V; Lariontsev, E G; Chekina, S N

    2011-01-01

    The synchronisation of periodic self-modulation oscillations in a ring Nd:YAG chip laser under an external periodic signal modulating the pump power has been experimentally investigated. A new quasi-periodic regime of synchronisation of self-modulation oscillations is found. The characteristic features of the behaviour of spectral and temporal structures of synchronised quasi-periodic oscillations with a change in the external signal frequency are studied. (control of laser radiation parameters)

  13. Cell intrinsic modulation of Wnt signaling controls neuroblast migration in C. elegans.

    Science.gov (United States)

    Mentink, Remco A; Middelkoop, Teije C; Rella, Lorenzo; Ji, Ni; Tang, Chung Yin; Betist, Marco C; van Oudenaarden, Alexander; Korswagen, Hendrik C

    2014-10-27

    Members of the Wnt family of secreted signaling proteins are key regulators of cell migration and axon guidance. In the nematode C. elegans, the migration of the QR neuroblast descendants requires multiple Wnt ligands and receptors. We found that the migration of the QR descendants is divided into three sequential phases that are each mediated by a distinct Wnt signaling mechanism. Importantly, the transition from the first to the second phase, which is the main determinant of the final position of the QR descendants along the anteroposterior body axis, is mediated through a cell-autonomous process in which the time-dependent expression of a Wnt receptor turns on the canonical Wnt/β-catenin signaling response that is required to terminate long-range anterior migration. Our results show that, in addition to direct guidance of cell migration by Wnt morphogenic gradients, cell migration can also be controlled indirectly through cell-intrinsic modulation of Wnt signaling responses.

  14. Optimization of carrier frequency and duty cycle for pulse modulation of biological signals.

    Science.gov (United States)

    Tandon, S N; Singh, S; Sharma, P K; Khosla, S

    1980-10-01

    Digital modulation techniques are commonly used for the recording and transmission of biological signals. Hitherto, the choice of subcarrier frequency for recording or transmission of biological signals has been arbitary and this usually results in poor signal to noise ratio (SNR) due to the limited frequency characteristics of the system. In the present study the frequency characteristics of the system (first order approximation) has been taken to be that of a Butterworth filter. Computations based on this assumption show that for a given input signal there exists an optimum subcarrier frequency and a corresponding optimum duty cycle which would give maximum SNR of the system. For convenience, a nomogram has been prepared and it has been shown that for a given frequency response of the system, the nomogram could be used for selecting an optimum subcarrier frequency and a corresponding duty cycle. The theoretical formulations have been verified with experimental work.

  15. Improved signal discrimination in tectonomagnetism: Discovery of a volcanomagnetic effect at Kilauea, Hawaii

    Science.gov (United States)

    Davis, P.M.; Stacey, F.D.; Zablocki, C.J.; Olson, J.V.

    1979-01-01

    Cancellation of extraterrestrial magnetic disturbances by taking simple differences between total field readings at spaced stations is imperfect. It is shown that improvement is possible when three component observatory data are available from a single station in the general, but not necessarily immediate, vicinity of an array of total field stations used in a tectonomagnetic study. The local effects of a magnetic disturbance field depend upon its orientation, so that local field differences are more effectively generated by certain orientations of the disturbance field. The orientation of the disturbance field which correlates best with a local difference field is determined by a least-squares method, so that the correlated vector signal can be routinely subtracted from the difference field record. Application of the technique to daily averages of records from three synchronised proton magnetometers on Kilauea volcano reveals a 1.5-nT change in the local field at the time of a flank eruption in May, 1973. This effect was obscured by noise in the raw difference field data. ?? 1979.

  16. Dual-tone optical vector millimeter wave signal generated by frequency-nonupling the radio frequency 16-star quadrature-amplitude-modulation signal

    Science.gov (United States)

    Wu, Tonggen; Ma, Jianxin

    2017-12-01

    This paper proposes an original scheme to generate the photonic dual-tone optical millimeter wave (MMW) carrying the 16-star quadrature-amplitude-modulation (QAM) signal via an optical phase modulator (PM) and an interleaver with adaptive photonic frequency-nonupling without phase precoding. To enable the generated optical vector MMW signal to resist the power fading effect caused by the fiber chromatic dispersion, the modulated -5th- and +4th-order sidebands are selected from the output of the PM, which is driven by the precoding 16-star QAM signal. The modulation index of the PM is optimized to gain the maximum opto-electrical conversion efficiency. A radio over fiber link is built by simulation, and the simulated constellations and the bit error rate graph demonstrate that the frequency-nonupling 16-star QAM MMW signal has good transmission performance. The simulation results agree well with our theoretical results.

  17. Frequency-dependent tACS modulation of BOLD signal during rhythmic visual stimulation.

    Science.gov (United States)

    Chai, Yuhui; Sheng, Jingwei; Bandettini, Peter A; Gao, Jia-Hong

    2018-05-01

    Transcranial alternating current stimulation (tACS) has emerged as a promising tool for modulating cortical oscillations. In previous electroencephalogram (EEG) studies, tACS has been found to modulate brain oscillatory activity in a frequency-specific manner. However, the spatial distribution and hemodynamic response for this modulation remains poorly understood. Functional magnetic resonance imaging (fMRI) has the advantage of measuring neuronal activity in regions not only below the tACS electrodes but also across the whole brain with high spatial resolution. Here, we measured fMRI signal while applying tACS to modulate rhythmic visual activity. During fMRI acquisition, tACS at different frequencies (4, 8, 16, and 32 Hz) was applied along with visual flicker stimulation at 8 and 16 Hz. We analyzed the blood-oxygen-level-dependent (BOLD) signal difference between tACS-ON vs tACS-OFF, and different frequency combinations (e.g., 4 Hz tACS, 8 Hz flicker vs 8 Hz tACS, 8 Hz flicker). We observed significant tACS modulation effects on BOLD responses when the tACS frequency matched the visual flicker frequency or the second harmonic frequency. The main effects were predominantly seen in regions that were activated by the visual task and targeted by the tACS current distribution. These findings bridge different scientific domains of tACS research and demonstrate that fMRI could localize the tACS effect on stimulus-induced brain rhythms, which could lead to a new approach for understanding the high-level cognitive process shaped by the ongoing oscillatory signal. © 2018 Wiley Periodicals, Inc.

  18. Electroabsorption modulators used for all-optical signal processing and labelling

    DEFF Research Database (Denmark)

    Xu, Lin

    2004-01-01

    This thesis concerns the applications of semiconductor components, primarily electroabsorption modulators (EAMs), in optical signal processing and labelling for future all optical communication networks. An introduction to electroabsorption modulators is given and several mechanisms that form...... function of an EAM is frequency dependent and the main improvement from an EAM-based regenerator is the enhancement of the ER and the suppression of the noise in a space bit. Applications of EAMs in optical label processing using various orthogonal labelling schemes are discussed. Through EAM...... encoding are –25.6/-28.1 dBm and –23.7/-21 dBm, respectively. Using an EAM for optical label insertion and a MZ-SOA for optical label erasure and payload regeneration in the ASK(10 Gb/s)/ Frequency Shift Keying (312 Mb/s) orthogonal modulation format, the complete functionality of a network node including...

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

    Science.gov (United States)

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

    2013-10-01

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

  20. Pressure modulation algorithm to separate cerebral hemodynamic signals from extracerebral artifacts

    OpenAIRE

    Baker, Wesley B.; Parthasarathy, Ashwin B.; Ko, Tiffany S.; Busch, David R.; Abramson, Kenneth; Tzeng, Shih-Yu; Mesquita, Rickson C.; Durduran, Turgut; Greenberg, Joel H.; Kung, David K.; Yodh, Arjun G.

    2015-01-01

    We introduce and validate a pressure measurement paradigm that reduces extracerebral contamination from superficial tissues in optical monitoring of cerebral blood flow with diffuse correlation spectroscopy (DCS). The scheme determines subject-specific contributions of extracerebral and cerebral tissues to the DCS signal by utilizing probe pressure modulation to induce variations in extracerebral blood flow. For analysis, the head is modeled as a two-layer medium and is probed with long and s...

  1. A molecular-sized optical logic circuit for digital modulation of a fluorescence signal

    Science.gov (United States)

    Nishimura, Takahiro; Tsuchida, Karin; Ogura, Yusuke; Tanida, Jun

    2018-03-01

    Fluorescence measurement allows simultaneous detection of multiple molecular species by using spectrally distinct fluorescence probes. However, due to the broad spectra of fluorescence emission, the multiplicity of fluorescence measurement is generally limited. To overcome this limitation, we propose a method to digitally modulate fluorescence output signals with a molecular-sized optical logic circuit by using optical control of fluorescence resonance energy transfer (FRET). The circuit receives a set of optical inputs represented with different light wavelengths, and then it switches high and low fluorescence intensity from a reporting molecule according to the result of the logic operation. By using combinational optical inputs in readout of fluorescence signals, the number of biomolecular species that can be identified is increased. To implement the FRET-based circuits, we designed two types of basic elements, YES and NOT switches. An YES switch produces a high-level output intensity when receiving a designated light wavelength input and a low-level intensity without the light irradiation. A NOT switch operates inversely to the YES switch. In experiments, we investigated the operation of the YES and NOT switches that receive a 532-nm light input and modulate the fluorescence intensity of Alexa Fluor 488. The experimental result demonstrates that the switches can modulate fluorescence signals according to the optical input.

  2. Perceived Discrimination, Psychological Distress, and Current Smoking Status: Results From the Behavioral Risk Factor Surveillance System Reactions to Race Module, 2004–2008

    Science.gov (United States)

    Peppone, Luke J.; Alcaraz, Kassandra; McQueen, Amy; Guido, Joseph J.; Carroll, Jennifer K.; Shacham, Enbal; Morrow, Gary R.

    2012-01-01

    Objectives. We examined the association between perceived discrimination and smoking status and whether psychological distress mediated this relationship in a large, multiethnic sample. Methods. We used 2004 through 2008 data from the Behavioral Risk Factor Surveillance System Reactions to Race module to conduct multivariate logistic regression analyses and tests of mediation examining associations between perceived discrimination in health care and workplace settings, psychological distress, and current smoking status. Results. Regardless of race/ethnicity, perceived discrimination was associated with increased odds of current smoking. Psychological distress was also a significant mediator of the discrimination–smoking association. Conclusions. Our results indicate that individuals who report discriminatory treatment in multiple domains may be more likely to smoke, in part, because of the psychological distress associated with such treatment. PMID:22420821

  3. Protein conservation and variation suggest mechanisms of cell type-specific modulation of signaling pathways.

    Directory of Open Access Journals (Sweden)

    Martin H Schaefer

    2014-06-01

    Full Text Available Many proteins and signaling pathways are present in most cell types and tissues and yet perform specialized functions. To elucidate mechanisms by which these ubiquitous pathways are modulated, we overlaid information about cross-cell line protein abundance and variability, and evolutionary conservation onto functional pathway components and topological layers in the pathway hierarchy. We found that the input (receptors and the output (transcription factors layers evolve more rapidly than proteins in the intermediary transmission layer. In contrast, protein expression variability decreases from the input to the output layer. We observed that the differences in protein variability between the input and transmission layer can be attributed to both the network position and the tendency of variable proteins to physically interact with constitutively expressed proteins. Differences in protein expression variability and conservation are also accompanied by the tendency of conserved and constitutively expressed proteins to acquire somatic mutations, while germline mutations tend to occur in cell type-specific proteins. Thus, conserved core proteins in the transmission layer could perform a fundamental role in most cell types and are therefore less tolerant to germline mutations. In summary, we propose that the core signal transmission machinery is largely modulated by a variable input layer through physical protein interactions. We hypothesize that the bow-tie organization of cellular signaling on the level of protein abundance variability contributes to the specificity of the signal response in different cell types.

  4. Effect of GABA agonists and GABA-A receptor modulators on cocaine- and food-maintained responding and cocaine discrimination in rats.

    Science.gov (United States)

    Barrett, Andrew C; Negus, S Stevens; Mello, Nancy K; Caine, S Barak

    2005-11-01

    Recent studies indicate that GABAergic ligands modulate abuse-related effects of cocaine. The goal of this study was to evaluate the effects of a mechanistically diverse group of GABAergic ligands on the discriminative stimulus and reinforcing effects of cocaine in rats. One group of rats was trained to discriminate 5.6 mg/kg cocaine from saline in a two-lever, food-reinforced, drug discrimination procedure. In two other groups, responding was maintained by cocaine (0-3.2 mg/kg/injection) or liquid food (0-100%) under a fixed ratio 5 schedule. Six GABA agonists were tested: the GABA-A receptor agonist muscimol, the GABA-B receptor agonist baclofen, the GABA transaminase inhibitor gamma-vinyl-GABA (GVG), and three GABA-A receptor modulators (the barbiturate pentobarbital, the high-efficacy benzodiazepine midazolam, and the low-efficacy benzodiazepine enazenil). When tested alone, none of the compounds substituted fully for the discriminative stimulus effects of cocaine. As acute pretreatments, select doses of midazolam and pentobarbital produced 2.2- to 3.6-fold rightward shifts in the cocaine dose-effect function. In contrast, muscimol, baclofen, GVG, and enazenil failed to alter the discriminative stimulus effects of cocaine. In assays of cocaine- and food-maintained responding, midazolam and pentobarbital decreased cocaine self-administration at doses 9.6- and 3.3-fold lower, respectively, than those that decreased food-maintained responding. In contrast, muscimol, baclofen, and GVG decreased cocaine self-administration at doses that also decreased food-maintained responding. Enazenil failed to alter cocaine self-administration. Together with previous studies, these data suggest that among mechanistically diverse GABA agonists, high-efficacy GABA-A modulators may be the most effective for modifying the abuse-related effects of cocaine.

  5. CD147 regulates extrinsic apoptosis in spermatocytes by modulating NFκB signaling pathways.

    Science.gov (United States)

    Wang, Chaoqun; Fok, Kin Lam; Cai, Zhiming; Chen, Hao; Chan, Hsiao Chang

    2017-01-10

    CD147 null mutant male mice are infertile with arrested spermatogenesis and increased apoptotic germ cells. Our previous studies have shown that CD147 prevents apoptosis in mouse spermatocytes but not spermatogonia. However, the underlying mechanism remains elusive. In the present study, we aim to determine the CD147-regulated apoptotic pathway in mouse spermatocytes. Our results showed that immunodepletion of CD147 triggered apoptosis through extrinsic apoptotic pathway in mouse testis and spermatocyte cell line (GC-2 cells), accompanied by activation of non-canonical NFκB signaling and suppression of canonical NFκB signaling. Furthermore, CD147 was found to interact with TRAF2, a factor known to regulate NFκB and extrinsic apoptotic signaling, and interfering CD147 led to the decrease of TRAF2. Consistently, depletion of CD147 by CRISPR/Cas9 technique in GC-2 cells down-regulated TRAF2 and resulted in cell death with suppressed canonical NFκB and activated non-canonical NFκB signaling. On the contrary, interfering of CD147 had no effect on NFκB signaling pathways as well as TRAF2 protein level in mouse spermatogonia cell line (GC-1 cells). Taken together, these results suggested that CD147 plays a key role in reducing extrinsic apoptosis in spermatocytes, but not spermatogonia, through modulating NFκB signaling pathway.

  6. Dopamine modulates acetylcholine release via octopamine and CREB signaling in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Satoshi Suo

    Full Text Available Animals change their behavior and metabolism in response to external stimuli. cAMP response element binding protein (CREB is a signal-activated transcription factor that enables the coupling of extracellular signals and gene expression to induce adaptive changes. Biogenic amine neurotransmitters regulate CREB and such regulation is important for long-term changes in various nervous system functions, including learning and drug addiction. In Caenorhabditis elegans, the amine neurotransmitter octopamine activates a CREB homolog, CRH-1, in cholinergic SIA neurons, whereas dopamine suppresses CREB activation by inhibiting octopamine signaling in response to food stimuli. However, the physiological role of this activation is unknown. In this study, the effect of dopamine, octopamine, and CREB on acetylcholine signaling was analyzed using the acetylcholinesterase inhibitor aldicarb. Mutants with decreased dopamine signaling exhibited reduced acetylcholine signaling, and octopamine and CREB functioned downstream of dopamine in this regulation. This study demonstrates that the regulation of CREB by amine neurotransmitters modulates acetylcholine release from the neurons of C. elegans.

  7. Cationic Polyamidoamine Dendrimers as Modulators of EGFR Signaling In Vitro and In Vivo.

    Directory of Open Access Journals (Sweden)

    Saghir Akhtar

    Full Text Available Cationic polyamidoamine (PAMAM dendrimers are branch-like spherical polymers being investigated for a variety of applications in nanomedicine including nucleic acid drug delivery. Emerging evidence suggests they exhibit intrinsic biological and toxicological effects but little is known of their interactions with signal transduction pathways. We previously showed that the activated (fragmented generation (G 6 PAMAM dendrimer, Superfect (SF, stimulated epidermal growth factor receptor (EGFR tyrosine kinase signaling-an important signaling cascade that regulates cell growth, survival and apoptosis- in cultured human embryonic kidney (HEK 293 cells. Here, we firstly studied the in vitro effects of Polyfect (PF, a non-activated (intact G6 PAMAM dendrimer, on EGFR tyrosine kinase signaling via extracellular-regulated kinase 1/2 (ERK1/2 and p38 mitogen-activated protein kinase (MAPK in cultured HEK 293 cells and then compared the in vivo effects of a single administration (10mg/kg i.p of PF or SF on EGFR signaling in the kidneys of normal and diabetic male Wistar rats. Polyfect exhibited a dose- and time-dependent inhibition of EGFR, ERK1/2 and p38 MAPK phosphorylation in HEK-293 cells similar to AG1478, a selective EGFR inhibitor. Administration of dendrimers to non-diabetic or diabetic animals for 24h showed that PF inhibited whereas SF stimulated EGFR phosphorylation in the kidneys of both sets of animals. PF-mediated inhibition of EGFR phosphorylation as well as SF or PF-mediated apoptosis in HEK 293 cells could be significantly reversed by co-treatment with antioxidants such as tempol implying that both these effects involved an oxidative stress-dependent mechanism. These results show for the first time that SF and PF PAMAM dendrimers can differentially modulate the important EGFR signal transduction pathway in vivo and may represent a novel class of EGFR modulators. These findings could have important clinical implications for the use of PAMAM

  8. The properties of ULF/VLF signals generated by the SURA facility without ionospheric currents modulation

    Science.gov (United States)

    Kotik, D. S.; Raybov, A. V.; Ermakova, E. N.

    2012-12-01

    traditional mechanism of ionospheric current modulation. Also this signals displayed unusual behavior during the magnetic storm deceasing in the amplitude. The work was supported by RFBR grants 11-02-00419, 11-02-97104 and RF Ministry of education and science by state contract 16.518.11.7066.;

  9. PARP-1 modulation of mTOR signaling in response to a DNA alkylating agent.

    Directory of Open Access Journals (Sweden)

    Chantal Ethier

    Full Text Available Poly(ADP-ribose polymerase-1 (PARP-1 is widely involved in cell death responses. Depending on the degree of injury and on cell type, PARP activation may lead to autophagy, apoptosis or necrosis. In HEK293 cells exposed to the alkylating agent N-methyl-N'-nitro-N'-nitrosoguanine (MNNG, we show that PARP-1 activation triggers a necrotic cell death response. The massive poly(ADP-ribose (PAR synthesis following PARP-1 activation leads to the modulation of mTORC1 pathway. Shortly after MNNG exposure, NAD⁺ and ATP levels decrease, while AMP levels drastically increase. We characterized at the molecular level the consequences of these altered nucleotide levels. First, AMP-activated protein kinase (AMPK is activated and the mTORC1 pathway is inhibited by the phosphorylation of Raptor, in an attempt to preserve cellular energy. Phosphorylation of the mTORC1 target S6 is decreased as well as the phosphorylation of the mTORC2 component Rictor on Thr1135. Finally, Akt phosphorylation on Ser473 is lost and then, cell death by necrosis occurs. Inhibition of PARP-1 with the potent PARP inhibitor AG14361 prevents all of these events. Moreover, the antioxidant N-acetyl-L-cysteine (NAC can also abrogate all the signaling events caused by MNNG exposure suggesting that reactive oxygen species (ROS production is involved in PARP-1 activation and modulation of mTOR signaling. In this study, we show that PARP-1 activation and PAR synthesis affect the energetic status of cells, inhibit the mTORC1 signaling pathway and possibly modulate the mTORC2 complex affecting cell fate. These results provide new evidence that cell death by necrosis is orchestrated by the balance between several signaling pathways, and that PARP-1 and PAR take part in these events.

  10. Separate and combined effects of the GABAA positive allosteric modulator diazepam and Δ⁹-THC in humans discriminating Δ⁹-THC.

    Science.gov (United States)

    Lile, Joshua A; Kelly, Thomas H; Hays, Lon R

    2014-10-01

    Our previous research suggested the involvement of γ-aminobutyric acid (GABA), in particular the GABAB receptor subtype, in the interoceptive effects of Δ(9)-tetrahydrocannabinol (Δ(9)-THC). The aim of the present study was to determine the potential involvement of the GABAA receptor subtype by assessing the separate and combined effects of the GABAA positive allosteric modulator diazepam and Δ(9)-THC using pharmacologically selective drug-discrimination procedures. Ten cannabis users learned to discriminate 30 mg oral Δ(9)-THC from placebo and then received diazepam (5 and 10mg), Δ(9)-THC (5, 15 and 30 mg) and placebo, alone and in combination. Self-report, task performance and physiological measures were also collected. Δ(9)-THC functioned as a discriminative stimulus, produced subjective effects typically associated with cannabinoids (e.g., High, Stoned, Like Drug) and elevated heart rate. Diazepam alone impaired performance on psychomotor performance tasks and increased ratings on a limited number of self-report questionnaire items (e.g., Any Effect, Sedated), but did not substitute for the Δ(9)-THC discriminative stimulus or alter the Δ(9)-THC discrimination dose-response function. Similarly, diazepam had limited impact on the other behavioral effects of Δ(9)-THC. These results suggest that the GABAA receptor subtype has minimal involvement in the interoceptive effects of Δ(9)-THC, and by extension cannabis, in humans. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  11. Comparing success levels of different neural network structures in extracting discriminative information from the response patterns of a temperature-modulated resistive gas sensor

    Science.gov (United States)

    Hosseini-Golgoo, S. M.; Bozorgi, H.; Saberkari, A.

    2015-06-01

    Performances of three neural networks, consisting of a multi-layer perceptron, a radial basis function, and a neuro-fuzzy network with local linear model tree training algorithm, in modeling and extracting discriminative features from the response patterns of a temperature-modulated resistive gas sensor are quantitatively compared. For response pattern recording, a voltage staircase containing five steps each with a 20 s plateau is applied to the micro-heater of the sensor, when 12 different target gases, each at 11 concentration levels, are present. In each test, the hidden layer neuron weights are taken as the discriminatory feature vector of the target gas. These vectors are then mapped to a 3D feature space using linear discriminant analysis. The discriminative information content of the feature vectors are determined by the calculation of the Fisher’s discriminant ratio, affording quantitative comparison among the success rates achieved by the different neural network structures. The results demonstrate a superior discrimination ratio for features extracted from local linear neuro-fuzzy and radial-basis-function networks with recognition rates of 96.27% and 90.74%, respectively.

  12. Comparing success levels of different neural network structures in extracting discriminative information from the response patterns of a temperature-modulated resistive gas sensor

    International Nuclear Information System (INIS)

    Hosseini-Golgoo, S M; Bozorgi, H; Saberkari, A

    2015-01-01

    Performances of three neural networks, consisting of a multi-layer perceptron, a radial basis function, and a neuro-fuzzy network with local linear model tree training algorithm, in modeling and extracting discriminative features from the response patterns of a temperature-modulated resistive gas sensor are quantitatively compared. For response pattern recording, a voltage staircase containing five steps each with a 20 s plateau is applied to the micro-heater of the sensor, when 12 different target gases, each at 11 concentration levels, are present. In each test, the hidden layer neuron weights are taken as the discriminatory feature vector of the target gas. These vectors are then mapped to a 3D feature space using linear discriminant analysis. The discriminative information content of the feature vectors are determined by the calculation of the Fisher’s discriminant ratio, affording quantitative comparison among the success rates achieved by the different neural network structures. The results demonstrate a superior discrimination ratio for features extracted from local linear neuro-fuzzy and radial-basis-function networks with recognition rates of 96.27% and 90.74%, respectively. (paper)

  13. Robustness of digitally modulated signal features against variation in HF noise model

    Directory of Open Access Journals (Sweden)

    Shoaib Mobien

    2011-01-01

    Full Text Available Abstract High frequency (HF band has both military and civilian uses. It can be used either as a primary or backup communication link. Automatic modulation classification (AMC is of an utmost importance in this band for the purpose of communications monitoring; e.g., signal intelligence and spectrum management. A widely used method for AMC is based on pattern recognition (PR. Such a method has two main steps: feature extraction and classification. The first step is generally performed in the presence of channel noise. Recent studies show that HF noise could be modeled by Gaussian or bi-kappa distributions, depending on day-time. Therefore, it is anticipated that change in noise model will have impact on features extraction stage. In this article, we investigate the robustness of well known digitally modulated signal features against variation in HF noise. Specifically, we consider temporal time domain (TTD features, higher order cumulants (HOC, and wavelet based features. In addition, we propose new features extracted from the constellation diagram and evaluate their robustness against the change in noise model. This study is targeting 2PSK, 4PSK, 8PSK, 16QAM, 32QAM, and 64QAM modulations, as they are commonly used in HF communications.

  14. Improving the signal-to-noise ratio in ultrasound-modulated optical tomography by a lock-in amplifier

    Science.gov (United States)

    Zhu, Lili; Wu, Jingping; Lin, Guimin; Hu, Liangjun; Li, Hui

    2016-10-01

    With high spatial resolution of ultrasonic location and high sensitivity of optical detection, ultrasound-modulated optical tomography (UOT) is a promising noninvasive biological tissue imaging technology. In biological tissue, the ultrasound-modulated light signals are very weak and are overwhelmed by the strong unmodulated light signals. It is a difficulty and key to efficiently pick out the weak modulated light from strong unmodulated light in UOT. Under the effect of an ultrasonic field, the scattering light intensity presents a periodic variation as the ultrasonic frequency changes. So the modulated light signals would be escape from the high unmodulated light signals, when the modulated light signals and the ultrasonic signal are processed cross correlation operation by a lock-in amplifier and without a chopper. Experimental results indicated that the signal-to-noise ratio of UOT is significantly improved by a lock-in amplifier, and the higher the repetition frequency of pulsed ultrasonic wave, the better the signal-to-noise ratio of UOT.

  15. Nanobody-Based Biologics for Modulating Purinergic Signaling in Inflammation and Immunity

    Directory of Open Access Journals (Sweden)

    Stephan Menzel

    2018-03-01

    Full Text Available Adenosine triphosphate (ATP and nicotinamide adenine dinucleotide (NAD+ are released as danger signals from cells during infection and sterile inflammation. In the extracellular compartment ATP is converted by CD39, CD73, and other ecto-enzymes into metabolites that modulate the activity of T cells and macrophages. While ATP mediates pro-inflammatory signals via P2X7 and other P2 receptors, adenosine triggers anti-inflammatory signaling via the adenosine 2a receptor (Adora2a and other P1 receptors. The latter also plays a role in maintaining an immunosuppressive tumor microenvironment. NAD+ is converted by CD38, CD203 and other ecto-enzymes to the Ca2+ mobilizing messengers cyclic ADP-ribose and ADP-ribose, and to adenosine. Recent findings on the roles of CD38, CD39, CD73, CD203, P2X7, and Adora2a in inflammation and immunity underscore the potential of these proteins as drug targets. However, available small molecule inhibitors often lack specificity and mediate unwanted off-target toxicity. Nanobodies – single domain antibodies derived from heavy chain antibodies that naturally occur in camelids – display a propensity to bind functional epitopes not accessible to conventional antibodies. Like conventional antibodies, nanobodies and nanobody-based biologics are highly specific and have well-understood, tunable in vivo pharmacodynamics with little if any toxicity. Nanobodies thus represent attractive alternatives to small molecule inhibitors for modulating purinergic signaling in inflammation and immunity. Here we review recent progress made in developing nanobodies against key targets of purinergic signaling.

  16. Nanobody-Based Biologics for Modulating Purinergic Signaling in Inflammation and Immunity.

    Science.gov (United States)

    Menzel, Stephan; Schwarz, Nicole; Haag, Friedrich; Koch-Nolte, Friedrich

    2018-01-01

    Adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD + ) are released as danger signals from cells during infection and sterile inflammation. In the extracellular compartment ATP is converted by CD39, CD73, and other ecto-enzymes into metabolites that modulate the activity of T cells and macrophages. While ATP mediates pro-inflammatory signals via P2X7 and other P2 receptors, adenosine triggers anti-inflammatory signaling via the adenosine 2a receptor (Adora2a) and other P1 receptors. The latter also plays a role in maintaining an immunosuppressive tumor microenvironment. NAD + is converted by CD38, CD203 and other ecto-enzymes to the Ca 2+ mobilizing messengers cyclic ADP-ribose and ADP-ribose, and to adenosine. Recent findings on the roles of CD38, CD39, CD73, CD203, P2X7, and Adora2a in inflammation and immunity underscore the potential of these proteins as drug targets. However, available small molecule inhibitors often lack specificity and mediate unwanted off-target toxicity. Nanobodies - single domain antibodies derived from heavy chain antibodies that naturally occur in camelids - display a propensity to bind functional epitopes not accessible to conventional antibodies. Like conventional antibodies, nanobodies and nanobody-based biologics are highly specific and have well-understood, tunable in vivo pharmacodynamics with little if any toxicity. Nanobodies thus represent attractive alternatives to small molecule inhibitors for modulating purinergic signaling in inflammation and immunity. Here we review recent progress made in developing nanobodies against key targets of purinergic signaling.

  17. Frequency modulator. Transmission of meteorological signals in LVC; Modulador de frecuencia. Transmision de senales meteorologicas en CLV

    Energy Technology Data Exchange (ETDEWEB)

    Rivero G, P.T.; Ramirez S, R.; Gonzalez M, J.L.; Rojas N, P.; Celis del Angel, L. [ININ, 52750 La marquesa, Estado de Mexico (Mexico)

    2007-07-01

    The development of the frequency modulator and demodulator circuit for transmission of meteorological signals by means of fiber optics of the meteorology station to the nuclear reactor unit 1 in the Laguna Verde Central in Veracruz is described. (Author)

  18. Phase Clustering Based Modulation Classification Algorithm for PSK Signal over Wireless Environment

    Directory of Open Access Journals (Sweden)

    Qi An

    2016-01-01

    Full Text Available Promptitude and accuracy of signals’ non-data-aided (NDA identification is one of the key technology demands in noncooperative wireless communication network, especially in information monitoring and other electronic warfare. Based on this background, this paper proposes a new signal classifier for phase shift keying (PSK signals. The periodicity of signal’s phase is utilized as the assorted character, with which a fractional function is constituted for phase clustering. Classification and the modulation order of intercepted signals can be achieved through its Fast Fourier Transform (FFT of the phase clustering function. Frequency offset is also considered for practical conditions. The accuracy of frequency offset estimation has a direct impact on its correction. Thus, a feasible solution is supplied. In this paper, an advanced estimator is proposed for estimating the frequency offset and balancing estimation accuracy and range under low signal-to-noise ratio (SNR conditions. The influence on estimation range brought by the maximum correlation interval is removed through the differential operation of the autocorrelation of the normalized baseband signal raised to the power of Q. Then, a weighted summation is adopted for an effective frequency estimation. Details of equations and relevant simulations are subsequently presented. The estimator proposed can reach an estimation accuracy of 10-4 even when the SNR is as low as -15 dB. Analytical formulas are expressed, and the corresponding simulations illustrate that the classifier proposed is more efficient than its counterparts even at low SNRs.

  19. Antioxidant and signal modulation properties of plant polyphenols in controlling vascular inflammation.

    Science.gov (United States)

    Kostyuk, Vladimir A; Potapovich, Alla I; Suhan, Tatyana O; de Luca, Chiara; Korkina, Liudmila G

    2011-05-11

    Oxidized low-density lipoproteins (oxLDL) play a critical role in the initiation of atherosclerosis through activation of inflammatory signaling. In the present work we investigated the role of antioxidant and signal modulation properties of plant polyphenols in controlling vascular inflammation. Significant decrease in intracellular NO level and superoxide overproduction was found in human umbilical vein endothelial cells (HUVEC) treated with oxLDL, but not with LDL. The redox imbalance was prevented by the addition of quercetin or resveratrol. Expression analysis of 14 genes associated with oxidative stress and inflammation revealed oxLDL-mediated up-regulation of genes specifically involved in leukocyte recruitment and adhesion. This up-regulation could be partially avoided by the addition of verbascoside or resveratrol, while treatment with quercetin resulted in a further increase in the expression of these genes. Lipopolysaccharide (LPS)-treated HUVEC were also used for the evaluation of anti-inflammatory potency of plant polyphenols. Significant differences between HUVEC treaded with oxLDL and LPS were found in both the expression pattern of inflammation-related genes and the effects of plant polyphenols on cellular responses. The present data indicate that plant polyphenols may affect vascular inflammation not only as antioxidants but also as modulators of inflammatory redox signaling pathways. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

  20. Analytical formulation of directly modulated OOFDM signals transmitted over an IM/DD dispersive link.

    Science.gov (United States)

    Sánchez, C; Ortega, B; Wei, J L; Tang, J; Capmany, J

    2013-03-25

    We provide an analytical study on the propagation effects of a directly modulated OOFDM signal through a dispersive fiber and subsequent photo-detection. The analysis includes the effects of the laser operation point and the interplay between chromatic dispersion and laser chirp. The final expression allows to understand the physics behind the transmission of a multi-carrier signal in the presence of residual frequency modulation and the description of the induced intermodulation distortion gives us a detailed insight into the diferent intermodulation products which impair the recovered signal at the receiver-end side. Numerical comparisons between transmission simulations results and those provided by evaluating the expression obtained are carried out for different laser operation points. Results obtained by changing the fiber length, laser parameters and using single mode fiber with negative and positive dispersion are calculated in order to demonstrate the validity and versatility of the theory provided in this paper. Therefore, a novel analytical formulation is presented as a versatile tool for the description and study of IM/DD OOFDM systems with variable design parameters.

  1. Astrophysics-independent bounds on the annual modulation of dark matter signals.

    Science.gov (United States)

    Herrero-Garcia, Juan; Schwetz, Thomas; Zupan, Jure

    2012-10-05

    We show how constraints on the time integrated event rate from a given dark matter (DM) direct detection experiment can be used to bound the amplitude of the annual modulation signal in another experiment. The method requires only mild assumptions about the properties of the local DM distribution: that it is temporally stable on the scale of months and spatially homogeneous on the ecliptic. We apply the method to the annual modulation signal in DAMA/LIBRA, which we compare to the bounds derived from XENON10, XENON100, cryogenic DM search, and SIMPLE data. Assuming a DM mass of 10 GeV, we show that under the above assumptions about the DM halo, a DM interpretation of the DAMA/LIBRA signal is excluded for several classes of models: at 6.3σ (4.6σ) for elastic isospin conserving (violating) spin-independent interactions, and at 4.9σ for elastic spin-dependent interactions on protons.

  2. A Sparse Modulation Signal Bispectrum Analysis Method for Rolling Element Bearing Diagnosis

    Directory of Open Access Journals (Sweden)

    Guangbin Wang

    2018-01-01

    Full Text Available Modulation signal bispectrum (MSB analysis is an effective method to obtain the fault frequency for rolling bearing, but harmonics make fault frequency dense and even frequency aliasing. Carrier frequency of bearing is generally determined by its structure and inherent characteristics and changes with the increase of the damage degree, so it is hard to be accurately found. To solve these problems, this paper proposes a sparse modulation signal bispectrum analysis method. Firstly the vibration signal is demodulated by MSB analysis and its bispectrum is obtained. After the frequency domain filtering, the carrier frequency is computed based on the characteristics of energy concentration at the carrier frequency on MSB. By shift-frequency MSB (SF-MSB, the carrier frequency is moved to the coordinate origin, the entire MSB is shifted for the same distance, and SF-MSB is obtained. At last, the bispectrum is shifted to the frequency zero point and diagonal slices are performed to obtain a sparse representation of MSB. Experimental results show that sparse MSB (S-MSB method can not only eliminate the interference of harmonic frequency, but also make the extracted characteristic frequency of fault more obvious.

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

    International Nuclear Information System (INIS)

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

    1991-10-01

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

  4. Custom chipset and compact module design for a 75–110 GHz laboratory signal source

    International Nuclear Information System (INIS)

    Morgan, Matthew A; Boyd, Tod A; Castro, Jason J

    2016-01-01

    We report on the development and characterization of a compact, full-waveguide bandwidth (WR-10) signal source for general-purpose testing of mm-wave components. The monolithic microwave integrated circuit (MMIC) based multichip module is designed for compactness and ease-of-use, especially in size-constrained test sets such as a wafer probe station. It takes as input a cm-wave continuous-wave (CW) reference and provides a factor of three frequency multiplication as well as amplification, output power adjustment, and in situ output power monitoring. It utilizes a number of custom MMIC chips such as a Schottky-diode limiter and a broadband mm-wave detector, both designed explicitly for this module, as well as custom millimeter-wave multipliers and amplifiers reported in previous papers. (paper)

  5. Linearized Optically Phase-Modulated Fiber Optic Links for Microwave Signal Transport

    Science.gov (United States)

    2009-03-03

    detectors (with internal 50- Ohm resistors) capable of 40-mA dc current per detector. With this link, the linearized SFDR would improve to 133 dB/Hz4/5...the IF) limitation on the signal. All calculations consider the 3dB power loss from the hybrid combiner and 6dB loss from parallel 50- Ohm resistors...283. [25] M. Nazarathy, J. Berger, A. Ley , I. Levi, and Y. Kagan, “Externally Modulated 80 Channel Am Catv Fiber-to-feeder Distribution System Over

  6. Designing Non-linear Frequency Modulated Signals For Medical Ultrasound Imaging

    DEFF Research Database (Denmark)

    Gran, Fredrik; Jensen, Jørgen Arendt

    2006-01-01

    In this paper a new method for designing non-linear frequency modulated (NLFM) waveforms for ultrasound imaging is proposed. The objective is to control the amplitude spectrum of the designed waveform and still keep a constant transmit amplitude, so that the transmitted energy is maximized....... The signal-to-noise-ratio can in this way be optimized. The waveform design is based on least squares optimization. A desired amplitude spectrum is chosen, hereafter the phase spectrum is chosen, so that the instantaneous frequency takes on the form of a third order polynomial. The finite energy waveform...

  7. Impact of MAC Delay on AUV Localization: Underwater Localization Based on Hyperbolic Frequency Modulation Signal.

    Science.gov (United States)

    Kim, Sungryul; Yoo, Younghwan

    2018-01-26

    Medium Access Control (MAC) delay which occurs between the anchor node's transmissions is one of the error sources in underwater localization. In particular, in AUV localization, the MAC delay significantly degrades the ranging accuracy. The Cramer-Rao Low Bound (CRLB) definition theoretically proves that the MAC delay significantly degrades the localization performance. This paper proposes underwater localization combined with multiple access technology to decouple the localization performance from the MAC delay. Towards this goal, we adopt hyperbolic frequency modulation (HFM) signal that provides multiplexing based on its good property, high-temporal correlation. Owing to the multiplexing ability of the HFM signal, the anchor nodes can transmit packets without MAC delay, i.e., simultaneous transmission is possible. In addition, the simulation results show that the simultaneous transmission is not an optional communication scheme, but essential for the localization of mobile object in underwater.

  8. Experiments of Multi-Level Read-Only Recording Using Readout Signal Wave-Shape Modulation

    International Nuclear Information System (INIS)

    Yi, Tang; Jing, Pei; Long-Fa, Pan; Yi, Ni; Hua, Hu; Bu-Qing, Zhang

    2008-01-01

    An innovative multilevel read-only recording method is proposed. In this method, a short pit/land is deliberately inserted to the original land/pit. This modifies the wave-shape of readout signal. Taking the wave-shape as the symbol of level detection, a signal wave-shape modulation (SWSM) multilevel method is realized. This method is carried out and validated on the DVD read-only manufacture and readout system. A capacity of 15 GB can be expected, and a bit error rate of 10 −4 is achieved. The capacity can meet the demand of high definition movie publication. This method also provides a potential multi-level solution for other storage formats and systems. (fundamental areas of phenomenology (including applications))

  9. GABA signalling modulates plant growth by directly regulating the activity of plant-specific anion transporters.

    Science.gov (United States)

    Ramesh, Sunita A; Tyerman, Stephen D; Xu, Bo; Bose, Jayakumar; Kaur, Satwinder; Conn, Vanessa; Domingos, Patricia; Ullah, Sana; Wege, Stefanie; Shabala, Sergey; Feijó, José A; Ryan, Peter R; Gilliham, Matthew; Gillham, Matthew

    2015-07-29

    The non-protein amino acid, gamma-aminobutyric acid (GABA) rapidly accumulates in plant tissues in response to biotic and abiotic stress, and regulates plant growth. Until now it was not known whether GABA exerts its effects in plants through the regulation of carbon metabolism or via an unidentified signalling pathway. Here, we demonstrate that anion flux through plant aluminium-activated malate transporter (ALMT) proteins is activated by anions and negatively regulated by GABA. Site-directed mutagenesis of selected amino acids within ALMT proteins abolishes GABA efficacy but does not alter other transport properties. GABA modulation of ALMT activity results in altered root growth and altered root tolerance to alkaline pH, acid pH and aluminium ions. We propose that GABA exerts its multiple physiological effects in plants via ALMT, including the regulation of pollen tube and root growth, and that GABA can finally be considered a legitimate signalling molecule in both the plant and animal kingdoms.

  10. Communicative Signals Promote Object Recognition Memory and Modulate the Right Posterior STS.

    Science.gov (United States)

    Redcay, Elizabeth; Ludlum, Ruth S; Velnoskey, Kayla R; Kanwal, Simren

    2016-01-01

    Detection of communicative signals is thought to facilitate knowledge acquisition early in life, but less is known about the role these signals play in adult learning or about the brain systems supporting sensitivity to communicative intent. The current study examined how ostensive gaze cues and communicative actions affect adult recognition memory and modulate neural activity as measured by fMRI. For both the behavioral and fMRI experiments, participants viewed a series of videos of an actress acting on one of two objects in front of her. Communicative context in the videos was manipulated in a 2 × 2 design in which the actress either had direct gaze (Gaze) or wore a visor (NoGaze) and either pointed at (Point) or reached for (Reach) one of the objects (target) in front of her. Participants then completed a recognition memory task with old (target and nontarget) objects and novel objects. Recognition memory for target objects in the Gaze conditions was greater than NoGaze, but no effects of gesture type were seen. Similarly, the fMRI video-viewing task revealed a significant effect of Gaze within right posterior STS (pSTS), but no significant effects of Gesture. Furthermore, pSTS sensitivity to Gaze conditions was related to greater memory for objects viewed in Gaze, as compared with NoGaze, conditions. Taken together, these results demonstrate that the ostensive, communicative signal of direct gaze preceding an object-directed action enhances recognition memory for attended items and modulates the pSTS response to object-directed actions. Thus, establishment of a communicative context through ostensive signals remains an important component of learning and memory into adulthood, and the pSTS may play a role in facilitating this type of social learning.

  11. External and internal limitations in amplitude-modulation processing

    DEFF Research Database (Denmark)

    Ewert, Stephan; Dau, Torsten

    2004-01-01

    Three experiments are presented to explore the relative role of "external" signal variability and "internal" resolution limitations of the auditory system in the detection and discrimination of amplitude modulations (AM). In the first experiment, AM-depth discrimination performance was determined......-filterbank models. The predictions revealed that AM-depth discrimination and AM detection are limited by a combination of the external signal variability and an internal "Weber-fraction" noise process....

  12. A cyclic GMP signalling module that regulates gliding motility in a malaria parasite.

    Directory of Open Access Journals (Sweden)

    Robert W Moon

    2009-09-01

    Full Text Available The ookinete is a motile stage in the malaria life cycle which forms in the mosquito blood meal from the zygote. Ookinetes use an acto-myosin motor to glide towards and penetrate the midgut wall to establish infection in the vector. The regulation of gliding motility is poorly understood. Through genetic interaction studies we here describe a signalling module that identifies guanosine 3', 5'-cyclic monophosphate (cGMP as an important second messenger regulating ookinete differentiation and motility. In ookinetes lacking the cyclic nucleotide degrading phosphodiesterase delta (PDEdelta, unregulated signalling through cGMP results in rounding up of the normally banana-shaped cells. This phenotype is suppressed in a double mutant additionally lacking guanylyl cyclase beta (GCbeta, showing that in ookinetes GCbeta is an important source for cGMP, and that PDEdelta is the relevant cGMP degrading enzyme. Inhibition of the cGMP-dependent protein kinase, PKG, blocks gliding, whereas enhanced signalling through cGMP restores normal gliding speed in a mutant lacking calcium dependent protein kinase 3, suggesting at least a partial overlap between calcium and cGMP dependent pathways. These data demonstrate an important function for signalling through cGMP, and most likely PKG, in dynamically regulating ookinete gliding during the transmission of malaria to the mosquito.

  13. Reliability-Weighted Integration of Audiovisual Signals Can Be Modulated by Top-down Attention

    Science.gov (United States)

    Noppeney, Uta

    2018-01-01

    Abstract Behaviorally, it is well established that human observers integrate signals near-optimally weighted in proportion to their reliabilities as predicted by maximum likelihood estimation. Yet, despite abundant behavioral evidence, it is unclear how the human brain accomplishes this feat. In a spatial ventriloquist paradigm, participants were presented with auditory, visual, and audiovisual signals and reported the location of the auditory or the visual signal. Combining psychophysics, multivariate functional MRI (fMRI) decoding, and models of maximum likelihood estimation (MLE), we characterized the computational operations underlying audiovisual integration at distinct cortical levels. We estimated observers’ behavioral weights by fitting psychometric functions to participants’ localization responses. Likewise, we estimated the neural weights by fitting neurometric functions to spatial locations decoded from regional fMRI activation patterns. Our results demonstrate that low-level auditory and visual areas encode predominantly the spatial location of the signal component of a region’s preferred auditory (or visual) modality. By contrast, intraparietal sulcus forms spatial representations by integrating auditory and visual signals weighted by their reliabilities. Critically, the neural and behavioral weights and the variance of the spatial representations depended not only on the sensory reliabilities as predicted by the MLE model but also on participants’ modality-specific attention and report (i.e., visual vs. auditory). These results suggest that audiovisual integration is not exclusively determined by bottom-up sensory reliabilities. Instead, modality-specific attention and report can flexibly modulate how intraparietal sulcus integrates sensory signals into spatial representations to guide behavioral responses (e.g., localization and orienting). PMID:29527567

  14. Nicotinic modulation of hippocampal cell signaling and associated effects on learning and memory.

    Science.gov (United States)

    Kutlu, Munir Gunes; Gould, Thomas J

    2016-03-01

    The hippocampus is a key brain structure involved in synaptic plasticity associated with long-term declarative memory formation. Importantly, nicotine and activation of nicotinic acetylcholine receptors (nAChRs) can alter hippocampal plasticity and these changes may occur through modulation of hippocampal kinases and transcription factors. Hippocampal kinases such as cAMP-dependent protein kinase (PKA), calcium/calmodulin-dependent protein kinases (CAMKs), extracellular signal-regulated kinases 1 and 2 (ERK1/2), and c-jun N-terminal kinase 1 (JNK1), and the transcription factor cAMP-response element-binding protein (CREB) that are activated either directly or indirectly by nicotine may modulate hippocampal plasticity and in parallel hippocampus-dependent learning and memory. Evidence suggests that nicotine may alter hippocampus-dependent learning by changing the time and magnitude of activation of kinases and transcription factors normally involved in learning and by recruiting additional cell signaling molecules. Understanding how nicotine alters learning and memory will advance basic understanding of the neural substrates of learning and aid in understanding mental disorders that involve cognitive and learning deficits. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. General Time-Division AltBOC Modulation Technique for GNSS Signals

    Directory of Open Access Journals (Sweden)

    Z. Zhou

    2018-04-01

    Full Text Available In this paper, a general time-division alternate binary offset carrier (GTD-AltBOC modulation method is proposed, which is an extension of TD-AltBOC and time-multiplexed offset-carrier quadrature phase shift keying (TMOC-QPSK with high design flexibility. In this method, binary complex subcarriers and a time-division technique with flexible time slot assignment are used to achieve constant envelope modulation of the signal components with a variable power allocation ratio (PAR. The underlying principle of GTD-AltBOC and the constraints related to the PAR are investigated. For the generation of GTD-AltBOC signals, a lookup table (LUT-based scheme is presented; the minimum required clock rate is half or less of that for existing non-time-division methods. The receiver processing complexities are analyzed for three typical receiving modes, and the power spectral densities (PSDs, cross-correlation functions, multiplexing efficiencies and code-tracking performance are simulated; the results show that GTD-AltBOC enables a significant decrease in receiving complexity compared with existing methods while maintaining high performance in terms of multiplexing efficiency and code tracking.

  16. Effects of ionizing radiation on purinergic signaling modulation in rat brain nerve cells

    International Nuclear Information System (INIS)

    Stanojevic, I.; Milosevic, M.; Drakulic, D.; Horvat, A.; Stanojevic, I.)

    2007-01-01

    Purinergic signaling is composed of three modulatory components: a) source of extracellular nucleotides, b) specific receptor expression for these transmitter molecules and c) ectonucleotidase selection that dictate cell response gradually degradation extracellular nucleotides to nucleosides. ATP acts as a fast excitatory transmitter in the CNS. Postsynaptic actions of ATP are mediated by an extended family of purinergic, P2X receptors, widely expressed throughout the CNS. NTPDases hydrolyse extracellular ATP and ADP to AMP and are responsive for purinergfic termination. To investigate if ionizing irradiation could modulate CNS purinergic signalization we monitored activity of NTPDases and abundance of P2X7 receptor in synaptic plasma membranes after whole-body acute irradiation using low (0,5Gy) or therapeutic (2Gy) doses, 1h i 72h after irradiating juvenile (15-day old) and adult (90-day old) rats. Acute irradiation modulate purinergic system components investigated at the different ways in the rat development brain SPM and in the adult brain dependent of dose and time after irradiation [sr

  17. TRPV1 and Endocannabinoids: Emerging Molecular Signals that Modulate Mammalian Vision

    Directory of Open Access Journals (Sweden)

    Daniel A. Ryskamp

    2014-09-01

    Full Text Available Transient Receptor Potential Vanilloid 1 (TRPV1 subunits form a polymodal cation channel responsive to capsaicin, heat, acidity and endogenous metabolites of polyunsaturated fatty acids. While originally reported to serve as a pain and heat detector in the peripheral nervous system, TRPV1 has been implicated in the modulation of blood flow and osmoregulation but also neurotransmission, postsynaptic neuronal excitability and synaptic plasticity within the central nervous system. In addition to its central role in nociception, evidence is accumulating that TRPV1 contributes to stimulus transduction and/or processing in other sensory modalities, including thermosensation, mechanotransduction and vision. For example, TRPV1, in conjunction with intrinsic cannabinoid signaling, might contribute to retinal ganglion cell (RGC axonal transport and excitability, cytokine release from microglial cells and regulation of retinal vasculature. While excessive TRPV1 activity was proposed to induce RGC excitotoxicity, physiological TRPV1 activity might serve a neuroprotective function within the complex context of retinal endocannabinoid signaling. In this review we evaluate the current evidence for localization and function of TRPV1 channels within the mammalian retina and explore the potential interaction of this intriguing nociceptor with endogenous agonists and modulators.

  18. Algorithm for the classification of multi-modulating signals on the electrocardiogram.

    Science.gov (United States)

    Mita, Mitsuo

    2007-03-01

    This article discusses the algorithm to measure electrocardiogram (ECG) and respiration simultaneously and to have the diagnostic potentiality for sleep apnoea from ECG recordings. The algorithm is composed by the combination with the three particular scale transform of a(j)(t), u(j)(t), o(j)(a(j)) and the statistical Fourier transform (SFT). Time and magnitude scale transforms of a(j)(t), u(j)(t) change the source into the periodic signal and tau(j) = o(j)(a(j)) confines its harmonics into a few instantaneous components at tau(j) being a common instant on two scales between t and tau(j). As a result, the multi-modulating source is decomposed by the SFT and is reconstructed into ECG, respiration and the other signals by inverse transform. The algorithm is expected to get the partial ventilation and the heart rate variability from scale transforms among a(j)(t), a(j+1)(t) and u(j+1)(t) joining with each modulation. The algorithm has a high potentiality of the clinical checkup for the diagnosis of sleep apnoea from ECG recordings.

  19. Effect of realistic astrophysical inputs on the phase and shape of the weakly interacting massive particles annual modulation signal

    International Nuclear Information System (INIS)

    Green, Anne M.

    2003-01-01

    The orbit of the Earth about the Sun produces an annual modulation in the weakly interacting massive particles (WIMP) direct detection rate. If the local WIMP velocity distribution is isotropic then the modulation is roughly sinusoidal with maximum in June; however, if the velocity distribution is anisotropic the phase and shape of the signal can change. Motivated by conflicting claims about the effect of uncertainties in the local velocity distribution on the interpretation of the DAMA annual modulation signal (and the possibility that the form of the modulation could be used to probe the structure of the Milky Way halo), we study the dependence of the annual modulation on various astrophysical inputs. We first examine the approximations used for the Earth's motion about the Sun and the Sun's velocity with respect to the Galactic rest frame. We find that overly simplistic assumptions lead to errors of up to ten days in the phase and up to tens of percent in the shape of the signal, even if the velocity distribution is isotropic. Crucially, if the components of the Earth's velocity perpendicular to the motion of the Sun are neglected, then the change in the phase which occurs for anisotropic velocity distributions is missed. We then examine how the annual modulation signal varies for physically and observationally well-motivated velocity distributions. We find that the phase of the signal changes by up to 20 days and the mean value and amplitude change by up to tens of percent

  20. An optimized cosine-modulated nonuniform filter bank design for subband coding of ECG signal

    Directory of Open Access Journals (Sweden)

    A. Kumar

    2015-07-01

    Full Text Available A simple iterative technique for the design of nonuniform cosine modulated filter banks (CMFBS is presented in this paper. The proposed technique employs a single parameter for optimization. The nonuniform cosine modulated filter banks are derived by merging the adjacent filters of uniform cosine modulated filter banks. The prototype filter is designed with the aid of different adjustable window functions such as Kaiser, Cosh and Exponential, and by using the constrained equiripple finite impulse response (FIR digital filter design technique. In this method, either cut off frequency or passband edge frequency is varied in order to adjust the filter coefficients so that reconstruction error could be optimized/minimized to zero. Performance and effectiveness of the proposed method in terms of peak reconstruction error (PRE, aliasing distortion (AD, computational (CPU time, and number of iteration (NOI have been shown through the numerical examples and comparative studies. Finally, the technique is exploited for the subband coding of electrocardiogram (ECG and speech signals.

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

    Directory of Open Access Journals (Sweden)

    Nadiatul Akmal Mohd-Radzman

    2013-10-01

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

  2. The SDF-1–CXCR4 signaling pathway: a molecular hub modulating neo-angiogenesis

    Science.gov (United States)

    Petit, Isabelle; Jin, David; Rafii, Shahin

    2010-01-01

    Pro-angiogenic bone marrow (BM) cells include subsets of hematopoietic cells that provide vascular support and endothelial progenitor cells (EPCs), which under certain permissive conditions could differentiate into functional vascular cells. Recent evidence demonstrates that the chemokine stromal-cell derived factor-1 (SDF-1, also known as CXCL12) has a major role in the recruitment and retention of CXCR4+ BM cells to the neo-angiogenic niches supporting revascularization of ischemic tissue and tumor growth. However, the precise mechanism by which activation of CXCR4 modulates neo-angiogenesis is not clear. SDF-1 not only promotes revascularization by engaging with CXCR4 expressed on the vascular cells but also supports mobilization of pro-angiogenic CXCR4+VEGFR1+ hematopoietic cells, thereby accelerating revascularization of ischemic organs. Here, we attempt to define the multiple functions of the SDF-1–CXCR4 signaling pathway in the regulation of neo-vascularization during acute ischemia and tumor growth. In particular, we introduce the concept that, by modulating plasma SDF-1 levels, the CXCR4 antagonist AMD3100 acutely promotes, while chronic AMD3100 treatment inhibits, mobilization of pro-angiogenic cells. We will also discuss strategies to modulate the mobilization of essential subsets of BM cells that participate in neo-angiogenesis, setting up the stage for enhancing revascularization or targeting tumor vessels by exploiting CXCR4 agonists and antagonists, respectively. PMID:17560169

  3. Physiological modules for generating discrete and rhythmic movements: component analysis of EMG signals.

    Science.gov (United States)

    Bengoetxea, Ana; Leurs, Françoise; Hoellinger, Thomas; Cebolla, Ana Maria; Dan, Bernard; Cheron, Guy; McIntyre, Joseph

    2014-01-01

    A central question in Neuroscience is that of how the nervous system generates the spatiotemporal commands needed to realize complex gestures, such as handwriting. A key postulate is that the central nervous system (CNS) builds up complex movements from a set of simpler motor primitives or control modules. In this study we examined the control modules underlying the generation of muscle activations when performing different types of movement: discrete, point-to-point movements in eight different directions and continuous figure-eight movements in both the normal, upright orientation and rotated 90°. To test for the effects of biomechanical constraints, movements were performed in the frontal-parallel or sagittal planes, corresponding to two different nominal flexion/abduction postures of the shoulder. In all cases we measured limb kinematics and surface electromyographic activity (EMG) signals for seven different muscles acting around the shoulder. We first performed principal component analysis (PCA) of the EMG signals on a movement-by-movement basis. We found a surprisingly consistent pattern of muscle groupings across movement types and movement planes, although we could detect systematic differences between the PCs derived from movements performed in each shoulder posture and between the principal components associated with the different orientations of the figure. Unexpectedly we found no systematic differences between the figure eights and the point-to-point movements. The first three principal components could be associated with a general co-contraction of all seven muscles plus two patterns of reciprocal activation. From these results, we surmise that both "discrete-rhythmic movements" such as the figure eight, and discrete point-to-point movement may be constructed from three different fundamental modules, one regulating the impedance of the limb over the time span of the movement and two others operating to generate movement, one aligned with the

  4. Designed modulation of sex steroid signaling inhibits telomerase activity and proliferation of human prostate cancer cells

    International Nuclear Information System (INIS)

    Verma, Vikas; Sharma, Vikas; Singh, Vishal; Sharma, Siddharth; Bishnoi, Ajay Kumar; Chandra, Vishal; Maikhuri, J.P.; Dwivedi, Anila; Kumar, Atul; Gupta, Gopal

    2014-01-01

    The predominant estrogen-receptor (ER)-β signaling in normal prostate is countered by increased ER-α signaling in prostate cancer (CaP), which in association with androgen-receptor (AR) signaling results in pathogenesis of the disease. However CaP treatments mostly target AR signaling which is initially effective but eventually leads to androgen resistance, hence simultaneous targeting of ERs has been proposed. A novel series of molecules were designed with multiple sex-steroid receptor modulating capabilities by coalescing the pharmacophores of known anti-CaP molecules that act via modulation of ER(α/β) and/or AR, viz. 3,3′diindolylmethane (DIM), mifepristone, toremifene, tamoxifen and raloxifene. N,N-diethyl-4-((2-(4-methoxyphenyl)-1H-indol-3-yl)methyl) aniline (DIMA) was identified as the most promising structure of this new series. DIMA increased annexin-V labelling, cell-cycle arrest and caspase-3 activity, and decreased expression of AR and prostate specific antigen in LNCaP cells, in vitro. Concurrently, DIMA increased ER-β, p21 and p27 protein levels in LNCaP cells and exhibited ∼ 5 times more selective binding for ER-β than ER-α, in comparison to raloxifene. DIMA exhibited a dose-dependent ER-β agonism and ER-α antagonism in classical gene reporter assay and decreased hTERT (catalytic subunit of telomerase) transcript levels in LNCaP at 3.0 μM (P < 0.05). DIMA also dose-dependently decreased telomerase enzyme activity in prostate cancer cells. It is thus concluded that DIMA acts as a multi-steroid receptor modulator and effectively inhibits proliferation of prostate cancer cells through ER-β mediated telomerase inhibition, by countering actions of ER-α and AR. Its unique molecular design can serve as a lead structure for generation of potent agents against endocrine malignancies like the CaP

  5. Designed modulation of sex steroid signaling inhibits telomerase activity and proliferation of human prostate cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Verma, Vikas; Sharma, Vikas; Singh, Vishal [Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow 226 031 (India); Sharma, Siddharth; Bishnoi, Ajay Kumar [Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226 031 (India); Chandra, Vishal; Maikhuri, J.P.; Dwivedi, Anila [Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow 226 031 (India); Kumar, Atul [Division of Medicinal and Process Chemistry, CSIR-Central Drug Research Institute, Lucknow 226 031 (India); Gupta, Gopal, E-mail: g_gupta@cdri.res.in [Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow 226 031 (India)

    2014-10-15

    The predominant estrogen-receptor (ER)-β signaling in normal prostate is countered by increased ER-α signaling in prostate cancer (CaP), which in association with androgen-receptor (AR) signaling results in pathogenesis of the disease. However CaP treatments mostly target AR signaling which is initially effective but eventually leads to androgen resistance, hence simultaneous targeting of ERs has been proposed. A novel series of molecules were designed with multiple sex-steroid receptor modulating capabilities by coalescing the pharmacophores of known anti-CaP molecules that act via modulation of ER(α/β) and/or AR, viz. 3,3′diindolylmethane (DIM), mifepristone, toremifene, tamoxifen and raloxifene. N,N-diethyl-4-((2-(4-methoxyphenyl)-1H-indol-3-yl)methyl) aniline (DIMA) was identified as the most promising structure of this new series. DIMA increased annexin-V labelling, cell-cycle arrest and caspase-3 activity, and decreased expression of AR and prostate specific antigen in LNCaP cells, in vitro. Concurrently, DIMA increased ER-β, p21 and p27 protein levels in LNCaP cells and exhibited ∼ 5 times more selective binding for ER-β than ER-α, in comparison to raloxifene. DIMA exhibited a dose-dependent ER-β agonism and ER-α antagonism in classical gene reporter assay and decreased hTERT (catalytic subunit of telomerase) transcript levels in LNCaP at 3.0 μM (P < 0.05). DIMA also dose-dependently decreased telomerase enzyme activity in prostate cancer cells. It is thus concluded that DIMA acts as a multi-steroid receptor modulator and effectively inhibits proliferation of prostate cancer cells through ER-β mediated telomerase inhibition, by countering actions of ER-α and AR. Its unique molecular design can serve as a lead structure for generation of potent agents against endocrine malignancies like the CaP.

  6. Neuronal discrimination capacity

    International Nuclear Information System (INIS)

    Deng Yingchun; Williams, Peter; Feng Jianfeng; Liu Feng

    2003-01-01

    We explore neuronal mechanisms of discriminating between masked signals. It is found that when the correlation between input signals is zero, the output signals are separable if and only if input signals are separable. With positively (negatively) correlated signals, the output signals are separable (mixed) even when input signals are mixed (separable). Exact values of discrimination capacity are obtained for two most interesting cases: the exactly balanced inhibitory and excitatory input case and the uncorrelated input case. Interestingly, the discrimination capacity obtained in these cases is independent of model parameters, input distribution and is universal. Our results also suggest a functional role of inhibitory inputs and correlated inputs or, more generally, the large variability of efferent spike trains observed in in vivo experiments: the larger the variability of efferent spike trains, the easier it is to discriminate between masked input signals

  7. Neuronal discrimination capacity

    Energy Technology Data Exchange (ETDEWEB)

    Deng Yingchun [Department of Mathematics, Hunan Normal University 410081, Changsha (China); COGS, University of Sussex at Brighton, BN1 9QH (United Kingdom); Williams, Peter; Feng Jianfeng [COGS, University of Sussex at Brighton, BN1 9QH (United Kingdom); Liu Feng [COGS, University of Sussex at Brighton, BN1 9QH (United Kingdom); Physics Department, Nanjing University (China)

    2003-12-19

    We explore neuronal mechanisms of discriminating between masked signals. It is found that when the correlation between input signals is zero, the output signals are separable if and only if input signals are separable. With positively (negatively) correlated signals, the output signals are separable (mixed) even when input signals are mixed (separable). Exact values of discrimination capacity are obtained for two most interesting cases: the exactly balanced inhibitory and excitatory input case and the uncorrelated input case. Interestingly, the discrimination capacity obtained in these cases is independent of model parameters, input distribution and is universal. Our results also suggest a functional role of inhibitory inputs and correlated inputs or, more generally, the large variability of efferent spike trains observed in in vivo experiments: the larger the variability of efferent spike trains, the easier it is to discriminate between masked input signals.

  8. Modulation of phytochrome signaling networks for improved biomass accumulation using a bioenergy crop model

    Energy Technology Data Exchange (ETDEWEB)

    Mockler, Todd C. [Donald Danforth Plant Science Center, Saint Louis, MO (United States)

    2016-11-07

    Plant growth and development, including stem elongation, flowering time, and shade-avoidance habits, are affected by wavelength composition (i.e., light quality) of the light environment. the molecular mechanisms underlying light perception and signaling pathways in plants have been best characterized in Arabidopsis thaliana where dozens of genes have been implicated in converging, complementary, and antagonistic pathways communicating light quality cues perceived by the phytochrome (red/far-red) cryptochrome (blue) and phototropin (blue) photorecptors. Light perception and signaling have been studied in grasses, including rice and sorghum but in much less detail than in Arabidopsis. During the course of the Mocker lab's DOE-funded wrok generating a gene expression atlas in Brachypodium distachyon we observed that Brachypodium plants grown in continuous monochromatic red light or continuous white light enriched in far-red light accumulated significantly more biomass and exhibited significantly greater seed yield than plants grown in monochromatic blue light or white light. This phenomenon was also observed in two other grasses, switchgrass and rice. We will systematically manipulate the expression of genes predicted to function in Brachypodium phytochrome signaling and assess the phenotypic consequences in transgenic Brachypodium plants in terms of morphology, stature, biomass accumulation, and cell wall composition. We will also interrogate direct interactions between candidate phytochrome signaling transcription factors and target promoters using a high-throughput yeast one-hybrid system. Brachypodium distachyon has emerged as a model grass species and is closely related to candidate feedstock crops for bioethanol production. Identification of genes capable of modifying growth characteristics of Brachypodium, when misexpressed, in particular increasing biomass accumulation, by modulating photoreceptor signaling will provide valuable candidates for

  9. C. elegans serine-threonine kinase KIN-29 modulates TGFβ signaling and regulates body size formation

    Directory of Open Access Journals (Sweden)

    Cohen Stephen

    2005-04-01

    Full Text Available Background In C. elegans there are two well-defined TGFβ-like signaling pathways. The Sma/Mab pathway affects body size morphogenesis, male tail development and spicule formation while the Daf pathway regulates entry into and exit out of the dauer state. To identify additional factors that modulate TGFβ signaling in the Sma/Mab pathway, we have undertaken a genetic screen for small animals and have identified kin-29. Results kin-29 encodes a protein with a cytoplasmic serine-threonine kinase and a novel C-terminal domain. The kinase domain is a distantly related member of the EMK (ELKL motif kinase family, which interacts with microtubules. We show that the serine-threonine kinase domain has in vitro activity. kin-29 mutations result in small animals, but do not affect male tail morphology as do several of the Sma/Mab signal transducers. Adult worms are smaller than the wild-type, but also develop more slowly. Rescue by kin-29 is achieved by expression in neurons or in the hypodermis. Interaction with the dauer pathway is observed in double mutant combinations, which have been seen with Sma/Mab pathway mutants. We show that kin-29 is epistatic to the ligand dbl-1, and lies upstream of the Sma/Mab pathway target gene, lon-1. Conclusion kin-29 is a new modulator of the Sma/Mab pathway. It functions in neurons and in the hypodermis to regulate body size, but does not affect all TGFβ outputs, such as tail morphogenesis.

  10. Signaling pathway underlying the octopaminergic modulation of myogenic contraction in the cricket lateral oviduct.

    Science.gov (United States)

    Tamashiro, Hirotake; Yoshino, Masami

    2014-12-01

    Octopamine (OA), a biogenic monoamine, is a neurotransmitter and neuromodulator in invertebrates. Here, we report the effect of OA on the spontaneous rhythmic contractions (SRCs) of the lateral oviduct of the cricket Gryllus bimaculatus and the possible signaling pathway involved. Application of OA increased both the frequency and amplitude of SRCs in a dose-dependent manner. The effect of OA was inhibited by subsequent application of the OA receptor antagonist epinastine, indicating that the action of OA is mediated by OA receptor. To investigate the predominant signaling pathway underlying the action of OA, we first examined a possible involvement of the cAMP/cAMP-dependent protein kinase A (PKA) signaling pathway. Application of the membrane-permeable cAMP analog 8-Br-cAMP had little effect on SRCs and the effect of OA was not influenced by subsequent application of the PKA inhibitor H89, indicating that the cAMP/PKA signaling pathway is not the predominant pathway in the action of OA. Next, we examined a possible involvement of the second messenger inositol 1,4,5-trisphosphate in the action of OA. The effect of OA on SRCs was inhibited by subsequent application of the phosphoinositide-specific phospholipase C (PLC) inhibitor U73122, indicating that the PLC pathway is involved in the action of OA. The OA-induced increase in the frequency of SRCs was inhibited by pretreatment of the cell with the ryanodine receptor antagonist tetracaine but was not significantly affected by the IP3 receptor antagonist 2-aminoethoxydiphenyl borate (2-APB). On the other hand, the OA-induced increase in the amplitude of SRCs was inhibited by pretreatment of the cells with 2-APB but was not significantly affected by tetracaine. Taken together, these results suggest that the OA-induced excitatory effect on SRCs is mediated by the PLC signaling pathway: Ca2+ release from IP3 receptors may contribute to the modulation of the amplitude of SRCs, whereas Ca2+ release from ryanodine

  11. Status of sensor qualification for the PS module with on-chip $p_T$ discrimination for the CMS tracker phase 2 upgrade

    CERN Document Server

    AUTHOR|(CDS)2095782

    2016-01-01

    The high luminosity upgrade of the LHC is targeted to deliver 3000 fb$^{-1}$ at a luminosity of $5\\times10^{34}$cm$^{-2}$s$^{-1}$. Higher granularity, 140 collisions per bunch crossing and existing bandwidth limitations require a reduction of the amount of data at module level. New modules have binary readout, on-chip $p_{\\mathrm{ T}}$ discrimination and capabilities to provide track finding data at 40 MHz to the L1-trigger. The CMS collaboration has undertaken R&D effort to develop new planar sensors for the pixel-strip (PS) module, which has to withstand $1\\times10^{15}$ cm$^{-2}$ 1 MeV neutron equivalent fluence in the innermost layer of the tracker. The module is composed of a strip sensor and a macro pixel sensor with 100$\\mu$m $\\times$ 1.5 mm pixel size. Sensors were characterized in the laboratory and the effects of different process parameters and sensor concepts were studied. This contribution presents a new sensor prototype with n-pixels in p-bulk material in planar technology for the PS module...

  12. SH2 Domains Serve as Lipid-Binding Modules for pTyr-Signaling Proteins.

    Science.gov (United States)

    Park, Mi-Jeong; Sheng, Ren; Silkov, Antonina; Jung, Da-Jung; Wang, Zhi-Gang; Xin, Yao; Kim, Hyunjin; Thiagarajan-Rosenkranz, Pallavi; Song, Seohyeon; Yoon, Youngdae; Nam, Wonhee; Kim, Ilshin; Kim, Eui; Lee, Dong-Gyu; Chen, Yong; Singaram, Indira; Wang, Li; Jang, Myoung Ho; Hwang, Cheol-Sang; Honig, Barry; Ryu, Sungho; Lorieau, Justin; Kim, You-Me; Cho, Wonhwa

    2016-04-07

    The Src-homology 2 (SH2) domain is a protein interaction domain that directs myriad phosphotyrosine (pY)-signaling pathways. Genome-wide screening of human SH2 domains reveals that ∼90% of SH2 domains bind plasma membrane lipids and many have high phosphoinositide specificity. They bind lipids using surface cationic patches separate from pY-binding pockets, thus binding lipids and the pY motif independently. The patches form grooves for specific lipid headgroup recognition or flat surfaces for non-specific membrane binding and both types of interaction are important for cellular function and regulation of SH2 domain-containing proteins. Cellular studies with ZAP70 showed that multiple lipids bind its C-terminal SH2 domain in a spatiotemporally specific manner and thereby exert exquisite spatiotemporal control over its protein binding and signaling activities in T cells. Collectively, this study reveals how lipids control SH2 domain-mediated cellular protein-protein interaction networks and suggest a new strategy for therapeutic modulation of pY-signaling pathways. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Raf kinase inhibitory protein: a signal transduction modulator and metastasis suppressor.

    Science.gov (United States)

    Granovsky, Alexey E; Rosner, Marsha Rich

    2008-04-01

    Cells have a multitude of controls to maintain their integrity and prevent random switching from one biological state to another. Raf Kinase Inhibitory Protein (RKIP), a member of the phosphatidylethanolamine binding protein (PEBP) family, is representative of a new class of modulators of signaling cascades that function to maintain the "yin yang" or balance of biological systems. RKIP inhibits MAP kinase (Raf-MEK-ERK), G protein-coupled receptor (GPCR) kinase and NFkappaB signaling cascades. Because RKIP targets different kinases dependent upon its state of phosphorylation, RKIP also acts to integrate crosstalk initiated by multiple environmental stimuli. Loss or depletion of RKIP results in disruption of the normal cellular stasis and can lead to chromosomal abnormalities and disease states such as cancer. Since RKIP and the PEBP family have been reviewed previously, the goal of this analysis is to provide an update and highlight some of the unique features of RKIP that make it a critical player in the regulation of cellular signaling processes.

  14. AtWRKY22 promotes susceptibility to aphids and modulates salicylic acid and jasmonic acid signalling.

    Science.gov (United States)

    Kloth, Karen J; Wiegers, Gerrie L; Busscher-Lange, Jacqueline; van Haarst, Jan C; Kruijer, Willem; Bouwmeester, Harro J; Dicke, Marcel; Jongsma, Maarten A

    2016-05-01

    Aphids induce many transcriptional perturbations in their host plants, but the signalling cascades responsible and the effects on plant resistance are largely unknown. Through a genome-wide association (GWA) mapping study in Arabidopsis thaliana, we identified WRKY22 as a candidate gene associated with feeding behaviour of the green peach aphid, Myzus persicae The transcription factor WRKY22 is known to be involved in pathogen-triggered immunity, and WRKY22 gene expression has been shown to be induced by aphids. Assessment of aphid population development and feeding behaviour on knockout mutants and overexpression lines showed that WRKY22 increases susceptibility to M. persicae via a mesophyll-located mechanism. mRNA sequencing analysis of aphid-infested wrky22 knockout plants revealed the up-regulation of genes involved in salicylic acid (SA) signalling and down-regulation of genes involved in plant growth and cell-wall loosening. In addition, mechanostimulation of knockout plants by clip cages up-regulated jasmonic acid (JA)-responsive genes, resulting in substantial negative JA-SA crosstalk. Based on this and previous studies, WRKY22 is considered to modulate the interplay between the SA and JA pathways in response to a wide range of biotic and abiotic stimuli. Its induction by aphids and its role in suppressing SA and JA signalling make WRKY22 a potential target for aphids to manipulate host plant defences. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  15. Disintegrins: integrin selective ligands which activate integrin-coupled signaling and modulate leukocyte functions

    Directory of Open Access Journals (Sweden)

    Barja-Fidalgo C.

    2005-01-01

    Full Text Available Extracellular matrix proteins and cell adhesion receptors (integrins play essential roles in the regulation of cell adhesion and migration. Interactions of integrins with the extracellular matrix proteins lead to phosphorylation of several intracellular proteins such as focal adhesion kinase, activating different signaling pathways responsible for the regulation of a variety of cell functions, including cytoskeleton mobilization. Once leukocytes are guided to sites of infection, inflammation, or antigen presentation, integrins can participate in the initiation, maintenance, or termination of the immune and inflammatory responses. The modulation of neutrophil activation through integrin-mediated pathways is important in the homeostatic control of the resolution of inflammatory states. In addition, during recirculation, T lymphocyte movement through distinct microenvironments is mediated by integrins, which are critical for cell cycle, differentiation and gene expression. Disintegrins are a family of low-molecular weight, cysteine-rich peptides first identified in snake venom, usually containing an RGD (Arg-Gly-Asp motif, which confers the ability to selectively bind to integrins, inhibiting integrin-related functions in different cell systems. In this review we show that, depending on the cell type and the microenvironment, disintegrins are able to antagonize the effects of integrins or to act agonistically by activating integrin-mediated signaling. Disintegrins have proven useful as tools to improve the understanding of the molecular events regulated by integrin signaling in leukocytes and prototypes in order to design therapies able to interfere with integrin-mediated effects.

  16. Genetic Disruption of 2-Arachidonoylglycerol Synthesis Reveals a Key Role for Endocannabinoid Signaling in Anxiety Modulation

    Directory of Open Access Journals (Sweden)

    Brian C. Shonesy

    2014-12-01

    Full Text Available Summary: Endocannabinoid (eCB signaling has been heavily implicated in the modulation of anxiety and depressive behaviors and emotional learning. However, the role of the most-abundant endocannabinoid 2-arachidonoylglycerol (2-AG in the physiological regulation of affective behaviors is not well understood. Here, we show that genetic deletion of the 2-AG synthetic enzyme diacylglycerol lipase α (DAGLα in mice reduces brain, but not circulating, 2-AG levels. DAGLα deletion also results in anxiety-like and sex-specific anhedonic phenotypes associated with impaired activity-dependent eCB retrograde signaling at amygdala glutamatergic synapses. Importantly, acute pharmacological normalization of 2-AG levels reverses both phenotypes of DAGLα-deficient mice. These data suggest 2-AG deficiency could contribute to the pathogenesis of affective disorders and that pharmacological normalization of 2-AG signaling could represent an approach for the treatment of mood and anxiety disorders. : The role of the primary endogenous cannabinoid 2-AG in mood and anxiety regulation is not well understood. Shonesy et al. show that deletion of a primary 2-AG synthetic enzyme, DAGLα, results in anxiety and sex-specific depressive phenotypes, which can be rapidly reversed by pharmacological normalization of endocannabinoid levels.

  17. PKB/Akt modulates TGF-beta signalling through a direct interaction with Smad3.

    Science.gov (United States)

    Remy, Ingrid; Montmarquette, Annie; Michnick, Stephen W

    2004-04-01

    Transforming growth factor beta (TGF-beta) has a major role in cell proliferation, differentiation and apoptosis in many cell types. Integration of the TGF-beta pathway with other signalling cascades that control the same cellular processes may modulate TGF-beta responses. Here we report the discovery of a new functional link between TGF-beta and growth factor signalling pathways, mediated by a physical interaction between the serine-threonine kinase PKB (protein kinase B)/Akt and the transcriptional activator Smad3. Formation of the complex is induced by insulin, but inhibited by TGF-beta stimulation, placing PKB-Smad3 at a point of convergence between these two pathways. PKB inhibits Smad3 by preventing its phosphorylation, binding to Smad4 and nuclear translocation. In contrast, Smad3 does not inhibit PKB. Inhibition of Smad3 by PKB occurs through a kinase-activity-independent mechanism, resulting in a decrease in Smad3-mediated transcription and protection of cells against TGF-beta-induced apoptosis. Consistently, knockdown of the endogenous PKB gene with small-interfering RNA (siRNA) has the opposite effect. Our results suggest a very simple mechanism for the integration of signals arising from growth-factor- and TGF-beta-mediated pathways.

  18. Feature selection using angle modulated simulated Kalman filter for peak classification of EEG signals.

    Science.gov (United States)

    Adam, Asrul; Ibrahim, Zuwairie; Mokhtar, Norrima; Shapiai, Mohd Ibrahim; Mubin, Marizan; Saad, Ismail

    2016-01-01

    In the existing electroencephalogram (EEG) signals peak classification research, the existing models, such as Dumpala, Acir, Liu, and Dingle peak models, employ different set of features. However, all these models may not be able to offer good performance for various applications and it is found to be problem dependent. Therefore, the objective of this study is to combine all the associated features from the existing models before selecting the best combination of features. A new optimization algorithm, namely as angle modulated simulated Kalman filter (AMSKF) will be employed as feature selector. Also, the neural network random weight method is utilized in the proposed AMSKF technique as a classifier. In the conducted experiment, 11,781 samples of peak candidate are employed in this study for the validation purpose. The samples are collected from three different peak event-related EEG signals of 30 healthy subjects; (1) single eye blink, (2) double eye blink, and (3) eye movement signals. The experimental results have shown that the proposed AMSKF feature selector is able to find the best combination of features and performs at par with the existing related studies of epileptic EEG events classification.

  19. RITA, a novel modulator of Notch signalling, acts via nuclear export of RBP-J.

    Science.gov (United States)

    Wacker, Stephan Armin; Alvarado, Cristobal; von Wichert, Götz; Knippschild, Uwe; Wiedenmann, Jörg; Clauss, Karen; Nienhaus, Gerd Ulrich; Hameister, Horst; Baumann, Bernd; Borggrefe, Tilman; Knöchel, Walter; Oswald, Franz

    2011-01-05

    The evolutionarily conserved Notch signal transduction pathway regulates fundamental cellular processes during embryonic development and in the adult. Ligand binding induces presenilin-dependent cleavage of the receptor and a subsequent nuclear translocation of the Notch intracellular domain (NICD). In the nucleus, NICD binds to the recombination signal sequence-binding protein J (RBP-J)/CBF-1 transcription factor to induce expression of Notch target genes. Here, we report the identification and functional characterization of RBP-J interacting and tubulin associated (RITA) (C12ORF52) as a novel RBP-J/CBF-1-interacting protein. RITA is a highly conserved 36 kDa protein that, most interestingly, binds to tubulin in the cytoplasm and shuttles rapidly between cytoplasm and nucleus. This shuttling RITA exports RBP-J/CBF-1 from the nucleus. Functionally, we show that RITA can reverse a Notch-induced loss of primary neurogenesis in Xenopus laevis. Furthermore, RITA is able to downregulate Notch-mediated transcription. Thus, we propose that RITA acts as a negative modulator of the Notch signalling pathway, controlling the level of nuclear RBP-J/CBF-1, where its amounts are limiting.

  20. Bystander effects of ionizing radiation can be modulated by signaling amines

    International Nuclear Information System (INIS)

    Poon, R.C.C.; Agnihotri, N.; Seymour, C.; Mothersill, C.

    2007-01-01

    Actual risk and risk management of exposure to ionizing radiation are among the most controversial areas in environmental health protection. Recent developments in radiobiology especially characterization of bystander effects have called into question established dogmas and are thought to cast doubt on the scientific basis of the risk assessment framework, leading to uncertainty for regulators and concern among affected populations. In this paper we test the hypothesis that small signaling molecules widely used throughout the animal kingdom for signaling stress or environmental change, such as 5-Hydroxytryptamine (5-HT, serotonin), L-DOPA, glycine or nicotine are involved in bystander signaling processes following ionizing radiation exposure. We report data which suggest that nano to micromolar concentrations of these agents can modulate bystander-induced cell death. Depletion of 5-HT present in tissue culture medium, occurred following irradiation of cells. This suggested that 5-HT might be bound by membrane receptors after irradiation. Expression of 5-HT type 3 receptors which are Ca 2+ ion channels was confirmed in the cells using immunocytochemistry and receptor expression could be increased using radiation or 5-HT exposure. Zofran and Kitryl, inhibitors of 5-HT type 3 receptors, and reserpine a generic serotonin antagonist block the bystander effect induced by radiation or by serotonin. The results may be important for the mechanistic understanding of how low doses of radiation interact with cells to produce biological effects

  1. Acetylbritannilactone Modulates Vascular Endothelial Growth Factor Signaling and Regulates Angiogenesis in Endothelial Cells.

    Directory of Open Access Journals (Sweden)

    Jingshan Zhao

    Full Text Available The present study was conducted to determine the effects of 1-O-acetylbritannilactone (ABL, a compound extracted from Inula britannica L., on vascular endothelial growth factor (VEGF signaling and angiogenesis in endothelial cells (ECs. We showed that ABL promotes VEGF-induced cell proliferation, growth, migration, and tube formation in cultured human ECs. Furthermore, the modulatory effect of ABL on VEGF-induced Akt, MAPK p42/44, and p38 phosphorylation, as well as on upstream VEGFR-2 phosphorylation, were associated with VEGF-dependent Matrigel angiogenesis in vivo. In addition, animals treated with ABL (26 mg/kg/day recovered blood flow significantly earlier than control animals, suggesting that ABL affects ischemia-mediated angiogenesis and arteriogenesis in vivo. Finally, we demonstrated that ABL strongly reduced the levels of VEGFR-2 on the cell surface, enhanced VEGFR-2 endocytosis, which consistent with inhibited VE-cadherin, a negative regulator of VEGF signaling associated with VEGFR-2 complex formation, but did not alter VE-cadherin or VEGFR-2 expression in ECs. Our results suggest that ABL may serve as a novel therapeutic intervention for various cardiovascular diseases, including chronic ischemia, by regulating VEGF signaling and modulating angiogenesis.

  2. RNF11 is a multifunctional modulator of growth factor receptor signalling and transcriptional regulation.

    Science.gov (United States)

    Azmi, Peter; Seth, Arun

    2005-11-01

    Our laboratory has found that the 154aa RING finger protein 11 (RNF11), has modular domains and motifs including a RING-H2 finger domain, a PY motif, an ubiquitin interacting motif (UIM), a 14-3-3 binding sequence and an AKT phosphorylation site. RNF11 represents a unique protein with no other known immediate family members yet described. Comparative genetic analysis has shown that RNF11 is highly conserved throughout evolution. This may indicate a conserved and non-redundant role for the RNF11 protein. Molecular binding assays using RNF11 have shown that RNF11 has important roles in growth factor signalling, ubiquitination and transcriptional regulation. RNF11 has been shown to interact with HECT-type E3 ubiquitin ligases Nedd4, AIP4, Smurf1 and Smurf2, as well as with Cullin1, the core protein in the multi-subunit SCF E3 ubiquitin ligase complex. Work done in our laboratory has shown that RNF11 is capable of antagonizing Smurf2-mediated inhibition of TGFbeta signalling. Furthermore, RNF11 is capable of degrading AMSH, a positive regulator of both TGFbeta and EGFR signalling pathways. Recently, we have found that RNF11 can directly enhance TGFbeta signalling through a direct association with Smad4, the common signal transducer and transcription factor in the TGFbeta, BMP, and Activin pathways. Through its association with Smad4 and other transcription factors, RNF11 may have a role in direct transcriptional regulation. Our laboratory and others have found nearly 80 protein interactions for RNF11, placing RNF11 at the cross-roads of cell signalling and transcriptional regulation. RNF11 is highly expressed in breast tumours. Deregulation of RNF11 function may prove to be harmful to patient therapeutic outcomes. RNF11 may therefore provide a novel target for cancer therapeutics. The purpose of this review is to discuss the role of RNF11 in cell signalling and transcription factor modulation with special attention given to the ubiquitin-proteasomal pathway, TGFbeta

  3. Development of Power Supply Management Module for Radio Signal Repeaters of Automatic Metering Reading System in Variable Solar Density Conditions

    Science.gov (United States)

    Kondratjevs, K.; Zabasta, A.; Selmanovs-Pless, V.

    2016-02-01

    In recent years, there has been significant research focus that revolves around harvesting and minimising energy consumption by wireless sensor network nodes. When a sensor node is depleted of energy, it becomes unresponsive and disconnected from the network that can significantly influence the performance of the whole network. The purpose of the present research is to create a power supply management module in order to provide stable operating voltage for autonomous operations of radio signal repeaters, sensors or gateways of WSN. The developed management module is composed of a solar panel, lithium battery and power supply management module. The novelty of the research is the management module, which ensures stable and uninterrupted operations of electronic equipment in various power supply modes in different situations, simultaneously ensuring energy protection and sustainability of the module components. The management module is able to provide power supply of 5 V for electronics scheme independently, without power interruption switching between power sources and power flows in different directions.

  4. Dopamine receptors modulate cytotoxicity of natural killer cells via cAMP-PKA-CREB signaling pathway.

    Directory of Open Access Journals (Sweden)

    Wei Zhao

    Full Text Available Dopamine (DA, a neurotransmitter in the nervous system, has been shown to modulate immune function. We have previously reported that five subtypes of DA receptors, including D1R, D2R, D3R, D4R and D5R, are expressed in T lymphocytes and they are involved in regulation of T cells. However, roles of these DA receptor subtypes and their coupled signal-transduction pathway in modulation of natural killer (NK cells still remain to be clarified. The spleen of mice was harvested and NK cells were isolated and purified by negative selection using magnetic activated cell sorting. After NK cells were incubated with various drugs for 4 h, flow cytometry measured cytotoxicity of NK cells against YAC-1 lymphoma cells. NK cells expressed the five subtypes of DA receptors at mRNA and protein levels. Activation of D1-like receptors (including D1R and D5R with agonist SKF38393 enhanced NK cell cytotoxicity, but activation of D2-like receptors (including D2R, D3R and D4R with agonist quinpirole attenuated NK cells. Simultaneously, SKF38393 elevated D1R and D5R expression, cAMP content, and phosphorylated cAMP-response element-binding (CREB level in NK cells, while quinpirole reduced D3R and D4R expression, cAMP content, and phosphorylated CREB level in NK cells. These effects of SKF38393 were blocked by SCH23390, an antagonist of D1-like receptors, and quinpirole effects were abolished by haloperidol, an antagonist of D2-like receptors. In support these results, H89, an inhibitor of phosphokinase A (PKA, prevented the SKF38393-dependent enhancement of NK cells and forskolin, an activator of adenylyl cyclase (AC, counteracted the quinpirole-dependent suppression of NK cells. These findings show that DA receptor subtypes are involved in modulation of NK cells and suggest that D1-like receptors facilitate NK cells by stimulating D1R/D5R-cAMP-PKA-CREB signaling pathway and D2-like receptors suppress NK cells by inhibiting D3R/D4R-cAMP-PKA-CREB signaling pathway. The

  5. PINK1 positively regulates IL-1β-mediated signaling through Tollip and IRAK1 modulation

    Directory of Open Access Journals (Sweden)

    Lee Hyun Jung

    2012-12-01

    Full Text Available Abstract Background Parkinson disease (PD is characterized by a slow, progressive degeneration of dopaminergic neurons in the substantianigra. The cause of neuronal loss in PD is not well understood, but several genetic loci, including PTEN-induced putative kinase 1 (PINK1, have been linked to early-onset autosomal recessive forms of familial PD. Neuroinflammation greatly contributes to PD neuronal degeneration and pathogenesis. IL-1 is one of the principal cytokines that regulates various immune and inflammatory responses via the activation of the transcription factors NF-κB and activating protein-1. Despite the close relationship between PD and neuroinflammation, the functional roles of PD-linked genes during inflammatory processes remain poorly understood. Methods To explore the functional roles of PINK1 in response to IL-1β stimulation, HEK293 cells, mouse embryonic fibroblasts derived from PINK1-null (PINK1−/− and control (PINK1+/+ mice, and 293 IL-1RI cells stably expressing type 1 IL-1 receptor were used. Immunoprecipitation and western blot analysis were performed to detect protein–protein interaction and protein ubiquitination. To confirm the effect of PINK1 on NF-κB activation, NF-κB-dependent firefly luciferase reporter assay was conducted. Results PINK1 specifically binds two components of the IL-1-mediated signaling cascade, Toll-interacting protein (Tollip and IL-1 receptor-associated kinase 1 (IRAK1. The association of PINK1 with Tollip, a negative regulator of IL-1β signaling, increases upon IL-1β stimulation, which then facilitates the dissociation of Tollip from IRAK1 as well as the assembly of the IRAK1–TNF receptor-associated factor 6 (TRAF6 complex. PINK1 also enhances Lys63-linked polyubiquitination of IRAK1, an essential modification of recruitment of NF-κB essential modulator and subsequent IκB kinase activation, and increases formation of the intermediate signalosome including IRAK1, TRAF6, and

  6. Dynamic characteristics of two-state lasing quantum dot lasers under large signal modulation

    International Nuclear Information System (INIS)

    Lv, Zun-Ren; Ji, Hai-Ming; Luo, Shuai; Gao, Feng; Xu, Feng; Yang, Tao; Xiao, De-Hang

    2015-01-01

    Large signal modulation characteristics of the simultaneous ground-state (GS) and excited-state (ES) lasing quantum dot lasers are theoretically investigated. Relaxation oscillations of ‘0 → 1’ and ‘1 → 0’ in the GS lasing region (Region I), the transition region from GS lasing to two-state lasing (Region II) and the two-state lasing region (Region III) are compared and analyzed. It is found that the overshooting power and settling time in both Regions I and III decrease as the bias current increases. However, there exist abnormal behaviors of the overshooting power and settling time in Region II owing to the occurrence of ES lasing, which lead to fuzzy eye diagrams of the GS and ES lasing. Moreover, the ES lasing in Region III possesses much better eye diagrams because of its shorter settling time and smaller overshooting power over the GS lasing in Region I

  7. A2A adenosine receptor ligand binding and signalling is allosterically modulated by adenosine deaminase.

    Science.gov (United States)

    Gracia, Eduard; Pérez-Capote, Kamil; Moreno, Estefanía; Barkešová, Jana; Mallol, Josefa; Lluís, Carme; Franco, Rafael; Cortés, Antoni; Casadó, Vicent; Canela, Enric I

    2011-05-01

    A2ARs (adenosine A2A receptors) are highly enriched in the striatum, which is the main motor control CNS (central nervous system) area. BRET (bioluminescence resonance energy transfer) assays showed that A2AR homomers may act as cell-surface ADA (adenosine deaminase; EC 3.5.4.4)-binding proteins. ADA binding affected the quaternary structure of A2ARs present on the cell surface. ADA binding to adenosine A2ARs increased both agonist and antagonist affinity on ligand binding to striatal membranes where these proteins are co-expressed. ADA also increased receptor-mediated ERK1/2 (extracellular-signal-regulated kinase 1/2) phosphorylation. Collectively, the results of the present study show that ADA, apart from regulating the concentration of extracellular adenosine, may behave as an allosteric modulator that markedly enhances ligand affinity and receptor function. This powerful regulation may have implications for the physiology and pharmacology of neuronal A2ARs.

  8. Randomly modulated periodic signals in Alberta's electricity market

    Energy Technology Data Exchange (ETDEWEB)

    Hinich, M. [Texas Univ., Austin, TX (United States); Serletis, A. [Calgary Univ., AB (Canada)

    2005-04-01

    The physical laws that determine the delivery of power across a transmission grid require a synchronized energy balance between the injection of power at generating points and offtake at demand points. Grid operators must continuously monitor the demand process and respond quickly to fluctuations in demand. This paper presented a parametric statistical model called Randomly Modulated Periodicity (RMP) which examined Alberta's spot wholesale power market, defined on hourly intervals. The concern was to test for periodic signals that can be perfectly predicted far into the future. A univariate approach was taken, although it was acknowledged that from an economic perspective, the interest in the price of electricity is in its relationship with the electricity load as well as with the prices of other primary fuel commodities. Sections 2 and 3 of the paper discussed the RMP model for the study of periodic signals. In section 4, randomly modulated periodicity was tested in hourly electricity prices and MWh demand for Alberta, over the deregulated period after 1996. It was concluded that electricity prices have low coherence with daily and weekly cycles. The mean value at each half hour of the daily demand and the weekend demand yielded good forecasts after the end of the data series. It was suggested that a statistical forecasting based on historical demand and co-factors such as the average hourly temperature per day and patterns of industrial usage should yield better short term forecasts. The development of a statistical technology for forecasting electricity demand is a challenging area of research. 6 refs., 4 figs.

  9. 25 Gbit/s differential phase-shift-keying signal generation using directly modulated quantum-dot semiconductor optical amplifiers

    International Nuclear Information System (INIS)

    Zeghuzi, A.; Schmeckebier, H.; Stubenrauch, M.; Bimberg, D.; Meuer, C.; Schubert, C.; Bunge, C.-A.

    2015-01-01

    Error-free generation of 25-Gbit/s differential phase-shift keying (DPSK) signals via direct modulation of InAs quantum-dot (QD) based semiconductor optical amplifiers (SOAs) is experimentally demonstrated with an input power level of −5 dBm. The QD SOAs emit in the 1.3-μm wavelength range and provide a small-signal fiber-to-fiber gain of 8 dB. Furthermore, error-free DPSK modulation is achieved for constant optical input power levels from 3 dBm down to only −11 dBm for a bit rate of 20 Gbit/s. Direct phase modulation of QD SOAs via current changes is thus demonstrated to be much faster than direct gain modulation

  10. Experimental muscle pain produces central modulation of proprioceptive signals arising from jaw muscle spindles.

    Science.gov (United States)

    Capra, N F; Ro, J Y

    2000-05-01

    The aim of the present study was to investigate the effects of intramuscular injection with hypertonic saline, a well-established experimental model for muscle pain, on central processing of proprioceptive input from jaw muscle spindle afferents. Fifty-seven cells were recorded from the medial edge of the subnucleus interpolaris (Vi) and the adjacent parvicellular reticular formation from 11 adult cats. These cells were characterized as central units receiving jaw muscle spindle input based on their responses to electrical stimulation of the masseter nerve, muscle palpation and jaw stretch. Forty-five cells, which were successfully tested with 5% hypertonic saline, were categorized as either dynamic-static (DS) (n=25) or static (S) (n=20) neurons based on their responses to different speeds and amplitudes of jaw movement. Seventy-six percent of the cells tested with an ipsilateral injection of hypertonic saline showed a significant modulation of mean firing rates (MFRs) during opening and/or holding phases. The most remarkable saline-induced change was a significant reduction of MFR during the hold phase in S units (100%, 18/18 modulated). Sixty-nine percent of the DS units (11/16 modulated) also showed significant changes in MFRs limited to the hold phase. However, in the DS neurons, the MFRs increased in seven units and decreased in four units. Finally, five DS neurons showed significant changes of MFRs during both opening and holding phases. Injections of isotonic saline into the ipsilateral masseter muscle had little effect, but hypertonic saline injections made into the contralateral masseter muscle produced similar results to ipsilateral injections with hypertonic saline. These results unequivocally demonstrate that intramuscular injection with an algesic substance, sufficient to produce muscle pain, produces significant changes in the proprioceptive properties of the jaw movement-related neurons. Potential mechanisms involved in saline-induced changes in the

  11. Search for an annual modulation of dark-matter signals with a germanium spectrometer at the Sierra Grande Laboratory

    CERN Document Server

    Abriola, D.; Brodzinski, R.L.; Collar, J.I.; Di Gregorio, D.E.; Farach, H.A.; Garcia, E.; Gattone, A.O.; Guerard, C.K.; Hasenbalg, F.; Huck, H.; Miley, H.S.; Morales, A.; Morales, J.; Ortiz de Solorzano, A.; Puimedon, J.; Reeves, J.H.; Salinas, A.; Sarsa, M.L.; Villar, J.A.

    1999-01-01

    Data collected during three years with a germanium spectrometer at the Sierra Grande underground laboratory have been analyzed for distinctive features of annual modulation of the signal induced by WIMP dark matter candidates. The main motivation for this analysis was the recent suggestion by the DAMA/NaI Collaboration that a yearly modulation signal could not be rejected at the 90% confidence level when analyzing data obtained with a high-mass low-background scintillator detector. We performed two different analyses of the data: First, the statistical distribution of modulation-significance variables (expected from an experiment running under the conditions of Sierra Grande) was compared with the same variables obtained from the data. Second, the data were analyzed in energy bins as an independent check of the first result and to allow for the possibility of a crossover in the expected signal. In both cases no statistically significant deviation from the null result was found, which could support the hypothe...

  12. Signal Detection Methods and Discriminant Analysis Applied to Categorization of Newspaper and Government Documents: A Preliminary Study.

    Science.gov (United States)

    Ng, Kwong Bor; Rieh, Soo Young; Kantor, Paul

    2000-01-01

    Discussion of natural language processing focuses on experiments using linear discriminant analysis to distinguish "Wall Street Journal" texts from "Federal Register" tests using information about the frequency of occurrence of word boundaries, sentence boundaries, and punctuation marks. Displays and interprets results in terms…

  13. Multi-Gigahertz radar range processing of baseband and RF carrier modulated signals in Tm:YAG

    International Nuclear Information System (INIS)

    Merkel, K.D.; Krishna Mohan, R.; Cole, Z.; Chang, T.; Olson, A.; Babbitt, W.R.

    2004-01-01

    An optical device is described and demonstrated that uses a spatial-spectral holographic material to perform coherent signal processing operations on analog, high-bandwidth optical signals with large time-bandwidth-products. Signal processing is performed as the material records the coherent spectral interference (or cross-power spectrum) of modulated optical signals as a spatial-spectral population grating between electronic transition states. Multiple exposures of processing pulse sequences are integrated with increasing grating strength. The device, coined as the Spatial-Spectral Coherent Holographic Integrating Processor (or S 2 -CHIP), is described as currently envisioned for a broadband, mid-to-high pulse repetition frequency range-Doppler radar signal processing system. Experiments were performed in Tm:YAG (0.1 at% at 5 K) to demonstrate time delay variation, integration dynamics, and effects of coding as applied to a radar range processor. These demonstrations used baseband modulation with a 1 gigabit per second (GPBS) bit rate and code length of 512 bits (512 ns), where delays up to 1.0 μs were resolved with greater than a 40 dB peak to RMS sidelobe ratio after 800 processing shots. Multi-GHz processing was demonstrated using a bit rate of 2.5 GBPS (baseband modulation) and code length of 2048 bits (819.2 ns). Processing of double-sideband modulated signals on a radio frequency (RF) carrier was demonstrated, where 512 bit, 1.0 GBPS codes were modulated on a 1.75 GHz carrier and then modulated on the optical carrier

  14. Time-frequency analysis of time-varying modulated signals based on improved energy separation by iterative generalized demodulation

    Science.gov (United States)

    Feng, Zhipeng; Chu, Fulei; Zuo, Ming J.

    2011-03-01

    Energy separation algorithm is good at tracking instantaneous changes in frequency and amplitude of modulated signals, but it is subject to the constraints of mono-component and narrow band. In most cases, time-varying modulated vibration signals of machinery consist of multiple components, and have so complicated instantaneous frequency trajectories on time-frequency plane that they overlap in frequency domain. For such signals, conventional filters fail to obtain mono-components of narrow band, and their rectangular decomposition of time-frequency plane may split instantaneous frequency trajectories thus resulting in information loss. Regarding the advantage of generalized demodulation method in decomposing multi-component signals into mono-components, an iterative generalized demodulation method is used as a preprocessing tool to separate signals into mono-components, so as to satisfy the requirements by energy separation algorithm. By this improvement, energy separation algorithm can be generalized to a broad range of signals, as long as the instantaneous frequency trajectories of signal components do not intersect on time-frequency plane. Due to the good adaptability of energy separation algorithm to instantaneous changes in signals and the mono-component decomposition nature of generalized demodulation, the derived time-frequency energy distribution has fine resolution and is free from cross term interferences. The good performance of the proposed time-frequency analysis is illustrated by analyses of a simulated signal and the on-site recorded nonstationary vibration signal of a hydroturbine rotor during a shut-down transient process, showing that it has potential to analyze time-varying modulated signals of multi-components.

  15. Assessing spectral and temporal processing in children and adults using temporal modulation transfer function (TMTF), Iterated Ripple Noise (IRN) perception, and spectral ripple discrimination (SRD).

    Science.gov (United States)

    Peter, Varghese; Wong, Kogo; Narne, Vijaya Kumar; Sharma, Mridula; Purdy, Suzanne C; McMahon, Catherine

    2014-02-01

    There are many clinically available tests for the assessment of auditory processing skills in children and adults. However, there is limited data available on the maturational effects on the performance on these tests. The current study investigated maturational effects on auditory processing abilities using three psychophysical measures: temporal modulation transfer function (TMTF), iterated ripple noise (IRN) perception, and spectral ripple discrimination (SRD). A cross-sectional study. Three groups of subjects were tested: 10 adults (18-30 yr), 10 older children (12-18 yr), and 10 young children (8-11 yr) Temporal envelope processing was measured by obtaining thresholds for amplitude modulation detection as a function of modulation frequency (TMTF; 4, 8, 16, 32, 64, and 128 Hz). Temporal fine structure processing was measured using IRN, and spectral processing was measured using SRD. The results showed that young children had significantly higher modulation thresholds at 4 Hz (TMTF) compared to the other two groups and poorer SRD scores compared to adults. The results on IRN did not differ across groups. The results suggest that different aspects of auditory processing mature at different age periods and these maturational effects need to be considered while assessing auditory processing in children. American Academy of Audiology.

  16. Immune evasion of porcine enteric coronaviruses and viral modulation of antiviral innate signaling.

    Science.gov (United States)

    Zhang, Qingzhan; Yoo, Dongwan

    2016-12-02

    Porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) are emerged and reemerging viruses in pigs, and together with transmissible gastroenteritis virus (TGEV), pose significant economic concerns to the swine industry. These viruses infect epithelial cells of the small intestine and cause watery diarrhea, dehydration, and a high mortality in neonatal piglets. Type I interferons (IFN-α/β) are major antiviral cytokines forming host innate immunity, and in turn, these enteric coronaviruses have evolved to modulate the host innate immune signaling during infection. Accumulating evidence however suggests that IFN induction and signaling in the intestinal epithelial cells differ from other epithelial cells, largely due to distinct features of the gut epithelial mucosal surface and commensal microflora, and it appears that type III interferon (IFN-λ) plays a key role to maintain the antiviral state in the gut. This review describes the recent understanding on the immune evasion strategies of porcine enteric coronaviruses and the role of different types of IFNs for intestinal antiviral innate immunity. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Glucose-ABL1-TOR Signaling Modulates Cell Cycle Tuning to Control Terminal Appressorial Cell Differentiation.

    Science.gov (United States)

    Marroquin-Guzman, Margarita; Sun, Guangchao; Wilson, Richard A

    2017-01-01

    The conserved target of rapamycin (TOR) pathway integrates growth and development with available nutrients, but how cellular glucose controls TOR function and signaling is poorly understood. Here, we provide functional evidence from the devastating rice blast fungus Magnaporthe oryzae that glucose can mediate TOR activity via the product of a novel carbon-responsive gene, ABL1, in order to tune cell cycle progression during infection-related development. Under nutrient-free conditions, wild type (WT) M. oryzae strains form terminal plant-infecting cells (appressoria) at the tips of germ tubes emerging from three-celled spores (conidia). WT appressorial development is accompanied by one round of mitosis followed by autophagic cell death of the conidium. In contrast, Δabl1 mutant strains undergo multiple rounds of accelerated mitosis in elongated germ tubes, produce few appressoria, and are abolished for autophagy. Treating WT spores with glucose or 2-deoxyglucose phenocopied Δabl1. Inactivating TOR in Δabl1 mutants or glucose-treated WT strains restored appressorium formation by promoting mitotic arrest at G1/G0 via an appressorium- and autophagy-inducing cell cycle delay at G2/M. Collectively, this work uncovers a novel glucose-ABL1-TOR signaling axis and shows it engages two metabolic checkpoints in order to modulate cell cycle tuning and mediate terminal appressorial cell differentiation. We thus provide new molecular insights into TOR regulation and cell development in response to glucose.

  18. Using Pulse Width Modulation for Wireless Transmission of Neural Signals in Multichannel Neural Recording Systems

    Science.gov (United States)

    Yin, Ming; Ghovanloo, Maysam

    2013-01-01

    We have used a well-known technique in wireless communication, pulse width modulation (PWM) of time division multiplexed (TDM) signals, within the architecture of a novel wireless integrated neural recording (WINeR) system. We have evaluated the performance of the PWM-based architecture and indicated its accuracy and potential sources of error through detailed theoretical analysis, simulations, and measurements on a setup consisting of a 15-channel WINeR prototype as the transmitter and two types of receivers; an Agilent 89600 vector signal analyzer and a custom wideband receiver, with 36 and 75 MHz of maximum bandwidth, respectively. Furthermore, we present simulation results from a realistic MATLAB-Simulink model of the entire WINeR system to observe the system behavior in response to changes in various parameters. We have concluded that the 15-ch WINeR prototype, which is fabricated in a 0.5-μm standard CMOS process and consumes 4.5 mW from ±1.5 V supplies, can acquire and wirelessly transmit up to 320 k-samples/s to a 75-MHz receiver with 8.4 bits of resolution, which is equivalent to a wireless data rate of ~ 2.26 Mb/s. PMID:19497823

  19. Differential signaling spread-spectrum modulation of the LED visible light wireless communications using a mobile-phone camera

    Science.gov (United States)

    Chen, Shih-Hao; Chow, Chi-Wai

    2015-02-01

    Visible light communication (VLC) using spread spectrum modulation (SSM) and differential signaling (DS), detected by a mobile-phone camera is proposed and demonstrated for the first time to provide high immunity to background ambient light interference. The SSM signal provides the coding gain while the DS scheme enhances the clock recovery particular under high background ambient light. Experiment results confirm the feasibility of the proposed scheme, showing that the proposed system has 6-dB gain comparing with the traditional on-off keying (OOK) modulation under background ambient light of 3000 lux. The direct incident ambient light to the mobile-phone camera is 520 lux.

  20. Screen for chemical modulators of autophagy reveals novel therapeutic inhibitors of mTORC1 signaling.

    Directory of Open Access Journals (Sweden)

    Aruna D Balgi

    Full Text Available BACKGROUND: Mammalian target of rapamycin complex 1 (mTORC1 is a protein kinase that relays nutrient availability signals to control numerous cellular functions including autophagy, a process of cellular self-eating activated by nutrient depletion. Addressing the therapeutic potential of modulating mTORC1 signaling and autophagy in human disease requires active chemicals with pharmacologically desirable properties. METHODOLOGY/PRINCIPAL FINDINGS: Using an automated cell-based assay, we screened a collection of >3,500 chemicals and identified three approved drugs (perhexiline, niclosamide, amiodarone and one pharmacological reagent (rottlerin capable of rapidly increasing autophagosome content. Biochemical assays showed that the four compounds stimulate autophagy and inhibit mTORC1 signaling in cells maintained in nutrient-rich conditions. The compounds did not inhibit mTORC2, which also contains mTOR as a catalytic subunit, suggesting that they do not inhibit mTOR catalytic activity but rather inhibit signaling to mTORC1. mTORC1 inhibition and autophagosome accumulation induced by perhexiline, niclosamide or rottlerin were rapidly reversed upon drug withdrawal whereas amiodarone inhibited mTORC1 essentially irreversibly. TSC2, a negative regulator of mTORC1, was required for inhibition of mTORC1 signaling by rottlerin but not for mTORC1 inhibition by perhexiline, niclosamide and amiodarone. Transient exposure of immortalized mouse embryo fibroblasts to these drugs was not toxic in nutrient-rich conditions but led to rapid cell death by apoptosis in starvation conditions, by a mechanism determined in large part by the tuberous sclerosis complex protein TSC2, an upstream regulator of mTORC1. By contrast, transient exposure to the mTORC1 inhibitor rapamycin caused essentially irreversible mTORC1 inhibition, sustained inhibition of cell growth and no selective cell killing in starvation. CONCLUSION/SIGNIFICANCE: The observation that drugs already

  1. RANK ligand signaling modulates the matrix metalloproteinase-9 gene expression during osteoclast differentiation

    International Nuclear Information System (INIS)

    Sundaram, Kumaran; Nishimura, Riko; Senn, Joseph; Youssef, Rimon F.; London, Steven D.; Reddy, Sakamuri V.

    2007-01-01

    the absence of RANKL. Taken together, our results suggest that RANKL signals through TRAF6 and that NFATc1 is a downstream effector of RANKL signaling to modulate MMP-9 gene expression during osteoclast differentiation

  2. Differential modulation of Beta-adrenergic receptor signaling by trace amine-associated receptor 1 agonists.

    Directory of Open Access Journals (Sweden)

    Gunnar Kleinau

    Full Text Available Trace amine-associated receptors (TAAR are rhodopsin-like G-protein-coupled receptors (GPCR. TAAR are involved in modulation of neuronal, cardiac and vascular functions and they are potentially linked with neurological disorders like schizophrenia and Parkinson's disease. Subtype TAAR1, the best characterized TAAR so far, is promiscuous for a wide set of ligands and is activated by trace amines tyramine (TYR, phenylethylamine (PEA, octopamine (OA, but also by thyronamines, dopamine, and psycho-active drugs. Unfortunately, effects of trace amines on signaling of the two homologous β-adrenergic receptors 1 (ADRB1 and 2 (ADRB2 have not been clarified yet in detail. We, therefore, tested TAAR1 agonists TYR, PEA and OA regarding their effects on ADRB1/2 signaling by co-stimulation studies. Surprisingly, trace amines TYR and PEA are partial allosteric antagonists at ADRB1/2, whereas OA is a partial orthosteric ADRB2-antagonist and ADRB1-agonist. To specify molecular reasons for TAAR1 ligand promiscuity and for observed differences in signaling effects on particular aminergic receptors we compared TAAR, tyramine (TAR octopamine (OAR, ADRB1/2 and dopamine receptors at the structural level. We found especially for TAAR1 that the remarkable ligand promiscuity is likely based on high amino acid similarity in the ligand-binding region compared with further aminergic receptors. On the other hand few TAAR specific properties in the ligand-binding site might determine differences in ligand-induced effects compared to ADRB1/2. Taken together, this study points to molecular details of TAAR1-ligand promiscuity and identified specific trace amines as allosteric or orthosteric ligands of particular β-adrenergic receptor subtypes.

  3. Rac1 modulates mammalian lung branching morphogenesis in part through canonical Wnt signaling.

    Science.gov (United States)

    Danopoulos, Soula; Krainock, Michael; Toubat, Omar; Thornton, Matthew; Grubbs, Brendan; Al Alam, Denise

    2016-12-01

    Lung branching morphogenesis relies on a number of factors, including proper epithelial cell proliferation and differentiation, cell polarity, and migration. Rac1, a small Rho GTPase, orchestrates a number of these cellular processes, including cell proliferation and differentiation, cellular alignment, and polarization. Furthermore, Rac1 modulates both noncanonical and canonical Wnt signaling, important pathways in lung branching morphogenesis. Culture of embryonic mouse lung explants in the presence of the Rac1 inhibitor (NSC23766) resulted in a dose-dependent decrease in branching. Increased cell death and BrdU uptake were notably seen in the mesenchyme, while no direct effect on the epithelium was observed. Moreover, vasculogenesis was impaired following Rac1 inhibition as shown by decreased Vegfa expression and impaired LacZ staining in Flk1-Lacz reporter mice. Rac1 inhibition decreased Fgf10 expression in conjunction with many of its associated factors. Moreover, using the reporter lines TOPGAL and Axin2-LacZ, there was an evident decrease in canonical Wnt signaling in the explants treated with the Rac1 inhibitor. Activation of canonical Wnt pathway using WNT3a or WNT7b only partially rescued the branching inhibition. Moreover, these results were validated on human explants, where Rac1 inhibition resulted in impaired branching and decreased AXIN2 and FGFR2b expression. We therefore conclude that Rac1 regulates lung branching morphogenesis, in part through canonical Wnt signaling. However, the exact mechanisms by which Rac1 interacts with canonical Wnt in human and mouse lung requires further investigation. Copyright © 2016 the American Physiological Society.

  4. A cytosolic juxtamembrane interface modulates plexin A3 oligomerization and signal transduction.

    Directory of Open Access Journals (Sweden)

    Rachael Barton

    Full Text Available Plexins (plxns are transmembrane (TM receptors involved in the guidance of vascular, lymphatic vessel, and neuron growth as well as cancer metastasis. Plxn signaling results in cytosolic GTPase-activating protein activity, and previous research implicates dimerization as important for activation of plxn signaling. Purified, soluble plxn extracellular and cytosolic domains exhibit only weak homomeric interactions, suggesting a role for the plxn TM and juxtamembrane regions in homooligomerization. In this study, we consider a heptad repeat in the Danio rerio PlxnA3 cytosolic juxtamembrane domain (JM for its ability to influence PlxnA3 homooligomerization in TM-domain containing constructs. Site-directed mutagenesis in conjunction with the AraTM assay and bioluminescent energy transfer (BRET² suggest an interface involving a JM heptad repeat, in particular residue M1281, regulates PlxnA3 homomeric interactions when examined in constructs containing an ectodomain, TM and JM domain. In the presence of a neuropilin-2a co-receptor and semaphorin 3F ligand, disruption to PlxnA3 homodimerization caused by an M1281F mutation is eliminated, suggesting destabilization of the PlxnA3 homodimer in the JM is not sufficient to disrupt co-receptor complex formation. In contrast, enhanced homodimerization of PlxnA3 caused by mutation M1281L remains even in the presence of ligand semaphorin 3F and co-receptor neuropilin-2a. Consistent with this pattern of PlxnA3 dimerization in the presence of ligand and co-receptor, destabilizing mutations to PlxnA3 homodimerization (M1281F are able to rescue motor patterning defects in sidetracked zebrafish embryos, whereas mutations that enhance PlxnA3 homodimerization (M1281L are not. Collectively, our results indicate the JM heptad repeat, in particular residue M1281, forms a switchable interface that modulates both PlxnA3 homomeric interactions and signal transduction.

  5. Nicotine induces resistance to chemotherapy by modulating mitochondrial signaling in lung cancer.

    Science.gov (United States)

    Zhang, Jingmei; Kamdar, Opal; Le, Wei; Rosen, Glenn D; Upadhyay, Daya

    2009-02-01

    Continued smoking causes tumor progression and resistance to therapy in lung cancer. Carcinogens possess the ability to block apoptosis, and thus may induce development of cancers and resistance to therapy. Tobacco carcinogens have been studied widely; however, little is known about the agents that inhibit apoptosis, such as nicotine. We determine whether mitochondrial signaling mediates antiapoptotic effects of nicotine in lung cancer. A549 cells were exposed to nicotine (1 muM) followed by cisplatin (35 muM) plus etoposide (20 muM) for 24 hours. We found that nicotine prevented chemotherapy-induced apoptosis, improved cell survival, and caused modest increases in DNA synthesis. Inhibition of mitogen-activated protein kinase (MAPK) and Akt prevented the antiapoptotic effects of nicotine and decreased chemotherapy-induced apoptosis. Small interfering RNA MAPK kinase-1 blocked antiapoptotic effects of nicotine, whereas small interfering RNA MAPK kinase-2 blocked chemotherapy-induced apoptosis. Nicotine prevented chemotherapy-induced reduction in mitochondrial membrane potential and caspase-9 activation. Antiapoptotic effects of nicotine were blocked by mitochondrial anion channel inhibitor, 4,4'diisothiocyanatostilbene-2,2'disulfonic acid. Chemotherapy enhanced translocation of proapoptotic Bax to the mitochondria, whereas nicotine blocked these effects. Nicotine up-regulated Akt-mediated antiapoptotic X-linked inhibitor of apoptosis protein and phosphorylated proapoptotic Bcl2-antagonist of cell death. The A549-rho0 cells, which lack mitochondrial DNA, demonstrated partial resistance to chemotherapy-induced apoptosis, but blocked the antiapoptotic effects of nicotine. Accordingly, we provide evidence that nicotine modulates mitochondrial signaling and inhibits chemotherapy-induced apoptosis in lung cancer. The mitochondrial regulation of nicotine imposes an important mechanism that can critically impair the treatment of lung cancer, because many cancer

  6. Four-deep charge-time and pulse-width scaling discriminator for delay line MWPC's

    International Nuclear Information System (INIS)

    Lee, K.L.; Kirsten, F.A.; Grigorian, A.; Guiragossian, Z.G.T.

    1976-01-01

    A discriminator has been developed for digitizing both intercepted total charge and location of electromagnetic shower and particle trajectories in multi-wire proportional chambers read by delay lines. Determination of shower trajectory is aided by video signal integration followed by centroid-locating discrimination. Calibrated run-down of the signal integrating capacitor gives the charge information above a given threshold level. The discriminator is designed to handle up to four shower-induced video signals per event by incorporating steering circuits within the module. Each video signal is examined for time over an adjustable threshold. Video pulses with separation of less than 20 nsec are treated as a single pulse. Counter-logic circuits indicate the number of video signals digitized. These signal processing circuits provide a first level of data sifting which otherwise must be carried out with additional discriminator channels and added complexity in data recognition

  7. Organic vapor discrimination with chemiresistor arrays of temperature modulated tin-oxide nanowires and thiolate-monolayer-protected gold nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Scholten, K; Bohrer, F I; Dattoli, E; Lu, W; Zellers, E T, E-mail: ezellers@umich.edu [Center for Wireless Integrated Microsystems, University of Michigan, Ann Arbor, MI 48109-2122 (United States)

    2011-03-25

    This paper explores the discrimination of organic vapors with arrays of chemiresistors (CRs) employing interface layers of tin-oxide nanowires (NWs) and thiolate-monolayer-protected gold nanoparticles (MPNs). The former devices use contact-printed mats of NWs on micro-hotplate membranes to bridge a pair of metal electrodes. Oxidation at the NW surface causes changes in charge transport, the temperature dependence of which differs among different vapors, permitting vapor discrimination. The latter devices use solvent cast films of MPNs on interdigital electrodes operated at room temperature. Sorption into the organic monolayers causes changes in film tunneling resistance that differ among different vapors and MPN structures, permitting vapor discrimination. Here, we compare the performance and assess the 'complementarity' of these two types of sensors. Calibrated responses from an NW CR operated at two different temperatures and from a set of four different MPN CRs were generated for three test vapors: n-hexane, toluene, and nitromethane. This pooled data set was then analyzed using principal components regression classification models with varying degrees of random error superimposed on the responses via Monte Carlo simulation in order to estimate the rates of recognition/discrimination for arrays comprising different combinations of sensors. Results indicate that the diversity of most of the dual MPN-CR arrays exceeds that of the dual NW-CR array. Additionally, in assessing all possible arrays of 4-6 CR sensors, the recognition rates of the hybrid arrays (i.e. MPN + NW) were no better than that of the 4-sensor array containing only MPN CRs.

  8. Reduction of pattern effects in SOA-based all-optical switches by using cross-gain modulated holding signal

    DEFF Research Database (Denmark)

    Bischoff, Svend; Mørk, Jesper

    2002-01-01

    The effective carrier lifetime of SOAs is typically shortened by an intense Continuous Wave (CW) holding signal. However, the SOA gain is reduced by the holding signal resulting in smaller gain and refractive index changes induced by the data signal. Accordingly, an optimum exists for the CW...... and data signal power. Here, we demonstrate that the modulation bandwidth (amplitude jitter) is significantly improved (reduced) by replacing the CW holding beam with a signal, which is low-pass filtered and inverted with respect to the data signal. Such a holding beam can be generated by XGM WC in an SOA......, and reduces the fluctuations of the total energy injected into the interferometer within a bit-slot. Thus, we demonstrate a technique for reducing pattern effects in SOAs by employing a partially inverted holding beam. The method should be useful for increasing the data rates of all-optical switches....

  9. Ebola virus modulates transforming growth factor β signaling and cellular markers of mesenchyme-like transition in hepatocytes.

    Science.gov (United States)

    Kindrachuk, Jason; Wahl-Jensen, Victoria; Safronetz, David; Trost, Brett; Hoenen, Thomas; Arsenault, Ryan; Feldmann, Friederike; Traynor, Dawn; Postnikova, Elena; Kusalik, Anthony; Napper, Scott; Blaney, Joseph E; Feldmann, Heinz; Jahrling, Peter B

    2014-09-01

    Ebola virus (EBOV) causes a severe hemorrhagic disease in humans and nonhuman primates, with a median case fatality rate of 78.4%. Although EBOV is considered a public health concern, there is a relative paucity of information regarding the modulation of the functional host response during infection. We employed temporal kinome analysis to investigate the relative early, intermediate, and late host kinome responses to EBOV infection in human hepatocytes. Pathway overrepresentation analysis and functional network analysis of kinome data revealed that transforming growth factor (TGF-β)-mediated signaling responses were temporally modulated in response to EBOV infection. Upregulation of TGF-β signaling in the kinome data sets correlated with the upregulation of TGF-β secretion from EBOV-infected cells. Kinase inhibitors targeting TGF-β signaling, or additional cell receptors and downstream signaling pathway intermediates identified from our kinome analysis, also inhibited EBOV replication. Further, the inhibition of select cell signaling intermediates identified from our kinome analysis provided partial protection in a lethal model of EBOV infection. To gain perspective on the cellular consequence of TGF-β signaling modulation during EBOV infection, we assessed cellular markers associated with upregulation of TGF-β signaling. We observed upregulation of matrix metalloproteinase 9, N-cadherin, and fibronectin expression with concomitant reductions in the expression of E-cadherin and claudin-1, responses that are standard characteristics of an epithelium-to-mesenchyme-like transition. Additionally, we identified phosphorylation events downstream of TGF-β that may contribute to this process. From these observations, we propose a model for a broader role of TGF-β-mediated signaling responses in the pathogenesis of Ebola virus disease. Ebola virus (EBOV), formerly Zaire ebolavirus, causes a severe hemorrhagic disease in humans and nonhuman primates and is the most

  10. Pulse-width discriminators

    International Nuclear Information System (INIS)

    Budyashov, Yu.G.; Grebenyuk, V.M.; Zinov, V.G.

    1978-01-01

    A pulse duration discriminator is described which is intended for processing signals from multilayer scintillators. The basic elements of the scintillator are: an input gate, a current generator, an integrating capacitor, a Schmidt trigger and an anticoincidence circuit. The basic circuit of the discriminator and its time diagrams explaining its operating are given. The discriminator is based on microcircuits. Pulse duration discrimination threshold changes continuously from 20 to 100 ns, while its amplitude threshold changes within 20 to 100 mV. The temperature instability of discrimination thresholds (both in pulse width and in amplitude) is better than 0.1 per cent/deg C

  11. Test beam demonstration of silicon microstrip modules with transverse momentum discrimination for the future CMS tracking detector

    Science.gov (United States)

    Adam, W.; Bergauer, T.; Brondolin, E.; Dragicevic, M.; Friedl, M.; Frühwirth, R.; Hoch, M.; Hrubec, J.; König, A.; Steininger, H.; Treberspurg, W.; Waltenberger, W.; Alderweireldt, S.; Beaumont, W.; Janssen, X.; Lauwers, J.; Van Mechelen, P.; Van Remortel, N.; Van Spilbeeck, A.; Beghin, D.; Brun, H.; Clerbaux, B.; De Lentdecker, G.; Delannoy, H.; Fasanella, G.; Favart, L.; Goldouzian, R.; Grebenyuk, A.; Karapostoli, G.; Lenzi, T.; Léonard, A.; Luetic, J.; Maerschalk, T.; Marinov, A.; Postiau, N.; Randle-Conde, A.; Seva, T.; Vanlaer, P.; Vannerom, D.; Yonamine, R.; Wang, Q.; Yang, Y.; Zenoni, F.; Zhang, F.; Abu Zeid, S.; Blekman, F.; De Bruyn, I.; De Clercq, J.; D'Hondt, J.; Deroover, K.; Lowette, S.; Moortgat, S.; Moreels, L.; Python, Q.; Skovpen, K.; Van Mulders, P.; Van Parijs, I.; Bakhshiansohi, H.; Bondu, O.; Brochet, S.; Bruno, G.; Caudron, A.; Delaere, C.; Delcourt, M.; De Visscher, S.; Francois, B.; Giammanco, A.; Jafari, A.; Cabrera Jamoulle, J.; De Favereau De Jeneret, J.; Komm, M.; Krintiras, G.; Lemaitre, V.; Magitteri, A.; Mertens, A.; Michotte, D.; Musich, M.; Piotrzkowski, K.; Quertenmont, L.; Szilasi, N.; Vidal Marono, M.; Wertz, S.; Beliy, N.; Caebergs, T.; Daubie, E.; Hammad, G. H.; Härkönen, J.; Lampén, T.; Luukka, P.; Peltola, T.; Tuominen, E.; Tuovinen, E.; Eerola, P.; Baulieu, G.; Boudoul, G.; Caponetto, L.; Combaret, C.; Contardo, D.; Dupasquier, T.; Gallbit, G.; Lumb, N.; Mirabito, L.; Perries, S.; Vander Donckt, M.; Viret, S.; Agram, J.-L.; Andrea, J.; Bloch, D.; Bonnin, C.; Brom, J.-M.; Chabert, E.; Chanon, N.; Charles, L.; Conte, E.; Fontaine, J.-Ch.; Gross, L.; Hosselet, J.; Jansova, M.; Tromson, D.; Autermann, C.; Feld, L.; Karpinski, W.; Kiesel, K. M.; Klein, K.; Lipinski, M.; Ostapchuk, A.; Pierschel, G.; Preuten, M.; Rauch, M.; Schael, S.; Schomakers, C.; Schulz, J.; Schwering, G.; Wlochal, M.; Zhukov, V.; Pistone, C.; Fluegge, G.; Kuensken, A.; Pooth, O.; Stahl, A.; Aldaya, M.; Asawatangtrakuldee, C.; Beernaert, K.; Bertsche, D.; Contreras-Campana, C.; Eckerlin, G.; Eckstein, D.; Eichhorn, T.; Gallo, E.; Garay Garcia, J.; Hansen, K.; Haranko, M.; Harb, A.; Hauk, J.; Keaveney, J.; Kalogeropoulos, A.; Kleinwort, C.; Lohmann, W.; Mankel, R.; Maser, H.; Mittag, G.; Muhl, C.; Mussgiller, A.; Pitzl, D.; Reichelt, O.; Savitskyi, M.; Schuetze, P.; Walsh, R.; Zuber, A.; Biskop, H.; Buhmann, P.; Centis-Vignali, M.; Garutti, E.; Haller, J.; Hoffmann, M.; Klanner, R.; Matysek, M.; Perieanu, A.; Scharf, Ch.; Schleper, P.; Schmidt, A.; Schwandt, J.; Sonneveld, J.; Steinbrück, G.; Vormwald, B.; Wellhausen, J.; Abbas, M.; Amstutz, C.; Barvich, T.; Barth, Ch.; Boegelspacher, F.; De Boer, W.; Butz, E.; Casele, M.; Colombo, F.; Dierlamm, A.; Freund, B.; Hartmann, F.; Heindl, S.; Husemann, U.; Kornmeyer, A.; Kudella, S.; Muller, Th.; Printz, M.; Simonis, H. J.; Steck, P.; Weber, M.; Weiler, Th.; Anagnostou, G.; Asenov, P.; Assiouras, P.; Daskalakis, G.; Kyriakis, A.; Loukas, D.; Paspalaki, L.; Siklér, F.; Veszprémi, V.; Bhardwaj, A.; Dalal, R.; Jain, G.; Ranjan, K.; Dutta, S.; Chowdhury, S. Roy; Bakhshiansohl, H.; Behnamian, H.; Khakzad, M.; Naseri, M.; Cariola, P.; Creanza, D.; De Palma, M.; De Robertis, G.; Fiore, L.; Franco, M.; Loddo, F.; Sala, G.; Silvestris, L.; Maggi, G.; My, S.; Selvaggi, G.; Albergo, S.; Costa, S.; Di Mattia, A.; Giordano, F.; Potenza, R.; Saizu, M. A.; Tricomi, A.; Tuve, C.; Barbagli, G.; Brianzi, M.; Ciaranfi, R.; Ciulli, V.; Civinini, C.; D'Alessandro, R.; Focardi, E.; Latino, G.; Lenzi, P.; Meschini, M.; Paoletti, S.; Russo, L.; Scarlini, E.; Sguazzoni, G.; Strom, D.; Viliani, L.; Ferro, F.; Lo Vetere, M.; Robutti, E.; Dinardo, M. E.; Fiorendi, S.; Gennai, S.; Malvezzi, S.; Manzoni, R. A.; Menasce, D.; Moroni, L.; Pedrini, D.; Azzi, P.; Bacchetta, N.; Bisello, D.; Dall'Osso, M.; Pozzobon, N.; Tosi, M.; De Canio, F.; Gaioni, L.; Manghisoni, M.; Nodari, B.; Riceputi, E.; Re, V.; Traversi, G.; Comotti, D.; Ratti, L.; Alunni Solestizi, L.; Biasini, M.; Bilei, G. M.; Cecchi, C.; Checcucci, B.; Ciangottini, D.; Fanò, L.; Gentsos, C.; Ionica, M.; Leonardi, R.; Manoni, E.; Mantovani, G.; Marconi, S.; Mariani, V.; Menichelli, M.; Modak, A.; Morozzi, A.; Moscatelli, F.; Passeri, D.; Placidi, P.; Postolache, V.; Rossi, A.; Saha, A.; Santocchia, A.; Storchi, L.; Spiga, D.; Androsov, K.; Azzurri, P.; Arezzini, S.; Bagliesi, G.; Basti, A.; Boccali, T.; Borrello, L.; Bosi, F.; Castaldi, R.; Ciampa, A.; Ciocci, M. A.; Dell'Orso, R.; Donato, S.; Fedi, G.; Giassi, A.; Grippo, M. T.; Ligabue, F.; Lomtadze, T.; Magazzu, G.; Martini, L.; Mazzoni, E.; Messineo, A.; Moggi, A.; Morsani, F.; Palla, F.; Palmonari, F.; Raffaelli, F.; Rizzi, A.; Savoy-Navarro, A.; Spagnolo, P.; Tenchini, R.; Tonelli, G.; Venturi, A.; Verdini, P. G.; Bellan, R.; Costa, M.; Covarelli, R.; Da Rocha Rolo, M.; Demaria, N.; Rivetti, A.; Dellacasa, G.; Mazza, G.; Migliore, E.; Monteil, E.; Pacher, L.; Ravera, F.; Solano, A.; Fernandez, M.; Gomez, G.; Jaramillo Echeverria, R.; Moya, D.; Gonzalez Sanchez, F. J.; Vila, I.; Virto, A. L.; Abbaneo, D.; Ahmed, I.; Albert, E.; Auzinger, G.; Berruti, G.; Bianchi, G.; Blanchot, G.; Bonnaud, J.; Caratelli, A.; Ceresa, D.; Christiansen, J.; Cichy, K.; Daguin, J.; D'Auria, A.; Detraz, S.; Deyrail, D.; Dondelewski, O.; Faccio, F.; Frank, N.; Gadek, T.; Gill, K.; Honma, A.; Hugo, G.; Jara Casas, L. M.; Kaplon, J.; Kornmayer, A.; Kottelat, L.; Kovacs, M.; Krammer, M.; Lenoir, P.; Mannelli, M.; Marchioro, A.; Marconi, S.; Mersi, S.; Martina, S.; Michelis, S.; Moll, M.; Onnela, A.; Orfanelli, S.; Pavis, S.; Peisert, A.; Pernot, J.-F.; Petagna, P.; Petrucciani, G.; Postema, H.; Rose, P.; Tropea, P.; Troska, J.; Tsirou, A.; Vasey, F.; Vichoudis, P.; Verlaat, B.; Zwalinski, L.; Bachmair, F.; Becker, R.; di Calafiori, D.; Casal, B.; Berger, P.; Djambazov, L.; Donega, M.; Grab, C.; Hits, D.; Hoss, J.; Kasieczka, G.; Lustermann, W.; Mangano, B.; Marionneau, M.; Martinez Ruiz del Arbol, P.; Masciovecchio, M.; Meinhard, M.; Perozzi, L.; Roeser, U.; Starodumov, A.; Tavolaro, V.; Wallny, R.; Zhu, D.; Amsler, C.; Bösiger, K.; Caminada, L.; Canelli, F.; Chiochia, V.; de Cosa, A.; Galloni, C.; Hreus, T.; Kilminster, B.; Lange, C.; Maier, R.; Ngadiuba, J.; Pinna, D.; Robmann, P.; Taroni, S.; Yang, Y.; Bertl, W.; Deiters, K.; Erdmann, W.; Horisberger, R.; Kaestli, H.-C.; Kotlinski, D.; Langenegger, U.; Meier, B.; Rohe, T.; Streuli, S.; Chen, P.-H.; Dietz, C.; Grundler, U.; Hou, W.-S.; Lu, R.-S.; Moya, M.; Cussans, D.; Flacher, H.; Goldstein, J.; Grimes, M.; Jacob, J.; Seif El Nasr-Storey, S.; Cole, J.; Hoad, C.; Hobson, P.; Morton, A.; Reid, I. D.; Auzinger, G.; Bainbridge, R.; Dauncey, P.; Fulcher, J.; Hall, G.; James, T.; Magnan, A.-M.; Pesaresi, M.; Raymond, D. M.; Uchida, K.; Braga, D.; Coughlan, J. A.; Harder, K.; Jones, L.; Ilic, J.; Murray, P.; Prydderch, M.; Tomalin, I. R.; Garabedian, A.; Heintz, U.; Narain, M.; Nelson, J.; Sagir, S.; Speer, T.; Swanson, J.; Tersegno, D.; Watson-Daniels, J.; Chertok, M.; Conway, J.; Conway, R.; Flores, C.; Lander, R.; Pellett, D.; Ricci-Tam, F.; Squires, M.; Thomson, J.; Yohay, R.; Burt, K.; Ellison, J.; Hanson, G.; Olmedo, M.; Si, W.; Yates, B. R.; Gerosa, R.; Sharma, V.; Vartak, A.; Yagil, A.; Zevi Della Porta, G.; Dutta, V.; Gouskos, L.; Incandela, J.; Kyre, S.; Mullin, S.; Qu, H.; White, D.; Dominguez, A.; Bartek, R.; Cumalat, J. P.; Ford, W. T.; Jensen, F.; Johnson, A.; Krohn, M.; Leontsinis, S.; Mulholland, T.; Stenson, K.; Wagner, S. R.; Apresyan, A.; Bolla, G.; Burkett, K.; Butler, J. N.; Cheung, H. W. K.; Chramowicz, J.; Christian, D.; Cooper, W. E.; Deptuch, G.; Derylo, G.; Gingu, C.; Grünendahl, S.; Hasegawa, S.; Hoff, J.; Howell, J.; Hrycyk, M.; Jindariani, S.; Johnson, M.; Kahlid, F.; Lei, C. M.; Lipton, R.; Lopes De Sá, R.; Liu, T.; Los, S.; Matulik, M.; Merkel, P.; Nahn, S.; Prosser, A.; Rivera, R.; Schneider, B.; Sellberg, G.; Shenai, A.; Spiegel, L.; Tran, N.; Uplegger, L.; Voirin, E.; Berry, D. R.; Chen, X.; Ennesser, L.; Evdokimov, A.; Evdokimov, O.; Gerber, C. E.; Hofman, D. J.; Makauda, S.; Mills, C.; Sandoval Gonzalez, I. D.; Alimena, J.; Antonelli, L. J.; Francis, B.; Hart, A.; Hill, C. S.; Parashar, N.; Stupak, J.; Bortoletto, D.; Bubna, M.; Hinton, N.; Jones, M.; Miller, D. H.; Shi, X.; Tan, P.; Baringer, P.; Bean, A.; Khalil, S.; Kropivnitskaya, A.; Majumder, D.; Wilson, G.; Ivanov, A.; Mendis, R.; Mitchell, T.; Skhirtladze, N.; Taylor, R.; Anderson, I.; Fehling, D.; Gritsan, A.; Maksimovic, P.; Martin, C.; Nash, K.; Osherson, M.; Swartz, M.; Xiao, M.; Acosta, J. G.; Cremaldi, L. M.; Oliveros, S.; Perera, L.; Summers, D.; Bloom, K.; Claes, D. R.; Fangmeier, C.; Gonzalez Suarez, R.; Monroy, J.; Siado, J.; Hahn, K.; Sevova, S.; Sung, K.; Trovato, M.; Bartz, E.; Gershtein, Y.; Halkiadakis, E.; Kyriacou, S.; Lath, A.; Nash, K.; Osherson, M.; Schnetzer, S.; Stone, R.; Walker, M.; Malik, S.; Norberg, S.; Ramirez Vargas, J. E.; Alyari, M.; Dolen, J.; Godshalk, A.; Harrington, C.; Iashvili, I.; Kharchilava, A.; Nguyen, D.; Parker, A.; Rappoccio, S.; Roozbahani, B.; Alexander, J.; Chaves, J.; Chu, J.; Dittmer, S.; McDermott, K.; Mirman, N.; Rinkevicius, A.; Ryd, A.; Salvati, E.; Skinnari, L.; Soffi, L.; Tao, Z.; Thom, J.; Tucker, J.; Zientek, M.; Akgün, B.; Ecklund, K. M.; Kilpatrick, M.; Nussbaum, T.; Zabel, J.; Betchart, B.; Covarelli, R.; Demina, R.; Hindrichs, O.; Petrillo, G.; Eusebi, R.; Patel, R.; Perloff, A.; Ulmer, K. A.; Delannoy, A. G.; D'Angelo, P.; Johns, W.

    2018-03-01

    A new CMS Tracker is under development for operation at the High Luminosity LHC from 2026 onwards. It includes an outer tracker based on dedicated modules that will reconstruct short track segments, called stubs, using spatially coincident clusters in two closely spaced silicon sensor layers. These modules allow the rejection of low transverse momentum track hits and reduce the data volume before transmission to the first level trigger. The inclusion of tracking information in the trigger decision is essential to limit the first level trigger accept rate. A customized front-end readout chip, the CMS Binary Chip (CBC), containing stub finding logic has been designed for this purpose. A prototype module, equipped with the CBC chip, has been constructed and operated for the first time in a 4 GeemVem/emc positron beam at DESY. The behaviour of the stub finding was studied for different angles of beam incidence on a module, which allows an estimate of the sensitivity to transverse momentum within the future CMS detector. A sharp transverse momentum threshold around 2 emVem/emc was demonstrated, which meets the requirement to reject a large fraction of low momentum tracks present in the LHC environment on-detector. This is the first realistic demonstration of a silicon tracking module that is able to select data, based on the particle's transverse momentum, for use in a first level trigger at the LHC . The results from this test are described here.

  12. Modulation of cannabinoid signaling by hippocampal 5-HT4 serotonergic system in fear conditioning.

    Science.gov (United States)

    Nasehi, Mohammad; Farrahizadeh, Maryam; Ebrahimi-Ghiri, Mohaddeseh; Zarrindast, Mohammad-Reza

    2016-09-01

    Behavioral studies have suggested a key role for the cannabinoid system in the modulation of conditioned fear memory. Likewise, much of the literature has revealed that the serotonergic system affects Pavlovian fear conditioning and extinction. A high level of functional overlap between the serotonin and cannabinoid systems has also been reported. To clarify the interaction between the hippocampal serotonin (5-HT4) receptor and the cannabinoid CB1 receptor in the acquisition of fear memory, the effects of 5-HT4 agents, arachidonylcyclopropylamide (ACPA; CB1 receptor agonist), and the combined use of these drugs on fear learning were studied in a fear conditioning task in adult male NMRI mice. Pre-training intraperitoneal administration of ACPA (0.1 mg/kg) decreased the percentage of freezing time in both context- and tone-dependent fear conditions, suggesting impairment of the acquisition of fear memory. Pre-training, intra-hippocampal (CA1) microinjection of RS67333, a 5-HT4 receptor agonist, at doses of 0.1 and 0.2 or 0.2 µg/mouse impaired contextual and tone fear memory, respectively. A subthreshold dose of RS67333 (0.005 µg/mouse) did not alter the ACPA response in either condition. Moreover, intra-CA1 microinjection of RS23597 as a 5-HT4 receptor antagonist did not alter context-dependent fear memory acquisition, but it did impair tone-dependent fear memory acquisition. However, a subthreshold dose of the RS23597 (0.01 µg/mouse) potentiated ACPA-induced fear memory impairment in both conditions. Therefore, we suggest that the blockade of hippocampal 5-HT4 serotonergic system modulates cannabinoid signaling induced by the activation of CB1 receptors in conditioned fear. © The Author(s) 2016.

  13. Extremely low frequency electromagnetic field exposure does not modulate Toll-like receptor signaling in human peripheral blood mononuclear cells

    NARCIS (Netherlands)

    Kleijn, de S.; Bouwens, M.; Verburg-van Kemenade, B.M.L.; Cuppen, J.J.M.; Ferwerda, G.; Hermans, P.

    2011-01-01

    The effects of extremely low frequency electromagnetic fields (ELF-EMF) on human health remain unclear. It has been reported that ELF-EMF may modulate the innate immune response to microorganisms in animal models and mammalian cell-lines. With the recently gained insight in innate immune signaling

  14. Nonlinearity and Phase Noise Tolerant 75-110 GHz Signal over Fiber System Using Phase Modulation Technique

    DEFF Research Database (Denmark)

    Deng, Lei; Pang, Xiaodan; Zhang, Xu

    2013-01-01

    We report on the transmission of 8 Gb/s 0 dB PAPR 16QAM-OFDM W-band (75-110 GHz) signals over 22.8km SMF without phase noise compensation by using a phase modulator in the optical heterodyne up-convertor....

  15. Design, parametrization, and pole placement of stabilizing output feedback compensators via injective cogenerator quotient signal modules.

    Science.gov (United States)

    Blumthaler, Ingrid; Oberst, Ulrich

    2012-03-01

    Control design belongs to the most important and difficult tasks of control engineering and has therefore been treated by many prominent researchers and in many textbooks, the systems being generally described by their transfer matrices or by Rosenbrock equations and more recently also as behaviors. Our approach to controller design uses, in addition to the ideas of our predecessors on coprime factorizations of transfer matrices and on the parametrization of stabilizing compensators, a new mathematical technique which enables simpler design and also new theorems in spite of the many outstanding results of the literature: (1) We use an injective cogenerator signal module ℱ over the polynomial algebra [Formula: see text] (F an infinite field), a saturated multiplicatively closed set T of stable polynomials and its quotient ring [Formula: see text] of stable rational functions. This enables the simultaneous treatment of continuous and discrete systems and of all notions of stability, called T-stability. We investigate stabilizing control design by output feedback of input/output (IO) behaviors and study the full feedback IO behavior, especially its autonomous part and not only its transfer matrix. (2) The new technique is characterized by the permanent application of the injective cogenerator quotient signal module [Formula: see text] and of quotient behaviors [Formula: see text] of [Formula: see text]-behaviors B. (3) For the control tasks of tracking, disturbance rejection, model matching, and decoupling and not necessarily proper plants we derive necessary and sufficient conditions for the existence of proper stabilizing compensators with proper and stable closed loop behaviors, parametrize all such compensators as IO behaviors and not only their transfer matrices and give new algorithms for their construction. Moreover we solve the problem of pole placement or spectral assignability for the complete feedback behavior. The properness of the full feedback behavior

  16. In-band 16-QAM and multi-carrier SCM modulation to label DPSK payload signals for IP packet routing.

    Science.gov (United States)

    Tafur Monroy, Idelfonso; Vegas Olmos, Juan; Garcia Larrode, Maria; Koonen, Ton; Díaz Jiménez, Cristina

    2006-02-06

    We present an experimental demonstration of the feasibility of in-band subcarrier multiplexing (SCM) for labeling of differential phase shift keying (DPSK) payload signals. We show that by proper selection of the value of the subcarrier frequency the effect of the superimposed SCM label on the performance of the DPSK signal is minimized. Furthermore, we show experimentally the advantages of using alternative modulation formats such as 16-QAM and multi-carrier SCM for optical labeling of a 10 Gb/s DPSK payload signal.

  17. Improvement of a predictive model of castration-resistant prostate cancer: functional genetic variants in TGFβ1 signaling pathway modulation.

    Directory of Open Access Journals (Sweden)

    Ana L Teixeira

    Full Text Available Prostate cancer (PC is the most frequently diagnosed cancer in men. The acquisition of castration-resistant (CR phenotype is associated with the activation of signaling pathways mediated by growth factors. The TGFβ1 and its receptors have an important role in tumor progression, being the pro-apoptotic function modulated by the expression of TGFBR2. A single nucleotide polymorphism -875 G > A in TGFBR2 gene has been described, which may influence the expression levels of the receptor. Our purpose was to investigate the potential role of TGFBR2-875G>A in PC risk and in the response to androgen deprivation therapy (ADT. TGFBR2-875G>A polymorphism was studied by allelic discrimination using real-time polymerase chain reaction (PCR in 891 patients with PC and 874 controls. A follow-up study was undertaken to evaluate response to ADT. The TGFBR2 and SMAD7 mRNA expression were analyzed by a quantitative real-time PCR. We found that TGFBR2-875GG homozygous patients present lower expression levels of TGFBR2 mRNA (AA/AG: 2(-ΔΔCT =1.5, P=0.016. GG genotype was also associated with higher Gleason grade (OR=1.51, P=0.019 and increased risk of an early relapse after ADT (HR=1.47, P=0.024. The concordance (c index analysis showed that the definition of profiles that contains information regarding tumor characteristics associated with genetic information present an increased capacity to predict the risk for CR development (c-index model 1: 0.683 vs model 2: 0.736 vs model 3: 0.746 vs model 4: 0.759. The TGFBR2-875G>A contribution to an early relapse in ADT patients, due to changes in mRNA expression, supports the involvement of TGFβ1 pathway in CRPC. Furthermore, according to our results, we hypothesize the potential benefits of the association of genetic information in predictive models of CR development.

  18. KIR2DL4 differentially signals downstream functions in human NK cells through distinct structural modules.

    Science.gov (United States)

    Miah, S M Shahjahan; Hughes, Tracey L; Campbell, Kerry S

    2008-03-01

    KIR2DL4 (2DL4) is a member of the killer cell Ig-like receptor (KIR) family in human NK cells. It can stimulate potent cytokine production and weak cytolytic activity in resting NK cells, but the mechanism for 2DL4-mediated signaling remains unclear. In this study we characterized the signaling pathways stimulated by 2DL4 engagement. In a human NK-like cell line, KHYG-1, cross-linking of 2DL4 activated MAPKs including JNK, ERK, and p38. Furthermore, 2DL4 cross-linking resulted in phosphorylation of IkappaB kinase beta (IKKbeta) and the phosphorylation and degradation of IkappaBalpha, which indicate activation of the classical NF-kappaB pathway. Engagement of 2DL4 was also shown to activate the transcription and translation of a variety of cytokine genes, including TNF-alpha, IFN-gamma, MIP1alpha, MIP1beta, and IL-8. Pharmacological inhibitors of JNK, MEK1/2 and p38, blocked IFN-gamma, IL-8, and MIP1alpha production, suggesting that MAPKs are regulating 2DL4-mediated cytokine production in a nonredundant manner. Activation of both p38 and ERK appear to be upstream of the stimulation of NF-kappaB. Mutation of a transmembrane arginine in 2DL4 to glycine (R/G mutant) abrogated FcepsilonRI-gamma association, as well as receptor-mediated cytolytic activity and calcium responses. Surprisingly, the R/G mutant still activated MAPKs and the NF-kappaB pathway and selectively stimulated the production of MIP1alpha, but not that of IFN-gamma or IL-8. In conclusion, we provide evidence that the activating functions of 2DL4 can be compartmentalized into two distinct structural modules: 1) through transmembrane association with FcepsilonRI-gamma; and 2) through another receptor domain independent of the transmembrane arginine.

  19. C. elegans VANG-1 modulates life span via insulin/IGF-1-like signaling.

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    Sebastian J Honnen

    Full Text Available The planar cell polarity (PCP pathway is highly conserved from Drosophila to humans and a PCP-like pathway has recently been described in the nematode Caenorhabditis elegans. The developmental function of this pathway is to coordinate the orientation of cells or structures within the plane of an epithelium or to organize cell-cell intercalation required for correct morphogenesis. Here, we describe a novel role of VANG-1, the only C. elegans ortholog of the conserved PCP component Strabismus/Van Gogh. We show that two alleles of vang-1 and depletion of the protein by RNAi cause an increase of mean life span up to 40%. Consistent with the longevity phenotype vang-1 animals also show enhanced resistance to thermal- and oxidative stress and decreased lipofuscin accumulation. In addition, vang-1 mutants show defects like reduced brood size, decreased ovulation rate and prolonged reproductive span, which are also related to gerontogenes. The germline, but not the intestine or neurons, seems to be the primary site of vang-1 function. Life span extension in vang-1 mutants depends on the insulin/IGF-1-like receptor DAF-2 and DAF-16/FoxO transcription factor. RNAi against the phase II detoxification transcription factor SKN-1/Nrf2 also reduced vang-1 life span that might be explained by gradual inhibition of insulin/IGF-1-like signaling in vang-1. This is the first time that a key player of the PCP pathway is shown to be involved in the insulin/IGF-1-like signaling dependent modulation of life span in C. elegans.

  20. Pedilanthus tithymaloides Inhibits HSV Infection by Modulating NF-κB Signaling.

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    Durbadal Ojha

    Full Text Available Pedilanthus tithymaloides (PT, a widely used ethnomedicinal plant, has been employed to treat a number of skin conditions. To extend its utility and to fully exploit its medicinal potential, we have evaluated the in vitro antiviral activity of a methanolic extract of PT leaves and its isolated compounds against Herpes Simplex Virus type 2 (HSV-2. Bioactivity-guided studies revealed that the extract and one of its constituents, luteolin, had potent antiviral activity against wild-type and clinical isolates of HSV-2 (EC50 48.5-52.6 and 22.4-27.5 μg/ml, respectively, with nearly complete inhibition at 86.5-101.8 and 40.2-49.6 μg/ml, respectively. The inhibitory effect was significant (p<0.001 when the drug was added 2 h prior to infection, and was effective up to 4 h post-infection. As viral replication requires NF-κB activation, we examined whether the observed extract-induced inhibition of HSV-2 was related to NF-κB inhibition. Interestingly, we observed that treatment of HSV-2-infected cells with extract or luteolin suppressed NF-κB activation. Although NF-κB, JNK and MAPK activation was compromised during HSV replication, neither the extract nor luteolin affected HSV-2-induced JNK1/2 and MAPK activation. Moreover, the PT leaf extract and luteolin potently down-regulated the expression of tumor necrosis factor (TNF-α, Interleukin (IL-1β, IL-6, NO and iNOS and the production of gamma interferon (IFN-γ, which are directly involved in controlling the NF-κB signaling pathway. Thus, our results indicate that both PT leaf extract and luteolin modulate the NF-κB signaling pathway, resulting in the inhibition of HSV-2 replication.

  1. An Endogenous Electron Spin Resonance (ESR signal discriminates nevi from melanomas in human specimens: a step forward in its diagnostic application.

    Directory of Open Access Journals (Sweden)

    Eleonora Cesareo

    Full Text Available Given the specific melanin-associated paramagnetic features, the Electron Spin Resonance (ESR, called also Electron Paramagnetic Resonance, EPR analysis has been proposed as a potential tool for non-invasive melanoma diagnosis. However, studies comparing human melanoma tissues to the most appropriate physiological counterpart (nevi have not been performed, and ESR direct correlation with melanoma clinical features has never been investigated. ESR spectrum was obtained from melanoma and non-melanoma cell-cultures as well as mouse melanoma and non-melanoma tissues and an endogenous ESR signal (g = 2.005 was found in human melanoma cells and in primary melanoma tissues explanted from mice, while it was always absent in non-melanoma samples. These characteristics of the measured ESR signal strongly suggested its connection with melanin. Quantitative analyses were then performed on paraffin-embedded human melanoma and nevus sections, and validated on an independent larger validation set, for a total of 112 sections (52 melanomas, 60 nevi. The ESR signal was significantly higher in melanomas (p = 0.0002 and was significantly different between "Low Breslow's and "High Breslow's" depth melanomas (p<0.0001. A direct correlation between ESR signal and Breslow's depth, expressed in millimetres, was found (R = 0.57; p<0.0001. The eu/pheomelanin ratio was found to be significantly different in melanomas "Low Breslow's" vs melanomas "High Breslow's" depth and in nevi vs melanomas "High Breslow's depth". Finally, ROC analysis using ESR data discriminated melanomas sections from nevi sections with up to 90% accuracy and p<0.0002. In the present study we report for the first time that ESR signal in human paraffin-embedded nevi is significantly lower than signal in human melanomas suggesting that spectrum variations may be related to qualitative melanin differences specifically occurring in melanoma cells. We therefore conclude that this ESR signal

  2. The APC/C Coordinates Retinal Differentiation with G1 Arrest through the Nek2-Dependent Modulation of Wingless Signaling.

    Science.gov (United States)

    Martins, Torcato; Meghini, Francesco; Florio, Francesca; Kimata, Yuu

    2017-01-09

    The cell cycle is coordinated with differentiation during animal development. Here we report a cell-cycle-independent developmental role for a master cell-cycle regulator, the anaphase-promoting complex or cyclosome (APC/C), in the regulation of cell fate through modulation of Wingless (Wg) signaling. The APC/C controls both cell-cycle progression and postmitotic processes through ubiquitin-dependent proteolysis. Through an RNAi screen in the developing Drosophila eye, we found that partial APC/C inactivation severely inhibits retinal differentiation independently of cell-cycle defects. The differentiation inhibition coincides with hyperactivation of Wg signaling caused by the accumulation of a Wg modulator, Drosophila Nek2 (dNek2). The APC/C degrades dNek2 upon synchronous G1 arrest prior to differentiation, which allows retinal differentiation through local suppression of Wg signaling. We also provide evidence that decapentaplegic signaling may posttranslationally regulate this APC/C function. Thus, the APC/C coordinates cell-fate determination with the cell cycle through the modulation of developmental signaling pathways. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  3. Role of adipokines signaling in the modulation of T cells function

    Directory of Open Access Journals (Sweden)

    Claudio eProcaccini

    2013-10-01

    Full Text Available The field that links immunity and metabolism is rapidly expanding. Apparently non-immunological disorders such as obesity and type 2 diabetes have been linked to immune dysregulation, suggesting that metabolic alterations can be induced by or be consequence of an altered self-immune tolerance. In this context, adipose tissue produces and releases a variety of proinflammatory and anti-inflammatory factors, termed adipokines, which can be considered as the bridge between obesity-related exogenous factors, such as nutrition and lifestyle, and the molecular events leading to metabolic syndrome, inflammatory and/or autoimmune conditions. In obesity, increased production of most adipokines impacts on multiple functions such as appetite and energy balance, modulation of immune responses, insulin sensitivity, angiogenesis, blood pressure, lipid metabolism, and so on. This report aims to discuss some of the recent topics of adipocytokine research and their related signaling pathways, that may be of particular importance as could lead to effective therapeutic strategies for obesity-associated diseases.

  4. The Potential Role of Cannabinoids in Modulating Serotonergic Signaling by Their Influence on Tryptophan Metabolism

    Directory of Open Access Journals (Sweden)

    Dietmar Fuchs

    2010-08-01

    Full Text Available Phytocannabinoids present in Cannabis plants are well known to exert potent anti-inflammatory and immunomodulatory effects. Previously, we have demonstrated that the psychoactive D9-tetrahydrocannabinol (THC and the non-psychotropic cannabidiol (CBD modulate mitogen-induced Th1-type immune responses in peripheral blood mononuclear cells (PBMC. The suppressive effect of both cannabinoids on mitogen-induced tryptophan degradation mediated by indoleamine-2,3-dioxygenase (IDO, suggests an additional mechanism by which antidepressive effects of cannabinoids might be linked to the serotonergic system. Here, we will review the role of tryptophan metabolism in the course of cell mediated immune responses and the relevance of cannabinoids in serotonergic signaling. We conclude that in particular the non-psychotropic CBD might be useful for the treatment of mood disorders in patients with inflammatory diseases, since this cannabinoid seems to be safe and its effects on activation-induced tryptophan degradation by CBD were more potent as compared to THC.

  5. The Adenovirus E1A C Terminus Suppresses a Delayed Antiviral Response and Modulates RAS Signaling.

    Science.gov (United States)

    Zemke, Nathan R; Berk, Arnold J

    2017-12-13

    The N-terminal half of adenovirus e1a assembles multimeric complexes with host proteins that repress innate immune responses and force host cells into S-phase. In contrast, the functions of e1a's C-terminal interactions with FOXK, DCAF7, and CtBP are unknown. We found that these interactions modulate RAS signaling, and that a single e1a molecule must bind all three of these host proteins to suppress activation of a subset of IFN-stimulated genes (ISGs). These ISGs were otherwise induced in primary respiratory epithelial cells at 12 hr p.i. This delayed activation of ISGs required IRF3 and coincided with an ∼10-fold increase in IRF3 from protein stabilization. The induced IRF3 bound to chromatin and localized to the promoters of activated ISGs. While IRF3, STAT1/2, and IRF9 all greatly increased in concentration, there were no corresponding mRNA increases, suggesting that e1a regulates the stabilities of these key activators of innate immune responses, as shown directly for IRF3. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Mediator Med23 deficiency enhances neural differentiation of murine embryonic stem cells through modulating BMP signaling.

    Science.gov (United States)

    Zhu, Wanqu; Yao, Xiao; Liang, Yan; Liang, Dan; Song, Lu; Jing, Naihe; Li, Jinsong; Wang, Gang

    2015-02-01

    Unraveling the mechanisms underlying early neural differentiation of embryonic stem cells (ESCs) is crucial to developing cell-based therapies of neurodegenerative diseases. Neural fate acquisition is proposed to be controlled by a 'default' mechanism, for which the molecular regulation is not well understood. In this study, we investigated the functional roles of Mediator Med23 in pluripotency and lineage commitment of murine ESCs. Unexpectedly, we found that, despite the largely unchanged pluripotency and self-renewal of ESCs, Med23 depletion rendered the cells prone to neural differentiation in different differentiation assays. Knockdown of two other Mediator subunits, Med1 and Med15, did not alter the neural differentiation of ESCs. Med15 knockdown selectively inhibited endoderm differentiation, suggesting the specificity of cell fate control by distinctive Mediator subunits. Gene profiling revealed that Med23 depletion attenuated BMP signaling in ESCs. Mechanistically, MED23 modulated Bmp4 expression by controlling the activity of ETS1, which is involved in Bmp4 promoter-enhancer communication. Interestingly, med23 knockdown in zebrafish embryos also enhanced neural development at early embryogenesis, which could be reversed by co-injection of bmp4 mRNA. Taken together, our study reveals an intrinsic, restrictive role of MED23 in early neural development, thus providing new molecular insights for neural fate determination. © 2015. Published by The Company of Biologists Ltd.

  7. Modulation of BCR Signaling by the Induced Dimerization of Receptor-Associated SYK

    Directory of Open Access Journals (Sweden)

    Mark L. Westbroek

    2017-12-01

    Full Text Available Clustering of the B cell antigen receptor (BCR by polyvalent antigens is transmitted through the SYK tyrosine kinase to the activation of multiple intracellular pathways that determine the physiological consequences of receptor engagement. To explore factors that modulate the quantity and quality of signals sent by the crosslinked BCR, we developed a novel chemical mediator of dimerization to induce clustering of receptor-associated SYK. To accomplish this, we fused SYK with E. coli dihydrofolate reductase (eDHFR, which binds the small molecule trimethoprim (TMP with high affinity and selectivity and synthesized a dimer of TMP with a flexible linker. The TMP dimer is able to induce the aggregation of eDHFR-linked SYK in live cells. The induced dimerization of SYK bound to the BCR differentially regulates the activation of downstream transcription factors, promoting the activation of Nuclear Factor of Activated T cells (NFAT without affecting the activation of NFκB. The dimerization of SYK enhances the duration but not the amplitude of calcium mobilization by enhancing the extent and duration of its interaction with the crosslinked BCR at the plasma membrane.

  8. Social discounting involves modulation of neural value signals by temporoparietal junction

    Science.gov (United States)

    Strombach, Tina; Weber, Bernd; Hangebrauk, Zsofia; Kenning, Peter; Karipidis, Iliana I.; Tobler, Philippe N.; Kalenscher, Tobias

    2015-01-01

    Most people are generous, but not toward everyone alike: generosity usually declines with social distance between individuals, a phenomenon called social discounting. Despite the pervasiveness of social discounting, social distance between actors has been surprisingly neglected in economic theory and neuroscientific research. We used functional magnetic resonance imaging (fMRI) to study the neural basis of this process to understand the neural underpinnings of social decision making. Participants chose between selfish and generous alternatives, yielding either a large reward for the participant alone, or smaller rewards for the participant and another individual at a particular social distance. We found that generous choices engaged the temporoparietal junction (TPJ). In particular, the TPJ activity was scaled to the social-distance–dependent conflict between selfish and generous motives during prosocial choice, consistent with ideas that the TPJ promotes generosity by facilitating overcoming egoism bias. Based on functional coupling data, we propose and provide evidence for a biologically plausible neural model according to which the TPJ supports social discounting by modulating basic neural value signals in the ventromedial prefrontal cortex to incorporate social-distance–dependent other-regarding preferences into an otherwise exclusively own-reward value representation. PMID:25605887

  9. TLR4 Signaling Pathway Modulators as Potential Therapeutics in Inflammation and Sepsis

    Directory of Open Access Journals (Sweden)

    Nikolay N. Kuzmich

    2017-10-01

    Full Text Available Toll-Like Receptor 4 (TLR4 signal pathway plays an important role in initiating the innate immune response and its activation by bacterial endotoxin is responsible for chronic and acute inflammatory disorders that are becoming more and more frequent in developed countries. Modulation of the TLR4 pathway is a potential strategy to specifically target these pathologies. Among the diseases caused by TLR4 abnormal activation by bacterial endotoxin, sepsis is the most dangerous one because it is a life-threatening acute system inflammatory condition that still lacks specific pharmacological treatment. Here, we review molecules at a preclinical or clinical phase of development, that are active in inhibiting the TLR4-MyD88 and TLR4-TRIF pathways in animal models. These are low-molecular weight compounds of natural and synthetic origin that can be considered leads for drug development. The results of in vivo studies in the sepsis model and the mechanisms of action of drug leads are presented and critically discussed, evidencing the differences in treatment results from rodents to humans.

  10. Modulation of legume defense signaling pathways by native and non-native pea aphid clones

    Directory of Open Access Journals (Sweden)

    Carlos Sanchez-Arcos

    2016-12-01

    suggest that A. pisum clones manipulate plant-defense signaling to their own advantage, and perform better on their native hosts due to their ability to modulate the SA- and JA-defense signaling pathways.

  11. Advanced signal processing analysis of laser-induced breakdown spectroscopy data for the discrimination of obsidian sources.

    Science.gov (United States)

    Remus, Jeremiah J; Harmon, Russell S; Hark, Richard R; Haverstock, Gregory; Baron, Dirk; Potter, Ian K; Bristol, Samantha K; East, Lucille J

    2012-03-01

    Obsidian is a natural glass of volcanic origin and a primary resource used by indigenous peoples across North America for making tools. Geochemical studies of obsidian enhance understanding of artifact production and procurement and remain a priority activity within the archaeological community. Laser-induced breakdown spectroscopy (LIBS) is an analytical technique being examined as a means for identifying obsidian from different sources on the basis of its 'geochemical fingerprint'. This study tested whether two major California obsidian centers could be distinguished from other obsidian localities and the extent to which subsources could be recognized within each of these centers. LIBS data sets were collected in two different spectral bands (350±130 nm and 690±115 nm) using a Nd:YAG 1064 nm laser operated at ~23 mJ, a Czerny-Turner spectrograph with 0.2-0.3 nm spectral resolution and a high performance imaging charge couple device (ICCD) detector. Classification of the samples was performed using partial least-squares discriminant analysis (PLSDA), a common chemometric technique for performing statistical regression on high-dimensional data. Discrimination of samples from the Coso Volcanic Field, Bodie Hills, and other major obsidian areas in north-central California was possible with an accuracy of greater than 90% using either spectral band. © 2012 Optical Society of America

  12. Distraction or cognitive overload? Using modulations of the autonomic nervous system to discriminate the possible negative effects of advanced assistance system.

    Science.gov (United States)

    Ruscio, D; Bos, A J; Ciceri, M R

    2017-06-01

    The interaction with Advanced Driver Assistance Systems has several positive implications for road safety, but also some potential downsides such as mental workload and automation complacency. Malleable attentional resources allocation theory describes two possible processes that can generate workload in interaction with advanced assisting devices. The purpose of the present study is to determine if specific analysis of the different modalities of autonomic control of nervous system can be used to discriminate different potential workload processes generated during assisted-driving tasks and automation complacency situations. Thirty-five drivers were tested in a virtual scenario while using head-up advanced warning assistance system. Repeated MANOVA were used to examine changes in autonomic activity across a combination of different user interactions generated by the advanced assistance system: (1) expected take-over request without anticipatory warning; (2) expected take-over request with two-second anticipatory warning; (3) unexpected take-over request with misleading warning; (4) unexpected take-over request without warning. Results shows that analysis of autonomic modulations can discriminate two different resources allocation processes, related to different behavioral performances. The user's interaction that required divided attention under expected situations produced performance enhancement and reciprocally-coupled parasympathetic inhibition with sympathetic activity. At the same time, supervising interactions that generated automation complacency were described specifically by uncoupled sympathetic activation. Safety implications for automated assistance systems developments are considered. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Response Analysis on Electrical Pulses under Severe Nuclear Accident Temperature Conditions Using an Abnormal Signal Simulation Analysis Module

    Directory of Open Access Journals (Sweden)

    Kil-Mo Koo

    2012-01-01

    Full Text Available Unlike design basis accidents, some inherent uncertainties of the reliability of instrumentations are expected while subjected to harsh environments (e.g., high temperature and pressure, high humidity, and high radioactivity occurring in severe nuclear accident conditions. Even under such conditions, an electrical signal should be within its expected range so that some mitigating actions can be taken based on the signal in the control room. For example, an industrial process control standard requires that the normal signal level for pressure, flow, and resistance temperature detector sensors be in the range of 4~20 mA for most instruments. Whereas, in the case that an abnormal signal is expected from an instrument, such a signal should be refined through a signal validation process so that the refined signal could be available in the control room. For some abnormal signals expected under severe accident conditions, to date, diagnostics and response analysis have been evaluated with an equivalent circuit model of real instruments, which is regarded as the best method. The main objective of this paper is to introduce a program designed to implement a diagnostic and response analysis for equivalent circuit modeling. The program links signal analysis tool code to abnormal signal simulation engine code not only as a one body order system, but also as a part of functions of a PC-based ASSA (abnormal signal simulation analysis module developed to obtain a varying range of the R-C circuit elements in high temperature conditions. As a result, a special function for abnormal pulse signal patterns can be obtained through the program, which in turn makes it possible to analyze the abnormal output pulse signals through a response characteristic of a 4~20 mA circuit model and a range of the elements changing with temperature under an accident condition.

  14. Coherent Detection of Wavelength Division Multiplexed Phase-Modulated Radio-over-Fibre Signals

    DEFF Research Database (Denmark)

    Zibar, Darko; Yu, Xianbin; Peucheret, Christophe

    2008-01-01

    A WDM phase-modulated Radio-over-Fibre link using digital coherent detection is experimentally demonstrated. 3 times 50 Mb/s WDM transmission of a BPSK modulated 5 GHz RF carrier is achieved over 25 km.......A WDM phase-modulated Radio-over-Fibre link using digital coherent detection is experimentally demonstrated. 3 times 50 Mb/s WDM transmission of a BPSK modulated 5 GHz RF carrier is achieved over 25 km....

  15. The Parsing Syllable Envelopes Test for Assessment of Amplitude Modulation Discrimination Skills in Children: Development, Normative Data, and Test-Retest Reliability Studies.

    Science.gov (United States)

    Cameron, Sharon; Chong-White, Nicky; Mealings, Kiri; Beechey, Tim; Dillon, Harvey; Young, Taegan

    2018-02-01

    Intensity peaks and valleys in the acoustic signal are salient cues to syllable structure, which is accepted to be a crucial early step in phonological processing. As such, the ability to detect low-rate (envelope) modulations in signal amplitude is essential to parse an incoming speech signal into smaller phonological units. The Parsing Syllable Envelopes (ParSE) test was developed to quantify the ability of children to recognize syllable boundaries using an amplitude modulation detection paradigm. The envelope of a 750-msec steady-state /a/ vowel is modulated into two or three pseudo-syllables using notches with modulation depths varying between 0% and 100% along an 11-step continuum. In an adaptive three-alternative forced-choice procedure, the participant identified whether one, two, or three pseudo-syllables were heard. Development of the ParSE stimuli and test protocols, and collection of normative and test-retest reliability data. Eleven adults (aged 23 yr 10 mo to 50 yr 9 mo, mean 32 yr 10 mo) and 134 typically developing, primary-school children (aged 6 yr 0 mo to 12 yr 4 mo, mean 9 yr 3 mo). There were 73 males and 72 females. Data were collected using a touchscreen computer. Psychometric functions (PFs) were automatically fit to individual data by the ParSE software. Performance was related to the modulation depth at which syllables can be detected with 88% accuracy (referred to as the upper boundary of the uncertainty region [UBUR]). A shallower PF slope reflected a greater level of uncertainty. Age effects were determined based on raw scores. z Scores were calculated to account for the effect of age on performance. Outliers, and individual data for which the confidence interval of the UBUR exceeded a maximum allowable value, were removed. Nonparametric tests were used as the data were skewed toward negative performance. Across participants, the performance criterion (UBUR) was met with a median modulation depth of 42%. The effect of age on the UBUR was

  16. Signal yields of keV electronic recoils and their discrimination from nuclear recoils in liquid xenon

    Science.gov (United States)

    Aprile, E.; Aalbers, J.; Agostini, F.; Alfonsi, M.; Amaro, F. D.; Anthony, M.; Arneodo, F.; Barrow, P.; Baudis, L.; Bauermeister, B.; Benabderrahmane, M. L.; Berger, T.; Breur, P. A.; Brown, A.; Brown, E.; Bruenner, S.; Bruno, G.; Budnik, R.; Bütikofer, L.; Calvén, J.; Cardoso, J. M. R.; Cervantes, M.; Cichon, D.; Coderre, D.; Colijn, A. P.; Conrad, J.; Cussonneau, J. P.; Decowski, M. P.; de Perio, P.; di Gangi, P.; di Giovanni, A.; Diglio, S.; Eurin, G.; Fei, J.; Ferella, A. D.; Fieguth, A.; Fulgione, W.; Gallo Rosso, A.; Galloway, M.; Gao, F.; Garbini, M.; Geis, C.; Goetzke, L. W.; Grandi, L.; Greene, Z.; Grignon, C.; Hasterok, C.; Hogenbirk, E.; Howlett, J.; Itay, R.; Kaminsky, B.; Kazama, S.; Kessler, G.; Kish, A.; Landsman, H.; Lang, R. F.; Lellouch, D.; Levinson, L.; Lin, Q.; Lindemann, S.; Lindner, M.; Lombardi, F.; Lopes, J. A. M.; Mahlstedt, J.; Manfredini, A.; Maris, I.; Marrodán Undagoitia, T.; Masbou, J.; Massoli, F. V.; Masson, D.; Mayani, D.; Messina, M.; Micheneau, K.; Molinario, A.; Morâ, K.; Murra, M.; Naganoma, J.; Ni, K.; Oberlack, U.; Pakarha, P.; Pelssers, B.; Persiani, R.; Piastra, F.; Pienaar, J.; Pizzella, V.; Piro, M.-C.; Plante, G.; Priel, N.; Ramírez García, D.; Rauch, L.; Reichard, S.; Reuter, C.; Rizzo, A.; Rupp, N.; Saldanha, R.; Dos Santos, J. M. F.; Sartorelli, G.; Scheibelhut, M.; Schindler, S.; Schreiner, J.; Schumann, M.; Scotto Lavina, L.; Selvi, M.; Shagin, P.; Shockley, E.; Silva, M.; Simgen, H.; Sivers, M. V.; Stein, A.; Thers, D.; Tiseni, A.; Trinchero, G.; Tunnell, C.; Vargas, M.; Wang, H.; Wang, Z.; Wei, Y.; Weinheimer, C.; Wittweg, C.; Wulf, J.; Ye, J.; Zhang, Y.; Zhu, T.; Xenon Collaboration

    2018-05-01

    We report on the response of liquid xenon to low energy electronic recoils below 15 keV from beta decays of tritium at drift fields of 92 V /cm , 154 V /cm and 366 V /cm using the XENON100 detector. A data-to-simulation fitting method based on Markov Chain Monte Carlo is used to extract the photon yields and recombination fluctuations from the experimental data. The photon yields measured at the two lower fields are in agreement with those from literature; additional measurements at a higher field of 366 V /cm are presented. The electronic and nuclear recoil discrimination as well as its dependence on the drift field and photon detection efficiency are investigated at these low energies. The results provide new measurements in the energy region of interest for dark matter searches using liquid xenon.

  17. Supernatant from bifidobacterium differentially modulates transduction signaling pathways for biological functions of human dendritic cells.

    Directory of Open Access Journals (Sweden)

    Cyrille Hoarau

    Full Text Available BACKGROUND: Probiotic bacteria have been shown to modulate immune responses and could have therapeutic effects in allergic and inflammatory disorders. However, the signaling pathways engaged by probiotics are poorly understood. We have previously reported that a fermentation product from Bifidobacterium breve C50 (BbC50sn could induce maturation, high IL-10 production and prolonged survival of DCs via a TLR2 pathway. We therefore studied the roles of mitogen-activated protein kinases (MAPK, glycogen synthase kinase-3 (GSK3 and phosphatidylinositol 3-kinase (PI3K pathways on biological functions of human monocyte-derived DCs treated with BbC50sn. METHODOLOGY/PRINCIPAL FINDINGS: DCs were differentiated from human monocytes with IL-4 and GM-CSF for 5 days and cultured with BbC50sn, lipopolysaccharide (LPS or Zymosan, with or without specific inhibitors of p38MAPK (SB203580, ERK (PD98059, PI3K (LY294002 and GSK3 (SB216763. We found that 1 the PI3K pathway was positively involved in the prolonged DC survival induced by BbC50sn, LPS and Zymosan in contrast to p38MAPK and GSK3 which negatively regulated DC survival; 2 p38MAPK and PI3K were positively involved in DC maturation, in contrast to ERK and GSK3 which negatively regulated DC maturation; 3 ERK and PI3K were positively involved in DC-IL-10 production, in contrast to GSK3 that was positively involved in DC-IL-12 production whereas p38MAPK was positively involved in both; 4 BbC50sn induced a PI3K/Akt phosphorylation similar to Zymosan and a p38MAPK phosphorylation similar to LPS. CONCLUSION/SIGNIFICANCE: We report for the first time that a fermentation product of a bifidobacteria can differentially activate MAPK, GSK3 and PI3K in order to modulate DC biological functions. These results give new insights on the fine-tuned balance between the maintenance of normal mucosal homeostasis to commensal and probiotic bacteria and the specific inflammatory immune responses to pathogen bacteria.

  18. Electrical system for pulse-width modulated control of a power inverter using phase-shifted carrier signals and related operating methods

    Science.gov (United States)

    Welchko, Brian A [Torrance, CA

    2012-02-14

    Systems and methods are provided for pulse-width modulated control of power inverter using phase-shifted carrier signals. An electrical system comprises an energy source and a motor. The motor has a first set of windings and a second set of windings, which are electrically isolated from each other. An inverter module is coupled between the energy source and the motor and comprises a first set of phase legs coupled to the first set of windings and a second set of phase legs coupled to the second set of windings. A controller is coupled to the inverter module and is configured to achieve a desired power flow between the energy source and the motor by modulating the first set of phase legs using a first carrier signal and modulating the second set of phase legs using a second carrier signal. The second carrier signal is phase-shifted relative to the first carrier signal.

  19. Dietary chlorophyllin abrogates TGFβ signaling to modulate the hallmark capabilities of cancer in an animal model of forestomach carcinogenesis.

    Science.gov (United States)

    Thiyagarajan, Paranthaman; Kavitha, Krishnamurthy; Thautam, Avaneesh; Dixit, Madhulika; Nagini, Siddavaram

    2014-07-01

    Transforming growth factor (TGF) β signaling pathway plays a central role in the regulation of a wide range of cellular processes involved in the acquisition of the malignant phenotype. The objective of the present study was to examine the effect of chlorophyllin, a semisynthetic derivative of chlorophyll on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)--induced rat forestomach carcinogenesis based on the modulation of TGFβ signaling and the downstream target genes associated with cell proliferation, apoptosis evasion, angiogenesis, invasion, and metastasis. We determined the effect of dietary chlorophyllin on TGFβ signaling and the downstream events-cell proliferation, apoptosis evasion, angiogenesis, invasion, and metastasis by semiquantitative and quantitative reverse transcription (RT)-PCR, Western blot, and immunohistochemical analyses. We further validated the inhibition of TGFβ signaling by chlorophyllin by performing molecular docking studies. We found that dietary supplementation of chlorophyllin at 4-mg/kg bw inhibits the development of MNNG-induced forestomach carcinomas by downregulating the expression of TGFβ RI, TGFβ RII, and Smad 2 and 4 and upregulating Smad 7, thereby abrogating canonical TGFβ signaling. Docking interactions also confirmed the inhibition of TGFβ signaling by chlorophyllin via inactivating TGFβ RI. Furthermore, attenuation of TGFβ signaling by chlorophyllin also blocked cell proliferation, angiogenesis, invasion, and metastasis, and induced mitochondria-mediated cell death. Dietary chlorophyllin that simultaneously abrogates TGFβ signaling pathway and the key hallmark events of cancer appear to be an ideal candidate for cancer chemoprevention.

  20. W-band OFDM photonic vector signal generation employing a single Mach-Zehnder modulator and precoding.

    Science.gov (United States)

    Xiao, Jiangnan; Li, Xinying; Xu, Yuming; Zhang, Ziran; Chen, Long; Yu, Jianjun

    2015-09-07

    We present a simple radio-over-fiber (RoF) link architecture for millimeter-wave orthogonal frequency division multiplexing (OFDM) transmission using only one Mach-Zehnder modulator (MZM) and precoding technique. In the transmission system, the amplitudes and the phase of the driving radio-frequency (RF) OFDM signal on each sub-carrier are precoded, to ensure that the OFDM signal after photodetector (PD) can be restored to original OFDM signal. The experimental results show that the bit-error ratios (BERs) of the transmission system are less than the forward-error-correction (FEC) threshold of 3.8 × 10(-3), which demonstrates that the generation of OFDM vector signal based on our proposed scheme can be employed in our system architecture.

  1. Simulated performance of an acoustic modem using phase-modulated signals in a time-varying, shallow-water environment

    DEFF Research Database (Denmark)

    Bjerrum-Niese, Christian; Jensen, Leif Bjørnø

    1996-01-01

    and dynamic multipath channel. Multipath arrivals at the receiver cause phase distortion and fading of the signal envelope. Yet, for extreme ratios of range to depth, the delays of multipath arrivals decrease, and the channel impulse response coherently contributes energy to the signal at short delays......Underwater acoustic modems using coherent modulation, such as phase-shift keying, have proven to efficiently exploit the bandlimited underwater acoustical communication channel. However, the performance of an acoustic modem, given as maximum range and data and error rate, is limited in the complex...... relative to the first arrival, while longer delays give rise to intersymbol interference. Following this, the signal-to-multipath ratio (SMR) is introduced. It is claimed that the SMR determines the performance rather than the signal-to-noise ratio (SNR). Using a ray model including temporal variations...

  2. Modulation of ASIC channels in rat cerebellar purkinje neurons by ischaemia-related signals

    Science.gov (United States)

    Allen, Nicola J; Attwell, David

    2002-01-01

    Acid-sensing ion channels (ASICs), activated by a decrease of extracellular pH, are found in neurons throughout the nervous system. They have an amino acid sequence similar to that of ion channels activated by membrane stretch, and have been implicated in touch sensation. Here we characterize the pH-dependent activation of ASICs in cerebellar Purkinje cells and investigate how they are modulated by factors released in ischaemia. Lowering the external pH from 7.4 activated an inward current at −66 mV, carried largely by Na+ ions, which was half-maximal for a step to pH 6.4 and was blocked by amiloride and gadolinium. The H+-gated current desensitized within a few seconds, but approximately 30% of cells showed a sustained inward current (11% of the peak current) in response to the maintained presence of pH 6 solution. The peak H+-evoked current was potentiated by membrane stretch (which occurs in ischaemia when [K+]o rises) and by arachidonic acid (which is released when [Ca2+]i rises in ischaemia). Arachidonic acid increased to 77% the fraction of cells showing a sustained current evoked by acid pH. The ASIC currents were also potentiated by lactate (which is released when metabolism becomes anaerobic in ischaemia) and by FMRFamide (which may mimic the action of related mammalian RFamide transmitters). These data reinforce suggestions of a mechanosensory aspect to ASIC channel function, and show that the activation of ASICs reflects the integration of multiple signals which are present during ischaemia. PMID:12205186

  3. High pressure modulated transport and signaling functions of membrane proteins in models and in vivo

    International Nuclear Information System (INIS)

    Vogel, R F; Linke, K; Teichert, H; Ehrmann, M A

    2008-01-01

    Cellular membranes serve in the separation of compartments, recognition of the environment, selective transport and signal transduction. Membrane lipids and membrane proteins play distinct roles in these processes, which are affected by environmental chemical (e. g. pH) or physical (e. g. pressure and temperature) changes. High hydrostatic pressure (HHP) affects fluidity and integrity of bacterial membranes instantly during the ramp, resulting in a loss of membrane potential and vital membrane protein functions. We have used the multiple drug transporter LmrA from Lactococcus lactis and ToxR, a membrane protein sensor from Photobacterium profundum, a deep-sea bacterium, and Vibrio cholerae to study membrane protein interaction and functionality in proteolioposomes and by the use of in vivo reporter systems, respectively. Both proteins require dimerization in the phospholipid bilayer for their functionality, which was favoured in the liquid crystalline lipid phase with ToxR and LmrA. Whereas LmrA, which resides in liposomes consisting of DMPC, DMPC/cholesterol or natural lipids, lost its ATPase activity above 20 or 40 MPa, it maintained its active dimeric structure in DOPC/DPPC/cholesterol liposomes up to 120 MPa. By using a specific indicator strain in which the dimerisation of ToxR initiates the transcription of lacZ it was demonstrated, that the amino acid sequence of the transmembrane domain influences HHP stability of ToxR dimerization in vivo. Thus, both the lipid structure and the nature of the protein affect membrane protein interaction. It is suggested that the protein structure determines basic functionality, e.g. principle ability or kinetics to dimerize to a functional complex, while the lipid environment modulates this property

  4. Resolving the contribution of the uncoupled phycobilisomes to cyanobacterial pulse-amplitude modulated (PAM) fluorometry signals.

    Science.gov (United States)

    Acuña, Alonso M; Snellenburg, Joris J; Gwizdala, Michal; Kirilovsky, Diana; van Grondelle, Rienk; van Stokkum, Ivo H M

    2016-01-01

    Pulse-amplitude modulated (PAM) fluorometry is extensively used to characterize photosynthetic organisms on the slow time-scale (1-1000 s). The saturation pulse method allows determination of the quantum yields of maximal (F(M)) and minimal fluorescence (F(0)), parameters related to the activity of the photosynthetic apparatus. Also, when the sample undergoes a certain light treatment during the measurement, the fluorescence quantum yields of the unquenched and the quenched states can be determined. In the case of cyanobacteria, however, the recorded fluorescence does not exclusively stem from the chlorophyll a in photosystem II (PSII). The phycobilins, the pigments of the cyanobacterial light-harvesting complexes, the phycobilisomes (PB), also contribute to the PAM signal, and therefore, F(0) and F(M) are no longer related to PSII only. We present a functional model that takes into account the presence of several fluorescent species whose concentrations can be resolved provided their fluorescence quantum yields are known. Data analysis of PAM measurements on in vivo cells of our model organism Synechocystis PCC6803 is discussed. Three different components are found necessary to fit the data: uncoupled PB (PB(free)), PB-PSII complexes, and free PSI. The free PSII contribution was negligible. The PB(free) contribution substantially increased in the mutants that lack the core terminal emitter subunits allophycocyanin D or allophycocyanin F. A positive correlation was found between the amount of PB(free) and the rate constants describing the binding of the activated orange carotenoid protein to PB, responsible for non-photochemical quenching.

  5. High pressure modulated transport and signaling functions of membrane proteins in models and in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Vogel, R F; Linke, K; Teichert, H; Ehrmann, M A [Technische Universitaet Muenchen, Technische Mikrobiologie, Weihenstephaner Steig 16, 85350 Freising (Germany)], E-mail: rudi.vogel@wzw.tum.de

    2008-07-15

    Cellular membranes serve in the separation of compartments, recognition of the environment, selective transport and signal transduction. Membrane lipids and membrane proteins play distinct roles in these processes, which are affected by environmental chemical (e. g. pH) or physical (e. g. pressure and temperature) changes. High hydrostatic pressure (HHP) affects fluidity and integrity of bacterial membranes instantly during the ramp, resulting in a loss of membrane potential and vital membrane protein functions. We have used the multiple drug transporter LmrA from Lactococcus lactis and ToxR, a membrane protein sensor from Photobacterium profundum, a deep-sea bacterium, and Vibrio cholerae to study membrane protein interaction and functionality in proteolioposomes and by the use of in vivo reporter systems, respectively. Both proteins require dimerization in the phospholipid bilayer for their functionality, which was favoured in the liquid crystalline lipid phase with ToxR and LmrA. Whereas LmrA, which resides in liposomes consisting of DMPC, DMPC/cholesterol or natural lipids, lost its ATPase activity above 20 or 40 MPa, it maintained its active dimeric structure in DOPC/DPPC/cholesterol liposomes up to 120 MPa. By using a specific indicator strain in which the dimerisation of ToxR initiates the transcription of lacZ it was demonstrated, that the amino acid sequence of the transmembrane domain influences HHP stability of ToxR dimerization in vivo. Thus, both the lipid structure and the nature of the protein affect membrane protein interaction. It is suggested that the protein structure determines basic functionality, e.g. principle ability or kinetics to dimerize to a functional complex, while the lipid environment modulates this property.

  6. High pressure modulated transport and signaling functions of membrane proteins in models and in vivo

    Science.gov (United States)

    Vogel, R. F.; Linke, K.; Teichert, H.; Ehrmann, M. A.

    2008-07-01

    Cellular membranes serve in the separation of compartments, recognition of the environment, selective transport and signal transduction. Membrane lipids and membrane proteins play distinct roles in these processes, which are affected by environmental chemical (e. g. pH) or physical (e. g. pressure and temperature) changes. High hydrostatic pressure (HHP) affects fluidity and integrity of bacterial membranes instantly during the ramp, resulting in a loss of membrane potential and vital membrane protein functions. We have used the multiple drug transporter LmrA from Lactococcus lactis and ToxR, a membrane protein sensor from Photobacterium profundum, a deep-sea bacterium, and Vibrio cholerae to study membrane protein interaction and functionality in proteolioposomes and by the use of in vivo reporter systems, respectively. Both proteins require dimerization in the phospholipid bilayer for their functionality, which was favoured in the liquid crystalline lipid phase with ToxR and LmrA. Whereas LmrA, which resides in liposomes consisting of DMPC, DMPC/cholesterol or natural lipids, lost its ATPase activity above 20 or 40 MPa, it maintained its active dimeric structure in DOPC/DPPC/cholesterol liposomes up to 120 MPa. By using a specific indicator strain in which the dimerisation of ToxR initiates the transcription of lacZ it was demonstrated, that the amino acid sequence of the transmembrane domain influences HHP stability of ToxR dimerization in vivo. Thus, both the lipid structure and the nature of the protein affect membrane protein interaction. It is suggested that the protein structure determines basic functionality, e.g. principle ability or kinetics to dimerize to a functional complex, while the lipid environment modulates this property.

  7. Tyrosine kinase signalling in breast cancer: Modulation of tyrosine kinase signalling in human breast cancer through altered expression of signalling intermediates

    International Nuclear Information System (INIS)

    Kairouz, Rania; Daly, Roger J

    2000-01-01

    The past decade has seen the definition of key signalling pathways downstream of receptor tyrosine kinases (RTKs) in terms of their components and the protein-protein interactions that facilitate signal transduction. Given the strong evidence that links signalling by certain families of RTKs to the progression of breast cancer, it is not surprising that the expression profile of key downstream signalling intermediates in this disease has also come under scrutiny, particularly because some exhibit transforming potential or amplify mitogenic signalling pathways when they are overexpressed. Reflecting the diverse cellular processes regulated by RTKs, it is now clear that altered expression of such signalling proteins in breast cancer may influence not only cellular proliferation (eg Grb2) but also the invasive properties of the cancer cells (eg EMS1/cortactin)

  8. Comparing auditory filter bandwidths, spectral ripple modulation detection, spectral ripple discrimination, and speech recognition: Normal and impaired hearing.

    Science.gov (United States)

    Davies-Venn, Evelyn; Nelson, Peggy; Souza, Pamela

    2015-07-01

    Some listeners with hearing loss show poor speech recognition scores in spite of using amplification that optimizes audibility. Beyond audibility, studies have suggested that suprathreshold abilities such as spectral and temporal processing may explain differences in amplified speech recognition scores. A variety of different methods has been used to measure spectral processing. However, the relationship between spectral processing and speech recognition is still inconclusive. This study evaluated the relationship between spectral processing and speech recognition in listeners with normal hearing and with hearing loss. Narrowband spectral resolution was assessed using auditory filter bandwidths estimated from simultaneous notched-noise masking. Broadband spectral processing was measured using the spectral ripple discrimination (SRD) task and the spectral ripple depth detection (SMD) task. Three different measures were used to assess unamplified and amplified speech recognition in quiet and noise. Stepwise multiple linear regression revealed that SMD at 2.0 cycles per octave (cpo) significantly predicted speech scores for amplified and unamplified speech in quiet and noise. Commonality analyses revealed that SMD at 2.0 cpo combined with SRD and equivalent rectangular bandwidth measures to explain most of the variance captured by the regression model. Results suggest that SMD and SRD may be promising clinical tools for diagnostic evaluation and predicting amplification outcomes.

  9. Comparing auditory filter bandwidths, spectral ripple modulation detection, spectral ripple discrimination, and speech recognition: Normal and impaired hearinga)

    Science.gov (United States)

    Davies-Venn, Evelyn; Nelson, Peggy; Souza, Pamela

    2015-01-01

    Some listeners with hearing loss show poor speech recognition scores in spite of using amplification that optimizes audibility. Beyond audibility, studies have suggested that suprathreshold abilities such as spectral and temporal processing may explain differences in amplified speech recognition scores. A variety of different methods has been used to measure spectral processing. However, the relationship between spectral processing and speech recognition is still inconclusive. This study evaluated the relationship between spectral processing and speech recognition in listeners with normal hearing and with hearing loss. Narrowband spectral resolution was assessed using auditory filter bandwidths estimated from simultaneous notched-noise masking. Broadband spectral processing was measured using the spectral ripple discrimination (SRD) task and the spectral ripple depth detection (SMD) task. Three different measures were used to assess unamplified and amplified speech recognition in quiet and noise. Stepwise multiple linear regression revealed that SMD at 2.0 cycles per octave (cpo) significantly predicted speech scores for amplified and unamplified speech in quiet and noise. Commonality analyses revealed that SMD at 2.0 cpo combined with SRD and equivalent rectangular bandwidth measures to explain most of the variance captured by the regression model. Results suggest that SMD and SRD may be promising clinical tools for diagnostic evaluation and predicting amplification outcomes. PMID:26233047

  10. Development of Power Supply Management Module for Radio Signal Repeaters of Automatic Metering Reading System in Variable Solar Density Conditions

    Directory of Open Access Journals (Sweden)

    Kondratjevs K.

    2016-02-01

    Full Text Available In recent years, there has been significant research focus that revolves around harvesting and minimising energy consumption by wireless sensor network nodes. When a sensor node is depleted of energy, it becomes unresponsive and disconnected from the network that can significantly influence the performance of the whole network. The purpose of the present research is to create a power supply management module in order to provide stable operating voltage for autonomous operations of radio signal repeaters, sensors or gateways of WSN. The developed management module is composed of a solar panel, lithium battery and power supply management module. The novelty of the research is the management module, which ensures stable and uninterrupted operations of electronic equipment in various power supply modes in different situations, simultaneously ensuring energy protection and sustainability of the module components. The management module is able to provide power supply of 5 V for electronics scheme independently, without power interruption switching between power sources and power flows in different directions.

  11. Principal component and discriminant analyses as powerful tools to support taxonomic identification and their use for functional and phylogenetic signal detection of isolated fossil shark teeth.

    Directory of Open Access Journals (Sweden)

    Giuseppe Marramà

    Full Text Available Identifying isolated teeth of fossil selachians only based on qualitative characters is sometimes hindered by similarity in their morphology, resulting often in heated taxonomic debates. On the other hand, the use of quantitative characters (i.e. measurements has been often neglected or underestimated in characterization and identification of fossil teeth of selachians. Here we show that, employing a robust methodological protocol based on principal component and discriminant analyses on a sample of 175 isolated fossil teeth of lamniform sharks, the traditional morphometrics can be useful to support and complement the classic taxonomic identification made on qualitative features. Furthermore, we show that discriminant analysis can be successfully useful to assign indeterminate isolated shark teeth to a certain taxon. Finally, the degree of separation of the clusters might be used to predict functional and probably also phylogenetic signals in lamniform shark teeth. However, this needs to be tested in the future employing teeth of more extant and extinct lamniform sharks and it must be pointed out that this approach does not replace in any way the qualitative analysis, but it is intended to complement and support it.

  12. Fringe Controls Naïve CD4+T Cells Differentiation through Modulating Notch Signaling in Asthmatic Rat Models

    Science.gov (United States)

    Gu, Wen; Xu, Weiguo; Ding, Tao; Guo, Xuejun

    2012-01-01

    The ability of Notch signaling to regulate T helper cell development and differentiation has been widely accepted. Fringe, O-fucose-β1,3-N-acetylglucosaminyltransferases modulate Notch receptor expression and promote the Notch signaling pathway through receptor-ligand binding. In this study, we assayed the expression levels of three Fringe homologs in naive CD4+T cells in asthmatic rats. We found that Radical Fringe (Rfng) was highly expressed, whereas both Lunatic Fringe (Lfng) and Manic Fringe (Mfng) were expressed at low levels. Down-regulation of Rfng using siRNA, and overexpression of Lfng or Mfng enhanced Th1 subset lineages and diminished Th2 subset lineages. Notch signaling was more activated in asthmatic naïve CD4+T cells than in control cells, and Lfng, but not Mfng or Rfng, partly inhibited Notch signaling in asthmatic naïve CD4+T lymphocytes. Lfng overexpression resulted in significantly decreased Th2 cytokine production in asthma, which was the same effect as the GSI (γ-secretase inhibitor) treatment alone, but had an increased effect on Th1 cytokines than GSI treatment. Collectively, these data identify the essential role of Fringe modulating naïve CD4+T cells differentiation through Notch signaling. Lfng regulated Th2 cells differentiation via a Notch-dependent manner and Th1 cells differentiation via a Notch-independent manner. Fringe could be a therapeutic strategy for the management and prevention of allergic asthma. PMID:23071776

  13. Fringe controls naïve CD4(+)T cells differentiation through modulating notch signaling in asthmatic rat models.

    Science.gov (United States)

    Gu, Wen; Xu, Weiguo; Ding, Tao; Guo, Xuejun

    2012-01-01

    The ability of Notch signaling to regulate T helper cell development and differentiation has been widely accepted. Fringe, O-fucose-β1,3-N-acetylglucosaminyltransferases modulate Notch receptor expression and promote the Notch signaling pathway through receptor-ligand binding. In this study, we assayed the expression levels of three Fringe homologs in naive CD4(+)T cells in asthmatic rats. We found that Radical Fringe (Rfng) was highly expressed, whereas both Lunatic Fringe (Lfng) and Manic Fringe (Mfng) were expressed at low levels. Down-regulation of Rfng using siRNA, and overexpression of Lfng or Mfng enhanced Th1 subset lineages and diminished Th2 subset lineages. Notch signaling was more activated in asthmatic naïve CD4(+)T cells than in control cells, and Lfng, but not Mfng or Rfng, partly inhibited Notch signaling in asthmatic naïve CD4(+)T lymphocytes. Lfng overexpression resulted in significantly decreased Th2 cytokine production in asthma, which was the same effect as the GSI (γ-secretase inhibitor) treatment alone, but had an increased effect on Th1 cytokines than GSI treatment. Collectively, these data identify the essential role of Fringe modulating naïve CD4(+)T cells differentiation through Notch signaling. Lfng regulated Th2 cells differentiation via a Notch-dependent manner and Th1 cells differentiation via a Notch-independent manner. Fringe could be a therapeutic strategy for the management and prevention of allergic asthma.

  14. The Natural Flavonoid Fisetin Inhibits Cellular Proliferation of Hepatic, Colorectal, and Pancreatic Cancer Cells through Modulation of Multiple Signaling Pathways.

    Science.gov (United States)

    Youns, Mаhmoud; Abdel Halim Hegazy, Wael

    2017-01-01

    Digestive cancers are major causes of mortality and morbidity worldwide. Fisetin, a naturally occurring flavonoid, has been previously shown anti-proliferative, anti-cancer, neuroprotective, and antioxidant activities. In our study, the anti-tumor activities in addition to regulatory effects of fisetin on some cancer cell lines were investigated. Data presented here showed that fisetin induces growth inhibition, and apoptosis in hepatic (HepG-2), colorectal (Caco-2) and pancreatic (Suit-2) cancer cell lines. Gene expression results showed that 1307 genes were significantly regulated in their expression in hepatic and pancreatic cell lines. 350 genes were commonly up-regulated and 353 genes were commonly down-regulated. Additionally, 604 genes were oppositely expressed in both tumor cells. CDK5 signaling, NRF2-mediated oxidative stress response, glucocorticoid signaling, and ERK/MAPK signaling were among most prominent signaling pathways modulating the growth inhibitory effects of fisetin on hepatic and pancreatic cancer cells. The present analysis showed, for the first time, that the anti-tumor effect of fisetin was mediated mainly through modulation of multiple signaling pathways and via activation of CDKN1A, SEMA3E, GADD45B and GADD45A and down-regulation of TOP2A, KIF20A, CCNB2 and CCNB1 genes.

  15. The Natural Flavonoid Fisetin Inhibits Cellular Proliferation of Hepatic, Colorectal, and Pancreatic Cancer Cells through Modulation of Multiple Signaling Pathways.

    Directory of Open Access Journals (Sweden)

    Mаhmoud Youns

    Full Text Available Digestive cancers are major causes of mortality and morbidity worldwide. Fisetin, a naturally occurring flavonoid, has been previously shown anti-proliferative, anti-cancer, neuroprotective, and antioxidant activities. In our study, the anti-tumor activities in addition to regulatory effects of fisetin on some cancer cell lines were investigated. Data presented here showed that fisetin induces growth inhibition, and apoptosis in hepatic (HepG-2, colorectal (Caco-2 and pancreatic (Suit-2 cancer cell lines. Gene expression results showed that 1307 genes were significantly regulated in their expression in hepatic and pancreatic cell lines. 350 genes were commonly up-regulated and 353 genes were commonly down-regulated. Additionally, 604 genes were oppositely expressed in both tumor cells. CDK5 signaling, NRF2-mediated oxidative stress response, glucocorticoid signaling, and ERK/MAPK signaling were among most prominent signaling pathways modulating the growth inhibitory effects of fisetin on hepatic and pancreatic cancer cells. The present analysis showed, for the first time, that the anti-tumor effect of fisetin was mediated mainly through modulation of multiple signaling pathways and via activation of CDKN1A, SEMA3E, GADD45B and GADD45A and down-regulation of TOP2A, KIF20A, CCNB2 and CCNB1 genes.

  16. The Natural Flavonoid Fisetin Inhibits Cellular Proliferation of Hepatic, Colorectal, and Pancreatic Cancer Cells through Modulation of Multiple Signaling Pathways

    Science.gov (United States)

    Youns, Mаhmoud; Abdel Halim Hegazy, Wael

    2017-01-01

    Digestive cancers are major causes of mortality and morbidity worldwide. Fisetin, a naturally occurring flavonoid, has been previously shown anti-proliferative, anti-cancer, neuroprotective, and antioxidant activities. In our study, the anti-tumor activities in addition to regulatory effects of fisetin on some cancer cell lines were investigated. Data presented here showed that fisetin induces growth inhibition, and apoptosis in hepatic (HepG-2), colorectal (Caco-2) and pancreatic (Suit-2) cancer cell lines. Gene expression results showed that 1307 genes were significantly regulated in their expression in hepatic and pancreatic cell lines. 350 genes were commonly up-regulated and 353 genes were commonly down-regulated. Additionally, 604 genes were oppositely expressed in both tumor cells. CDK5 signaling, NRF2-mediated oxidative stress response, glucocorticoid signaling, and ERK/MAPK signaling were among most prominent signaling pathways modulating the growth inhibitory effects of fisetin on hepatic and pancreatic cancer cells. The present analysis showed, for the first time, that the anti-tumor effect of fisetin was mediated mainly through modulation of multiple signaling pathways and via activation of CDKN1A, SEMA3E, GADD45B and GADD45A and down-regulation of TOP2A, KIF20A, CCNB2 and CCNB1 genes. PMID:28052097

  17. Signal discrimination of ULF electromagnetic data with using singular spectrum analysis – an attempt to detect train noise

    OpenAIRE

    Saito, S.; Kaida, D.; Hattori, K.; Febriani, F.; Yoshino, C.

    2011-01-01

    Electromagnetic phenomena associated with crustal activities have been reported in a wide frequency range (DC-HF). In particular, ULF electromagnetic phenomena are the most promising among them because of the deeper skin depth. However, ULF geoelctromagnetic data are a superposition of signals of different origins. They originated from interactions between the geomagnetic field and the solar wind, leak current by a DC-driven train (train noise), precipitation, and so on. In general, the inten...

  18. Modulation detection as a function of carrier frequency and level

    NARCIS (Netherlands)

    Fassel, R.; Kohlrausch, A.G.

    1995-01-01

    This paper describes recent experiments investigating temporal processing in the auditory system. Subjects had to discriminate sinusoidal signals with a flat temporal envelope from those with a sinusoidal amplitude modulation. The modulation depth at threshold was measured for a wide range of

  19. Seven novel probe systems for real-time PCR provide absolute single-base discrimination, higher signaling, and generic components.

    Science.gov (United States)

    Murray, James L; Hu, Peixu; Shafer, David A

    2014-11-01

    We have developed novel probe systems for real-time PCR that provide higher specificity, greater sensitivity, and lower cost relative to dual-labeled probes. The seven DNA Detection Switch (DDS)-probe systems reported here employ two interacting polynucleotide components: a fluorescently labeled probe and a quencher antiprobe. High-fidelity detection is achieved with three DDS designs: two internal probes (internal DDS and Flip probes) and a primer probe (ZIPR probe), wherein each probe is combined with a carefully engineered, slightly mismatched, error-checking antiprobe. The antiprobe blocks off-target detection over a wide range of temperatures and facilitates multiplexing. Other designs (Universal probe, Half-Universal probe, and MacMan probe) use generic components that enable low-cost detection. Finally, single-molecule G-Force probes employ guanine-mediated fluorescent quenching by forming a hairpin between adjacent C-rich and G-rich sequences. Examples provided show how these probe technologies discriminate drug-resistant Mycobacterium tuberculosis mutants, Escherichia coli O157:H7, oncogenic EGFR deletion mutations, hepatitis B virus, influenza A/B strains, and single-nucleotide polymorphisms in the human VKORC1 gene. Copyright © 2014 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  20. Implications of Green Tea and Its Constituents in the Prevention of Cancer via the Modulation of Cell Signalling Pathway

    Science.gov (United States)

    Rahmani, Arshad H.; Al shabrmi, Fahad M.; Allemailem, Khaled S.; Aly, Salah M.; Khan, Masood A.

    2015-01-01

    Green tea is commonly used as a beverage worldwide, especially in China, Japan, Morocco, and Saudi Arabia. Green tea and its constituents have been considered very effective in the prevention and treatment of various diseases. It contains a variety of catechins, which show a pivotal role in the modulation of biological activities and also act as chemopreventive agents. Earlier studies have confirmed that green tea and its chief constituent epigallocatechin gallate (EGCG) have a potential role in the management of cancer through the modulation of cell signaling pathways. In this review, we focused on the beneficial effects of green tea and its constituents in the cancer prevention and treatment and its impact on modulation of molecular pathways. PMID:25977926

  1. Efficient and Robust Detection of GFSK Signals under Dispersive Channel, Modulation Index, and Carrier Frequency Offset Conditions

    Directory of Open Access Journals (Sweden)

    Stephan Weiss

    2005-09-01

    Full Text Available Gaussian frequency shift keying is the modulation scheme specified for Bluetooth. Signal adversities typical in Bluetooth networks include AWGN, multipath propagation, carrier frequency, and modulation index offsets. In our effort to realise a robust but efficient Bluetooth receiver, we adopt a high-performance matched-filter-based detector, which is near optimal in AWGN, but requires a prohibitively costly filter bank for processing of K bits worth of the received signal. However, through filtering over a single bit period and performing phase propagation of intermediate results over successive single-bit stages, we eliminate redundancy involved in providing the matched filter outputs and reduce its complexity by up to 90% (for K=9. The constant modulus signal characteristic and the potential for carrier frequency offsets make the constant modulus algorithm (CMA suitable for channel equalisation, and we demonstrate its effectiveness in this paper. We also introduce a stochastic gradient-based algorithm for carrier frequency offset correction, and show that the relative rotation between successive intermediate filter outputs enables us to detect and correct offsets in modulation index.

  2. The Mediator Kinase Module Restrains Epidermal Growth Factor Receptor Signaling and Represses Vulval Cell Fate Specification in Caenorhabditis elegans.

    Science.gov (United States)

    Grants, Jennifer M; Ying, Lisa T L; Yoda, Akinori; You, Charlotte C; Okano, Hideyuki; Sawa, Hitoshi; Taubert, Stefan

    2016-02-01

    Cell signaling pathways that control proliferation and determine cell fates are tightly regulated to prevent developmental anomalies and cancer. Transcription factors and coregulators are important effectors of signaling pathway output, as they regulate downstream gene programs. In Caenorhabditis elegans, several subunits of the Mediator transcriptional coregulator complex promote or inhibit vulva development, but pertinent mechanisms are poorly defined. Here, we show that Mediator's dissociable cyclin dependent kinase 8 (CDK8) module (CKM), consisting of cdk-8, cic-1/Cyclin C, mdt-12/dpy-22, and mdt-13/let-19, is required to inhibit ectopic vulval cell fates downstream of the epidermal growth factor receptor (EGFR)-Ras-extracellular signal-regulated kinase (ERK) pathway. cdk-8 inhibits ectopic vulva formation by acting downstream of mpk-1/ERK, cell autonomously in vulval cells, and in a kinase-dependent manner. We also provide evidence that the CKM acts as a corepressor for the Ets-family transcription factor LIN-1, as cdk-8 promotes transcriptional repression by LIN-1. In addition, we find that CKM mutation alters Mediator subunit requirements in vulva development: the mdt-23/sur-2 subunit, which is required for vulva development in wild-type worms, is dispensable for ectopic vulva formation in CKM mutants, which instead display hallmarks of unrestrained Mediator tail module activity. We propose a model whereby the CKM controls EGFR-Ras-ERK transcriptional output by corepressing LIN-1 and by fine tuning Mediator specificity, thus balancing transcriptional repression vs. activation in a critical developmental signaling pathway. Collectively, these data offer an explanation for CKM repression of EGFR signaling output and ectopic vulva formation and provide the first evidence of Mediator CKM-tail module subunit crosstalk in animals. Copyright © 2016 by the Genetics Society of America.

  3. Discrimination of bladder cancer cells from normal urothelial cells with high specificity and sensitivity: combined application of atomic force microscopy and modulated Raman spectroscopy.

    Science.gov (United States)

    Canetta, Elisabetta; Riches, Andrew; Borger, Eva; Herrington, Simon; Dholakia, Kishan; Adya, Ashok K

    2014-05-01

    Atomic force microscopy (AFM) and modulated Raman spectroscopy (MRS) were used to discriminate between living normal human urothelial cells (SV-HUC-1) and bladder tumour cells (MGH-U1) with high specificity and sensitivity. MGH-U1 cells were 1.5-fold smaller, 1.7-fold thicker and 1.4-fold rougher than normal SV-HUC-1 cells. The adhesion energy was 2.6-fold higher in the MGH-U1 cells compared to normal SV-HUC-1 cells, which possibly indicates that bladder tumour cells are more deformable than normal cells. The elastic modulus of MGH-U1 cells was 12-fold lower than SV-HUC-1 cells, suggesting a higher elasticity of the bladder cancer cell membranes. The biochemical fingerprints of cancer cells displayed a higher DNA and lipid content, probably due to an increase in the nuclear to cytoplasm ratio. Normal cells were characterized by higher protein contents. AFM studies revealed a decrease in the lateral dimensions and an increase in thickness of cancer cells compared to normal cells; these studies authenticate the observations from MRS. Nanostructural, nanomechanical and biochemical profiles of bladder cells provide qualitative and quantitative markers to differentiate between normal and cancerous cells at the single cellular level. AFM and MRS allow discrimination between adhesion energy, elasticity and Raman spectra of SV-HUC-1 and MGH-U1 cells with high specificity (83, 98 and 95%) and sensitivity (97, 93 and 98%). Such single-cell-level studies could have a pivotal impact on the development of AFM-Raman combined methodologies for cancer profiling and screening with translational significance. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  4. Digital dewaxing of Raman signals: discrimination between nevi and melanoma spectra obtained from paraffin-embedded skin biopsies.

    Science.gov (United States)

    Tfayli, Ali; Gobinet, Cyril; Vrabie, Valeriu; Huez, Regis; Manfait, Michel; Piot, Olivier

    2009-05-01

    Malignant melanoma (MM) is the most severe tumor affecting the skin and accounts for three quarters of all skin cancer deaths. Raman spectroscopy is a promising nondestructive tool that has been increasingly used for characterization of the molecular features of cancerous tissues. Different multivariate statistical analysis techniques are used in order to extract relevant information that can be considered as functional spectroscopic descriptors of a particular pathology. Paraffin embedding (waxing) is a highly efficient process used to conserve biopsies in tumor banks for several years. However, the use of non-dewaxed formalin-fixed paraffin-embedded tissues for Raman spectroscopic investigations remains very restricted, limiting the development of the technique as a routine analytical tool for biomedical purposes. This is due to the highly intense signal of paraffin, which masks important vibrations of the biological tissues. In addition to being time consuming and chemical intensive, chemical dewaxing methods are not efficient and they leave traces of the paraffin in tissues, which affects the Raman signal. In the present study, we use independent component analysis (ICA) on Raman spectral images collected on melanoma and nevus samples. The sources obtained from these images are then used to eliminate, using non-negativity constrained least squares (NCLS), the paraffin contribution from each individual spectrum of the spectral images of nevi and melanomas. Corrected spectra of both types of lesion are then compared and classified into dendrograms using hierarchical cluster analysis (HCA).

  5. Bone morphogenetic protein 2 signaling negatively modulates lymphatic development in vertebrate embryos

    DEFF Research Database (Denmark)

    Dunworth, William P; Cardona-Costa, Jose; Bozkulak, Esra Cagavi

    2014-01-01

    : Our aim was to delineate the role of bone morphogenetic protein (BMP) 2 signaling in lymphatic development. METHODS AND RESULTS: BMP2 signaling negatively regulates the formation of LECs. Developing LECs lack any detectable BMP signaling activity in both zebrafish and mouse embryos, and excess BMP2...... signaling in zebrafish embryos and mouse embryonic stem cell-derived embryoid bodies substantially decrease the emergence of LECs. Mechanistically, BMP2 signaling induces expression of miR-31 and miR-181a in a SMAD-dependent mechanism, which in turn results in attenuated expression of prospero homeobox...

  6. Morin Attenuates Ovalbumin-Induced Airway Inflammation by Modulating Oxidative Stress-Responsive MAPK Signaling

    Directory of Open Access Journals (Sweden)

    Yuan Ma

    2016-01-01

    Full Text Available Asthma is one of the most common inflammatory diseases characterized by airway hyperresponsiveness, inflammation, and remodeling. Morin, an active ingredient obtained from Moraceae plants, has been demonstrated to have promising anti-inflammatory activities in a range of disorders. However, its impacts on pulmonary diseases, particularly on asthma, have not been clarified. This study was designed to investigate whether morin alleviates airway inflammation in chronic asthma with an emphasis on oxidative stress modulation. In vivo, ovalbumin- (OVA- sensitized mice were administered with morin or dexamethasone before challenge. Bronchoalveolar lavage fluid (BALF and lung tissues were obtained to perform cell counts, histological analysis, and enzyme-linked immunosorbent assay. In vitro, human bronchial epithelial cells (BECs were challenged by tumor necrosis factor alpha (TNF-α. The supernatant was collected for the detection of the proinflammatory proteins, and the cells were collected for reactive oxygen species (ROS/mitogen-activated protein kinase (MAPK evaluations. Severe inflammatory responses and remodeling were observed in the airways of the OVA-sensitized mice. Treatment with morin dramatically attenuated the extensive trafficking of inflammatory cells into the BALF and inhibited their infiltration around the respiratory tracts and vessels. Morin administration also significantly suppressed goblet cell hyperplasia and collagen deposition/fibrosis and dose-dependently inhibited the OVA-induced increases in IgE, TNF-α, interleukin- (IL- 4, IL-13, matrix metalloproteinase-9, and malondialdehyde. In human BECs challenged by TNF-α, the levels of proteins such as eotaxin-1, monocyte chemoattractant protein-1, IL-8 and intercellular adhesion molecule-1, were consistently significantly decreased by morin. Western blotting and the 2′,7′-dichlorofluorescein assay revealed that the increases in intracellular ROS and MAPK phosphorylation were

  7. Effects of signal modulation and coloured cross-correlation of coloured noises on the diffusion of a harmonic oscillator

    Institute of Scientific and Technical Information of China (English)

    Liu Li; Zhang Liang-Ying; Cao Li

    2009-01-01

    The diffusion in a harmonic oscillator driven by coloured noises ζ(t) and η(t) with coloured cross-correlation in which one of the noises is modulated by a biased periodic signal is investigated. The exact expression of diffusion coefficient d as a function of noise parameter, signal parameter, and oscillator frequency is derived. The findings in this paper are as follows. 1) The curves of d versus noise intensity D and d versus noises cross-correlation time τ_3 exist as two different phases. The transition between the two phases arises from the change of the cross-correlation coefficient λ of the two Orustein-Uhlenbeck (O-U) noises. 2) Changing the value of τ3, the curves of d versus Q, the intensity of colored noise that is modulated by the signal, can transform from a phase having a minimum to a monotonic phase. 3)Changing the value of signal amplitude A, d versus Q curves can transform from a phase having a minimum to a monotonic phase. The above-mentioned results demonstrate that a like noise-induced transition appears in the model.

  8. Unfolding Role of a Danger Molecule Adenosine Signaling in Modulation of Microbial Infection and Host Cell Response

    Directory of Open Access Journals (Sweden)

    Jaden S. Lee

    2018-01-01

    Full Text Available Ectonucleotidases CD39 and CD73, specific nucleotide metabolizing enzymes located on the surface of the host, can convert a pro-inflammatory environment driven by a danger molecule extracellular-ATP to an adenosine-mediated anti-inflammatory milieu. Accordingly, CD39/CD73 signaling has been strongly implicated in modulating the intensity, duration, and composition of purinergic danger signals delivered to host. Recent studies have eluted potential roles for CD39 and CD73 in selective triggering of a variety of host immune cells and molecules in the presence of pathogenic microorganisms or microbial virulence molecules. Growing evidence also suggests that CD39 and CD73 present complimentary, but likely differential, actions against pathogens to shape the course and severity of microbial infection as well as the associated immune response. Similarly, adenosine receptors A2A and A2B have been proposed to be major immunomodulators of adenosine signaling during chronic inflammatory conditions induced by opportunistic pathogens, such as oral colonizer Porphyromonas gingivalis. Therefore, we here review the recent studies that demonstrate how complex network of molecules in the extracellular adenosine signaling machinery and their interactions can reshape immune responses and may also be targeted by opportunistic pathogens to establish successful colonization in human mucosal tissues and modulate the host immune response.

  9. Effects of signal modulation and coloured cross-correlation of coloured noises on the diffusion of a harmonic oscillator

    International Nuclear Information System (INIS)

    Li, Liu; Li, Cao; Liang-Ying, Zhang

    2009-01-01

    The diffusion in a harmonic oscillator driven by coloured noises ζ(t) and η(t) with coloured cross-correlation in which one of the noises is modulated by a biased periodic signal is investigated. The exact expression of diffusion coefficient d as a function of noise parameter, signal parameter, and oscillator frequency is derived. The findings in this paper are as follows. 1) The curves of d versus noise intensity D and d versus noises cross-correlation time τ 3 exist as two different phases. The transition between the two phases arises from the change of the cross-correlation coefficient λ of the two Ornstein–Uhlenbeck (O-U) noises. 2) Changing the value of τ 3 , the curves of d versus Q, the intensity of colored noise that is modulated by the signal, can transform from a phase having a minimum to a monotonic phase. 3) Changing the value of signal amplitude A, d versus Q curves can transform from a phase having a minimum to a monotonic phase. The above-mentioned results demonstrate that a like noise-induced transition appears in the model. (general)

  10. GPER1-mediated IGFBP-1 induction modulates IGF-1-dependent signaling in tamoxifen-treated breast cancer cells.

    Science.gov (United States)

    Vaziri-Gohar, Ali; Houston, Kevin D

    2016-02-15

    Tamoxifen, a selective estrogen receptor modulator, is a commonly prescribed adjuvant therapy for estrogen receptor-α (ERα)-positive breast cancer patients. To determine if extracellular factors contribute to the modulation of IGF-1 signaling after tamoxifen treatment, MCF-7 cells were treated with IGF-1 in conditioned medium (CM) obtained from 4-OHT-treated MCF-7 cells and the accumulation of phospho-Akt (S473) was measured. CM inhibited IGF-1-dependent cell signaling and suggesting the involvement of extracellular factors (ie. IGFBPs). A significant increase in IGFBP-1 mRNA and extracellular IGFBP-1 protein was observed in 4-OHT-treated MCF-7 cells. Knockdown experiments demonstrated that both GPER1 and CREB mediate IGFBP-1 induction. Furthermore, experiments showed that 4-OHT-dependent IGFBP-1 transcription is downstream of GPER1-activation in breast cancer cells. Additionally, neutralization and knockdown experiments demonstrated a role for IGFBP-1 in the observed inhibition of IGF-1 signaling. These results suggested that 4-OHT inhibits IGF-1 signaling via GPER1 and CREB mediated extracellular IGFBP-1 accumulation in breast cancer cells. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  11. Brain signal variability is modulated as a function of internal and external demand in younger and older adults.

    Science.gov (United States)

    Grady, Cheryl L; Garrett, Douglas D

    2018-04-01

    Variability in the Blood Oxygen-Level Dependent (BOLD) signal from fMRI is often associated with better cognitive performance and younger age. It has been proposed that neural variability enables flexible responding to uncertainty in a changing environment. However, signal variability reflecting environmental uncertainty may reduce to the extent that a task depends on internally-directed attention and is supported by neural "solutions" that are schematic and relatively stable within each individual. Accordingly, we examined the hypothesis that BOLD variability will be low at rest, higher during internally-directed tasks, and higher still during externally-directed tasks, and that this effect will be reduced with aging. Modulation of BOLD variability across conditions was consistent with these hypotheses, and was associated with faster and more stable behavioral performance in both young and older adults. These data support the idea that brain signal variability may modulate in response to environmental uncertainty, which is presumed to be greater in the external environment than in the internal milieu. Reduced flexibility of signal variability with age may indicate less ability to switch between internal and external brain states. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Behavioral Correlates of 50-kHz Ultrasonic Vocalizations in Rats: Progressive Operant Discrimination Learning Reduces Frequency Modulation and Increases Overall Amplitude

    Directory of Open Access Journals (Sweden)

    Shoko Yuki

    2014-11-01

    Full Text Available Ultrasonic vocalizations (USVs in rats are thought to contain ecological signals reflecting emotional states. These USVs are centered on 50-kHz, and frequency modulation (FM is hypothesized to indicate positive emotion; however, results from recent studies are inconsistent with this hypothesis. We suspected that such inconsistencies might result from ambiguity in defining frequency modulation, and problems with acoustic analyses and behavioral protocols. We addressed these problems by applying quantitative methods for USV analyses and using a food reward operant paradigm. Our results revealed that frequency modulation varied according to the degree of positive outcomes, but the direction of change was opposite to what had been observed in previous studies. The FM in 50-kHz USVs decreased as animals learned the task and obtained more reinforcement, while USV amplitude increased as learning progressed. To reconcile these results with those from prior studies, we suggest that FM in 50-kHz USVs should be taken as an index of reward prediction errors, and USV amplitude should be considered as an index of positive emotion.

  13. Self-aligned BCB planarization method for high-frequency signal injection in a VCSEL with an integrated modulator

    Science.gov (United States)

    Marigo-Lombart, Ludovic; Doucet, Jean-Baptiste; Lecestre, Aurélie; Reig, Benjamin; Rousset, Bernard; Thienpont, Hugo; Panajotov, Krassimir; Almuneau, Guilhem

    2016-04-01

    The huge increase of datacom capacities requires lasers sources with more and more bandwidth performances. Vertical-Cavity Surface-Emitting Lasers (VCSEL) in direct modulation is a good candidate, already widely used for short communication links such as in datacenters. Recently several different approaches have been proposed to further extend the direct modulation bandwidth of these devices, by improving the VCSEL structure, or by combining the VCSEL with another high speed element such as lateral slow light modulator or transistor/laser based structure (TVCSEL). We propose to increase the modulation bandwidth by vertically integrating a continuous-wave VCSEL with a high-speed electro-modulator. This vertical structure implies multiple electrodes with sufficiently good electrical separation between the different input electrical signals. This high frequency modulation requires both good electrical insulation between metal electrodes and an optimized design of the coplanar lines. BenzoCyclobutene (BCB) thanks to its low dielectric constant, low losses, low moisture absorption and good thermal stability, is often used as insulating layer. Also, BCB planarization offers the advantages of simpler and more reliable technological process flow in such integrated VCSEL/modulator structures with important reliefs. As described by Burdeaux et al. a degree of planarization (DOP) of about 95% can be achieved by simple spin coating whatever the device thickness. In most of the cases, the BCB planarization process requires an additional photolithography step in order to open an access to the mesa surface, thus involving a tight mask alignment and resulting in a degraded planarization. In this paper, we propose a self-aligned process with improved BCB planarization by combining a hot isostatic pressing derived from nanoimprint techniques with a dry plasma etching step.

  14. A mixed signal multi-chip module with high speed serial output links for the ATLAS Level-1 trigger

    CERN Document Server

    Pfeiffer, U

    2000-01-01

    We have built and tested a mixed signal multi-chip module (MCM) to be used in the Level-1 Pre-Processor system for the Calorimeter Trigger of the ATLAS experiment at CERN. The MCM performs high speed digital signal processing on four analogue input signals. Results are transmitted serially at a serial data rate of 800 MBd. Nine chips of different technologies are mounted on a four layer Cu substrate. ADC converters and serialiser chips are the major consumers of electrical power on the MCM, which amounts to 9 W for all dies. Special cut-out areas are used to dissipate heat directly to the copper substrate. In this paper we report on design criteria, chosen MCM technology for substrate and die mounting, experiences with the MCM operation and measurement results. (4 refs).

  15. Structural Discrimination

    DEFF Research Database (Denmark)

    Thorsen, Mira Skadegård

    discrimination as two ways of articulating particular, opaque forms of racial discrimination that occur in everyday Danish (and other) contexts, and have therefore become normalized. I present and discuss discrimination as it surfaces in data from my empirical studies of discrimination in Danish contexts...

  16. The Orphan G Protein-coupled Receptor Gpr175 (Tpra40) Enhances Hedgehog Signaling by Modulating cAMP Levels.

    Science.gov (United States)

    Singh, Jaskirat; Wen, Xiaohui; Scales, Suzie J

    2015-12-04

    The Hedgehog (Hh) signaling pathway plays an essential role in vertebrate embryonic tissue patterning of many developing organs. Signaling occurs predominantly in primary cilia and is initiated by the entry of the G protein-coupled receptor (GPCR)-like protein Smoothened into cilia and culminates in gene transcription via the Gli family of transcription factors upon their nuclear entry. Here we identify an orphan GPCR, Gpr175 (also known as Tpra1 or Tpra40: transmembrane protein, adipocyte associated 1 or of 40 kDa), which also localizes to primary cilia upon Hh stimulation and positively regulates Hh signaling. Interaction experiments place Gpr175 at the level of PKA and upstream of the Gαi component of heterotrimeric G proteins, which itself localizes to cilia and can modulate Hh signaling. Gpr175 or Gαi1 depletion leads to increases in cellular cAMP levels and in Gli3 processing into its repressor form. Thus we propose that Gpr175 coupled to Gαi1 normally functions to inhibit the production of cAMP by adenylyl cyclase upon Hh stimulation, thus maximizing signaling by turning off PKA activity and hence Gli3 repressor formation. Taken together our data suggest that Gpr175 is a novel positive regulator of the Hh signaling pathway. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. Kinesin Khc-73/KIF13B modulates retrograde BMP signaling by influencing endosomal dynamics at the Drosophila neuromuscular junction.

    Science.gov (United States)

    Liao, Edward H; Gray, Lindsay; Tsurudome, Kazuya; El-Mounzer, Wassim; Elazzouzi, Fatima; Baim, Christopher; Farzin, Sarah; Calderon, Mario R; Kauwe, Grant; Haghighi, A Pejmun

    2018-01-01

    Retrograde signaling is essential for neuronal growth, function and survival; however, we know little about how signaling endosomes might be directed from synaptic terminals onto retrograde axonal pathways. We have identified Khc-73, a plus-end directed microtubule motor protein, as a regulator of sorting of endosomes in Drosophila larval motor neurons. The number of synaptic boutons and the amount of neurotransmitter release at the Khc-73 mutant larval neuromuscular junction (NMJ) are normal, but we find a significant decrease in the number of presynaptic release sites. This defect in Khc-73 mutant larvae can be genetically enhanced by a partial genetic loss of Bone Morphogenic Protein (BMP) signaling or suppressed by activation of BMP signaling in motoneurons. Consistently, activation of BMP signaling that normally enhances the accumulation of phosphorylated form of BMP transcription factor Mad in the nuclei, can be suppressed by genetic removal of Khc-73. Using a number of assays including live imaging in larval motor neurons, we show that loss of Khc-73 curbs the ability of retrograde-bound endosomes to leave the synaptic area and join the retrograde axonal pathway. Our findings identify Khc-73 as a regulator of endosomal traffic at the synapse and modulator of retrograde BMP signaling in motoneurons.

  18. Human glutathione S-transferase P1-1 functions as an estrogen receptor α signaling modulator

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xiyuan [Department of Biological Science, Sookmyung Women’s University, Seoul (Korea, Republic of); An, Byoung Ha [Department of Food and Nutrition, College of Life Science, Sookmyung Women’s University, Seoul (Korea, Republic of); Kim, Min Jung; Park, Jong Hoon [Department of Biological Science, Sookmyung Women’s University, Seoul (Korea, Republic of); Kang, Young Sook [Department of Pharmacy, College of Pharmacy, Sookmyung Women’s University, Seoul (Korea, Republic of); Chang, Minsun, E-mail: minsunchang@sm.ac.kr [Department of Medical and Pharmaceutical Science, College of Science, Sookmyung Women’s University, Seoul (Korea, Republic of)

    2014-09-26

    Highlights: • GSTP induces the classical ERα signaling event. • The functional GSTP is a prerequisite for GSTP-induced ERα transcription activity. • The expression of RIP140, a transcription cofactor, was inhibited by GSTP protein. • We propose the novel non-enzymatic role of GSTP. - Abstract: Estrogen receptor α (ERα) plays a crucial role in estrogen-mediated signaling pathways and exerts its action as a nuclear transcription factor. Binding of the ligand-activated ERα to the estrogen response element (ERE) is a central part of ERα-associated signal transduction pathways and its aberrant modulation is associated with many disease conditions. Human glutathione S-transferase P1-1 (GSTP) functions as an enzyme in conjugation reactions in drug metabolism and as a regulator of kinase signaling pathways. It is overexpressed in tumors following chemotherapy and has been associated with a poor prognosis in breast cancer. In this study, a novel regulatory function of GSTP has been proposed in which GSTP modulates ERE-mediated ERα signaling events. Ectopic expression of GSTP was able to induce the ERα and ERE-mediated transcriptional activities in ERα-positive but GSTP-negative MCF7 human breast cancer cells. This inductive effect of GSTP on the ERE-transcription activity was diminished when the cells express a mutated form of the enzyme or are treated with a GSTP-specific chemical inhibitor. It was found that GSTP inhibited the expression of the receptor interacting protein 140 (RIP140), a negative regulator of ERα transcription, at both mRNA and protein levels. Our study suggests a novel non-enzymatic role of GSTP which plays a significant role in regulating the classical ERα signaling pathways via modification of transcription cofactors such as RIP140.

  19. A microRNA-mediated regulatory loop modulates NOTCH and MYC oncogenic signals in B- and T-cell malignancies.

    Science.gov (United States)

    Ortega, M; Bhatnagar, H; Lin, A-P; Wang, L; Aster, J C; Sill, H; Aguiar, R C T

    2015-04-01

    Growing evidence suggests that microRNAs (miRNAs) facilitate the cross-talk between transcriptional modules and signal transduction pathways. MYC and NOTCH1 contribute to the pathogenesis of lymphoid malignancies. NOTCH induces MYC, connecting two signaling programs that enhance oncogenicity. Here we show that this relationship is bidirectional and that MYC, via a miRNA intermediary, modulates NOTCH. MicroRNA-30a (miR-30a), a member of a family of miRNAs that are transcriptionally suppressed by MYC, directly binds to and inhibits NOTCH1 and NOTCH2 expression. Using a murine model and genetically modified human cell lines, we confirmed that miR-30a influences NOTCH expression in a MYC-dependent fashion. In turn, through genetic modulation, we demonstrated that intracellular NOTCH1 and NOTCH2, by inducing MYC, suppressed miR-30a. Conversely, pharmacological inhibition of NOTCH decreased MYC expression and ultimately de-repressed miR-30a. Examination of genetic models of gain and loss of miR-30a in diffuse large B-cell lymphoma (DLBCL) and T-acute lymphoblastic leukemia (T-ALL) cells suggested a tumor-suppressive role for this miRNA. Finally, the activity of the miR-30a-NOTCH-MYC loop was validated in primary DLBCL and T-ALL samples. These data define the presence of a miRNA-mediated regulatory circuitry that may modulate the oncogenic signals originating from NOTCH and MYC.

  20. D1 dopamine receptor signaling is modulated by the R7 RGS protein EAT-16 and the R7 binding protein RSBP-1 in Caenoerhabditis elegans motor neurons.

    Directory of Open Access Journals (Sweden)

    Khursheed A Wani

    Full Text Available Dopamine signaling modulates voluntary movement and reward-driven behaviors by acting through G protein-coupled receptors in striatal neurons, and defects in dopamine signaling underlie Parkinson's disease and drug addiction. Despite the importance of understanding how dopamine modifies the activity of striatal neurons to control basal ganglia output, the molecular mechanisms that control dopamine signaling remain largely unclear. Dopamine signaling also controls locomotion behavior in Caenorhabditis elegans. To better understand how dopamine acts in the brain we performed a large-scale dsRNA interference screen in C. elegans for genes required for endogenous dopamine signaling and identified six genes (eat-16, rsbp-1, unc-43, flp-1, grk-1, and cat-1 required for dopamine-mediated behavior. We then used a combination of mutant analysis and cell-specific transgenic rescue experiments to investigate the functional interaction between the proteins encoded by two of these genes, eat-16 and rsbp-1, within single cell types and to examine their role in the modulation of dopamine receptor signaling. We found that EAT-16 and RSBP-1 act together to modulate dopamine signaling and that while they are coexpressed with both D1-like and D2-like dopamine receptors, they do not modulate D2 receptor signaling. Instead, EAT-16 and RSBP-1 act together to selectively inhibit D1 dopamine receptor signaling in cholinergic motor neurons to modulate locomotion behavior.

  1. Diode-laser-pump module with integrated signal ports for pumping amplifying fibers and method

    Science.gov (United States)

    Savage-Leuchs,; Matthias, P [Woodinville, WA

    2009-05-26

    Apparatus and method for collimating pump light of a first wavelength from laser diode(s) into a collimated beam within an enclosure having first and second optical ports, directing pump light from the collimated beam to the first port; and directing signal light inside the enclosure between the first and second port. The signal and pump wavelengths are different. The enclosure provides a pump block having a first port that emits pump light to a gain fiber outside the enclosure and that also passes signal light either into or out of the enclosure, and another port that passes signal light either out of or into the enclosure. Some embodiments use a dichroic mirror to direct pump light to the first port and direct signal light between the first and second ports. Some embodiments include a wavelength-conversion device to change the wavelength of at least some of the signal light.

  2. XUV pulse effect on signal modulations of harmonic spectra from H ...

    Indian Academy of Sciences (India)

    LIQIANG FENG

    2018-03-24

    Mar 24, 2018 ... 2Laboratory of Modern Physics, Liaoning University of Technology, ... Molecular high-order harmonic generation; amplitude modulation of harmonics; frequency .... Here, mp, R and z are the mass of H or T, the internu-.

  3. Capacity upgrade in short-reach optical fibre networks: simultaneous 4-PAM 20 Gbps data and polarization-modulated PPS clock signal using a single VCSEL carrier

    Science.gov (United States)

    Isoe, G. M.; Wassin, S.; Gamatham, R. R. G.; Leitch, A. W. R.; Gibbon, T. B.

    2017-11-01

    In this work, a four-level pulse amplitude modulation (4-PAM) format with a polarization-modulated pulse per second (PPS) clock signal using a single vertical cavity surface emitting laser (VCSEL) carrier is for the first time experimentally demonstrated. We propose uncomplex alternative technique for increasing capacity and flexibility in short-reach optical communication links through multi-signal modulation onto a single VCSEL carrier. A 20 Gbps 4-PAM data signal is directly modulated onto a single mode 10 GHz bandwidth VCSEL carrier at 1310 nm, therefore, doubling the network bit rate. Carrier spectral efficiency is further maximized by exploiting the inherent orthogonal polarization switching of the VCSEL carrier with changing bias in transmission of a PPS clock signal. We, therefore, simultaneously transmit a 20 Gbps 4-PAM data signal and a polarization-based PPS clock signal using a single VCSEL carrier. It is the first time a signal VCSEL carrier is reported to simultaneously transmit a directly modulated 20 Gbps 4-PAM data signal and a polarization-based PPS clock signal. We further demonstrate on the design of a software-defined digital signal processing (DSP)-assisted receiver as an alternative to costly receiver hardware. Experimental results show that a 3.21 km fibre transmission with simultaneous 20 Gbps 4-PAM data signal and polarization-based PPS clock signal introduced a penalty of 3.76 dB. The contribution of polarization-based PPS clock signal to this penalty was found out to be 0.41 dB. Simultaneous distribution of data and timing clock signals over shared network infrastructure significantly increases the aggregated data rate at different optical network units (ONUs), without costly investment.

  4. Toward selective, sensitive, and discriminative detection of Hg(2+) and Cd(2+)via pH-modulated surface chemistry of glutathione-capped gold nanoclusters.

    Science.gov (United States)

    Huang, Pengcheng; Li, Sha; Gao, Nan; Wu, Fangying

    2015-11-07

    Heavy metal pollution can exert severe effects on the environment and human health. Simple, selective, and sensitive detection of heavy metal ions, especially two or more, using a single probe, is thereby of great importance. In this study, we report a new and facile strategy for discriminative detection of Hg(2+) and Cd(2+) with high selectivity and sensitivity via pH-modulated surface chemistry of the glutathione-capped gold NCs (GSH-Au NCs). By simply adjusting pH values of the colloidal solution of the NCs, Hg(2+) could specifically turn off the fluorescence under acidic pH, however, Cd(2+) could exclusively turn on the fluorescence under alkaline pH. This enables the NCs to serve as a dual fluorescent sensor for Hg(2+) and Cd(2+). We demonstrate that these two opposing sensing modes are presumably due to different interaction mechanisms: Hg(2+) induces aggregation by dissociating GSH from the Au surface via robust coordination and, Cd(2+) could passivate the Au surface by forming a Cd-GSH complex with a compact structure. Finally, the present strategy is successfully exploited to separately determine Hg(2+) and Cd(2+) in environmental water samples.

  5. CAMAC-controlled 4-level discriminator with four settable threshold levels

    International Nuclear Information System (INIS)

    Ujiie, N.; Ikeda, M.

    1989-01-01

    A CAMAC-controlled discriminator containing four input channels per module has been developed to provide a fast trigger signal for the TOPAZ barrel electromagnetic calorimeter. The calorimeter consists of 4300 lead-glass counters constructed and operated at the e + e - collider at KEK. The performance of the discriminator obtained in a test and in a real setup with cosmic ray is described. (orig.)

  6. ß-Adrenergic Receptor Signaling and Modulation of Long-Term Potentiation in the Mammalian Hippocampus

    Science.gov (United States)

    O'Dell, Thomas J.; Connor, Steven A.; Guglietta, Ryan; Nguyen, Peter V.

    2015-01-01

    Encoding new information in the brain requires changes in synaptic strength. Neuromodulatory transmitters can facilitate synaptic plasticity by modifying the actions and expression of specific signaling cascades, transmitter receptors and their associated signaling complexes, genes, and effector proteins. One critical neuromodulator in the…

  7. Cftr Modulates Wnt/β-Catenin Signaling and Stem Cell Proliferation in Murine Intestine

    Directory of Open Access Journals (Sweden)

    Ashlee M. Strubberg

    2018-01-01

    Conclusions: CF intestine shows increased ISC proliferation and Wnt/β-catenin signaling. Loss of Cftr increases pHi in ISCs, which stabilizes the plasma membrane association of the Wnt transducer Dvl, likely facilitating Wnt/β-catenin signaling. Absence of Cftr-dependent suppression of ISC proliferation in the CF intestine may contribute to increased risk for intestinal tumors.

  8. GDSL LIPASE1 Modulates Plant Immunity through Feedback Regulation of Ethylene Signaling1[W

    Science.gov (United States)

    Kim, Hye Gi; Kwon, Sun Jae; Jang, Young Jin; Nam, Myung Hee; Chung, Joo Hee; Na, Yun-Cheol; Guo, Hongwei; Park, Ohkmae K.

    2013-01-01

    Ethylene is a key signal in the regulation of plant defense responses. It is required for the expression and function of GDSL LIPASE1 (GLIP1) in Arabidopsis (Arabidopsis thaliana), which plays an important role in plant immunity. Here, we explore molecular mechanisms underlying the relationship between GLIP1 and ethylene signaling by an epistatic analysis of ethylene response mutants and GLIP1-overexpressing (35S:GLIP1) plants. We show that GLIP1 expression is regulated by ethylene signaling components and, further, that GLIP1 expression or application of petiole exudates from 35S:GLIP1 plants affects ethylene signaling both positively and negatively, leading to ETHYLENE RESPONSE FACTOR1 activation and ETHYLENE INSENSITIVE3 (EIN3) down-regulation, respectively. Additionally, 35S:GLIP1 plants or their exudates increase the expression of the salicylic acid biosynthesis gene SALICYLIC ACID INDUCTION-DEFICIENT2, known to be inhibited by EIN3 and EIN3-LIKE1. These results suggest that GLIP1 regulates plant immunity through positive and negative feedback regulation of ethylene signaling, and this is mediated by its activity to accumulate a systemic signal(s) in the phloem. We propose a model explaining how GLIP1 regulates the fine-tuning of ethylene signaling and ethylene-salicylic acid cross talk. PMID:24170202

  9. β-Adrenergic receptor signaling and modulation of long-term potentiation in the mammalian hippocampus

    OpenAIRE

    O'Dell, Thomas J.; Connor, Steven A.; Guglietta, Ryan; Nguyen, Peter V.

    2015-01-01

    Encoding new information in the brain requires changes in synaptic strength. Neuromodulatory transmitters can facilitate synaptic plasticity by modifying the actions and expression of specific signaling cascades, transmitter receptors and their associated signaling complexes, genes, and effector proteins. One critical neuromodulator in the mammalian brain is norepinephrine (NE), which regulates multiple brain functions such as attention, perception, arousal, sleep, learning, and memory. The m...

  10. Primary cilia modulate Ihh signal transduction in response to hydrostatic loading of growth plate chondrocytes.

    Science.gov (United States)

    Shao, Yvonne Y; Wang, Lai; Welter, Jean F; Ballock, R Tracy

    2012-01-01

    Indian hedgehog (Ihh) is a key component of the regulatory apparatus governing chondrocyte proliferation and differentiation in the growth plate. Recent studies have demonstrated that the primary cilium is the site of Ihh signaling within the cell, and that primary cilia are essential for bone and cartilage formation. Primary cilia are also postulated to act as mechanosensory organelles that transduce mechanical forces acting on the cell into biological signals. In this study, we used a hydrostatic compression system to examine Ihh signal transduction under the influence of mechanical load. Our results demonstrate that hydrostatic compression increased both Ihh gene expression and Ihh-responsive Gli-luciferase activity. These increases were aborted by disrupting the primary cilia structure with chloral hydrate. These results suggest that growth plate chondrocytes respond to hydrostatic loading by increasing Ihh signaling, and that the primary cilium is required for this mechano-biological signal transduction to occur. Copyright © 2011 Elsevier Inc. All rights reserved.

  11. Primary Cilia Modulate IHH Signal Transduction in Response to Hydrostatic Loading of Growth Plate Chondrocytes

    Science.gov (United States)

    Shao, Y, Yvonne Y.; Wang, Lai; Welter, J, Jean F.; Ballock, R. Tracy

    2011-01-01

    Indian Hedgehog (Ihh) is a key component of the regulatory apparatus governing chondrocyte proliferation and differentiation in the growth plate. Recent studies have demonstrated that the primary cilium is the site of Ihh signaling within the cell, and that primary cilia are essential for bone and cartilage formation. Primary cilia are also postulated to act as mechanosensory organelles that transduce mechanical forces acting on the cell into biological signals. In this study, we used a hydrostatic compression system to examine Ihh signal transduction under the influence of mechanical load. Our results demonstrate that hydrostatic compression increased both Ihh gene expression and Ihh-responsive Gli-luciferase activity. These increases were aborted by disrupting the primary cilia structure with chloral hydrate. These results suggest that growth plate chondrocytes respond to hydrostatic loading by increasing Ihh signaling, and that the primary cilium is required for this mechano-biological signal transduction to occur. PMID:21930256

  12. Receiver Signal to Noise Ratios for IPDA Lidars Using Sine-wave and Pulsed Laser Modulation and Direct Detections

    Science.gov (United States)

    Sun, Xiaoli; Abshire, James B.

    2011-01-01

    Integrated path differential absorption (IPDA) lidar can be used to remotely measure the column density of gases in the path to a scattering target [1]. The total column gas molecular density can be derived from the ratio of the laser echo signal power with the laser wavelength on the gas absorption line (on-line) to that off the line (off-line). 80th coherent detection and direct detection IPDA lidar have been used successfully in the past in horizontal path and airborne remote sensing measurements. However, for space based measurements, the signal propagation losses are often orders of magnitude higher and it is important to use the most efficient laser modulation and detection technique to minimize the average laser power and the electrical power from the spacecraft. This paper gives an analysis the receiver signal to noise ratio (SNR) of several laser modulation and detection techniques versus the average received laser power under similar operation environments. Coherent detection [2] can give the best receiver performance when the local oscillator laser is relatively strong and the heterodyne mixing losses are negligible. Coherent detection has a high signal gain and a very narrow bandwidth for the background light and detector dark noise. However, coherent detection must maintain a high degree of coherence between the local oscillator laser and the received signal in both temporal and spatial modes. This often results in a high system complexity and low overall measurement efficiency. For measurements through atmosphere the coherence diameter of the received signal also limits the useful size of the receiver telescope. Direct detection IPDA lidars are simpler to build and have fewer constraints on the transmitter and receiver components. They can use much larger size 'photon-bucket' type telescopes to reduce the demands on the laser transmitter. Here we consider the two most widely used direct detection IPDA lidar techniques. The first technique uses two CW

  13. Modulation of Ras signaling alters the toxicity of hydroquinone, a benzene metabolite and component of cigarette smoke

    International Nuclear Information System (INIS)

    North, Matthew; Shuga, Joe; Fromowitz, Michele; Loguinov, Alexandre; Shannon, Kevin; Zhang, Luoping; Smith, Martyn T; Vulpe, Chris D

    2014-01-01

    Benzene is an established human leukemogen, with a ubiquitous environmental presence leading to significant population exposure. In a genome-wide functional screen in the yeast Saccharomyces cerevisiae, inactivation of IRA2, a yeast ortholog of the human tumor suppressor gene NF1 (Neurofibromin), enhanced sensitivity to hydroquinone, an important benzene metabolite. Increased Ras signaling is implicated as a causal factor in the increased pre-disposition to leukemia of individuals with mutations in NF1. Growth inhibition of yeast by hydroquinone was assessed in mutant strains exhibiting varying levels of Ras activity. Subsequently, effects of hydroquinone on both genotoxicity (measured by micronucleus formation) and proliferation of WT and Nf1 null murine hematopoietic precursors were assessed. Here we show that the Ras status of both yeast and mammalian cells modulates hydroquinone toxicity, indicating potential synergy between Ras signaling and benzene toxicity. Specifically, enhanced Ras signaling increases both hydroquinone-mediated growth inhibition in yeast and genotoxicity in mammalian hematopoetic precursors as measured by an in vitro erythroid micronucleus assay. Hydroquinone also increases proliferation of CFU-GM progenitor cells in mice with Nf1 null bone marrow relative to WT, the same cell type associated with benzene-associated leukemia. Together our findings show that hydroquinone toxicity is modulated by Ras signaling. Individuals with abnormal Ras signaling could be more vulnerable to developing myeloid diseases after exposure to benzene. We note that hydroquinone is used cosmetically as a skin-bleaching agent, including by individuals with cafe-au-lait spots (which may be present in individuals with neurofibromatosis who have a mutation in NF1), which could be unadvisable given our findings

  14. Cell signaling heterogeneity is modulated by both cell-intrinsic and -extrinsic mechanisms: An integrated approach to understanding targeted therapy.

    Science.gov (United States)

    Kim, Eunjung; Kim, Jae-Young; Smith, Matthew A; Haura, Eric B; Anderson, Alexander R A

    2018-03-01

    During the last decade, our understanding of cancer cell signaling networks has significantly improved, leading to the development of various targeted therapies that have elicited profound but, unfortunately, short-lived responses. This is, in part, due to the fact that these targeted therapies ignore context and average out heterogeneity. Here, we present a mathematical framework that addresses the impact of signaling heterogeneity on targeted therapy outcomes. We employ a simplified oncogenic rat sarcoma (RAS)-driven mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase-protein kinase B (PI3K-AKT) signaling pathway in lung cancer as an experimental model system and develop a network model of the pathway. We measure how inhibition of the pathway modulates protein phosphorylation as well as cell viability under different microenvironmental conditions. Training the model on this data using Monte Carlo simulation results in a suite of in silico cells whose relative protein activities and cell viability match experimental observation. The calibrated model predicts distributional responses to kinase inhibitors and suggests drug resistance mechanisms that can be exploited in drug combination strategies. The suggested combination strategies are validated using in vitro experimental data. The validated in silico cells are further interrogated through an unsupervised clustering analysis and then integrated into a mathematical model of tumor growth in a homogeneous and resource-limited microenvironment. We assess posttreatment heterogeneity and predict vast differences across treatments with similar efficacy, further emphasizing that heterogeneity should modulate treatment strategies. The signaling model is also integrated into a hybrid cellular automata (HCA) model of tumor growth in a spatially heterogeneous microenvironment. As a proof of concept, we simulate tumor responses to targeted therapies in a spatially segregated tissue structure containing tumor

  15. NADPH Oxidase 1 Modulates WNT and NOTCH1 Signaling To Control the Fate of Proliferative Progenitor Cells in the Colon▿

    Science.gov (United States)

    Coant, Nicolas; Ben Mkaddem, Sanae; Pedruzzi, Eric; Guichard, Cécile; Tréton, Xavier; Ducroc, Robert; Freund, Jean-Noel; Cazals-Hatem, Dominique; Bouhnik, Yoram; Woerther, Paul-Louis; Skurnik, David; Grodet, Alain; Fay, Michèle; Biard, Denis; Lesuffleur, Thécla; Deffert, Christine; Moreau, Richard; Groyer, André; Krause, Karl-Heinz; Daniel, Fanny; Ogier-Denis, Eric

    2010-01-01

    The homeostatic self-renewal of the colonic epithelium requires coordinated regulation of the canonical Wnt/β-catenin and Notch signaling pathways to control proliferation and lineage commitment of multipotent stem cells. However, the molecular mechanisms by which the Wnt/β-catenin and Notch1 pathways interplay in controlling cell proliferation and fate in the colon are poorly understood. Here we show that NADPH oxidase 1 (NOX1), a reactive oxygen species (ROS)-producing oxidase that is highly expressed in colonic epithelial cells, is a pivotal determinant of cell proliferation and fate that integrates Wnt/β-catenin and Notch1 signals. NOX1-deficient mice reveal a massive conversion of progenitor cells into postmitotic goblet cells at the cost of colonocytes due to the concerted repression of phosphatidylinositol 3-kinase (PI3K)/AKT/Wnt/β-catenin and Notch1 signaling. This conversion correlates with the following: (i) the redox-dependent activation of the dual phosphatase PTEN, causing the inactivation of the Wnt pathway effector β-catenin, and (ii) the downregulation of Notch1 signaling that provokes derepression of mouse atonal homolog 1 (Math1) expression. We conclude that NOX1 controls the balance between goblet and absorptive cell types in the colon by coordinately modulating PI3K/AKT/Wnt/β-catenin and Notch1 signaling. This finding provides the molecular basis for the role of NOX1 in cell proliferation and postmitotic differentiation. PMID:20351171

  16. Analysis of Maneuvering Targets with Complex Motions by Two-Dimensional Product Modified Lv's Distribution for Quadratic Frequency Modulation Signals.

    Science.gov (United States)

    Jing, Fulong; Jiao, Shuhong; Hou, Changbo; Si, Weijian; Wang, Yu

    2017-06-21

    For targets with complex motion, such as ships fluctuating with oceanic waves and high maneuvering airplanes, azimuth echo signals can be modeled as multicomponent quadratic frequency modulation (QFM) signals after migration compensation and phase adjustment. For the QFM signal model, the chirp rate (CR) and the quadratic chirp rate (QCR) are two important physical quantities, which need to be estimated. For multicomponent QFM signals, the cross terms create a challenge for detection, which needs to be addressed. In this paper, by employing a novel multi-scale parametric symmetric self-correlation function (PSSF) and modified scaled Fourier transform (mSFT), an effective parameter estimation algorithm is proposed-referred to as the Two-Dimensional product modified Lv's distribution (2D-PMLVD)-for QFM signals. The 2D-PMLVD is simple and can be easily implemented by using fast Fourier transform (FFT) and complex multiplication. These measures are analyzed in the paper, including the principle, the cross term, anti-noise performance, and computational complexity. Compared to the other three representative methods, the 2D-PMLVD can achieve better anti-noise performance. The 2D-PMLVD, which is free of searching and has no identifiability problems, is more suitable for multicomponent situations. Through several simulations and analyses, the effectiveness of the proposed estimation algorithm is verified.

  17. The NLR-related protein NWD1 is associated with prostate cancer and modulates androgen receptor signaling.

    Science.gov (United States)

    Correa, Ricardo G; Krajewska, Maryla; Ware, Carl F; Gerlic, Motti; Reed, John C

    2014-03-30

    Prostate cancer (PCa) is among the leading causes of cancer-related death in men. Androgen receptor (AR) signaling plays a seminal role in prostate development and homeostasis, and dysregulation of this pathway is intimately linked to prostate cancer pathogenesis and progression. Here, we identify the cytosolic NLR-related protein NWD1 as a novel modulator of AR signaling. We determined that expression of NWD1 becomes elevated during prostate cancer progression, based on analysis of primary tumor specimens. Experiments with cultured cells showed that NWD1 expression is up-regulated by the sex-determining region Y (SRY) family proteins. Gene silencing procedures, in conjunction with transcriptional profiling, showed that NWD1 is required for expression of PDEF (prostate-derived Ets factor), which is known to bind and co-regulate AR. Of note, NWD1 modulates AR protein levels. Depleting NWD1 in PCa cell lines reduces AR levels and suppresses activity of androgen-driven reporter genes. NWD1 knockdown potently suppressed growth of androgen-dependent LNCaP prostate cancer cells, thus showing its functional importance in an AR-dependent tumor cell model. Proteomic analysis suggested that NWD1 associates with various molecular chaperones commonly related to AR complexes. Altogether, these data suggest a role for tumor-associated over-expression of NWD1 in dysregulation of AR signaling in PCa.

  18. Demonstration of DFT-spread 256QAM-OFDM signal transmission with cost-effective directly modulated laser.

    Science.gov (United States)

    Li, Fan; Yu, Jianjun; Fang, Yuan; Dong, Ze; Li, Xinying; Chen, Lin

    2014-04-07

    We experimentally demonstrated a 256-ary quadrature amplitude modulation (256QAM) direct-detection optical orthogonal frequency division multiplexing (DDO-OFDM) transmission system utilizing a cost-effective directly modulated laser (DML). Intra-symbol frequency-domain averaging (ISFA) is applied to suppress in-band noise while the channel response estimation and Discrete Fourier Transform-spread (DFT-spread) is used to reduce the peak-to-average power ratio (PAPR) of the transmitted OFDM signal. The bit-error ratio (BER) of 15-Gbit/s 256QAM-OFDM signal has been measured after 20-km SSMF transmission that is less than 7% forward-error-correction (FEC) threshold of 3.8 × 10(-3) as the launch power into fiber is set at 6dBm. For 11.85-Gbit/s 256QAM-OFDM signal, with the aid of ISFA-based channel estimation and PAPR reduction enabled by DFT-spread, the BER after 20-km SSMF transmission can be improved from 6.4 × 10(-3) to 6.8 × 10(-4) when the received optical power is -6dBm.

  19. A hepatic amino acid/mTOR/S6K-dependent signalling pathway modulates systemic lipid metabolism via neuronal signals.

    Science.gov (United States)

    Uno, Kenji; Yamada, Tetsuya; Ishigaki, Yasushi; Imai, Junta; Hasegawa, Yutaka; Sawada, Shojiro; Kaneko, Keizo; Ono, Hiraku; Asano, Tomoichiro; Oka, Yoshitomo; Katagiri, Hideki

    2015-08-13

    Metabolism is coordinated among tissues and organs via neuronal signals. Levels of circulating amino acids (AAs), which are elevated in obesity, activate the intracellular target of rapamycin complex-1 (mTORC1)/S6kinase (S6K) pathway in the liver. Here we demonstrate that hepatic AA/mTORC1/S6K signalling modulates systemic lipid metabolism via a mechanism involving neuronal inter-tissue communication. Hepatic expression of an AA transporter, SNAT2, activates the mTORC1/S6K pathway, and markedly elevates serum triglycerides (TGs), while downregulating adipose lipoprotein lipase (LPL). Hepatic Rheb or active-S6K expression have similar metabolic effects, whereas hepatic expression of dominant-negative-S6K inhibits TG elevation in SNAT2 mice. Denervation, pharmacological deafferentation and β-blocker administration suppress obesity-related hypertriglyceridemia with adipose LPL upregulation, suggesting that signals are transduced between liver and adipose tissue via a neuronal pathway consisting of afferent vagal and efferent sympathetic nerves. Thus, the neuronal mechanism uncovered here serves to coordinate amino acid and lipid levels and contributes to the development of obesity-related hypertriglyceridemia.

  20. Hippocampal dendritic spines remodeling and fear memory are modulated by GABAergic signaling within the basolateral amygdala complex.

    Science.gov (United States)

    Giachero, Marcelo; Calfa, Gaston D; Molina, Victor A

    2015-05-01

    GABAergic signaling in the basolateral amygdala complex (BLA) plays a crucial role on the modulation of the stress influence on fear memory. Moreover, accumulating evidence suggests that the dorsal hippocampus (DH) is a downstream target of BLA neurons in contextual fear. Given that hippocampal structural plasticity is proposed to provide a substrate for the storage of long-term memories, the main aim of this study is to evaluate the modulation of GABA neurotransmission in the BLA on spine density in the DH following stress on contextual fear learning. The present findings show that prior stressful experience promoted contextual fear memory and enhanced spine density in the DH. Intra-BLA infusion of midazolam, a positive modulator of GABAa sites, prevented the facilitating influence of stress on both fear retention and hippocampal dendritic spine remodeling. Similarly to the stress-induced effects, the blockade of GABAa sites within the BLA ameliorated fear memory emergence and induced structural remodeling in the DH. These findings suggest that GABAergic transmission in BLA modulates the structural changes in DH associated to the influence of stress on fear memory. © 2015 Wiley Periodicals, Inc.

  1. Atorvastatin calcium inhibits phenotypic modulation of PDGF-BB-induced VSMCs via down-regulation the Akt signaling pathway.

    Science.gov (United States)

    Chen, Shuang; Liu, Baoqin; Kong, Dehui; Li, Si; Li, Chao; Wang, Huaqin; Sun, Yingxian

    2015-01-01

    Plasticity of vascular smooth muscle cells (VSMCs) plays a central role in the onset and progression of proliferative vascular diseases. In adult tissue, VSMCs exist in a physiological contractile-quiescent phenotype, which is defined by lack of the ability of proliferation and migration, while high expression of contractile marker proteins. After injury to the vessel, VSMC shifts from a contractile phenotype to a pathological synthetic phenotype, associated with increased proliferation, migration and matrix secretion. It has been demonstrated that PDGF-BB is a critical mediator of VSMCs phenotypic switch. Atorvastatin calcium, a selective inhibitor of 3-hydroxy-3-methyl-glutaryl l coenzyme A (HMG-CoA) reductase, exhibits various protective effects against VSMCs. In this study, we investigated the effects of atorvastatin calcium on phenotype modulation of PDGF-BB-induced VSMCs and the related intracellular signal transduction pathways. Treatment of VSMCs with atorvastatin calcium showed dose-dependent inhibition of PDGF-BB-induced proliferation. Atorvastatin calcium co-treatment inhibited the phenotype modulation and cytoskeleton rearrangements and improved the expression of contractile phenotype marker proteins such as α-SM actin, SM22α and calponin in comparison with PDGF-BB alone stimulated VSMCs. Although Akt phosphorylation was strongly elicited by PDGF-BB, Akt activation was attenuated when PDGF-BB was co-administrated with atorvastatin calcium. In conclusion, atorvastatin calcium inhibits phenotype modulation of PDGF-BB-induced VSMCs and activation of the Akt signaling pathway, indicating that Akt might play a vital role in the modulation of phenotype.

  2. Balancing awareness: Vestibular signals modulate visual consciousness in the absence of awareness.

    Science.gov (United States)

    Salomon, Roy; Kaliuzhna, Mariia; Herbelin, Bruno; Blanke, Olaf

    2015-11-01

    The processing of visual and vestibular information is crucial for perceiving self-motion. Visual cues, such as optic flow, have been shown to induce and alter vestibular percepts, yet the role of vestibular information in shaping visual awareness remains unclear. Here we investigated if vestibular signals influence the access to awareness of invisible visual signals. Using natural vestibular stimulation (passive yaw rotations) on a vestibular self-motion platform, and optic flow masked through continuous flash suppression (CFS) we tested if congruent visual-vestibular information would break interocular suppression more rapidly than incongruent information. We found that when the unseen optic flow was congruent with the vestibular signals perceptual suppression as quantified with the CFS paradigm was broken more rapidly than when it was incongruent. We argue that vestibular signals impact the formation of visual awareness through enhanced access to awareness for congruent multisensory stimulation. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Capacity-Approaching Modulation Formats for Optical Transmission Systems: Signal shaping and advanced de/muxing for efficient resource exploitation

    DEFF Research Database (Denmark)

    Estaran Tolosa, Jose Manuel

    Aiming for efficient fiber-optic data transport, this thesis addresses three scenario-specific modulation and/or multiplexing techniques which, leveraging digital signal processing, can further exploit the available resources.The considered environments are: (i) (ultra) long-haul networks, where we...... focus on improving the receiver sensitivity; (ii) metropolitan area networks, where the target is providing spectral and rate adaptability with fine granularity and easy reconfigurability; and (iii) short-haul networks, where facilitating more affordable throughput scaling is pursued. Functioning...

  4. Rictor positively regulates B cell receptor signaling by modulating actin reorganization via ezrin.

    Directory of Open Access Journals (Sweden)

    Lu Huang

    2017-08-01

    Full Text Available As the central hub of the metabolism machinery, the mammalian target of rapamycin complex 2 (mTORC2 has been well studied in lymphocytes. As an obligatory component of mTORC2, the role of Rictor in T cells is well established. However, the role of Rictor in B cells still remains elusive. Rictor is involved in B cell development, especially the peripheral development. However, the role of Rictor on B cell receptor (BCR signaling as well as the underlying cellular and molecular mechanism is still unknown. This study used B cell-specfic Rictor knockout (KO mice to investigate how Rictor regulates BCR signaling. We found that the key positive and negative BCR signaling molecules, phosphorylated Brutons tyrosine kinase (pBtk and phosphorylated SH2-containing inositol phosphatase (pSHIP, are reduced and enhanced, respectively, in Rictor KO B cells. This suggests that Rictor positively regulates the early events of BCR signaling. We found that the cellular filamentous actin (F-actin is drastically increased in Rictor KO B cells after BCR stimulation through dysregulating the dephosphorylation of ezrin. The high actin-ezrin intensity area restricts the lateral movement of BCRs upon stimulation, consequently reducing BCR clustering and BCR signaling. The reduction in the initiation of BCR signaling caused by actin alteration is associated with a decreased humoral immune response in Rictor KO mice. The inhibition of actin polymerization with latrunculin in Rictor KO B cells rescues the defects of BCR signaling and B cell differentiation. Overall, our study provides a new pathway linking cell metablism to BCR activation, in which Rictor regulates BCR signaling via actin reorganization.

  5. Signaling and Adaptation Modulate the Dynamics of the Photosensoric Complex of Natronomonas pharaonis.

    Directory of Open Access Journals (Sweden)

    Philipp S Orekhov

    2015-10-01

    Full Text Available Motile bacteria and archaea respond to chemical and physical stimuli seeking optimal conditions for survival. To this end transmembrane chemo- and photoreceptors organized in large arrays initiate signaling cascades and ultimately regulate the rotation of flagellar motors. To unravel the molecular mechanism of signaling in an archaeal phototaxis complex we performed coarse-grained molecular dynamics simulations of a trimer of receptor/transducer dimers, namely NpSRII/NpHtrII from Natronomonas pharaonis. Signaling is regulated by a reversible methylation mechanism called adaptation, which also influences the level of basal receptor activation. Mimicking two extreme methylation states in our simulations we found conformational changes for the transmembrane region of NpSRII/NpHtrII which resemble experimentally observed light-induced changes. Further downstream in the cytoplasmic domain of the transducer the signal propagates via distinct changes in the dynamics of HAMP1, HAMP2, the adaptation domain and the binding region for the kinase CheA, where conformational rearrangements were found to be subtle. Overall these observations suggest a signaling mechanism based on dynamic allostery resembling models previously proposed for E. coli chemoreceptors, indicating similar properties of signal transduction for archaeal photoreceptors and bacterial chemoreceptors.

  6. Macrophage migration inhibitory factor (MIF) modulates trophic signaling through interaction with serine protease HTRA1

    DEFF Research Database (Denmark)

    Fex Svenningsen, Åsa; Loering, Svenja; Sørensen, Anna Lahn

    2017-01-01

    Macrophage migration inhibitory factor (MIF), a small conserved protein, is abundant in the immune- and central nervous system (CNS). MIF has several receptors and binding partners that can modulate its action on a cel-lular level. It is upregulated in neurodegenerative diseases and cancer although...

  7. Clock recovery PLL with gated PFD for NRZ ON-OFF Modulated Signals in a retinal implant system.

    Science.gov (United States)

    Brendler, Christian; Aryan, Naser Pour; Rieger, Viola; Rothermel, Albrecht

    2013-01-01

    A Clock Recovery Phase Locked Loop with Gated Phase Frequency Detector (GPLL) for NRZ ON-OFF Modulated Signals with low data transmission rates for an inductively powered subretinal implant system is presented. Low data transmission rate leads to a long absence of inductive powering in the system when zeros are transmitted. Consequently there is no possibility to extract any clock in these pauses, thus the digital circuitry can not work any more. Compared to a commonly used PLL for clock extraction, no certain amount of data transitions is needed. This is achieved by having two operating modes. In one mode the GPLL tracks the HF input signal. In the other, the GPLL is an adjustable oscillator oscillating at the last used frequency. The proposed GPLL is fabricated and measured using a 350 nm High Voltage CMOS technology.

  8. Real-time photonic sampling with improved signal-to-noise and distortion ratio using polarization-dependent modulators

    Science.gov (United States)

    Liang, Dong; Zhang, Zhiyao; Liu, Yong; Li, Xiaojun; Jiang, Wei; Tan, Qinggui

    2018-04-01

    A real-time photonic sampling structure with effective nonlinearity suppression and excellent signal-to-noise ratio (SNR) performance is proposed. The key points of this scheme are the polarization-dependent modulators (P-DMZMs) and the sagnac loop structure. Thanks to the polarization sensitive characteristic of P-DMZMs, the differences between transfer functions of the fundamental signal and the distortion become visible. Meanwhile, the selection of specific biases in P-DMZMs is helpful to achieve a preferable linearized performance with a low noise level for real-time photonic sampling. Compared with the quadrature-biased scheme, the proposed scheme is capable of valid nonlinearity suppression and is able to provide a better SNR performance even in a large frequency range. The proposed scheme is proved to be effective and easily implemented for real time photonic applications.

  9. Nonstructural 3 Protein of Hepatitis C Virus Modulates the Tribbles Homolog 3/Akt Signaling Pathway for Persistent Viral Infection

    Science.gov (United States)

    Tran, Si C.; Pham, Tu M.; Nguyen, Lam N.; Park, Eun-Mee; Lim, Yun-Sook

    2016-01-01

    ABSTRACT Hepatitis C virus (HCV) infection often causes chronic hepatitis, liver cirrhosis, and ultimately hepatocellular carcinoma. However, the mechanisms underlying HCV-induced liver pathogenesis are still not fully understood. By transcriptome sequencing (RNA-Seq) analysis, we recently identified host genes that were significantly differentially expressed in cell culture-grown HCV (HCVcc)-infected cells. Of these, tribbles homolog 3 (TRIB3) was selected for further characterization. TRIB3 was initially identified as a binding partner of protein kinase B (also known as Akt). TRIB3 blocks the phosphorylation of Akt and induces apoptosis under endoplasmic reticulum (ER) stress conditions. HCV has been shown to enhance Akt phosphorylation for its own propagation. In the present study, we demonstrated that both mRNA and protein levels of TRIB3 were increased in the context of HCV replication. We further showed that promoter activity of TRIB3 was increased by HCV-induced ER stress. Silencing of TRIB3 resulted in increased RNA and protein levels of HCV, whereas overexpression of TRIB3 decreased HCV replication. By employing an HCV pseudoparticle entry assay, we further showed that TRIB3 was a negative host factor involved in HCV entry. Both in vitro binding and immunoprecipitation assays demonstrated that HCV NS3 specifically interacted with TRIB3. Consequently, the association of TRIB3 and Akt was disrupted by HCV NS3, and thus, TRIB3-Akt signaling was impaired in HCV-infected cells. Moreover, HCV modulated TRIB3 to promote extracellular signal-regulated kinase (ERK) phosphorylation, activator protein 1 (AP-1) activity, and cell migration. Collectively, these data indicate that HCV exploits the TRIB3-Akt signaling pathway to promote persistent viral infection and may contribute to HCV-mediated pathogenesis. IMPORTANCE TRIB3 is a pseudokinase protein that acts as an adaptor in signaling pathways for important cellular processes. So far, the functional involvement of

  10. Central GLP-1 receptor activation modulates cocaine-evoked phasic dopamine signaling in the nucleus accumbens core.

    Science.gov (United States)

    Fortin, Samantha M; Roitman, Mitchell F

    2017-07-01

    Drugs of abuse increase the frequency and magnitude of brief (1-3s), high concentration (phasic) dopamine release events in terminal regions. These are thought to be a critical part of drug reinforcement and ultimately the development of addiction. Recently, metabolic regulatory peptides, including the satiety signal glucagon-like peptide-1 (GLP-1), have been shown to modulate cocaine reward-driven behavior and sustained dopamine levels after cocaine administration. Here, we use fast-scan cyclic voltammetry (FSCV) to explore GLP-1 receptor (GLP-1R) modulation of dynamic dopamine release in the nucleus accumbens (NAc) during cocaine administration. We analyzed dopamine release events in both the NAc shell and core, as these two subregions are differentially affected by cocaine and uniquely contribute to motivated behavior. We found that central delivery of the GLP-1R agonist Exendin-4 suppressed the induction of phasic dopamine release events by intravenous cocaine. This effect was selective for dopamine signaling in the NAc core. Suppression of phasic signaling in the core by Exendin-4 could not be attributed to interference with cocaine binding to one of its major substrates, the dopamine transporter, as cocaine-induced increases in reuptake were unaffected. The results suggest that GLP-1R activation, instead, exerts its suppressive effects by altering dopamine release - possibly by suppressing the excitability of dopamine neurons. Given the role of NAc core dopamine in the generation of conditioned responses based on associative learning, suppression of cocaine-induced dopamine signaling in this subregion by GLP-1R agonism may decrease the reinforcing properties of cocaine. Thus, GLP-1Rs remain viable targets for the treatment and prevention of cocaine seeking, taking and relapse. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Modulating Wnt Signaling Rescues Palate Morphogenesis in Pax9 Mutant Mice.

    Science.gov (United States)

    Li, C; Lan, Y; Krumlauf, R; Jiang, R

    2017-10-01

    Cleft palate is a common birth defect caused by disruption of palatogenesis during embryonic development. Although mutations disrupting components of the Wnt signaling pathway have been associated with cleft lip and palate in humans and mice, the mechanisms involving canonical Wnt signaling and its regulation in secondary palate development are not well understood. Here, we report that canonical Wnt signaling plays an important role in Pax9-mediated regulation of secondary palate development. We found that cleft palate pathogenesis in Pax9-deficient embryos is accompanied by significantly reduced expression of Axin2, an endogenous target of canonical Wnt signaling, in the developing palatal mesenchyme, particularly in the posterior regions of the palatal shelves. We found that expression of Dkk2, encoding a secreted Wnt antagonist, is significantly increased whereas the levels of active β-catenin protein, the essential transcriptional coactivator of canonical Wnt signaling, is significantly decreased in the posterior regions of the palatal shelves in embryonic day 13.5 Pax9-deficent embryos in comparison with control littermates. We show that small molecule-mediated inhibition of Dickkopf (DKK) activity in utero during palatal shelf morphogenesis partly rescued secondary palate development in Pax9-deficient embryos. Moreover, we found that genetic inactivation of Wise, which is expressed in the developing palatal shelves and encodes another secreted antagonist of canonical Wnt signaling, also rescued palate morphogenesis in Pax9-deficient mice. Furthermore, whereas Pax9 del/del embryos exhibit defects in palatal shelf elevation/reorientation and significant reduction in accumulation of hyaluronic acid-a high molecular extracellular matrix glycosaminoglycan implicated in playing an important role in palatal shelf elevation-80% of Pax9 del/del ;Wise -/- double-mutant mouse embryos exhibit rescued palatal shelf elevation/reorientation, accompanied by restored

  12. Spatial attention related SEP amplitude modulations covary with BOLD signal in S1--a simultaneous EEG--fMRI study.

    Science.gov (United States)

    Schubert, Ruth; Ritter, Petra; Wüstenberg, Torsten; Preuschhof, Claudia; Curio, Gabriel; Sommer, Werner; Villringer, Arno

    2008-11-01

    Recent studies investigating the influence of spatial-selective attention on primary somatosensory processing have produced inconsistent results. The aim of this study was to explore the influence of tactile spatial-selective attention on spatiotemporal aspects of evoked neuronal activity in the primary somatosensory cortex (S1). We employed simultaneous electroencephalography (EEG)-functional magnetic resonance imaging (fMRI) in 14 right-handed subjects during bilateral index finger Braille stimulation to investigate the relationship between attentional effects on somatosensory evoked potential (SEP) components and the blood oxygenation level-dependent (BOLD) signal. The 1st reliable EEG response following left tactile stimulation (P50) was significantly enhanced by spatial-selective attention, which has not been reported before. FMRI analysis revealed increased activity in contralateral S1. Remarkably, the effect of attention on the P50 component as well as long-latency SEP components starting at 190 ms for left stimuli correlated with attentional effects on the BOLD signal in contralateral S1. The implications are 2-fold: First, the correlation between early and long-latency SEP components and the BOLD effect suggest that spatial-selective attention enhances processing in S1 at 2 time points: During an early passage of the signal and during a later passage, probably via re-entrant feedback from higher cortical areas. Second, attentional modulations of the fast electrophysiological signals and the slow hemodynamic response are linearly related in S1.

  13. Long-Term Expansion, Enhanced Chondrogenic Potential, and Suppression of Endochondral Ossification of Adult Human MSCs via WNT Signaling Modulation

    Directory of Open Access Journals (Sweden)

    Roberto Narcisi

    2015-03-01

    Full Text Available Mesenchymal stem cells (MSCs are a potential source of chondrogenic cells for the treatment of cartilage disorders, but loss of chondrogenic potential during in vitro expansion and the propensity of cartilage to undergo hypertrophic maturation impede their therapeutic application. Here we report that the signaling protein WNT3A, in combination with FGF2, supports long-term expansion of human bone marrow-derived MSCs. The cells retained their chondrogenic potential and other phenotypic and functional properties of multipotent MSCs, which were gradually lost in the absence of WNT3A. Moreover, we discovered that endogenous WNT signals are the main drivers of the hypertrophic maturation that follows chondrogenic differentiation. Inhibition of WNT signals during differentiation prevented calcification and maintained cartilage properties following implantation in a mouse model. By maintaining potency during expansion and preventing hypertrophic maturation following differentiation, the modulation of WNT signaling removes two major obstacles that impede the clinical application of MSCs in cartilage repair.

  14. Modulation of apical constriction by Wnt signaling is required for lung epithelial shape transition.

    Science.gov (United States)

    Fumoto, Katsumi; Takigawa-Imamura, Hisako; Sumiyama, Kenta; Kaneiwa, Tomoyuki; Kikuchi, Akira

    2017-01-01

    In lung development, the apically constricted columnar epithelium forms numerous buds during the pseudoglandular stage. Subsequently, these epithelial cells change shape into the flat or cuboidal pneumocytes that form the air sacs during the canalicular and saccular (canalicular-saccular) stages, yet the impact of cell shape on tissue morphogenesis remains unclear. Here, we show that the expression of Wnt components is decreased in the canalicular-saccular stages, and that genetically constitutive activation of Wnt signaling impairs air sac formation by inducing apical constriction in the epithelium as seen in the pseudoglandular stage. Organ culture models also demonstrate that Wnt signaling induces apical constriction through apical actomyosin cytoskeletal organization. Mathematical modeling reveals that apical constriction induces bud formation and that loss of apical constriction is required for the formation of an air sac-like structure. We identify MAP/microtubule affinity-regulating kinase 1 (Mark1) as a downstream molecule of Wnt signaling and show that it is required for apical cytoskeletal organization and bud formation. These results suggest that Wnt signaling is required for bud formation by inducing apical constriction during the pseudoglandular stage, whereas loss of Wnt signaling is necessary for air sac formation in the canalicular-saccular stages. © 2017. Published by The Company of Biologists Ltd.

  15. Stochastic resonance for signal-modulated pump noise in a single-mode laser

    Institute of Scientific and Technical Information of China (English)

    Liangying Zhang; Li Cao; Fahui Zhu

    2006-01-01

    By adopting the gain-noise model of the single-mode laser in which with bias and periodical signals serve as inputs, combining with the effect of coloured pump noise, we use the linear approximation method to calculate the power spectrum and signal-to-noise ratio (SNR) of the laser intensity under the condition of pump noise and quantum noise cross-related in the form of δ function. It is found that with the change of pump noise correlation time, both SNR and the output power will occur stochastic resonance (SR). If the bias signal α is very small, changing the intensities of pump noise and quantum noise respectively does not lead to the appearance of SR in the SNR; while α increases to a certain number, SR appears.

  16. Telomerase activity promotes osteoblast differentiation by modulating IGF-signaling pathway

    DEFF Research Database (Denmark)

    Saeed, Hamid; Qiu, Weimin; Li, Chen

    2015-01-01

    -regulation of several components of insulin-like growth factor (IGF) signaling. Specifically, a significant increase in IGF-induced AKT phosphorylation and alkaline phosphatase (ALP) activity were observed in hMSC-TERT. Enhanced ALP activity was reduced in presence of IGF1 receptor inhibitor: picropodophyllin....... In addition, telomerase deficiency caused significant reduction in IGF signaling proteins in osteoblastic cells cultured from telomerase deficient mice (Terc (-/-)). The low bone mass exhibited by Terc (-/-) mice was associated with significant reduction in serum levels of IGF1 and IGFBP3 as well as reduced...... skeletal mRNA expression of Igf1, Igf2, Igf2r, Igfbp5 and Igfbp6. IGF1-induced osteoblast differentiation was also impaired in Terc (-/-) MSC. In conclusion, our data demonstrate that impaired IGF/AKT signaling contributes to the observed decreased bone mass and bone formation exhibited by telomerase...

  17. Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network

    Science.gov (United States)

    Nwachukwu, Jerome C; Srinivasan, Sathish; Bruno, Nelson E; Parent, Alexander A; Hughes, Travis S; Pollock, Julie A; Gjyshi, Olsi; Cavett, Valerie; Nowak, Jason; Garcia-Ordonez, Ruben D; Houtman, René; Griffin, Patrick R; Kojetin, Douglas J; Katzenellenbogen, John A; Conkright, Michael D; Nettles, Kendall W

    2014-01-01

    Resveratrol has beneficial effects on aging, inflammation and metabolism, which are thought to result from activation of the lysine deacetylase, sirtuin 1 (SIRT1), the cAMP pathway, or AMP-activated protein kinase. In this study, we report that resveratrol acts as a pathway-selective estrogen receptor-α (ERα) ligand to modulate the inflammatory response but not cell proliferation. A crystal structure of the ERα ligand-binding domain (LBD) as a complex with resveratrol revealed a unique perturbation of the coactivator-binding surface, consistent with an altered coregulator recruitment profile. Gene expression analyses revealed significant overlap of TNFα genes modulated by resveratrol and estradiol. Furthermore, the ability of resveratrol to suppress interleukin-6 transcription was shown to require ERα and several ERα coregulators, suggesting that ERα functions as a primary conduit for resveratrol activity. DOI: http://dx.doi.org/10.7554/eLife.02057.001 PMID:24771768

  18. Research on the range side lobe suppression method for modulated stepped frequency radar signals

    Science.gov (United States)

    Liu, Yinkai; Shan, Tao; Feng, Yuan

    2018-05-01

    The magnitude of time-domain range sidelobe of modulated stepped frequency radar affects the imaging quality of inverse synthetic aperture radar (ISAR). In this paper, the cause of high sidelobe in modulated stepped frequency radar imaging is analyzed first in real environment. Then, the chaos particle swarm optimization (CPSO) is used to select the amplitude and phase compensation factors according to the minimum sidelobe criterion. Finally, the compensated one-dimensional range images are obtained. Experimental results show that the amplitude-phase compensation method based on CPSO algorithm can effectively reduce the sidelobe peak value of one-dimensional range images, which outperforms the common sidelobe suppression methods and avoids the coverage of weak scattering points by strong scattering points due to the high sidelobes.

  19. Lentiviral Modulation of Wnt/β-Catenin Signaling Affects In Vivo LTP.

    Science.gov (United States)

    Ivanova, Olga Ya; Dobryakova, Yulia V; Salozhin, Sergey V; Aniol, Viktor A; Onufriev, Mikhail V; Gulyaeva, Natalia V; Markevich, Vladimir A

    2017-10-01

    Wnt signaling is involved in hippocampal development and synaptogenesis. Numerous recent studies have been focused on the role of Wnt ligands in the regulation of synaptic plasticity. Inhibitors and activators of canonical Wnt signaling were demonstrated to decrease or increase, respectively, in vitro long-term potentiation (LTP) maintenance in hippocampal slices (Chen et al. in J Biol Chem 281:11910-11916, 2006; Vargas et al. in J Neurosci 34:2191-2202, 2014, Vargas et al. in Exp Neurol 264:14-25, 2015). Using lentiviral approach to down- and up-regulate the canonical Wnt signaling, we explored whether Wnt/β-catenin signaling is critical for the in vivo LTP. Chronic suppression of Wnt signaling induced an impairment of in vivo LTP expression 14 days after lentiviral suspension injection, while overexpression of Wnt3 was associated with a transient enhancement of in vivo LTP magnitude. Both effects were related to the early phase LTP and did not affect LTP maintenance. A loss-of-function study demonstrated decreased initial paired pulse facilitation ratio, β-catenin, and phGSK-3β levels. A gain-of-function study revealed not only an increase in PSD-95, β-catenin, and Cyclin D1 protein levels, but also a reduced phGSK-3β level and enhanced GSK-3β kinase activity. These results suggest a presynaptic dysfunction predominantly underlying LTP impairment while postsynaptic modifications are primarily involved in transient LTP amplification. This study is the first demonstration of the involvement of Wnt/β-catenin signaling in synaptic plasticity regulation in an in vivo LTP model.

  20. Schisantherin A suppresses osteoclast formation and wear particle-induced osteolysis via modulating RANKL signaling pathways

    Energy Technology Data Exchange (ETDEWEB)

    He, Yi; Zhang, Qing; Shen, Yi; Chen, Xia; Zhou, Feng; Peng, Dan, E-mail: xyeypd@163.com

    2014-07-04

    Highlights: • Schisantherin A suppresses osteoclasts formation and function in vitro. • Schisantherin A impairs RANKL signaling pathway. • Schisantherin A suppresses osteolysis in vivo. • Schisantherin A may be used for treating osteoclast related diseases. - Abstract: Receptor activator of NF-κB ligand (RANKL) plays critical role in osteoclastogenesis. Targeting RANKL signaling pathways has been a promising strategy for treating osteoclast related bone diseases such as osteoporosis and aseptic prosthetic loosening. Schisantherin A (SA), a dibenzocyclooctadiene lignan isolated from the fruit of Schisandra sphenanthera, has been used as an antitussive, tonic, and sedative agent, but its effect on osteoclasts has been hitherto unknown. In the present study, SA was found to inhibit RANKL-induced osteoclast formation and bone resorption. The osteoclastic specific marker genes induced by RANKL including c-Src, SA inhibited OSCAR, cathepsin K and TRAP in a dose dependent manner. Further signal transduction studies revealed that SA down-regulate RANKL-induced nuclear factor-kappaB (NF-κB) signaling activation by suppressing the phosphorylation and degradation of IκBα, and subsequently preventing the NF-κB transcriptional activity. Moreover, SA also decreased the RANKL-induced MAPKs signaling pathway, including JNK and ERK1/2 posphorylation while had no obvious effects on p38 activation. Finally, SA suppressed the NF-κB and MAPKs subsequent gene expression of NFATc1 and c-Fos. In vivo studies, SA inhibited osteoclast function and exhibited bone protection effect in wear-particle-induced bone erosion model. Taken together, SA could attenuate osteoclast formation and wear particle-induced osteolysis by mediating RANKL signaling pathways. These data indicated that SA is a promising therapeutic natural compound for the treatment of osteoclast-related prosthesis loosening.

  1. Optimum Boundaries of Signal-to-Noise Ratio for Adaptive Code Modulations

    Science.gov (United States)

    2017-11-14

    possible ACM modes. This will decrease the searching time by half when compared to the mode search using a linear searching ( sequential ) method. The... simultaneously on with same 10 dB transmit power gain and parameters………………………………………………………………65 Fig. B-12. PSD when signal is transmitted from vector network...dB transmit power gain. Observe in Fig. B-11 that the peak height of the summed signal PSD increases when the second USRP 2932 is simultaneously

  2. IFT20 modulates ciliary PDGFRα signaling by regulating the stability of Cbl E3 ubiquitin ligases

    DEFF Research Database (Denmark)

    Schmid, Fabian Marc; Schou, Kenneth Bødtker; Vilhelm, Martin Juel

    2018-01-01

    ciliogenesis, and ciliary localization of the receptor is required for its appropriate ligand-mediated activation by PDGF-AA. However, the mechanisms regulating sorting of PDGFRα and feedback inhibition of PDGFRα signaling at the cilium are unknown. Here, we provide evidence that intraflagellar transport...... protein 20 (IFT20) interacts with E3 ubiquitin ligases c-Cbl and Cbl-b and is required for Cbl-mediated ubiquitination and internalization of PDGFRα for feedback inhibition of receptor signaling. In wild-type cells treated with PDGF-AA, c-Cbl becomes enriched in the cilium, and the receptor...

  3. Calculus of the Power Spectral Density of Ultra Wide Band Pulse Position Modulation Signals Coded with Totally Flipped Code

    Directory of Open Access Journals (Sweden)

    DURNEA, T. N.

    2009-02-01

    Full Text Available UWB-PPM systems were noted to have a power spectral density (p.s.d. consisting of a continuous portion and a line spectrum, which is composed of energy components placed at discrete frequencies. These components are the major source of interference to narrowband systems operating in the same frequency interval and deny harmless coexistence of UWB-PPM and narrowband systems. A new code denoted as Totally Flipped Code (TFC is applied to them in order to eliminate these discrete spectral components. The coded signal transports the information inside pulse position and will have the amplitude coded to generate a continuous p.s.d. We have designed the code and calculated the power spectral density of the coded signals. The power spectrum has no discrete components and its envelope is largely flat inside the bandwidth with a maximum at its center and a null at D.C. These characteristics make this code suited for implementation in the UWB systems based on PPM-type modulation as it assures a continuous spectrum and keeps PPM modulation performances.

  4. The Influence of the External Signal Modulation Waveform and Frequency on the Performance of a Photonic Forced Oscillator.

    Science.gov (United States)

    Sánchez-Castro, Noemi; Palomino-Ovando, Martha Alicia; Estrada-Wiese, Denise; Valladares, Nydia Xcaret; Del Río, Jesus Antonio; de la Mora, Maria Beatriz; Doti, Rafael; Faubert, Jocelyn; Lugo, Jesus Eduardo

    2018-05-21

    Photonic crystals have been an object of interest because of their properties to inhibit certain wavelengths and allow the transmission of others. Using these properties, we designed a photonic structure known as photodyne formed by two porous silicon one-dimensional photonic crystals with an air defect between them. When the photodyne is illuminated with appropriate light, it allows us to generate electromagnetic forces within the structure that can be maximized if the light becomes localized inside the defect region. These electromagnetic forces allow the microcavity to oscillate mechanically. In the experiment, a chopper was driven by a signal generator to modulate the laser light that was used. The driven frequency and the signal modulation waveform (rectangular, sinusoidal or triangular) were changed with the idea to find optimal conditions for the structure to oscillate. The microcavity displacement amplitude, velocity amplitude and Fourier spectrum of the latter and its frequency were measured by means of a vibrometer. The mechanical oscillations are modeled and compared with the experimental results and show good agreement. For external frequency values of 5 Hz and 10 Hz, the best option was a sinusoidal waveform, which gave higher photodyne displacements and velocity amplitudes. Nonetheless, for an external frequency of 15 Hz, the best option was the rectangular waveform.

  5. Nuclear import of glucokinase in pancreatic beta-cells is mediated by a nuclear localization signal and modulated by SUMOylation.

    Science.gov (United States)

    Johansson, Bente Berg; Fjeld, Karianne; Solheim, Marie Holm; Shirakawa, Jun; Zhang, Enming; Keindl, Magdalena; Hu, Jiang; Lindqvist, Andreas; Døskeland, Anne; Mellgren, Gunnar; Flatmark, Torgeir; Njølstad, Pål Rasmus; Kulkarni, Rohit N; Wierup, Nils; Aukrust, Ingvild; Bjørkhaug, Lise

    2017-10-15

    The localization of glucokinase in pancreatic beta-cell nuclei is a controversial issue. Although previous reports suggest such a localization, the mechanism for its import has so far not been identified. Using immunofluorescence, subcellular fractionation and mass spectrometry, we present evidence in support of glucokinase localization in beta-cell nuclei of human and mouse pancreatic sections, as well as in human and mouse isolated islets, and murine MIN6 cells. We have identified a conserved, seven-residue nuclear localization signal ( 30 LKKVMRR 36 ) in the human enzyme. Substituting the residues KK 31,32 and RR 35,36 with AA led to a loss of its nuclear localization in transfected cells. Furthermore, our data indicates that SUMOylation of glucokinase modulates its nuclear import, while high glucose concentrations do not significantly alter the enzyme nuclear/cytosolic ratio. Thus, for the first time, we provide data in support of a nuclear import of glucokinase mediated by a redundant mechanism, involving a nuclear localization signal, and which is modulated by its SUMOylation. These findings add new knowledge to the functional role of glucokinase in the pancreatic beta-cell. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. The Influence of the External Signal Modulation Waveform and Frequency on the Performance of a Photonic Forced Oscillator

    Directory of Open Access Journals (Sweden)

    Noemi Sánchez-Castro

    2018-05-01

    Full Text Available Photonic crystals have been an object of interest because of their properties to inhibit certain wavelengths and allow the transmission of others. Using these properties, we designed a photonic structure known as photodyne formed by two porous silicon one-dimensional photonic crystals with an air defect between them. When the photodyne is illuminated with appropriate light, it allows us to generate electromagnetic forces within the structure that can be maximized if the light becomes localized inside the defect region. These electromagnetic forces allow the microcavity to oscillate mechanically. In the experiment, a chopper was driven by a signal generator to modulate the laser light that was used. The driven frequency and the signal modulation waveform (rectangular, sinusoidal or triangular were changed with the idea to find optimal conditions for the structure to oscillate. The microcavity displacement amplitude, velocity amplitude and Fourier spectrum of the latter and its frequency were measured by means of a vibrometer. The mechanical oscillations are modeled and compared with the experimental results and show good agreement. For external frequency values of 5 Hz and 10 Hz, the best option was a sinusoidal waveform, which gave higher photodyne displacements and velocity amplitudes. Nonetheless, for an external frequency of 15 Hz, the best option was the rectangular waveform.

  7. Zizyphin modulates calcium signalling in human taste bud cells and fat taste perception in the mouse.

    Science.gov (United States)

    Murtaza, Babar; Berrichi, Meryem; Bennamar, Chahid; Tordjmann, Thierry; Djeziri, Fatima Z; Hichami, Aziz; Leemput, Julia; Belarbi, Meriem; Ozdener, Hakan; Khan, Naim A

    2017-10-01

    Zizyphin, isolated from Zizyphus sps. leaf extracts, has been shown to modulate sugar taste perception, and the palatability of a sweet solution is increased by the addition of fatty acids. We, therefore, studied whether zizyphin also modulates fat taste perception. Zizyphin was purified from edible fruit of Zizyphus lotus L. Zizyphin-induced increases in [Ca 2+ ]i in human taste bud cells (hTBC). Zizyphin shared the endoplasmic reticulum Ca 2+ pool and also recruited, in part, Ca 2+ from extracellular environment via the opening of store-operated Ca 2+ channels. Zizyphin exerted additive actions on linoleic acid (LA)-induced increases in [Ca 2+ ]i in these cells, indicating that zizyphin does not exert its action via fatty acid receptors. However, zizyphin seemed to exert, at least in part, its action via bile acid receptor Takeda-G-protein-receptor-5 in hTBC. In behavioural tests, mice exhibited preference for both LA and zizyphin. Interestingly, zizyphin increased the preference for a solution containing-LA. This study is the first evidence of the modulation of fat taste perception by zizyphin at the cellular level in hTBC. Our study might be helpful for considering the synthesis of zizyphin analogues as 'taste modifiers' with a potential in the management of obesity and lipid-mediated disorders. © 2017 Société Française de Pharmacologie et de Thérapeutique.

  8. High-resolution focal plane array IR detection modules and digital signal processing technologies at AIM

    Science.gov (United States)

    Cabanski, Wolfgang A.; Breiter, Rainer; Koch, R.; Mauk, Karl-Heinz; Rode, Werner; Ziegler, Johann; Eberhardt, Kurt; Oelmaier, Reinhard; Schneider, Harald; Walther, Martin

    2000-07-01

    Full video format focal plane array (FPA) modules with up to 640 X 512 pixels have been developed for high resolution imaging applications in either mercury cadmium telluride (MCT) mid wave (MWIR) infrared (IR) or platinum silicide (PtSi) and quantum well infrared photodetector (QWIP) technology as low cost alternatives to MCT for high performance IR imaging in the MWIR or long wave spectral band (LWIR). For the QWIP's, a new photovoltaic technology was introduced for improved NETD performance and higher dynamic range. MCT units provide fast frame rates > 100 Hz together with state of the art thermal resolution NETD hardware platforms and software for image visualization and nonuniformity correction including scene based self learning algorithms had to be developed to accomplish for the high data rates of up to 18 M pixels/s with 14-bit deep data, allowing to take into account nonlinear effects to access the full NETD by accurate reduction of residual fixed pattern noise. The main features of these modules are summarized together with measured performance data for long range detection systems with moderately fast to slow F-numbers like F/2.0 - F/3.5. An outlook shows most recent activities at AIM, heading for multicolor and faster frame rate detector modules based on MCT devices.

  9. Integrins as Modulators of Transforming Growth Factor Beta Signaling in Dermal Fibroblasts During Skin Regeneration After Injury.

    Science.gov (United States)

    Boo, Stellar; Dagnino, Lina

    2013-06-01

    Abnormal wound repair results from disorders in granulation tissue remodeling, and can lead to hypertrophic scarring and fibrosis. Excessive scarring can compromise tissue function and decrease tissue resistance to additional injuries. The development of potential therapies to minimize scarring is, thus, necessary to address an important clinical problem. It has been clearly established that multiple cytokines and growth factors participate in the regulation of cutaneous wound healing. More recently, it has become apparent that these factors do not necessarily activate isolated signaling pathways. Rather, in some cases, there is cross-modulation of several cellular pathways involved in this process. Two of the key pathways that modulate each other during wound healing are activated by transforming growth factor-β and by extracellular matrix proteins acting through integrins. The pathogenesis of excessive scarring upon wound healing is not fully understood, as a result of the complexity of this process. However, the fact that many pathways combine to produce fibrosis provides multiple potential therapeutic targets. Some of them have been identified, such as focal adhesion kinase and integrin-linked kinase. Currently, a major challenge is to develop pharmacological inhibitors of these proteins with therapeutic value to promote efficient wound repair. The ability to better understand how different pathways crosstalk during wound repair and to identify and pharmacologically modulate key factors that contribute to the regulation of multiple wound-healing pathways could potentially provide effective therapeutic targets to decrease or prevent excessive scar formation and/or development of fibrosis.

  10. Cell intrinsic modulation of Wnt signaling controls neuroblast migration in C. elegans

    NARCIS (Netherlands)

    Mentink, Remco A; Middelkoop, Teije C; Rella, Lorenzo; Ji, Ni; Tang, Chung Yin; Betist, Marco C; van Oudenaarden, Alexander; Korswagen, Hendrik C

    2014-01-01

    Members of the Wnt family of secreted signaling proteins are key regulators of cell migration and axon guidance. In the nematode C. elegans, the migration of the QR neuroblast descendants requires multiple Wnt ligands and receptors. We found that the migration of the QR descendants is divided into

  11. Information transfer through a signaling module with feedback: A perturbative approach

    Czech Academy of Sciences Publication Activity Database

    Aquino, G.; Zápotocký, Martin

    2015-01-01

    Roč. 136, Oct (2015), s. 66-72 ISSN 0303-2647 R&D Projects: GA ČR(CZ) GBP304/12/G069 Institutional support: RVO:67985823 Keywords : signal transduction * communication channel * poisson process * information theory * feedback loop * Non-Markovian process Subject RIV: ED - Physiology Impact factor: 1.495, year: 2015

  12. CXXC5 is a novel BMP4-regulated modulator of Wnt signaling in neural stem cells

    Czech Academy of Sciences Publication Activity Database

    Andersson, T.; Södersten, E.; Duckworth, J.K.; Cascante, A.; Fritz, N.; Sacchetti, P.; Červenka, I.; Bryja, Vítězslav; Hermanson, O.

    2008-01-01

    Roč. 284, č. 6 (2008), s. 3672-3681 ISSN 0021-9258 Grant - others:GA AV ČR(CZ) KJB501630801 Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : Wnt signaling * CXXC5 * neural stem cells Subject RIV: BO - Biophysics Impact factor: 5.520, year: 2008

  13. An Intestinal Farnesoid X Receptor–Ceramide Signaling Axis Modulates Hepatic Gluconeogenesis in Mice

    Science.gov (United States)

    Xie, Cen; Shi, Jingmin; Gao, Xiaoxia; Sun, Dongxue; Sun, Lulu; Wang, Ting; Takahashi, Shogo; Anitha, Mallappa; Krausz, Kristopher W.; Patterson, Andrew D.

    2017-01-01

    Increasing evidence supports the view that intestinal farnesoid X receptor (FXR) is involved in glucose tolerance and that FXR signaling can be profoundly impacted by the gut microbiota. Selective manipulation of the gut microbiota–FXR signaling axis was reported to significantly impact glucose intolerance, but the precise molecular mechanism remains largely unknown. Here, caffeic acid phenethyl ester (CAPE), an over-the-counter dietary supplement and an inhibitor of bacterial bile salt hydrolase, increased levels of intestinal tauro-β-muricholic acid, which selectively suppresses intestinal FXR signaling. Intestinal FXR inhibition decreased ceramide levels by suppressing expression of genes involved in ceramide synthesis specifically in the intestinal ileum epithelial cells. The lower serum ceramides mediated decreased hepatic mitochondrial acetyl-CoA levels and pyruvate carboxylase (PC) activities and attenuated hepatic gluconeogenesis, independent of body weight change and hepatic insulin signaling in vivo; this was reversed by treatment of mice with ceramides or the FXR agonist GW4064. Ceramides substantially attenuated mitochondrial citrate synthase activities primarily through the induction of endoplasmic reticulum stress, which triggers increased hepatic mitochondrial acetyl-CoA levels and PC activities. These results reveal a mechanism by which the dietary supplement CAPE and intestinal FXR regulates hepatic gluconeogenesis and suggest that inhibiting intestinal FXR is a strategy for treating hyperglycemia. PMID:28223344

  14. Modulating Neurotrophin Receptor Signaling as a Therapeutic Strategy for Huntington’s Disease

    Science.gov (United States)

    Simmons, Danielle A.

    2017-01-01

    Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG repeat expansions in the IT15 gene which encodes the huntingtin (HTT) protein. Currently, no treatments capable of preventing or slowing disease progression exist. Disease modifying therapeutics for HD would be expected to target a comprehensive set of degenerative processes given the diverse mechanisms contributing to HD pathogenesis including neuroinflammation, excitotoxicity, and transcription dysregulation. A major contributor to HD-related degeneration is mutant HTT-induced loss of neurotrophic support. Thus, neurotrophin (NT) receptors have emerged as therapeutic targets in HD. The considerable overlap between NT signaling networks and those dysregulated by mutant HTT provides strong theoretical support for this approach. This review will focus on the contributions of disrupted NT signaling in HD-related neurodegeneration and how targeting NT receptors to augment pro-survival signaling and/or to inhibit degenerative signaling may combat HD pathologies. Therapeutic strategies involving NT delivery, peptidomimetics, and the targeting of specific NT receptors (e.g., Trks or p75NTR), particularly with small molecule ligands, are discussed. PMID:29254102

  15. A novel Modulation Topology for Power Converters utilizing Multiple Carrier Signals

    DEFF Research Database (Denmark)

    Knott, Arnold; Pfaffinger, Gerhard; Andersen, Michael Andreas E.

    2008-01-01

    Power converters are known to generate spectral components in the range of interest of electromagnetic compatibility measurements. Common approaches to manipulate some selected components in these frequency ranges are shown here. These approaches add components to the input signal of the modulato...

  16. Ciliopathy proteins regulate paracrine signaling by modulating proteasomal degradation of mediators

    Science.gov (United States)

    Liu, Yangfan P.; Tsai, I-Chun; Morleo, Manuela; Oh, Edwin C.; Leitch, Carmen C.; Massa, Filomena; Lee, Byung-Hoon; Parker, David S.; Finley, Daniel; Zaghloul, Norann A.; Franco, Brunella; Katsanis, Nicholas

    2014-01-01

    Cilia are critical mediators of paracrine signaling; however, it is unknown whether proteins that contribute to ciliopathies converge on multiple paracrine pathways through a common mechanism. Here, we show that loss of cilopathy-associated proteins Bardet-Biedl syndrome 4 (BBS4) or oral-facial-digital syndrome 1 (OFD1) results in the accumulation of signaling mediators normally targeted for proteasomal degradation. In WT cells, several BBS proteins and OFD1 interacted with proteasomal subunits, and loss of either BBS4 or OFD1 led to depletion of multiple subunits from the centrosomal proteasome. Furthermore, overexpression of proteasomal regulatory components or treatment with proteasomal activators sulforaphane (SFN) and mevalonolactone (MVA) ameliorated signaling defects in cells lacking BBS1, BBS4, and OFD1, in morphant zebrafish embryos, and in induced neurons from Ofd1-deficient mice. Finally, we tested the hypothesis that other proteasome-dependent pathways not known to be associated with ciliopathies are defective in the absence of ciliopathy proteins. We found that loss of BBS1, BBS4, or OFD1 led to decreased NF-κB activity and concomitant IκBβ accumulation and that these defects were ameliorated with SFN treatment. Taken together, our data indicate that basal body proteasomal regulation governs paracrine signaling pathways and suggest that augmenting proteasomal function might benefit ciliopathy patients. PMID:24691443

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

    DEFF Research Database (Denmark)

    1998-01-01

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

  18. Glial GABA Transporters as Modulators of Inhibitory Signalling in Epilepsy and Stroke

    DEFF Research Database (Denmark)

    Lie, Maria E K; Al-Khawaja, Anas; Damgaard, Maria

    2017-01-01

    is to provide an overview of glial GATs in regulating tonic inhibition, especially in epilepsy and stroke. This entails a comprehensive summary of changes known to occur in GAT expression levels and signalling following epileptic and ischemic insults. Further, we discuss the accumulating pharmacological...

  19. Nitric oxide-induced murine hematopoietic stem cell fate involves multiple signaling proteins, gene expression, and redox modulation.

    Science.gov (United States)

    Nogueira-Pedro, Amanda; Dias, Carolina C; Regina, Helena; Segreto, C; Addios, Priscilla C; Lungato, Lisandro; D'Almeida, Vania; Barros, Carlos C; Higa, Elisa M S; Buri, Marcus V; Ferreira, Alice T; Paredes-Gamero, Edgar Julian

    2014-11-01

    There are a growing number of reports showing the influence of redox modulation in cellular signaling. Although the regulation of hematopoiesis by reactive oxygen species (ROS) and reactive nitrogen species (RNS) has been described, their direct participation in the differentiation of hematopoietic stem cells (HSCs) remains unclear. In this work, the direct role of nitric oxide (NO(•)), a RNS, in the modulation of hematopoiesis was investigated using two sources of NO(•) , one produced by endothelial cells stimulated with carbachol in vitro and another using the NO(•)-donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) in vivo. Two main NO(•) effects were observed: proliferation of HSCs-especially of the short-term HSCs-and its commitment and terminal differentiation to the myeloid lineage. NO(•)-induced proliferation was characterized by the increase in the number of cycling HSCs and hematopoietic progenitor cells positive to BrdU and Ki-67, upregulation of Notch-1, Cx43, PECAM-1, CaR, ERK1/2, Akt, p38, PKC, and c-Myc. NO(•)-induced HSCs differentiation was characterized by the increase in granulocytic-macrophage progenitors, granulocyte-macrophage colony forming units, mature myeloid cells, upregulation of PU.1, and C/EBPα genes concomitantly to the downregulation of GATA-3 and Ikz-3 genes, activation of Stat5 and downregulation of the other analyzed proteins mentioned above. Also, redox status modulation differed between proliferation and differentiation responses, which is likely associated with the transition of the proliferative to differentiation status. Our findings provide evidence of the role of NO(•) in inducing HSCs proliferation and myeloid differentiation involving multiple signaling. © 2014 AlphaMed Press.

  20. Amphetamine modulates brain signal variability and working memory in younger and older adults.

    Science.gov (United States)

    Garrett, Douglas D; Nagel, Irene E; Preuschhof, Claudia; Burzynska, Agnieszka Z; Marchner, Janina; Wiegert, Steffen; Jungehülsing, Gerhard J; Nyberg, Lars; Villringer, Arno; Li, Shu-Chen; Heekeren, Hauke R; Bäckman, Lars; Lindenberger, Ulman

    2015-06-16

    Better-performing younger adults typically express greater brain signal variability relative to older, poorer performers. Mechanisms for age and performance-graded differences in brain dynamics have, however, not yet been uncovered. Given the age-related decline of the dopamine (DA) system in normal cognitive aging, DA neuromodulation is one plausible mechanism. Hence, agents that boost systemic DA [such as d-amphetamine (AMPH)] may help to restore deficient signal variability levels. Furthermore, despite the standard practice of counterbalancing drug session order (AMPH first vs. placebo first), it remains understudied how AMPH may interact with practice effects, possibly influencing whether DA up-regulation is functional. We examined the effects of AMPH on functional-MRI-based blood oxygen level-dependent (BOLD) signal variability (SD(BOLD)) in younger and older adults during a working memory task (letter n-back). Older adults expressed lower brain signal variability at placebo, but met or exceeded young adult SD(BOLD) levels in the presence of AMPH. Drug session order greatly moderated change-change relations between AMPH-driven SD(BOLD) and reaction time means (RT(mean)) and SDs (RT(SD)). Older adults who received AMPH in the first session tended to improve in RT(mean) and RT(SD) when SD(BOLD) was boosted on AMPH, whereas younger and older adults who received AMPH in the second session showed either a performance improvement when SD(BOLD) decreased (for RT(mean)) or no effect at all (for RT(SD)). The present findings support the hypothesis that age differences in brain signal variability reflect aging-induced changes in dopaminergic neuromodulation. The observed interactions among AMPH, age, and session order highlight the state- and practice-dependent neurochemical basis of human brain dynamics.

  1. Halofuginone has anti-proliferative effects in acute promyelocytic leukemia by modulating the transforming growth factor beta signaling pathway.

    Directory of Open Access Journals (Sweden)

    Lorena L de Figueiredo-Pontes

    Full Text Available Promyelocytic leukemia-retinoic acid receptor alpha (PML-RARα expression in acute promyelocytic leukemia (APL impairs transforming growth factor beta (TGFβ signaling, leading to cell growth advantage. Halofuginone (HF, a low-molecular-weight alkaloid that modulates TGFβ signaling, was used to treat APL cell lines and non-obese diabetic/severe combined immunodeficiency (NOD/SCID mice subjected to transplantation with leukemic cells from human chorionic gonadotrophin-PML-RARα transgenic mice (TG. Cell cycle analysis using incorporated bromodeoxyuridine and 7-amino-actinomycin D showed that, in NB4 and NB4-R2 APL cell lines, HF inhibited cellular proliferation (P<0.001 and induced apoptosis (P = 0.002 after a 24-hour incubation. Addition of TGFβ revealed that NB4 cells were resistant to its growth-suppressive effects and that HF induced these effects in the presence or absence of the cytokine. Cell growth inhibition was associated with up-regulation of TGFβ target genes involved in cell cycle regulation (TGFB, TGFBRI, SMAD3, p15, and p21 and down-regulation of MYC. Additionally, TGFβ protein levels were decreased in leukemic TG animals and HF in vivo could restore TGFβ values to normal. To test the in vivo anti-leukemic activity of HF, we transplanted NOD/SCID mice with TG leukemic cells and treated them with HF for 21 days. HF induced partial hematological remission in the peripheral blood, bone marrow, and spleen. Together, these results suggest that HF has anti-proliferative and anti-leukemic effects by reversing the TGFβ blockade in APL. Since loss of the TGFβ response in leukemic cells may be an important second oncogenic hit, modulation of TGFβ signaling may be of therapeutic interest.

  2. Modulation of IL-33/ST2-TIR and TLR signalling pathway by fingolimod and analogues in immune cells.

    Science.gov (United States)

    Rüger, K; Ottenlinger, F; Schröder, M; Zivković, A; Stark, H; Pfeilschifter, J M; Radeke, H H

    2014-12-01

    For the immune modulatory drug fingolimod (FTY720), lymphocyte sequestration has been extensively studied and accepted as mode of action. Further, direct effects on immune cell signalling are incompletely understood. Herein, we used the parent drug and newly synthesized analogues to investigate their effects on dendritic cell (DC) calcium signalling and on Th1, Th2 and Th17 responses. DC calcium signalling was determined with a single cell-based confocal assay and IL-33/ST2-TIR Th2-like response with ST2-transduced EL4-6.1 thymoma cells. The Th1/Th17 responses were examined with a LPS/TLR-enhanced antigen presentation assay with OVA-TCRtg CD4 and CD8 spleen cells. Our results revealed a comparable influence of fingolimod and S1P on intracellular calcium level in DC, while an oxy-derivative of fingolimod exhibited an EC50 of 3.3 nm, being 14 times more potent than FTY720-P. The IL-33/ST2-TIR Th2-like response in ST2-EL4 cells was inhibited by fingolimod and analogues at varying degrees. Using the OVA-TCRtg LPS/TLR-enhanced spleen cell assay, we found that fingolimod inhibited both IL-17 and IFN-γ production. In contrast, fingolimod phosphate failed to decrease Th1 cytokines. Interestingly, the effects of the parent compound fingolimod were modulated by the PP2A inhibitor okadaic acid, thus suggesting PP2A as relevant intracellular target. These studies describe detailed immune-modulating properties of fingolimod, including interference with a prototypical Th2 response via IL-33/ST2-TIR. Moreover, differential effects of fingolimod versus its phosphorylated derivative on TLR-activated and antigen-dependent Th1 activation suggest PP2A as an additional target of fingolimod immune therapy. Together with the analogues tested, these data may guide the development of more specific fingolimod derivatives. © 2014 John Wiley & Sons Ltd.

  3. Use of modulated excitation signals in ultrasound. Part II: Design and performance for medical imaging applications

    DEFF Research Database (Denmark)

    Misaridis, Thanassis; Jensen, Jørgen Arendt

    2005-01-01

    ultrasound presents design methods of linear FM signals and mismatched filters, in order to meet the higher demands on resolution in ultrasound imaging. It is shown that for the small time-bandwidth (TB) products available in ultrasound, the rectangular spectrum approximation is not valid, which reduces....... The method is evaluated first for resolution performance and axial sidelobes through simulations with the program Field II. A coded excitation ultrasound imaging system based on a commercial scanner and a 4 MHz probe driven by coded sequences is presented and used for the clinical evaluation of the coded...... excitation/compression scheme. The clinical images show a significant improvement in penetration depth and contrast, while they preserve both axial and lateral resolution. At the maximum acquisition depth of 15 cm, there is an improvement of more than 10 dB in the signal-to-noise ratio of the images...

  4. Chemogenetic Modulation of G Protein-Coupled Receptor Signalling in Visual Attention Research

    DEFF Research Database (Denmark)

    Jørgensen, Søren H; Fitzpatrick, Ciarán Martin; Gether, Ulrik

    2017-01-01

    Exclusively Activated by Designer Drugs (DREADDs). The DREADD technology is an emerging and transformative method that allows selective manipulation of G protein-coupled receptor (GPCR) signalling, and its broad-ranging usefulness in attention research is now beginning to emerge. We first describe......Attention is a fundamental cognitive process involved in nearly all aspects of life. Abnormal attentional control is a symptom of many neurological disorders, most notably recognized in ADHD (attention deficit hyperactivity disorder). Although attentional performance and its malfunction has been...... the different DREADDs available and explain how unprecedented specificity of neuronal signalling can be achieved using DREADDs. We next discuss various studies performed in animal models of visual attention, where different brain regions and neuronal populations have been probed by DREADDs. We highlight...

  5. Perturbation of cellular signaling cascades modulated by ionizing radiation and environmental stress

    International Nuclear Information System (INIS)

    Ugolini, M.

    2014-01-01

    Cellular signaling plays a central role in the regulation of several cell functions, which can be perturbed by different external stimuli, including environmental stress and ionizing radiation. The dysregulation of intra- and extracellular mechanisms may alter the correct behaviour of cells. The aim of this work was to investigate the activation of strongly interlaced intracellular signaling pathways, following the exposure to low- and medium-doses of X-rays, with a focus on the mechanisms involved in the inflammatory- and apoptotic-related responses. In particular, the temporal dynamics of the ERK1/2 and PKB/AKT pathways and their possible dose dependences were investigated. The presented results indicate a clear dose dependence of such pathways only at early time points, suggesting a fast response of the system to X-rays and the need for further studies at shorter times after exposures.

  6. Fluoxetine Regulates Neurogenesis In Vitro Through Modulation of GSK-3β/β-Catenin Signaling

    Science.gov (United States)

    Hui, Jiaojie; Zhang, Jianping; Kim, Hoon; Tong, Chang; Ying, Qilong; Li, Zaiwang; Mao, Xuqiang; Shi, Guofeng; Yan, Jie; Zhang, Zhijun

    2015-01-01

    Background: It is generally accepted that chronic treatment with antidepressants increases hippocampal neurogenesis, but the molecular mechanisms underlying their effects are unknown. Recently, glycogen synthase kinase-3 beta (GSK-3β)/β-catenin signaling was shown to be involved in the mechanism of how antidepressants might influence hippocampal neurogenesis. Methods: The aim of this study was to determine whether GSK-3β/β-catenin signaling is involved in the alteration of neurogenesis as a result of treatment with fluoxetine, a selective serotonin reuptake inhibitor. The mechanisms involved in fluoxetine’s regulation of GSK-3β/β-catenin signaling pathway were also examined. Results: Our results demonstrated that fluoxetine increased the proliferation of embryonic neural precursor cells (NPCs) by up-regulating the phosphorylation of Ser9 on GSK-3β and increasing the level of nuclear β-catenin. The overexpression of a stabilized β-catenin protein (ΔN89 β-catenin) significantly increased NPC proliferation, while inhibition of β-catenin expression in NPCs led to a significant decrease in the proliferation and reduced the proliferative effects induced by fluoxetine. The effects of fluoxetine-induced up-regulation of both phosphorylation of Ser9 on GSK-3β and nuclear β-catenin were significantly prevented by the 5-hydroxytryptamine-1A (5-HT1A) receptor antagonist WAY-100635. Conclusions: The results demonstrate that fluoxetine may increase neurogenesis via the GSK-3β/β-catenin signaling pathway that links postsynaptic 5-HT1A receptor activation. PMID:25522429

  7. SGIP1 alters internalization and modulates signaling of activated cannabinoid receptor 1 in a biased manner

    Czech Academy of Sciences Publication Activity Database

    Hájková, Alena; Techlovská, Šárka; Dvořáková, Michaela; Chambers, Jayne Nicole; Kumpošt, Jiří; Hubálková, Pavla; Prezeau, L.; Blahoš, Jaroslav

    2016-01-01

    Roč. 107, léto (2016), s. 201-214 ISSN 0028-3908 R&D Projects: GA ČR GAP303/12/2408 Institutional support: RVO:68378050 Keywords : Seven transmembrane receptors * G-protein coupled receptors * Cannabinoid receptor 1 * Protein-protein interactions * Bias signaling * Receptor endocytosis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.012, year: 2016

  8. Sub-chronic agmatine treatment modulates hippocampal neuroplasticity and cell survival signaling pathways in mice.

    Science.gov (United States)

    Freitas, Andiara E; Bettio, Luis E B; Neis, Vivian B; Moretti, Morgana; Ribeiro, Camille M; Lopes, Mark W; Leal, Rodrigo B; Rodrigues, Ana Lúcia S

    2014-11-01

    Agmatine is an endogenous neuromodulator which, based on animal and human studies, is a putative novel antidepressant drug. In this study, we investigated the ability of sub-chronic (21 days) p.o. agmatine administration to produce an antidepressant-like effect in the tail suspension test and examined the hippocampal cell signaling pathways implicated in such an effect. Agmatine at doses of 0.01 and 0.1 mg/kg (p.o.) produced a significant antidepressant-like effect in the tail suspension test and no effect in the open-field test. Additionally, agmatine (0.001-0.1 mg/kg, p.o.) increased the phosphorylation of protein kinase A substrates (237-258% of control), protein kinase B/Akt (Ser(473)) (116-127% of control), glycogen synthase kinase-3β (Ser(9)) (110-113% of control), extracellular signal-regulated kinases 1/2 (119-137% and 121-138% of control, respectively) and cAMP response elements (Ser(133)) (127-152% of control), and brain-derived-neurotrophic factor (137-175% of control) immunocontent in a dose-dependent manner in the hippocampus. Agmatine (0.001-0.1 mg/kg, p.o.) also reduced the c-jun N-terminal kinase 1/2 phosphorylation (77-71% and 65-51% of control, respectively). Neither protein kinase C nor p38(MAPK) phosphorylation was altered under any experimental conditions. Taken together, the present study extends the available data on the mechanisms that underlie the antidepressant action of agmatine by showing an antidepressant-like effect following sub-chronic administration. In addition, our results are the first to demonstrate the ability of agmatine to elicit the activation of cellular signaling pathways associated with neuroplasticity/cell survival and the inhibition of signaling pathways associated with cell death in the hippocampus. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. The Cannabinoid Receptor CB1 Modulates the Signaling Properties of the Lysophosphatidylinositol Receptor GPR55*

    Science.gov (United States)

    Kargl, Julia; Balenga, Nariman; Parzmair, Gerald P.; Brown, Andrew J.; Heinemann, Akos; Waldhoer, Maria

    2012-01-01

    The G protein-coupled receptor (GPCR) 55 (GPR55) and the cannabinoid receptor 1 (CB1R) are co-expressed in many tissues, predominantly in the central nervous system. Seven transmembrane spanning (7TM) receptors/GPCRs can form homo- and heteromers and initiate distinct signaling pathways. Recently, several synthetic CB1 receptor inverse agonists/antagonists, such as SR141716A, AM251, and AM281, were reported to activate GPR55. Of these, SR141716A was marketed as a promising anti-obesity drug, but was withdrawn from the market because of severe side effects. Here, we tested whether GPR55 and CB1 receptors are capable of (i) forming heteromers and (ii) whether such heteromers could exhibit novel signaling patterns. We show that GPR55 and CB1 receptors alter each others signaling properties in human embryonic kidney (HEK293) cells. We demonstrate that the co-expression of FLAG-CB1 receptors in cells stably expressing HA-GPR55 specifically inhibits GPR55-mediated transcription factor activation, such as nuclear factor of activated T-cells and serum response element, as well as extracellular signal-regulated kinases (ERK1/2) activation. GPR55 and CB1 receptors can form heteromers, but the internalization of both receptors is not affected. In addition, we observe that the presence of GPR55 enhances CB1R-mediated ERK1/2 and nuclear factor of activated T-cell activation. Our data provide the first evidence that GPR55 can form heteromers with another 7TM/GPCR and that this interaction with the CB1 receptor has functional consequences in vitro. The GPR55-CB1R heteromer may play an important physiological and/or pathophysiological role in tissues endogenously co-expressing both receptors. PMID:23161546

  10. GID1 modulates stomatal response and submergence tolerance involving abscisic acid and gibberellic acid signaling in rice.

    Science.gov (United States)

    Du, Hao; Chang, Yu; Huang, Fei; Xiong, Lizhong

    2015-11-01

    Plant responses to abiotic stresses are coordinated by arrays of growth and developmental programs. Gibberellic acid (GA) and abscisic acid (ABA) play critical roles in the developmental programs and environmental responses, respectively, through complex signaling and metabolism networks. However, crosstalk between the two phytohormones in stress responses remains largely unknown. In this study, we report that GIBBERELLIN-INSENSITIVE DWARF 1 (GID1), a soluble receptor for GA, regulates stomatal development and patterning in rice (Oryza sativa L.). The gid1 mutant showed impaired biosynthesis of endogenous ABA under drought stress conditions, but it exhibited enhanced sensitivity to exogenous ABA. Scanning electron microscope and infrared thermal image analysis indicated an increase in the stomatal conductance in the gid1 mutant under drought conditions. Interestingly, the gid1 mutant had increased levels of chlorophyll and carbohydrates under submergence conditions, and showed enhanced reactive oxygen species (ROS)-scavenging ability and submergence tolerance compared with the wild-type. Further analyses suggested that the function of GID1 in submergence responses is partially dependent on ABA, and GA signaling by GID1 is involved in submergence tolerance by modulating carbohydrate consumption. Taken together, these findings suggest GID1 plays distinct roles in stomatal response and submergence tolerance through both the ABA and GA signaling pathways in rice. © 2014 Institute of Botany, Chinese Academy of Sciences.

  11. Sprouty4 is an endogenous negative modulator of TrkA signaling and neuronal differentiation induced by NGF.

    Directory of Open Access Journals (Sweden)

    Fernando C Alsina

    Full Text Available The Sprouty (Spry family of proteins represents endogenous regulators of downstream signaling pathways induced by receptor tyrosine kinases (RTKs. Using real time PCR, we detect a significant increase in the expression of Spry4 mRNA in response to NGF, indicating that Spry4 could modulate intracellular signaling pathways and biological processes induced by NGF and its receptor TrkA. In this work, we demonstrate that overexpression of wild-type Spry4 causes a significant reduction in MAPK and Rac1 activation and neurite outgrowth induced by NGF. At molecular level, our findings indicate that ectopic expression of a mutated form of Spry4 (Y53A, in which a conserved tyrosine residue was replaced, fail to block both TrkA-mediated Erk/MAPK activation and neurite outgrowth induced by NGF, suggesting that an intact tyrosine 53 site is required for the inhibitory effect of Spry4 on NGF signaling. Downregulation of Spry4 using small interference RNA knockdown experiments potentiates PC12 cell differentiation and MAPK activation in response to NGF. Together, these findings establish a new physiological mechanism through which Spry4 regulates neurite outgrowth reducing not only the MAPK pathway but also restricting Rac1 activation in response to NGF.

  12. Fisetin and hesperetin induced apoptosis and cell cycle arrest in chronic myeloid leukemia cells accompanied by modulation of cellular signaling.

    Science.gov (United States)

    Adan, Aysun; Baran, Yusuf

    2016-05-01

    Fisetin and hesperetin, naturally occurring flavonoids, have been reported as novel antioxidants with chemopreventive/chemotherapeutic potential against various types of cancer. However, their mechanism of action in CML is still unknown. This particular study aims to evaluate the therapeutic potentials of fisetin and hesperetin and their effects on cell proliferation, apoptosis, and cell cycle progression in human K562 CML cells. The results indicated that fisetin and hesperetin inhibited cell proliferation and triggered programmed cell death in these cells. The latter was confırmed by mitochondrial membrane depolarization and an increase in caspase-3 activation. In addition to that, we have detected S and G2/M cell cycle arrests and G0/G1 arrest upon fisetin and hesperetin treatment, respectively. To identify the altered genes and genetic networks in response to fisetin and hesperetin, whole-genome microarray analysis was performed. The microarray gene profiling analysis revealed some important signaling pathways including JAK/STAT pathway, KIT receptor signaling, and growth hormone receptor signaling that were altered upon fisetin and hesperetin treatment. Moreover, microarray data suggested potential candidate genes for targeted CML therapy. Fisetin and hesperetin significantly modulated the expression of genes involved in cell proliferation and division, apoptosis, cell cycle regulation, and other significant cellular processes such as replication, transcription, and translation. In conclusion, our results suggest that fisetin and hesperetin as potential natural agents for CML therapy.

  13. WISP3 (CCN6 Is a Secreted Tumor-Suppressor Protein that Modulates IGF Signaling in Inflammatory Breast Cancer

    Directory of Open Access Journals (Sweden)

    Celina G. Kleer

    2004-03-01

    Full Text Available Inflammatory breast cancer (IBC is the most lethal form of locally advanced breast cancer. We have found that WISP3 is lost in 80% of human IBC tumors and that it has growth- and angiogenesis-inhibitory functions in breast cancer in vitro and in vivo. WISP3 is a cysteine-rich, putatively secreted protein that belongs to the CCN family. It contains a signal peptide at the N-terminus and four highly conserved motifs. Here, for the first time, we investigate the function of WISP3 protein in relationship to its structural features. We found that WISP3 is secreted into the conditioned media and into the lumens of normal breast ducts. Once secreted, WISP3 was able to decrease, directly or through induction of other molecule(s, the IGF-1-induced activation of the IGF-IR, and two of its main downstream signaling molecules, IRS1 and ERK-1/2, in SUM149 IBC cells. Furthermore, WISP3 containing conditioned media decreased the growth rate of SUM149 cells. This work sheds light into the mechanism of WISP3 function by demonstrating that it is secreted and that, once in the extracellular media, it induces a series of molecular events that leads to modulation of IGF-IR signaling pathways and cellular growth in IBC cells.

  14. Arabidopsis scaffold protein RACK1A modulates rare sugar D-allose regulated gibberellin signaling.

    Science.gov (United States)

    Fennell, Herman; Olawin, Abdulquadri; Mizanur, Rahman M; Izumori, Ken; Chen, Jin-Gui; Ullah, Hemayet

    2012-11-01

    As energy sources and structural components, sugars are the central regulators of plant growth and development. In addition to the abundant natural sugars in plants, more than 50 different kinds of rare sugars exist in nature, several of which show distinct roles in plant growth and development. Recently, one of the rare sugars, D-allose, an epimer of D-glucose at C3, is found to suppress plant hormone gibberellin (GA) signaling in rice. Scaffold protein RACK1A in the model plant Arabidopsis is implicated in the GA pathway as rack1a knockout mutants show insensitivity to GA in GA-induced seed germination. Using genetic knockout lines and a reporter gene, the functional role of RACK1A in the D-allose pathway was investigated. It was found that the rack1a knockout seeds showed hypersensitivity to D-allose-induced inhibition of seed germination, implicating a role for RACK1A in the D-allose mediated suppression of seed germination. On the other hand, a functional RACK1A in the background of the double knockout mutations in the other two RACK1 isoforms, rack1b/rack1c, showed significant resistance to the D-allose induced inhibition of seed germination. The collective results implicate the RACK1A in the D-allose mediated seed germination inhibition pathway. Elucidation of the rare sugar signaling mechanism will help to advance understanding of this less studied but important cellular signaling pathway.

  15. The Hepatitis B Virus X Protein Elevates Cytosolic Calcium Signals by Modulating Mitochondrial Calcium Uptake

    Science.gov (United States)

    Yang, Bei

    2012-01-01

    Chronic hepatitis B virus (HBV) infections are associated with the development of hepatocellular carcinoma (HCC). The HBV X protein (HBx) is thought to play an important role in the development of HBV-associated HCC. One fundamental HBx function is elevation of cytosolic calcium signals; this HBx activity has been linked to HBx stimulation of cell proliferation and transcription pathways, as well as HBV replication. Exactly how HBx elevates cytosolic calcium signals is not clear. The studies described here show that HBx stimulates calcium entry into cells, resulting in an increased plateau level of inositol 1,4,5-triphosphate (IP3)-linked calcium signals. This increased calcium plateau can be inhibited by blocking mitochondrial calcium uptake and store-operated calcium entry (SOCE). Blocking SOCE also reduced HBV replication. Finally, these studies also demonstrate that there is increased mitochondrial calcium uptake in HBx-expressing cells. Cumulatively, these studies suggest that HBx can increase mitochondrial calcium uptake and promote increased SOCE to sustain higher cytosolic calcium and stimulate HBV replication. PMID:22031934

  16. Urtica dioica modulates hippocampal insulin signaling and recognition memory deficit in streptozotocin induced diabetic mice.

    Science.gov (United States)

    Patel, Sita Sharan; Gupta, Sahil; Udayabanu, Malairaman

    2016-06-01

    Diabetes mellitus has been associated with functional abnormalities in the hippocampus and performance of cognitive function. Urtica dioica (UD) has been used in the treatment of diabetes. In our previous report we observed that UD extract attenuate diabetes mediated associative and spatial memory dysfunction. The present study aimed to evaluate the effect of UD extract on mouse model of diabetes-induced recognition memory deficit and explore the possible mechanism behind it. Streptozotocin (STZ) (50 mg/kg, i.p. consecutively for 5 days) was used to induce diabetes followed by UD extract (50 mg/kg, oral) or rosiglitazone (ROSI) (5 mg/kg, oral) administration for 8 weeks. STZ induced diabetic mice showed significant decrease in hippocampal insulin signaling and translocation of glucose transporter type 4 (GLUT4) to neuronal membrane resulting in cognitive dysfunction and hypolocomotion. UD treatment effectively improved hippocampal insulin signaling, glucose tolerance and recognition memory performance in diabetic mice, which was comparable to ROSI. Further, diabetes mediated oxidative stress and inflammation was reversed by chronic UD or ROSI administration. UD leaves extract acts via insulin signaling pathway and might prove to be effective for the diabetes mediated central nervous system complications.

  17. Modulation of the TGFβ/Smad signaling pathway in mesangial cells by CTGF/CCN2

    International Nuclear Information System (INIS)

    Abdel Wahab, Nadia; Weston, Benjamin S.; Mason, Roger M.

    2005-01-01

    Transforming growth factor-beta (TGFβ) drives fibrosis in diseases such as diabetic nephropathy (DN). Connective tissue growth factor (CTGF; CCN2) has also been implicated in this, but the molecular mechanism is unknown. We show that CTGF enhances the TGFβ/Smad signaling pathway by transcriptional suppression of Smad 7 following rapid and sustained induction of the transcription factor TIEG-1. Smad 7 is a known antagonist of TGFβ signaling and TIEG-1 is a known repressor of Smad 7 transcription. CTGF enhanced TGFβ-induced phosphorylation and nuclear translocation of Smad 2 and Smad 3 in mesangial cells. Antisense oligonucleotides directed against TIEG-1 prevented CTGF-induced downregulation of Smad 7. CTGF enhanced TGFβ-stimulated transcription of the SBE4-Luc reporter gene and this was markedly reduced by TIEG-1 antisense oligonucleotides. Expression of the TGFβ-responsive genes PAI-1 and Col III over 48 h was maximally stimulated by TGFβ + CTGF compared to TGFβ alone, while CTGF alone had no significant effect. TGFβ-stimulated expression of these genes was markedly reduced by both CTGF and TIEG-1 antisense oligonucleotides, consistent with the endogenous induction of CTGF by TGFβ. We propose that under pathological conditions, where CTGF expression is elevated, CTGF blocks the negative feedback loop provided by Smad 7, allowing continued activation of the TGFβ signaling pathway

  18. Hepatitis C Virus Core Protein Modulates Endoglin (CD105) Signaling Pathway for Liver Pathogenesis.

    Science.gov (United States)

    Kwon, Young-Chan; Sasaki, Reina; Meyer, Keith; Ray, Ranjit

    2017-11-01

    Endoglin is part of the TGF-β receptor complex and has a crucial role in fibrogenesis and angiogenesis. It is also an important protein for tumor growth, survival, and cancer cell metastasis. In a previous study, we have shown that hepatitis C virus (HCV) infection induces epithelial-mesenchymal transition (EMT) state and cancer stem-like cell (CSC) properties in human hepatocytes. Our array data suggested that endoglin (CD105) mRNA is significantly upregulated in HCV-associated CSCs. In this study, we have observed increased endoglin expression on the cell surface of an HCV core-expressing hepatocellular carcinoma (HepG2) cell line or immortalized human hepatocytes (IHH) and activation of its downstream signaling molecules. The status of phospho-SMAD1/5 and the expression of inhibitor of DNA binding protein 1 (ID1) were upregulated in HCV-infected cells or viral core gene-transfected cells. Additionally, we observed upregulation of endoglin/ID1 mRNA expression in chronic HCV patient liver biopsy samples. CSC generation by HCV core protein was dependent on the endoglin signaling pathway using activin receptor-like kinase 1 (ALK1) Fc blocking peptide and endoglin small interfering RNA (siRNA). Further, follow-up from in vitro analysis suggested that the antiapoptosis Bcl2 protein, proliferation-related cyclin D1 protein, and CSC-associated Hes1, Notch1, Nanog, and Sox2 proteins are enhanced during infection or ectopic expression of HCV core protein. IMPORTANCE Endoglin plays a crucial role in fibrogenesis and angiogenesis and is an important protein for tumor growth, survival, and cancer cell metastasis. Endoglin enhances ALK1-SMAD1/5 signaling in different cell types, leading to increased proliferation and migration responses. We have observed endoglin expression on the HCV core-expressing cell surface of human hepatocyte origin and activation of phospho-SMAD1/5 and ID1 downstream signaling molecules. ID1 protein plays a role in CSC properties, and we found that

  19. Pten Regulates Retinal Amacrine Cell Number by Modulating Akt, Tgfβ, and Erk Signaling.

    Science.gov (United States)

    Tachibana, Nobuhiko; Cantrup, Robert; Dixit, Rajiv; Touahri, Yacine; Kaushik, Gaurav; Zinyk, Dawn; Daftarian, Narsis; Biernaskie, Jeff; McFarlane, Sarah; Schuurmans, Carol

    2016-09-07

    All tissues are genetically programmed to acquire an optimal size that is defined by total cell number and individual cellular dimensions. The retina contains stereotyped proportions of one glial and six neuronal cell types that are generated in overlapping waves. How multipotent retinal progenitors know when to switch from making one cell type to the next so that appropriate numbers of each cell type are generated is poorly understood. Pten is a phosphatase that controls progenitor cell proliferation and differentiation in several lineages. Here, using a conditional loss-of-function strategy, we found that Pten regulates retinal cell division and is required to produce the full complement of rod photoreceptors and amacrine cells in mouse. We focused on amacrine cell number control, identifying three downstream Pten effector pathways. First, phosphoinositide 3-kinase/Akt signaling is hyperactivated in Pten conditional knock-out (cKO) retinas, and misexpression of constitutively active Akt (Akt-CA) in retinal explants phenocopies the reduction in amacrine cell production observed in Pten cKOs. Second, Akt-CA activates Tgfβ signaling in retinal explants, which is a negative feedback pathway for amacrine cell production. Accordingly, Tgfβ signaling is elevated in Pten cKO retinas, and epistatic analyses placed Pten downstream of TgfβRII in amacrine cell number control. Finally, Pten regulates Raf/Mek/Erk signaling levels to promote the differentiation of all amacrine cell subtypes, which are each reduced in number in Pten cKOs. Pten is thus a positive regulator of amacrine cell production, acting via multiple downstream pathways, highlighting its diverse actions as a mediator of cell number control. Despite the importance of size for optimal organ function, how individual cell types are generated in correct proportions is poorly understood. There are several ways to control cell number, including readouts of organ function (e.g., secreted hormones reach functional

  20. RhoA/ROCK signaling regulates smooth muscle phenotypic modulation and vascular remodeling via the JNK pathway and vimentin cytoskeleton.

    Science.gov (United States)

    Tang, Lian; Dai, Fan; Liu, Yan; Yu, Xiaoqiang; Huang, Chao; Wang, Yuqin; Yao, Wenjuan

    2018-05-20

    The RhoA/ROCK signaling pathway regulates cell morphology, adhesion, proliferation, and migration. In this study, we investigated the regulatory role of RhoA/ROCK signaling on PDGF-BB-mediated smooth muscle phenotypic modulation and vascular remodeling and clarified the molecular mechanisms behind these effects. PDGF-BB treatment induced the activation of RhoA, ROCK, PDGF-Rβ, and the expression of PDGF-Rβ in HA-VSMCs (human aortic vascular smooth muscle cells). PDGF-Rβ inhibition and RhoA suppression blocked PDGF-BB-induced RhoA activation and ROCK induction. In addition, PDGF-BB-mediated cell proliferation and migration were suppressed by PDGF-Rβ inhibition, RhoA suppression, and ROCK inhibition, suggesting that PDGF-BB promotes phenotypic modulation of HA-VSMCs by activating the RhoA/ROCK pathway via the PDGF receptor. Moreover, suppressing both ROCK1 and ROCK2 blocked cell cycle progression from G0/G1 to S phase by decreasing the transcription and protein expression of cyclin D1, CDK2, and CDK4 via JNK/c-Jun pathway, thus reducing cell proliferation in PDGF-BB-treated HA-VSMCs. ROCK1 deletion, rather than ROCK2 suppression, significantly inhibited PDGF-BB-induced migration by reducing the expression of vimentin and preventing the remodeling of vimentin and phospho-vimentin. Furthermore, ROCK1 deletion suppressed vimentin by inhibiting the phosphorylation of Smad2/3 and the nuclear translocation of Smad4. These findings suggested that ROCK1 and ROCK2 might play different roles in PDGF-BB-mediated cell proliferation and migration in HA-VSMCs. In addition, PDGF-BB and its receptor participated in neointima formation and vascular remodeling by promoting cell cycle protein expression via the JNK pathway and enhancing vimentin expression in a rat balloon injury model; effects that were inhibited by treatment with fasudil. Together, the results of this study reveal a novel mechanism through which RhoA/ROCK signaling regulates smooth muscle phenotypic modulation and

  1. Tumor Architecture and Notch Signaling Modulate Drug Response in Basal Cell Carcinoma.

    Science.gov (United States)

    Eberl, Markus; Mangelberger, Doris; Swanson, Jacob B; Verhaegen, Monique E; Harms, Paul W; Frohm, Marcus L; Dlugosz, Andrzej A; Wong, Sunny Y

    2018-02-12

    Hedgehog (Hh) pathway inhibitors such as vismodegib are highly effective for treating basal cell carcinoma (BCC); however, residual tumor cells frequently persist and regenerate the primary tumor upon drug discontinuation. Here, we show that BCCs are organized into two molecularly and functionally distinct compartments. Whereas interior Hh + /Notch + suprabasal cells undergo apoptosis in response to vismodegib, peripheral Hh +++ /Notch - basal cells survive throughout treatment. Inhibiting Notch specifically promotes tumor persistence without causing drug resistance, while activating Notch is sufficient to regress already established lesions. Altogether, these findings suggest that the three-dimensional architecture of BCCs establishes a natural hierarchy of drug response in the tumor and that this hierarchy can be overcome, for better or worse, by modulating Notch. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. FHA domains as phospho-threonine binding modules in cell signaling.

    Science.gov (United States)

    Hammet, Andrew; Pike, Brietta L; McNees, Carolyn J; Conlan, Lindus A; Tenis, Nora; Heierhorst, Jörg

    2003-01-01

    Forkhead-associated (FHA) domains are present in >200 diverse proteins in all phyla from bacteria to mammals and seem to be particularly prevalent in proteins with cell cycle control functions. Recent work from several laboratories has considerably improved our understanding of the structure and function of these domains that were virtually unknown a few years ago, and the first disease associations of FHA domains have now emerged. FHA domains form 11-stranded beta-sandwiches that contain some 100-180 amino acid residues with a high degree of sequence diversity. FHA domains act as phosphorylation-dependent protein-protein interaction modules that preferentially bind to phospho-threonine residues in their targets. Interestingly, point mutations in the human CHK2 gene that lead to single-residue amino acid substitutions in the FHA domain of this cell cycle checkpoint kinase have been found to cause a subset of cases of the Li-Fraumeni multi-cancer syndrome.

  3. Glutamate signalling and secretory phospholipase A2 modulate the release of arachidonic acid from neuronal membranes

    DEFF Research Database (Denmark)

    Rodriguez De Turco, Elena B; Jackson, Fannie R; DeCoster, Mark A

    2002-01-01

    The lipid mediators generated by phospholipases A(2) (PLA(2)), free arachidonic acid (AA), eicosanoids, and platelet-activating factor, modulate neuronal activity; when overproduced, some of them become potent neurotoxins. We have shown, using primary cortical neuron cultures, that glutamate...... and secretory PLA(2) (sPLA(2)) from bee venom (bv sPLA(2)) and Taipan snake venom (OS2) elicit synergy in inducing neuronal cell death. Low concentrations of sPLA(2) are selective ligands of cell-surface sPLA(2) receptors. We investigated which neuronal arachidonoyl phospholipids are targeted by glutamate......) and in minor changes in other phospholipids. A similar profile, although of greater magnitude, was observed 20 hr posttreatment. Glutamate (80 microM) induced much less mobilization of (3)H-AA than did sPLA(2) and resulted in a threefold greater degradation of (3)H-AA PE than of (3)H-AA PC by 20 hr...

  4. A terahertz EO detector with large dynamical range, high modulation depth and signal-noise ratio

    Science.gov (United States)

    Pan, Xinjian; Cai, Yi; Zeng, Xuanke; Zheng, Shuiqin; Li, Jingzhen; Xu, Shixiang

    2017-05-01

    The paper presents a novel design for terahertz (THz) free-space time domain electro-optic (EO) detection where the static birefringent phases of the two balanced arms are set close to zero but opposite to each other. Our theoretical and numerical analyses show this design has much stronger ability to cancel the optical background noise than both THz ellipsometer and traditional crossed polarizer geometry (CPG). Its optical modulation depth is about twice as high as that of traditional CPG, but about ten times as high as that of THz ellipsometer. As for the dynamical range, our improved design is comparable to the THz ellipsometer but obviously larger than the traditional CPG. Some experiments for comparing our improved CPG with traditional CPG agree well with the corresponding theoretical predictions. Our experiments also show that the splitting ratio of the used non-polarization beam splitter is critical for the performance of our design.

  5. Drug Modulators of B Cell Signaling Pathways and Epstein-Barr Virus Lytic Activation.

    Science.gov (United States)

    Kosowicz, John G; Lee, Jaeyeun; Peiffer, Brandon; Guo, Zufeng; Chen, Jianmeng; Liao, Gangling; Hayward, S Diane; Liu, Jun O; Ambinder, Richard F

    2017-08-15

    Epstein-Barr virus (EBV) is a ubiquitous human gammaherpesvirus that establishes a latency reservoir in B cells. In this work, we show that ibrutinib, idelalisib, and dasatinib, drugs that block B cell receptor (BCR) signaling and are used in the treatment of hematologic malignancies, block BCR-mediated lytic induction at clinically relevant doses. We confirm that the immunosuppressive drugs cyclosporine and tacrolimus also inhibit BCR-mediated lytic induction but find that rapamycin does not inhibit BCR-mediated lytic induction. Further investigation shows that mammalian target of rapamycin complex 2 (mTORC2) contributes to BCR-mediated lytic induction and that FK506-binding protein 12 (FKBP12) binding alone is not adequate to block activation. Finally, we show that BCR signaling can activate EBV lytic induction in freshly isolated B cells from peripheral blood mononuclear cells (PBMCs) and that activation can be inhibited by ibrutinib or idelalisib. IMPORTANCE EBV establishes viral latency in B cells. Activation of the B cell receptor pathway activates lytic viral expression in cell lines. Here we show that drugs that inhibit important kinases in the BCR signaling pathway inhibit activation of lytic viral expression but do not inhibit several other lytic activation pathways. Immunosuppressant drugs such as cyclosporine and tacrolimus but not rapamycin also inhibit BCR-mediated EBV activation. Finally, we show that BCR activation of lytic infection occurs not only in tumor cell lines but also in freshly isolated B cells from patients and that this activation can be blocked by BCR inhibitors. Copyright © 2017 American Society for Microbiology.

  6. Arabidopsis scaffold protein RACK1A modulates rare sugar D-allose regulated gibberellin signaling

    OpenAIRE

    Fennell, Herman; Olawin, Abdulquadri; Mizanur, Rahman M.; Izumori, Ken; Chen, Jin-Gui; Ullah, Hemayet

    2012-01-01

    As energy sources and structural components, sugars are the central regulators of plant growth and development. In addition to the abundant natural sugars in plants, more than 50 different kinds of rare sugars exist in nature, several of which show distinct roles in plant growth and development. Recently, one of the rare sugars, D-allose, an epimer of D-glucose at C3, is found to suppress plant hormone gibberellin (GA) signaling in rice. Scaffold protein RACK1A in the model plant Arabidopsis ...

  7. The cannabinoid CB1 receptor and mTORC1 signalling pathways interact to modulate glucose homeostasis in mice

    Directory of Open Access Journals (Sweden)

    Francisco J. Bermudez-Silva

    2016-01-01

    Full Text Available The endocannabinoid system (ECS is an intercellular signalling mechanism that is present in the islets of Langerhans and plays a role in the modulation of insulin secretion and expansion of the β-cell mass. The downstream signalling pathways mediating these effects are poorly understood. Mammalian target of rapamycin complex 1 (mTORC1 signalling is a key intracellular pathway involved in energy homeostasis and is known to importantly affect the physiology of pancreatic islets. We investigated the possible relationship between cannabinoid type 1 (CB1 receptor signalling and the mTORC1 pathway in the endocrine pancreas of mice by using pharmacological analysis as well as mice genetically lacking the CB1 receptor or the downstream target of mTORC1, the kinase p70S6K1. In vitro static secretion experiments on islets, western blotting, and in vivo glucose and insulin tolerance tests were performed. The CB1 receptor antagonist rimonabant decreased glucose-stimulated insulin secretion (GSIS at 0.1 µM while increasing phosphorylation of p70S6K1 and ribosomal protein S6 (rpS6 within the islets. Specific pharmacological blockade of mTORC1 by 3 nM rapamycin, as well as genetic deletion of p70S6K1, impaired the CB1-antagonist-mediated decrease in GSIS. In vivo experiments showed that 3 mg/kg body weight rimonabant decreased insulin levels and induced glucose intolerance in lean mice without altering peripheral insulin sensitivity; this effect was prevented by peripheral administration of low doses of rapamycin (0.1 mg/kg body weight, which increased insulin sensitivity. These findings suggest a functional interaction between the ECS and the mTORC1 pathway within the endocrine pancreas and at the whole-organism level, which could have implications for the development of new therapeutic approaches for pancreatic β-cell diseases.

  8. Equation-of-state dependent features in shock-oscillation modulated neutrino and gravitational-wave signals from supernovae

    Science.gov (United States)

    Marek, A.; Janka, H.-T.; Müller, E.

    2009-03-01

    We present two-dimensional (axisymmetric) neutrino-hydrodynamic simulations of the long-time accretion phase of a 15 M_⊙ progenitor star after core bounce and before the launch of a supernova explosion, when non-radial hydrodynamic instabilities like convection occur in different regions of the collapsing stellar core and the standing accretion shock instability (SASI) leads to large-amplitude oscillations of the stalled shock with a period of tens of milliseconds. Our simulations were performed with the Prometheus-Vertex code, which includes a multi-flavor, energy-dependent neutrino transport scheme and employs an effective relativistic gravitational potential. Testing the influence of a stiff and a soft equation of state for hot neutron star matter, we find that the non-radial mass motions in the supernova core impose a time variability on the neutrino and gravitational-wave signals with larger amplitudes, as well as higher frequencies in the case of a more compact nascent neutron star. After the prompt shock-breakout burst of electron neutrinos, a more compact accreting remnant produces higher neutrino luminosities and higher mean neutrino energies. The observable neutrino emission in the SASI sloshing direction exhibits a modulation of several ten percent in the luminosities and around 1 MeV in the mean energies with most power at typical SASI frequencies between roughly 20 and 100 Hz. The modulation is caused by quasi-periodic variations in the mass accretion rate of the neutron star in each hemisphere. At times later than ~50-100 ms after bounce, the gravitational-wave amplitude is dominated by the growing low-frequency (⪉200 Hz) signal associated with anisotropic neutrino emission. A high-frequency wave signal results from nonradial gas flows in the outer layers of the anisotropically accreting neutron star. Right after bounce such nonradial mass motions occur due to prompt post-shock convection in both considered cases and contribute mostly to the early

  9. PCA3 noncoding RNA is involved in the control of prostate-cancer cell survival and modulates androgen receptor signaling

    International Nuclear Information System (INIS)

    Ferreira, Luciana Bueno; Gimba, Etel Rodrigues Pereira; Palumbo, Antonio; Mello, Kivvi Duarte de; Sternberg, Cinthya; Caetano, Mauricio S; Oliveira, Felipe Leite de; Neves, Adriana Freitas; Nasciutti, Luiz Eurico; Goulart, Luiz Ricardo

    2012-01-01

    PCA3 is a non-coding RNA (ncRNA) that is highly expressed in prostate cancer (PCa) cells, but its functional role is unknown. To investigate its putative function in PCa biology, we used gene expression knockdown by small interference RNA, and also analyzed its involvement in androgen receptor (AR) signaling. LNCaP and PC3 cells were used as in vitro models for these functional assays, and three different siRNA sequences were specifically designed to target PCA3 exon 4. Transfected cells were analyzed by real-time qRT-PCR and cell growth, viability, and apoptosis assays. Associations between PCA3 and the androgen-receptor (AR) signaling pathway were investigated by treating LNCaP cells with 100 nM dihydrotestosterone (DHT) and with its antagonist (flutamide), and analyzing the expression of some AR-modulated genes (TMPRSS2, NDRG1, GREB1, PSA, AR, FGF8, CdK1, CdK2 and PMEPA1). PCA3 expression levels were investigated in different cell compartments by using differential centrifugation and qRT-PCR. LNCaP siPCA3-transfected cells significantly inhibited cell growth and viability, and increased the proportion of cells in the sub G0/G1 phase of the cell cycle and the percentage of pyknotic nuclei, compared to those transfected with scramble siRNA (siSCr)-transfected cells. DHT-treated LNCaP cells induced a significant upregulation of PCA3 expression, which was reversed by flutamide. In siPCA3/LNCaP-transfected cells, the expression of AR target genes was downregulated compared to siSCr-transfected cells. The siPCA3 transfection also counteracted DHT stimulatory effects on the AR signaling cascade, significantly downregulating expression of the AR target gene. Analysis of PCA3 expression in different cell compartments provided evidence that the main functional roles of PCA3 occur in the nuclei and microsomal cell fractions. Our findings suggest that the ncRNA PCA3 is involved in the control of PCa cell survival, in part through modulating AR signaling, which may raise new

  10. Asexual sporulation signalling regulates autolysis of Aspergillus nidulans via modulating the chitinase ChiB production.

    Science.gov (United States)

    Pócsi, I; Leiter, E; Kwon, N-J; Shin, K-S; Kwon, G-S; Pusztahelyi, T; Emri, T; Abuknesha, R A; Price, R G; Yu, J-H

    2009-08-01

    Elucidation of the regulation of ChiB production in Aspergillus nidulans. Mutational inactivation of the A. nidulans chiB gene resulted in a nonautolytic phenotype. To better understand the mechanisms controlling both developmental progression and fungal autolysis, we examined a range of autolysis-associated parameters in A. nidulans developmental and/or autolytic mutants. Investigation of disorganization of mycelial pellets, loss of biomass, extra-/intracellular chitinase activities, ChiB production and chiB mRNA levels in various cultures revealed that, in submerged cultures, initialization of autolysis and stationary phase-induced ChiB production are intimately coupled, and that both processes are controlled by the FluG-BrlA asexual sporulation regulatory pathway. ChiB production does not affect the progression of apoptotic cell death in the aging A. nidulans cultures. The endochitinase ChiB plays an important role in autolysis of A. nidulans, and its production is initiated by FluG-BrlA signalling. Despite the fact that apoptosis is an inseparable part of fungal autolysis, its regulation is independent to FluG-initiated sporulation signalling. Deletion of chiB and fluG homologues in industrial filamentous fungal strains may stabilize the hyphal structures in the autolytic phase of growth and limit the release of autolytic hydrolases into the culture medium.

  11. Signaling beyond Punching Holes: Modulation of Cellular Responses by Vibrio cholerae Cytolysin

    Directory of Open Access Journals (Sweden)

    Barkha Khilwani

    2015-08-01

    Full Text Available Pore-forming toxins (PFTs are a distinct class of membrane-damaging cytolytic proteins that contribute significantly towards the virulence processes employed by various pathogenic bacteria. Vibrio cholerae cytolysin (VCC is a prominent member of the beta-barrel PFT (beta-PFT family. It is secreted by most of the pathogenic strains of the intestinal pathogen V. cholerae. Owing to its potent membrane-damaging cell-killing activity, VCC is believed to play critical roles in V. cholerae pathogenesis, particularly in those strains that lack the cholera toxin. Large numbers of studies have explored the mechanistic basis of the cell-killing activity of VCC. Consistent with the beta-PFT mode of action, VCC has been shown to act on the target cells by forming transmembrane oligomeric beta-barrel pores, thereby leading to permeabilization of the target cell membranes. Apart from the pore-formation-induced direct cell-killing action, VCC exhibits the potential to initiate a plethora of signal transduction pathways that may lead to apoptosis, or may act to enhance the cell survival/activation responses, depending on the type of target cells. In this review, we will present a concise view of our current understanding regarding the multiple aspects of these cellular responses, and their underlying signaling mechanisms, evoked by VCC.

  12. Fish Suppressors of Cytokine Signaling (SOCS): Gene Discovery, Modulation of Expression and Function

    Science.gov (United States)

    Wang, Tiehui; Gorgoglione, Bartolomeo; Maehr, Tanja; Holland, Jason W.; Vecino, Jose L. González; Wadsworth, Simon; Secombes, Christopher J.

    2011-01-01

    The intracellular suppressors of cytokine signaling (SOCS) family members, including CISH and SOCS1 to 7 in mammals, are important regulators of cytokine signaling pathways. So far, the orthologues of all the eight mammalian SOCS members have been identified in fish, with several of them having multiple copies. Whilst fish CISH, SOCS3, and SOCS5 paralogues are possibly the result of the fish-specific whole genome duplication event, gene duplication or lineage-specific genome duplication may also contribute to some paralogues, as with the three trout SOCS2s and three zebrafish SOCS5s. Fish SOCS genes are broadly expressed and also show species-specific expression patterns. They can be upregulated by cytokines, such as IFN-γ, TNF-α, IL-1β, IL-6, and IL-21, by immune stimulants such as LPS, poly I:C, and PMA, as well as by viral, bacterial, and parasitic infections in member- and species-dependent manners. Initial functional studies demonstrate conserved mechanisms of fish SOCS action via JAK/STAT pathways. PMID:22203897

  13. Transmembrane collagen XVII modulates integrin dependent keratinocyte migration via PI3K/Rac1 signaling.

    Directory of Open Access Journals (Sweden)

    Stefanie Löffek

    Full Text Available The hemidesmosomal transmembrane component collagen XVII (ColXVII plays an important role in the anchorage of the epidermis to the underlying basement membrane. However, this adhesion protein seems to be also involved in the regulation of keratinocyte migration, since its expression in these cells is strongly elevated during reepithelialization of acute wounds and in the invasive front of squamous cell carcinoma, while its absence in ColXVII-deficient keratinocytes leads to altered cell motility. Using a genetic model of murine Col17a1⁻/⁻ keratinocytes we elucidated ColXVII mediated signaling pathways in cell adhesion and migration. Col17a1⁻/⁻ keratinocytes exhibited increased spreading on laminin 332 and accelerated, but less directed cell motility. These effects were accompanied by increased expression of the integrin subunits β4 and β1. The migratory phenotype, as evidenced by formation of multiple unstable lamellipodia, was associated with enhanced phosphoinositide 3-kinase (PI3K activity. Dissection of the signaling pathway uncovered enhanced phosphorylation of the β4 integrin subunit and the focal adhesion kinase (FAK as activators of PI3K. This resulted in elevated Rac1 activity as a downstream consequence. These results provide mechanistic evidence that ColXVII coordinates keratinocyte adhesion and directed motility by interfering integrin dependent PI3K activation and by stabilizing lamellipodia at the leading edge of reepithelializing wounds and in invasive squamous cell carcinoma.

  14. Antioxidant proteins TSA and PAG interact synergistically with Presenilin to modulate Notch signaling in Drosophila.

    Science.gov (United States)

    Wangler, Michael F; Reiter, Lawrence T; Zimm, Georgianna; Trimble-Morgan, Jennifer; Wu, Jane; Bier, Ethan

    2011-07-01

    Alzheimer's disease (AD) pathogenesis is characterized by senile plaques in the brain and evidence of oxidative damage. Oxidative stress may precede plaque formation in AD; however, the link between oxidative damage and plaque formation remains unknown. Presenilins are transmembrane proteins in which mutations lead to accelerated plaque formation and early-onset familial Alzheimer's disease. Presenilins physically interact with two antioxidant enzymes thiol-specific antioxidant (TSA) and proliferation-associated gene (PAG) of the peroxiredoxin family. The functional consequences of these interactions are unclear. In the current study we expressed a presenilin transgene in Drosophila wing and sensory organ precursors of the fly. This caused phenotypes typical of Notch signaling loss-of-function mutations. We found that while expression of TSA or PAG alone produced no phenotype, co-expression of TSA and PAG with presenilin led to an enhanced Notch loss-of-function phenotype. This phenotype was more severe and more penetrant than that caused by the expression of Psn alone. In order to determine whether these phenotypes were indeed affecting Notch signaling, this experiment was performed in a genetic background carrying an activated Notch (Abruptex) allele. The phenotypes were almost completely rescued by this activated Notch allele. These results link peroxiredoxins with the in vivo function of Presenilin, which ultimately connects two key pathogenetic mechanisms in AD, namely, antioxidant activity and plaque formation, and raises the possibility of a role for peroxiredoxin family members in Alzheimer's pathogenesis.

  15. Melatonin Signaling and Its Modulation of PfNF-YB Transcription Factor Expression in Plasmodium falciparum

    Directory of Open Access Journals (Sweden)

    Célia R. S. Garcia

    2013-07-01

    Full Text Available Malaria is one of the most severe tropical infectious diseases. More than 220 million people around the world have a clinical malaria infection and about one million die because of Plasmodium annually. This parasitic pathogen replicates efficiently in its human host making it difficult to eradicate. It is transmitted by mosquito vectors and so far mosquito control programs have not effectively eliminated this transmission. Because of malaria’s enormous health and economic impact and the need to develop new control and eventual elimination strategies, a big research effort has been made to better understand the biology of this parasite and its interactions with its vertebrate host. Determination of the genome sequence and organization, the elucidation of the role of key proteins, and cell signaling studies have helped to develop an understanding of the molecular mechanisms that provide the parasite’s versatility. The parasite can sense its environment and adapt to benefit its survival, indeed this is essential for it to complete its life cycle. For many years we have studied how the Plasmodium parasite is able to sense melatonin. In this review we discuss the melatonin signaling pathway and its role in the control of Plasmodium replication and development.

  16. Hippocampal leptin signaling reduces food intake and modulates food-related memory processing.

    Science.gov (United States)

    Kanoski, Scott E; Hayes, Matthew R; Greenwald, Holly S; Fortin, Samantha M; Gianessi, Carol A; Gilbert, Jennifer R; Grill, Harvey J

    2011-08-01

    The increase in obesity prevalence highlights the need for a more comprehensive understanding of the neural systems controlling food intake; one that extends beyond food intake driven by metabolic need and considers that driven by higher-order cognitive factors. The hippocampus, a brain structure involved in learning and memory function, has recently been linked with food intake control. Here we examine whether administration of the adiposity hormone leptin to the dorsal and ventral sub-regions of the hippocampus influences food intake and memory for food. Leptin (0.1 μg) delivered bilaterally to the ventral hippocampus suppressed food intake and body weight measured 24 h after administration; a higher dose (0.4 μg) was needed to suppress intake following dorsal hippocampal delivery. Leptin administration to the ventral but not dorsal hippocampus blocked the expression of a conditioned place preference for food and increased the latency to run for food in an operant runway paradigm. Additionally, ventral but not dorsal hippocampal leptin delivery suppressed memory consolidation for the spatial location of food, whereas hippocampal leptin delivery had no effect on memory consolidation in a non-spatial appetitive response paradigm. Collectively these findings indicate that ventral hippocampal leptin signaling contributes to the inhibition of food-related memories elicited by contextual stimuli. To conclude, the results support a role for hippocampal leptin signaling in the control of food intake and food-related memory processing.

  17. Road crossing behavior under traffic light conflict: Modulating effects of green light duration and signal congruency.

    Science.gov (United States)

    Lange, Florian; Haiduk, Michael; Boos, Moritz; Tinschert, Peter; Schwarze, Anke; Eggert, Frank

    2016-10-01

    A large number of pedestrians and cyclists regularly ignore the traffic lights to cross the road illegally. In a recent analysis, illegal road crossing behavior has been shown to be enhanced in the presence of incongruent stimulus configurations. Pedestrians and cyclists are more likely to cross against a red light when exposed to an irrelevant conflicting green light. Here, we present experimental and observational data on the factors moderating the risk associated with incongruent traffic lights. In an observational study, we demonstrated that the conflict-related increase in illegal crossing rates is reduced when pedestrian and cyclist green light periods are long. In a laboratory experiment, we manipulated the color of the irrelevant signals to expose participants to different degrees of incongruency. Results revealed that individuals' performance gradually varied as a function of incongruency, suggesting that the negative impact of a conflicting green light can be reduced by slightly adjusting its color. Our findings highlight that the observation of real-world behavior at intersections and the experimental analysis of psychological processes under controlled laboratory conditions can complement each other in identifying risk factors of risky road crossing behavior. Based on this combination, our study elaborates on promising measures to improve safety at signalized intersections. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Cocaine- and amphetamine-regulated transcript (CART signaling within the paraventricular thalamus modulates cocaine-seeking behaviour.

    Directory of Open Access Journals (Sweden)

    Morgan H James

    Full Text Available BACKGROUND: Cocaine- and amphetamine-regulated transcript (CART has been demonstrated to play a role in regulating the rewarding and reinforcing effects of various drugs of abuse. A recent study demonstrated that i.c.v. administration of CART negatively modulates reinstatement of alcohol seeking, however, the site(s of action remains unclear. We investigated the paraventricular thalamus (PVT as a potential site of relapse-relevant CART signaling, as this region is known to receive dense innervation from CART-containing hypothalamic cells and to project to a number of regions known to be involved in mediating reinstatement, including the nucleus accumbens (NAC, medial prefrontal cortex (mPFC and basolateral amygdala (BLA. METHODOLOGY/PRINCIPAL FINDINGS: Male rats were trained to self-administer cocaine before being extinguished to a set criterion. One day following extinction, animals received intra-PVT infusions of saline, tetrodotoxin (TTX; 2.5 ng, CART (0.625 µg or 2.5 µg or no injection, followed by a cocaine prime (10 mg/kg, i.p.. Animals were then tested under extinction conditions for one hour. Treatment with either TTX or CART resulted in a significant attenuation of drug-seeking behaviour following cocaine-prime, with the 2.5 µg dose of CART having the greatest effect. This effect was specific to the PVT region, as misplaced injections of both TTX and CART resulted in responding that was identical to controls. CONCLUSIONS/SIGNIFICANCE: We show for the first time that CART signaling within the PVT acts to inhibit drug-primed reinstatement of cocaine seeking behaviour, presumably by negatively modulating PVT efferents that are important for drug seeking, including the NAC, mPFC and BLA. In this way, we identify a possible target for future pharmacological interventions designed to suppress drug seeking.

  19. Modulation of Rat 50-kHz Ultrasonic Vocalizations by Glucocorticoid Signaling: Possible Relevance to Reward and Motivation.

    Science.gov (United States)

    Simola, Nicola; Paci, Elena; Serra, Marcello; Costa, Giulia; Morelli, Micaela

    2018-01-01

    Rats emit 50-kHz ultrasonic vocalizations (USVs) to communicate positive emotional states, and these USVs are increasingly being investigated in preclinical studies on reward and motivation. Although it is the activation of dopamine receptors that initiates the emission of 50-kHz USVs, non-dopaminergic mechanisms may modulate calling in the 50 kHz frequency band. To further elucidate these mechanisms, the present study investigated whether the pharmacological manipulation of glucocorticoid signaling influenced calling. Rats were administered corticosterone (1-5 mg/kg, s.c.), the glucocorticoid receptor antagonist mifepristone (40 or 100 mg/kg, s.c.), or the corticosterone synthesis inhibitor metyrapone (50 or 100 mg/kg, i.p.). The effects of these drugs on calling initiation and on calling recorded during nonaggressive social contacts or after the administration of amphetamine (0.25 or 1 mg/kg, i.p.) were then evaluated. Corticosterone failed to initiate the emission of 50-kHz USVs and did not influence pro-social and amphetamine-stimulated calling. Similarly, mifepristone and metyrapone did not initiate calling. However, metyrapone suppressed pro-social calling and calling stimulated by a moderate dose (1 mg/kg, i.p.) of amphetamine. Conversely, mifepristone attenuated calling stimulated by a low (0.25 mg/kg, i.p.), but not moderate (1 mg/kg, i.p.), dose of amphetamine and had no influence on pro-social calling. The present results demonstrate that glucocorticoid signaling modulates calling in the 50 kHz frequency band only in certain conditions and suggest that mechanisms different from the inhibition of corticosterone synthesis may participate in the suppression of calling by metyrapone. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  20. Astrocyte IP3R2-dependent Ca2+ signaling is not a major modulator of neuronal pathways governing behavior.

    Directory of Open Access Journals (Sweden)

    Jeremy ePetravicz

    2014-11-01

    Full Text Available Calcium-dependent release of gliotransmitters by astrocytes is reported to play a critical role in synaptic transmission and be necessary for long-term potentiation (LTP, long-term depression (LTD and other forms of synaptic modulation that are correlates of learning and memory . Further, physiological processes reported to be dependent on Ca2+ fluxes in astrocytes include functional hyperemia, sleep, and regulation of breathing. The preponderance of findings indicate that most, if not all, receptor dependent Ca2+ fluxes within astrocytes are due to release of Ca2+ through IP3 receptor/channels in the endoplasmic reticulum. Findings from several laboratories indicate that astrocytes only express IP3 receptor type 2 (IP3R2 and that a knockout of IP3R2 obliterates the GPCR-dependent astrocytic Ca2+ responses. Assuming that astrocytic Ca2+ fluxes play a critical role in synaptic physiology, it would be predicted that eliminating of astrocytic Ca2+ fluxes would lead to marked changes in behavioral tests. Here, we tested this hypothesis by conducting a broad series of behavioral tests that recruited multiple brain regions, on an IP3R2 conditional knockout mouse model. We present the novel finding that behavioral processes are unaffected by lack of astrocyte IP3R-mediated Ca2+ signals. IP3R2 cKO animals display no change in anxiety or depressive behaviors, and no alteration to motor and sensory function. Morris water maze testing, a behavioral correlate of learning and memory, was unaffected by lack of astrocyte IP3R2-mediated Ca2+-signaling. Therefore, in contrast to the prevailing literature, we find that neither receptor-driven astrocyte Ca2+ fluxes nor, by extension, gliotransmission is likely to be a major modulating force on the physiological processes underlying behavior.

  1. Atg12 Maintains Skeletal Integrity by Modulating Pro-Osteoclastogenic Signals and Chondrocyte Differentiation

    Science.gov (United States)

    Tahimic, Candice; Bahl, Disha; Shirazi-Fard, Yasaman; Marsh, Timothy; Schreurs, Anne-Sofie; Rael, Victoria E.; Glikbarg, Chloe; Debnath, Jayantha; Globus, Ruth K.

    2016-01-01

    Weightlessness and radiation, two unique elements of space, profoundly decreases bone mass. This bone loss is attributed to increased activity of bone-resorbing osteoclasts and functional changes in bone-forming osteoblasts, cells that give rise to mature osteocytes. Our long-term goal is to identify signaling pathways that may be targeted to mitigate bone loss in scenarios of space exploration, radiotherapy and accidental radiation exposure. We have previously shown that exposure of MLO-Y4 osteocyte-like cells to simulated space radiation (56Fe) increased the expression of the pro-osteoclastogenic gene rankl and decreased protein levels of LC3B-II, a key player in autophagy. In this current study, we aimed to further elucidate the role of autophagy in maintaining structural integrity of the skeleton. We hypothesize that loss of autophagy in bone leads to an imbalance in pro-osteoclastogenic and pro-osteogenic signals, resulting in net bone loss. To test our hypothesis we performed global postnatal deletion of Atg12 using tamoxifeninducible Cre recombinase under the control of the CAG promoter. Six-week-old CAGCreERT2/ FloxAtg12 animals were treated daily with Tamoxifen or Vehicle (Control, oil only) for five days and euthanasia performed two weeks after the onset of treatment. Percent change in body weights (prior to treatment and at euthanasia) was not significantly different between treatment groups within the same gender. Compared to Vehicle (Control) groups, Tamoxifen (Atg12 iKO) groups showed decreased LC3B-I to II conversion and increased p62 protein levels, consistent with loss of autophagy. Quantitative PCR revealed increased expression of proosteoclastogenic cytokines mcp1 and rankl in bone and marrow respectively in male iKOs compared to male controls. Expression levels of these genes were not significantly altered in the Atg12 iKO females compared to females controls. Microcomputed tomography of tibiae revealed decreased cortical bone volume, cortical

  2. Pathogenic Leptospires Modulate Protein Expression and Post-translational Modifications in Response to Mammalian Host Signals.

    Science.gov (United States)

    Nally, Jarlath E; Grassmann, Andre A; Planchon, Sébastien; Sergeant, Kjell; Renaut, Jenny; Seshu, Janakiram; McBride, Alan J; Caimano, Melissa J

    2017-01-01

    Pathogenic species of Leptospira cause leptospirosis, a bacterial zoonotic disease with a global distribution affecting over one million people annually. Reservoir hosts of leptospirosis, including rodents, dogs, and cattle, exhibit little to no signs of disease but shed large numbers of organisms in their urine. Transmission occurs when mucosal surfaces or abraded skin come into contact with infected urine or urine-contaminated water or soil. Whilst little is known about how Leptospira adapt to and persist within a reservoir host, in vitro studies suggest that leptospires alter their transcriptomic and proteomic profiles in response to environmental signals encountered during mammalian infection. We applied the dialysis membrane chamber (DMC) peritoneal implant model to compare the whole cell proteome of in vivo derived leptospires with that of leptospires cultivated in vitro at 30°C and 37°C by 2-dimensional difference in-gel electrophoresis (2-D DIGE). Of 1,735 protein spots aligned across 9 2-D DIGE gels, 202 protein spots were differentially expressed ( p 1.25 or expressed proteins were excised for identification by mass spectrometry. Data are available via ProteomeXchange with identifier PXD006995. The greatest differences were detected when DMC-cultivated leptospires were compared with IV30- or IV37-cultivated leptospires, including the increased expression of multiple isoforms of Loa22, a known virulence factor. Unexpectedly, 20 protein isoforms of LipL32 and 7 isoforms of LipL41 were uniformly identified by DIGE as differentially expressed, suggesting that unique post-translational modifications (PTMs) are operative in response to mammalian host conditions. To test this hypothesis, a rat model of persistent renal colonization was used to isolate leptospires directly from the urine of experimentally infected rats. Comparison of urinary derived leptospires to IV30 leptospires by 2-D immunoblotting confirmed that modification of proteins with

  3. Pathogenic Leptospires Modulate Protein Expression and Post-translational Modifications in Response to Mammalian Host Signals

    Directory of Open Access Journals (Sweden)

    Jarlath E. Nally

    2017-08-01

    Full Text Available Pathogenic species of Leptospira cause leptospirosis, a bacterial zoonotic disease with a global distribution affecting over one million people annually. Reservoir hosts of leptospirosis, including rodents, dogs, and cattle, exhibit little to no signs of disease but shed large numbers of organisms in their urine. Transmission occurs when mucosal surfaces or abraded skin come into contact with infected urine or urine-contaminated water or soil. Whilst little is known about how Leptospira adapt to and persist within a reservoir host, in vitro studies suggest that leptospires alter their transcriptomic and proteomic profiles in response to environmental signals encountered during mammalian infection. We applied the dialysis membrane chamber (DMC peritoneal implant model to compare the whole cell proteome of in vivo derived leptospires with that of leptospires cultivated in vitro at 30°C and 37°C by 2-dimensional difference in-gel electrophoresis (2-D DIGE. Of 1,735 protein spots aligned across 9 2-D DIGE gels, 202 protein spots were differentially expressed (p < 0.05, fold change >1.25 or < −1.25 across all three conditions. Differentially expressed proteins were excised for identification by mass spectrometry. Data are available via ProteomeXchange with identifier PXD006995. The greatest differences were detected when DMC-cultivated leptospires were compared with IV30- or IV37-cultivated leptospires, including the increased expression of multiple isoforms of Loa22, a known virulence factor. Unexpectedly, 20 protein isoforms of LipL32 and 7 isoforms of LipL41 were uniformly identified by DIGE as differentially expressed, suggesting that unique post-translational modifications (PTMs are operative in response to mammalian host conditions. To test this hypothesis, a rat model of persistent renal colonization was used to isolate leptospires directly from the urine of experimentally infected rats. Comparison of urinary derived leptospires to IV30

  4. Effects of activated fibroblasts on phenotype modulation, EGFR signalling and cell cycle regulation in OSCC cells

    Energy Technology Data Exchange (ETDEWEB)

    Berndt, Alexander, E-mail: alexander.berndt@med.uni-jena.de [Center for Molecular Biomedicine, Institute of Pathology, Jena University Hospital, 07740 Jena (Germany); Büttner, Robert, E-mail: Robert-Buettner@gmx.net [Institute of Biochemistry and Biophysics, Friedrich Schiller University Jena, 07740 Jena (Germany); Gühne, Stefanie, E-mail: stefanie_guehne@gmx.net [Center for Molecular Biomedicine, Institute of Pathology, Jena University Hospital, 07740 Jena (Germany); Gleinig, Anna, E-mail: annagleinig@yahoo.com [Center for Molecular Biomedicine, Institute of Pathology, Jena University Hospital, 07740 Jena (Germany); Richter, Petra, E-mail: P.Richter@med.uni-jena.de [Center for Molecular Biomedicine, Institute of Pathology, Jena University Hospital, 07740 Jena (Germany); Chen, Yuan, E-mail: Yuan.Chen@med.uni-jena.de [Center for Molecular Biomedicine, Institute of Pathology, Jena University Hospital, 07740 Jena (Germany); Franz, Marcus, E-mail: Marcus.Franz@med.uni-jena.de [Clinic of Internal Medicine I, Jena University Hospital, 07740 Jena (Germany); Liebmann, Claus, E-mail: Claus.Liebmann@uni-jena.de [Institute of Biochemistry and Biophysics, Friedrich Schiller University Jena, 07740 Jena (Germany)

    2014-04-01

    Crosstalk between carcinoma associated fibroblasts (CAFs) and oral squamous cell carcinoma (OSCC) cells is suggested to mediate phenotype transition of cancer cells as a prerequisite for tumour progression, to predict patients’ outcome, and to influence the efficacy of EGFR inhibitor therapies. Here we investigate the influence of activated fibroblasts as a model for CAFs on phenotype and EGFR signalling in OSCC cells in vitro. For this, immortalised hTERT-BJ1 fibroblasts were activated with TGFβ1 and PDGFAB to generate a myofibroblast or proliferative phenotype, respectively. Conditioned media (FCM{sub TGF}, FCM{sub PDGF}) were used to stimulate PE/CA-PJ15 OSCC cells. Results were compared to the effect of conditioned media of non-stimulated fibroblasts (FCM{sub B}). FCM{sub TGF} stimulation leads to an up-regulation of vimentin in the OSCC cells and an enhancement of invasive behaviour, indicating EMT-like effects. Similarly, FCM{sub TGF}≫FCM{sub PDGF} induced up-regulation of EGFR, but not of ErbB2/ErbB3. In addition, we detected an increase in basal activities of ERK, PI3K/Akt and Stat3 (FCM{sub TGF}>FCM{sub PDGF}) accompanied by protein interaction of vimentin with pERK. These effects are correlated with an increased proliferation. In summary, our results suggest that the activated myofibroblast phenotype provides soluble factors which are able to induce EMT-like phenomena and to increase EGFR signalling as well as cell proliferation in OSCC cells. Our results indicate a possible influence of activated myofibroblasts on EGFR-inhibitor therapy. Therefore, CAFs may serve as promising novel targets for combined therapy strategies. - Highlights: • A cell culture model for cancer associated fibroblasts is described. • The mutual interaction with OSCC cells leads to up-regulation of EGFR in tumour cells. • mCAF induces EGFR downstream signalling with increased proliferation in OSCC. • Erk activation is associated with protein interaction with vimentin

  5. Effects of activated fibroblasts on phenotype modulation, EGFR signalling and cell cycle regulation in OSCC cells